Response to an Abnormal Ovarian Cancer Screening Test Result: Test of the Social Cognitive Processing and Cognitive Social Health Information Processing Models

PubMed Central

Andrykowski, Michael A.; Pavlik, Edward J.

2009-01-01

All cancer screening tests produce a proportion of abnormal results requiring follow-up. Consequently, the cancer screening setting is a natural laboratory for examining psychological and behavioral response to a threatening health-related event. This study tested hypotheses derived from the Social Cognitive Processing and Cognitive-Social Health Information Processing models in trying to understand response to an abnormal ovarian cancer (OC) screening test result. Women (n=278) receiving an abnormal screening test result a mean of 7 weeks earlier were assessed prior to a repeat screening test intended to clarify their previous abnormal result. Measures of disposition (optimism, informational coping style), social environment (social support and constraint), emotional processing, distress, and benefit finding were obtained. Regression analyses indicated greater distress was associated with greater social constraint and emotional processing and a monitoring coping style in women with a family history of OC. Distress was unrelated to social support. Greater benefit finding was associated with both greater social constraint and support and greater distress. The primacy of social constraint in accounting for both benefit-finding and distress was noteworthy and warrants further research on the role of social constraint in adaptation to stressful events. PMID:20419561

Abnormal pap tests among women living in a Hispanic migrant farmworker community: A narrative of health literacy.

PubMed

Vamos, Cheryl A; Lockhart, Elizabeth; Vázquez-Otero, Coralia; Thompson, Erika L; Proctor, Sara; Wells, Kristen J; Daley, Ellen M

2016-08-01

This study explored narrative responses following abnormal Pap tests among Hispanic migrant farmworkers ( N = 18; ages 22-50 years) via in-depth interviews in Florida. Qualitative analyses utilized health literacy domains (obtain/process/understand/communicate) as a conceptual framework. Participants described how they (1) obtained information about getting a Pap test, (2) processed positive and negative reactions following results, (3) understood results and recommended health-promoting behaviors, and (4) communicated and received social support. Women had disparate reactions and understanding following an abnormal Pap result. Health literacy was a meaningful conceptual framework to understand assets and gaps among women receiving an abnormal Pap test result. Future interventions should incorporate health literacy domains and facilitate patient-provider communications and social support to assist women in decision-making and health-promoting behaviors, ultimately decreasing cancer disparities.

Abnormal behavior and associated risk factors in captive baboons (Papio hamadryas spp.).

PubMed

Lutz, Corrine K; Williams, Priscilla C; Sharp, R Mark

2014-04-01

Abnormal behavior, ranging from motor stereotypies to self-injurious behavior, has been documented in captive nonhuman primates, with risk factors including nursery rearing, single housing, and veterinary procedures. Much of this research has focused on macaque monkeys; less is known about the extent of and risk factors for abnormal behavior in baboons. Because abnormal behavior can be indicative of poor welfare, either past or present, the purpose of this study was to survey the presence of abnormal behavior in captive baboons and to identify potential risk factors for these behaviors with an aim of prevention. Subjects were 144 baboons (119 females, 25 males) aged 3-29 (median = 9.18) years temporarily singly housed for research or clinical reasons. A 15-min focal observation was conducted on each subject using the Noldus Observer® program. Abnormal behavior was observed in 26% of the subjects, with motor stereotypy (e.g., pace, rock, swing) being the most common. Motor stereotypy was negatively associated with age when first singly housed (P < 0.005) while self-directed behavior (e.g., hair pull, self-bite) was positively associated with the lifetime number of days singly housed (P < 0.05) and the average number of blood draws per year (P < 0.05). In addition, abnormal appetitive behavior was associated with being male (P < 0.05). Although the baboons in this study exhibited relatively low levels of abnormal behavior, the risk factors for these behaviors (e.g., social restriction, routine veterinary procedures, and sex) appear to remain consistent across primate species. © 2013 Wiley Periodicals, Inc.

Autism Spectrum Disorder as Early Neurodevelopmental Disorder: Evidence from the Brain Imaging Abnormalities in 2-3 Years Old Toddlers

ERIC Educational Resources Information Center

Xiao, Zhou; Qiu, Ting; Ke, Xiaoyan; Xiao, Xiang; Xiao, Ting; Liang, Fengjing; Zou, Bing; Huang, Haiqing; Fang, Hui; Chu, Kangkang; Zhang, Jiuping; Liu, Yijun

2014-01-01

Autism spectrum disorder (ASD) is a complex neurodevelopmental condition that occurs within the first 3 years of life, which is marked by social skills and communication deficits along with stereotyped repetitive behavior. Although great efforts have been made to clarify the underlying neuroanatomical abnormalities and brain-behavior relationships…

Multiple autism-like behaviors in a novel transgenic mouse model

PubMed Central

Hamilton, Shannon M.; Spencer, Corinne M.; Harrison, Wilbur R.; Yuva-Paylor, Lisa A.; Graham, Deanna F.; Daza, Ray A.M.; Hevner, Robert F.; Overbeek, Paul A.; Paylor, Richard

2011-01-01

Autism spectrum disorder (ASD) diagnoses are behaviorally-based with no defined universal biomarkers, occur at a 1:110 ratio in the population, and predominantly affect males compared to females at approximately a 4:1 ratio. One approach to investigate and identify causes of ASD is to use organisms that display abnormal behavioral responses that model ASD-related impairments. This study describes a novel transgenic mouse, MALTT, which was generated using a forward genetics approach. It was determined that the transgene integrated within a noncoding region on the X chromosome. The MALTT line exhibited a complete repertoire of ASD-like behavioral deficits in all three domains required for an ASD diagnosis: reciprocal social interaction, communication, and repetitive or inflexible behaviors. Specifically, MALTT male mice showed deficits in social interaction and interest, abnormalities in pup and juvenile ultrasonic vocalization communications, and exhibited a repetitive stereotypy. Abnormalities were also observed in the domain of sensory function, a secondary phenotype prevalently associated with ASD. Mapping and expression studies suggested that the Fam46 gene family may be linked to the observed ASD-related behaviors. The MALTT line provides a unique genetic model for examining the underlying biological mechanisms involved in ASD-related behaviors. PMID:21093492

Reduced expression of the NMDA receptor-interacting protein SynGAP causes behavioral abnormalities that model symptoms of Schizophrenia.

PubMed

Guo, Xiaochuan; Hamilton, Peter J; Reish, Nicholas J; Sweatt, J David; Miller, Courtney A; Rumbaugh, Gavin

2009-06-01

Abnormal function of NMDA receptors is believed to be a contributing factor to the pathophysiology of schizophrenia. NMDAR subunits and postsynaptic-interacting proteins of these channels are abnormally expressed in some patients with this illness. In mice, reduced NMDAR expression leads to behaviors analogous to symptoms of schizophrenia, but reports of animals with mutations in core postsynaptic density proteins having similar a phenotype have yet to be reported. Here we show that reduced expression of the neuronal RasGAP and NMDAR-associated protein, SynGAP, results in abnormal behaviors strikingly similar to that reported in mice with reduced NMDAR function. SynGAP mutant mice exhibited nonhabituating and persistent hyperactivity that was ameliorated by the antipsychotic clozapine. An NMDAR antagonist, MK-801, induced hyperactivity in normal mice but SynGAP mutants were less responsive, suggesting that NMDAR hypofunction contributes to this behavioral abnormality. SynGAP mutants exhibited enhanced startle reactivity and impaired sensory-motor gating. These mice also displayed a complete lack of social memory and a propensity toward social isolation. Finally, SynGAP mutants had deficits in cued fear conditioning and working memory, indicating abnormal function of circuits that control emotion and choice. Our results demonstrate that SynGAP mutant mice have gross neurological deficits similar to other mouse models of schizophrenia. Because SynGAP interacts with NMDARs, and the signaling activity of this protein is regulated by these channels, our data in dicate that SynGAP lies downstream of NMDARs and is a required intermediate for normal neural circuit function and behavior. Taken together, these data support the idea that schizophrenia may arise from abnormal signaling pathways that are mediated by NMDA receptors.

Unusual social behavior in HPC-1/syntaxin1A knockout mice is caused by disruption of the oxytocinergic neural system.

PubMed

Fujiwara, Tomonori; Sanada, Masumi; Kofuji, Takefumi; Akagawa, Kimio

2016-07-01

HPC-1/syntaxin1A (STX1A), a neuronal soluble N-ethylmaleimide-sensitive fusion attachment protein receptor, contributes to neural function in the CNS by regulating transmitter release. Recent studies reported that STX1A is associated with human neuropsychological disorders, such as autism spectrum disorder and attention deficit hyperactivity disorder. Previously, we showed that STX1A null mutant mice (STX1A KO) exhibit neuropsychological abnormalities, such as fear memory deficits, attenuation of latent inhibition, and unusual social behavior. These observations suggested that STX1A may be involved in the neuropsychological basis of these abnormalities. Here, to study the neural basis of social behavior, we analyzed the profile of unusual social behavior in STX1A KO with a social novelty preference test, which is a useful method for quantification of social behavior. Interestingly, the unusual social behavior in STX1A KO was partially rescued by intracerebroventricular administration of oxytocin (OXT). In vivo microdialysis studies revealed that the extracellular OXT concentration in the CNS of STX1A KO was significantly lower compared with wild-type mice. Furthermore, dopamine-induced OXT release was reduced in STX1A KO. These results suggested that STX1A plays an important role in social behavior through regulation of the OXTergic neural system. Dopamine (DA) release is reduced in CNS of syntaxin1A null mutant mice (STX1A KO). Unusual social behavior was observed in STX1A KO. We found that oxytocin (OXT) release, which was stimulated by DA, was reduced and was rescued the unusual social behavior in STX1A KO was rescued by OXT. These results indicated that STX1A plays an important role in promoting social behavior through regulation of DA-induced OXT release in amygdala. © 2016 International Society for Neurochemistry.

Neural correlates of genetically abnormal social cognition in Williams syndrome.

PubMed

Meyer-Lindenberg, Andreas; Hariri, Ahmad R; Munoz, Karen E; Mervis, Carolyn B; Mattay, Venkata S; Morris, Colleen A; Berman, Karen Faith

2005-08-01

Williams-Beuren syndrome (WBS), caused by a microdeletion of approximately 21 genes on chromosome 7q11.23, is characterized by unique hypersociability combined with increased non-social anxiety. Using functional neuroimaging, we found reduced amygdala activation in individuals with WBS for threatening faces but increased activation for threatening scenes, relative to matched normal controls. Activation and interactions of prefrontal regions linked to amygdala, especially orbitofrontal cortex, were abnormal, suggesting a genetically controlled neural circuitry for regulating human social behavior.

Comprehensive Behavioral Analysis of Activating Transcription Factor 5-Deficient Mice

PubMed Central

Umemura, Mariko; Ogura, Tae; Matsuzaki, Ayako; Nakano, Haruo; Takao, Keizo; Miyakawa, Tsuyoshi; Takahashi, Yuji

2017-01-01

Activating transcription factor 5 (ATF5) is a member of the CREB/ATF family of basic leucine zipper transcription factors. We previously reported that ATF5-deficient (ATF5-/-) mice demonstrated abnormal olfactory bulb development due to impaired interneuron supply. Furthermore, ATF5-/- mice were less aggressive than ATF5+/+ mice. Although ATF5 is widely expressed in the brain, and involved in the regulation of proliferation and development of neurons, the physiological role of ATF5 in the higher brain remains unknown. Our objective was to investigate the physiological role of ATF5 in the higher brain. We performed a comprehensive behavioral analysis using ATF5-/- mice and wild type littermates. ATF5-/- mice exhibited abnormal locomotor activity in the open field test. They also exhibited abnormal anxiety-like behavior in the light/dark transition test and open field test. Furthermore, ATF5-/- mice displayed reduced social interaction in the Crawley’s social interaction test and increased pain sensitivity in the hot plate test compared with wild type. Finally, behavioral flexibility was reduced in the T-maze test in ATF5-/- mice compared with wild type. In addition, we demonstrated that ATF5-/- mice display disturbances of monoamine neurotransmitter levels in several brain regions. These results indicate that ATF5 deficiency elicits abnormal behaviors and the disturbance of monoamine neurotransmitter levels in the brain. The behavioral abnormalities of ATF5-/- mice may be due to the disturbance of monoamine levels. Taken together, these findings suggest that ATF5-/- mice may be a unique animal model of some psychiatric disorders. PMID:28744205

Psychosocial correlates, outcome, and stability of abnormal adolescent eating behavior in community samples of young people.

PubMed

Steinhausen, Hans-Christoph; Gavez, Silvia; Winkler Metzke, Christa

2005-03-01

The current study investigated psychosocial correlates of abnormal adolescent eating behavior at three times during adolescence and young adulthood and its association with psychiatric diagnosis in young adulthood in a community sample. Sixty-four (10.5%) high-risk subjects (mean age 15 years) with abnormal eating behavior were identified at Time 1, another 252 (16.9%) were identified at Time 2 (mean age 16.2 years), and 164 (16.9%) were identified at Time 3 (mean age 19.7 years) and compared with three control groups matched for age and gender. Dependent measures included emotional and behavioral problems, life events, coping capacities, self-related cognition, social network, and family functions. Outcome was measured additionally by structured psychiatric interviews, and stability of abnormal eating behavior was studied in a longitudinal sample of 330 subjects. Few subjects showed more than one of five criteria of abnormal eating behavior. High-risk subjects shared a very similar pattern at all three times. They were characterized by higher scores for emotional and behavioral problems, more life events including more negative impact, less active coping, lower self-esteem, and less family cohesion. Among 10 major psychiatric disorders, only clinical eating disorders at Time 3 shared a significant association with abnormal eating disorder at the same time whereas high-risk status at Times 1 and 2 did not predict any psychiatric disorder at Time 3. Stability of abnormal eating behavior across time was very low. Stability of abnormal eating behavior across time was very low. Abnormal eating behavior in adolescence and young adulthood is clearly associated with various indicators of psychosocial maladaption. In adolescence, it does not significantly predict any psychiatric disorder including eating disorder in young adulthood and it is predominantly a transient feature. (c) 2005 by Wiley Periodicals, Inc.

Characterization of the of the Pathological and Biochemical Markers That Correlate to the Clinical Features of Autism. Subproject 2. Contribution of Significant Delay of Neuronal Development and Metabolic Shift of Neurons to Clinical Phenotype of Autism

DTIC Science & Technology

2013-04-01

skills, (e) problems with generalization of previously acquired skills, (f) rigidity and resistance to change, (g) social and communication ...their known role in social behavior, communication , and stereotypic behavior results in identification of a structural component of functional deficits...neurons. These abnormalities may contribute to social and communication deficits, and restricted repetitive and stereotyped patterns of behavior. 3

Economic games quantify diminished sense of guilt in patients with damage to the prefrontal cortex

PubMed Central

Krajbich, Ian; Adolphs, Ralph; Tranel, Daniel; Denburg, Natalie L.; Camerer, Colin F.

2009-01-01

Damage to the ventromedial prefrontal cortex (VMPFC) impairs concern for other people, as reflected in the dysfunctional real-life social behavior of patients with such damage, as well as their abnormal performances on tasks ranging from moral judgment to economic games. Despite these convergent data, we lack a formal model of how, and to what degree, VMPFC lesions affect an individual’s social decision-making. Here we provide a quantification of these effects using a formal economic model of choice that incorporates terms for the disutility of unequal payoffs, with parameters that index behaviors normally evoked by guilt and envy. Six patients with focal VMPFC lesions participated in a battery of economic games that measured concern about payoffs to themselves and to others: dictator, ultimatum, and trust games. We analyzed each task individually, but also derived estimates of the guilt and envy parameters from aggregate behavior across all of the tasks. Compared to control subjects, the patients donated significantly less and were less trustworthy, and overall our model found a significant insensitivity to guilt. Despite these abnormalities, the patients had normal expectations about what other people would do, and they also did not simply generate behavior that was more noisy. Instead, the findings argue for a specific insensitivity to guilt, an abnormality that we suggest characterizes a key contribution made by the VMPFC to social behavior. PMID:19228971

Economic games quantify diminished sense of guilt in patients with damage to the prefrontal cortex.

PubMed

Krajbich, Ian; Adolphs, Ralph; Tranel, Daniel; Denburg, Natalie L; Camerer, Colin F

2009-02-18

Damage to the ventromedial prefrontal cortex (VMPFC) impairs concern for other people, as reflected in the dysfunctional real-life social behavior of patients with such damage, as well as their abnormal performances on tasks ranging from moral judgment to economic games. Despite these convergent data, we lack a formal model of how, and to what degree, VMPFC lesions affect an individual's social decision-making. Here we provide a quantification of these effects using a formal economic model of choice that incorporates terms for the disutility of unequal payoffs, with parameters that index behaviors normally evoked by guilt and envy. Six patients with focal VMPFC lesions participated in a battery of economic games that measured concern about payoffs to themselves and to others: dictator, ultimatum, and trust games. We analyzed each task individually, but also derived estimates of the guilt and envy parameters from aggregate behavior across all of the tasks. Compared with control subjects, the patients donated significantly less and were less trustworthy, and overall our model found a significant insensitivity to guilt. Despite these abnormalities, the patients had normal expectations about what other people would do, and they also did not simply generate behavior that was more noisy. Instead, the findings argue for a specific insensitivity to guilt, an abnormality that we suggest characterizes a key contribution made by the VMPFC to social behavior.

Striatal Circuits as a Common Node for Autism Pathophysiology

PubMed Central

Fuccillo, Marc V.

2016-01-01

Autism spectrum disorders (ASD) are characterized by two seemingly unrelated symptom domains—deficits in social interactions and restrictive, repetitive patterns of behavioral output. Whether the diverse nature of ASD symptomatology represents distributed dysfunction of brain networks or abnormalities within specific neural circuits is unclear. Striatal dysfunction is postulated to underlie the repetitive motor behaviors seen in ASD, and neurological and brain-imaging studies have supported this assumption. However, as our appreciation of striatal function expands to include regulation of behavioral flexibility, motivational state, goal-directed learning, and attention, we consider whether alterations in striatal physiology are a central node mediating a range of autism-associated behaviors, including social and cognitive deficits that are hallmarks of the disease. This review investigates multiple genetic mouse models of ASD to explore whether abnormalities in striatal circuits constitute a common pathophysiological mechanism in the development of autism-related behaviors. Despite the heterogeneity of genetic insult investigated, numerous genetic ASD models display alterations in the structure and function of striatal circuits, as well as abnormal behaviors including repetitive grooming, stereotypic motor routines, deficits in social interaction and decision-making. Comparative analysis in rodents provides a unique opportunity to leverage growing genetic association data to reveal canonical neural circuits whose dysfunction directly contributes to discrete aspects of ASD symptomatology. The description of such circuits could provide both organizing principles for understanding the complex genetic etiology of ASD as well as novel treatment routes. Furthermore, this focus on striatal mechanisms of behavioral regulation may also prove useful for exploring the pathogenesis of other neuropsychiatric diseases, which display overlapping behavioral deficits with ASD. PMID:26903795

Viewing Social Scenes: A Visual Scan-Path Study Comparing Fragile X Syndrome and Williams Syndrome

ERIC Educational Resources Information Center

Williams, Tracey A.; Porter, Melanie A.; Langdon, Robyn

2013-01-01

Fragile X syndrome (FXS) and Williams syndrome (WS) are both genetic disorders which present with similar cognitive-behavioral problems, but distinct social phenotypes. Despite these social differences both syndromes display poor social relations which may result from abnormal social processing. This study aimed to manipulate the location of…

Neurocognitive, Social-Behavioral, and Adaptive Functioning in Preschool Children with Mild to Moderate Kidney Disease

PubMed Central

Hooper, Stephen R.; Gerson, Arlene C.; Johnson, Rebecca J.; Mendley, Susan R.; Shinnar, Shlomo; Lande, Marc B.; Matheson, Matthew B.; Gipson, Debbie S.; Morgenstern, Bruce; Warady, Bradley A.; Furth, Susan L.

2016-01-01

Objective The negative impact of End Stage Kidney Disease on cognitive function in children is well established, but no studies have examined the neurocognitive, social-behavioral, and adaptive behavior skills of preschool children with mild to moderate chronic kidney disease (CKD). Methods Participants included 124 preschool children with mild to moderate CKD, ages 12-68 months (median=3.7 years), and an associated mean glomerular filtration rate (GFR) of 50.0 ml/min per 1.73m2. In addition to level of function and percent of participants scoring≥1SD below the test mean, regression models examined the associations between biomarkers of CKD (GFR, anemia, hypertension, seizures, abnormal birth history), and Developmental Level/IQ, attention regulation, and parent ratings of executive functions, social-behavior, and adaptive behaviors. Results Median scores for all measures were in the average range; however, 27% were deemed at-risk for a Developmental Level/IQ<85, 20% were at-risk for attention variability, and parent ratings indicated 30% and 37% to be at-risk for executive dysfunction and adaptive behavior problems, respectively. Approximately 43% were deemed at-risk on two or more measures. None of the disease-related variables were significantly associated with these outcomes, although the presence of hypertension approached significance for attention variability (p<.09). Abnormal birth history and lower maternal education were significantly related to lower Developmental Level/IQ; seizures were related to lower parental ratings of executive function and adaptive behavior; and abnormal birth history was significantly related to lower ratings of adaptive behavior. When predicting risk status, the logistic regression did evidence both higher GFR and the lack of anemia to be associated with more intact Developmental Level/IQ. Conclusions These findings suggest relatively intact functioning for preschool children with mild to moderate CKD, but the need for ongoing developmental surveillance in this population remains warranted, particularly for those with abnormal birth histories, seizures, and heightened disease severity. PMID:26890559

Impairment of social behavior and communication in mice lacking the Uba6-dependent ubiquitin activation system.

PubMed

Lee, Ji Yeon; Kwak, Minseok; Lee, Peter C W

2015-03-15

The Uba6-Use1 ubiquitin enzyme cascade is a poorly understood arm of the ubiquitin-proteasome system required for mouse development. Recently, we reported that Uba6 brain-specific knockout (termed NKO) mice display abnormal social behavior and neuronal development due to a decreased spine density and accumulation of Ube3a and Shank3. To better characterize a potential role for NKO mice in autism spectrum disorders (ASDs), we performed a comprehensive behavioral characterization of the social behavior and communication of NKO mice. Our behavioral results confirmed that NKO mice display social impairments, as indicated by fewer vocalizations and decreased social interaction. We conclude that UBA6 NKO mice represent a novel ASD mouse model of anti-social and less verbal behavioral symptoms. Copyright © 2014 Elsevier B.V. All rights reserved.

Absence of social conditioned place preference in BTBR T+tf/J mice: relevance for social motivation testing in rodent models of autism

PubMed Central

Pearson, Brandon L.; Bettis, Jaclyn K.; Meyza, Ksenia Z.; Yamamoto, Lace Y.; Blanchard, D. Caroline; Blanchard, Robert J.

2012-01-01

A major goal of translation research in autism is to characterize the physiological and psychological processes underlying behavioral abnormalities. Since autism reflects impairments in social motivation, we modified the mouse three-chamber social approach apparatus for use as a social conditioned place preference arena. We paired one of two unique contexts with social interactions in juvenile mice for five or ten conditioning sessions in BTBR T+tf/J mice and a control strain with normal approach behaviors (C57BL/6J) since the BTBR T+tf/J inbred mouse strain displays a variety of behavioral alterations analogous to symptoms of autism spectrum disorders. While C57BL/6J mice formed a conditioned place preference to the context associated with social interactions, particularly those receiving ten days of conditioning, BTBR T+tf/J mice did not. Neither absence of social proximity nor avoidance due to high rates of autogrooming appeared to underlie the impaired positive incentive value of the unconditioned social stimulus in the BTBR T+tf/J strain. These data contribute to a growing body of evidence suggesting that the BTBR T+tf/J strain shows impairments in all diagnostic domains of autism including social motivation. Additionally, social conditioning testing might provide an important social motivation measure in other rodent models of neuropsychiatric disorders characterized by social abnormalities. PMID:22562042

Shoaling develops with age in Zebrafish (Danio rerio)

PubMed Central

Buske, Christine; Gerlai, Robert

2010-01-01

The biological mechanisms of human social behavior are complex. Animal models may facilitate the understanding of these mechanisms and may help one to develop treatment strategies for abnormal human social behavior, a core symptom in numerous clinical conditions. The zebrafish is perhaps the most social vertebrate among commonly used laboratory species. Given its practical features and the numerous genetic tools developed for it, it should be a promising tool. Zebrafish shoal, i.e. form tight multimember groups, but the ontogenesis of this behavior has not been described. Analyzing the development of shoaling is a step towards discovering the mechanisms of this behavior. Here we study age-dependent changes of shoaling in zebrafish from day 7 post fertilization to over 5 months of age by measuring the distance between all pairs of fish in freely swimming groups of ten subjects. Our longitudinal (repeated measure within subject) and cross sectional (non-repeated measure between subject) analyses both demonstrated a significant increase of shoaling with age (decreased distance between shoal members). Given the sophisticated genetic and developmental biology methods already available for zebrafish, we argue that our behavioral results open a new avenue towards the understanding of the development of vertebrate social behavior and of its mechanisms and abnormalities. PMID:20837077

Social learning requires plasticity enhanced by fluoxetine through prefrontal Bdnf-TrkB signaling to limit aggression induced by post-weaning social isolation

PubMed Central

Umemori, Juzoh; Tóth, Máté; Biró, László; Miskolczi, Christina; Balázsfi, Diána; Zelena, Dóra; Castrén, Eero

2017-01-01

Escalated or abnormal aggression induced by early adverse experiences is a growing issue of social concern and urges the development of effective treatment strategies. Here we report that synergistic interactions between psychosocial and biological factors specifically ameliorate escalated aggression induced by early adverse experiences. Rats reared in isolation from weaning until early adulthood showed abnormal forms of aggression and social deficits that were temporarily ameliorated by re-socialization, but aggression again escalated in a novel environment. We demonstrate that when re-socialization was combined with the antidepressant fluoxetine, which has been shown to reactivate juvenile-like state of plasticity, escalated aggression was greatly attenuated, while neither treatment alone was effective. Early isolation induced a permanent, re-socialization resistant reduction in Bdnf expression in the amygdala and the infralimbic cortex. Only the combined treatment of fluoxetine and re-socialization was able to recover Bdnf expression via epigenetic regulation. Moreover, the behavior improvement after the combined treatment was dependent on TrkB activity. Combined treatment specifically strengthened the input from the ventral hippocampus to the mPFC suggesting that this pathway is an important mediator of the beneficial behavioral effects of the combined psychosocial and pharmacological treatment of abnormal aggression. Our findings suggest that synergy between pharmacological induction of plasticity and psychosocial rehabilitation could enhance the efficacy of therapies for pathological aggression. PMID:28685757

Epigenetic regulation of dorsal raphe GABA(B1a) associated with isolation-induced abnormal responses to social stimulation in mice.

PubMed

Araki, Ryota; Hiraki, Yosuke; Nishida, Shoji; Kuramoto, Nobuyuki; Matsumoto, Kinzo; Yabe, Takeshi

2016-02-01

In isolation-reared mice, social encounter stimulation induces locomotor hyperactivity and activation of the dorsal raphe nucleus (DRN), suggesting that dysregulation of dorsal raphe function may be involved in abnormal behaviors. In this study, we examined the involvement of dorsal raphe GABAergic dysregulation in the abnormal behaviors of isolation-reared mice. We also studied an epigenetic mechanism underlying abnormalities of the dorsal raphe GABAergic system. Both mRNA and protein levels of GABA(B1a), a GABA(B) receptor subunit, were increased in the DRN of isolation-reared mice, compared with these levels in group-reared mice. In contrast, mRNA levels for other GABAergic system-related genes (GABA(A) receptor α1, β2 and γ2 subunits, GABA(B) receptor 1b and 2 subunits, and glutamate decarboxylase 67 and 65) were unchanged. Intra-DRN microinjection of 0.06 nmol baclofen (a GABA(B) receptor agonist) exacerbated encounter-induced hyperactivity and aggressive behavior, while microinjection of 0.3 nmol phaclofen (a GABA(B) receptor antagonist) attenuated encounter-induced hyperactivity and aggressive behavior in isolation-reared mice. Furthermore, microinjection of 0.06 nmol baclofen elicited encounter-induced hyperactivity in group-reared mice. Neither baclofen nor phaclofen affected immobility time in the forced swim test and hyperactivity in a novel environment of isolation reared mice. Bisulfite sequence analyses revealed that the DNA methylation level of the CpG island around the transcription start site (TSS) of GABA(B1a) was decreased in the DRN of isolation-reared mice. Chromatin immunoprecipitation analysis showed that histone H3 was hyperacetylated around the TSS of GABA(B1a) in the DRN of isolation-reared mice. These findings indicate that an increase in dorsal raphe GABA(B1a) expression via epigenetic regulation is associated with abnormal responses to social stimulation such as encounter-induced hyperactivity and aggressive behavior in isolation-reared mice. Copyright © 2015 Elsevier Ltd. All rights reserved.

Mice with reduced NMDA receptor expression: more consistent with autism than schizophrenia?

PubMed

Gandal, M J; Anderson, R L; Billingslea, E N; Carlson, G C; Roberts, T P L; Siegel, S J

2012-08-01

Reduced NMDA-receptor (NMDAR) function has been implicated in the pathophysiology of neuropsychiatric disease, most strongly in schizophrenia but also recently in autism spectrum disorders (ASD). To determine the direct contribution of NMDAR dysfunction to disease phenotypes, a mouse model with constitutively reduced expression of the obligatory NR1 subunit has been developed and extensively investigated. Adult NR1(neo-/-) mice show multiple abnormal behaviors, including reduced social interactions, locomotor hyperactivity, self-injury, deficits in prepulse inhibition (PPI) and sensory hypersensitivity, among others. Whereas such phenotypes have largely been interpreted in the context of schizophrenia, these behavioral abnormalities are rather non-specific and are frequently present across models of diseases characterized by negative symptom domains. This study investigated auditory electrophysiological and behavioral paradigms relevant to autism, to determine whether NMDAR hypofunction may be more consistent with adult ASD-like phenotypes. Indeed, transgenic mice showed behavioral deficits relevant to all core ASD symptoms, including decreased social interactions, altered ultrasonic vocalizations and increased repetitive behaviors. NMDAR disruption recapitulated clinical endophenotypes including reduced PPI, auditory-evoked response N1 latency delay and reduced gamma synchrony. Auditory electrophysiological abnormalities more closely resembled those seen in clinical studies of autism than schizophrenia. These results suggest that NMDAR hypofunction may be associated with a continuum of neuropsychiatric diseases, including schizophrenia and autism. Neural synchrony abnormalities suggest an imbalance of glutamatergic and GABAergic coupling and may provide a target, along with behavioral phenotypes, for preclinical screening of novel therapeutics. © 2012 The Authors. Genes, Brain and Behavior © 2012 Blackwell Publishing Ltd and International Behavioural and Neural Genetics Society.

Autism, the superior temporal sulcus and social perception.

PubMed

Zilbovicius, Monica; Meresse, Isabelle; Chabane, Nadia; Brunelle, Francis; Samson, Yves; Boddaert, Nathalie

2006-07-01

The most common clinical sign of autism spectrum disorders (ASD) is social interaction impairment, which is associated with communication deficits and stereotyped behaviors. Based on recent brain-imaging results, our hypothesis is that abnormalities in the superior temporal sulcus (STS) are highly implicated in ASD. STS abnormalities are characterized by decreased gray matter concentration, rest hypoperfusion and abnormal activation during social tasks. STS anatomical and functional anomalies occurring during early brain development could constitute the first step in the cascade of neural dysfunction underlying ASD. We will focus this review on the STS, which has been highly implicated in social cognition. We will review recent data on the contribution of the STS to normal social cognition and review brain-imaging data implicating this area in ASD. This review is part of the INMED/TINS special issue "Nature and nurture in brain development and neurological disorders", based on presentations at the annual INMED/TINS symposium (http://inmednet.com/).

Theory of mind mediates the prospective relationship between abnormal social brain network morphology and chronic behavior problems after pediatric traumatic brain injury.

PubMed

Ryan, Nicholas P; Catroppa, Cathy; Beare, Richard; Silk, Timothy J; Crossley, Louise; Beauchamp, Miriam H; Yeates, Keith Owen; Anderson, Vicki A

2016-04-01

Childhood and adolescence coincide with rapid maturation and synaptic reorganization of distributed neural networks that underlie complex cognitive-affective behaviors. These regions, referred to collectively as the 'social brain network' (SBN) are commonly vulnerable to disruption from pediatric traumatic brain injury (TBI); however, the mechanisms that link morphological changes in the SBN to behavior problems in this population remain unclear. In 98 children and adolescents with mild to severe TBI, we acquired 3D T1-weighted MRIs at 2-8 weeks post-injury. For comparison, 33 typically developing controls of similar age, sex and education were scanned. All participants were assessed on measures of Theory of Mind (ToM) at 6 months post-injury and parents provided ratings of behavior problems at 24-months post-injury. Severe TBI was associated with volumetric reductions in the overall SBN package, as well as regional gray matter structural change in multiple component regions of the SBN. When compared with TD controls and children with milder injuries, the severe TBI group had significantly poorer ToM, which was associated with more frequent behavior problems and abnormal SBN morphology. Mediation analysis indicated that impaired theory of mind mediated the prospective relationship between abnormal SBN morphology and more frequent chronic behavior problems. Our findings suggest that sub-acute alterations in SBN morphology indirectly contribute to long-term behavior problems via their influence on ToM. Volumetric change in the SBN and its putative hub regions may represent useful imaging biomarkers for prediction of post-acute social cognitive impairment, which may in turn elevate risk for chronic behavior problems. © The Author (2016). Published by Oxford University Press. For Permissions, please email: journals.permissions@oup.com.

Theory of mind mediates the prospective relationship between abnormal social brain network morphology and chronic behavior problems after pediatric traumatic brain injury

PubMed Central

Ryan, Nicholas P.; Catroppa, Cathy; Beare, Richard; Silk, Timothy J.; Crossley, Louise; Beauchamp, Miriam H.; Yeates, Keith Owen; Anderson, Vicki A.

2016-01-01

Childhood and adolescence coincide with rapid maturation and synaptic reorganization of distributed neural networks that underlie complex cognitive-affective behaviors. These regions, referred to collectively as the ‘social brain network’ (SBN) are commonly vulnerable to disruption from pediatric traumatic brain injury (TBI); however, the mechanisms that link morphological changes in the SBN to behavior problems in this population remain unclear. In 98 children and adolescents with mild to severe TBI, we acquired 3D T1-weighted MRIs at 2–8 weeks post-injury. For comparison, 33 typically developing controls of similar age, sex and education were scanned. All participants were assessed on measures of Theory of Mind (ToM) at 6 months post-injury and parents provided ratings of behavior problems at 24-months post-injury. Severe TBI was associated with volumetric reductions in the overall SBN package, as well as regional gray matter structural change in multiple component regions of the SBN. When compared with TD controls and children with milder injuries, the severe TBI group had significantly poorer ToM, which was associated with more frequent behavior problems and abnormal SBN morphology. Mediation analysis indicated that impaired theory of mind mediated the prospective relationship between abnormal SBN morphology and more frequent chronic behavior problems. Our findings suggest that sub-acute alterations in SBN morphology indirectly contribute to long-term behavior problems via their influence on ToM. Volumetric change in the SBN and its putative hub regions may represent useful imaging biomarkers for prediction of post-acute social cognitive impairment, which may in turn elevate risk for chronic behavior problems. PMID:26796967

Progranulin haploinsufficiency causes biphasic social dominance abnormalities in the tube test.

PubMed

Arrant, A E; Filiano, A J; Warmus, B A; Hall, A M; Roberson, E D

2016-07-01

Loss-of-function mutations in progranulin (GRN) are a major autosomal dominant cause of frontotemporal dementia (FTD), a neurodegenerative disorder in which social behavior is disrupted. Progranulin-insufficient mice, both Grn(+/-) and Grn(-/-) , are used as models of FTD due to GRN mutations, with Grn(+/-) mice mimicking the progranulin haploinsufficiency of FTD patients with GRN mutations. Grn(+/-) mice have increased social dominance in the tube test at 6 months of age, although this phenotype has not been reported in Grn(-/-) mice. In this study, we investigated how the tube test phenotype of progranulin-insufficient mice changes with age, determined its robustness under several testing conditions, and explored the associated cellular mechanisms. We observed biphasic social dominance abnormalities in Grn(+/-) mice: at 6-8 months, Grn(+/-) mice were more dominant than wild-type littermates, while after 9 months of age, Grn(+/-) mice were less dominant. In contrast, Grn(-/-) mice did not exhibit abnormal social dominance, suggesting that progranulin haploinsufficiency has distinct effects from complete progranulin deficiency. The biphasic tube test phenotype of Grn(+/-) mice was associated with abnormal cellular signaling and neuronal morphology in the amygdala and prefrontal cortex. At 6-9 months, Grn(+/-) mice exhibited increased mTORC2/Akt signaling in the amygdala and enhanced dendritic arbors in the basomedial amygdala, and at 9-16 months Grn(+/-) mice exhibited diminished basal dendritic arbors in the prelimbic cortex. These data show a progressive change in tube test dominance in Grn(+/-) mice and highlight potential underlying mechanisms by which progranulin insufficiency may disrupt social behavior. © 2016 John Wiley & Sons Ltd and International Behavioural and Neural Genetics Society.

The Development of Face Processing in Autism

ERIC Educational Resources Information Center

Sasson, Noah J.

2006-01-01

Both behavioral and neuroimaging evidence indicate that individuals with autism demonstrate marked abnormalities in the processing of faces. These abnormalities are often explained as either the result of an innate impairment to specialized neural systems or as a secondary consequence of reduced levels of social interest. A review of the…

Sociability Deficits and Altered Amygdala Circuits in Mice Lacking Pcdh10, an Autism Associated Gene.

PubMed

Schoch, Hannah; Kreibich, Arati S; Ferri, Sarah L; White, Rachel S; Bohorquez, Dominique; Banerjee, Anamika; Port, Russell G; Dow, Holly C; Cordero, Lucero; Pallathra, Ashley A; Kim, Hyong; Li, Hongzhe; Bilker, Warren B; Hirano, Shinji; Schultz, Robert T; Borgmann-Winter, Karin; Hahn, Chang-Gyu; Feldmeyer, Dirk; Carlson, Gregory C; Abel, Ted; Brodkin, Edward S

2017-02-01

Behavioral symptoms in individuals with autism spectrum disorder (ASD) have been attributed to abnormal neuronal connectivity, but the molecular bases of these behavioral and brain phenotypes are largely unknown. Human genetic studies have implicated PCDH10, a member of the δ2 subfamily of nonclustered protocadherin genes, in ASD. PCDH10 expression is enriched in the basolateral amygdala, a brain region implicated in the social deficits of ASD. Previous reports indicate that Pcdh10 plays a role in axon outgrowth and glutamatergic synapse elimination, but its roles in social behaviors and amygdala neuronal connectivity are unknown. We hypothesized that haploinsufficiency of Pcdh10 would reduce social approach behavior and alter the structure and function of amygdala circuits. Mice lacking one copy of Pcdh10 (Pcdh10 +/- ) and wild-type littermates were assessed for social approach and other behaviors. The lateral/basolateral amygdala was assessed for dendritic spine number and morphology, and amygdala circuit function was studied using voltage-sensitive dye imaging. Expression of Pcdh10 and N-methyl-D-aspartate receptor (NMDAR) subunits was assessed in postsynaptic density fractions of the amygdala. Male Pcdh10 +/- mice have reduced social approach behavior, as well as impaired gamma synchronization, abnormal spine morphology, and reduced levels of NMDAR subunits in the amygdala. Social approach deficits in Pcdh10 +/- male mice were rescued with acute treatment with the NMDAR partial agonist d-cycloserine. Our studies reveal that male Pcdh10 +/- mice have synaptic and behavioral deficits, and establish Pcdh10 +/- mice as a novel genetic model for investigating neural circuitry and behavioral changes relevant to ASD. Copyright © 2016 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

The Non-Peptide Vasopressin V1b Receptor Antagonist, SSR149415, Ameliorates Spermatogenesis Function in a Mouse Model of Chronic Social Defeat Stress.

PubMed

Wang, Bin; Zhou, Jian; Zhuang, Yan-Yan; Wang, Liang-Liang; Pu, Jin-Xian; Huang, Yu-Hua; Xia, Fei; Lv, Jin-Xing

2017-11-01

To determine the effects of SSR149415 on testis and spermatogenesis in male mice subjected to chronic social defeat stress, C57BL/6 male mice were divided into two groups: Control and Stress. Then Stress group was subdivided into four subgroups administered water, SSR149415 (1 mg/kg/day), SSR149415 (10 mg/kg/day), SSR149415 (30 mg/kg/day), respectively. The behavioral alterations revealed by social interaction test and open field test were measured. The physical indices, including body weight and gonad weight (testis and epididymis) as well as testis/body weight and cauda epididymis/body weight were detected. Serum hormones, including testosterone, luteinizing hormone (LH), and follicle-stimulating hormone (FSH) were determined. Sperm count and abnormality as well as testicular histology structure were assessed. The germ cells apoptosis were also evaluated. Chronic social defeat stress-induced behavioral abnormality, as well as gonad atrophy (testis and epididymis) was significantly alleviated in stressed male mice exposed to SSR149415. Regressed serum testosterone levels and elevated serum FSH and LH levels exhibited by stressed male mice were observably reversed following SSR149415 administration. Chronic social defeat stress-induced damage in testicular histology structure and semen quality were also improved after SSR149415 administration. In addition, SSR149415 significantly reversed chronic social defeat stress-induced germ cells apoptosis. Overall, we provide clear evidence indicating the amelioration of chronic social defeat stress-induced behavioral abnormality and testicular dysfunction via SSR149415, promoting the development of drug-directed therapy against this disease. J. Cell. Biochem. 118: 3891-3898, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

Trust and Deception in Children with Autism Spectrum Disorders: A Social Learning Perspective.

PubMed

Yang, Yiying; Tian, Yuan; Fang, Jing; Lu, Haoyang; Wei, Kunlin; Yi, Li

2017-03-01

Previous research has demonstrated abnormal trust and deception behaviors in children with Autism Spectrum Disorders (ASD), and we aimed to examine whether these abnormalities were primarily due to their specific deficits in social learning. We tested 42 high-functioning children with ASD and 38 age- and ability-matched typically developing (TD) children in trust and deception tasks and a novel condition with reduced social components. Results indicated that while TD children improved their performance with more social components, children with ASD lacked this additional performance gain, though they performed similarly as TD children in the condition with reduced social components. Our findings highlight that deficits of ASD in trust and deception are primarily associated with failure of use of social cues.

Sociopathic behavior and dementia.

PubMed

Cipriani, Gabriele; Borin, Gemma; Vedovello, Marcella; Di Fiorino, Andrea; Nuti, Angelo

2013-06-01

The maintenance of appropriate social behavior is a very complex process with many contributing factors. Social and moral judgments rely on the proper functioning of neural circuits concerned with complex cognitive and emotional processes. Damage to these systems may lead to distinct social behavior abnormalities. When patients present with dysmoral behavior for the first time, as a change from a prior pervasive pattern of behavior, clinicians need to consider a possible, causative brain disorder. The aim is to explore sociopathy as a manifestation of dementia. We searched electronic databases and key journals for original research and review articles on sociopathy in demented patients using the search terms "sociopathy, acquired sociopathy, sociopathic behavior, dementia, and personality". In conclusion, dementia onset may be heralded by changes in personality including alteration in social interpersonal behavior, personal regulation, and empathy. The sociopathy of dementia differs from antisocial/psychopathic personality disorders.

Autism, oxytocin and interoception

PubMed Central

Quattrocki, E.; Friston, Karl

2014-01-01

Autism is a pervasive developmental disorder characterized by profound social and verbal communication deficits, stereotypical motor behaviors, restricted interests, and cognitive abnormalities. Autism affects approximately 1% of children in developing countries. Given this prevalence, identifying risk factors and therapeutic interventions are pressing objectives—objectives that rest on neurobiologically grounded and psychologically informed theories about the underlying pathophysiology. In this article, we review the evidence that autism could result from a dysfunctional oxytocin system early in life. As a mediator of successful procreation, not only in the reproductive system, but also in the brain, oxytocin plays a crucial role in sculpting socio-sexual behavior. Formulated within a (Bayesian) predictive coding framework, we propose that oxytocin encodes the saliency or precision of interoceptive signals and enables the neuronal plasticity necessary for acquiring a generative model of the emotional and social ‘self.’ An aberrant oxytocin system in infancy could therefore help explain the marked deficits in language and social communication – as well as the sensory, autonomic, motor, behavioral, and cognitive abnormalities – seen in autism. PMID:25277283

Impaired Object Recognition but Normal Social Behavior and Ultrasonic Communication in Cofilin1 Mutant Mice

PubMed Central

Sungur, A. Özge; Stemmler, Lea; Wöhr, Markus; Rust, Marco B.

2018-01-01

Autism spectrum disorder (ASD), schizophrenia (SCZ) and intellectual disability (ID) show a remarkable overlap in symptoms, including impairments in cognition, social behavior and communication. Human genetic studies revealed an enrichment of mutations in actin-related genes for these disorders, and some of the strongest candidate genes control actin dynamics. These findings led to the hypotheses: (i) that ASD, SCZ and ID share common disease mechanisms; and (ii) that, at least in a subgroup of affected individuals, defects in the actin cytoskeleton cause or contribute to their pathologies. Cofilin1 emerged as a key regulator of actin dynamics and we previously demonstrated its critical role for synaptic plasticity and associative learning. Notably, recent studies revealed an over-activation of cofilin1 in mutant mice displaying ASD- or SCZ-like behavioral phenotypes, suggesting that dysregulated cofilin1-dependent actin dynamics contribute to their behavioral abnormalities, such as deficits in social behavior. These findings let us hypothesize: (i) that, apart from cognitive impairments, cofilin1 mutants display additional behavioral deficits with relevance to ASD or SCZ; and (ii) that our cofilin1 mutants represent a valuable tool to study the underlying disease mechanisms. To test our hypotheses, we compared social behavior and ultrasonic communication of juvenile mutants to control littermates, and we did not obtain evidence for impaired direct reciprocal social interaction, social approach or social memory. Moreover, concomitant emission of ultrasonic vocalizations was not affected and time-locked to social activity, supporting the notion that ultrasonic vocalizations serve a pro-social communicative function as social contact calls maintaining social proximity. Finally, cofilin1 mutants did not display abnormal repetitive behaviors. Instead, they performed weaker in novel object recognition, thereby demonstrating that cofilin1 is relevant not only for associative learning, but also for “non-matching-to-sample” learning. Here we report the absence of an ASD- or a SCZ-like phenotype in cofilin1 mutants, and we conclude that cofilin1 is relevant specifically for non-social cognition. PMID:29515378

Abnormal Neural Activation to Faces in the Parents of Children with Autism

PubMed Central

Yucel, G. H.; Belger, A.; Bizzell, J.; Parlier, M.; Adolphs, R.; Piven, J.

2015-01-01

Parents of children with an autism spectrum disorder (ASD) show subtle deficits in aspects of social behavior and face processing, which resemble those seen in ASD, referred to as the “Broad Autism Phenotype ” (BAP). While abnormal activation in ASD has been reported in several brain structures linked to social cognition, little is known regarding patterns in the BAP. We compared autism parents with control parents with no family history of ASD using 2 well-validated face-processing tasks. Results indicated increased activation in the autism parents to faces in the amygdala (AMY) and the fusiform gyrus (FG), 2 core face-processing regions. Exploratory analyses revealed hyper-activation of lateral occipital cortex (LOC) bilaterally in autism parents with aloof personality (“BAP+”). Findings suggest that abnormalities of the AMY and FG are related to underlying genetic liability for ASD, whereas abnormalities in the LOC and right FG are more specific to behavioral features of the BAP. Results extend our knowledge of neural circuitry underlying abnormal face processing beyond those previously reported in ASD to individuals with shared genetic liability for autism and a subset of genetically related individuals with the BAP. PMID:25056573

Nutrition and behavior of lemurs.

PubMed

Junge, Randall E; Williams, Cathy V; Campbell, Jennifer

2009-05-01

Attention to nutritional and behavioral factors is important for appropriate care of lemurs in captivity. Although only a few species are commonly held in captivity, differences between them are important. Knowledge of feeding ecology and natural diet guide nutrition guidelines, as well as management and prevention of common nutrition-related disorders, including obesity, diabetes, and iron-storage disease. Behavioral characteristics that influence captive management are related to social organization, reproductive behavior, territoriality, and infant care. Housing animals in appropriate social groupings in adequately complex environments reduces abnormal behaviors, and addition of enrichment activities and operant conditioning encourages normal behaviors.

Genetic Removal of Matrix Metalloproteinase 9 Rescues the Symptoms of Fragile X Syndrome in a Mouse Model

PubMed Central

Sidhu, Harpreet; Dansie, Lorraine E.; Hickmott, Peter W.

2014-01-01

Fmr1 knock-out (ko) mice display key features of fragile X syndrome (FXS), including delayed dendritic spine maturation and FXS-associated behaviors, such as poor socialization, obsessive-compulsive behavior, and hyperactivity. Here we provide conclusive evidence that matrix metalloproteinase-9 (MMP-9) is necessary to the development of FXS-associated defects in Fmr1 ko mice. Genetic disruption of Mmp-9 rescued key aspects of Fmr1 deficiency, including dendritic spine abnormalities, abnormal mGluR5-dependent LTD, as well as aberrant behaviors in open field and social novelty tests. Remarkably, MMP-9 deficiency also corrected non-neural features of Fmr1 deficiency—specifically macroorchidism—indicating that MMP-9 dysregulation contributes to FXS-associated abnormalities outside the CNS. Further, MMP-9 deficiency suppressed elevations of Akt, mammalian target of rapamycin, and eukaryotic translation initiation factor 4E phosphorylation seen in Fmr1 ko mice, which are also associated with other autistic spectrum disorders. These findings establish that MMP-9 is critical to the mechanisms responsible for neural and non-neural aspects of the FXS phenotype. PMID:25057190

Abnormal Social Reward Responses in Anorexia Nervosa: An fMRI Study.

PubMed

Via, Esther; Soriano-Mas, Carles; Sánchez, Isabel; Forcano, Laura; Harrison, Ben J; Davey, Christopher G; Pujol, Jesús; Martínez-Zalacaín, Ignacio; Menchón, José M; Fernández-Aranda, Fernando; Cardoner, Narcís

2015-01-01

Patients with anorexia nervosa (AN) display impaired social interactions, implicated in the development and prognosis of the disorder. Importantly, social behavior is modulated by reward-based processes, and dysfunctional at-brain-level reward responses have been involved in AN neurobiological models. However, no prior evidence exists of whether these neural alterations would be equally present in social contexts. In this study, we conducted a cross-sectional social-judgment functional magnetic resonance imaging (fMRI) study of 20 restrictive-subtype AN patients and 20 matched healthy controls. Brain activity during acceptance and rejection was investigated and correlated with severity measures (Eating Disorder Inventory -EDI-2) and with personality traits of interest known to modulate social behavior (The Sensitivity to Punishment and Sensitivity to Reward Questionnaire). Patients showed hypoactivation of the dorsomedial prefrontal cortex (DMPFC) during social acceptance and hyperactivation of visual areas during social rejection. Ventral striatum activation during rejection was positively correlated in patients with clinical severity scores. During acceptance, activation of the frontal opercula-anterior insula and dorsomedial/dorsolateral prefrontal cortices was differentially associated with reward sensitivity between groups. These results suggest an abnormal motivational drive for social stimuli, and involve overlapping social cognition and reward systems leading to a disruption of adaptive responses in the processing of social reward. The specific association of reward-related regions with clinical and psychometric measures suggests the putative involvement of reward structures in the maintenance of pathological behaviors in AN.

Three-Week Isolation Does Not Lead to Depressive-Like Disorders in Rats.

PubMed

Gorlova, A V; Pavlov, D A; Zubkov, E A; Morozova, A Yu; Inozemtsev, A N; Chekhonin, V P

2018-06-19

We studied the effects of social isolation for 1, 2 or 3 weeks on behavioral reactions of male rats. As social isolation is a common model for inducing depressive-like state in rodents, classical tests for depressive-like behavioral features were conducted: Porsolt forced swimming test and tests for anhedonia and social interest. None of the experimental groups showed statistically significant disorders in comparison with the control group kept under standard conditions. Thus, social isolation for up to 3 weeks did not cause behavioral abnormalities in male rats. Single housing can be used in other models of induction of depressive-like states, but the use of this paradigm as an independent model for the development of depressive-like behavior requires longer period of social isolation.

Aversive disinhibition of behavior and striatal signaling in social avoidance.

PubMed

Ly, Verena; Cools, Roshan; Roelofs, Karin

2014-10-01

Social avoidance is a major factor contributing to the development and maintenance of anxiety and depressive symptoms. Converging evidence suggests that social avoidance is associated with abnormal aversive processing and hyperactive amygdala signaling. However, what are the consequences of such abnormal aversive processing for action and for the neural mechanisms implementing action is unclear. Existing literature is conflicting, pointing at either enhanced or reduced action inhibition. We investigated the interaction between aversion and action in social avoidance by comparing the effects of aversive vs appetitive faces on a go/no-go task and associated striatal signals in 42 high and low socially avoidant individuals. We combined fMRI with a novel probabilistic learning task, in which emotional valence (angry and happy faces) and optimal response (go- and no-go-responses) were manipulated independently. High compared with low socially avoidant individuals showed reduced behavioral inhibition (proportion no-go-responses) for angry relative to happy faces. This behavioral disinhibition correlated with greater striatal signal during no-go-responses for angry relative to happy faces. The results suggest that social avoidant coping style is accompanied by disinhibition of action and striatal signal in the context of social threat. The findings concur with recent theorizing about aversive disinhibition and affective disorders. © The Author (2013). Published by Oxford University Press. For Permissions, please email: journals.permissions@oup.com.

Developmental social isolation affects adult behavior, social interaction, and dopamine metabolite levels in zebrafish.

PubMed

Shams, Soaleha; Amlani, Shahid; Buske, Christine; Chatterjee, Diptendu; Gerlai, Robert

2018-01-01

The zebrafish is a social vertebrate and an excellent translational model for a variety of human disorders. Abnormal social behavior is a hallmark of several human brain disorders. Social behavioral problems can arise as a result of adverse early social environment. Little is known about the effects of early social isolation in adult zebrafish. We compared zebrafish that were isolated for either short (7 days) or long duration (180 days) to socially housed zebrafish, testing their behavior across ontogenesis (ages 10, 30, 60, 90, 120, 180 days), and shoal cohesion and whole-brain monoamines and their metabolites in adulthood. Long social isolation increased locomotion and decreased shoal cohesion and anxiety in the open-field in adult. Additionally, both short and long social isolation reduced dopamine metabolite levels in response to social stimuli. Thus, early social isolation has lasting effects in zebrafish, and may be employed to generate zebrafish models of human neuropsychiatric conditions. © 2017 Wiley Periodicals, Inc.

Touch Processing and Social Behavior in ASD

ERIC Educational Resources Information Center

Miguel, Helga O.; Sampaio, Adriana; Martínez-Regueiro, Rocío; Gómez-Guerrero, Lorena; López-Dóriga, Cristina Gutiérrez; Gómez, Sonia; Carracedo, Ángel; Fernández-Prieto, Montse

2017-01-01

Abnormal patterns of touch processing have been linked to core symptoms in ASD. This study examined the relation between tactile processing patterns and social problems in 44 children and adolescents with ASD, aged 6-14 (M = 8.39 ± 2.35). Multiple linear regression indicated significant associations between touch processing and social problems. No…

Social isolation and chronic handling alter endocannabinoid signaling and behavioral reactivity to context in adult rats

PubMed Central

Sciolino, Natale R.; Bortolato, Marco; Eisenstein, Sarah A.; Fu, Jin; Oveisi, Fariba; Hohmann, Andrea G.; Piomelli, Daniele

2010-01-01

Social deprivation in early life disrupts emotionality and attentional processes in humans. Rearing rats in isolation reproduces some of these abnormalities, which are attenuated by daily handling. However, the neurochemical mechanisms underlying these responses remain poorly understood. We hypothesized that post-weaning social isolation alters the endocannabinoid system, a neuromodulatory system that controls emotional responding. We characterized behavioral consequences of social isolation and evaluated whether handling would reverse social isolation-induced alterations in behavioral reactivity to context and the endocannabinoid system. At weaning, pups were single or group housed and concomitantly handled or not handled daily until adulthood. Rats were tested in emotionality- and attentional-sensitive behavioral assays (open field, elevated plus maze, startle and prepulse inhibition). Cannabinoid receptor densities and endocannabinoid levels were quantified in a separate group of rats. Social isolation negatively altered behavioral responding. Socially-isolated rats that were handled showed less deficits in the open field, elevated plus maze, and prepulse inhibition tests. Social isolation produced site-specific alterations (supraoptic nucleus, ventrolateral thalamus, rostral striatum) in cannabinoid receptor densities compared to group rearing. Handling altered the endocannabinoid system in neural circuitry controlling emotional expression. Handling altered endocannabinoid content (prefrontal and piriform cortices, nucleus accumbens) and cannabinoid receptor densities (lateral globus pallidus, cingulate and piriform cortices, hippocampus) in a region-specific manner. Some effects of social isolation on the endocannabinoid system were moderated by handling. Isolates were unresponsive to handling-induced increases in cannabinoid receptor densities (caudal striatum, anterior thalamus), but were sensitive to handling-induced increases in endocannabinoid content (piriform cortex), compared to group-reared rats. Our findings suggest alterations in the endocannabinoid system may contribute to the abnormal isolate phenotype. Handling modifies the endocannabinoid system and behavioral reactivity to context, but surmounts only some effects of social isolation. These data implicate a pivotal role for the endocannabinoid system in stress adaptation and emotionality-related disturbances. PMID:20394803

Relationship between the broad autism phenotype, social relationships and mental health for mothers of children with autism spectrum disorder.

PubMed

Pruitt, Megan M; Rhoden, Madeline; Ekas, Naomi V

2018-02-01

This study aimed to examine the mechanisms responsible for the association between the broad autism phenotype and depressive symptoms in mothers of a child with autism spectrum disorder. A total of 98 mothers who had a child with autism spectrum disorder between the ages of 2 and 16 years completed assessments of maternal broad autism phenotype, child behavior problems, romantic relationship satisfaction, friend support, family support, and maternal depressive symptoms. Results indicated that only romantic relationship satisfaction was a significant mediator of the relationship between maternal broad autism phenotype social abnormalities and maternal depressive symptoms, where greater broad autism phenotype social abnormalities were associated with lower relationship satisfaction, which in turn was associated with increased depressive symptoms. Child behavior problems were directly related to increased depressive symptoms. Implications regarding maternal mental health outcomes within this population as well as intervention implications are discussed.

Stressing out the Social Network.

PubMed

Kirkby, Lowry A; Sohal, Vikaas S

2016-07-20

In this issue of Neuron, Hultman et al. (2016) find that stress-induced abnormal social behavior reflects aberrant prefrontal regulation of downstream limbic networks. This illustrates how linking aberrant network dynamics to neuropsychiatric disorders may lead to new circuit-based therapeutic interventions. Copyright © 2016. Published by Elsevier Inc.

Abnormal Neural Activation to Faces in the Parents of Children with Autism.

PubMed

Yucel, G H; Belger, A; Bizzell, J; Parlier, M; Adolphs, R; Piven, J

2015-12-01

Parents of children with an autism spectrum disorder (ASD) show subtle deficits in aspects of social behavior and face processing, which resemble those seen in ASD, referred to as the "Broad Autism Phenotype " (BAP). While abnormal activation in ASD has been reported in several brain structures linked to social cognition, little is known regarding patterns in the BAP. We compared autism parents with control parents with no family history of ASD using 2 well-validated face-processing tasks. Results indicated increased activation in the autism parents to faces in the amygdala (AMY) and the fusiform gyrus (FG), 2 core face-processing regions. Exploratory analyses revealed hyper-activation of lateral occipital cortex (LOC) bilaterally in autism parents with aloof personality ("BAP+"). Findings suggest that abnormalities of the AMY and FG are related to underlying genetic liability for ASD, whereas abnormalities in the LOC and right FG are more specific to behavioral features of the BAP. Results extend our knowledge of neural circuitry underlying abnormal face processing beyond those previously reported in ASD to individuals with shared genetic liability for autism and a subset of genetically related individuals with the BAP. © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Activation of the maternal immune system during pregnancy alters behavioral development of rhesus monkey offspring.

PubMed

Bauman, Melissa D; Iosif, Ana-Maria; Smith, Stephen E P; Bregere, Catherine; Amaral, David G; Patterson, Paul H

2014-02-15

Maternal infection during pregnancy is associated with an increased risk of schizophrenia and autism in the offspring. Supporting this correlation, experimentally activating the maternal immune system during pregnancy in rodents produces offspring with abnormal brain and behavioral development. We have developed a nonhuman primate model to bridge the gap between clinical populations and rodent models of maternal immune activation (MIA). A modified form of the viral mimic, synthetic double-stranded RNA (polyinosinic:polycytidylic acid stabilized with poly-L-lysine) was delivered to two separate groups of pregnant rhesus monkeys to induce MIA: 1) late first trimester MIA (n = 6), and 2) late second trimester MIA (n = 7). Control animals (n = 11) received saline injections at the same first or second trimester time points or were untreated. Sickness behavior, temperature, and cytokine profiles of the pregnant monkeys confirmed a strong inflammatory response to MIA. Behavioral development of the offspring was studied for 24 months. Following weaning at 6 months of age, MIA offspring exhibited abnormal responses to separation from their mothers. As the animals matured, MIA offspring displayed increased repetitive behaviors and decreased affiliative vocalizations. When evaluated with unfamiliar conspecifics, first trimester MIA offspring deviated from species-typical macaque social behavior by inappropriately approaching and remaining in immediate proximity of an unfamiliar animal. In this rhesus monkey model, MIA yields offspring with abnormal repetitive behaviors, communication, and social interactions. These results extended the findings in rodent MIA models to more human-like behaviors resembling those in both autism and schizophrenia. Copyright © 2014 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

Long-term effects of neonatal medial temporal ablations on socioemotional behavior in monkeys

PubMed Central

Málková, Ludise; Mishkin, Mortimer; Suomi, Stephen J.; Bachevalier, Jocelyne

2010-01-01

Socioemotional abnormalities, including low levels of social interaction and high levels of self-directed activity, were reported when rhesus monkeys with neonatal ablations of either the medial temporal lobe (AH) or the inferior temporal cortex (TE) were paired with unoperated peers at two and six months of age, though these abnormalities were more severe in the AH group (Bachevalier et al., 2001). As they reached adulthood (Experiment 1), the same monkeys were re-evaluated in the same dyads and their reactivity to novel toys, social status, and reactions to separation from age-matched peers were also assessed. Group TE now showed few if any of the abnormal behaviors observed when they were infants. By contrast, Group AH continued to display low levels of social interaction, high levels of self-directed activity and submissive behavior, and reduced responses to separation, although they reacted normally to novel toys. To determine whether this degree of socioemotional impairment was less severe than that produced by the same damage in adulthood, we assessed dyadic social interactions of monkeys raised until adulthood in laboratory conditions similar to those of the earlier groups and then given the AH ablation (Experiment 2). Two months postoperatively these adult-lesioned monkeys showed a small reduction in social interactions that became more pronounced six months postoperatively, yet remained less severe than that seen in the infant-lesioned monkeys. Also, except for an increase in food and water consumption throughout this 6-month period, they showed no other socioemotional effects. The finding that neonatal AH lesions produce more severe socioemotional disturbances than the same lesion in adulthood is the reverse of the effect commonly reported for other cognitive functions after cerebral damage. PMID:21133531

Prenatally stressed piglets 'shut down' in response to separation, oxytocin modulates some effects

USDA-ARS?s Scientific Manuscript database

Prenatal stress (PNS) effects may enhance offspring’s survival traits. Yet, PNS could be maladaptive for captive animals, causing anxiety and abnormal social development. Oxytocin (OT) reduces anxiety while OT deficiency results in social behavior alteration. We hypothesized that PNS piglets would b...

Neural Correlates of Verbal and Nonverbal Semantic Integration in Children with Autism Spectrum Disorders

ERIC Educational Resources Information Center

McCleery, Joseph P.; Ceponiene, Rita; Burner, Karen M.; Townsend, Jeanne; Kinnear, Mikaela; Schreibman, Laura

2010-01-01

Background: Autism is a pervasive developmental disorder characterized by deficits in social-emotional, social-communicative, and language skills. Behavioral and neuroimaging studies have found that children with autism spectrum disorders (ASD) evidence abnormalities in semantic processing, with particular difficulties in verbal comprehension.…

The Interplay between Emotion and Cognition in Autism Spectrum Disorder: Implications for Developmental Theory

PubMed Central

Gaigg, Sebastian B.

2012-01-01

Autism Spectrum Disorder (ASD) is a neurodevelopmental disorder that is clinically defined by abnormalities in reciprocal social and communicative behaviors and an inflexible adherence to routinised patterns of thought and behavior. Laboratory studies repeatedly demonstrate that autistic individuals experience difficulties in recognizing and understanding the emotional expressions of others and naturalistic observations show that they use such expressions infrequently and inappropriately to regulate social exchanges. Dominant theories attribute this facet of the ASD phenotype to abnormalities in a social brain network that mediates social-motivational and social-cognitive processes such as face processing, mental state understanding, and empathy. Such theories imply that only emotion related processes relevant to social cognition are compromised in ASD but accumulating evidence suggests that the disorder may be characterized by more widespread anomalies in the domain of emotions. In this review I summarize the relevant literature and argue that the social-emotional characteristics of ASD may be better understood in terms of a disruption in the domain-general interplay between emotion and cognition. More specifically I will suggest that ASD is the developmental consequence of early emerging anomalies in how emotional responses to the environment modulate a wide range of cognitive processes including those that are relevant to navigating the social world. PMID:23316143

The Interplay between Emotion and Cognition in Autism Spectrum Disorder: Implications for Developmental Theory.

PubMed

Gaigg, Sebastian B

2012-01-01

Autism Spectrum Disorder (ASD) is a neurodevelopmental disorder that is clinically defined by abnormalities in reciprocal social and communicative behaviors and an inflexible adherence to routinised patterns of thought and behavior. Laboratory studies repeatedly demonstrate that autistic individuals experience difficulties in recognizing and understanding the emotional expressions of others and naturalistic observations show that they use such expressions infrequently and inappropriately to regulate social exchanges. Dominant theories attribute this facet of the ASD phenotype to abnormalities in a social brain network that mediates social-motivational and social-cognitive processes such as face processing, mental state understanding, and empathy. Such theories imply that only emotion related processes relevant to social cognition are compromised in ASD but accumulating evidence suggests that the disorder may be characterized by more widespread anomalies in the domain of emotions. In this review I summarize the relevant literature and argue that the social-emotional characteristics of ASD may be better understood in terms of a disruption in the domain-general interplay between emotion and cognition. More specifically I will suggest that ASD is the developmental consequence of early emerging anomalies in how emotional responses to the environment modulate a wide range of cognitive processes including those that are relevant to navigating the social world.

Autism-Relevant Social Abnormalities and Cognitive Deficits in Engrailed-2 Knockout Mice

PubMed Central

Brielmaier, Jennifer; Matteson, Paul G.; Silverman, Jill L.; Senerth, Julia M.; Kelly, Samantha; Genestine, Matthieu; Millonig, James H.

2012-01-01

ENGRAILED 2 (En2), a homeobox transcription factor, functions as a patterning gene in the early development and connectivity of rodent hindbrain and cerebellum, and regulates neurogenesis and development of monoaminergic pathways. To further understand the neurobiological functions of En2, we conducted neuroanatomical expression profiling of En2 wildtype mice. RTQPCR assays demonstrated that En2 is expressed in adult brain structures including the somatosensory cortex, hippocampus, striatum, thalamus, hypothalamus and brainstem. Human genetic studies indicate that EN2 is associated with autism. To determine the consequences of En2 mutations on mouse behaviors, including outcomes potentially relevant to autism, we conducted comprehensive phenotyping of social, communication, repetitive, and cognitive behaviors. En2 null mutants exhibited robust deficits in reciprocal social interactions as juveniles and adults, and absence of sociability in adults, replicated in two independent cohorts. Fear conditioning and water maze learning were impaired in En2 null mutants. High immobility in the forced swim test, reduced prepulse inhibition, mild motor coordination impairments and reduced grip strength were detected in En2 null mutants. No genotype differences were found on measures of ultrasonic vocalizations in social contexts, and no stereotyped or repetitive behaviors were observed. Developmental milestones, general health, olfactory abilities, exploratory locomotor activity, anxiety-like behaviors and pain responses did not differ across genotypes, indicating that the behavioral abnormalities detected in En2 null mutants were not attributable to physical or procedural confounds. Our findings provide new insight into the role of En2 in complex behaviors and suggest that disturbances in En2 signaling may contribute to neuropsychiatric disorders marked by social and cognitive deficits, including autism spectrum disorders. PMID:22829897

Improvement by methylphenidate and atomoxetine of social interaction deficits and recognition memory impairment in a mouse model of valproic acid-induced autism.

PubMed

Hara, Yuta; Ago, Yukio; Taruta, Atsuki; Katashiba, Keisuke; Hasebe, Shigeru; Takano, Erika; Onaka, Yusuke; Hashimoto, Hitoshi; Matsuda, Toshio; Takuma, Kazuhiro

2016-09-01

Rodents exposed prenatally to valproic acid (VPA) show autism-related behavioral abnormalities. We recently found that prenatal VPA exposure causes a reduction of dopaminergic activity in the prefrontal cortex of male, but not female, mice. This suggests that reduced prefrontal dopaminergic activity is associated with behavioral abnormalities in VPA-treated mice. In the present study, we examined whether the attention deficit/hyperactivity disorder drugs methylphenidate and atomoxetine (which increase dopamine release in the prefrontal cortex, but not striatum, in mice) could alleviate the behavioral abnormalities and changes in dendritic spine morphology induced by prenatal VPA exposure. We found that methylphenidate and atomoxetine increased prefrontal dopamine and noradrenaline release in VPA-treated mice. Acute treatment with methylphenidate or atomoxetine did not alleviate the social interaction deficits or recognition memory impairment in VPA-treated mice, while chronic treatment for 2 weeks did. Methylphenidate or atomoxetine for 2 weeks also improved the prenatal VPA-induced decrease in dendritic spine density in the prefrontal cortex. The effects of these drugs on behaviors and dendritic spine morphology were antagonized by concomitant treatment with the dopamine-D1 receptor antagonist SCH39166 or the dopamine-D2 receptor antagonist raclopride, but not by the α2 -adrenoceptor antagonist idazoxan. These findings suggest that chronic treatment with methylphenidate or atomoxetine improves abnormal behaviors and diminishes the reduction in spine density in VPA-treated mice via a prefrontal dopaminergic system-dependent mechanism. Autism Res 2016, 9: 926-939. © 2015 International Society for Autism Research, Wiley Periodicals, Inc. © 2015 International Society for Autism Research, Wiley Periodicals, Inc.

Excessive Aggression as Model of Violence: A Critical Evaluation of Current Preclinical Methods

PubMed Central

Miczek, Klaus A.; de Boer, Sietse F.; Haller, Jozsef

2013-01-01

Rationale Preclinical experimental models of pathological aggressive behavior are a sorely understudied and difficult research area. Objectives How valid, reliable, productive and informative are the most frequently used animal models of excessive aggressive behavior? Methods The rationale, key methodological features, supporting data and arguments as well as their disadvantages and limitations of the most frequently used animal models for excessive aggressive behavior are summarized and their validity and reliability are evaluated. Results Excessive aggressive behavior is validly and reliably seen in (1) a proportion of feral-derived rats and selectively bred mice, (2) rats with compromised adrenal function resulting in a hypoglucocorticoid state, (3) a significant minority of mice, rats and monkeys after consumption of a moderate dose of alcohol, and (4) resident animals of various species after social instigation. Limitations of these procedures include restrictive animal research regulations, the requirement of expertise in surgical, pharmacological and behavioral techniques, and the behaviorally impoverished mouse strains that are used in molecular genetics research. Promising recent initiatives for novel experimental models include aggressive behaviors that are evoked by optogenetic stimulation and induced by the manipulation of early social experiences such as isolation rearing or social stress. Conclusions One of the most significant challenges for animal models of excessive, potentially abnormal aggressive behavior is the characterization of distinctive neurobiological mechanisms that differ from those governing species-typical aggressive behavior. Identifying novel targets for effective intervention requires increased understanding of the distinctive molecular, cellular and circuit mechanisms for each type of abnormal aggressive behavior. PMID:23430160

ENU-mutagenesis mice with a non-synonymous mutation in Grin1 exhibit abnormal anxiety-like behaviors, impaired fear memory, and decreased acoustic startle response

PubMed Central

2013-01-01

Background The Grin1 (glutamate receptor, ionotropic, NMDA1) gene expresses a subunit of N-methyl-D-aspartate (NMDA) receptors that is considered to play an important role in excitatory neurotransmission, synaptic plasticity, and brain development. Grin1 is a candidate susceptibility gene for neuropsychiatric disorders, including schizophrenia, bipolar disorder, and attention deficit/hyperactivity disorder (ADHD). In our previous study, we examined an N-ethyl-N-nitrosourea (ENU)-generated mutant mouse strain (Grin1Rgsc174/Grin1+) that has a non-synonymous mutation in Grin1. These mutant mice showed hyperactivity, increased novelty-seeking to objects, and abnormal social interactions. Therefore, Grin1Rgsc174/Grin1+ mice may serve as a potential animal model of neuropsychiatric disorders. However, other behavioral characteristics related to these disorders, such as working memory function and sensorimotor gating, have not been fully explored in these mutant mice. In this study, to further investigate the behavioral phenotypes of Grin1Rgsc174/Grin1+ mice, we subjected them to a comprehensive battery of behavioral tests. Results There was no significant difference in nociception between Grin1Rgsc174/Grin1+ and wild-type mice. The mutants did not display any abnormalities in the Porsolt forced swim and tail suspension tests. We confirmed the previous observations that the locomotor activity of these mutant mice increased in the open field and home cage activity tests. They displayed abnormal anxiety-like behaviors in the light/dark transition and the elevated plus maze tests. Both contextual and cued fear memory were severely deficient in the fear conditioning test. The mutant mice exhibited slightly impaired working memory in the eight-arm radial maze test. The startle amplitude was markedly decreased in Grin1Rgsc174/Grin1+ mice, whereas no significant differences between genotypes were detected in the prepulse inhibition (PPI) test. The mutant mice showed no obvious deficits in social behaviors in three different social interaction tests. Conclusions This study demonstrated that the Grin1Rgsc174/Grin1+ mutation causes abnormal anxiety-like behaviors, a deficiency in fear memory, and a decreased startle amplitude in mice. Although Grin1Rgsc174/Grin1+ mice only partially recapitulate symptoms of patients with ADHD, schizophrenia, and bipolar disorder, they may serve as a unique animal model of a certain subpopulation of patients with these disorders. PMID:23688147

Comprehensive behavioral analysis of pituitary adenylate cyclase-activating polypeptide (PACAP) knockout mice

PubMed Central

Hattori, Satoko; Takao, Keizo; Tanda, Koichi; Toyama, Keiko; Shintani, Norihito; Baba, Akemichi; Hashimoto, Hitoshi; Miyakawa, Tsuyoshi

2012-01-01

Pituitary adenylate cyclase-activating polypeptide (PACAP) is a neuropeptide acting as a neurotransmitter, neuromodulator, or neurotrophic factor. PACAP is widely expressed throughout the brain and exerts its functions through the PACAP-specific receptor (PAC1). Recent studies reveal that genetic variants of the PACAP and PAC1 genes are associated with mental disorders, and several behavioral abnormalities of PACAP knockout (KO) mice are reported. However, an insufficient number of backcrosses was made using PACAP KO mice on the C57BL/6J background due to their postnatal mortality. To elucidate the effects of PACAP on neuropsychiatric function, the PACAP gene was knocked out in F1 hybrid mice (C57BL/6J × 129SvEv) for appropriate control of the genetic background. The PACAP KO mice were then subjected to a behavioral test battery. PACAP deficiency had no significant effects on neurological screen. As shown previously, the mice exhibited significantly increased locomotor activity in a novel environment and abnormal anxiety-like behavior, while no obvious differences between genotypes were shown in home cage (HC) activity. In contrast to previous reports, the PACAP KO mice showed normal prepulse inhibition (PPI) and slightly decreased depression-like behavior. Previous study demonstrates that the social interaction (SI) in a resident-intruder test was decreased in PACAP KO mice. On the other hand, we showed that PACAP KO mice exhibited increased SI in Crawley's three-chamber social approach test, although PACAP KO had no significant impact on SI in a HC. PACAP KO mice also exhibited mild performance deficit in working memory in an eight-arm radial maze (RM) and the T-maze (TM), while they did not show any significant abnormalities in the left-right discrimination task in the TM. These results suggest that PACAP has an important role in the regulation of locomotor activity, social behavior, anxiety-like behavior and, potentially, working memory. PMID:23060763

Social and monetary reward processing in autism spectrum disorders

PubMed Central

2012-01-01

Background Social motivation theory suggests that deficits in social reward processing underlie social impairments in autism spectrum disorders (ASD). However, the extent to which abnormalities in reward processing generalize to other classes of stimuli remains unresolved. The aim of the current study was to examine if reward processing abnormalities in ASD are specific to social stimuli or can be generalized to other classes of reward. Additionally, we sought to examine the results in the light of behavioral impairments in ASD. Methods Participants performed adapted versions of the social and monetary incentive delay tasks. Data from 21 unmedicated right-handed male participants with ASD and 21 age- and IQ-matched controls were analyzed using a factorial design to examine the blood-oxygen-level-dependent (BOLD) response during the anticipation and receipt of both reward types. Results Behaviorally, the ASD group showed less of a reduction in reaction time (RT) for rewarded compared to unrewarded trials than the control group. In terms of the fMRI results, there were no significant group differences in reward circuitry during reward anticipation. During the receipt of rewards, there was a significant interaction between group and reward type in the left dorsal striatum (DS). The ASD group showed reduced activity in the DS compared to controls for social rewards but not monetary rewards and decreased activation for social rewards compared to monetary rewards. Controls showed no significant difference between the two reward types. Increased activation in the DS during social reward processing was associated with faster response times for rewarded trials, compared to unrewarded trials, in both groups. This is in line with behavioral results indicating that the ASD group showed less of a reduction in RT for rewarded compared to unrewarded trials. Additionally, de-activation to social rewards was associated with increased repetitive behavior in ASD. Conclusions In line with social motivation theory, the ASD group showed reduced activation, compared to controls, during the receipt of social rewards in the DS. Groups did not differ significantly during the processing of monetary rewards. BOLD activation in the DS, during social reward processing, was associated with behavioral impairments in ASD. PMID:23014171

Social and monetary reward processing in autism spectrum disorders.

PubMed

Delmonte, Sonja; Balsters, Joshua H; McGrath, Jane; Fitzgerald, Jacqueline; Brennan, Sean; Fagan, Andrew J; Gallagher, Louise

2012-09-26

Social motivation theory suggests that deficits in social reward processing underlie social impairments in autism spectrum disorders (ASD). However, the extent to which abnormalities in reward processing generalize to other classes of stimuli remains unresolved. The aim of the current study was to examine if reward processing abnormalities in ASD are specific to social stimuli or can be generalized to other classes of reward. Additionally, we sought to examine the results in the light of behavioral impairments in ASD. Participants performed adapted versions of the social and monetary incentive delay tasks. Data from 21 unmedicated right-handed male participants with ASD and 21 age- and IQ-matched controls were analyzed using a factorial design to examine the blood-oxygen-level-dependent (BOLD) response during the anticipation and receipt of both reward types. Behaviorally, the ASD group showed less of a reduction in reaction time (RT) for rewarded compared to unrewarded trials than the control group. In terms of the fMRI results, there were no significant group differences in reward circuitry during reward anticipation. During the receipt of rewards, there was a significant interaction between group and reward type in the left dorsal striatum (DS). The ASD group showed reduced activity in the DS compared to controls for social rewards but not monetary rewards and decreased activation for social rewards compared to monetary rewards. Controls showed no significant difference between the two reward types. Increased activation in the DS during social reward processing was associated with faster response times for rewarded trials, compared to unrewarded trials, in both groups. This is in line with behavioral results indicating that the ASD group showed less of a reduction in RT for rewarded compared to unrewarded trials. Additionally, de-activation to social rewards was associated with increased repetitive behavior in ASD. In line with social motivation theory, the ASD group showed reduced activation, compared to controls, during the receipt of social rewards in the DS. Groups did not differ significantly during the processing of monetary rewards. BOLD activation in the DS, during social reward processing, was associated with behavioral impairments in ASD.

Development of Abnormality Detection System for Bathers using Ultrasonic Sensors

NASA Astrophysics Data System (ADS)

Ohnishi, Yosuke; Abe, Takehiko; Nambo, Hidetaka; Kimura, Haruhiko; Ogoshi, Yasuhiro

This paper proposes an abnormality detection system for bather sitting in bathtub. Increasing number of in-bathtub drowning accidents in Japan draws attention. Behind this large number of bathing accidents, Japan's unique social and cultural background come surface. For majority of people in Japan, bathing serves purpose in deep warming up of body, relax and enjoyable time. Therefore it is the custom for the Japanese to soak in bathtub. However overexposure to hot water may cause dizziness or fainting, which is possible to cause in-bathtub drowning. For drowning prevention, the system detects bather's abnormal state using an ultrasonic sensor array. The array, which has many ultrasonic sensors, is installed on the ceiling of bathroom above bathtub. The abnormality detection system uses the following two methods: posture detection and behavior detection. The function of posture detection is to estimate the risk of drowning by monitoring bather's posture. Meanwhile, the function of behavior detection is to estimate the risk of drowning by monitoring bather's behavior. By using these methods, the system detects bathers' different state from normal. As a result of experiment with a subject in the bathtub, the system was possible to detect abnormal state using subject's posture and behavior. Therefore the system is useful for monitoring bather to prevent drowning in bathtub.

Social tension as precursor of large damaging earthquake: legend or reality?

NASA Astrophysics Data System (ADS)

Molchanov, O.

2008-11-01

Using case study of earthquake (EQ) activity and war conflicts in Caucasus during 1975 2002 time interval and correlation analysis of global distribution of damaging EQs and war-related social tension during 1901 2005 period we conclude:

• There is a statistically reliable increase of social tension several years (or several months in case study) before damaging EQs,
• There is evident decrease of social tension several years after damaging EQs, probably due to society consolidation,
• Preseismic effect is absent for the large EQs in unpopulated areas,
• There is some factual background for legendary belief in Almighty retribution for social abnormal behavior.

The role of the medial prefrontal cortex in the play fighting of rats.

PubMed

Bell, Heather C; McCaffrey, David R; Forgie, Margaret L; Kolb, Bryan; Pellis, Sergio M

2009-12-01

Although decorticated rats are able to engage in play, their play is abnormal in three ways. First, decorticates do not display the normal, age-related shifts in defensive strategies during development. Second, decorticates do not modify their defensive tactics in response to the social identity of their partners. Third, decorticates display a global shift in defensive tactics from more complex to less complex strategies. It has been shown that lesions of the motor cortex (MC) selectively produce the abnormal developmental effects on play, and that lesions of the orbitofrontal cortex (OFC) selectively produce the deficits in behavioral discrimination between social partners. In the current set of experiments, we demonstrate that lesions of the medial prefrontal cortex (mPFC) produce the shift from more complex to less complex defensive tactics, while leaving intact the age-related and partner-related modulation of defensive strategies. Thus, we have evidence for a triple dissociation of function between the MC, the OFC, and the mPFC with respect to social play behavior.

Perinatal exposure to low-dose imidacloprid causes ADHD-like symptoms: Evidences from an invertebrate model study.

PubMed

Kim, Seoyoung; Lee, Hee-Seok; Park, Yooheon

2017-12-01

The fundamental diagnoses of attention deficit hyperactivity disorder (ADHD) and autism consists of inattention, hyperactivity, and impulsivity, which lead to abnormal social interactions and repetitive and restricted behavior. Several food contaminants are suspected of being a possible contributing factor to the present-day increase in diseases, such as obesity and ADHD, and pesticides are also considered as a contributor to the increased prevalence of ADHD. Imidacloprid is a neonicotinoid insecticide with lower toxicity to mammals. Based on recent reports on neurobehavioral studies using an invertebrate model system, we have assessed ADHD-related impairments to test the effects of low-dose exposure to imidacloprid in Drosophila melanogaster through behavior assays, such as abnormal social interaction, repetitive behaviors, and significant deficiency in locomotion in an open field arena, a decision-making process. Drosophila stocks were treated with imidacloprid at the level of 200 pM. Social interaction among the flies was disturbed by imidacloprid. Travelled distance and velocity was also increased by the treatment. The difference in velocity between the treatment group and the control group was significant, revealing that imidacloprid-exposed flies moved faster and longer than control flies. This study illustrated the behavioral deficiency in Drosophila due to the low-dose imidacloprid exposure. Copyright © 2017 Elsevier Ltd. All rights reserved.

Searching for the gut microbial contributing factors to social behavior in rodent models of autism spectrum disorder.

PubMed

Needham, Brittany D; Tang, Weiyi; Wu, Wei-Li

2018-05-01

Social impairment is one of the major symptoms in multiple psychiatric disorders, including autism spectrum disorder (ASD). Accumulated studies indicate a crucial role for the gut microbiota in social development, but these mechanisms remain unclear. This review focuses on two strategies adopted to elucidate the complicated relationship between gut bacteria and host social behavior. In a top-down approach, researchers have attempted to correlate behavioral abnormalities with altered gut microbial profiles in rodent models of ASD, including BTBR mice, maternal immune activation (MIA), maternal valproic acid (VPA) and maternal high-fat diet (MHFD) offspring. In a bottom-up approach, researchers use germ-free (GF) animals, antibiotics, probiotics or pathogens to manipulate the intestinal environment and ascertain effects on social behavior. The combination of both approaches will hopefully pinpoint specific bacterial communities that control host social behavior. Further discussion of how brain development and circuitry is impacted by depletion of gut microbiota is also included. The converging evidence strongly suggests that gut microbes affect host social behavior through the alteration of brain neural circuits. Investigation of intestinal microbiota and host social behavior will unveil any bidirectional communication between the gut and brain and provide alternative therapeutic targets for ASD. © 2018 Wiley Periodicals, Inc. Develop Neurobiol 78: 474-499, 2018. © 2018 Wiley Periodicals, Inc.

On the Control of Social Approach-Avoidance Behavior: Neural and Endocrine Mechanisms.

PubMed

Kaldewaij, Reinoud; Koch, Saskia B J; Volman, Inge; Toni, Ivan; Roelofs, Karin

The ability to control our automatic action tendencies is crucial for adequate social interactions. Emotional events trigger automatic approach and avoidance tendencies. Although these actions may be generally adaptive, the capacity to override these emotional reactions may be key to flexible behavior during social interaction. The present chapter provides a review of the neuroendocrine mechanisms underlying this ability and their relation to social psychopathologies. Aberrant social behavior, such as observed in social anxiety or psychopathy, is marked by abnormalities in approach-avoidance tendencies and the ability to control them. Key neural regions involved in the regulation of approach-avoidance behavior are the amygdala, widely implicated in automatic emotional processing, and the anterior prefrontal cortex, which exerts control over the amygdala. Hormones, especially testosterone and cortisol, have been shown to affect approach-avoidance behavior and the associated neural mechanisms. The present chapter also discusses ways to directly influence social approach and avoidance behavior and will end with a research agenda to further advance this important research field. Control over approach-avoidance tendencies may serve as an exemplar of emotional action regulation and might have a great value in understanding the underlying mechanisms of the development of affective disorders.

Environmental enrichment attenuates behavioral abnormalities in valproic acid-exposed autism model mice.

PubMed

Yamaguchi, Hiroshi; Hara, Yuta; Ago, Yukio; Takano, Erika; Hasebe, Shigeru; Nakazawa, Takanobu; Hashimoto, Hitoshi; Matsuda, Toshio; Takuma, Kazuhiro

2017-08-30

We recently demonstrated that prenatal exposure to valproic acid (VPA) at embryonic day 12.5 causes autism spectrum disorder (ASD)-like phenotypes such as hypolocomotion, anxiety-like behavior, social deficits and cognitive impairment in mice and that it decreases dendritic spine density in the hippocampal CA1 region. Previous studies show that some abnormal behaviors are improved by environmental enrichment in ASD rodent models, but it is not known whether environmental enrichment improves cognitive impairment. In the present study, we examined the effects of early environmental enrichment on behavioral abnormalities and neuromorphological changes in prenatal VPA-treated mice. We also examined the role of dendritic spine formation and synaptic protein expression in the hippocampus. Mice were housed for 4 weeks from 4 weeks of age under either a standard or enriched environment. Enriched housing was found to increase hippocampal brain-derived neurotrophic factor mRNA levels in both control and VPA-exposed mice. Furthermore, in VPA-treated mice, the environmental enrichment improved anxiety-like behavior, social deficits and cognitive impairment, but not hypolocomotion. Prenatal VPA treatment caused loss of dendritic spines in the hippocampal CA1 region and decreases in mRNA levels of postsynaptic density protein-95 and SH3 and multiple ankyrin repeat domains 2 in the hippocampus. These hippocampal changes were improved by the enriched housing. These findings suggest that the environmental enrichment improved most ASD-like behaviors including cognitive impairment in the VPA-treated mice by enhancing dendritic spine function. Copyright © 2017 Elsevier B.V. All rights reserved.

Immune Abnormalities in Autism Spectrum Disorder-Could They Hold Promise for Causative Treatment?

PubMed

Gładysz, Dominika; Krzywdzińska, Amanda; Hozyasz, Kamil K

2018-01-06

Autism spectrum disorders (ASD) are characterized by impairments in language and communication development, social behavior, and the occurrence of stereotypic patterns of behavior and interests. Despite substantial speculation about causes of ASD, its exact etiology remains unknown. Recent studies highlight a link between immune dysfunction and behavioral traits. Various immune anomalies, including humoral and cellular immunity along with abnormalities at the molecular level, have been reported. There is evidence of altered immune function both in cerebrospinal fluid and peripheral blood. Several studies hypothesize a role for neuroinflammation in ASD and are supported by brain tissue and cerebrospinal fluid analysis, as well as evidence of microglial activation. It has been shown that immune abnormalities occur in a substantial number of individuals with ASD. Identifying subgroups with immune system dysregulation and linking specific cellular immunophenotypes to different symptoms would be key to defining a group of patients with immune abnormalities as a major etiology underlying behavioral symptoms. These determinations would provide the opportunity to investigate causative treatments for a defined patient group that may specifically benefit from such an approach. This review summarizes recent insights into immune system dysfunction in individuals with ASD and discusses the potential implications for future therapies.

Genetics Home Reference: beta-ureidopropionase deficiency

MedlinePlus

... disability, and autistic behaviors that affect communication and social interaction. Some people with this condition have an abnormally ... Accessibility FOIA Viewers & Players U.S. Department of Health & Human Services National Institutes of Health National Library of ...

The contributions of oxytocin and vasopressin pathway genes to human behavior.

PubMed

Ebstein, Richard P; Knafo, Ariel; Mankuta, David; Chew, Soo Hong; Lai, Poh San

2012-03-01

Arginine vasopressin (AVP) and oxytocin (OXT) are social hormones and mediate affiliative behaviors in mammals and as recently demonstrated, also in humans. There is intense interest in how these simple nonapeptides mediate normal and abnormal behavior, especially regarding disorders of the social brain such as autism that are characterized by deficits in social communication and social skills. The current review examines in detail the behavioral genetics of the first level of human AVP-OXT pathway genes including arginine vasopressin 1a receptor (AVPR1a), oxytocin receptor (OXTR), AVP (AVP-neurophysin II [NPII]) and OXT (OXT neurophysin I [NPI]), oxytocinase/vasopressinase (LNPEP), ADP-ribosyl cyclase (CD38) and arginine vasopressin 1b receptor (AVPR1b). Wherever possible we discuss evidence from a variety of research tracks including molecular genetics, imaging genomics, pharmacology and endocrinology that support the conclusions drawn from association studies of social phenotypes and detail how common polymorphisms in AVP-OXT pathway genes contribute to the behavioral hard wiring that enables individual Homo sapiens to interact successfully with conspecifics. This article is part of a Special Issue entitled Oxytocin, Vasopressin, and Social Behavior. Copyright © 2011 Elsevier Inc. All rights reserved.

Long-term effects of neonatal medial temporal ablations on socioemotional behavior in monkeys (Macaca mulatta).

PubMed

Malkova, Ludise; Mishkin, Mortimer; Suomi, Stephen J; Bachevalier, Jocelyne

2010-12-01

Socioemotional abnormalities, including decreased social interactions and increased self-directed activity, were reported when rhesus monkeys with neonatal ablations of either the medial temporal lobe (AH) or the inferior temporal cortex (TE) were paired with unoperated peers at two and six months of age, though these abnormalities were more severe in Group AH (Bachevalier et al., 2001). As adults (Experiment 1), the monkeys were re-evaluated in the same dyads and their reactivity to novel toys, social status, and reactions to separation were also assessed. Group TE now showed only few if any of the abnormal behaviors observed in infancy. In contrast, Group AH continued to display decreased social interactions and increased self-directed activity and showed also increased submission and reduced responses to separation, but normal reactivity to novel toys. To determine whether this degree of socioemotional impairment was less severe than that produced by the same damage in adulthood, we assessed dyadic social interactions of monkeys raised until adulthood in laboratory conditions similar to those in Experiment 1 and then given the AH ablations (Experiment 2). Two months postoperatively these monkeys showed a small reduction in social interactions that became more pronounced six months postoperatively, yet remained less severe than that seen in the infant-lesioned monkeys. No other socioemotional effects, except for an increase in food/water consumption, were observed. The finding that neonatal AH lesions produce more severe socioemotional disturbances than the same lesion in adulthood is the reverse of the effect commonly reported for other cognitive functions after cerebral damage. © 2010 APA, all rights reserved.

Cerebro-cerebellar circuits in autism spectrum disorder.

PubMed

D'Mello, Anila M; Stoodley, Catherine J

2015-01-01

The cerebellum is one of the most consistent sites of abnormality in autism spectrum disorder (ASD) and cerebellar damage is associated with an increased risk of ASD symptoms, suggesting that cerebellar dysfunction may play a crucial role in the etiology of ASD. The cerebellum forms multiple closed-loop circuits with cerebral cortical regions that underpin movement, language, and social processing. Through these circuits, cerebellar dysfunction could impact the core ASD symptoms of social and communication deficits and repetitive and stereotyped behaviors. The emerging topography of sensorimotor, cognitive, and affective subregions in the cerebellum provides a new framework for interpreting the significance of regional cerebellar findings in ASD and their relationship to broader cerebro-cerebellar circuits. Further, recent research supports the idea that the integrity of cerebro-cerebellar loops might be important for early cortical development; disruptions in specific cerebro-cerebellar loops in ASD might impede the specialization of cortical regions involved in motor control, language, and social interaction, leading to impairments in these domains. Consistent with this concept, structural, and functional differences in sensorimotor regions of the cerebellum and sensorimotor cerebro-cerebellar circuits are associated with deficits in motor control and increased repetitive and stereotyped behaviors in ASD. Further, communication and social impairments are associated with atypical activation and structure in cerebro-cerebellar loops underpinning language and social cognition. Finally, there is converging evidence from structural, functional, and connectivity neuroimaging studies that cerebellar right Crus I/II abnormalities are related to more severe ASD impairments in all domains. We propose that cerebellar abnormalities may disrupt optimization of both structure and function in specific cerebro-cerebellar circuits in ASD.

Cerebro-cerebellar circuits in autism spectrum disorder

PubMed Central

D'Mello, Anila M.; Stoodley, Catherine J.

2015-01-01

The cerebellum is one of the most consistent sites of abnormality in autism spectrum disorder (ASD) and cerebellar damage is associated with an increased risk of ASD symptoms, suggesting that cerebellar dysfunction may play a crucial role in the etiology of ASD. The cerebellum forms multiple closed-loop circuits with cerebral cortical regions that underpin movement, language, and social processing. Through these circuits, cerebellar dysfunction could impact the core ASD symptoms of social and communication deficits and repetitive and stereotyped behaviors. The emerging topography of sensorimotor, cognitive, and affective subregions in the cerebellum provides a new framework for interpreting the significance of regional cerebellar findings in ASD and their relationship to broader cerebro-cerebellar circuits. Further, recent research supports the idea that the integrity of cerebro-cerebellar loops might be important for early cortical development; disruptions in specific cerebro-cerebellar loops in ASD might impede the specialization of cortical regions involved in motor control, language, and social interaction, leading to impairments in these domains. Consistent with this concept, structural, and functional differences in sensorimotor regions of the cerebellum and sensorimotor cerebro-cerebellar circuits are associated with deficits in motor control and increased repetitive and stereotyped behaviors in ASD. Further, communication and social impairments are associated with atypical activation and structure in cerebro-cerebellar loops underpinning language and social cognition. Finally, there is converging evidence from structural, functional, and connectivity neuroimaging studies that cerebellar right Crus I/II abnormalities are related to more severe ASD impairments in all domains. We propose that cerebellar abnormalities may disrupt optimization of both structure and function in specific cerebro-cerebellar circuits in ASD. PMID:26594140

Social behavior impairment in offspring exposed to maternal seizures in utero.

PubMed

Novaes, Gisane Faria; Amado, Debora; Scorza, Fulvio Alexandre; Cysneiros, Roberta Monterazzo

2012-06-01

Human and animal models have demonstrated that maternal seizures in utero could be deleterious to the development of the offspring. This study focused on the social behavior of offspring exposed to seizures in utero. A pilocarpine model of temporal lobe epilepsy was induced in female Wistar rats that were mated after the first spontaneous seizure. Early after birth, pups from an epileptic mother were reared by a control mother. To evaluate the influence of the adoption process, two other groups were added: rat pups from control mothers cross-fostered with other control mothers, and rat pups reared by their birth mother. Animals exposed to seizures in utero showed impaired social behavior with no signs of anxiety-like behavior. This study demonstrated that epileptic seizures during pregnancy could be harmful to brain development and may increase the risk of developing neurodevelopmental disorders. The mechanisms underlying the abnormalities of social behavior are not well understood, and further studies in this field are warranted.

Early social enrichment rescues adult behavioral and brain abnormalities in a mouse model of fragile X syndrome.

PubMed

Oddi, Diego; Subashi, Enejda; Middei, Silvia; Bellocchio, Luigi; Lemaire-Mayo, Valerie; Guzmán, Manuel; Crusio, Wim E; D'Amato, Francesca R; Pietropaolo, Susanna

2015-03-13

Converging lines of evidence support the use of environmental stimulation to ameliorate the symptoms of a variety of neurodevelopmental disorders. Applying these interventions at very early ages is critical to achieve a marked reduction of the pathological phenotypes. Here we evaluated the impact of early social enrichment in Fmr1-KO mice, a genetic mouse model of fragile X syndrome (FXS), a major developmental disorder and the most frequent monogenic cause of autism. Enrichment was achieved by providing male KO pups and their WT littermates with enhanced social stimulation, housing them from birth until weaning with the mother and an additional nonlactating female. At adulthood they were tested for locomotor, social, and cognitive abilities; furthermore, dendritic alterations were assessed in the hippocampus and amygdala, two brain regions known to be involved in the control of the examined behaviors and affected by spine pathology in Fmr1-KOs. Enrichment rescued the behavioral FXS-like deficits displayed in adulthood by Fmr1-KO mice, that is, hyperactivity, reduced social interactions, and cognitive deficits. Early social enrichment also eliminated the abnormalities shown by adult KO mice in the morphology of hippocampal and amygdala dendritic spines, namely an enhanced density of immature vs mature types. Importantly, enrichment did not induce neurobehavioral changes in WT mice, thus supporting specific effects on FXS-like pathology. These findings show that early environmental stimulation has profound and long-term beneficial effects on the pathological FXS phenotype, thereby encouraging the use of nonpharmacological interventions for the treatment of this and perhaps other neurodevelopmental diseases.

Genetic manipulation of STEP reverses behavioral abnormalities in a fragile X syndrome mouse model.

PubMed

Goebel-Goody, S M; Wilson-Wallis, E D; Royston, S; Tagliatela, S M; Naegele, J R; Lombroso, P J

2012-07-01

Fragile X syndrome (FXS), the most common inherited form of intellectual disability and prevailing known genetic basis of autism, is caused by an expansion in the Fmr1 gene that prevents transcription and translation of fragile X mental retardation protein (FMRP). FMRP binds to and controls translation of mRNAs downstream of metabotropic glutamate receptor (mGluR) activation. Recent work shows that FMRP interacts with the transcript encoding striatal-enriched protein tyrosine phosphatase (STEP; Ptpn5). STEP opposes synaptic strengthening and promotes synaptic weakening by dephosphorylating its substrates, including ERK1/2, p38, Fyn and Pyk2, and subunits of N-methyl-d-aspartate (NMDA) and AMPA receptors. Here, we show that basal levels of STEP are elevated and mGluR-dependent STEP synthesis is absent in Fmr1(KO) mice. We hypothesized that the weakened synaptic strength and behavioral abnormalities reported in FXS may be linked to excess levels of STEP. To test this hypothesis, we reduced or eliminated STEP genetically in Fmr1(KO) mice and assessed mice in a battery of behavioral tests. In addition to attenuating audiogenic seizures and seizure-induced c-Fos activation in the periaqueductal gray, genetically reducing STEP in Fmr1(KO) mice reversed characteristic social abnormalities, including approach, investigation and anxiety. Loss of STEP also corrected select nonsocial anxiety-related behaviors in Fmr1(KO) mice, such as light-side exploration in the light/dark box. Our findings indicate that genetically reducing STEP significantly diminishes seizures and restores select social and nonsocial anxiety-related behaviors in Fmr1(KO) mice, suggesting that strategies to inhibit STEP activity may be effective for treating patients with FXS. © 2012 The Authors. Genes, Brain and Behavior © 2012 Blackwell Publishing Ltd and International Behavioural and Neural Genetics Society.

Behavioral and regulatory abnormalities in mice deficient in the NPAS1 and NPAS3 transcription factors.

PubMed

Erbel-Sieler, Claudia; Dudley, Carol; Zhou, Yudong; Wu, Xinle; Estill, Sandi Jo; Han, Tina; Diaz-Arrastia, Ramon; Brunskill, Eric W; Potter, S Steven; McKnight, Steven L

2004-09-14

Laboratory mice bearing inactivating mutations in the genes encoding the NPAS1 and NPAS3 transcription factors have been shown to exhibit a spectrum of behavioral and neurochemical abnormalities. Behavioral abnormalities included diminished startle response, as measured by prepulse inhibition, and impaired social recognition. NPAS1/NPAS3-deficient mice also exhibited stereotypic darting behavior at weaning and increased locomotor activity. Immunohistochemical staining assays showed that the NPAS1 and NPAS3 proteins are expressed in inhibitory interneurons and that the viability and anatomical distribution of these neurons are unaffected by the absence of either transcription factor. Adult brain tissues from NPAS3- and NPAS1/NPAS3-deficient mice exhibited a distinct reduction in reelin, a large, secreted protein whose expression has been reported to be attenuated in the postmortem brain tissue of patients with schizophrenia. These observations raise the possibility that a regulatory program controlled in inhibitory interneurons by the NPAS1 and NPAS3 transcription factors may be either substantively or tangentially relevant to psychosis.

Behavioral and regulatory abnormalities in mice deficient in the NPAS1 and NPAS3 transcription factors

PubMed Central

Erbel-Sieler, Claudia; Dudley, Carol; Zhou, Yudong; Wu, Xinle; Estill, Sandi Jo; Han, Tina; Diaz-Arrastia, Ramon; Brunskill, Eric W.; Potter, S. Steven; McKnight, Steven L.

2004-01-01

Laboratory mice bearing inactivating mutations in the genes encoding the NPAS1 and NPAS3 transcription factors have been shown to exhibit a spectrum of behavioral and neurochemical abnormalities. Behavioral abnormalities included diminished startle response, as measured by prepulse inhibition, and impaired social recognition. NPAS1/NPAS3-deficient mice also exhibited stereotypic darting behavior at weaning and increased locomotor activity. Immunohistochemical staining assays showed that the NPAS1 and NPAS3 proteins are expressed in inhibitory interneurons and that the viability and anatomical distribution of these neurons are unaffected by the absence of either transcription factor. Adult brain tissues from NPAS3- and NPAS1/NPAS3-deficient mice exhibited a distinct reduction in reelin, a large, secreted protein whose expression has been reported to be attenuated in the postmortem brain tissue of patients with schizophrenia. These observations raise the possibility that a regulatory program controlled in inhibitory interneurons by the NPAS1 and NPAS3 transcription factors may be either substantively or tangentially relevant to psychosis. PMID:15347806

Neural systems for social cognition in Klinefelter syndrome (47,XXY): evidence from fMRI.

PubMed

van Rijn, Sophie; Swaab, Hanna; Baas, Daan; de Haan, Edward; Kahn, René S; Aleman, André

2012-08-01

Klinefelter syndrome (KS) is a chromosomal condition (47, XXY) that may help us to unravel gene-brain behavior pathways to psychopathology. The phenotype includes social cognitive impairments and increased risk for autism traits. We used functional MRI to study neural mechanisms underlying social information processing. Eighteen nonclinical controls and thirteen men with XXY were scanned during judgments of faces with regard to trustworthiness and age. While judging faces as untrustworthy in comparison to trustworthy, men with XXY displayed less activation than controls in (i) the amygdala, which plays a key role in screening information for socio-emotional significance, (ii) the insula, which plays a role in subjective emotional experience, as well as (iii) the fusiform gyrus and (iv) the superior temporal sulcus, which are both involved in the perceptual processing of faces and which were also less involved during age judgments in men with XXY. This is the first study showing that KS can be associated with reduced involvement of the neural network subserving social cognition. Studying KS may increase our understanding of the genetic and hormonal basis of neural dysfunctions contributing to abnormalities in social cognition and behavior, which are considered core abnormalities in psychiatric disorders such as autism and schizophrenia.

Omnivores Going Astray: A Review and New Synthesis of Abnormal Behavior in Pigs and Laying Hens

PubMed Central

Brunberg, Emma I.; Rodenburg, T. Bas; Rydhmer, Lotta; Kjaer, Joergen B.; Jensen, Per; Keeling, Linda J.

2016-01-01

Pigs and poultry are by far the most omnivorous of the domesticated farm animals and it is in their nature to be highly explorative. In the barren production environments, this motivation to explore can be expressed as abnormal oral manipulation directed toward pen mates. Tail biting (TB) in pigs and feather pecking (FP) in laying hens are examples of unwanted behaviors that are detrimental to the welfare of the animals. The aim of this review is to draw these two seemingly similar abnormalities together in a common framework, in order to seek underlying mechanisms and principles. Both TB and FP are affected by the physical and social environment, but not all individuals in a group express these behaviors and individual genetic and neurobiological characteristics play an important role. By synthesizing what is known about environmental and individual influences, we suggest a novel possible mechanism, common for pigs and poultry, involving the brain–gut–microbiota axis. PMID:27500137

Implicit Social Biases in People with Autism

PubMed Central

Birmingham, Elina; Stanley, Damian; Nair, Remya; Adolphs, Ralph

2015-01-01

Implicit social biases are ubiquitous and are known to influence social behavior. A core diagnostic criterion of Autism Spectrum Disorder (ASD) is abnormal social behavior. Here we investigated the extent to which individuals with ASD might show a specific attenuation of implicit social biases, using the Implicit Association Test (IAT) across Social (gender, race) and Nonsocial (flowers/insect, shoes) categories. High-functioning adults with ASD showed intact but reduced IAT effects relative to healthy controls. Importantly, we observed no selective attenuation of implicit social (vs. nonsocial) biases in our ASD population. To extend these results, we collected data from a large online sample of the general population, and explored correlations between autistic traits and IAT effects. No associations were found between autistic traits and IAT effects for any of the categories tested in our online sample. Taken together, these results suggest that implicit social biases, as measured by the IAT, are largely intact in ASD. PMID:26386014

[Genotype-related changes in the reproductive function under social hierarchy in laboratory male mice].

PubMed

Osadchuk, L V; Salomacheva, I N; Osadchuk, A V

2010-01-01

The study was designed to investigate genetic differences in reproductive consequences of social hierarchy using inbred mice strains BALB/cLac, PT and CBA/Lac. Two adult males of different genotypes were housed together for 5 days. Hierarchical status of both partners was determined by asymmetry in agonistic behavior. The number of epididymal sperm and a proportion of abnormal sperm, weights of reproductive organs, serum concentration and testicular content of testosterone, and the testosterone response to introduction of a receptive female were determined. The testosterone measures were significantly decreased in the PT strain, the epididymal sperm number was significantly decreased in the BALB/cLac strain and a proportion of abnormal sperm heads was significantly increase in the CBA/Lac (in both dominants and subordinates) as compared to control mice. The testicular testosterone response to a receptive female and precopulatory behavior was unchanged in dominants and suppressed in subordinates of the BALB/cLac strain. The results indicate that in laboratory mice the pattern of reproductive response to social hierarchy is determined by genetic background.

Sulforaphane treatment of autism spectrum disorder (ASD)

PubMed Central

Singh, Kanwaljit; Connors, Susan L.; Macklin, Eric A.; Smith, Kirby D.; Fahey, Jed W.; Talalay, Paul; Zimmerman, Andrew W.

2014-01-01

Autism spectrum disorder (ASD), characterized by both impaired communication and social interaction, and by stereotypic behavior, affects about 1 in 68, predominantly males. The medico-economic burdens of ASD are enormous, and no recognized treatment targets the core features of ASD. In a placebo-controlled, double-blind, randomized trial, young men (aged 13–27) with moderate to severe ASD received the phytochemical sulforaphane (n = 29)—derived from broccoli sprout extracts—or indistinguishable placebo (n = 15). The effects on behavior of daily oral doses of sulforaphane (50–150 µmol) for 18 wk, followed by 4 wk without treatment, were quantified by three widely accepted behavioral measures completed by parents/caregivers and physicians: the Aberrant Behavior Checklist (ABC), Social Responsiveness Scale (SRS), and Clinical Global Impression Improvement Scale (CGI-I). Initial scores for ABC and SRS were closely matched for participants assigned to placebo and sulforaphane. After 18 wk, participants receiving placebo experienced minimal change (<3.3%), whereas those receiving sulforaphane showed substantial declines (improvement of behavior): 34% for ABC (P < 0.001, comparing treatments) and 17% for SRS scores (P = 0.017). On CGI-I, a significantly greater number of participants receiving sulforaphane had improvement in social interaction, abnormal behavior, and verbal communication (P = 0.015–0.007). Upon discontinuation of sulforaphane, total scores on all scales rose toward pretreatment levels. Dietary sulforaphane, of recognized low toxicity, was selected for its capacity to reverse abnormalities that have been associated with ASD, including oxidative stress and lower antioxidant capacity, depressed glutathione synthesis, reduced mitochondrial function and oxidative phosphorylation, increased lipid peroxidation, and neuroinflammmation. PMID:25313065

Sulforaphane treatment of autism spectrum disorder (ASD).

PubMed

Singh, Kanwaljit; Connors, Susan L; Macklin, Eric A; Smith, Kirby D; Fahey, Jed W; Talalay, Paul; Zimmerman, Andrew W

2014-10-28

Autism spectrum disorder (ASD), characterized by both impaired communication and social interaction, and by stereotypic behavior, affects about 1 in 68, predominantly males. The medico-economic burdens of ASD are enormous, and no recognized treatment targets the core features of ASD. In a placebo-controlled, double-blind, randomized trial, young men (aged 13-27) with moderate to severe ASD received the phytochemical sulforaphane (n = 29)--derived from broccoli sprout extracts--or indistinguishable placebo (n = 15). The effects on behavior of daily oral doses of sulforaphane (50-150 µmol) for 18 wk, followed by 4 wk without treatment, were quantified by three widely accepted behavioral measures completed by parents/caregivers and physicians: the Aberrant Behavior Checklist (ABC), Social Responsiveness Scale (SRS), and Clinical Global Impression Improvement Scale (CGI-I). Initial scores for ABC and SRS were closely matched for participants assigned to placebo and sulforaphane. After 18 wk, participants receiving placebo experienced minimal change (<3.3%), whereas those receiving sulforaphane showed substantial declines (improvement of behavior): 34% for ABC (P < 0.001, comparing treatments) and 17% for SRS scores (P = 0.017). On CGI-I, a significantly greater number of participants receiving sulforaphane had improvement in social interaction, abnormal behavior, and verbal communication (P = 0.015-0.007). Upon discontinuation of sulforaphane, total scores on all scales rose toward pretreatment levels. Dietary sulforaphane, of recognized low toxicity, was selected for its capacity to reverse abnormalities that have been associated with ASD, including oxidative stress and lower antioxidant capacity, depressed glutathione synthesis, reduced mitochondrial function and oxidative phosphorylation, increased lipid peroxidation, and neuroinflammmation.

Characterization of the Pathological and Biochemical Markers that Correlate to the Clinical Features of Autism: The Neuropathological Markers of Abnormal Brain Development and Aging in Autism

DTIC Science & Technology

2010-10-21

generalization of previously acquired skills, (f) rigidity and resistance to change, (g) social and communication defi cits, and (h) diffi culty in...defects and three diagnostic domains of autism (social and communication deficits, and ritualistic behaviors) and intellectual deficits. This process is...including: (a) qualitative impairments in reciprocal social interactions, (b) qualitative impairments in verbal and nonverbal communication , (c

Uncovering the Social Deficits in the Autistic Brain. A Source-Based Morphometric Study

PubMed Central

Grecucci, Alessandro; Rubicondo, Danilo; Siugzdaite, Roma; Surian, Luca; Job, Remo

2016-01-01

Autism is a neurodevelopmental disorder that mainly affects social interaction and communication. Evidence from behavioral and functional MRI studies supports the hypothesis that dysfunctional mechanisms involving social brain structures play a major role in autistic symptomatology. However, the investigation of anatomical abnormalities in the brain of people with autism has led to inconsistent results. We investigated whether specific brain regions, known to display functional abnormalities in autism, may exhibit mutual and peculiar patterns of covariance in their gray-matter concentrations. We analyzed structural MRI images of 32 young men affected by autistic disorder (AD) and 50 healthy controls. Controls were matched for sex, age, handedness. IQ scores were also monitored to avoid confounding. A multivariate Source-Based Morphometry (SBM) was applied for the first time on AD and controls to detect maximally independent networks of gray matter. Group comparison revealed a gray-matter source that showed differences in AD compared to controls. This network includes broad temporal regions involved in social cognition and high-level visual processing, but also motor and executive areas of the frontal lobe. Notably, we found that gray matter differences, as reflected by SBM, significantly correlated with social and behavioral deficits displayed by AD individuals and encoded via the Autism Diagnostic Observation Schedule scores. These findings provide support for current hypotheses about the neural basis of atypical social and mental states information processing in autism. PMID:27630538

Autism: Clinical and Research Issues.

ERIC Educational Resources Information Center

Accardo, Pasquale J., Ed.; Magnusen, Christy, Ed.; Capute, Arnold J., Ed.

This text examines the characteristics that define autism: impairments in communication; abnormal social development; and clinically significant odd behaviors. Specific chapters include: (1) Neural Mechanisms in Autism (Andrew W. Zimmerman and Barry Gordon); (2) Epidemiology of Autism and Other Pervasive Developmental Disorders: Current…

Conceptualizing neurodevelopmental disorders through a mechanistic understanding of fragile X syndrome and Williams syndrome.

PubMed

Fung, Lawrence K; Quintin, Eve-Marie; Haas, Brian W; Reiss, Allan L

2012-04-01

The overarching goal of this review is to compare and contrast the cognitive-behavioral features of fragile X syndrome (FraX) and Williams syndrome and to review the putative neural and molecular underpinnings of these features. Information is presented in a framework that provides guiding principles for conceptualizing gene-brain-behavior associations in neurodevelopmental disorders. Abnormalities, in particular cognitive-behavioral domains with similarities in underlying neurodevelopmental correlates, occur in both FraX and Williams syndrome including aberrant frontostriatal pathways leading to executive function deficits, and magnocellular/dorsal visual stream, superior parietal lobe, inferior parietal lobe, and postcentral gyrus abnormalities contributing to deficits in visuospatial function. Compelling cognitive-behavioral and neurodevelopmental contrasts also exist in these two disorders, for example, aberrant amygdala and fusiform cortex structure and function occurring in the context of contrasting social behavioral phenotypes, and temporal cortical and cerebellar abnormalities potentially underlying differences in language function. Abnormal dendritic development is a shared neurodevelopmental morphologic feature between FraX and Williams syndrome. Commonalities in molecular machinery and processes across FraX and Williams syndrome occur as well - microRNAs involved in translational regulation of major synaptic proteins; scaffolding proteins in excitatory synapses; and proteins involved in axonal development. Although the genetic variations leading to FraX and Williams syndrome are different, important similarities and contrasts in the phenotype, neurocircuitry, molecular machinery, and cellular processes in these two disorders allow for a unique approach to conceptualizing gene-brain-behavior links occurring in neurodevelopmental disorders.

Abnormal brain structure implicated in stimulant drug addiction.

PubMed

Ersche, Karen D; Jones, P Simon; Williams, Guy B; Turton, Abigail J; Robbins, Trevor W; Bullmore, Edward T

2012-02-03

Addiction to drugs is a major contemporary public health issue, characterized by maladaptive behavior to obtain and consume an increasing amount of drugs at the expense of the individual's health and social and personal life. We discovered abnormalities in fronto-striatal brain systems implicated in self-control in both stimulant-dependent individuals and their biological siblings who have no history of chronic drug abuse; these findings support the idea of an underlying neurocognitive endophenotype for stimulant drug addiction.

Disruption of the non-canonical Wnt gene PRICKLE2 leads to autism-like behaviors with evidence for hippocampal synaptic dysfunction

PubMed Central

Sowers, L. P.; Loo, L.; Wu, Y.; Campbell, E.; Ulrich, J. D.; Wu, S.; Paemka, L.; Wassink, T.; Meyer, K.; Bing, X.; El-Shanti, H.; Usachev, Y. M.; Ueno, N.; Manak, R. J.; Shepherd, A. J.; Ferguson, P. J.; Darbro, B. W.; Richerson, G. B.; Mohapatra, D. P.; Wemmie, J. A.; Bassuk, A. G.

2014-01-01

Autism spectrum disorders (ASDs) have been suggested to arise from abnormalities in the canonical and non-canonical Wnt signaling pathways. However, a direct connection between a human variant in a Wnt pathway gene and ASD-relevant brain pathology has not been established. Prickle2 (Pk2) is a post-synaptic non-canonical Wnt signaling protein shown to interact with post synaptic density 95 (PSD-95). Here we show that mice with disruption in Prickle2 display behavioral abnormalities including altered social interaction, learning abnormalities, and behavioral inflexibility. Prickle2 disruption in mouse hippocampal neurons led to reductions in dendrite branching, synapse number, and post-synaptic density size. Consistent with these findings, Prickle2 null neurons show decreased frequency and size of spontaneous miniature synaptic currents. These behavioral and physiological abnormalities in Prickle2 disrupted mice are consistent with ASD-like phenotypes present in other mouse models of ASDs. In 384 individuals with autism, we identified two with distinct, heterozygous, rare, non-synonymous PRICKLE2 variants (p.E8Q and p.V153I) that were shared by their affected siblings and inherited paternally. Unlike wild-type PRICKLE2, the PRICKLE2 variants found in ASD patients exhibit deficits in morphological and electrophysiological assays. These data suggest that these PRICKLE2 variants cause a critical loss of PRICKLE2 function. The data presented here provide new insight into the biological roles of Prickle2, its behavioral importance, and suggest disruptions in non-canonical Wnt genes such as PRICKLE2 may contribute to synaptic abnormalities underlying ASDs. PMID:23711981

Gabrb3 gene deficient mice exhibit impaired social and exploratory behaviors, deficits in non-selective attention and hypoplasia of cerebellar vermal lobules: a potential model of autism spectrum disorder

PubMed Central

DeLorey, Timothy M.; Sahbaie, Peyman; Hashemi, Ezzat; Homanics, Gregg E.; Clark, J. David

2009-01-01

Objective GABAA receptors play an important regulatory role in the developmental events leading to the formation of complex neuronal networks and to the behaviors they govern. The primary aim of this study was to assess whether gabrb3 gene deficient (gabrb3-/-) mice exhibit abnormal social behavior, a core deficit associated with autism spectrum disorder. Methods Social and exploratory behaviors along with non-selective attention were assessed in gabrb3-/-, littermates (gabrb3+/+) and progenitor strains, C57BL/6J and 129/SvJ. In addition, semi-quantitative assessments of the size of cerebellar vermal lobules were performed on gabrb3+/+ and gabrb3-/- mice. Results Relative to controls, gabrb3-/- mice exhibited significant deficits in activities related to social behavior including sociability, social novelty and nesting. In addition, gabrb3-/- mice also exhibited differences in exploratory behavior compared to controls, as well as reductions in the frequency and duration of rearing episodes, suggested as being an index of non-selective attention. Gabrb3-/- mice also displayed significant hypoplasia of the cerebellar vermis compared to gabrb3+/+ mice. Conclusions The observed behavioral deficits, especially regarding social behaviors, strengthens the face validity of the gabrb3 gene deficient mouse as being a model of autism spectrum disorder. PMID:17983671

Visual attention shifting in autism spectrum disorders.

PubMed

Richard, Annette E; Lajiness-O'Neill, Renee

2015-01-01

Abnormal visual attention has been frequently observed in autism spectrum disorders (ASD). Abnormal shifting of visual attention is related to abnormal development of social cognition and has been identified as a key neuropsychological finding in ASD. Better characterizing attention shifting in ASD and its relationship with social functioning may help to identify new targets for intervention and improving social communication in these disorders. Thus, the current study investigated deficits in attention shifting in ASD as well as relationships between attention shifting and social communication in ASD and neurotypicals (NT). To investigate deficits in visual attention shifting in ASD, 20 ASD and 20 age- and gender-matched NT completed visual search (VS) and Navon tasks with attention-shifting demands as well as a set-shifting task. VS was a feature search task with targets defined in one of two dimensions; Navon required identification of a target letter presented at the global or local level. Psychomotor and processing speed were entered as covariates. Relationships between visual attention shifting, set shifting, and social functioning were also examined. ASD and NT showed comparable costs of shifting attention. However, psychomotor and processing speed were slower in ASD than in NT, and psychomotor and processing speed were positively correlated with attention-shifting costs on Navon and VS, respectively, for both groups. Attention shifting on VS and Navon were correlated among NT, while attention shifting on Navon was correlated with set shifting among ASD. Attention-shifting costs on Navon were positively correlated with restricted and repetitive behaviors among ASD. Relationships between attention shifting and psychomotor and processing speed, as well as relationships between measures of different aspects of visual attention shifting, suggest inefficient top-down influences over preattentive visual processing in ASD. Inefficient attention shifting may be related to restricted and repetitive behaviors in these disorders.

Social anhedonia is associated with neural abnormalities during face emotion processing.

PubMed

Germine, Laura T; Garrido, Lucia; Bruce, Lori; Hooker, Christine

2011-10-01

Human beings are social organisms with an intrinsic desire to seek and participate in social interactions. Social anhedonia is a personality trait characterized by a reduced desire for social affiliation and reduced pleasure derived from interpersonal interactions. Abnormally high levels of social anhedonia prospectively predict the development of schizophrenia and contribute to poorer outcomes for schizophrenia patients. Despite the strong association between social anhedonia and schizophrenia, the neural mechanisms that underlie individual differences in social anhedonia have not been studied and are thus poorly understood. Deficits in face emotion recognition are related to poorer social outcomes in schizophrenia, and it has been suggested that face emotion recognition deficits may be a behavioral marker for schizophrenia liability. In the current study, we used functional magnetic resonance imaging (fMRI) to see whether there are differences in the brain networks underlying basic face emotion processing in a community sample of individuals low vs. high in social anhedonia. We isolated the neural mechanisms related to face emotion processing by comparing face emotion discrimination with four other baseline conditions (identity discrimination of emotional faces, identity discrimination of neutral faces, object discrimination, and pattern discrimination). Results showed a group (high/low social anhedonia) × condition (emotion discrimination/control condition) interaction in the anterior portion of the rostral medial prefrontal cortex, right superior temporal gyrus, and left somatosensory cortex. As predicted, high (relative to low) social anhedonia participants showed less neural activity in face emotion processing regions during emotion discrimination as compared to each control condition. The findings suggest that social anhedonia is associated with abnormalities in networks responsible for basic processes associated with social cognition, and provide a starting point for understanding the neural basis of social motivation and our drive to seek social affiliation. Copyright © 2011 Elsevier Inc. All rights reserved.

Subthalamic nucleus modulates social and anxogenic-like behaviors.

PubMed

Reymann, Jean-Michel; Naudet, Florian; Pihan, Morgane; Saïkali, Stephan; Laviolle, Bruno; Bentué-Ferrer, Danièle

2013-09-01

In Parkinson's disease, global social maladjustment and anxiety are frequent after subthalamic nucleus (STN) stimulation and are generally considered to be linked with sociofamilial alterations induced by the motor effects of stimulation. We hypothesized that the STN is per se involved in these changes and aimed to explore the role of STN in social and anxogenic-like behaviors using an animal model. Nineteen male Wistar rats with bilateral lesions of the STN were compared with 26 sham-lesioned rats by synchronizing an ethological approach based upon direct observation of social behaviors and a standardized approach, the elevated plus maze (EPM). Comparisons between groups were performed by a Mann-Whitney-Wilcoxon test. Lesioned rats showed impairments in their social (P=0.05) and aggressive behaviors with a diminution of attacking (P=0.04) and chasing (P=0.06). In the EPM, concerning the open arms, the percentage of distance, time, inactive time, and entry were significantly decreased in lesioned rats (P=0.02, P=0.01, P=0.04, and P=0.05). The time spent in non-protected head dips was also diminished in the lesioned rats (P=0.01). These results strongly implicate the STN in social behavior and anxogenic-like behavior. In human, as DBS induces changes in the underlying dynamics of the stimulated brain networks, it could create an abnormal brain state in which anxiety and social behavior are altered. These results highlight another level of complexity of the behavioral changes after stimulation. Copyright © 2013 Elsevier B.V. All rights reserved.

Chronic Desipramine Treatment Rescues Depression-Related, Social and Cognitive Deficits in Engrailed-2 Knockout Mice

PubMed Central

Brielmaier, Jennifer; Senerth, Julia M.; Silverman, Jill L.; Matteson, Paul G.; Millonig, James H.; DiCicco-Bloom, Emanuel; Crawley, Jacqueline N.

2014-01-01

Engrailed-2 (En2) is a homeobox transcription factor that regulates neurodevelopmental processes including neuronal connectivity and elaboration of monoaminergic neurons in the ventral hindbrain. We previously reported abnormalities in brain noradrenergic concentrations in En2 null mutant mice that were accompanied by increased immobility in the forced swim test, relevant to depression. An EN2 genetic polymorphism has been associated with autism spectrum disorders (ASD), and mice with a deletion in En2 display social abnormalities and cognitive deficits that may be relevant to multiple neuropsychiatric conditions. The present study evaluated the ability of chronic treatment with desipramine (DMI), a selective norepinephrine reuptake inhibitor and classical antidepressant, to reverse behavioral abnormalities in En2 −/− mice. DMI treatment significantly reduced immobility in the tail suspension and forced swim tests, restored sociability in the three-chambered social approach task, and reversed impairments in contextual fear conditioning in En2 −/− mice. Our findings indicate that modulation of brain noradrenergic systems rescues the depression-related phenotype in En2 −/− mice and suggest new roles for norepinephrine in the pathophysiology of the social and cognitive deficits seen in neuropsychiatric disorders such as autism or schizophrenia. PMID:24730055

Region specific up-regulation of oxytocin receptors in the opioid oprm1 (-/-) mouse model of autism.

PubMed

Gigliucci, Valentina; Leonzino, Marianna; Busnelli, Marta; Luchetti, Alessandra; Palladino, Viola Stella; D'Amato, Francesca R; Chini, Bice

2014-01-01

Autism spectrum disorders (ASDs) are characterized by impaired communication, social impairments, and restricted and repetitive behaviors and interests. Recently, altered motivation and reward processes have been suggested to participate in the physiopathology of ASDs, and μ-opioid receptors (MORs) have been investigated in relation to social reward due to their involvement in the neural circuitry of reward. Mice lacking a functional MOR gene (Oprm1 (-/-) mice) display abnormal social behavior and major autistic-like core symptoms, making them an animal model of autism. The oxytocin (OXT) system is a key regulator of social behavior and co-operates with the opioidergic system in the modulation of social behavior. To better understand the opioid-OXT interplay in the central nervous system, we first determined the expression of the oxytocin receptor (OXTR) in the brain of WT C57BL6/J mice by quantitative autoradiography; we then evaluated OXTR regional alterations in Oprm1 (-/-) mice. Moreover, we tested these mice in a paradigm of social behavior, the male-female social interaction test, and analyzed the effects of acute intranasal OXT treatment on their performance. In autoradiography, Oprm1 (-/-) mice selectively displayed increased OXTR expression in the Medial Anterior Olfactory Nucleus, the Central and Medial Amygdaloid nuclei, and the Nucleus Accumbens. Our behavioral results confirmed that Oprm1 (-/-) male mice displayed social impairments, as indicated by reduced ultrasonic calls, and that these were rescued by a single intranasal administration of OXT. Taken together, our results provide evidence of an interaction between OXT and opioids in socially relevant brain areas and in the modulation of social behavior. Moreover, they suggest that the oxytocinergic system may act as a compensative mechanism to bypass and/or restore alterations in circuits linked to impaired social behavior.

Game Theory Paradigm: A New Tool for Investigating Social Dysfunction in Major Depressive Disorders

PubMed Central

Wang, Yun; Yang, Liu-Qing; Li, Shu; Zhou, Yuan

2015-01-01

Social dysfunction is a prominent source of distress and disability in patients with major depressive disorder (MDD) but is commonly omitted from current clinical studies, although some researchers propose an evolutionary strategy to understand these negative outcomes. Limited knowledge about the neural basis of social dysfunction in MDD results from traditional paradigms, which lack insights into social interactions. Game theoretical modeling offers a new tool for investigating social-interaction impairments in neuropsychiatric disorders. This review first introduces three widely used games from game theory and the major behavioral and neuroimaging findings obtained using these games in healthy populations. We also address the factors that modulate behaviors in games and their neural bases. We then summarize the current findings obtained by using these games in depressed patients and discuss the clinical implications of these abnormal game behaviors. Finally, we briefly discuss future prospects that may further elucidate the clinical use of a game theory paradigm in MDD. PMID:26441689

Game Theory Paradigm: A New Tool for Investigating Social Dysfunction in Major Depressive Disorders.

PubMed

Wang, Yun; Yang, Liu-Qing; Li, Shu; Zhou, Yuan

2015-01-01

Social dysfunction is a prominent source of distress and disability in patients with major depressive disorder (MDD) but is commonly omitted from current clinical studies, although some researchers propose an evolutionary strategy to understand these negative outcomes. Limited knowledge about the neural basis of social dysfunction in MDD results from traditional paradigms, which lack insights into social interactions. Game theoretical modeling offers a new tool for investigating social-interaction impairments in neuropsychiatric disorders. This review first introduces three widely used games from game theory and the major behavioral and neuroimaging findings obtained using these games in healthy populations. We also address the factors that modulate behaviors in games and their neural bases. We then summarize the current findings obtained by using these games in depressed patients and discuss the clinical implications of these abnormal game behaviors. Finally, we briefly discuss future prospects that may further elucidate the clinical use of a game theory paradigm in MDD.

Diagnosis, treatment, and neurobiology of autism in children.

PubMed

Lainhart, J E; Piven, J

1995-08-01

Autism is a developmental neuropsychiatric disorder defined by the presence of social and communicative deficits, restricted and repetitive behaviors and interests, and a characteristic course. Research suggests that hereditary factors play a principal role in the etiology of most cases. A phenotype broader than autism, including milder social and language-based cognitive deficits, appears to be inherited. Although the pathogenesis is unknown, neurobiologic mechanisms clearly underlie the disorder. Neuropathologic studies have demonstrated abnormalities in limbic structures, the cerebellum, and the cortex. New advances in behavioral therapies and pharmacologic treatment are important components of successful multidisciplinary treatment of this disorder.

Behavioral Effects of an Enhanced Enrichment Program for Group-Housed Sooty Mangabeys (Cercocebus atys)

PubMed Central

Crast, Jessica; Bloomsmith, Mollie A; Jonesteller, Trina J

2016-01-01

Evaluating the behavioral effects of enrichment on animals housed in biomedical facilities is necessary to effectively support their care and wellbeing. We tested the cumulative effects of an enhanced enrichment program on sooty mangabey behavior: locomotion, feeding and foraging, manipulating items in the enclosure, social affiliation, aggression, and abnormal behavior. The enhanced enrichment program included the addition of a substrate (timothy hay), widely distributing small pieces of produce and a forage mixture in the hay, adding structures and perching, and increasing the variety of food items, foraging devices, and other manipulable items. We tested 10 groups living in runs (n = 54) by using an ABA experimental design (phase A, standard enrichment; phase B, enhanced enrichment) and Wilcoxon signed-rank tests to compare behavior across phases. During phase B, subjects significantly increased feeding, foraging, and manipulation of items, and they decreased self-grooming, social affiliation, and aggression. Combined enrichment use increased from approximately 10% to 21% of the mangabeys’ time. Enhanced enrichment did not affect locomotion or abnormal behavior. The increases in feeding, foraging, and manipulation during enhanced enrichment were driven primarily by the subjects’ preference for foraging in the hay: it was the most effective component of the program in promoting feeding and foraging behavior, which comprises the majority of wild sooty mangabeys’ daily activity. Developing an effective, species-appropriate, and comprehensive enrichment program is essential to successfully promote the health and wellbeing of captive NHP. PMID:27931313

Behavioral Effects of an Enhanced Enrichment Program for Group-Housed Sooty Mangabeys (Cercocebus atys).

PubMed

Crast, Jessica; Bloomsmith, Mollie A; Jonesteller, Trina J

2016-11-01

Evaluating the behavioral effects of enrichment on animals housed in biomedical facilities is necessary to effectively support their care and wellbeing. We tested the cumulative effects of an enhanced enrichment program on sooty mangabey behavior: locomotion, feeding and foraging, manipulating items in the enclosure, social affiliation, aggression, and abnormal behavior. The enhanced enrichment program included the addition of a substrate (timothy hay), widely distributing small pieces of produce and a forage mixture in the hay, adding structures and perching, and increasing the variety of food items, foraging devices, and other manipulable items. We tested 10 groups living in runs (n = 54) by using an ABA experimental design (phase A, standard enrichment; phase B, enhanced enrichment) and Wilcoxon signed-rank tests to compare behavior across phases. During phase B, subjects significantly increased feeding, foraging, and manipulation of items, and they decreased self-grooming, social affiliation, and aggression. Combined enrichment use increased from approximately 10% to 21% of the mangabeys' time. Enhanced enrichment did not affect locomotion or abnormal behavior. The increases in feeding, foraging, and manipulation during enhanced enrichment were driven primarily by the subjects' preference for foraging in the hay: it was the most effective component of the program in promoting feeding and foraging behavior, which comprises the majority of wild sooty mangabeys' daily activity. Developing an effective, species-appropriate, and comprehensive enrichment program is essential to successfully promote the health and wellbeing of captive NHP.

Altered behavior and neural activity in conspecific cagemates co-housed with mouse models of brain disorders.

PubMed

Yang, Hyunwoo; Jung, Seungmoon; Seo, Jinsoo; Khalid, Arshi; Yoo, Jung-Seok; Park, Jihyun; Kim, Soyun; Moon, Jangsup; Lee, Soon-Tae; Jung, Keun-Hwa; Chu, Kon; Lee, Sang Kun; Jeon, Daejong

2016-09-01

The psychosocial environment is one of the major contributors of social stress. Family members or caregivers who consistently communicate with individuals with brain disorders are considered at risk for physical and mental health deterioration, possibly leading to mental disorders. However, the underlying neural mechanisms of this phenomenon remain poorly understood. To address this, we developed a social stress paradigm in which a mouse model of epilepsy or depression was housed long-term (>4weeks) with normal conspecifics. We characterized the behavioral phenotypes and electrophysiologically investigated the neural activity of conspecific cagemate mice. The cagemates exhibited deficits in behavioral tasks assessing anxiety, locomotion, learning/memory, and depression-like behavior. Furthermore, they showed severe social impairment in social behavioral tasks involving social interaction or aggression. Strikingly, behavioral dysfunction remained in the cagemates 4weeks following co-housing cessation with the mouse models. In an electrophysiological study, the cagemates showed an increased number of spikes in medial prefrontal cortex (mPFC) neurons. Our results demonstrate that conspecifics co-housed with mouse models of brain disorders develop chronic behavioral dysfunctions, and suggest a possible association between abnormal mPFC neural activity and their behavioral pathogenesis. These findings contribute to the understanding of the psychosocial and psychiatric symptoms frequently present in families or caregivers of patients with brain disorders. Copyright © 2016 Elsevier Inc. All rights reserved.

Assessment and Treatment in Autism Spectrum Disorders: A Focus on Genetics and Psychiatry

PubMed Central

Butler, Merlin G.; Youngs, Erin L.; Roberts, Jennifer L.; Hellings, Jessica A.

2012-01-01

Autism spectrum disorders (ASDs) are neurobehavioral disorders characterized by abnormalities in three behavioral domains including social interaction, impaired communication, and repetitive stereotypic behaviors. ASD affects approximately 1% of children and is on the rise with significant genetic mechanisms underlying these disorders. We review the current understanding of the role of genetic and metabolic factors contributing to ASD with the use of new genetic technology. Fifty percent is diagnosed with chromosomal abnormalities, small DNA deletions/duplications, single-gene conditions, or metabolic disturbances. Genetic evaluation is discussed along with psychiatric treatment and approaches for selection of medication to treat associated challenging behaviors or comorbidities seen in ASD. We emphasize the importance of prioritizing treatment based on target symptom clusters and in what order for individuals with ASD, as the treatment may vary from patient to patient. PMID:22934170

Conceptualizing neurodevelopmental disorders through a mechanistic understanding of fragile X syndrome and Williams syndrome

PubMed Central

Fung, Lawrence K.; Quintin, Eve-Marie; Haas, Brian W.

2013-01-01

Purpose of review The overarching goal of this review is to compare and contrast the cognitive-behavioral features of fragile X syndrome (FraX) and Williams syndrome and to review the putative neural and molecular underpinnings of these features. Information is presented in a framework that provides guiding principles for conceptualizing gene-brain-behavior associations in neurodevelopmental disorders. Recent findings Abnormalities, in particular cognitive-behavioral domains with similarities in underlying neurodevelopmental correlates, occur in both FraX and Williams syndrome including aberrant frontostriatal pathways leading to executive function deficits, and magnocellular/dorsal visual stream, superior parietal lobe, inferior parietal lobe, and postcentral gyrus abnormalities contributing to deficits in visuospatial function. Compelling cognitive–behavioral and neurodevelopmental contrasts also exist in these two disorders, for example, aberrant amygdala and fusiform cortex structure and function occurring in the context of contrasting social behavioral phenotypes, and temporal cortical and cerebellar abnormalities potentially underlying differences in language function. Abnormal dendritic development is a shared neurodevelopmental morphologic feature between FraX and Williams syndrome. Commonalities in molecular machinery and processes across FraX and Williams syndrome occur as well – microRNAs involved in translational regulation of major synaptic proteins; scaffolding proteins in excitatory synapses; and proteins involved in axonal development. Summary Although the genetic variations leading to FraX and Williams syndrome are different, important similarities and contrasts in the phenotype, neurocircuitry, molecular machinery, and cellular processes in these two disorders allow for a unique approach to conceptualizing gene–brain–behavior links occurring in neurodevelopmental disorders. PMID:22395002

GABAB-mediated rescue of altered excitatory-inhibitory balance, gamma synchrony and behavioral deficits following constitutive NMDAR-hypofunction.

PubMed

Gandal, M J; Sisti, J; Klook, K; Ortinski, P I; Leitman, V; Liang, Y; Thieu, T; Anderson, R; Pierce, R C; Jonak, G; Gur, R E; Carlson, G; Siegel, S J

2012-07-17

Reduced N-methyl-D-aspartate-receptor (NMDAR) signaling has been associated with schizophrenia, autism and intellectual disability. NMDAR-hypofunction is thought to contribute to social, cognitive and gamma (30-80 Hz) oscillatory abnormalities, phenotypes common to these disorders. However, circuit-level mechanisms underlying such deficits remain unclear. This study investigated the relationship between gamma synchrony, excitatory-inhibitory (E/I) signaling, and behavioral phenotypes in NMDA-NR1(neo-/-) mice, which have constitutively reduced expression of the obligate NR1 subunit to model disrupted developmental NMDAR function. Constitutive NMDAR-hypofunction caused a loss of E/I balance, with an increase in intrinsic pyramidal cell excitability and a selective disruption of parvalbumin-expressing interneurons. Disrupted E/I coupling was associated with deficits in auditory-evoked gamma signal-to-noise ratio (SNR). Gamma-band abnormalities predicted deficits in spatial working memory and social preference, linking cellular changes in E/I signaling to target behaviors. The GABA(B)-receptor agonist baclofen improved E/I balance, gamma-SNR and broadly reversed behavioral deficits. These data demonstrate a clinically relevant, highly translatable neural-activity-based biomarker for preclinical screening and therapeutic development across a broad range of disorders that share common endophenotypes and disrupted NMDA-receptor signaling.

Facial affect processing and depression susceptibility: cognitive biases and cognitive neuroscience.

PubMed

Bistricky, Steven L; Ingram, Rick E; Atchley, Ruth Ann

2011-11-01

Facial affect processing is essential to social development and functioning and is particularly relevant to models of depression. Although cognitive and interpersonal theories have long described different pathways to depression, cognitive-interpersonal and evolutionary social risk models of depression focus on the interrelation of interpersonal experience, cognition, and social behavior. We therefore review the burgeoning depressive facial affect processing literature and examine its potential for integrating disciplines, theories, and research. In particular, we evaluate studies in which information processing or cognitive neuroscience paradigms were used to assess facial affect processing in depressed and depression-susceptible populations. Most studies have assessed and supported cognitive models. This research suggests that depressed and depression-vulnerable groups show abnormal facial affect interpretation, attention, and memory, although findings vary based on depression severity, comorbid anxiety, or length of time faces are viewed. Facial affect processing biases appear to correspond with distinct neural activity patterns and increased depressive emotion and thought. Biases typically emerge in depressed moods but are occasionally found in the absence of such moods. Indirect evidence suggests that childhood neglect might cultivate abnormal facial affect processing, which can impede social functioning in ways consistent with cognitive-interpersonal and interpersonal models. However, reviewed studies provide mixed support for the social risk model prediction that depressive states prompt cognitive hypervigilance to social threat information. We recommend prospective interdisciplinary research examining whether facial affect processing abnormalities promote-or are promoted by-depressogenic attachment experiences, negative thinking, and social dysfunction.

Social phobia: etiology, neurobiology, and treatment.

PubMed

Coupland, N J

2001-01-01

Social phobia is a common and often disabling condition, with an etiology that is not established. There is evidence at several levels for an interplay of biological and psychological processes in social phobia. Genetic studies show that both genetic and environmental factors are important, with evidence pointing to associations with 2 genetic conditions, autism and fragile X syndrome. Behavioral inhibition has emerged as an important precursor to social phobia and possibly to other anxiety disorders. Epidemiologic and clinical studies have suggested that factors within the family environment, such as overprotection, overcontrol, modeling of anxiety, criticism, and in some cases abuse, can play a role in the development of social phobia. During childhood, complex interactions between brain system disturbances that mediate responses to negative social cues and factors in the social setting may lead to the development of a distorted set of internal "blueprints" for social behavior. The impact of severe social anxiety on brain systems that mediate behavioral change may prevent patients from learning better "blueprints." These can be taught through cognitive-behavioral therapies. The effective control of social anxiety with medications enables patients to recover; whether recovery can last after discontinuation of medications may depend on whether a new "blueprint" has been developed and whether stable changes in affected brain systems have occurred. Neuroimaging techniques are at the early stage of identifying abnormalities at the neurotransmitter and systems levels.

The 7q11.23 Microduplication Syndrome: A Clinical Report with Review of Literature

PubMed Central

Abbas, Elham; Cox, Devin M.; Smith, Teri; Butler, Merlin G.

2016-01-01

We report a 14-year-old adolescent girl with selective mutism (SM) and a 7q11.23 microduplication detected by chromosomal microarray (CMA) analysis and reviewed the literature from 18 published clinical reports. Our patient had specific phobias, SM, extreme anxiety, obesity, cutis marmorata, and a round appearing face with a short neck and over folded ears. We reviewed the published clinical, cognitive, behavioral, and cytogenetic findings grouped by speech and language delay, growth and development, craniofacial, clinical, and behavior and cognitive features due to the 7q11.23 microduplication. This microduplication syndrome is characterized by speech delay (91%), social anxiety (42%), attention deficit hyperactivity disorder (ADHD, 37%), autism spectrum disorder (29%), and separation anxiety (13%). Other findings include abnormal brain imaging (80%), congenital heart and vascular defects (54%), and mild intellectual disability (38%). We then compared the phenotype with Williams–Beuren syndrome (WBS) which is due to a deletion of the same chromosome region. Both syndromes have abnormal brain imaging, hypotonia, delayed motor development, joint laxity, mild intellectual disability, ADHD, autism, and poor visuospatial skills but opposite or dissimilar findings regarding speech and behavioral patterns, cardiovascular problems, and social interaction. Those with WBS are prone to have hyperverbal speech, lack of stranger anxiety, and supravalvular aortic stenosis while those with the 7q11.23 microduplication have speech delay, SM, social anxiety, and are prone to aortic dilatation. PMID:27617154

The 7q11.23 Microduplication Syndrome: A Clinical Report with Review of Literature.

PubMed

Abbas, Elham; Cox, Devin M; Smith, Teri; Butler, Merlin G

2016-09-01

We report a 14-year-old adolescent girl with selective mutism (SM) and a 7q11.23 microduplication detected by chromosomal microarray (CMA) analysis and reviewed the literature from 18 published clinical reports. Our patient had specific phobias, SM, extreme anxiety, obesity, cutis marmorata, and a round appearing face with a short neck and over folded ears. We reviewed the published clinical, cognitive, behavioral, and cytogenetic findings grouped by speech and language delay, growth and development, craniofacial, clinical, and behavior and cognitive features due to the 7q11.23 microduplication. This microduplication syndrome is characterized by speech delay (91%), social anxiety (42%), attention deficit hyperactivity disorder (ADHD, 37%), autism spectrum disorder (29%), and separation anxiety (13%). Other findings include abnormal brain imaging (80%), congenital heart and vascular defects (54%), and mild intellectual disability (38%). We then compared the phenotype with Williams-Beuren syndrome (WBS) which is due to a deletion of the same chromosome region. Both syndromes have abnormal brain imaging, hypotonia, delayed motor development, joint laxity, mild intellectual disability, ADHD, autism, and poor visuospatial skills but opposite or dissimilar findings regarding speech and behavioral patterns, cardiovascular problems, and social interaction. Those with WBS are prone to have hyperverbal speech, lack of stranger anxiety, and supravalvular aortic stenosis while those with the 7q11.23 microduplication have speech delay, SM, social anxiety, and are prone to aortic dilatation.

Autism-related behavioral abnormalities in synapsin knockout mice.

PubMed

Greco, Barbara; Managò, Francesca; Tucci, Valter; Kao, Hung-Teh; Valtorta, Flavia; Benfenati, Fabio

2013-08-15

Several synaptic genes predisposing to autism-spectrum disorder (ASD) have been identified. Nonsense and missense mutations in the SYN1 gene encoding for Synapsin I have been identified in families segregating for idiopathic epilepsy and ASD and genetic mapping analyses have identified variations in the SYN2 gene as significantly contributing to epilepsy predisposition. Synapsins (Syn I/II/III) are a multigene family of synaptic vesicle-associated phosphoproteins playing multiple roles in synaptic development, transmission and plasticity. Lack of SynI and/or SynII triggers a strong epileptic phenotype in mice associated with mild cognitive impairments that are also present in the non-epileptic SynIII(-/-) mice. SynII(-/-) and SynIII(-/-) mice also display schizophrenia-like traits, suggesting that Syns could be involved in the regulation of social behavior. Here, we studied social interaction and novelty, social recognition and social dominance, social transmission of food preference and social memory in groups of male SynI(-/-), SynII(-/-) and SynIII(-/-) mice before and after the appearance of the epileptic phenotype and compared their performances with control mice. We found that deletion of Syn isoforms widely impairs social behaviors and repetitive behaviors, resulting in ASD-related phenotypes. SynI or SynIII deletion altered social behavior, whereas SynII deletion extensively impaired various aspects of social behavior and memory, altered exploration of a novel environment and increased self-grooming. Social impairments of SynI(-/-) and SynII(-/-) mice were evident also before the onset of seizures. The results demonstrate an involvement of Syns in generation of the behavioral traits of ASD and identify Syn knockout mice as a useful experimental model of ASD and epilepsy. Copyright © 2013 Elsevier B.V. All rights reserved.

Oxytocin enhances gaze-following responses to videos of natural social behavior in adult male rhesus monkeys

PubMed Central

Putnam, P.T.; Roman, J.M.; Zimmerman, P.E.; Gothard, K.M.

2017-01-01

Gaze following is a basic building block of social behavior that has been observed in multiple species, including primates. The absence of gaze following is associated with abnormal development of social cognition, such as in autism spectrum disorders (ASD). Some social deficits in ASD, including the failure to look at eyes and the inability to recognize facial expressions, are ameliorated by intranasal administration of oxytocin (IN-OT). Here we tested the hypothesis that IN-OT might enhance social processes that require active engagement with a social partner, such as gaze following. Alternatively, IN-OT may only enhance the perceptual salience of the eyes, and may not modify behavioral responses to social signals. To test this hypothesis, we presented four monkeys with videos of conspecifics displaying natural behaviors. Each video was viewed multiple times before and after the monkeys received intranasally either 50 IU of OT or saline. We found that despite a gradual decrease in attention to the repeated viewing of the same videos (habituation), IN-OT consistently increased the frequency of gaze following saccades. Further analysis confirmed that these behaviors did not occur randomly, but rather predictably in response to the same segments of the videos. These findings suggest that in response to more naturalistic social stimuli IN-OT enhances the propensity to interact with a social partner rather than merely elevating the perceptual salience of the eyes. In light of these findings, gaze following may serve as a metric for pro-social effects of oxytocin that target social action more than social perception. PMID:27343726

A Scale of Socioemotional Dysfunction in Frontotemporal Dementia

PubMed Central

Barsuglia, Joseph P.; Kaiser, Natalie C.; Wilkins, Stacy Schantz; Joshi, Aditi; Barrows, Robin J.; Paholpak, Pongsatorn; Panchal, Hemali Vijay; Jimenez, Elvira E.; Mather, Michelle J.; Mendez, Mario F.

2014-01-01

Early social dysfunction is a hallmark symptom of behavioral variant frontotemporal dementia (bvFTD); however, validated measures for assessing social deficits in dementia are needed. The purpose of the current study was to examine the utility of a novel informant-based measure of social impairment, the Socioemotional Dysfunction Scale (SDS) in early-onset dementia. Sixteen bvFTD and 18 early-onset Alzheimer’s disease (EOAD) participants received standard clinical neuropsychological measures and neuroimaging. Caregiver informants were administered the SDS. Individuals with bvFTD exhibited greater social dysfunction on the SDS compared with the EOAD group; t(32) = 6.32, p < .001. The scale demonstrated preliminary evidence for discriminating these frequently misdiagnosed groups (area under the curve = 0.920, p = <.001) and internal consistency α = 0.977. The SDS demonstrated initial evidence as an effective measure for detecting abnormal social behavior and discriminating bvFTD from EOAD. Future validation is recommended in larger and more diverse patient groups. PMID:25331776

Wistar audiogenic rats display abnormal behavioral traits associated with artificial selection for seizure susceptibility.

PubMed

Castro, Gabriel Perfeito; Medeiros, Daniel de Castro; Guarnieri, Leonardo de Oliveira; Mourão, Flávio Afonso Gonçalves; Pinto, Hyorrana Priscila Pereira; Pereira, Grace Schenatto; Moraes, Márcio Flávio Dutra

2017-06-01

Accumulating evidence from different animal models has contributed to the understanding of the bidirectional comorbidity associations between the epileptic condition and behavioral abnormalities. A strain of animals inbred to enhance seizure predisposition to high-intensity sound stimulation, the Wistar audiogenic rat (WAR), underwent several behavioral tests: forced swim test (FST), open-field test (OFT), sucrose preference test (SPT), elevated plus maze (EPM), social preference (SP), marble burying test (MBT), inhibitory avoidance (IAT), and two-way active avoidance (TWAA). The choice of tests aimed to investigate the correlation between underlying circuits believed to be participating in both WAR's innate susceptibility to sound-triggered seizures and the neurobiological substrates associated with test performance. Comparing WAR with its Wistar counterpart (i.e., resistant to audiogenic seizures) showed that WARs present behavioral despair traits (e.g., increased FST immobility) but no evidence of anhedonic behavior (e.g., increased sucrose consumption in SPT) or social impairment (e.g., no difference regarding juvenile exploration in SP). In addition, tests suggested that WARs are unable to properly evaluate degrees of aversiveness (e.g., performance on OFT, EPM, MBT, IAT, and TWAA). The particularities of the WAR model opens new venues to further untangle the neurobiology underlying the co-morbidity of behavioral disorders and epilepsy. This article is part of a Special Issue entitled "Genetic and Reflex Epilepsies, Audiogenic Seizures and Strains: From Experimental Models to the Clinic". Copyright © 2015 Elsevier Inc. All rights reserved.

BTBR T+tf/J MICE: AUTISM-RELEVANT BEHAVIORS AND REDUCED FRACTONE-ASSOCIATED HEPARAN SULFATE

PubMed Central

Blanchard, D. Caroline; Defensor, Erwin B.; Meyza, Ksenia Z.; Pobbe, Roger L.H.; Pearson, Brandon L.; Bolivar, Valerie J.; Blanchard, Robert J.

2011-01-01

BTBR T+tf/J (BTBR) mice have emerged as strong candidates to serve as models of a range of autism-relevant behaviors, showing deficiencies in social behaviors; reduced or unusual ultrasonic vocalizations in conspecific situations; and enhanced, repetitive self grooming. Recent studies have described their behaviors in a seminatural Visible Burrow System (VBS); a social proximity test in which avoidance of a conspecific is impossible; and in an object approach and investigation test evaluating attention to specific objects and potential stereotypies in the order of approaching/investigating objects. VBS results confirmed strong BTBR avoidance of conspecifics and in the social proximity test, BTBR showed dramatic differences in several close-in behaviors, including specific avoidance of a nose-to-nose contact that may potentially be related to gaze-avoidance. Diazepam normalized social avoidance by BTBRs in a three-chamber test, and some additional behaviors –but not nose to nose avoidance- in the social proximity test. BTBR also showed higher levels of preference for particular objects, and higher levels of sequences investigating 3- or 4- objects in the same order. Heparan sulfate (HS) associated with fractal structures in the subventricular zone of the lateral ventricles was severely reduced in BTBR. HS may modulate the functions of a range of growth and guidance factors during development, and HS abnormalities are associated with relevant brain (callosal agenesis) and behavioral (reductions in sociality) changes; suggesting the value of examination of the dynamics of the HS system in the context of autism. PMID:21741402

Pornography, Human Mutilation and Psychological Dysfunction.

ERIC Educational Resources Information Center

Shaughnessy, Michael F.

Pornography is widely available and inevitably linked to crime and abnormal behavior. Social scientists must be concerned with the long-term effects on consenting adults and children and adolescents of exposure to pornography and human mutilation. An experiment in which a treatment group is exposed to pornography and a control group is exposed…

Norm Theory: Comparing Reality to Its Alternatives.

ERIC Educational Resources Information Center

Kahneman, Daniel; Miller, Dale T.

1986-01-01

A theory of norms and normality is applied to some phenomena of emotional responses, social judgment, and conversations about causes. Norm theory is applied in analyses of enhanced emotional response to events that have abnormal causes, of generation of prediction from observations of behavior, and of the role of norms. (Author/LMO)

The Effects of Tryptophan on Everyday Interpersonal Encounters and Social Cognitions in Individuals with a Family History of Depression.

PubMed

Hogenelst, Koen; Schoevers, Robert A; Aan Het Rot, Marije

2015-03-02

Individuals with a family history of depression show subtle abnormalities in the processing of social stimuli. This could negatively affect their interpersonal functioning and contribute to their depression risk. Repeated administration of the serotonin precursor tryptophan has previously been shown to increase agreeable behavior and reduce quarrelsome behavior in irritable people, who are also considered at risk for depression. To examine the effects of tryptophan on social functioning in individuals with a family history of depression, 40 men and women with at least one first-degree relative with depression received tryptophan (1g three times a day) and placebo for 14 days each in a double-blind crossover design and recorded their social behavior and mood during everyday interpersonal encounters. Participants also provided daily ratings of their positive and negative cognitions concerning their social functioning. Tryptophan improved mood. Unexpectedly, tryptophan increased quarrelsome behavior and reduced agreeable behavior, specifically during interactions at home. The behavioral effects of tryptophan were not moderated by mood or by the interaction partner. Negative social cognitions were lower when tryptophan was given second and lower during placebo when placebo was given second. Overall, tryptophan may not alter social behavior in individuals with a family history of depression as it does in irritable people. However, the behavioral effects of tryptophan at home might be seen as a way for individuals with a family history of depression to achieve more control. Over time, this may positively influence the way they feel and think about themselves in a social context. © The Author 2015. Published by Oxford University Press on behalf of CINP.

Social defeat models in animal science: What we have learned from rodent models.

PubMed

Toyoda, Atsushi

2017-07-01

Studies on stress and its impacts on animals are very important in many fields of science, including animal science, because various stresses influence animal production and animal welfare. In particular, the social stresses within animal groups have profound impact on animals, with the potential to induce abnormal behaviors and health problems. In humans, social stress induces several health problems, including psychiatric disorders. In animal stress models, social defeat models are well characterized and used in various research fields, particularly in studies concerning mental disorders. Recently, we have focused on behavior, nutrition and metabolism in rodent models of social defeat to elucidate how social stresses affect animals. In this review, recent significant progress in studies related to animal social defeat models are described. In the field of animal science, these stress models may contribute to advances in the development of functional foods and in the management of animal welfare. © 2017 The Authors. Animal Science Journal published by John Wiley & Sons Australia, Ltd on behalf of Japanese Society of Animal Science.

[Behavioral and cognitive profile of corpus callosum agenesia - Review].

PubMed

Lábadi, Beatrix; Beke, Anna Maria

2016-11-30

Agenesis of corpus callosum is a relatively frequent congenital cerebral malformation including dysplasia, total or partial absence of corpus callosum. The agenesis of corpus callosum can be occured in isolated form without accompanying somatic or central nervous system abnormalities and it can be associated with other central nervus system malformations. The behavioral and cognitive outcome is more favorable for patients with isolated agenesis of corpus callous than syndromic form of corpus callosum. The aim of this study is to review recent research on behavioral and social-cognitive functions in individuals with agenesis of corpus callosum. Developmental delay is common especially in higher-order cognitive and social functions. An internet database search was performed to identify publications on the subject. Fifty-five publications in English corresponded to the criteria. These studies reported deficits in language, social cognition and emotions in individuals with agenesis of corpus callosum which is known as primary corpus callous syndrome. The results indicate that individuals with agenesis of corpus callosum have deficiency in social-cognitive domain (recognition of emotions, weakness in paralinguistic aspects of language and mentalizing abilities). The impaired social cognition can be manifested in behavioral problems like autism and attention deficit hyperactivity disorder.

Assessment of Glutamate Transporter GLAST (EAAT1)-Deficient Mice for Phenotypes Relevant to the Negative and Executive/Cognitive Symptoms of Schizophrenia

PubMed Central

Karlsson, Rose-Marie; Tanaka, Kohichi; Saksida, Lisa M; Bussey, Timothy J; Heilig, Markus; Holmes, Andrew

2012-01-01

Glutamatergic dysfunction is increasingly implicated in the pathophysiology of schizophrenia. Current models postulate that dysfunction of glutamate and its receptors underlie many of the symptoms in this disease. However, the mechanisms involved are not well understood. Although elucidating the role for glutamate transporters in the disease has been limited by the absence of pharmacological tools that selectively target the transporter, we recently showed that glial glutamate and aspartate transporter (GLAST; excitatory amino-acid transporter 1) mutant mice exhibit abnormalities on behavioral measures thought to model the positive symptoms of schizophrenia, some of which were rescued by treatment with either haloperidol or the mGlu2/3 agonist, LY379268 the mGlu2/3 agonist, LY379268. To further determine the role of GLAST in schizophrenia-related behaviors we tested GLAST mutant mice on a series of behavioral paradigms associated with the negative (social withdrawal, anhedonia), sensorimotor gating (prepulse inhibition of startle), and executive/cognitive (discrimination learning, extinction) symptoms of schizophrenia. GLAST knockout (KO) mice showed poor nesting behavior and abnormal sociability, whereas KO and heterozygous (HET) both demonstrated lesser preference for a novel social stimulus compared to wild-type littermate controls. GLAST KO, but not HET, had a significantly reduced acoustic startle response, but no significant deficit in prepulse inhibition of startle. GLAST KO and HET showed normal sucrose preference. In an instrumental visual discrimination task, KO showed impaired learning. By contrast, acquisition and extinction of a simple instrumental response was normal. The mGlu2/3 agonist, LY379268, failed to rescue the discrimination impairment in KO mice. These findings demonstrate that gene deletion of GLAST produces select phenotypic abnormalities related to the negative and cognitive symptoms of schizophrenia. PMID:19078949

Pattern of brain activation during social cognitive tasks is related to social competence in siblings discordant for schizophrenia.

PubMed

Villarreal, Mirta F; Drucaroff, Lucas J; Goldschmidt, Micaela G; de Achával, Delfina; Costanzo, Elsa Y; Castro, Mariana N; Ladrón-de-Guevara, M Soledad; Busatto Filho, Geraldo; Nemeroff, Charles B; Guinjoan, Salvador M

2014-09-01

Measures of social competence are closely related to actual community functioning in patients with schizophrenia. However, the neurobiological mechanisms underlying competence in schizophrenia are not fully understood. We hypothesized that social deficits in schizophrenia are explained, at least in part, by abnormally lateralized patterns of brain activation in response to tasks engaging social cognition, as compared to healthy individuals. We predicted such patterns would be partly heritable, and therefore affected in patients' nonpsychotic siblings as well. We used a functional magnetic resonance image paradigm to characterize brain activation induced by theory of mind tasks, and two tests of social competence, the Test of Adaptive Behavior in Schizophrenia (TABS), and the Social Skills Performance Assessment (SSPA) in siblings discordant for schizophrenia and comparable healthy controls (n = 14 per group). Healthy individuals showed the strongest correlation between social competence and activation of right hemisphere structures involved in social cognitive processing, whereas in patients, the correlation pattern was lateralized to left hemisphere areas. Unaffected siblings of patients exhibited a pattern intermediate between the other groups. These results support the hypothesis that schizophrenia may be characterized by an abnormal functioning of nondominant hemisphere structures involved in the processing of socially salient information. Copyright © 2014 Elsevier Ltd. All rights reserved.

Grey matter abnormalities in social anxiety disorder: a pilot study.

PubMed

Syal, Supriya; Hattingh, Coenraad J; Fouché, Jean-Paul; Spottiswoode, Bruce; Carey, Paul D; Lochner, Christine; Stein, Dan J

2012-09-01

While a number of studies have explored the functional neuroanatomy of social anxiety disorder (SAD), data on grey matter integrity are lacking. We conducted structural MRI scans to examine the cortical thickness of grey matter in individuals with SAD. 13 unmedicated adult patients with a primary diagnosis of generalized social anxiety disorder and 13 demographically (age, gender and education) matched healthy controls underwent 3T structural magnetic resonance imaging. Cortical thickness and subcortical volumes were estimated using an automated algorithm (Freesurfer Version 4.5). Compared to controls, social anxiety disorder patients showed significant bilateral cortical thinning in the fusiform and post central regions. Additionally, right hemisphere specific thinning was found in the frontal, temporal, parietal and insular cortices of individuals with social anxiety disorder. Although uncorrected cortical grey matter volumes were significantly lower in individuals with SAD, we did not detect volumetric differences in corrected amygdala, hippocampal or cortical grey matter volumes across study groups. Structural differences in grey matter thickness between SAD patients and controls highlight the diffuse neuroanatomical networks involved in both social anxiety and social behavior. Additional work is needed to investigate the causal mechanisms involved in such structural abnormalities in SAD.

Induction of Social Behavior in Zebrafish: Live Versus Computer Animated Fish as Stimuli

PubMed Central

Qin, Meiying; Wong, Albert; Seguin, Diane

2014-01-01

Abstract The zebrafish offers an excellent compromise between system complexity and practical simplicity and has been suggested as a translational research tool for the analysis of human brain disorders associated with abnormalities of social behavior. Unlike laboratory rodents zebrafish are diurnal, thus visual cues may be easily utilized in the analysis of their behavior and brain function. Visual cues, including the sight of conspecifics, have been employed to induce social behavior in zebrafish. However, the method of presentation of these cues and the question of whether computer animated images versus live stimulus fish have differential effects have not been systematically analyzed. Here, we compare the effects of five stimulus presentation types: live conspecifics in the experimental tank or outside the tank, playback of video-recorded live conspecifics, computer animated images of conspecifics presented by two software applications, the previously employed General Fish Animator, and a new application Zebrafish Presenter. We report that all stimuli were equally effective and induced a robust social response (shoaling) manifesting as reduced distance between stimulus and experimental fish. We conclude that presentation of live stimulus fish, or 3D images, is not required and 2D computer animated images are sufficient to induce robust and consistent social behavioral responses in zebrafish. PMID:24575942

Induction of social behavior in zebrafish: live versus computer animated fish as stimuli.

PubMed

Qin, Meiying; Wong, Albert; Seguin, Diane; Gerlai, Robert

2014-06-01

The zebrafish offers an excellent compromise between system complexity and practical simplicity and has been suggested as a translational research tool for the analysis of human brain disorders associated with abnormalities of social behavior. Unlike laboratory rodents zebrafish are diurnal, thus visual cues may be easily utilized in the analysis of their behavior and brain function. Visual cues, including the sight of conspecifics, have been employed to induce social behavior in zebrafish. However, the method of presentation of these cues and the question of whether computer animated images versus live stimulus fish have differential effects have not been systematically analyzed. Here, we compare the effects of five stimulus presentation types: live conspecifics in the experimental tank or outside the tank, playback of video-recorded live conspecifics, computer animated images of conspecifics presented by two software applications, the previously employed General Fish Animator, and a new application Zebrafish Presenter. We report that all stimuli were equally effective and induced a robust social response (shoaling) manifesting as reduced distance between stimulus and experimental fish. We conclude that presentation of live stimulus fish, or 3D images, is not required and 2D computer animated images are sufficient to induce robust and consistent social behavioral responses in zebrafish.

Neuropharmacological sequelae of persistent CNS viral infections: lessons from Borna disease virus.

PubMed

Solbrig, Marylou V; Koob, George F

2003-03-01

Borna Disease Virus (BDV) is a neurotropic RNA virus that is worldwide in distribution, causing movement and behavior disorders in a wide range of animal species. BDV has also been reported to be associated with neuropsychiatric diseases of humans by serologic study and by recovery of nucleic acid or virus from blood or brain. Natural infections of horses and sheep produce encephalitis with erratic excited behaviors, hyperkinetic movement or gait abnormalities; naturally infected cats have ataxic "staggering disease." Experimentally infected primates develop hyperactivity, aggression, disinhibition, then apathy; prosimians (lower primates) have hyperactivity, circadian disruption, abnormal social and dominance behaviors, and postural disorders. However, the neuropharmacological determinants of BD phenotypes in laboratory and natural hosts are incompletely understood. Here we review how experimentally infected rodents have provided models for examining behavioral, pharmacologic, and biochemical responses to viral challenge, and how rodents experimentally infected as neonates or as adolescents are providing models for examining age-specific neuropharmacological adaptations to viral injury.

Autistic behavior in Scn1a+/− mice and rescue by enhanced GABAergic transmission

PubMed Central

Han, Sung; Tai, Chao; Westenbroek, Ruth E.; Yu, Frank H.; Cheah, Christine S.; Potter, Gregory B.; Rubenstein, John L.; Scheuer, Todd; de la Iglesia, Horacio O; Catterall, William A

2012-01-01

Haploinsufficiency of the SCN1A gene encoding voltage-gated sodium channel NaV1.1 causes Dravet Syndrome (DS), a childhood neuropsychiatric disorder including recurrent intractable seizures, cognitive deficit, and autism-spectrum behaviors. The neural mechanisms responsible for cognitive deficit and autism-spectrum behaviors in DS are poorly understood. Here we show that mice with Scn1a haploinsufficiency display hyperactivity, stereotyped behaviors, social interaction deficits, and impaired context-dependent spatial memory. Olfactory sensitivity is retained, but novel food odors and social odors are aversive to Scn1a+/− mice. GABAergic neurotransmission is specifically impaired by this mutation, and selective deletion of NaV1.1 channels in forebrain interneurons is sufficient to cause these behavioral and cognitive impairments. Remarkably, treatment with low-dose clonazepam, a positive allosteric modulator of GABAA receptors, completely rescued the abnormal social behaviors and deficits in fear memory in DS mice, demonstrating that they are caused by impaired GABAergic neurotransmission and not by neuronal damage from recurrent seizures. These results demonstrate a critical role for NaV1.1 channels in neuropsychiatric functions and provide a potential therapeutic strategy for cognitive deficit and autism-spectrum behaviors in DS. PMID:22914087

Post-weaning social isolation increases activity in a novel environment but decreases defensive burying and subchronic MK-801 enhances the activity but not the burying effect in rats.

PubMed

Simpson, Sarah M; Menard, Janet L; Reynolds, James N; Beninger, Richard J

2010-03-01

Subchronic treatment with a non-competitive glutamate NMDA-receptor antagonist [e.g., MK-801 or phencyclidine] or social isolation (SI) from weaning (age 21 days) to adulthood (age 56 days) produce deficits similar to some of the positive and negative symptoms of schizophrenia. Few studies have evaluated the effects of these treatments on emotional behavior. We hypothesized that subchronic MK-801, post-weaning SI or the two in combination would alter activity in a novel environment, anxiety-like behaviors in the elevated plus-maze, coping responses in the defensive burying paradigm and social behavior. In experiment 1, SI rats (n=17) showed increased locomotor activity when exposed to a novel environment, no change in plus-maze behavior and decreased defensive burying when compared to group housed rats (n=16). Subchronic MK-801 enhanced the increase in activity but not the decrease in burying in SI rats. Experiment 2 evaluated the effects on social behavior of post-weaning SI. The locomotor and burying results of experiment 1 were replicated and SI rats (n=9) were found to decrease orientation towards a novel conspecific social target when compared to group housed rats (n=8). The behavioral abnormalities of SI rats may be a manifestation of GABAergic dysfunction that has recently become evident in schizophrenia. (c) 2009 Elsevier Inc. All rights reserved.

Loss of Sodium-Activated Potassium Channel Slack and FMRP Differentially Affect Social Behavior in Mice.

PubMed

Bausch, Anne E; Ehinger, Rebekka; Straubinger, Julia; Zerfass, Patrick; Nann, Yvette; Lukowski, Robert

2018-05-31

The sodium-activated potassium channel Slack (Slo2.2) is widely expressed in central and peripheral neurons where it is supposed to shape firing properties important for neuronal excitability. Slack activity is enhanced by interaction with the Fragile-X-Mental-Retardation-Protein (FMRP) and loss of FMRP leads to decreased sodium-activated potassium currents in medial nucleus of the trapezoid body neurons of the Fmr1-knockout (KO) mouse representing a mouse model of the human Fragile-X-Syndrome (FXS) and autism. Autism is a frequent comorbidity of FXS, but it is unclear whether Slack is involved in autistic or related conditions of FXS in vivo. By applying a wide range of behavioral tests, we compared social and autism-related behaviors in Slack- and FMRP-deficient mice. In our hands, as expected, FMRP-deficiency causes autism-related behavioral changes in nesting and in a marble-burying test. In contrast, Slack-deficient males exhibited specific abnormalities in sociability in direct and indirect social interaction tests. Hence, we show for the first time that a proper Slack channel function is mandatory for normal social behavior in mice. Nevertheless, as deficits in social behaviors seem to occur independently from each other in FMRP and Slack null mutants, we conclude that Slack is not involved in the autistic phenotype of FMRP KO mice. Copyright © 2018 IBRO. Published by Elsevier Ltd. All rights reserved.

Effects of Social Injustice on Breast Health–Seeking Behaviors of Low-Income Women

PubMed Central

Bowen, Shelly-Ann; Williams, Edith M.; Stoneberg-Cooper, Chayah M.; Glover, Saundra H.; Williams, Michelle S.; Byrd, Michael D.

2014-01-01

Purpose The study uses qualitative research to gain a better understanding of what occurs after low-income women receive an abnormal breast screening and the factors that influence their decisions and behavior. A heuristic model is presented for understanding this complexity. Design Qualitative research methods used to elicited social and cultural themes related to breast cancer screening follow-up. Setting Individual telephone interviews were conducted with 16 women with confirmed breast anomaly. Participants Low-income women screened through a national breast cancer early detection program. Method Grounded theory using selective coding was employed to elicit factors that influenced the understanding and follow-up of an abnormal breast screening result. Interviews were digitally recorded, transcribed, and uploaded into NVivo 8, a qualitative management and analysis software package. Results For women (16, or 72% of case management referrals) below 250% of the poverty level, the impact of social and economic inequities creates a psychosocial context underlined by structural and cultural barriers to treatment that forecasts the mechanism that generates differences in health outcomes. The absence of insurance due to underemployment and unemployment and inadequate public infrastructure intensified emotional stress impacting participants’ health decisions. Conclusion The findings that emerged offer explanations of how consistent patterns of social injustice impact treatment decisions in a high-risk vulnerable population that have implications for health promotion research and systems-level program improvement and development. PMID:23448411

Activation of Supraoptic Oxytocin Neurons by Secretin Facilitates Social Recognition.

PubMed

Takayanagi, Yuki; Yoshida, Masahide; Takashima, Akihide; Takanami, Keiko; Yoshida, Shoma; Nishimori, Katsuhiko; Nishijima, Ichiko; Sakamoto, Hirotaka; Yamagata, Takanori; Onaka, Tatsushi

2017-02-01

Social recognition underlies social behavior in animals, and patients with psychiatric disorders associated with social deficits show abnormalities in social recognition. Oxytocin is implicated in social behavior and has received attention as an effective treatment for sociobehavioral deficits. Secretin receptor-deficient mice show deficits in social behavior. The relationship between oxytocin and secretin concerning social behavior remains to be determined. Expression of c-Fos in oxytocin neurons and release of oxytocin from their dendrites after secretin application were investigated. Social recognition was examined after intracerebroventricular or local injection of secretin, oxytocin, or an oxytocin receptor antagonist in rats, oxytocin receptor-deficient mice, and secretin receptor-deficient mice. Electron and light microscopic immunohistochemical analysis was also performed to determine whether oxytocin neurons extend their dendrites into the medial amygdala. Supraoptic oxytocin neurons expressed the secretin receptor. Secretin activated supraoptic oxytocin neurons and facilitated oxytocin release from dendrites. Secretin increased acquisition of social recognition in an oxytocin receptor-dependent manner. Local application of secretin into the supraoptic nucleus facilitated social recognition, and this facilitation was blocked by an oxytocin receptor antagonist injected into, but not outside of, the medial amygdala. In the medial amygdala, dendrite-like thick oxytocin processes were found to extend from the supraoptic nucleus. Furthermore, oxytocin treatment restored deficits of social recognition in secretin receptor-deficient mice. The results of our study demonstrate that secretin-induced dendritic oxytocin release from supraoptic neurons enhances social recognition. The newly defined secretin-oxytocin system may lead to a possible treatment for social deficits. Copyright © 2016 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

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2012-07-02

... teacher implementation of school-based mental health programs. Journal of Abnormal Child Psychology, 33(6... the Implementation of a Social and Emotional Learning Curriculum. School Psychology Review, 38(4), 510... Sustaining School-Wide Positive Behavior Support. School Psychology Review, 35(2), 245-259. Turnbull, A...

Emotion Dysregulation and the Core Features of Autism Spectrum Disorder

ERIC Educational Resources Information Center

Samson, Andrea C.; Phillips, Jennifer M.; Parker, Karen J.; Shah, Shweta; Gross, James J.; Hardan, Antonio Y.

2014-01-01

The aim of this study was to examine the relationship between emotion dysregulation and the core features of Autism Spectrum Disorder (ASD), which include social/communication deficits, restricted/repetitive behaviors, and sensory abnormalities. An 18-item Emotion Dysregulation Index was developed on the basis of expert ratings of the Child…

A New Neurobehavioral Model of Autism in Mice: Pre-and Postnatal Exposure to Sodium Valproate

ERIC Educational Resources Information Center

Wagner, George C.; Reuhl, Kenneth R.; Cheh, Michelle; McRae, Paulette; Halladay, Alycia K.

2006-01-01

Autism symptoms, including impairments in language development, social interactions, and motor skills, have been difficult to model in rodents. Since children exposed in utero to sodium valproate (VPA) demonstrate behavioral and neuroanatomical abnormalities similar to those seen in autism, the neurodevelopmental effects of this antiepileptic…

Temporary Basolateral Amygdala Lesions Disrupt Acquisition of Socially Transmitted Food Preferences in Rats

ERIC Educational Resources Information Center

Fontanini, Alfredo; Katz, Donald B.; Wang, Yunyan

2006-01-01

Lesions of the basolateral amygdala (BLA) have long been associated with abnormalities of taste-related behaviors and with failure in a variety of taste- and odor-related learning paradigms, including taste-potentiated odor aversion, conditioned taste preference, and conditioned taste aversion. Still, the general role of the amygdala in…

Viewing social scenes: a visual scan-path study comparing fragile X syndrome and Williams syndrome.

PubMed

Williams, Tracey A; Porter, Melanie A; Langdon, Robyn

2013-08-01

Fragile X syndrome (FXS) and Williams syndrome (WS) are both genetic disorders which present with similar cognitive-behavioral problems, but distinct social phenotypes. Despite these social differences both syndromes display poor social relations which may result from abnormal social processing. This study aimed to manipulate the location of socially salient information within scenes to investigate the visual attentional mechanisms of: capture, disengagement, and/or general engagement. Findings revealed that individuals with FXS avoid social information presented centrally, at least initially. The WS findings, on the other hand, provided some evidence that difficulties with attentional disengagement, rather than attentional capture, may play a role in the WS social phenotype. These findings are discussed in relation to the distinct social phenotypes of these two disorders.

Juvenile social defeat stress exposure persistently impairs social behaviors and neurogenesis.

PubMed

Mouri, Akihiro; Ukai, Mayu; Uchida, Mizuki; Hasegawa, Sho; Taniguchi, Masayuki; Ito, Takahiro; Hida, Hirotake; Yoshimi, Akira; Yamada, Kiyofumi; Kunimoto, Shohko; Ozaki, Norio; Nabeshima, Toshitaka; Noda, Yukihiro

2018-05-01

Adverse juvenile experiences, including physical abuse, often have negative health consequences later in life. We investigated the influence of social defeat stress exposure as juveniles on neuropsychological behaviors, and the causal role of glucocorticoids in abnormal behaviors and impairment of neurogenesis in mice exposed to the stress. The juvenile (24-day-old) and adult (70-day-old) male C57BL/6J mice were exposed to social defeat stress induced by an aggressive ICR mouse. Social defeat stress exposure as juveniles, even for 1 day, induced persistent social avoidance to the unfamiliar ICR mouse in the social interaction test, but that was not observed in mice exposed to the stress as adults. Social avoidance by the stress exposure as juveniles for 10 consecutive days was observed, when the target mouse was not only unfamiliar ICR but also another C57BL/J mouse, but not an absent or an anesthetized ICR mouse. The stress exposure did not induce anxiety- and depression-like behaviors in spontaneous locomotor activity, elevated plus-maze test, marble-burying test, forced swimming test, or sucrose preference test. Serum corticosterone levels increased immediately after the stress exposure. The hippocampal neurogenesis was suppressed 1 day and 4 weeks after the stress exposure. Administration of mifepristone, a glucocorticoid receptor antagonist, prior to each stress exposure, blocked the persistent social avoidance and suppression of neurogenesis. In conclusion, social avoidance induced by social defeat stress exposure as juveniles are more persistent than that as adults. These social avoidances are associated with suppression of hippocampal neurogenesis via glucocorticoid receptors. Copyright © 2018 Elsevier Ltd. All rights reserved.

Anterior insular cortex regulation in autism spectrum disorders

PubMed Central

Caria, Andrea; de Falco, Simona

2015-01-01

Autism spectrum disorders (ASDs) comprise a heterogeneous set of neurodevelopmental disorders characterized by dramatic impairments of interpersonal behavior, communication, and empathy. Recent neuroimaging studies suggested that ASD are disorders characterized by widespread abnormalities involving distributed brain network, though clear evidence of differences in large-scale brain network interactions underlying the cognitive and behavioral symptoms of ASD are still lacking. Consistent findings of anterior insula cortex hypoactivation and dysconnectivity during tasks related to emotional and social processing indicates its dysfunctional role in ASD. In parallel, increasing evidence showed that successful control of anterior insula activity can be attained using real-time fMRI paradigms. More importantly, successful regulation of this region was associated with changes in behavior and brain connectivity in both healthy individuals and psychiatric patients. Building on these results we here propose and discuss the use of real-time fMRI neurofeedback in ASD aiming at improving emotional and social behavior. PMID:25798096

[Age-related aspects of male rats sexual behavior with different senescence rates].

PubMed

Amstislavskaia, T G; Gladkikh, D V; Belousova, I I; Maslova, L N; Kolosova, N G

2010-01-01

Social and sexual behavior of males Wistar and senescence-accelerated OXYS rats was studied. The experimental model excluding direct interaction between partners showed that the exploratory activity decreased with aging in rats of both strains, but social motivation didn't change. No interstrain differences in intensity of sexual motivation in the presence of an inaccessible receptive female were observed in 4-month rats. The level of sexual motivation of 12-month Wistar rats didn't differ from that of 4-month animals. However, in 12-month OXYS males, sexual motivation was decreased as compared to both 4- and 12-month Wistar rats. The same regularities were found under conditions of direct interaction with a partner. Behavioral changes in 12-month OXYS rats were considered as genetically determinate abnormality at the initial stage of sexual behavior, i.e., sexual motivation. The results suggest the accelerated senescence of the reproductive system of OXYS rats.

[Pedophilia--a review of literature, casuistics, doubts].

PubMed

Łucka, Izabela; Dziemian, Anna

2014-01-01

The main purpose of this article is presentation of several basic issues related to the phenomenon of child sexual molesters and recognition of pedophilia as a significant social problem. The article, supplemented by casuistic illustration showing adolescents with sexual behavior disorders is giving rise to the following question: do they progress in their inappropriate behaviors to grow into adult molesters or do they stop anywhere along the way of their development? Casuistry, in the intention of the authors, is the background for discussion about prevention of child sexual abuse. This article presents also a review of the current knowledge about child sexual molesters. The topics include: the definition of pedophilia itself, which varies in the literature depending on the types of activities, kinds of victims and the circumstances in which the perpetrator acts, through to the recognition of symptoms of pedophilia as well as its consequences. It includes both intra-familial and extra-familial child sexual abuse and their offenders. The more, that the history of child sexual abuse is associated with numerous long-term physical, psychological, behavioral, interpersonal and social effects on the victim. The examinations made among pedophilic molesters have shown structural and functional temporal-limbic abnormalities, including abnormalities in the amygdala and it is possible that the pedophilic inclinations are secondary to neurodevelopmental perturbations and other neuropsychiatric syndromes.

Characterizing abnormal behavior in a large population of zoo-housed chimpanzees: prevalence and potential influencing factors

PubMed Central

Jacobson, Sarah L.; Bloomsmith, Mollie A.

2016-01-01

Abnormal behaviors in captive animals are generally defined as behaviors that are atypical for the species and are often considered to be indicators of poor welfare. Although some abnormal behaviors have been empirically linked to conditions related to elevated stress and compromised welfare in primates, others have little or no evidence on which to base such a relationship. The objective of this study was to investigate a recent claim that abnormal behavior is endemic in the captive population by surveying a broad sample of chimpanzees (Pan troglodytes), while also considering factors associated with the origins of these behaviors. We surveyed animal care staff from 26 accredited zoos to assess the prevalence of abnormal behavior in a large sample of chimpanzees in the United States for which we had information on origin and rearing history. Our results demonstrated that 64% of this sample was reported to engage in some form of abnormal behavior in the past two years and 48% of chimpanzees engaged in abnormal behavior other than coprophagy. Logistic regression models were used to analyze the historical variables that best predicted the occurrence of all abnormal behavior, any abnormal behavior that was not coprophagy, and coprophagy. Rearing had opposing effects on the occurrence of coprophagy and the other abnormal behaviors such that mother-reared individuals were more likely to perform coprophagy, whereas non-mother-reared individuals were more likely to perform other abnormal behaviors. These results support the assertion that coprophagy may be classified separately when assessing abnormal behavior and the welfare of captive chimpanzees. This robust evaluation of the prevalence of abnormal behavior in our sample from the U.S. zoo population also demonstrates the importance of considering the contribution of historical variables to present behavior, in order to better understand the causes of these behaviors and any potential relationship to psychological wellbeing. PMID:27478710

Touch Processing and Social Behavior in ASD.

PubMed

O Miguel, Helga; Sampaio, Adriana; Martínez-Regueiro, Rocío; Gómez-Guerrero, Lorena; López-Dóriga, Cristina Gutiérrez; Gómez, Sonia; Carracedo, Ángel; Fernández-Prieto, Montse

2017-08-01

Abnormal patterns of touch processing have been linked to core symptoms in ASD. This study examined the relation between tactile processing patterns and social problems in 44 children and adolescents with ASD, aged 6-14 (M = 8.39 ± 2.35). Multiple linear regression indicated significant associations between touch processing and social problems. No such relationships were found for social problems and autism severity. Within touch processing, patterns of hyper-responsiveness and hypo-responsiveness best predicted social problems, whereas sensory-seeking did not. These results support that atypical touch processing in individuals with ASD might be contributing to the social problems they present. Moreover, it the need to explore more in depth the contribution of sensory features to the ASD phenotype.

Advances in the Research of Melatonin in Autism Spectrum Disorders: Literature Review and New Perspectives

PubMed Central

Tordjman, Sylvie; Najjar, Imen; Bellissant, Eric; Anderson, George M.; Barburoth, Marianne; Cohen, David; Jaafari, Nemat; Schischmanoff, Olivier; Fagard, Rémi; Lagdas, Enas; Kermarrec, Solenn; Ribardiere, Sophie; Botbol, Michel; Fougerou, Claire; Bronsard, Guillaume; Vernay-Leconte, Julie

2013-01-01

Abnormalities in melatonin physiology may be involved or closely linked to the pathophysiology and behavioral expression of autistic disorder, given its role in neurodevelopment and reports of sleep-wake rhythm disturbances, decreased nocturnal melatonin production, and beneficial therapeutic effects of melatonin in individuals with autism. In addition, melatonin, as a pineal gland hormone produced from serotonin, is of special interest in autistic disorder given reported alterations in central and peripheral serotonin neurobiology. More specifically, the role of melatonin in the ontogenetic establishment of circadian rhythms and the synchronization of peripheral oscillators opens interesting perspectives to ascertain better the mechanisms underlying the significant relationship found between lower nocturnal melatonin excretion and increased severity of autistic social communication impairments, especially for verbal communication and social imitative play. In this article, first we review the studies on melatonin levels and the treatment studies of melatonin in autistic disorder. Then, we discuss the relationships between melatonin and autistic behavioral impairments with regard to social communication (verbal and non-verbal communication, social interaction), and repetitive behaviors or interests with difficulties adapting to change. In conclusion, we emphasize that randomized clinical trials in autism spectrum disorders are warranted to establish potential therapeutic efficacy of melatonin for social communication impairments and stereotyped behaviors or interests. PMID:24129182

Advances in the research of melatonin in autism spectrum disorders: literature review and new perspectives.

PubMed

Tordjman, Sylvie; Najjar, Imen; Bellissant, Eric; Anderson, George M; Barburoth, Marianne; Cohen, David; Jaafari, Nemat; Schischmanoff, Olivier; Fagard, Rémi; Lagdas, Enas; Kermarrec, Solenn; Ribardiere, Sophie; Botbol, Michel; Fougerou, Claire; Bronsard, Guillaume; Vernay-Leconte, Julie

2013-10-14

Abnormalities in melatonin physiology may be involved or closely linked to the pathophysiology and behavioral expression of autistic disorder, given its role in neurodevelopment and reports of sleep-wake rhythm disturbances, decreased nocturnal melatonin production, and beneficial therapeutic effects of melatonin in individuals with autism. In addition, melatonin, as a pineal gland hormone produced from serotonin, is of special interest in autistic disorder given reported alterations in central and peripheral serotonin neurobiology. More specifically, the role of melatonin in the ontogenetic establishment of circadian rhythms and the synchronization of peripheral oscillators opens interesting perspectives to ascertain better the mechanisms underlying the significant relationship found between lower nocturnal melatonin excretion and increased severity of autistic social communication impairments, especially for verbal communication and social imitative play. In this article, first we review the studies on melatonin levels and the treatment studies of melatonin in autistic disorder. Then, we discuss the relationships between melatonin and autistic behavioral impairments with regard to social communication (verbal and non-verbal communication, social interaction), and repetitive behaviors or interests with difficulties adapting to change. In conclusion, we emphasize that randomized clinical trials in autism spectrum disorders are warranted to establish potential therapeutic efficacy of melatonin for social communication impairments and stereotyped behaviors or interests.

Prenatal exposure to moderate levels of ethanol alters social behavior in adult rats: relationship to structural plasticity and immediate early gene expression in frontal cortex.

PubMed

Hamilton, Derek A; Akers, Katherine G; Rice, James P; Johnson, Travis E; Candelaria-Cook, Felicha T; Maes, Levi I; Rosenberg, Martina; Valenzuela, C Fernando; Savage, Daniel D

2010-03-05

The goals of the present study were to characterize the effects of prenatal exposure to moderate levels of ethanol on adult social behavior, and to evaluate fetal-ethanol-related effects on dendritic morphology, structural plasticity and activity-related immediate early gene (IEG) expression in the agranular insular (AID) and prelimbic (Cg3) regions of frontal cortex. Baseline fetal-ethanol-related alterations in social behavior were limited to reductions in social investigation in males. Repeated experience with novel cage-mates resulted in comparable increases in wrestling and social investigation among saccharin- and ethanol-exposed females, whereas social behavioral effects among males were more evident in ethanol-exposed animals. Male ethanol-exposed rats also displayed profound increases in wrestling when social interaction was motivated by 24h of isolation. Baseline decreases in dendritic length and spine density in AID were observed in ethanol-exposed rats that were always housed with the same cage-mate. Modest experience-related decreases in dendritic length and spine density in AID were observed in saccharin-exposed rats housed with various cage-mates. In contrast, fetal-ethanol-exposed rats displayed experience-related increases in dendritic length in AID, and no experience-related changes in spine density. The only effect observed in Cg3 was a baseline increase in basilar dendritic length among male ethanol-exposed rats. Robust increases in activity-related IEG expression in AID (c-fos and Arc) and Cg3 (c-fos) were observed following social interaction in saccharin-exposed rats, however, activity-related increases in IEG expression were not observed in fetal-ethanol-exposed rats in either region. The results indicate that deficits in social behavior are among the long-lasting behavioral consequences of moderate ethanol exposure during brain development, and implicate AID, and to a lesser degree Cg3, in fetal-ethanol-related social behavior abnormalities. Copyright 2009 Elsevier B.V. All rights reserved.

Deficient gaze pattern during virtual multiparty conversation in patients with schizophrenia.

PubMed

Han, Kiwan; Shin, Jungeun; Yoon, Sang Young; Jang, Dong-Pyo; Kim, Jae-Jin

2014-06-01

Virtual reality has been used to measure abnormal social characteristics, particularly in one-to-one situations. In real life, however, conversations with multiple companions are common and more complicated than two-party conversations. In this study, we explored the features of social behaviors in patients with schizophrenia during virtual multiparty conversations. Twenty-three patients with schizophrenia and 22 healthy controls performed the virtual three-party conversation task, which included leading and aiding avatars, positive- and negative-emotion-laden situations, and listening and speaking phases. Patients showed a significant negative correlation in the listening phase between the amount of gaze on the between-avatar space and reasoning ability, and demonstrated increased gaze on the between-avatar space in the speaking phase that was uncorrelated with attentional ability. These results suggest that patients with schizophrenia have active avoidance of eye contact during three-party conversations. Virtual reality may provide a useful way to measure abnormal social characteristics during multiparty conversations in schizophrenia. Copyright © 2014 Elsevier Ltd. All rights reserved.

Evaluation of emotional behaviors in young offspring of C57BL/6J mice after gestational and/or perinatal exposure to nicotine in six different time-windows.

PubMed

Alkam, Tursun; Kim, Hyoung-Chun; Hiramatsu, Masayuki; Mamiya, Takayoshi; Aoyama, Yuki; Nitta, Atsumi; Yamada, Kiyofumi; Nabeshima, Toshitaka

2013-02-15

Nicotine replacement treatments are being alternatively applied as an aid to smoking cessation during pregnancy. However, the effects of nicotine exposed at the prenatal stage on the emotional behaviors in offspring are not well understood due to the lack of systematic investigations. The current study has therefore initially aimed to evaluate emotional behaviors in young mouse offspring (postnatal day 28-36) which experienced gestational and/or perinatal nicotine exposure (GPNE) in six different time-windows. Pregnant C57BL/6J mice were exposed to nicotine via sweetened (2% sucrose) drinking water during 6 different time-windows including gestational day 0-day 13 (G0-G13), G14-perinatal day 0 (P0), G0-P0, G14-P7, G0-P7, and P0-P7. During P28-P36 days, both male and female offspring were given a battery of behavioral tests including light and dark box test, marble burying behavior test, novelty-suppressed feeding test, sociability and social novelty preference test, social avoidance tube test, and elevated plus maze test. GPNE during G0-P0, G14-P0, G14-P7, and G0-P7 induced abnormal behaviors in male and female offspring to different extent. Results indicated that nicotine at any time points of gestational and/or perinatal period impairs emotional behaviors in offspring, and suggested certain time-windows for further neurochemical or molecular studies in relation with GPNE-induced emotional abnormalities. Copyright © 2012 Elsevier B.V. All rights reserved.

Autistic-spectrum disorders in Down syndrome: further delineation and distinction from other behavioral abnormalities.

PubMed

Carter, John C; Capone, George T; Gray, Robert M; Cox, Christiane S; Kaufmann, Walter E

2007-01-05

The present study extends our previous work characterizing the behavioral features of autistic-spectrum disorder (ASD) in Down syndrome (DS) using the Aberrant Behavior Checklist (ABC) and Autism Behavior Checklist (AutBehav). We examined which specific behaviors distinguished the behavioral phenotype of DS + ASD from other aberrant behavior disorders in DS, by determining the relative contribution of ABC and AutBehav subscales and items to the diagnosis of ASD. A total of 127 subjects (aged 2-24 years; mean age: 8.4 years; approximately 70% male), comprising: a cohort of 64 children and adolescents with DS and co-morbid ASD (DS + ASD), 19 with DS and stereotypic movement disorder (DS + SMD), 18 with DS and disruptive behaviors (DS + DB), and 26 with DS and no co-morbid behavior disorders (DS + none) were examined using the aforementioned measures of aberrant behavior. We found that subjects with DS + ASD showed the most severe aberrant behavior, especially stereotypy compared to DS + none and lethargy/social withdrawal and relating problems compared to DS + SMD. Specifically, relatively simple stereotypic behavior differentiated DS + ASD from DS + DB, whereas odd/bizarre stereotypic and anxious behavior characterized DS + ASD relative to DS + SMD and DS + none. Additionally, in a subset of subjects with DS + ASD and anxiety, social withdrawal was particularly pronounced. Overall, our findings indicate that a diagnosis of DS + ASD represents a distinctive set of aberrant behaviors marked by characteristic odd/bizarre stereotypic behavior, anxiety, and social withdrawal.

Abnormal Behavior in Relation to Cage Size in Rhesus Monkeys

ERIC Educational Resources Information Center

Paulk, H. H.; And Others

1977-01-01

Examines the effects of cage size on stereotyped and normal locomotion and on other abnormal behaviors in singly caged animals, whether observed abnormal behaviors tend to co-occur, and if the development of an abnormal behavior repertoire leads to reduction in the number of normal behavior categories. (Author/RK)

Synaptic dysfunction and abnormal behaviors in mice lacking major isoforms of Shank3.

PubMed

Wang, Xiaoming; McCoy, Portia A; Rodriguiz, Ramona M; Pan, Yanzhen; Je, H Shawn; Roberts, Adam C; Kim, Caroline J; Berrios, Janet; Colvin, Jennifer S; Bousquet-Moore, Danielle; Lorenzo, Isabel; Wu, Gangyi; Weinberg, Richard J; Ehlers, Michael D; Philpot, Benjamin D; Beaudet, Arthur L; Wetsel, William C; Jiang, Yong-Hui

2011-08-01

SHANK3 is a synaptic scaffolding protein enriched in the postsynaptic density (PSD) of excitatory synapses. Small microdeletions and point mutations in SHANK3 have been identified in a small subgroup of individuals with autism spectrum disorder (ASD) and intellectual disability. SHANK3 also plays a key role in the chromosome 22q13.3 microdeletion syndrome (Phelan-McDermid syndrome), which includes ASD and cognitive dysfunction as major clinical features. To evaluate the role of Shank3 in vivo, we disrupted major isoforms of the gene in mice by deleting exons 4-9. Isoform-specific Shank3(e4-9) homozygous mutant mice display abnormal social behaviors, communication patterns, repetitive behaviors and learning and memory. Shank3(e4-9) male mice display more severe impairments than females in motor coordination. Shank3(e4-9) mice have reduced levels of Homer1b/c, GKAP and GluA1 at the PSD, and show attenuated activity-dependent redistribution of GluA1-containing AMPA receptors. Subtle morphological alterations in dendritic spines are also observed. Although synaptic transmission is normal in CA1 hippocampus, long-term potentiation is deficient in Shank3(e4-9) mice. We conclude that loss of major Shank3 species produces biochemical, cellular and morphological changes, leading to behavioral abnormalities in mice that bear similarities to human ASD patients with SHANK3 mutations.

The evolutionarily conserved G protein-coupled receptor SREB2/GPR85 influences brain size, behavior, and vulnerability to schizophrenia.

PubMed

Matsumoto, Mitsuyuki; Straub, Richard E; Marenco, Stefano; Nicodemus, Kristin K; Matsumoto, Shun-Ichiro; Fujikawa, Akihiko; Miyoshi, Sosuke; Shobo, Miwako; Takahashi, Shinji; Yarimizu, Junko; Yuri, Masatoshi; Hiramoto, Masashi; Morita, Shuji; Yokota, Hiroyuki; Sasayama, Takeshi; Terai, Kazuhiro; Yoshino, Masayasu; Miyake, Akira; Callicott, Joseph H; Egan, Michael F; Meyer-Lindenberg, Andreas; Kempf, Lucas; Honea, Robyn; Vakkalanka, Radha Krishna; Takasaki, Jun; Kamohara, Masazumi; Soga, Takatoshi; Hiyama, Hideki; Ishii, Hiroyuki; Matsuo, Ayako; Nishimura, Shintaro; Matsuoka, Nobuya; Kobori, Masato; Matsushime, Hitoshi; Katoh, Masao; Furuichi, Kiyoshi; Weinberger, Daniel R

2008-04-22

The G protein-coupled receptor (GPCR) family is highly diversified and involved in many forms of information processing. SREB2 (GPR85) is the most conserved GPCR throughout vertebrate evolution and is expressed abundantly in brain structures exhibiting high levels of plasticity, e.g., the hippocampal dentate gyrus. Here, we show that SREB2 is involved in determining brain size, modulating diverse behaviors, and potentially in vulnerability to schizophrenia. Mild overexpression of SREB2 caused significant brain weight reduction and ventricular enlargement in transgenic (Tg) mice as well as behavioral abnormalities mirroring psychiatric disorders, e.g., decreased social interaction, abnormal sensorimotor gating, and impaired memory. SREB2 KO mice showed a reciprocal phenotype, a significant increase in brain weight accompanying a trend toward enhanced memory without apparent other behavioral abnormalities. In both Tg and KO mice, no gross malformation of brain structures was observed. Because of phenotypic overlap between SREB2 Tg mice and schizophrenia, we sought a possible link between the two. Minor alleles of two SREB2 SNPs, located in intron 2 and in the 3' UTR, were overtransmitted to schizophrenia patients in a family-based sample and showed an allele load association with reduced hippocampal gray matter volume in patients. Our data implicate SREB2 as a potential risk factor for psychiatric disorders and its pathway as a target for psychiatric therapy.

Alleviation of N-Methyl-D-Aspartate Receptor-Dependent Long-Term Depression via Regulation of the Glycogen Synthase Kinase-3β Pathway in the Amygdala of a Valproic Acid-Induced Animal Model of Autism.

PubMed

Wu, Han-Fang; Chen, Po See; Chen, Yi-Ju; Lee, Chi-Wei; Chen, I-Tuan; Lin, Hui-Ching

2017-09-01

The amygdala plays crucial roles in socio-emotional behavior and cognition, both of which are abnormal in autism spectrum disorder (ASD). Valproic acid (VPA)-exposed rat offspring have demonstrated ASD phenotypes and amygdala excitatory/inhibitory imbalance. However, the role of glutamatergic synapses in this imbalance remains unclear. In this study, we used a VPA-induced ASD-like model to assess glutamatergic synapse-dependent long-term depression (LTD) and depotentiation (DPT) in the amygdala. We first confirmed that the VPA-exposed offspring exhibited sociability deficits, anxiety, depression-like behavior, and abnormal nociception thresholds. Then, electrophysiological examination showed a significantly decreased paired-pulse ratio in the amygdala. In addition, both NMDA-dependent LTD and DPT were absent from the amygdala. Furthermore, we found that the levels of glycogen synthase kinase3β (GSK-3β) phosphorylation and β-catenin were significantly higher in the amygdala of the experimental animals than in the controls. Local infusion of phosphatidylinositol 3-kinase (PI3K) inhibitor wortmannin into the amygdala reversed the increased phosphorylation level and impaired social behavior. Taken together, the results suggested that NMDA receptor-related synaptic plasticity is dysfunctional in VPA-exposed offspring. In addition, GSK-3β in the amygdala is critical for synaptic plasticity at the glutamatergic synapses and is related to social behavior. Its role in the underlying mechanism of ASD merits further investigation.

Interpersonal distance and social anxiety in autistic spectrum disorders: A behavioral and ERP study.

PubMed

Perry, Anat; Levy-Gigi, Einat; Richter-Levin, Gal; Shamay-Tsoory, Simone G

2015-08-01

An inherent feature of social interactions is the use of social space or interpersonal distance-the space between one individual and another. Because social deficits are core symptoms of Autistic Spectrum Disorder (ASD), we hypothesized that individuals on this spectrum will exhibit abnormal interpersonal distance preferences. The literature on interpersonal distance in ASD is not conclusive. While some studies show preferences for closer distances among this group, others show preferences for farther distances than controls. A common symptom of ASD that may explain the variance in responses to interpersonal distance in this population is social anxiety (SA), which has been shown to correlate with interpersonal distance preferences. In the current study, we investigated interpersonal distance preferences in a group of individuals with ASD using both behavioral and ERP measures. We found greater variance in interpersonal distance preferences in the ASD group than in the control group. Furthermore, we showed that this variance can be explained by differences in SA level and can be predicted by the N1 amplitude, an early ERP component related to attention and discrimination processes. These results hint at the early sensory and attentional processes that may be affecting higher social behaviors, both in subclinical and in clinical populations.

Autism spectrum disorder: does neuroimaging support the DSM-5 proposal for a symptom dyad? A systematic review of functional magnetic resonance imaging and diffusion tensor imaging studies.

PubMed

Pina-Camacho, Laura; Villero, Sonia; Fraguas, David; Boada, Leticia; Janssen, Joost; Navas-Sánchez, Francisco J; Mayoral, Maria; Llorente, Cloe; Arango, Celso; Parellada, Mara

2012-07-01

A systematic review of 208 studies comprising functional magnetic resonance imaging and diffusion tensor imaging data in patients with 'autism spectrum disorder' (ASD) was conducted, in order to determine whether these data support the forthcoming DSM-5 proposal of a social communication and behavioral symptom dyad. Studies consistently reported abnormal function and structure of fronto-temporal and limbic networks with social and pragmatic language deficits, of temporo-parieto-occipital networks with syntactic-semantic language deficits, and of fronto-striato-cerebellar networks with repetitive behaviors and restricted interests in ASD patients. Therefore, this review partially supports the DSM-5 proposal for the ASD dyad.

Hearing regulates Drosophila aggression.

PubMed

Versteven, Marijke; Vanden Broeck, Lies; Geurten, Bart; Zwarts, Liesbeth; Decraecker, Lisse; Beelen, Melissa; Göpfert, Martin C; Heinrich, Ralf; Callaerts, Patrick

2017-02-21

Aggression is a universal social behavior important for the acquisition of food, mates, territory, and social status. Aggression in Drosophila is context-dependent and can thus be expected to involve inputs from multiple sensory modalities. Here, we use mechanical disruption and genetic approaches in Drosophila melanogaster to identify hearing as an important sensory modality in the context of intermale aggressive behavior. We demonstrate that neuronal silencing and targeted knockdown of hearing genes in the fly's auditory organ elicit abnormal aggression. Further, we show that exposure to courtship or aggression song has opposite effects on aggression. Our data define the importance of hearing in the control of Drosophila intermale aggression and open perspectives to decipher how hearing and other sensory modalities are integrated at the neural circuit level.

Hearing regulates Drosophila aggression

PubMed Central

Versteven, Marijke; Vanden Broeck, Lies; Geurten, Bart; Zwarts, Liesbeth; Decraecker, Lisse; Beelen, Melissa; Göpfert, Martin C.; Heinrich, Ralf; Callaerts, Patrick

2017-01-01

Aggression is a universal social behavior important for the acquisition of food, mates, territory, and social status. Aggression in Drosophila is context-dependent and can thus be expected to involve inputs from multiple sensory modalities. Here, we use mechanical disruption and genetic approaches in Drosophila melanogaster to identify hearing as an important sensory modality in the context of intermale aggressive behavior. We demonstrate that neuronal silencing and targeted knockdown of hearing genes in the fly’s auditory organ elicit abnormal aggression. Further, we show that exposure to courtship or aggression song has opposite effects on aggression. Our data define the importance of hearing in the control of Drosophila intermale aggression and open perspectives to decipher how hearing and other sensory modalities are integrated at the neural circuit level. PMID:28115690

The role of the hippocampus in flexible cognition and social behavior

PubMed Central

Rubin, Rachael D.; Watson, Patrick D.; Duff, Melissa C.; Cohen, Neal J.

2014-01-01

Successful behavior requires actively acquiring and representing information about the environment and people, and manipulating and using those acquired representations flexibly to optimally act in and on the world. The frontal lobes have figured prominently in most accounts of flexible or goal-directed behavior, as evidenced by often-reported behavioral inflexibility in individuals with frontal lobe dysfunction. Here, we propose that the hippocampus also plays a critical role by forming and reconstructing relational memory representations that underlie flexible cognition and social behavior. There is mounting evidence that damage to the hippocampus can produce inflexible and maladaptive behavior when such behavior places high demands on the generation, recombination, and flexible use of information. This is seen in abilities as diverse as memory, navigation, exploration, imagination, creativity, decision-making, character judgments, establishing and maintaining social bonds, empathy, social discourse, and language use. Thus, the hippocampus, together with its extensive interconnections with other neural systems, supports the flexible use of information in general. Further, we suggest that this understanding has important clinical implications. Hippocampal abnormalities can produce profound deficits in real-world situations, which typically place high demands on the flexible use of information, but are not always obvious on diagnostic tools tuned to frontal lobe function. This review documents the role of the hippocampus in supporting flexible representations and aims to expand our understanding of the dynamic networks that operate as we move through and create meaning of our world. PMID:25324753

The role of the hippocampus in flexible cognition and social behavior.

PubMed

Rubin, Rachael D; Watson, Patrick D; Duff, Melissa C; Cohen, Neal J

2014-01-01

Successful behavior requires actively acquiring and representing information about the environment and people, and manipulating and using those acquired representations flexibly to optimally act in and on the world. The frontal lobes have figured prominently in most accounts of flexible or goal-directed behavior, as evidenced by often-reported behavioral inflexibility in individuals with frontal lobe dysfunction. Here, we propose that the hippocampus also plays a critical role by forming and reconstructing relational memory representations that underlie flexible cognition and social behavior. There is mounting evidence that damage to the hippocampus can produce inflexible and maladaptive behavior when such behavior places high demands on the generation, recombination, and flexible use of information. This is seen in abilities as diverse as memory, navigation, exploration, imagination, creativity, decision-making, character judgments, establishing and maintaining social bonds, empathy, social discourse, and language use. Thus, the hippocampus, together with its extensive interconnections with other neural systems, supports the flexible use of information in general. Further, we suggest that this understanding has important clinical implications. Hippocampal abnormalities can produce profound deficits in real-world situations, which typically place high demands on the flexible use of information, but are not always obvious on diagnostic tools tuned to frontal lobe function. This review documents the role of the hippocampus in supporting flexible representations and aims to expand our understanding of the dynamic networks that operate as we move through and create meaning of our world.

Developmental disruption of amygdala transcriptome and socioemotional behavior in rats exposed to valproic acid prenatally.

PubMed

Barrett, Catherine E; Hennessey, Thomas M; Gordon, Katelyn M; Ryan, Steve J; McNair, Morgan L; Ressler, Kerry J; Rainnie, Donald G

2017-01-01

The amygdala controls socioemotional behavior and has consistently been implicated in the etiology of autism spectrum disorder (ASD). Precocious amygdala development is commonly reported in ASD youth with the degree of overgrowth positively correlated to the severity of ASD symptoms. Prenatal exposure to VPA leads to an ASD phenotype in both humans and rats and has become a commonly used tool to model the complexity of ASD symptoms in the laboratory. Here, we examined abnormalities in gene expression in the amygdala and socioemotional behavior across development in the valproic acid (VPA) rat model of ASD. Rat dams received oral gavage of VPA (500 mg/kg) or saline daily between E11 and 13. Socioemotional behavior was tracked across development in both sexes. RNA sequencing and proteomics were performed on amygdala samples from male rats across development. Effects of VPA on time spent in social proximity and anxiety-like behavior were sex dependent, with social abnormalities presenting in males and heightened anxiety in females. Across time VPA stunted developmental and immune, but enhanced cellular death and disorder, pathways in the amygdala relative to saline controls. At postnatal day 10, gene pathways involved in nervous system and cellular development displayed predicted activations in prenatally exposed VPA amygdala samples. By juvenile age, however, transcriptomic and proteomic pathways displayed reductions in cellular growth and neural development. Alterations in immune pathways, calcium signaling, Rho GTPases, and protein kinase A signaling were also observed. As behavioral, developmental, and genomic alterations are similar to those reported in ASD, these results lend support to prenatal exposure to VPA as a useful tool for understanding how developmental insults to molecular pathways in the amygdala give rise to ASD-related syndromes.

Systemic lupus erythematosus in three ethnic groups. V. Acculturation, health-related attitudes and behaviors, and disease activity in Hispanic patients from the LUMINA cohort. LUMINA Study Group. Lupus in Minority Populations, Nature versus Nurture.

PubMed

Alarcón, G S; Rodríguez, J L; Benavides, G; Brooks, K; Kurusz, H; Reveille, J D

1999-08-01

To assess the relationship between acculturation and clinical, socioeconomic-demographic, and behavioral/psychosocial features in Hispanic patients with systemic lupus erythematosus (SLE) from the LUMINA (Lupus in Minority Populations, Nature versus Nurture) cohort. An empirically derived questionnaire was administered to 67 Mexican American SLE patients participating in a longitudinal study of outcome. This questionnaire inquired about place of birth, upbringing and length of stay in the United States, language (proficiency, usage, and preferences; English/bilingual versus Spanish), type of neighborhood, self-identity, and social interactions. Responses to this questionnaire and an informal interaction with a single bilingual, bicultural Mexican American research assistant were used to generate a score on a 10-cm anchored visual analog scale (VAS) (0 = no acculturation and 10 = maximum acculturation). The responses to the questionnaire were then quantified and scored by a physician who was unaware of the VAS. A composite score was then obtained utilizing 4 of the 6 components of the instrument. The VAS was found to have adequate sensitivity (91%), specificity (88%), and overall predictive value (89%) when the composite score was used as the validity criterion. Therefore, the VAS was used in all subsequent analyses; the median in this VAS separated patients into high and low acculturation groups. The relationship between acculturation and sociodemographic, behavioral/psychosocial (social support, abnormal illness-related behaviors, and helplessness) and clinical variables (disease duration, onset type, number of American College of Rheumatology criteria met, disease activity, and damage) at study entry was then explored. Patients in the low acculturation group had fewer years of education, were less likely to have private health insurance, and had less social support as compared with those in the high acculturation group; they also exhibited less disease activity as determined by the overall physician and patient global assessments of the Systemic Lupus Activity Measure. Abnormal illness-related behaviors and helplessness were not increased in the low acculturation group. Low levels of acculturation were associated with indicators of low socioeconomic status, but also with less disease activity at enrollment into LUMINA; they were, however, not associated with more abnormal illness-related behaviors or with helplessness, as measured in this study. The possible impact of acculturation and of its mediators in the course and outcome of SLE among Hispanic patients needs to be determined longitudinally.

Insulin-Like Growth Factor II Targets the mTOR Pathway to Reverse Autism-Like Phenotypes in Mice.

PubMed

Steinmetz, Adam B; Stern, Sarah A; Kohtz, Amy S; Descalzi, Giannina; Alberini, Cristina M

2018-01-24

Autism spectrum disorder (ASD) is a developmental disability characterized by impairments in social interaction and repetitive behavior, and is also associated with cognitive deficits. There is no current treatment that can ameliorate most of the ASD symptomatology; thus, identifying novel therapies is urgently needed. We used male BTBR T + Itpr3 tf /J (BTBR) mice, a model that reproduces most of the core behavioral phenotypes of ASD, to test the effects of systemic administration of insulin-like growth factor II (IGF-II), a polypeptide that crosses the blood-brain barrier and acts as a cognitive enhancer. We show that systemic IGF-II treatments reverse the typical defects in social interaction, cognitive/executive functions, and repetitive behaviors reflective of ASD-like phenotypes. In BTBR mice, IGF-II, via IGF-II receptor, but not via IGF-I receptor, reverses the abnormal levels of the AMPK-mTOR-S6K pathway and of active translation at synapses. Thus, IGF-II may represent a novel potential therapy for ASD. SIGNIFICANCE STATEMENT Currently, there is no effective treatment for autism spectrum disorder (ASD), a developmental disability affecting a high number of children. Using a mouse model that expresses most of the key core as well as associated behavioral deficits of ASD, that are, social, cognitive, and repetitive behaviors, we report that a systemic administration of the polypeptide insulin-like growth factor II (IGF-II) reverses all these deficits. The effects of IGF-II occur via IGF-II receptors, and not IGF-I receptors, and target both basal and learning-dependent molecular abnormalities found in several ASD mice models, including those of identified genetic mutations. We suggest that IGF-II represents a potential novel therapeutic target for ASD. Copyright © 2018 the authors 0270-6474/18/371015-15$15.00/0.

Autism-related neuroligin-3 mutation alters social behavior and spatial learning.

PubMed

Jaramillo, Thomas C; Liu, Shunan; Pettersen, Ami; Birnbaum, Shari G; Powell, Craig M

2014-04-01

Multiple candidate genes have been identified for autism spectrum disorders. While some of these genes reach genome-wide significance, others, such as the R451C point mutation in the synaptic cell adhesion molecule neuroligin-3, appear to be rare. Interestingly, two brothers with the same R451C point mutation in neuroligin-3 present clinically on seemingly disparate sides of the autism spectrum. These clinical findings suggest genetic background may play a role in modifying the penetrance of a particular autism-associated mutation. Animal models may contribute additional support for such mutations as functionally relevant and can provide mechanistic insights. Previously, in collaboration with the Südhof laboratory, we reported that mice with an R451C substitution in neuroligin-3 displayed social deficits and enhanced spatial learning. While some of these behavioral abnormalities have since been replicated independently in the Südhof laboratory, observations from the Crawley laboratory failed to replicate these findings in a similar neuroligin-3 mutant mouse model and suggested that genetic background may contribute to variation in observations across laboratories. Therefore, we sought to replicate our findings in the neuroligin-3 R451C point mutant knock-in mouse model (NL3R451C) in a different genetic background. We backcrossed our NL3R451C mouse line onto a 129S2/SvPasCrl genetic background and repeated a subset of our previous behavioral testing. NL3R451C mice on a 129S2/SvPasCrl displayed social deficits, enhanced spatial learning, and increased locomotor activity. These data extend our previous findings that NL3R451C mice exhibit autism-relevant behavioral abnormalities and further suggest that different genetic backgrounds can modify this behavioral phenotype through epistatic genetic interactions. © 2014 International Society for Autism Research, Wiley Periodicals, Inc.

Readiness to change and brain damage in patients with chronic alcoholism.

PubMed

Le Berre, Anne-Pascale; Rauchs, Géraldine; La Joie, Renaud; Segobin, Shailendra; Mézenge, Florence; Boudehent, Céline; Vabret, François; Viader, Fausto; Eustache, Francis; Pitel, Anne-Lise; Beaunieux, Hélène

2013-09-30

High motivation to change is a crucial triggering factor to patients' engagement in clinical treatment. This study investigates whether the low readiness to change observed in some alcoholic inpatients at treatment entry could, at least partially, be linked with macrostructural gray matter abnormalities in critical brain regions. Participants comprised 31 alcoholic patients and 27 controls, who underwent 1.5-T magnetic resonance imaging. The Readiness to Change Questionnaire, designed to assess three stages of motivation to change (precontemplation, contemplation and action stages), was completed by all patients, who were then divided into "Action" (i.e., patients in action stage) and "PreAction" (i.e., patients in precontemplation or in contemplation stage) subgroups. The PreAction subgroup, but not the Action subgroup, had gray matter volume deficits compared with controls. Unlike the patients in the Action subgroup, the PreAction patients had gray matter abnormalities in the cerebellum (Crus I), fusiform gyri and frontal cortex. The low level of motivation to modify drinking behavior observed in some alcoholic patients at treatment entry may be related to macrostructural brain abnormalities in regions subtending cognitive, emotional and social abilities. These brain volume deficits may result in impairment of critical abilities such as decision making, executive functions and social cognition skills. Those abilities may be needed to resolve ambivalence toward alcohol addiction and to apply "processes of change", which are essential for activating the desire to change problematic behavior. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

Epileptic encephalopathy with continuous spike-waves during sleep: the need for transition from childhood to adulthood medical care appears to be related to etiology.

PubMed

de Saint-Martin, Anne; Rudolf, Gabrielle; Seegmuller, Caroline; Valenti-Hirsch, Maria Paola; Hirsch, Edouard

2014-08-01

Epileptic encephalopathy with continuous diffuse spike-waves during slow-wave sleep (ECSWS) presents clinically with infrequent nocturnal focal seizures, atypical absences related to secondary bilateral synchrony, negative myoclonia, and atonic and rare generalized tonic-clonic seizures. The unique electroencephalography (EEG) pattern found in ECSWS consists of continuous, diffuse, bilateral spike-waves during slow-wave sleep. Despite the eventual disappearance of clinical seizures and EEG abnormalities by adolescence, the prognosis is guarded in most cases because of neuropsychological and behavioral deficits. ECSWS has a heterogeneous etiology (genetic, structural, and unknown). Because epilepsy and electroencephalography (EEG) abnormalities in epileptic encephalopathy with continuous diffuse spike-waves during slow-wave sleep (ECSWS) are self-limited and age related, the need for ongoing medical care and transition to adult care might be questioned. For adolescents in whom etiology remains unknown (possibly genetic) and who experience the disappearance of seizures and EEG abnormalities, there is rarely need for long-term neurologic follow-up, because often a relatively normal cognitive and social evolution follows. However, the majority of patients with structural and possibly "genetic syndromic" etiologies will have persistent cognitive deficits and will need suitable socioeducative care. Therefore, the transition process in ECSWS will depend mainly on etiology and its related features (epileptic active phase duration, and cognitive and behavioral evolution) and revolve around neuropsychological and social support rather than medical and pharmacologic follow-up. Wiley Periodicals, Inc. © 2014 International League Against Epilepsy.

Altered cingulo-striatal function underlies reward drive deficits in schizophrenia.

PubMed

Park, Il Ho; Chun, Ji Won; Park, Hae-Jeong; Koo, Min-Seong; Park, Sunyoung; Kim, Seok-Hyeong; Kim, Jae-Jin

2015-02-01

Amotivation in schizophrenia is assumed to involve dysfunctional dopaminergic signaling of reward prediction or anticipation. It is unclear, however, whether the translation of neural representation of reward value to behavioral drive is affected in schizophrenia. In order to examine how abnormal neural processing of response valuation and initiation affects incentive motivation in schizophrenia, we conducted functional MRI using a deterministic reinforcement learning task with variable intervals of contingency reversals in 20 clinically stable patients with schizophrenia and 20 healthy controls. Behaviorally, the advantage of positive over negative reinforcer in reinforcement-related responsiveness was not observed in patients. Patients showed altered response valuation and initiation-related striatal activity and deficient rostro-ventral anterior cingulate cortex activation during reward approach initiation. Among these neural abnormalities, rostro-ventral anterior cingulate cortex activation was correlated with positive reinforcement-related responsiveness in controls and social anhedonia and social amotivation subdomain scores in patients. Our findings indicate that the central role of the anterior cingulate cortex is in translating action value into driving force of action, and underscore the role of the cingulo-striatal network in amotivation in schizophrenia. Copyright © 2014 Elsevier B.V. All rights reserved.

A two-hit model of suicide-trait-related behaviors in the context of a schizophrenia-like phenotype: Distinct effects of lithium chloride and clozapine.

PubMed

Deslauriers, Jessica; Belleville, Karine; Beaudet, Nicolas; Sarret, Philippe; Grignon, Sylvain

2016-03-15

Schizophrenia patients show a high rate of premature mortality due to suicide. The pathophysiological mechanisms of these suicidal behaviors in schizophrenia do not appear to involve serotonergic neurotransmission as found in the general population. Our aim was to develop an in vivo model of schizophrenia presenting suicide-trait-related behaviors such as aggressiveness, impulsivity, anxiety and helplessness. We opted for a two-hit model: C57BL/6 dams were injected with polyI:C on gestational day 12. The pups were submitted to social isolation for 4weeks after weaning. During the last week of social isolation and 30min before behavioral testing, the mice received vehicle, lithium chloride or clozapine. Lithium chloride is well known for its suicide preventive effects in the non-schizophrenic population, while clozapine is the antipsychotic with the best-established suicide preventive effect. The two-hit model induced several schizophrenia-related and suicide-trait-related behaviors in male, but not female, mice. Additionally, lithium chloride improved prepulse inhibition, aggressiveness, impulsivity and anxiety-like behavior in socially isolated mice only, whereas clozapine prevented behavioral abnormalities mainly in mice prenatally exposed to polyI:C and submitted to isolated rearing. The distinct effects of lithium chloride and clozapine suggested that mice prenatally exposed to polyI:C and submitted to social isolation presented a distinct phenotype from that of mice submitted to social isolation only. Because diagnosing suicidal risk in patients is a challenge for psychiatrists given the lack of specific clinical predictors, our in vivo model could help in gaining a better understanding of the mechanisms underlying suicidal behavior in the context of schizophrenia. Copyright © 2016 Elsevier Inc. All rights reserved.

A humanoid mouse model of autism.

PubMed

Takumi, Toru

2010-10-01

Even now fruit of the human genome project is available, we have difficulties to approach neuropsychiatric disorders at the molecular level. Autism is a complex psychiatric illness but has received considerable attention as a developmental brain disorder not only from basic researchers but also from society. Substantial evidence suggests that chromosomal abnormalities contribute to autism risk. The duplication of human chromosome 15q11-13 is known to be the most frequent cytogenetic abnormality in autism. We succeeded to generate mice with a 6.3-Mb-wide interstitial duplication in mouse chromosome 7c that is highly syntenic to human 15q11-13 by using a Cre-loxP-based chromosome-engineering technique. The only paternally duplicated mice display autistic behavioral features such as poor social interaction and stereotypical behavior, and exhibit a developmental abnormality in ultrasonic vocalizations as well as anxiety. The detailed analysis focusing on a non-coding small nucleolar RNA, MBII52, within the duplicated region, revealed that the paternally duplicated mice alter the editing ratio of serotonin (5-HT) 2c receptor pre-mRNA and intracellular calcium responses by a 5-HT2c receptor specific agonist are changed in neurons. This result may explain one of molecular mechanisms of abnormal behaviors in the paternal duplicated mice. The first chromosome-engineered mouse model for human chromosome 15q11-13 duplication fulfills not only face validity of human autistic phenotypes but also construct validity based on human chromosome abnormality. This model will be a founder mouse for forward genetics of autistic disease and an invaluable tool for its therapeutic development. Copyright © 2010 Elsevier B.V. All rights reserved.

Behavioral and neuroanatomical abnormalities in pleiotrophin knockout mice.

PubMed

Krellman, Jason W; Ruiz, Henry H; Marciano, Veronica A; Mondrow, Bracha; Croll, Susan D

2014-01-01

Pleiotrophin (PTN) is an extracellular matrix-associated protein with neurotrophic and neuroprotective effects that is involved in a variety of neurodevelopmental processes. Data regarding the cognitive-behavioral and neuroanatomical phenotype of pleiotrophin knockout (KO) mice is limited. The purpose of this study was to more fully characterize this phenotype, with emphasis on the domains of learning and memory, cognitive-behavioral flexibility, exploratory behavior and anxiety, social behavior, and the neuronal and vascular microstructure of the lateral entorhinal cortex (EC). PTN KOs exhibited cognitive rigidity, heightened anxiety, behavioral reticence in novel contexts and novel social interactions suggestive of neophobia, and lamina-specific decreases in neuronal area and increases in neuronal density in the lateral EC. Initial learning of spatial and other associative tasks, as well as vascular density in the lateral EC, was normal in the KOs. These data suggest that the absence of PTN in vivo is associated with disruption of specific cognitive and affective processes, raising the possibility that further study of PTN KOs might have implications for the study of human disorders with similar features.

Social stress induces neurovascular pathology promoting depression

PubMed Central

Menard, Caroline; Pfau, Madeline L.; Hodes, Georgia E.; Kana, Veronika; Wang, Victoria X.; Bouchard, Sylvain; Takahashi, Aki; Flanigan, Meghan E.; Aleyasin, Hossein; LeClair, Katherine B.; Janssen, William G.; Labonté, Benoit; Parise, Eric M.; Lorsch, Zachary S.; Golden, Sam A.; Heshmati, Mitra; Tamminga, Carol; Turecki, Gustavo; Campbell, Matthew; Fayad, Zahi; Tang, Cheuk Ying; Merad, Miriam; Russo, Scott J.

2017-01-01

Studies suggest that heightened peripheral inflammation contributes to the pathogenesis of major depressive disorder. We investigated the effect of chronic social defeat stress, a mouse model of depression, on blood-brain barrier (BBB) permeability and infiltration of peripheral immune signals. We found reduced expression of endothelial cell tight junction protein claudin-5 (cldn5) and abnormal blood vessel morphology in nucleus accumbens (NAc) of stress-susceptible but not resilient mice. CLDN5 expression was also decreased in NAc of depressed patients. Cldn5 down-regulation was sufficient to induce depression-like behaviors following subthreshold social stress while chronic antidepressant treatment rescued cldn5 loss and promoted resilience. Reduced BBB integrity in NAc of stress-susceptible or AAV-shRNA-cldn5-injected mice caused infiltration of peripheral cytokine interleukin-6 (IL-6) into brain parenchyma and subsequent expression of depression-like behaviors. These findings suggest that chronic social stress alters BBB integrity through loss of tight junction protein cldn5, promoting peripheral IL-6 passage across the BBB and depression. PMID:29184215

Cortical Structure Alterations and Social Behavior Impairment in p50-Deficient Mice.

PubMed

Bonini, Sara Anna; Mastinu, Andrea; Maccarinelli, Giuseppina; Mitola, Stefania; Premoli, Marika; La Rosa, Luca Rosario; Ferrari-Toninelli, Giulia; Grilli, Mariagrazia; Memo, Maurizio

2016-06-01

Alterations in genes that regulate neurodevelopment can lead to cortical malformations, resulting in malfunction during postnatal life. The NF-κB pathway has a key role during neurodevelopment by regulating the maintenance of the neural progenitor cell pool and inhibiting neuronal differentiation. In this study, we evaluated whether mice lacking the NF-κB p50 subunit (KO) present alterations in cortical structure and associated behavioral impairment. We found that, compared with wild type (WT), KO mice at postnatal day 2 present an increase in radial glial cells, an increase in Reelin protein expression levels, in addition to an increase of specific layer thickness. Moreover, adult KO mice display abnormal columnar organization in the somatosensory cortex, a specific decrease in somatostatin- and parvalbumin-expressing interneurons, altered neurite orientation, and a decrease in Synapsin I protein levels. Concerning behavior, KO mice, in addition to an increase in locomotor and exploratory activity, display impairment in social behaviors, with a reduction in social interaction. Finally, we found that risperidone treatment decreased hyperactivity of KO mice, but had no effect on defective social interaction. Altogether, these data add complexity to a growing body of data, suggesting a link between dysregulation of the NF-κB pathway and neurodevelopmental disorders pathogenesis. © The Author 2016. Published by Oxford University Press.

Programming social behavior by the maternal fragile X protein.

PubMed

Zupan, B; Sharma, A; Frazier, A; Klein, S; Toth, M

2016-07-01

The developing fetus and neonate are highly sensitive to maternal environment. Besides the well-documented effects of maternal stress, nutrition and infections, maternal mutations, by altering the fetal, perinatal and/or early postnatal environment, can impact the behavior of genetically normal offspring. Mutation/premutation in the X-linked FMR1 (encoding the translational regulator FMRP) in females, although primarily responsible for causing fragile X syndrome (FXS) in their children, may also elicit such maternal effects. We showed that a deficit in maternal FMRP in mice results in hyperactivity in the genetically normal offspring. To test if maternal FMRP has a broader intergenerational effect, we measured social behavior, a core dimension of neurodevelopmental disorders, in offspring of FMRP-deficient dams. We found that male offspring of Fmr1(+/-) mothers, independent of their own Fmr1 genotype, exhibit increased approach and reduced avoidance toward conspecific strangers, reminiscent of 'indiscriminate friendliness' or the lack of stranger anxiety, diagnosed in neglected children and in patients with Asperger's and Williams syndrome. Furthermore, social interaction failed to activate mesolimbic/amygdala regions, encoding social aversion, in these mice, providing a neurobiological basis for the behavioral abnormality. This work identifies a novel role for FMRP that extends its function beyond the well-established genetic function into intergenerational non-genetic inheritance/programming of social behavior and the corresponding neuronal circuit. As FXS premutation and some psychiatric conditions that can be associated with reduced FMRP expression are more prevalent in mothers than full FMR1 mutation, our findings potentially broaden the significance of FMRP-dependent programming of social behavior beyond the FXS population. © 2016 John Wiley & Sons Ltd and International Behavioural and Neural Genetics Society.

Pharmacologic rescue of impaired cognitive flexibility, social deficits, increased aggression, and seizure susceptibility in oxytocin receptor null mice: a neurobehavioral model of autism.

PubMed

Sala, Mariaelvina; Braida, Daniela; Lentini, Daniela; Busnelli, Marta; Bulgheroni, Elisabetta; Capurro, Valeria; Finardi, Annamaria; Donzelli, Andrea; Pattini, Linda; Rubino, Tiziana; Parolaro, Daniela; Nishimori, Katsuhiko; Parenti, Marco; Chini, Bice

2011-05-01

Oxytocin (OT) has been suggested as a treatment to improve social behavior in autistic patients. Accordingly, the OT (Oxt(-/-)) and the OT receptor null mice (Oxtr(-/-)) display autistic-like deficits in social behavior, increased aggression, and reduced ultrasonic vocalization. Oxtr(-/-) mice were characterized for general health, sociability, social novelty, cognitive flexibility, aggression, and seizure susceptibility. Because vasopressin (AVP) and OT cooperate in controlling social behavior, learning, and aggression, they were tested for possible rescue of the impaired behaviors. Primary hyppocampal cultures from Oxtr(+/+) and Oxtr(-/-) mouse embryos were established to investigate the balance between gamma-aminobutyric acid (GABA) and glutamate synapses and the expression levels of OT and AVP (V1a) receptors were determined by autoradiography. Oxtr(-/-) mice display two additional, highly relevant, phenotypic characteristics: 1) a resistance to change in a learned pattern of behavior, comparable to restricted interests and repetitive behavior in autism, and 2) an increased susceptibility to seizures, a frequent and clinically relevant symptom of autism. We also show that intracerebral administration of both OT and AVP lowers aggression and fully reverts social and learning defects by acting on V1a receptors and that seizure susceptibility is antagonized by peripherally administered OT. Finally, we detect a decreased ratio of GABA-ergic versus total presynapses in hippocampal neurons of Oxtr(-/-) mice. Autistic-like symptoms are rescued on administration of AVP and OT to young Oxtr(-/-) adult animals. The Oxtr(-/-) mouse is thus instrumental to investigate the neurochemical and synaptic abnormalities underlying autistic-like disturbances and to test new strategies of pharmacologic intervention. Copyright © 2011 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

A review of social skills deficits in individuals with fetal alcohol spectrum disorders and prenatal alcohol exposure: profiles, mechanisms, and interventions.

PubMed

Kully-Martens, Katrina; Denys, Kennedy; Treit, Sarah; Tamana, Sukhpreet; Rasmussen, Carmen

2012-04-01

Individuals gestationally exposed to alcohol experience a multitude of sociobehavioral impairments, including deficits in adaptive behaviors such as social skills. The goal of this report is to critically review research on social skills deficits in individuals with prenatal alcohol exposure, including individuals with and without fetal alcohol spectrum disorders (FASD). Social deficits are found in alcohol-exposed children, adults, and adolescents with and without a clinical presentation. These deficits tend to persist across the lifespan and may even worsen with age. Social deficits in this population appear to be independent of facial dysmorphology and IQ and are worse than can be predicted based on atypical behaviors alone. Abnormalities in neurobiology, executive function, sensory processing, and communication likely interact with contextual influences to produce the range of social deficits observed in FASD. Future investigations should strive to reconcile the relationship between social skills deficits in FASD and variables such as gender, age, cognitive profile, and structural and functional brain impairments to enable better characterization of the deficits observed in this population, which will enhance diagnosis and improve remediation. Copyright © 2011 by the Research Society on Alcoholism.

Looking you in the mouth: abnormal gaze in autism resulting from impaired top-down modulation of visual attention.

PubMed

Neumann, Dirk; Spezio, Michael L; Piven, Joseph; Adolphs, Ralph

2006-12-01

People with autism are impaired in their social behavior, including their eye contact with others, but the processes that underlie this impairment remain elusive. We combined high-resolution eye tracking with computational modeling in a group of 10 high-functioning individuals with autism to address this issue. The group fixated the location of the mouth in facial expressions more than did matched controls, even when the mouth was not shown, even in faces that were inverted and most noticeably at latencies of 200-400 ms. Comparisons with a computational model of visual saliency argue that the abnormal bias for fixating the mouth in autism is not driven by an exaggerated sensitivity to the bottom-up saliency of the features, but rather by an abnormal top-down strategy for allocating visual attention.

Chronic minocycline treatment improves social recognition memory in adult male Fmr1 knockout mice.

PubMed

Yau, Suk Yu; Chiu, Christine; Vetrici, Mariana; Christie, Brian R

2016-10-01

Fragile X syndrome (FXS) is caused by a mutation in the Fmr1 gene that leads to silencing of the gene and a loss of its gene product, Fragile X mental retardation protein (FMRP). Some of the key behavioral phenotypes for FXS include abnormal social anxiety and sociability. Here we show that Fmr1 knock-out (KO) mice exhibit impaired social recognition when presented with a novel mouse, and they display normal social interactions in other sociability tests. Administering minocycline to Fmr1 KO mice throughout critical stages of neural development improved social recognition memory in the novel mouse recognition task. To determine if synaptic changes in the prefrontal cortex (PFC) could have played a role in this improvement, we examined PSD-95, a member of the membrane-associated guanylate kinase family, and signaling molecules (ERK1/2, and Akt) linked to synaptic plasticity in the PFC. Our analyses indicated that while minocycline treatment can enhance behavioral performance, it does not enhance expression of PSD-95, ERK1/2 or Akt in the PFC. Copyright © 2016 Elsevier B.V. All rights reserved.

Endogenous vasopressin, innate anxiety, and the emission of pro-social 50-kHz ultrasonic vocalizations during social play behavior in juvenile rats.

PubMed

Lukas, Michael; Wöhr, Markus

2015-06-01

Although the involvement of the neuropeptide arginine vasopressin (AVP) in rodent social interaction is already extensively characterized, little is known about its role in social communication. Rats communicate in the ultrasonic range by means of ultrasonic vocalizations (USV). Depending on developmental stage and affective state, rats emit various distinct types of USV, with appetitive 50-kHz USV being induced by positive social interactions, like juvenile social play, probably serving an affiliative communicative function, namely to (re)establish or induce social proximity. In rats and mice selectively bred for low (LAB) and high (HAB) anxiety-related behavior, the emission of isolation-induced distress USV during maternal deprivation as pups correlates with innate high levels of hypothalamic AVP availability. Moreover, male LAB and HAB rats express deficits in social approach towards conspecifics, together with high and/or abnormal forms of aggression when confronted with harmless opponents, possibly due to a lack of social communication skills. The aim of this study was therefore (1) to investigate and characterize social play behavior and concomitant pro-social 50-kHz USV emission in male and female, juvenile LAB and HAB rats and to compare them to non-selected Wistar (NAB) rats; and (2) to link these findings pharmacologically to the central AVP system via applying an AVP 1a receptor (V1aR) antagonist (0.75 μg; Manning compound) or synthetic AVP (1 ng) into the lateral ventricle of male juvenile NAB rats. Our results show that reduced social play behavior in highly anxious male and female, juvenile HAB rats is accompanied by low amounts of pro-social 50-kHz USV, as compared to respective LAB and NAB rats, possibly reflecting a lack of positive affective states in expectation of or following social interactions in these individuals. Secondly, although synthetic AVP did not alter social play behavior and pro-social 50-kHz USV, we demonstrated for the first time that a blockade of the central AVP system not only reduces juvenile social play behavior, but at the same time pro-social 50-kHz USV emission rates, indicating an involvement of the social neuropeptide in regulating affiliative communication in rodents. Copyright © 2015 Elsevier Ltd. All rights reserved.

Modulation of social deficits and repetitive behaviors in a mouse model of autism: the role of the nicotinic cholinergic system.

PubMed

Wang, Li; Almeida, Luis E F; Spornick, Nicholas A; Kenyon, Nicholas; Kamimura, Sayuri; Khaibullina, Alfia; Nouraie, Mehdi; Quezado, Zenaide M N

2015-12-01

Accumulating evidence implicates the nicotinic cholinergic system in autism spectrum disorder (ASD) pathobiology. Neuropathologic studies suggest that nicotinic acetylcholine (ACh) receptor (nAChR) subtypes are altered in brain of autistic individuals. In addition, strategies that increase ACh, the neurotransmitter for nicotinic and muscarinic receptors, appear to improve cognitive deficits in neuropsychiatric disorders and ASD. The aim of this study is to examine the role of the nicotinic cholinergic system on social and repetitive behavior abnormalities and exploratory physical activity in a well-studied model of autism, the BTBR T(+) Itpr3 (tf) /J (BTBR) mouse. Using a protocol known to up-regulate expression of brain nAChR subtypes, we measured behavior outcomes before and after BTBR and C57BL/6J (B6) mice were treated (4 weeks) with vehicle or nicotine (50, 100, 200, or 400 μg/ml). Increasing nicotine doses were associated with decreases in water intake, increases in plasma cotinine levels, and at the higher dose (400 μg/ml) with weight loss in BTBR mice. At lower (50, 100 μg/ml) but not higher (200, 400 μg/ml) doses, nicotine increased social interactions in BTBR and B6 mice and at higher, but not lower doses, it decreased repetitive behavior in BTBR. In the open-field test, nicotine at 200 and 400 μg/ml, but not 100 μg/ml compared with vehicle, decreased overall physical activity in BTBR mice. These findings support the hypotheses that the nicotinic cholinergic system modulates social and repetitive behaviors and may be a therapeutic target to treat behavior deficits in ASD. Further, the BTBR mouse may be valuable for investigations of the role of nAChRs in social deficits and repetitive behavior.

The Emergence of Network Inefficiencies in Infants With Autism Spectrum Disorder.

PubMed

Lewis, John D; Evans, Alan C; Pruett, John R; Botteron, Kelly N; McKinstry, Robert C; Zwaigenbaum, Lonnie; Estes, Annette M; Collins, D Louis; Kostopoulos, Penelope; Gerig, Guido; Dager, Stephen R; Paterson, Sarah; Schultz, Robert T; Styner, Martin A; Hazlett, Heather C; Piven, Joseph

2017-08-01

Autism spectrum disorder (ASD) is a developmental disorder defined by behavioral features that emerge during the first years of life. Research indicates that abnormalities in brain connectivity are associated with these behavioral features. However, the inclusion of individuals past the age of onset of the defining behaviors complicates interpretation of the observed abnormalities: they may be cascade effects of earlier neuropathology and behavioral abnormalities. Our recent study of network efficiency in a cohort of 24-month-olds at high and low familial risk for ASD reduced this confound; we reported reduced network efficiencies in toddlers classified with ASD. The current study maps the emergence of these inefficiencies in the first year of life. This study uses data from 260 infants at 6 and 12 months of age, including 116 infants with longitudinal data. As in our earlier study, we use diffusion data to obtain measures of the length and strength of connections between brain regions to compute network efficiency. We assess group differences in efficiency within linear mixed-effects models determined by the Akaike information criterion. Inefficiencies in high-risk infants later classified with ASD were detected from 6 months onward in regions involved in low-level sensory processing. In addition, within the high-risk infants, these inefficiencies predicted 24-month symptom severity. These results suggest that infants with ASD, even before 6 months of age, have deficits in connectivity related to low-level processing, which contribute to a developmental cascade affecting brain organization and eventually higher-level cognitive processes and social behavior. Copyright © 2017 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

Change in children's school behavior after mass administration of praziquantel for Schistosoma mansoni infection in endemic areas of western Kenya: A pilot study using the Behavioral Assessment System for Children (BASC-2).

PubMed

Musuva, Rosemary; Shen, Ye; Wei, Xianjue; Binder, Sue; Ivy, Julianne A; Secor, W Evan; Montgomery, Susan P; King, Charles H; Mwinzi, Pauline N M

2017-01-01

Schistosomiasis is a parasite-related chronic inflammatory condition that can cause anemia, decreased growth, liver abnormalities, and deficits in cognitive functioning among children. This study used the Behavior Assessment System for Children (BASC-2) to collect data on thirty-six 9-12 year old school-attending children's behavioral profiles in an Schistosoma mansoni-endemic area of western Kenya, before and after treatment with praziquantel for S. mansoni infection. BASC-2 T scores were significantly reduced post-treatment (p < 0.05) for each of the 'negative' behavior categories including externalizing problems (hyperactivity, aggression, and conduct problems that are disruptive in nature), internalizing problems (anxiety, depression, somatization, atypicality, and withdrawal), school problems (academic difficulties, included attention problems and learning problems), and the composite behavioral symptoms index (BSI), signifying improved behavior. While the observed improvement in the 'positive' behavior category of adaptive skills (adaptability, functional communication, social skills, leadership, and study skills) was not statistically significant, there were significant improvements in two adaptive skills subcategories: social skills and study skills. Results of this study suggest that children have better school-related behaviors without heavy S. mansoni infection, and that infected children's behaviors, especially disruptive problem behaviors, improve significantly after praziquantel treatment.

Self-regulation of brain oscillations as a treatment for aberrant brain connections in children with autism.

PubMed

Pineda, J A; Juavinett, A; Datko, M

2012-12-01

Autism is a highly varied developmental disorder typically characterized by deficits in reciprocal social interaction, difficulties with verbal and nonverbal communication, and restricted interests and repetitive behaviors. Although a wide range of behavioral, pharmacological, and alternative medicine strategies have been reported to ameliorate specific symptoms for some individuals, there is at present no cure for the condition. Nonetheless, among the many incompatible observations about aspects of the development, anatomy, and functionality of the autistic brain, it is widely agreed that it is characterized by widespread aberrant connectivity. Such disordered connectivity, be it increased, decreased, or otherwise compromised, may complicate healthy synchronization and communication among and within different neural circuits, thereby producing abnormal processing of sensory inputs necessary for normal social life. It is widely accepted that the innate properties of brain electrical activity produce pacemaker elements and linked networks that oscillate synchronously or asynchronously, likely reflecting a type of functional connectivity. Using phase coherence in multiple frequency EEG bands as a measure of functional connectivity, studies have shown evidence for both global hypoconnectivity and local hyperconnectivity in individuals with ASD. However, the nature of the brain's experience-dependent structural plasticity suggests that these abnormal patterns may be reversed with the proper type of treatment. Indeed, neurofeedback (NF) training, an intervention based on operant conditioning that results in self-regulation of brain electrical oscillations, has shown promise in addressing marked abnormalities in functional and structural connectivity. It is hypothesized that neurofeedback produces positive behavioral changes in ASD children by normalizing the aberrant connections within and between neural circuits. NF exploits the brain's plasticity to normalize aberrant connectivity patterns apparent in the autistic brain. By grounding this training in known anatomical (e.g., mirror neuron system) and functional markers (e.g., mu rhythms) of autism, NF training holds promise to support current treatments for this complex disorder. The proposed hypothesis specifically states that neurofeedback-induced alpha mu (8-12Hz) rhythm suppression or desynchronization, a marker of cortical activation, should induce neuroplastic changes and lead to normalization in relevant mirroring networks that have been associated with higher-order social cognition. Copyright © 2012 Elsevier Ltd. All rights reserved.

Conspecific Interactions in Adult Laboratory Rodents: Friends or Foes?

PubMed

Lukas, Michael; de Jong, Trynke R

2017-01-01

Interactions between adult conspecifics, including sexual behaviors, affiliation, and aggression are crucial for the well-being, survival, and reproduction of mammals. This holds true for any mammalian species, but certainly for humans: An inability to optimally navigate the social system can have a strong negative impact on physical and mental health. Translational rodent models have been used for decades to unravel the neural pathways and substrates involved in normal and abnormal conspecific interactions. Researchers in the field of translational social neuroscience face a double challenge: Not only do they need to pay considerable attention to the behavioral ecology of their model species or their ancestors, they also have to expect a relatively large variability in behavior and adjust their experimental design accordingly. In this chapter, we will lay out traditional and novel rodent models and paradigms to study sexual, affiliative, and aggressive interactions among adult conspecifics. We will discuss the merits and main findings and briefly consider the most promising novel directions. Finally, we review the modulatory involvement of two major players in mammal social interaction: the central oxytocin and vasopressin system.

Sickness-induced changes in physiology do not affect fecundity or same-sex behavior.

PubMed

Sylvia, Kristyn E; Báez Ramos, Patricia; Demas, Gregory E

2018-02-01

Previous work in our lab has shown that early-life infection affects female reproductive physiology and function (i.e., smaller ovaries, abnormal estrous cycles) and alters investigation and aggression towards male conspecifics in a reproductive context. Although many studies have investigated the effects of postnatal immune challenge on physiological and behavioral development, fewer studies have examined whether these changes have ultimate effects on reproduction. In the current study, we paired Siberian hamsters (Phodopus sungorus) and simulated a bacterial infection in early life by administering lipopolysaccharide (LPS) to male and female pups on pnd3 and pnd5. In adulthood, hamsters were paired with novel individuals of the same sex, and we scored an array of social behaviors (e.g., investigation, aggression). We then paired animals with individuals of the opposite sex for 5 consecutive nights, providing them with the opportunity to mate. We found that females exhibited impaired reproductive physiology and function in adulthood (i.e., smaller ovaries and abnormal estrous cycles), similar to our previous work. However, both LPS-treated males and females exhibited similar same-sex social behavior when compared with saline-treated controls, they successfully mated, and there were no significant changes in fecundity. These data suggest that the physiological changes in response to neonatal immune challenge may not have long-term effects on reproductive success in a controlled environment. Collectively, the results of this study are particularly important when investigating the relationships between physiology and behavior within an ultimate context. Animals exposed to early-life stress may in fact be capable of compensating for changes in physiology in order to survive and reproduce in some contexts. Copyright © 2017 Elsevier Inc. All rights reserved.

Reduced Serotonin Receptor Subtypes in a Limbic and a Neocortical Region in Autism

PubMed Central

Oblak, Adrian; Gibbs, Terrell T.; Blatt, Gene J.

2013-01-01

Autism is a behaviorally defined, neurological disorder with symptom onset before the age of three. Abnormalities in social-emotional behaviors are a core deficit in autism and are characterized by impaired reciprocal social interaction, lack of facial expressions, and the inability to recognize familiar faces. The posterior cingulate cortex (PCC) and fusiform gyrus (FG) are two regions within an extensive limbic-cortical network that contribute to social-emotional behaviors. Evidence indicates that changes in brains of individuals with autism begin prenatally. Serotonin (5HT) is one of the earliest expressed neurotransmitters, and plays an important role in synaptogenesis, neurite outgrowth, and neuronal migration. Abnormalities in 5HT systems have been implicated in several psychiatric disorders including autism, as evidenced by immunology, imaging, genetics, pharmacotherapy, and neuropathology. Although information is known regarding peripheral 5HT in autism, there is emerging evidence that 5HT systems in the CNS, including various 5HT receptor subtypes and transporters, are affected in autism. The present study demonstrated significant reductions in 5HT1A receptor binding density in superficial and deep layers of the PCC and FG, and in the density of 5HT2A receptors in superficial layers of the PCC and FG. Significant reduction in the density of serotonin transporters (5-HTT) was also found in the deep layers of the FG, but normal levels were demonstrated in both layers of the PCC and superficial layers of the FG. These studies provide potential substrates for decreased 5-HT modulation/innervation in the autism brain, and implicate two 5-HT receptor subtypes as potential neuromarkers for novel or existing pharmacotherapies. PMID:23894004

Reduced serotonin receptor subtypes in a limbic and a neocortical region in autism.

PubMed

Oblak, Adrian; Gibbs, Terrell T; Blatt, Gene J

2013-12-01

Autism is a behaviorally defined, neurological disorder with symptom onset before the age of 3. Abnormalities in social-emotional behaviors are a core deficit in autism, and are characterized by impaired reciprocal-social interaction, lack of facial expressions, and the inability to recognize familiar faces. The posterior cingulate cortex (PCC) and fusiform gyrus (FG) are two regions within an extensive limbic-cortical network that contribute to social-emotional behaviors. Evidence indicates that changes in brains of individuals with autism begin prenatally. Serotonin (5-HT) is one of the earliest expressed neurotransmitters, and plays an important role in synaptogenesis, neurite outgrowth, and neuronal migration. Abnormalities in 5-HT systems have been implicated in several psychiatric disorders, including autism, as evidenced by immunology, imaging, genetics, pharmacotherapy, and neuropathology. Although information is known regarding peripheral 5-HT in autism, there is emerging evidence that 5-HT systems in the central nervous system, including various 5-HT receptor subtypes and transporters, are affected in autism. The present study demonstrated significant reductions in 5-HT1A receptor-binding density in superficial and deep layers of the PCC and FG, and in the density of 5-HT(2A) receptors in superficial layers of the PCC and FG. A significant reduction in the density of serotonin transporters (5-HTT) was also found in the deep layers of the FG, but normal levels were demonstrated in both layers of the PCC and superficial layers of the FG. This study provides potential substrates for decreased 5-HT modulation/innervation in the autism brain, and implicate two 5-HT receptor subtypes as potential neuromarkers for novel or existing pharmacotherapies. © 2013 International Society for Autism Research, Wiley Periodicals, Inc.

[The relationship between the abnormal behavior and serum C-reactive protein in children with obstructive sleep apnea-hypopnea syndrome].

PubMed

Wang, Yan; Li, Yanzhong; Wang, Xin

2009-12-01

To explore the pathogenesis of abnormal behavior in children with obstructive sleep apnea-hypopnea syndrome (OSAHS). The behavioral problems and C-reactive protein were measured in 40 children with OSAHS and 30 children with habitual snoring who underwent overnight Polysomnography, 40 cases of healthy children for the control group. The ratio of abnormal behavior in OSAHS and habitual snoring children was significantly higher than that of the healthy control group, while no significant difference between the two groups. The content of C-reactive protein in OSAHS children (4.24 mg/L) was significantly higher than habitual snoring (2.76 mg/L) and healthy control group (1.27 mg/L); in habitual snoring children C-reactive protein was higher than in healthy control group. The content of serum C-reactive protein in OSAHS children accompanied by abnormal behavior (4.63 mg/L) was significantly higher than that without abnormal behavior (3.23 mg/L). The content of serum C-reactive protein content in habitual snoring children accompanied by abnormal behavior (3.63 mg/L) was significantly higher than that without abnormal behavior (1.76 mg/L). OSAHS and habitual snoring children have more behavior problems. C-reactive protein levels are higher in children with OSAHS and habitual snoring, and the levels of C-reactive protein are related to the abnormal behavior in these children.

Deficiency of Shank2 causes mania-like behavior that responds to mood stabilizers

PubMed Central

Pappas, Andrea L.; Bey, Alexandra L.; Wang, Xiaoming; Rossi, Mark; Kim, Yong Ho; Yan, Haidun; Porkka, Fiona; Duffney, Lara J.; Phillips, Samantha M.; Cao, Xinyu; Ding, Jin-dong; Rodriguiz, Ramona M.; Yin, Henry H.; Wetsel, William C.

2017-01-01

Genetic defects in the synaptic scaffolding protein gene, SHANK2, are linked to a variety of neuropsychiatric disorders, including autism spectrum disorders, schizophrenia, intellectual disability, and bipolar disorder, but the molecular mechanisms underlying the pleotropic effects of SHANK2 mutations are poorly understood. We generated and characterized a line of Shank2 mutant mice by deleting exon 24 (Δe24). Shank2Δe24–/– mice engage in significantly increased locomotor activity, display abnormal reward-seeking behavior, are anhedonic, have perturbations in circadian rhythms, and show deficits in social and cognitive behaviors. While these phenotypes recapitulate the pleotropic behaviors associated with human SHANK2-related disorders, major behavioral features in these mice are reminiscent of bipolar disorder. For instance, their hyperactivity was augmented with amphetamine but was normalized with the mood stabilizers lithium and valproate. Shank2 deficiency limited to the forebrain recapitulated the bipolar mania phenotype. The composition and functions of NMDA and AMPA receptors were altered at Shank2-deficient synapses, hinting toward the mechanism underlying these behavioral abnormalities. Human genetic findings support construct validity, and the behavioral features in Shank2 Δe24 mice support face and predictive validities of this model for bipolar mania. Further genetic studies to understand the contribution of SHANK2 deficiencies in bipolar disorder are warranted. PMID:29046483

Animal model of autism induced by prenatal exposure to valproate: behavioral changes and liver parameters.

PubMed

Bambini-Junior, Victorio; Rodrigues, Leticia; Behr, Guilherme Antônio; Moreira, José Cláudio Fonseca; Riesgo, Rudimar; Gottfried, Carmem

2011-08-23

Autism is characterized by behavioral impairments in three main domains: social interaction; language, communication and imaginative play; and range of interests and activities. This syndrome has attracted social attention by its high prevalence. The animal model induced by prenatal exposure to valproic acid (VPA) has been proposed to study autism. Several characteristics of behavioral abnormalities found in the VPA rats, such as repetitive/stereotypic-like activity and deficit in social interaction have been correlated with autism. Features like flexibility to change strategy, social memory and metabolic status of the induced rats have not been examined. Thus, the main aim of this work was to investigate additional behavioral rodent similarities with autism, as well as, liver redox parameters after prenatal exposure to VPA. Young rats from the VPA group presented aberrant approach to a stranger rat, decreased conditioned place preference to conspecifics, normal spatial learning and a lack of flexibility to change their strategy. As adults, they presented inappropriate social approach to a stranger rat, decreased preference for social novelty, apparently normal social recognition and no spatial learning deficits. Examination of the liver from the VPA group presented significantly increased (12%) levels of catalase (CAT) activity, no alteration in superoxide dismutase (SOD) activity and a decrease in the SOD/CAT ratio. TBARS, sulfhydril and carbonyl contents, and serum levels of aminotransferases remained unchanged. In summary, rats prenatally exposed to VPA presented decreased flexibility to change strategy and social impairments similar to the autism symptoms, contributing to the understanding of neurodevelopmental symptoms and oxidative imbalance associated to the autism spectrum disorder. Copyright © 2011. Published by Elsevier B.V.

Is autism a disease of the cerebellum? An integration of clinical and pre-clinical research

PubMed Central

Rogers, Tiffany D.; McKimm, Eric; Dickson, Price E.; Goldowitz, Dan; Blaha, Charles D.; Mittleman, Guy

2013-01-01

Autism spectrum disorders are a group of neurodevelopmental disorders characterized by deficits in social skills and communication, stereotyped and repetitive behavior, and a range of deficits in cognitive function. While the etiology of autism is unknown, current research indicates that abnormalities of the cerebellum, now believed to be involved in cognitive function and the prefrontal cortex (PFC), are associated with autism. The current paper proposes that impaired cerebello-cortical circuitry could, at least in part, underlie autistic symptoms. The use of animal models that allow for manipulation of genetic and environmental influences are an effective means of elucidating both distal and proximal etiological factors in autism and their potential impact on cerebello-cortical circuitry. Some existing rodent models of autism, as well as some models not previously applied to the study of the disorder, display cerebellar and behavioral abnormalities that parallel those commonly seen in autistic patients. The novel findings produced from research utilizing rodent models could provide a better understanding of the neurochemical and behavioral impact of changes in cerebello-cortical circuitry in autism. PMID:23717269

[Autoaggression and pulse rate--a longitudinal study].

PubMed

Rohmann, U H; Elbing, U; Hartmann, H

1988-12-01

This article presents a model of autoaggressive behavior in which a distinction is made between determining and maintaining factors. Specific environmental, in particular social, and organismic variables are linked to them. The two types of variables interact, thus causing or maintaining autoaggressive behavior. A theory of autoaggression must therefore rely on multicausal/multimodal explanations. A connection between autoaggression and a high level of arousal suggests itself. In this single-case longitudinal study a comparison was made between heart rate and frequency of autoaggressive behavior. High heart rates were found to be correlated with low frequencies of autoaggressive behavior and vice versa. Decreasing autoaggressive behavior was coupled with increasing muscle relaxation and increasing motor activity. However, abnormally high heart rates were associated with both low and high levels of motor activity.

Autism-Like Behavior in BTBR Mice Is Improved by Electroconvulsive Therapy.

PubMed

Hagen, Eunice; Shprung, Dana; Minakova, Elena; Washington, James; Kumar, Udaya; Shin, Don; Sankar, Raman; Mazarati, Andrey

2015-07-01

Autism is a developmental disorder characterized by impairments in social and communication abilities, as well as by restricted and repetitive behaviors. Incidence of autism is higher than earlier estimates, and treatments have limited efficacy and are costly. Limited clinical and experimental evidence suggest that patients with autism may benefit from electroconvulsive therapy (ECT). We examined the therapeutic potential of ECT in BTBR T+ tf/j mice, which represent a validated model of autism. A series of 13 electroconvulsive shocks (ECS) delivered twice a day over 7 days reversed core autism-like behavioral abnormalities-impaired sociability, social novelty, and repetitive behavior-when the animals were tested 24 h after the last ECS. The effect lasted up to 2 weeks after ECT. Neither single ECS nor a series of 6 ECS modified animals' behavior. Chronic infusion into the lateral brain ventricle of a preferential oxytocin receptor blocker (2S)-2-Amino-N-[(1S,2S,4R)-7,7-dimethyl-1-[[[4-(2-methylphenyl)-1-piperazinyl]sulfonyl]methyl]bicyclo[2.2.1]hept-2-yl]-4-(methylsulfonyl)butanamide hydrochloride abolished ECT-induced improvement of sociability and mitigated improvement of social novelty but did not affect ECT-induced reversal of repetitive behavior. These proof-of-principle experiments suggest that ECT may, indeed, be useful in the treatment of autism, and that its therapeutic effects may be mediated, in part, by central oxytocin signaling.

Evaluation of the neuroactive steroid ganaxolone on social and repetitive behaviors in the BTBR mouse model of autism.

PubMed

Kazdoba, Tatiana M; Hagerman, Randi J; Zolkowska, Dorota; Rogawski, Michael A; Crawley, Jacqueline N

2016-01-01

Abnormalities in excitatory/inhibitory neurotransmission are hypothesized to contribute to autism spectrum disorder (ASD) etiology. BTBR T (+) Itpr3 (tf) /J (BTBR), an inbred mouse strain, displays social deficits and repetitive self-grooming, offering face validity to ASD diagnostic symptoms. Reduced GABAergic neurotransmission in BTBR suggests that GABAA receptor positive allosteric modulators (PAMs) could improve ASD-relevant BTBR phenotypes. The neuroactive steroid ganaxolone acts as a PAM, displaying anticonvulsant properties in rodent epilepsy models and an anxiolytic-like profile in the elevated plus-maze. We evaluated ganaxolone in BTBR and C57BL/6J mice in standardized assays for sociability and repetitive behaviors. Open field and anxiety-related behaviors were tested as internal controls and for comparison with the existing neuroactive steroid literature. Ganaxolone improved aspects of social approach and reciprocal social interactions in BTBR, with no effect on repetitive self-grooming, and no detrimental effects in C57BL/6J. Ganaxolone increased overall exploratory activity in BTBR and C57BL/6J in the open field, social approach, and elevated plus-maze, introducing a confound for the interpretation of social improvements. Allopregnanolone and diazepam similarly increased total entries in the elevated plus-maze, indicating that behavioral activation may be a general property of GABAA receptor PAMs in these strains. Ganaxolone shows promise for improving sociability. In addition, ganaxolone, as well as other GABAA receptor PAMs, enhanced overall BTBR activity. The translational implications of specific sociability improvements and nonspecific behavioral activation by ganaxolone in the BTBR model remain to be determined. Future studies to explore whether PAMs provide a novel profile with unique benefits for ASD treatment will be worthwhile.

Evaluation of the neuroactive steroid ganaxolone on social and repetitive behaviors in the BTBR mouse model of autism

PubMed Central

Kazdoba, Tatiana M.; Hagerman, Randi J.; Zolkowska, Dorota; Rogawski, Michael A.; Crawley, Jacqueline N.

2015-01-01

Rationale Abnormalities in excitatory/inhibitory neurotransmission are hypothesized to contribute to autism spectrum disorder (ASD) etiology. BTBR, an inbred mouse strain, displays social deficits and repetitive self-grooming, offering face validity to ASD diagnostic symptoms. Reduced GABAergic neurotransmission in BTBR suggests that GABAA receptor positive allosteric modulators (PAMs) could improve ASD-relevant BTBR phenotypes. The neuroactive steroid ganaxolone acts as a PAM, displaying anticonvulsant properties in rodent epilepsy models and an anxiolytic-like profile in the elevated plus-maze. Objectives We evaluated ganaxolone in BTBR and C57BL/6J mice in standardized assays for sociability and repetitive behaviors. Open field and anxiety-related behaviors were tested as internal controls and for comparison with the existing neuroactive steroid literature. Results Ganaxolone improved aspects of social approach and reciprocal social interactions in BTBR, with no effect on repetitive self-grooming, and no detrimental effects in C57BL/6J. Ganaxolone increased overall exploratory activity in BTBR and C57BL/6J in the open field, social approach, and elevated plus-maze, introducing a confound for the interpretation of social improvements. Allopregnanolone and diazepam similarly increased total entries in the elevated plus-maze, indicating that behavioral activation may be a general property of GABAA receptor PAMs in these strains. Conclusions Ganaxolone shows promise for improving sociability. In addition, ganaxolone, as well as other GABAA receptor PAMs, enhanced overall BTBR activity. The translational implications of specific sociability improvements and non-specific behavioral activation by ganaxolone in the BTBR model remains to be determined. Future studies to explore whether PAMs provide a novel profile with unique benefits for ASD treatment will be worthwhile. PMID:26525567

Using novel control groups to dissect the amygdala's role in Williams syndrome.

PubMed

Thornton-Wells, Tricia A; Avery, Suzanne N; Blackford, Jennifer Urbano

2011-07-01

Williams syndrome is a neurodevelopmental disorder with an intriguing behavioral phenotype-hypersociability combined with significant non-social fears. Previous studies have demonstrated abnormalities in amygdala function in individuals with Williams syndrome compared to typically-developing controls. However, it remains unclear whether the findings are related to the atypical neurodevelopment of Williams syndrome, or are also associated with behavioral traits at the extreme end of a normal continuum. We used functional magnetic resonance imaging (fMRI) to compare amygdala blood-oxygenation-level-dependent (BOLD) responses to non-social and social images in individuals with Williams syndrome compared to either individuals with inhibited temperament (high non-social fear) or individuals with uninhibited temperament (high sociability). Individuals with Williams syndrome had larger amygdala BOLD responses when viewing the non-social fear images than the inhibited temperament control group. In contrast, when viewing both fear and neutral social images, individuals with Williams syndrome did not show smaller amygdala BOLD responses relative to the uninhibited temperament control group, but instead had amygdala responses proportionate to their sociability. These results suggest heightened amygdala response to non-social fear images is characteristic of WS, whereas, variability in amygdala response to social fear images is proportionate to, and might be explained by, levels of trait sociability.

The Effect of Otolith Malformation on Behavior and Cortisol Levels in Juvenile Red Drum Fish (Sciaenops ocellatus)

PubMed Central

Browning, Zoe S; Wilkes, Allison A; Moore, Erica J; Lancon, Trevor W; Clubb, Fred J

2012-01-01

Captive-raised red drum fish were observed with phenotypic abnormalities, including deformities of the spine, jaw, and cephalic region, that were consistent with vitamin C deficiency during the larval stage. In light of their visible exterior skeletal abnormalities, we suspected that the affected fish would also have abnormal otoliths. Otoliths are dense calcareous structures that function in fish hearing. We hypothesized that abnormal fish would have irregular otoliths that would alter behavior and cortisol levels as compared with those of phenotypically normal fish. The normal and abnormal fish had statistically significant differences in behavior, cortisol levels, and otolith volume and density. MicroCT assessment of abnormal fish revealed operculum abnormalities, malocclusions, and several types of otolith malformations. Therefore, the affected fish had not only an abnormal skeletal appearance but also significantly abnormal behavior and cortisol responses. PMID:23043776

Brain Growth Rate Abnormalities Visualized in Adolescents with Autism

PubMed Central

Hua, Xue; Thompson, Paul M.; Leow, Alex D.; Madsen, Sarah K.; Caplan, Rochelle; Alger, Jeffry R.; O’Neill, Joseph; Joshi, Kishori; Smalley, Susan L.; Toga, Arthur W.; Levitt, Jennifer G.

2014-01-01

Autism spectrum disorder (ASD) is a heterogeneous disorder of brain development with wide-ranging cognitive deficits. Typically diagnosed before age 3, ASD is behaviorally defined but patients are thought to have protracted alterations in brain maturation. With longitudinal magnetic resonance imaging (MRI), we mapped an anomalous developmental trajectory of the brains of autistic compared to those of typically developing children and adolescents. Using tensor-based morphometry (TBM), we created 3D maps visualizing regional tissue growth rates based on longitudinal brain MRI scans of 13 autistic and 7 typically developing boys (mean age/inter-scan interval: autism 12.0 ± 2.3 years/2.9 ± 0.9 years; control 12.3 ± 2.4/2.8 ± 0.8). The typically developing boys demonstrated strong whole-brain white matter growth during this period, but the autistic boys showed abnormally slowed white matter development (p = 0.03, corrected), especially in the parietal (p = 0.008), temporal (p = 0.03) and occipital lobes (p =0.02). We also visualized abnormal overgrowth in autism in some gray matter structures, such as the putamen and anterior cingulate cortex. Our findings reveal aberrant growth rates in brain regions implicated in social impairment, communication deficits and repetitive behaviors in autism, suggesting that growth rate abnormalities persist into adolescence. TBM revealed persisting growth rate anomalies long after diagnosis, which has implications for evaluation of therapeutic effects. PMID:22021093

Brain growth rate abnormalities visualized in adolescents with autism.

PubMed

Hua, Xue; Thompson, Paul M; Leow, Alex D; Madsen, Sarah K; Caplan, Rochelle; Alger, Jeffry R; O'Neill, Joseph; Joshi, Kishori; Smalley, Susan L; Toga, Arthur W; Levitt, Jennifer G

2013-02-01

Autism spectrum disorder is a heterogeneous disorder of brain development with wide ranging cognitive deficits. Typically diagnosed before age 3, autism spectrum disorder is behaviorally defined but patients are thought to have protracted alterations in brain maturation. With longitudinal magnetic resonance imaging (MRI), we mapped an anomalous developmental trajectory of the brains of autistic compared with those of typically developing children and adolescents. Using tensor-based morphometry, we created 3D maps visualizing regional tissue growth rates based on longitudinal brain MRI scans of 13 autistic and seven typically developing boys (mean age/interscan interval: autism 12.0 ± 2.3 years/2.9 ± 0.9 years; control 12.3 ± 2.4/2.8 ± 0.8). The typically developing boys demonstrated strong whole brain white matter growth during this period, but the autistic boys showed abnormally slowed white matter development (P = 0.03, corrected), especially in the parietal (P = 0.008), temporal (P = 0.03), and occipital lobes (P = 0.02). We also visualized abnormal overgrowth in autism in gray matter structures such as the putamen and anterior cingulate cortex. Our findings reveal aberrant growth rates in brain regions implicated in social impairment, communication deficits and repetitive behaviors in autism, suggesting that growth rate abnormalities persist into adolescence. Tensor-based morphometry revealed persisting growth rate anomalies long after diagnosis, which has implications for evaluation of therapeutic effects. Copyright © 2011 Wiley Periodicals, Inc.

Sociosexual and Communication Deficits after Traumatic Injury to the Developing Murine Brain

PubMed Central

Semple, Bridgette D.; Noble-Haeusslein, Linda J.; Jun Kwon, Yong; Sam, Pingdewinde N.; Gibson, A. Matt; Grissom, Sarah; Brown, Sienna; Adahman, Zahra; Hollingsworth, Christopher A.; Kwakye, Alexander; Gimlin, Kayleen; Wilde, Elisabeth A.; Hanten, Gerri; Levin, Harvey S.; Schenk, A. Katrin

2014-01-01

Despite the life-long implications of social and communication dysfunction after pediatric traumatic brain injury, there is a poor understanding of these deficits in terms of their developmental trajectory and underlying mechanisms. In a well-characterized murine model of pediatric brain injury, we recently demonstrated that pronounced deficits in social interactions emerge across maturation to adulthood after injury at postnatal day (p) 21, approximating a toddler-aged child. Extending these findings, we here hypothesized that these social deficits are dependent upon brain maturation at the time of injury, and coincide with abnormal sociosexual behaviors and communication. Age-dependent vulnerability of the developing brain to social deficits was addressed by comparing behavioral and neuroanatomical outcomes in mice injured at either a pediatric age (p21) or during adolescence (p35). Sociosexual behaviors including social investigation and mounting were evaluated in a resident-intruder paradigm at adulthood. These outcomes were complemented by assays of urine scent marking and ultrasonic vocalizations as indices of social communication. We provide evidence of sociosexual deficits after brain injury at p21, which manifest as reduced mounting behavior and scent marking towards an unfamiliar female at adulthood. In contrast, with the exception of the loss of social recognition in a three-chamber social approach task, mice that received TBI at adolescence were remarkably resilient to social deficits at adulthood. Increased emission of ultrasonic vocalizations (USVs) as well as preferential emission of high frequency USVs after injury was dependent upon both the stimulus and prior social experience. Contrary to the hypothesis that changes in white matter volume may underlie social dysfunction, injury at both p21 and p35 resulted in a similar degree of atrophy of the corpus callosum by adulthood. However, loss of hippocampal tissue was greater after p21 compared to p35 injury, suggesting that a longer period of lesion progression or differences in the kinetics of secondary pathogenesis after p21 injury may contribute to observed behavioral differences. Together, these findings indicate vulnerability of the developing brain to social dysfunction, and suggest that a younger age-at-insult results in poorer social and sociosexual outcomes. PMID:25106033

Autism, epilepsy, and synaptopathies: a not rare association.

PubMed

Keller, Roberto; Basta, Roberta; Salerno, Luana; Elia, Maurizio

2017-08-01

Autism spectrum disorders (ASD) are neurodevelopmental disorders typically diagnosed in childhood, characterized by core social dysfunction, rigid and repetitive behaviors, restricted interests, and abnormal sensorial sensitivity. ASD belong to multifactorial diseases: both genetic and environmental factors have been considered as potential risk factors for their onset. ASD are often associated with neurological conditions: the co-occurrence of epilepsy is well documented and there is also evidence of a higher prevalence of EEG abnormalities with 4-86% of individuals with ASD presenting epileptiform or not epileptiform EEG abnormalities. The presence of epilepsy in people with ASD may be determined by several structural alterations, genetic conditions, or metabolic dysfunctions, known to play a role in the emergence of both epilepsy and autism. The purpose of this article is to discuss precisely such latter cause of the autism-epilepsy association, focusing specifically on those "synaptic genes," whose mutation predisposes to both the diseases.

Exogenous and evoked oxytocin restores social behavior in the Cntnap2 mouse model of autism

PubMed Central

Peñagarikano, Olga; Lázaro, María T.; Lu, Xiao-Hong; Gordon, Aaron; Dong, Hongmei; Lam, Hoa A.; Peles, Elior; Maidment, Nigel T.; Murphy, Niall P.; Yang, X. William; Golshani, Peyman; Geschwind, Daniel H.

2015-01-01

Mouse models of neuropsychiatric diseases provide a platform for mechanistic understanding and development of new therapies. We previously demonstrated that knockout of the mouse homologue of CNTNAP2, in which mutant forms cause Cortical Dysplasia and Focal Epilepsy syndrome (CDFE), displays many features parallel to the human disorder. Since CDFE has high penetrance for autism spectrum disorder (ASD) we performed an in vivo screen for drugs that treat abnormal social behavior in Cntnap2 mutant mice and found that acute administration of the neuropeptide oxytocin improved social deficits. We found a decrease in the number of oxytocin immunoreactive neurons in the paraventricular nucleus (PVN) of the hypothalamus in mutant mice and an overall decrease in brain oxytocin levels. Administration of a selective melanocortin receptor 4 agonist, which causes endogenous oxytocin release, also acutely rescued the social deficits, an effect blocked by an oxytocin antagonist. We confirmed that oxytocin neurons mediated the behavioral improvement by activating endogenous oxytocin neurons in the paraventricular hypothalamus with Designer Receptors Exclusively Activated by Designer Drugs (DREADD). Last, we showed that chronic early postnatal treatment with oxytocin led to more lasting behavioral recovery and restored oxytocin immunoreactivity in the PVN. These data demonstrate dysregulation of the oxytocin system in Cntnap2 knockout mice and suggest that there may be critical developmental windows for optimal treatment. PMID:25609168

Atypical birdsong and artificial languages provide insights into how communication systems are shaped by learning, use, and transmission.

PubMed

Fehér, Olga

2017-02-01

In this article, I argue that a comparative approach focusing on the cognitive capacities and behavioral mechanisms that underlie vocal learning in songbirds and humans can provide valuable insights into the evolutionary origins of language. The experimental approaches I discuss use abnormal song and atypical linguistic input to study the processes of individual learning, social interaction, and cultural transmission. Atypical input places increased learning and communicative pressure on learners, so exploring how they respond to this type of input provides a particularly clear picture of the biases and constraints at work during learning and use. Furthermore, simulating the cultural transmission of these unnatural communication systems in the laboratory informs us about how learning and social biases influence the structure of communication systems in the long run. Findings based on these methods suggest fundamental similarities in the basic social-cognitive mechanisms underlying vocal learning in birds and humans, and continuing research promises insights into the uniquely human mechanisms and into how human cognition and social behavior interact, and ultimately impact on the evolution of language.

Altered Connectivity and Action Model Formation in Autism Is Autism

PubMed Central

Mostofsky, Stewart H.; Ewen, Joshua B.

2014-01-01

Internal action models refer to sensory-motor programs that form the brain basis for a wide range of skilled behavior and for understanding others’ actions. Development of these action models, particularly those reliant on visual cues from the external world, depends on connectivity between distant brain regions. Studies of children with autism reveal anomalous patterns of motor learning and impaired execution of skilled motor gestures. These findings robustly correlate with measures of social and communicative function, suggesting that anomalous action model formation may contribute to impaired development of social and communicative (as well as motor) capacity in autism. Examination of the pattern of behavioral findings, as well as convergent data from neuroimaging techniques, further suggests that autism-associated action model formation may be related to abnormalities in neural connectivity, particularly decreased function of long-range connections. This line of study can lead to important advances in understanding the neural basis of autism and, more critically, can be used to guide effective therapies targeted at improving social, communicative, and motor function. PMID:21467306

Self-Rehabilitation of a Captive American Crow at Binghamton Zoo.

PubMed

Davie, Clara; Clark, Anne B

2017-01-01

The behavioral transition from an entirely unflighted-to-flighted, female yearling American crow (Corvus brachyrhynchos) in captivity in a specially designed exhibit was documented at the Binghamton Zoo at Ross Park in Binghamton, NY. Upon arrival, the focal crow had no complete primary feathers or retrices and had been in captivity since fledging. She apparently had never flown successfully and was using her legs and an abnormal body orientation to cushion her landing on the ground. In a social and physical environment with 3 flying companion crows and staggered perches, she developed and appeared to "practice" routines that ultimately resulted in her recovering normal body posture and flight ability. The crow's practice routine was recorded during daily observations using an ethogram of social and locomotor behaviors. Both enclosure design and the social environment may have provided an ideal setting for the self-motivation of practice and this recovery. Attention to the potential for such practice could facilitate rehabilitation in individuals for whom rehabilitation was not thought possible.

Individual differences in the peripheral immune system promote resilience versus susceptibility to social stress.

PubMed

Hodes, Georgia E; Pfau, Madeline L; Leboeuf, Marylene; Golden, Sam A; Christoffel, Daniel J; Bregman, Dana; Rebusi, Nicole; Heshmati, Mitra; Aleyasin, Hossein; Warren, Brandon L; Lebonté, Benoit; Horn, Sarah; Lapidus, Kyle A; Stelzhammer, Viktoria; Wong, Erik H F; Bahn, Sabine; Krishnan, Vaishnav; Bolaños-Guzman, Carlos A; Murrough, James W; Merad, Miriam; Russo, Scott J

2014-11-11

Depression and anxiety disorders are associated with increased release of peripheral cytokines; however, their functional relevance remains unknown. Using a social stress model in mice, we find preexisting individual differences in the sensitivity of the peripheral immune system that predict and promote vulnerability to social stress. Cytokine profiles were obtained 20 min after the first social stress exposure. Of the cytokines regulated by stress, IL-6 was most highly up-regulated only in mice that ultimately developed a susceptible behavioral phenotype following a subsequent chronic stress, and levels remained elevated for at least 1 mo. We confirmed a similar elevation of serum IL-6 in two separate cohorts of patients with treatment-resistant major depressive disorder. Before any physical contact in mice, we observed individual differences in IL-6 levels from ex vivo stimulated leukocytes that predict susceptibility versus resilience to a subsequent stressor. To shift the sensitivity of the peripheral immune system to a pro- or antidepressant state, bone marrow (BM) chimeras were generated by transplanting hematopoietic progenitor cells from stress-susceptible mice releasing high IL-6 or from IL-6 knockout (IL-6(-/-)) mice. Stress-susceptible BM chimeras exhibited increased social avoidance behavior after exposure to either subthreshold repeated social defeat stress (RSDS) or a purely emotional stressor termed witness defeat. IL-6(-/-) BM chimeric and IL-6(-/-) mice, as well as those treated with a systemic IL-6 monoclonal antibody, were resilient to social stress. These data establish that preexisting differences in stress-responsive IL-6 release from BM-derived leukocytes functionally contribute to social stress-induced behavioral abnormalities.

Diminished self-conscious emotional responding in frontotemporal lobar degeneration patients.

PubMed

Sturm, Virginia E; Ascher, Elizabeth A; Miller, Bruce L; Levenson, Robert W

2008-12-01

Frontotemporal lobar degeneration (FTLD) is a neurodegenerative disease that dramatically alters social and emotional behavior. Recent work has suggested that self-conscious emotions (e.g., embarrassment) may be particularly vulnerable to disruption in this disease. Self-conscious emotions require the ability to monitor the self in relation to others. These abilities are thought to be subserved by brain regions (e.g., medial prefrontal, anterior cingulate, and insula) that are particularly vulnerable to damage in FTLD. This study examined emotional responding (expressive behavior, peripheral physiology, and subjective experience) in 24 FTLD patients and 16 cognitively normal control participants using a karaoke task known to elicit self-conscious emotion reliably and a nonemotional control task (isometric handgrip). Results indicated that FTLD patients showed diminished self-conscious emotional behavior (embarrassment and amusement) and diminished physiological responding while watching themselves singing. No differences were found between patients and controls in the nonemotional control task. These findings offer evidence of marked disruption of self-conscious emotional responding in FTLD. Diminished self-conscious emotional responding likely contributes significantly to social inappropriateness and other behavioral abnormalities in FTLD. 2008 APA, all rights reserved

Diminished Self-Conscious Emotional Responding in Frontotemporal Lobar Degeneration Patients

PubMed Central

Sturm, Virginia E.; Ascher, Elizabeth A.; Miller, Bruce L.; Levenson, Robert W.

2009-01-01

Frontotemporal lobar degeneration (FTLD) is a neurodegenerative disease that dramatically alters social and emotional behavior. Recent work has suggested that self-conscious emotions (e.g., embarrassment) may be particularly vulnerable to disruption in this disease. Self-conscious emotions require the ability to monitor the self in relation to others. These abilities are thought to be subserved by brain regions (e.g., medial prefrontal, anterior cingulate, and insula) that are particularly vulnerable to damage in FTLD. This study examined emotional responding (expressive behavior, peripheral physiology, and subjective experience) in 24 FTLD patients and 16 cognitively normal control participants using a karaoke task known to elicit self-conscious emotion reliably and a nonemotional control task (isometric handgrip). Results indicated that FTLD patients showed diminished self-conscious emotional behavior (embarrassment and amusement) and diminished physiological responding while watching themselves singing. No differences were found between patients and controls in the nonemotional control task. These findings offer evidence of marked disruption of self-conscious emotional responding in FTLD. Diminished self-conscious emotional responding likely contributes significantly to social inappropriateness and other behavioral abnormalities in FTLD. PMID:19102597

Neurologic abnormalities in murderers.

PubMed

Blake, P Y; Pincus, J H; Buckner, C

1995-09-01

Thirty-one individuals awaiting trial or sentencing for murder or undergoing an appeal process requested a neurologic examination through legal counsel. We attempted in each instance to obtain EEG, MRI or CT, and neuropsychological testing. Neurologic examination revealed evidence of "frontal" dysfunction in 20 (64.5%). There were symptoms or some other evidence of temporal lobe abnormality in nine (29%). We made a specific neurologic diagnosis in 20 individuals (64.5%), including borderline or full mental retardation (9) and cerebral palsy (2), among others. Neuropsychological testing revealed abnormalities in all subjects tested. There were EEG abnormalities in eight of the 20 subjects tested, consisting mainly of bilateral sharp waves with slowing. There were MRI or CT abnormalities in nine of the 19 subjects tested, consisting primarily of atrophy and white matter changes. Psychiatric diagnoses included paranoid schizophrenia (8), dissociative disorder (4), and depression (9). Virtually all subjects had paranoid ideas and misunderstood social situations. There was a documented history of profound, protracted physical abuse in 26 (83.8%) and of sexual abuse in 10 (32.3%). It is likely that prolonged, severe physical abuse, paranoia, and neurologic brain dysfunction interact to form the matrix of violent behavior.

Response mechanisms to joint exposure of triclosan and its chlorinated derivatives on zebrafish (Danio rerio) behavior.

PubMed

Liu, Jinfeng; Sun, Limei; Zhang, Hongqin; Shi, Mengru; Dahlgren, Randy A; Wang, Xuedong; Wang, Huili

2018-02-01

Triclosan (TCS), 2,4,6-trichlorophenol (2,4,6-TCP) and 2,4-dichlorophenol (2,4-DCP) frequently co-exist in real-world aquatic environments; the latter two contaminants contributing to TCS photolytic products or chlorinated derivatives. There is a paucity of information regarding their joint toxicity to aquatic organisms leading us to study their effects on the swimming behavior of zebrafish (Danio rerio). Herein, we reported that 0.28 mg/L TDT exposure (mixtures of TCS, 2,4,6-TCP and 2,4-DCP) enhanced 24-hpf embryonic spontaneous movement frequency, 96-hpf larval activity; however, the 0.56 and 1.12 mg/L TDT treatments decreased all of these behavioral endpoints. All adult behavioral tests demonstrated that chronic TDT exposure (0.14 mg/L) led to hyperactivity and restlessness in adult zebrafish. A 0.14 mg/L TD DATE /@ "M/d/yyyy" 11/21/2017T treatment led to anxiety-like behavior in a bottom dwelling test and excessive panic and low hedging capacity in a conditioned place preference test. Social interaction test demonstrated that zebrafish preferred quiet and isolated space in response to TDT stress. Zebrafish memory was significantly decreased in a T-maze experiment. Whole mount in situ hybridization of pax2a and bcl2l11 genes revealed that their differential expression in the brain and skeleton were related to the corresponding phenotypic behavioral abnormality. A series of biomarker and estrogen receptor assays demonstrated that TDT acute exposure caused abnormal energy metabolism and neurological diseases. AO staining revealed that TDT exposure produced vascular ablation in the head, as well as the occurrence of massive apoptosis in the brain. TEM observation showed pyknosis of nucleus following TDT exposure. These results allow assessment of mechanisms for zebrafish abnormal behavior in response to TDT exposure, and are useful for early intervention and gene therapy of contaminant-induced diseases. Copyright © 2017 Elsevier Ltd. All rights reserved.

Annual Symposium, Psychology in the Air Force (5th), 8 April - 10 April 1976

DTIC Science & Technology

1976-06-01

approach . Miller, Robert B., Psychological Considerations in the Design of Training Equipment, WADC-TR-54-563, Wright-Patterson AFB, OH, Wright Air... Abnormal and Social Psychology , 1963, 66, 207-216. Berkley, C. S. & Sproule, C. F. Test anxiety and test-unsophistication: The effects, the cures. Public...SYMPOSIUM PROCEEDINGS Proceedings of the 5th Symposium on Psychology in the Air Force. Sponsored by the Department of Behavioral Sciences and

Toward a definition of "hypersexuality" in children and adolescents.

PubMed

Adelson, Stewart; Bell, Robinette; Graff, Adam; Goldenberg, David; Haase, Elizabeth; Downey, Jennifer I; Friedman, Richard C

2012-09-01

Recent psychiatric literature has used the term "hypersexuality" to denote pathologically increased sexual behavior in children and adolescents. Various patterns of increased sexuality have been described in youth, including sexuality that is excessive, developmentally precocious, compulsive, aggressive, or otherwise socially inappropriate. Such "hypersexual" behavior in children and adolescents is associated with a variety of factors. Social factors include sexual abuse, physical abuse, life stress, and impaired family relationships. Psychiatric factors include emotional and behavioral problems in general, posttraumatic stress disorder and dissociative symptoms in particular, and possibly bipolar disorder. Despite the importance of increased sexual behavior in youth as a possible sign of these problems, there is currently no uniform definition in psychiatric literature of the term "hypersexuality" applied to children and adolescents. The usefulness of this term depends upon the degree to which it can be defined, measured, and distinguished from non-pathological juvenile sexual behavior. Research instruments are described that may be useful in measuring levels of sexual behavior in children and adolescents. Elements of a definition of juvenile hypersexuality are proposed based upon current knowledge about children and adolescents' sexuality in both normal development and a variety of conditions in which it is increased. Care is warranted in distinguishing between normal and abnormal sexual behavior in youth because of the variety of factors that can affect its measurement.

Network analysis reveals disrupted functional brain circuitry in drug-naive social anxiety disorder.

PubMed

Yang, Xun; Liu, Jin; Meng, Yajing; Xia, Mingrui; Cui, Zaixu; Wu, Xi; Hu, Xinyu; Zhang, Wei; Gong, Gaolang; Gong, Qiyong; Sweeney, John A; He, Yong

2017-12-07

Social anxiety disorder (SAD) is a common and disabling condition characterized by excessive fear and avoidance of public scrutiny. Psychoradiology studies have suggested that the emotional and behavior deficits in SAD are associated with abnormalities in regional brain function and functional connectivity. However, little is known about whether intrinsic functional brain networks in patients with SAD are topologically disrupted. Here, we collected resting-state fMRI data from 33 drug-naive patients with SAD and 32 healthy controls (HC), constructed functional networks with 34 predefined regions based on previous meta-analytic research with task-based fMRI in SAD, and performed network-based statistic and graph-theory analyses. The network-based statistic analysis revealed a single connected abnormal circuitry including the frontolimbic circuit (termed the "fear circuit", including the dorsolateral prefrontal cortex, ventral medial prefrontal cortex and insula) and posterior cingulate/occipital areas supporting perceptual processing. In this single altered network, patients with SAD had higher functional connectivity than HC. At the global level, graph-theory analysis revealed that the patients exhibited a lower normalized characteristic path length than HC, which suggests a disorder-related shift of network topology toward randomized configurations. SAD-related deficits in nodal degree, efficiency and participation coefficient were detected in the parahippocampal gyrus, posterior cingulate cortex, dorsolateral prefrontal cortex, insula and the calcarine sulcus. Aspects of abnormal connectivity were associated with anxiety symptoms. These findings highlight the aberrant topological organization of functional brain network organization in SAD, which provides insights into the neural mechanisms underlying excessive fear and avoidance of social interactions in patients with debilitating social anxiety. Copyright © 2017. Published by Elsevier Inc.

Ts1Cje Down syndrome model mice exhibit environmental stimuli-triggered locomotor hyperactivity and sociability concurrent with increased flux through central dopamine and serotonin metabolism.

PubMed

Shimohata, Atsushi; Ishihara, Keiichi; Hattori, Satoko; Miyamoto, Hiroyuki; Morishita, Hiromasa; Ornthanalai, Guy; Raveau, Matthieu; Ebrahim, Abdul Shukkur; Amano, Kenji; Yamada, Kazuyuki; Sago, Haruhiko; Akiba, Satoshi; Mataga, Nobuko; Murphy, Niall P; Miyakawa, Tsuyoshi; Yamakawa, Kazuhiro

2017-07-01

Ts1Cje mice have a segmental trisomy of chromosome 16 that is orthologous to human chromosome 21 and display Down syndrome-like cognitive impairments. Despite the occurrence of affective and emotional impairments in patients with Down syndrome, these parameters are poorly documented in Down syndrome mouse models, including Ts1Cje mice. Here, we conducted comprehensive behavioral analyses, including anxiety-, sociability-, and depression-related tasks, and biochemical analyses of monoamines and their metabolites in Ts1Cje mice. Ts1Cje mice showed enhanced locomotor activity in novel environments and increased social contact with unfamiliar partners when compared with wild-type littermates, but a significantly lower activity in familiar environments. Ts1Cje mice also exhibited some signs of decreased depression like-behavior. Furthermore, Ts1Cje mice showed monoamine abnormalities, including increased extracellular dopamine and serotonin, and enhanced catabolism in the striatum and ventral forebrain. This study constitutes the first report of deviated monoamine metabolism that may help explain the basis for abnormal behaviors, including the environmental stimuli-triggered hyperactivity, increased sociability and decreased depression-like behavior in Ts1Cje mice. Copyright © 2017 Elsevier Inc. All rights reserved.

GABA-B Agonist Baclofen Normalizes Auditory-Evoked Neural Oscillations and Behavioral Deficits in the Fmr1 Knockout Mouse Model of Fragile X Syndrome

PubMed Central

Featherstone, R.; Naschek, M.; Nam, J.; Du, A.; Wright, S.; Weger, R.; Akuzawa, S.

2017-01-01

Abstract Fragile X syndrome is a genetic condition resulting from FMR1 gene mutation that leads to intellectual disability, autism-like symptoms, and sensory hypersensitivity. Arbaclofen, a GABA-B agonist, has shown efficacy in some individuals with FXS but has become unavailable after unsuccessful clinical trials, prompting interest in publicly available, racemic baclofen. The present study investigated whether racemic baclofen can remediate abnormalities of neural circuit function, sensory processing, and behavior in Fmr1 knockout mice, a rodent model of fragile X syndrome. Fmr1 knockout mice showed increased baseline and auditory-evoked high-frequency gamma (30–80 Hz) power relative to C57BL/6 controls, as measured by electroencephalography. These deficits were accompanied by decreased T maze spontaneous alternation, decreased social interactions, and increased open field center time, suggestive of diminished working memory, sociability, and anxiety-like behavior, respectively. Abnormal auditory-evoked gamma oscillations, working memory, and anxiety-related behavior were normalized by treatment with baclofen, but impaired sociability was not. Improvements in working memory were evident predominantly in mice whose auditory-evoked gamma oscillations were dampened by baclofen. These findings suggest that racemic baclofen may be useful for targeting sensory and cognitive disturbances in fragile X syndrome. PMID:28451631

Autism and epistemology IV: Does autism need a theory of mind?

PubMed

Fisch, Gene S

2013-10-01

In their article, "Does the autistic child have a 'theory of mind'?," Baron-Cohen et al. [1985] proposed a novel paradigm to explain social impairment in children diagnosed as autistic (AD). Much research has been undertaken since their article went to print. The purpose of this commentary is to gauge whether Theory of Mind (ToM)-or lack thereof-is a valid model for explaining abnormal social behavior in children with AD. ToM is defined as "the ability to impute mental states to oneself and to others" and "the ability to make inferences about what other people believe to be the case." The source for their model was provided by an article published earlier by Premack and Woodruff, "Does the chimpanzee have a theory of mind?" Later research in chimpanzees did not support a ToM in primates. From the outset, ToM as a neurocognitive model of autism has had many shortcomings-methodological, logical, and empirical. Other ToM assumptions, for example, its universality in all children in all cultures and socioeconomic conditions, are not supported by data. The age at which a ToM emerges, or events that presage a ToM, are too often not corroborated. Recent studies of mirror neurons, their location and interconnections in brain, their relationship to social behavior and language, and the effect of lesions there on speech, language and social behavior, strongly suggests that a neurobiological as opposed to neurocognitive model of autism is a more parsimonious explanation for the social and behavioral phenotypes observed in autism. Copyright © 2013 Wiley Periodicals, Inc.

Exogenous and evoked oxytocin restores social behavior in the Cntnap2 mouse model of autism.

PubMed

Peñagarikano, Olga; Lázaro, María T; Lu, Xiao-Hong; Gordon, Aaron; Dong, Hongmei; Lam, Hoa A; Peles, Elior; Maidment, Nigel T; Murphy, Niall P; Yang, X William; Golshani, Peyman; Geschwind, Daniel H

2015-01-21

Mouse models of neuropsychiatric diseases provide a platform for mechanistic understanding and development of new therapies. We previously demonstrated that knockout of the mouse homolog of CNTNAP2 (contactin-associated protein-like 2), in which mutations cause cortical dysplasia and focal epilepsy (CDFE) syndrome, displays many features that parallel those of the human disorder. Because CDFE has high penetrance for autism spectrum disorder (ASD), we performed an in vivo screen for drugs that ameliorate abnormal social behavior in Cntnap2 mutant mice and found that acute administration of the neuropeptide oxytocin improved social deficits. We found a decrease in the number of oxytocin immunoreactive neurons in the paraventricular nucleus (PVN) of the hypothalamus in mutant mice and an overall decrease in brain oxytocin levels. Administration of a selective melanocortin receptor 4 agonist, which causes endogenous oxytocin release, also acutely rescued the social deficits, an effect blocked by an oxytocin antagonist. We confirmed that oxytocin neurons mediated the behavioral improvement by activating endogenous oxytocin neurons in the paraventricular hypothalamus with Designer Receptors Exclusively Activated by Designer Drugs (DREADD). Last, we showed that chronic early postnatal treatment with oxytocin led to more lasting behavioral recovery and restored oxytocin immunoreactivity in the PVN. These data demonstrate dysregulation of the oxytocin system in Cntnap2 knockout mice and suggest that there may be critical developmental windows for optimal treatment to rectify this deficit. Copyright © 2015, American Association for the Advancement of Science.

Repetitive Self-Grooming Behavior in the BTBR Mouse Model of Autism is Blocked by the mGluR5 Antagonist MPEP

PubMed Central

Silverman, Jill L; Tolu, Seda S; Barkan, Charlotte L; Crawley, Jacqueline N

2010-01-01

Autism is a neurodevelopmental disorder characterized by abnormal reciprocal social interactions, communication deficits, and repetitive behaviors with restricted interests. BTBR T+tf/J (BTBR) is an inbred mouse strain that shows robust behavioral phenotypes with analogies to all three of the diagnostic symptoms of autism, including well-replicated deficits in reciprocal social interactions and social approach, unusual patterns of ultrasonic vocalization, and high levels of repetitive self-grooming. These phenotypes offer straightforward behavioral assays for translational investigations of pharmacological compounds. Two suggested treatments for autism were evaluated in the BTBR mouse model. Methyl-6-phenylethynyl-pyridine (MPEP), an antagonist of the mGluR5 metabotropic glutamate receptor, blocks aberrant phenotypes in the Fmr1 mouse model of Fragile X, a comorbid neurodevelopmental disorder with autistic features. Risperidone has been approved by the United States Food and Drug Administration for the treatment of irritability, tantrums, and self-injurious behavior in autistic individuals. We evaluated the actions of MPEP and risperidone on two BTBR phenotypes, low sociability and high repetitive self-grooming. Open field activity served as an independent control for non-social exploratory activity and motor functions. C57BL/6J (B6), an inbred strain with high sociability and low self-grooming, served as the strain control. MPEP significantly reduced repetitive self-grooming in BTBR, at doses that had no sedating effects on open field activity. Risperidone reduced repetitive self-grooming in BTBR, but only at doses that induced sedation in both strains. No overall improvements in sociability were detected in BTBR after treatment with either MPEP or risperidone. Our findings suggest that antagonists of mGluR5 receptors may have selective therapeutic efficacy in treating repetitive behaviors in autism. PMID:20032969

Experience and the developing prefrontal cortex

PubMed Central

Kolb, Bryan; Mychasiuk, Richelle; Muhammad, Arif; Li, Yilin; Frost, Douglas O.; Gibb, Robbin

2012-01-01

The prefrontal cortex (PFC) receives input from all other cortical regions and functions to plan and direct motor, cognitive, affective, and social behavior across time. It has a prolonged development, which allows the acquisition of complex cognitive abilities through experience but makes it susceptible to factors that can lead to abnormal functioning, which is often manifested in neuropsychiatric disorders. When the PFC is exposed to different environmental events during development, such as sensory stimuli, stress, drugs, hormones, and social experiences (including both parental and peer interactions), the developing PFC may develop in different ways. The goal of the current review is to illustrate how the circuitry of the developing PFC can be sculpted by a wide range of pre- and postnatal factors. We begin with an overview of prefrontal functioning and development, and we conclude with a consideration of how early experiences influence prefrontal development and behavior. PMID:23045653

Dynamic and social behaviors of human pluripotent stem cells.

PubMed

Phadnis, Smruti M; Loewke, Nathan O; Dimov, Ivan K; Pai, Sunil; Amwake, Christine E; Solgaard, Olav; Baer, Thomas M; Chen, Bertha; Reijo Pera, Renee A

2015-09-18

Human pluripotent stem cells (hPSCs) can self-renew or differentiate to diverse cell types, thus providing a platform for basic and clinical applications. However, pluripotent stem cell populations are heterogeneous and functional properties at the single cell level are poorly documented leading to inefficiencies in differentiation and concerns regarding reproducibility and safety. Here, we use non-invasive time-lapse imaging to continuously examine hPSC maintenance and differentiation and to predict cell viability and fate. We document dynamic behaviors and social interactions that prospectively distinguish hPSC survival, self-renewal, and differentiation. Results highlight the molecular role of E-cadherin not only for cell-cell contact but also for clonal propagation of hPSCs. Results indicate that use of continuous time-lapse imaging can distinguish cellular heterogeneity with respect to pluripotency as well as a subset of karyotypic abnormalities whose dynamic properties were monitored.

Dynamic and social behaviors of human pluripotent stem cells

PubMed Central

Phadnis, Smruti M.; Loewke, Nathan O.; Dimov, Ivan K.; Pai, Sunil; Amwake, Christine E.; Solgaard, Olav; Baer, Thomas M.; Chen, Bertha; Pera, Renee A. Reijo

2015-01-01

Human pluripotent stem cells (hPSCs) can self-renew or differentiate to diverse cell types, thus providing a platform for basic and clinical applications. However, pluripotent stem cell populations are heterogeneous and functional properties at the single cell level are poorly documented leading to inefficiencies in differentiation and concerns regarding reproducibility and safety. Here, we use non-invasive time-lapse imaging to continuously examine hPSC maintenance and differentiation and to predict cell viability and fate. We document dynamic behaviors and social interactions that prospectively distinguish hPSC survival, self-renewal, and differentiation. Results highlight the molecular role of E-cadherin not only for cell-cell contact but also for clonal propagation of hPSCs. Results indicate that use of continuous time-lapse imaging can distinguish cellular heterogeneity with respect to pluripotency as well as a subset of karyotypic abnormalities whose dynamic properties were monitored. PMID:26381699

Pathobiological and Behavioral Effects of Lead Intoxication in the Infant Rhesus Monkey

PubMed Central

Allen, J. R.; McWey, P. J.; Suomi, S. J.

1974-01-01

When infant rhesus monkeys were exposed to lead via the addition of lead acetate (0.5–9 mg/kg body weight) to their formula or by the consumption of lead particles from lead-based surrogate mothers, they developed symptoms of lead intoxication within 6 weeks. Seizures, muscular tremors, and altered social interaction were the predominant changes. Visual impairment was also apparent in the more severely affected animals. In the animals showing obvious symptoms lead levels varied between 300 to 500 μg/100 ml of blood. Even in those animals having blood lead levels below 100 μg, hyperactivity and insomnia were observed. When the exposure to lead was eliminated, seizures subsided and visual impairment was reduced; however, the abnormal social interaction persisted. These animals also experienced a gradual decline in hematocrit and hemoglobin values during the period of examination. Liver and kidney biopsies obtained from these lead-exposed animals revealed characteristic intranuclear inclusions. When adolescent and adult monkeys were exposed to doses of lead acetate similar to those employed in the infant experiments, lead levels in excess of 200 μg/100 ml of blood were recorded. However, there were no obvious behavioral abnormalities observed. There were, however, numerous lead inclusion bodies in kidney biopsy specimens from these animals. These data suggest that, like man, the infant nonhuman primate is much more susceptible to lead intoxication than is the adult. The clinical and behavioral changes recorded in these infant rhesus monkeys suggest their use as an experimental model to evaluate lead intoxication. ImagesFIGURE 6. PMID:4208658

The Relationship between Personality Dimensions and Resiliency to Environmental Stress in Orange-Winged Amazon Parrots (Amazona amazonica), as Indicated by the Development of Abnormal Behaviors.

PubMed

Cussen, Victoria A; Mench, Joy A

2015-01-01

Parrots are popular companion animals, but are frequently relinquished because of behavioral problems, including abnormal repetitive behaviors like feather damaging behavior and stereotypy. In addition to contributing to pet relinquishment, these behaviors are important as potential indicators of diminished psychological well-being. While abnormal behaviors are common in captive animals, their presence and/or severity varies between animals of the same species that are experiencing the same environmental conditions. Personality differences could contribute to this observed individual variation, as they are known risk factors for stress sensitivity and affective disorders in humans. The goal of this study was to assess the relationship between personality and the development and severity of abnormal behaviors in captive-bred orange-winged Amazon parrots (Amazona amazonica). We monitored between-individual behavioral differences in enrichment-reared parrots of known personality types before, during, and after enrichment deprivation. We predicted that parrots with higher scores for neurotic-like personality traits would be more susceptible to enrichment deprivation and develop more abnormal behaviors. Our results partially supported this hypothesis, but also showed that distinct personality dimensions were related to different forms of abnormal behavior. While neuroticism-like traits were linked to feather damaging behavior, extraversion-like traits were negatively related to stereotypic behavior. More extraverted birds showed resiliency to environmental stress, developing fewer stereotypies during enrichment deprivation and showing lower levels of these behaviors following re-enrichment. Our data, together with the results of the few studies conducted on other species, suggest that, as in humans, certain personality types render individual animals more susceptible or resilient to environmental stress. Further, this susceptibility/resiliency can have a long-term effect on behavior, as evidenced by behavioral changes that persisted despite re-enrichment. Ours is the first study evaluating the relationship between personality dimensions, environment, and abnormal behaviors in an avian species.

The Relationship between Personality Dimensions and Resiliency to Environmental Stress in Orange-Winged Amazon Parrots (Amazona amazonica), as Indicated by the Development of Abnormal Behaviors

PubMed Central

Cussen, Victoria A.; Mench, Joy A.

2015-01-01

Parrots are popular companion animals, but are frequently relinquished because of behavioral problems, including abnormal repetitive behaviors like feather damaging behavior and stereotypy. In addition to contributing to pet relinquishment, these behaviors are important as potential indicators of diminished psychological well-being. While abnormal behaviors are common in captive animals, their presence and/or severity varies between animals of the same species that are experiencing the same environmental conditions. Personality differences could contribute to this observed individual variation, as they are known risk factors for stress sensitivity and affective disorders in humans. The goal of this study was to assess the relationship between personality and the development and severity of abnormal behaviors in captive-bred orange-winged Amazon parrots (Amazona amazonica). We monitored between-individual behavioral differences in enrichment-reared parrots of known personality types before, during, and after enrichment deprivation. We predicted that parrots with higher scores for neurotic-like personality traits would be more susceptible to enrichment deprivation and develop more abnormal behaviors. Our results partially supported this hypothesis, but also showed that distinct personality dimensions were related to different forms of abnormal behavior. While neuroticism-like traits were linked to feather damaging behavior, extraversion-like traits were negatively related to stereotypic behavior. More extraverted birds showed resiliency to environmental stress, developing fewer stereotypies during enrichment deprivation and showing lower levels of these behaviors following re-enrichment. Our data, together with the results of the few studies conducted on other species, suggest that, as in humans, certain personality types render individual animals more susceptible or resilient to environmental stress. Further, this susceptibility/resiliency can have a long-term effect on behavior, as evidenced by behavioral changes that persisted despite re-enrichment. Ours is the first study evaluating the relationship between personality dimensions, environment, and abnormal behaviors in an avian species. PMID:26114423

Vigilance-avoidance and disengagement are differentially associated with fear and avoidant behaviors in social anxiety.

PubMed

Evans, Travis C; Walukevich, Katherine A; Britton, Jennifer C

2016-07-15

Individuals with Social Anxiety Disorder (SAD) often exhibit preferential attention for social threat, demonstrating abnormal orientation to threat (i.e., vigilance-avoidance) and/or difficulty disengaging from threat. However, no research has compared the relationship between attention indices (i.e., vigilance-avoidance, difficulty disengaging from threat) and characteristic features of the disorder such as fear during social situations (social fear) and avoidant behaviors (social avoidance). To address this issue, seventy adults (19.29±1.47 years, 33 females) were separated into low (n=37) or high (n=33) socially anxious groups using clinical cutoff scores on the Social Interaction Anxiety Scale (SIAS). Participants in both groups completed a dot-probe task with congruent, incongruent, and neutral trials to obtain measures of vigilance-avoidance and difficulty disengaging. Using linear regression, we examined the associations each attention index shared with self-reported social fear and social avoidance. Exclusively in the high anxious group, greater vigilance towards threat was associated with higher self-reported social fear, but not with social avoidance. However, difficulty disengaging was not associated with either social measure. In the low anxiety group, no relationships between attention indices and either social measure emerged. Future research with clinical samples is necessary to replicate and extend these findings. The small sample size studied may have limited our ability to detect other smaller effects. Indices of attention bias may contribute differently to the etiology and maintenance of SAD, which offers important implications for novel treatments that target attention. Copyright © 2016 Elsevier B.V. All rights reserved.

Supplementation of Korean Red Ginseng improves behavior deviations in animal models of autism

PubMed Central

Gonzales, Edson Luck T.; Jang, Jong-Hwa; Mabunga, Darine Froy N.; Kim, Ji-Woon; Ko, Mee Jung; Cho, Kyu Suk; Bahn, Geon Ho; Hong, Minha; Ryu, Jong Hoon; Kim, Hee Jin; Cheong, Jae Hoon; Shin, Chan Young

2016-01-01

Background Autism spectrum disorder (ASD) is heterogeneous neurodevelopmental disorders that primarily display social and communication impairments and restricted/repetitive behaviors. ASD prevalence has increased in recent years, yet very limited therapeutic targets and treatments are available to counteract the incapacitating disorder. Korean Red Ginseng (KRG) is a popular herbal plant in South Korea known for its wide range of therapeutic effects and nutritional benefits and has recently been gaining great scientific attention, particularly for its positive effects in the central nervous system. Objectives Thus, in this study, we investigated the therapeutic potential of KRG in alleviating the neurobehavioral deficits found in the valproic acid (VPA)-exposed mice models of ASD. Design Starting at 21 days old (P21), VPA-exposed mice were given daily oral administrations of KRG solution (100 or 200 mg/kg) until the termination of all experiments. From P28, mice behaviors were assessed in terms of social interaction capacity (P28–29), locomotor activity (P30), repetitive behaviors (P32), short-term spatial working memory (P34), motor coordination (P36), and seizure susceptibility (P38). Results VPA-exposed mice showed sociability and social novelty preference deficits, hyperactivity, increased repetitive behavior, impaired spatial working memory, slightly affected motor coordination, and high seizure susceptibility. Remarkably, long-term KRG treatment in both dosages normalized all the ASD-related behaviors in VPA-exposed mice, except motor coordination ability. Conclusion As a food and herbal supplement with various known benefits, KRG demonstrated its therapeutic potential in rescuing abnormal behaviors related to autism caused by prenatal environmental exposure to VPA. PMID:26837496

Neurodevelopment of children under 3 years of age with Smith-Magenis syndrome.

PubMed

Wolters, Pamela L; Gropman, Andrea L; Martin, Staci C; Smith, Michaele R; Hildenbrand, Hanna L; Brewer, Carmen C; Smith, Ann C M

2009-10-01

Systematic data regarding early neurodevelopmental functioning in Smith-Magenis syndrome are limited. Eleven children with Smith-Magenis syndrome less than 3 years of age (mean, 19 months; range, 5-34 months) received prospective multidisciplinary assessments using standardized measures. The total sample scored in the moderately to severely delayed range in cognitive functioning, expressive language, and motor skills and exhibited generalized hypotonia, oral-motor abnormalities, and middle ear dysfunction. Socialization skills were average, and significantly higher than daily living, communication, and motor abilities, which were below average. Mean behavior ratings were in the nonautistic range. According to exploratory analyses, the toddler subgroup scored significantly lower than the infant subgroup in cognition, expressive language, and adaptive behavior, suggesting that the toddlers were more delayed than the infants relative to their respective peers. Infants aged approximately 1 year or younger exhibited cognitive, language, and motor skills that ranged from average to delayed, but with age-appropriate social skills and minimal maladaptive behaviors. At ages 2 to 3 years, the toddlers consistently exhibited cognitive, expressive language, adaptive behavior, and motor delays and mildly to moderately autistic behaviors. Combining age groups in studies may mask developmental and behavioral differences. Increased knowledge of these early neurodevelopmental characteristics should facilitate diagnosis and appropriate intervention.

Brain Region-Specific Expression of Genes Mapped within Quantitative Trait Loci for Behavioral Responsiveness to Acute Stress in Fisher 344 and Wistar Kyoto Male Rats (Postprint)

DTIC Science & Technology

2018-03-12

Integrative Genomics Viewer (Broad Institute, Cambridge, Massachusetts), we iden- tified the coding sequence variations between the F344 and WKY... abnormalities and disturbances in brain metabolism resem- bling those in depressive states [74]. Ifna2 is also known to induce memory, concentration, and...Variant and Chronic Interpersonal Stress Prospectively Predicts Social Anxiety and Depression Symptoms Over Six Years. Clinical psychological science

Abnormal network connectivity in frontotemporal dementia: evidence for prefrontal isolation.

PubMed

Farb, Norman A S; Grady, Cheryl L; Strother, Stephen; Tang-Wai, David F; Masellis, Mario; Black, Sandra; Freedman, Morris; Pollock, Bruce G; Campbell, Karen L; Hasher, Lynn; Chow, Tiffany W

2013-01-01

Degraded social function, disinhibition, and stereotypy are defining characteristics of frontotemporal dementia (FTD), manifesting in both the behavioral variant of frontotemporal dementia (bvFTD) and semantic dementia (SD) subtypes. Recent neuroimaging research also associates FTD with alterations in the brain's intrinsic connectivity networks. The present study explored the relationship between neural network connectivity and specific behavioral symptoms in FTD. Resting-state functional magnetic resonance imaging was employed to investigate neural network changes in bvFTD and SD. We used independent components analysis (ICA) to examine changes in frontolimbic network connectivity, as well as several metrics of local network strength, such as the fractional amplitude of low-frequency fluctuations, regional homogeneity, and seed-based functional connectivity. For each analysis, we compared each FTD subgroup to healthy controls, characterizing general and subtype-unique network changes. The relationship between abnormal connectivity in FTD and behavior disturbances was explored. Across multiple analytic approaches, both bvFTD and SD were associated with disrupted frontolimbic connectivity and elevated local connectivity within the prefrontal cortex. Even after controlling for structural atrophy, prefrontal hyperconnectivity was robustly associated with apathy scores. Frontolimbic disconnection was associated with lower disinhibition scores, suggesting that abnormal frontolimbic connectivity contributes to positive symptoms in dementia. Unique to bvFTD, stereotypy was associated with elevated default network connectivity in the right angular gyrus. The behavioral variant was also associated with marginally higher apathy scores and a more diffuse pattern of prefrontal hyperconnectivity than SD. The present findings support a theory of FTD as a disorder of frontolimbic disconnection leading to unconstrained prefrontal connectivity. Prefrontal hyperconnectivity may represent a compensatory response to the absence of affective feedback during the planning and execution of behavior. Increased reliance upon prefrontal processes in isolation from subcortical structures appears to be maladaptive and may drive behavioral withdrawal that is commonly observed in later phases of neurodegeneration. Copyright © 2012 Elsevier Ltd. All rights reserved.

Disruption of social approach by MK-801, amphetamine, and fluoxetine in adolescent C57BL/6J mice.

PubMed

Moy, Sheryl S; Nonneman, Randal J; Shafer, Geoffrey O; Nikolova, Viktoriya D; Riddick, Natallia V; Agster, Kara L; Baker, Lorinda K; Knapp, Darin J

2013-01-01

Autism is a severe neurodevelopmental disorder, diagnosed on the basis of core behavioral symptoms. Although the mechanistic basis for the disorder is not yet known, genetic analyses have suggested a role for abnormal excitatory/inhibitory signaling systems in brain, including dysregulation of glutamatergic neurotransmission. In mice, the constitutive knockdown of NMDA receptors leads to social deficits, repetitive behavior, and self-injurious responses that reflect aspects of the autism clinical profile. However, social phenotypes differ with age: mice with reduced NMDA-receptor function exhibit hypersociability in adolescence, but markedly deficient sociability in adulthood. The present studies determined whether acute disruption of NMDA neurotransmission leads to exaggerated social approach, similar to that observed with constitutive disruption, in adolescent C57BL/6J mice. The effects of MK-801, an NMDA receptor antagonist, were compared with amphetamine, a dopamine agonist, and fluoxetine, a selective serotonin reuptake inhibitor, on performance in a three-chamber choice task. Results showed that acute treatment with MK-801 led to social approach deficits at doses without effects on entry numbers. Amphetamine also decreased social preference, but increased number of entries at every dose. Fluoxetine (10 mg/kg) had selective effects on social novelty preference. Withdrawal from a chronic ethanol regimen decreased activity, but did not attenuate sociability. Low doses of MK-801 and amphetamine were also evaluated in a marble-burying assay for repetitive behavior. MK-801, at a dose that did not disrupt sociability or alter entries, led to a profound reduction in marble-burying. Overall, these findings demonstrate that moderate alteration of NMDA, dopamine, or serotonin function can attenuate social preference in wild type mice. Copyright © 2012 Elsevier Inc. All rights reserved.

Disruption of social approach by MK-801, amphetamine, and fluoxetine in adolescent C57BL/6J mice

PubMed Central

Moy, Sheryl S.; Nonneman, Randal J.; Shafer, Geoffrey O.; Nikolova, Viktoriya D.; Riddick, Natallia V.; Agster, Kara L.; Baker, Lorinda K.; Knapp, Darin J.

2012-01-01

Autism is a severe neurodevelopmental disorder, diagnosed on the basis of core behavioral symptoms. Although the mechanistic basis for the disorder is not yet known, genetic analyses have suggested a role for abnormal excitatory/inhibitory signaling systems in brain, including dysregulation of glutamatergic neurotransmission. In mice, the constitutive knockdown of NMDA receptors leads to social deficits, repetitive behavior, and self-injurious responses that reflect aspects of the autism clinical profile. However, social phenotypes differ with age: mice with reduced NMDA-receptor function exhibit hypersociability in adolescence, but markedly deficient sociability in adulthood. The present studies determined whether acute disruption of NMDA neurotransmission leads to exaggerated social approach, similar to that observed with constitutive disruption, in adolescent C57BL/6J mice. The effects of MK-801, an NMDA receptor antagonist, were compared with amphetamine, a dopamine agonist, and fluoxetine, a selective serotonin reuptake inhibitor, on performance in a three-chamber choice task. Results showed that acute treatment with MK-801 led to social approach deficits at doses without effects on entry numbers. Amphetamine also decreased social preference, but increased number of entries at every dose. Fluoxetine (10 mg/kg) had selective effects on social novelty preference. Withdrawal from a chronic ethanol regimen decreased activity, but did not attenuate sociability. Low doses of MK-801 and amphetamine were also evaluated in a marble-burying assay for repetitive behavior. MK-801, at a dose that did not disrupt sociability or alter entries, led to a profound reduction in marble-burying. Overall, these findings demonstrate that moderate alteration of NMDA, dopamine, or serotonin function can attenuate social preference in wild type mice. PMID:22898204

Impaired self-awareness in human addiction: Deficient attribution of personal relevance

PubMed Central

Moeller, Scott J.; Goldstein, Rita Z.

2014-01-01

Compromised self-awareness of illness-related deficits and behaviors in psychopathology (e.g., schizophrenia) has been associated with deficient functioning of cortical midline regions including the ventromedial prefrontal cortex (vmPFC), implicated in personal relevance. Here, we review and critically analyze recent evidence to suggest that vmPFC abnormalities could similarly underlie deficient tagging of personal relevance in drug addiction, evidenced by a constellation of behaviors encompassing drug-biased attention, negative outcome insensitivity, self-report/behavior dissociation, and social inappropriateness. This novel framework might clarify, for example, why drug-addicted individuals often ruin long-standing relationships or forego important job opportunities while continuing to engage in uncontrolled drug-taking. Therapeutic interventions targeting personal relevance and associated vmPFC functioning could enhance self-awareness and facilitate more adaptive behavior in this chronically relapsing psychopathology. PMID:25278368

[An autopsied case of senile onset frontotemporal lobar degeneration].

PubMed

Iwasaki, Yasushi; Mori, Keiko; Ito, Masumi; Deguchi, Akira; Yoshida, Mari

2011-06-01

A Japanese male with no family history of neurological disease or dementia showed behavioral abnormalities including egocentric and antisocial behavior at the age of 80. Over the next few years, other psychiatric symptoms such as allotriophagy and stereotypical behavior were also observed and his abnormal behavior became a social problem. Neurological examination revealed no apparent motor abnormalities, pyramidal and extrapyramidal signs, or ataxia. Aphasia, including semantic dementia was not apparent. The severity of memory disturbance was relatively milder than his psychiatric symptoms. Daily living activities and conversational ability were relatively maintained until shortly before his death at the age of 86. The clinical diagnosis was Alzheimer disease. Autopsy revealed that the brain weighed 950 g; frontotemporal atrophy with lateral ventricular dilatation was apparent. Neuron loss, gliosis, and tissue rarefaction were recognized in the frontotemporal cortex, subiculum, transentorhinal cortex, amygdala, and insular cortex and were particularly noticeable in the superficial layer of the cortex. Many ubiquitin-positive/TDP-43 positive but tau-negative dystrophic neurites with a few neuronal cytoplasmic inclusions were widely observed. Neuronal cytoplasmic inclusions were also observed in the dentate gyrus of the hippocampus. Although the spinal cord was not investigated, there was no apparent involvement of the motor neuron system. Small numbers of neurofibrillary tangles and senile plaques were observed, corresponding to Braak stage II and CERAD stage B, respectively. Argyrophilic grains, Lewy bodies and Pick bodies were not observed. The patient was pathologically diagnosed with frontotemporal lobar degeneration with ubiquitin-positive/TDP-43-positive inclusions (FTLD-TDP) and without motor neuron disease. No mutation was found in the TDP-43 gene. We considered the psychiatric symptoms and head CT findings of the present patient to be important observations for helping to discriminate between Alzheimer disease or other neurodegenerative diseases with dementia, and FTLD-TDP.

Neurodevelopment and executive function in autism.

PubMed

O'Hearn, Kirsten; Asato, Miya; Ordaz, Sarah; Luna, Beatriz

2008-01-01

Autism is a neurodevelopmental disorder characterized by social and communication deficits, and repetitive behavior. Studies investigating the integrity of brain systems in autism suggest a wide range of gray and white matter abnormalities that are present early in life and change with development. These abnormalities predominantly affect association areas and undermine functional integration. Executive function, which has a protracted development into adolescence and reflects the integration of complex widely distributed brain function, is also affected in autism. Evidence from studies probing response inhibition and working memory indicate impairments in these core components of executive function, as well as compensatory mechanisms that permit normative function in autism. Studies also demonstrate age-related improvements in executive function from childhood to adolescence in autism, indicating the presence of plasticity and suggesting a prolonged window for effective treatment. Despite developmental gains, mature executive functioning is limited in autism, reflecting abnormalities in wide-spread brain networks that may lead to impaired processing of complex information across all domains.

New experimental treatments for core social domain in autism spectrum disorders.

PubMed

Canitano, Roberto

2014-01-01

Current therapeutics in autism spectrum disorders (ASD) only treat the associated symptoms, without addressing core social dysfunctions. A paradigm shift in research of the pathogenesis of ASD, its synaptic abnormalities and altered signaling in multiple dynamic systems, have led to new experimental treatments for treating the core social abnormalities of ASD. NMDA antagonists, especially memantine, have been introduced in clinical trials addressing glutamatergic transmission in children and adolescents with ASD. GABAergic signaling has been targeted in trials using the GABAB receptor agonist arbaclofen for ASD patients with promising results. Oxytocin has been recognized as implicated in social development and affiliative behaviors. Preliminary findings from clinical trials using oxytocin in children with ASD show encouraging improvements in social cognition, but larger studies are needed. In two of the single gene disorders associated with ASD, Insulin Growth Factor (IGF-1) is a new treatment that has been tested in Rett syndrome and Phelan-McDermid syndrome (Chromosome 22 deletion syndrome). IGF-1 has been demonstrated to reverse the reduction in the number of excitatory synapses and the density of neurons that characterize these conditions in animal studies and it is being introduced as an experimental treatment. As a novel approach to verify treatment efficacy, neural processing modifications were recently evaluated by fMRI after a pivotal response training intervention. Another study of neural changes in response to treatment examined variations in EEG signaling in patients after an Early Start Denver Model (ESDM) intervention.

Associations between feelings of social anxiety and emotion perception.

PubMed

Lynn, Spencer K; Bui, Eric; Hoeppner, Susanne S; O'Day, Emily B; Palitz, Sophie A; Barrett, Lisa Feldman; Simon, Naomi M

2018-06-01

Abnormally biased perceptual judgment is a feature of many psychiatric disorders. Thus, individuals with social anxiety disorder are biased to recall or interpret social events negatively. Cognitive behavioral therapy addresses such bias by teaching patients, via verbal instruction, to become aware of and change pathological misjudgment. The present study examined whether targeting verbal instruction to specific decision parameters that influence perceptual judgment may affect changes in anger perception. We used a signal detection framework to decompose anger perception into three decision parameters (base rate of encountering anger vs. no-anger, payoff for correct vs. incorrect categorization of face stimuli, and perceptual similarity of angry vs. not-angry facial expressions). We created brief verbal instructions that emphasized each parameter separately. Participants with social anxiety disorder, generalized anxiety disorder, and healthy controls, were assigned to one of the three instruction conditions. We compared anger perception pre-vs. post-instruction. Base rate and payoff instructions affected response bias over and above practice effects, across the three groups. There was no interaction with diagnosis. The ability to target specific decision parameters that underlie perceptual judgment suggests that cognitive behavioral therapy might be improved by tailoring it to patients' individual parameter "estimation" deficits. Copyright © 2017 Elsevier Ltd. All rights reserved.

Social Competence of Preschool Children Born Very Preterm

PubMed Central

Jones, Kelly M.; Champion, Patricia R.; Woodward, Lianne J.

2014-01-01

Background Relatively little is known about the early social development of children born very preterm despite clear suggestions of later interpersonal difficulties. Aims To compare the social competence of very preterm (VPT) and full term (FT) born children at age 4 and identify infant, social and family factors associated with later risk. Study design Prospective longitudinal study. Subjects A regionally representative cohort of 103 VPT (≤32 weeks gestation) children and a comparison group of 105 FT children (36-41 weeks gestation) born between 1998 and 2000. Outcome measures At corrected age 4 years, a range of parent report, observational and laboratory measures assessed children's emotional and behavioral adjustment, emotional regulation, social interactive behavior and theory of mind understanding. Extensive perinatal, social background and family functioning data were also available from birth to age 4. Results Compared to their FT peers, VPT born children had poorer emotional and behavioural adjustment, were less effective in regulating their emotions, had lower levels of positive peer play and had less synchronous interactions with their parents. Within the VPT group, predictors of poor social competence included family socioeconomic disadvantage, extreme prematurity, severity of cerebral white matter abnormalities and early childhood exposure to high levels of maternal anxiety and negative parenting. Conclusions VPT pre-schoolers are characterized by a range of subtle social difficulties likely to adversely affect their ability to establish and maintain positive relationships with others. These difficulties need to be monitored alongside other potential neurodevelopmental concerns and parents supported to actively nurture child social competence. PMID:23870752

Sodium nitroprusside is effective in preventing and/or reversing the development of schizophrenia-related behaviors in an animal model: The SHR strain.

PubMed

Diana, Mariana C; Peres, Fernanda F; Justi, Veronica; Bressan, Rodrigo A; Lacerda, Acioly L T; Crippa, José Alexandre; Hallak, Jaime E C; Abilio, Vanesssa Costhek

2018-04-14

The treatment of schizophrenia with antipsychotics is still unsatisfactory. Therefore, the search for new treatments and prevention is crucial, and animal models are fundamental tools for this objective. Preclinical and clinical data evidence the antipsychotic profile of sodium nitroprusside (SNP), a nitric oxide (NO) donor. We aimed to investigate SNP in treating and/or preventing the schizophrenia-related behaviors presented by the spontaneously hypertensive rats (SHR) strain. Wistar rats (WR) and SHRs were submitted to two schemes of treatment: (i) a single injection of SNP or vehicle in adulthood; (ii) a long-term early treatment from 30 to 60 postnatal day with SNP or vehicle. The following behaviors were evaluated 24 hours after the acute treatment or 30 days after the long-term treatment: locomotion, social interaction, and contextual fear conditioning. Spontaneously hypertensive rats presented hyperlocomotion, decreased social interaction, and impaired contextual fear conditioning. Single injection of SNP decreased social interaction in both strains and induced a deficit in contextual fear conditioning in WR. Oppositely, early treatment with SNP prevented the behavioral abnormalities in adult SHRs without promoting any effects in WR. Our preclinical data point to SNP as a preventive and safe strategy with a broad range of effectiveness to the positive, negative, and cognitive symptoms of schizophrenia. © 2018 John Wiley & Sons Ltd.

[Attention deficit hyperactivity disorder and epilepsy in childhood].

PubMed

Idiazábal-Alecha, M Angeles; Kosno, Magdalena

2012-02-29

Both attention deficit hyperactivity disorder (ADHD) and epilepsy are common disorders in childhood. ADHD and epilepsy can be detrimental to the behavior, learning and social relations of affected children. Children with epilepsy and ADHD tend to be at higher risk of school difficulties compared with children who suffer from epilepsy only. We review the works on the prevalence of ADHD in the epileptic population, the prevalence of epilepsy in children with ADHD, and electroencephalographic abnormalities observed in patients with ADHD. The prevalence of ADHD in childhood epilepsy is higher than in the general population and as is the rate of epilepsy in ADHD. Further studies are required to assess the bidirectional relationship between ADHD and epilepsy and the impact of electroencephalographic abnormalities in the clinical course of these patients.

[Fibromyalgia].

PubMed

Jäckel, W H; Genth, E

2007-11-01

The characteristic symptoms of fibromyalgia are chronic widespread musculoskeletal pain in various parts of the body and abnormal tenderness at 18 specified tender points. Associated symptoms often reported include stiffness, sleep disorders, fatigue, and problems with concentration. The prevalence is about 3.5% for women and 0.5% for men. The impact of the disease is considerable both for those directly affected (restriction in activities of daily living and in ability to take part in family, professional, and social life) and for society as a whole (direct and indirect costs). The disease usually has a chronic course. An abnormality of the central pain-processing mechanisms is highly relevant for the pathogenesis. In addition to early diagnosis and intensive patient education, pharmacotherapy, exercise therapy, behavior therapy, and multidisciplinary treatment are particularly important for the management of fibromyalgia.

Violence Victimization, Social Support, and Papanicolaou Smear Outcomes: A Longitudinal Study from Adolescence to Young Adulthood.

PubMed

Hsieh, Hsing-Fang; Heinze, Justin E; Lang, Ian; Mistry, Ritesh; Buu, Anne; Zimmerman, Marc A

2017-12-01

African American youth are among those at greatest risk for experiencing violence victimization. Notably, the mortality rate of cervical cancer for African American women is also twice that of white women. To date, we know of no literature using longitudinal data to examine how violence victimization relates to Papanicolaou (Pap) smear results or cervical cancer in this population. Our study examines how violence victimization during adolescence (age 15 to 18) influences psychological distress, perceived social support, heavy substance abuse, and sexual risk behaviors during emerging adulthood (age 20 to 23), and subsequent Pap smear outcomes during young adulthood (age 29 to 32). This study is based on 12 waves of data collected in a longitudinal study of 360 African American women from mid-adolescence (ninth grade, mean age = 14.8 years) to young adulthood (mean age = 32.0 years). We used structural equation modeling analysis to examine the hypothesized model. Violence victimization during adolescence had a direct effect on decreased social support, increased psychological distress, and increased heavy cigarette use during emerging adulthood. Better social support was also associated with fewer sexual partners during emerging adulthood and lower odds of abnormal Pap smear results during young adulthood. The effect of violence victimization on abnormal Pap smear was mediated by social support. Our results show that violence victimization during adolescence has long-term negative effects through multiple pathways that persist into adulthood. Our findings also suggest that social support may help to compensate against other risk factors. Interventions designed to address the perceived support may help victims cope with their experience.

Amygdala response to faces parallels social behavior in Williams syndrome

PubMed Central

Snyder, Abraham Z.; Haist, Frank; Raichle, Marcus E.; Bellugi, Ursula; Stiles, Joan

2009-01-01

Individuals with Williams syndrome (WS), a genetically determined disorder, show relatively strong face-processing abilities despite poor visuospatial skills and depressed intellectual function. Interestingly, beginning early in childhood they also show an unusually high level of interest in face-to-face social interaction. We employed functional magnetic resonance imaging (fMRI) to investigate physiological responses in face-sensitive brain regions, including ventral occipito-temporal cortex and the amygdala, in this unique genetic disorder. Participants included 17 individuals with WS, 17 age- and gender-matched healthy adults (chronological age-matched controls, CA) and 17 typically developing 8- to 9-year-old children (developmental age controls, DA). While engaged in a face discrimination task, WS participants failed to recruit the amygdala, unlike both CA and DA controls. WS fMRI responses in ventral occipito-temporal cortex, however, were comparable to those of DA controls. Given the integral role of the amygdala in social behavior, the failure of WS participants to recruit this region during face processing may be a neural correlate of the abnormally high sociability that characterizes this disorder. PMID:19633063

Behavioral patterns of environmental performance evaluation programs.

PubMed

Li, Wanxin; Mauerhofer, Volker

2016-11-01

During the past decades numerous environmental performance evaluation programs have been developed and implemented on different geographic scales. This paper develops a taxonomy of environmental management behavioral patterns in order to provide a practical comparison tool for environmental performance evaluation programs. Ten such programs purposively selected are mapped against the identified four behavioral patterns in the form of diagnosis, negotiation, learning, and socialization and learning. Overall, we found that schemes which serve to diagnose environmental abnormalities are mainly externally imposed and have been developed as a result of technical debates concerning data sources, methodology and ranking criteria. Learning oriented scheme is featured by processes through which free exchange of ideas, mutual and adaptive learning can occur. Scheme developed by higher authority for influencing behaviors of lower levels of government has been adopted by the evaluated to signal their excellent environmental performance. The socializing and learning classified evaluation schemes have incorporated dialogue, participation, and capacity building in program design. In conclusion we consider the 'fitness for purpose' of the various schemes, the merits of our analytical model and the future possibilities of fostering capacity building in the realm of wicked environmental challenges. Copyright © 2016 Elsevier Ltd. All rights reserved.

Altered attentional and perceptual processes as indexed by N170 during gaze perception in schizophrenia: Relationship with perceived threat and paranoid delusions.

PubMed

Tso, Ivy F; Calwas, Anita M; Chun, Jinsoo; Mueller, Savanna A; Taylor, Stephan F; Deldin, Patricia J

2015-08-01

Using gaze information to orient attention and guide behavior is critical to social adaptation. Previous studies have suggested that abnormal gaze perception in schizophrenia (SCZ) may originate in abnormal early attentional and perceptual processes and may be related to paranoid symptoms. Using event-related brain potentials (ERPs), this study investigated altered early attentional and perceptual processes during gaze perception and their relationship to paranoid delusions in SCZ. Twenty-eight individuals with SCZ or schizoaffective disorder and 32 demographically matched healthy controls (HCs) completed a gaze-discrimination task with face stimuli varying in gaze direction (direct, averted), head orientation (forward, deviated), and emotion (neutral, fearful). ERPs were recorded during the task. Participants rated experienced threat from each face after the task. Participants with SCZ were as accurate as, though slower than, HCs on the task. Participants with SCZ displayed enlarged N170 responses over the left hemisphere to averted gaze presented in fearful relative to neutral faces, indicating a heightened encoding sensitivity to faces signaling external threat. This abnormality was correlated with increased perceived threat and paranoid delusions. Participants with SCZ also showed a reduction of N170 modulation by head orientation (normally increased amplitude to deviated faces relative to forward faces), suggesting less integration of contextual cues of head orientation in gaze perception. The psychophysiological deviations observed during gaze discrimination in SCZ underscore the role of early attentional and perceptual abnormalities in social information processing and paranoid symptoms of SCZ. (c) 2015 APA, all rights reserved).

Early Social Enrichment Improves Social Motivation and Skills in a Monogenic Mouse Model of Autism, the Oprm1 (-/-) Mouse.

PubMed

Garbugino, Luciana; Centofante, Eleonora; D'Amato, Francesca R

2016-01-01

Environmental enrichment has been proven to have positive effects on both behavioral and physiological phenotypes in rodent models of mental and neurodevelopmental disorders. In this study, we used mice lacking the µ-opioid receptor gene (Oprm1 (-/-)), which has been shown to have deficits in social competence and communication, to assess the hypothesis that early enrichment can ameliorate sociability during development and adulthood. Due to the immaturity of sensory-motor capabilities of young pups, we chose as environmental stimulation a second lactating female, who provided extra maternal care and stimulation from birth. The results show that double mothering normalized the abnormal response to maternal separation in Oprm1 (-/-) pups and increased social motivation in juveniles and adult knockout mice. Additionally, we observed that Oprm1 (-/-) mice act as less attractive social partners than wild types, which suggests that social motivation can be modulated by the stimulus employed. This experiment supports previous findings suggesting that early social environmental stimulation has profound and long-term beneficial effects, encouraging the use of nonpharmacological interventions for the treatment of social defects in neurodevelopmental diseases.

Developmental antecedents of abnormal eating attitudes and behaviors in adolescence.

PubMed

Le Grange, Daniel; O'Connor, Meredith; Hughes, Elizabeth K; Macdonald, Jacqui; Little, Keriann; Olsson, Craig A

2014-11-01

This study capitalizes on developmental data from an Australian population-based birth cohort to identify developmental markers of abnormal eating attitudes and behaviors in adolescence. The aims were twofold: (1) to develop a comprehensive path model identifying infant and childhood developmental correlates of Abnormal Eating Attitudes and Behaviors in adolescence, and (2) to explore potential gender differences. Data were drawn from a 30-year longitudinal study that has followed the health and development of a population based cohort across 15 waves of data collection from infancy since 1983: The Australian Temperament Project. Participants in this analysis were the 1,300 youth who completed the 11th survey at 15-16 years (1998) and who completed the eating disorder inventory at this time point. Developmental correlates of Abnormal Eating Attitudes and Behaviors in mid-adolescence were temperamental persistence, early gestational age, persistent high weight, teen depression, stronger peer relationships, maternal dieting behavior, and pubertal timing. Overall, these factors accounted for 28% of the variance in Abnormal Eating Attitudes and Behaviors at 15-16 years of age. Depressive symptoms, maternal dieting behavior, and early puberty were more important factors for girls. Late puberty was a more important factor for boys. Findings address an important gap in our understanding of the etiology of Abnormal Eating Attitudes and Behaviors in adolescence and suggest multiple targets for preventive intervention. © 2014 Wiley Periodicals, Inc.

Safety evaluation of laninamivir octanoate hydrate through analysis of adverse events reported during early post-marketing phase vigilance.

PubMed

Nakano, Takashi; Okumura, Akihisa; Tanabe, Takuya; Niwa, Shimpei; Fukushima, Masato; Yonemochi, Rie; Eda, Hisano; Tsutsumi, Hiroyuki

2013-06-01

Abnormal behavior and delirium are common in children with influenza. While abnormal behavior and delirium are considered to be associated with influenza encephalopathy, an increased risk of such neuropsychiatric symptoms in patients receiving neuraminidase inhibitor treatment is suspected. Laninamivir octanoate hydrate, recently approved in Japan, is a long-acting neuraminidase inhibitor. It is important to establish a safety profile for laninamivir early, based on post-marketing experiences. Spontaneous safety reports collected in the early post-marketing phase vigilance were analyzed. Adverse events of interest such as abnormal behavior/delirium, dizziness/vertigo, respiratory disorders, shock/syncope, and any other serious events were intensively reviewed by the Safety Evaluation Committee. Abnormal behavior/delirium was a frequently reported event. Almost all the reported cases were considered to be due to influenza and not laninamivir. There were 32 cases of abnormal behavior/delirium that could lead to dangerous accidents, and these were observed more frequently in males and teenagers. Syncope probably related to the act of inhalation per se of laninamivir was reported during this survey. This safety review revealed that the safety profile of laninamivir for abnormal behavior/delirium and syncope was similar to that of other neuraminidase inhibitors. As stated in the labeling, teenage patients inhaling laninamivir should remain under constant parental supervision for at least 2 days and should be closely monitored for behavioral changes to prevent serious accidents associated with abnormal behavior/delirium. Furthermore, to avoid syncope because of inhalation, patients should be instructed to inhale in a relaxed sitting position.

Severe abnormal behavior incidence after administration of neuraminidase inhibitors using the national database of medical claims.

PubMed

Nakamura, Yuuki; Sugawara, Tamie; Ohkusa, Yasushi; Taniguchi, Kiyosu; Miyazaki, Chiaki; Momoi, Mariko; Okabe, Nobuhiko

2018-03-01

An earlier study using the number of abnormal behaviors reported to the study group as the numerator and the number of influenza patient prescribed each neuraminidase inhibitor (NI) estimated by respective pharmaceutical companies found no significant difference among incidence rates of the most severe abnormal behaviors by type of NI throughout Japan. However, the dataset for the denominator used in that earlier study was the estimated number of prescriptions. In the present study, to compare the incidence rates of abnormal behavior more precisely among influenza patients administered several sorts of NI or administered no NI, we used data obtained from the National Database of Electronic Medical Claims (NDBEMC) as the denominator to reach a definitive conclusion. Results show that patients not administered any NI (hereinafter un-administered) or those administered peramivir sometimes showed higher risk of abnormal behavior than those administered oseltamivir, zanamivir, or laninamivir. However, the un-administered or peramivir patients were fewer than those taking other NI. Therefore, accumulation of data through continued research is expected to be necessary to reach a definitive conclusion about the relation between abnormal behavior and NI in influenza patients. Since severe abnormal behaviors with all types of NI or of un-administered patients have been reported, there are some risks in the administration of NI or even in un-administered cases. Therefore, we infer that the policy mandating package inserts in all types of NI. Copyright © 2017. Published by Elsevier Ltd.

Neural systems for social cognition: gray matter volume abnormalities in boys at high genetic risk of autism symptoms, and a comparison with idiopathic autism spectrum disorder.

PubMed

Goddard, Marcia N; Swaab, Hanna; Rombouts, Serge A R B; van Rijn, Sophie

2016-09-01

Klinefelter syndrome (47, XXY) is associated with several physical, cognitive, and behavioral consequences. In terms of social development, there is an increased risk of autism symptomatology. However, it remains unclear how social deficits are related to abnormal brain development and to what degree underlying mechanisms of social dysfunction in 47, XXY are similar to, or different from, those in idiopathic autism (ASD). This study was aimed at investigating the neural architecture of brain structures related to social information processing in boys with 47, XXY, also in comparison with boys with idiopathic ASD. MRI scans of 16 boys with 47, XXY, 16 with ASD, and 16 nonclinical, male controls were analyzed using voxel-based morphometry (VBM). A region of interest mask containing the superior temporal cortex, amygdala, orbitofrontal cortex (OFC), insular cortex, and medial frontal cortex was used. The Social Responsiveness Scale (SRS) was used to assess degree of autism spectrum symptoms. The 47, XXY group could not be distinguished from the ASD group on mean SRS scores, and their scores were significantly higher than in controls. VBM showed that boys with 47, XXY have significant gray matter volume reductions in the left and right insula, and the left OFC, compared with controls and boys with ASD. Additionally, boys with 47, XXY had significantly less gray matter in the right superior temporal gyrus than controls. These results imply social challenges associated with 47, XXY may be rooted in neural anatomy, and autism symptoms in boys with 47, XXY and boys with ASD might have, at least partially, different underlying etiologies.

Feedforward and Feedback Motor Control Abnormalities Implicate Cerebellar Dysfunctions in Autism Spectrum Disorder

PubMed Central

Mohanty, Suman; Greene, Rachel K.; Cook, Edwin H.; Vaillancourt, David E.; Sweeney, John A.

2015-01-01

Sensorimotor abnormalities are common in autism spectrum disorder (ASD) and among the earliest manifestations of the disorder. They have been studied far less than the social-communication and cognitive deficits that define ASD, but a mechanistic understanding of sensorimotor abnormalities in ASD may provide key insights into the neural underpinnings of the disorder. In this human study, we examined rapid, precision grip force contractions to determine whether feedforward mechanisms supporting initial motor output before sensory feedback can be processed are disrupted in ASD. Sustained force contractions also were examined to determine whether reactive adjustments to ongoing motor behavior based on visual feedback are altered. Sustained force was studied across multiple force levels and visual gains to assess motor and visuomotor mechanisms, respectively. Primary force contractions of individuals with ASD showed greater peak rate of force increases and large transient overshoots. Individuals with ASD also showed increased sustained force variability that scaled with force level and was more severe when visual gain was highly amplified or highly degraded. When sustaining a constant force level, their reactive adjustments were more periodic than controls, and they showed increased reliance on slower feedback mechanisms. Feedforward and feedback mechanism alterations each were associated with more severe social-communication impairments in ASD. These findings implicate anterior cerebellar circuits involved in feedforward motor control and posterior cerebellar circuits involved in transforming visual feedback into precise motor adjustments in ASD. PMID:25653359

Rats selectively bred for low levels of play-induced 50 kHz vocalizations as a model for autism spectrum disorders: a role for NMDA receptors.

PubMed

Burgdorf, Jeffrey; Moskal, Joseph R; Brudzynski, Stefan M; Panksepp, Jaak

2013-08-15

Early childhood autism is characterized by deficits in social approach and play behaviors, socio-emotional relatedness, and communication/speech abnormalities, as well as repetitive behaviors. These core neuropsychological features of autism can be modeled in laboratory rats, and the results may be useful for drug discovery and therapeutic development. We review data that show that rats selectively bred for low rates of play-related pro-social ultrasonic vocalizations (USVs) can be used to model social deficit symptoms of autism. Low-line animals engage in less social contact time with conspecifics, show lower rates of play induced pro-social USVs, and show an increased proportion of non-frequency modulated (i.e. monotonous) ultrasonic vocalizations compared to non-selectively bred random-line animals. Gene expression patterns in the low-line animals show significant enrichment in autism-associated genes, and the NMDA receptor family was identified as a significant hub. Treatment of low-line animals with the NMDAR functional glycine site partial agonist, GLYX-13, rescued the deficits in play-induced pro-social 50-kHz USVs and reduced monotonous USVs. Since the NMDA receptor has been implicated in the genesis of autistic symptoms, it is possible that GLYX-13 may be of therapeutic value in the treatment of autism. Copyright © 2013 Elsevier B.V. All rights reserved.

Rats selectively bred for low levels of play-induced 50 kHz vocalizations as a model for Autism Spectrum Disorders: a role for NMDA receptors

PubMed Central

Burgdorf, Jeffrey; Moskal, Joseph R.; Brudzynski, Stefan M.; Panksepp, Jaak

2016-01-01

Early childhood autism is characterized by deficits in social approach and play behaviors, socio-emotional relatedness, and communication/speech abnormalities, as well as repetitive behaviors. These core neuropsychological features of autism can be modeled in laboratory rats, and the results may be useful for drug discovery and therapeutic development. We review data that show that rats selectively bred for low rates of play-related pro-social ultrasonic vocalizations (USVs) can be used to model social deficit symptoms of autism. Low-line animals engage in less social contact time with conspecifics, show lower rates of play induced pro-social USVs, and show an increased proportion of non-frequency modulated (i.e. monotonous) ultrasonic vocalizations compared to non-selectively bred random-line animals. Gene expression patterns in the low-line animals show significant enrichment in autism-associated genes, and the NMDA receptor family was identified as a significant hub. Treatment of low-line animals with the NMDAR functional glycine site partial agonist, GLYX-13, rescued the deficits in play-induced pro-social 50-kHz USVs and reduced monotonous USVs. Since the NMDA receptor has been implicated in the genesis of autistic symptoms, it is possible that GLYX-13 may be of therapeutic value in the treatment of autism. PMID:23623884

Effects of prenatal dexamethasone treatment on physical growth, pituitary-adrenal hormones, and performance of motor, motivational, and cognitive tasks in juvenile and adolescent common marmoset monkeys.

PubMed

Hauser, Jonas; Knapman, Alana; Zürcher, Nicole R; Pilloud, Sonia; Maier, Claudia; Diaz-Heijtz, Rochellys; Forssberg, Hans; Dettling, Andrea; Feldon, Joram; Pryce, Christopher R

2008-12-01

Synthetic glucocorticoids such as dexamethasone (DEX) are commonly used to prevent respiratory distress syndrome in preterm infants, but there is emerging evidence of subsequent neurobehavioral abnormalities (e.g. problems with inattention/hyperactivity). In the present study, we exposed pregnant common marmosets (Callithrix jacchus, primates) to daily repeated DEX (5 mg/kg by mouth) during either early (d 42-48) or late (d 90-96) pregnancy (gestation period of 144 days). Relative to control, and with a longitudinal design, we investigated DEX effects in offspring in terms of physical growth, plasma ACTH and cortisol titers, social and maintenance behaviors, skilled motor reaching, motivation for palatable reward, and learning between infancy and adolescence. Early DEX resulted in reduced sociability in infants and increased motivation for palatable reward in adolescents. Late DEX resulted in a mild transient increase in knee-heel length in infants and enhanced reversal learning of stimulus-reward association in adolescents. There was no effect of either early or late DEX on basal plasma ACTH or cortisol titers. Both treatments resulted in impaired skilled motor reaching in juveniles, which attenuated in early DEX but persisted in late DEX across test sessions. The increased palatable-reward motivation and decreased social motivation observed in early DEX subjects provide experimental support for the clinical reports that prenatal glucocorticoid treatment impairs social development and predisposes to metabolic syndrome. These novel primate findings indicate that fetal glucocorticoid overexposure can lead to abnormal development of motor, affective, and cognitive behaviors. Importantly, the outcome is highly dependent upon the timing of glucocorticoid overexposure.

Oseltamivir use and severe abnormal behavior in Japanese children and adolescents with influenza: Is a self-controlled case series study applicable?

PubMed

Fukushima, Wakaba; Ozasa, Kotaro; Okumura, Akihisa; Mori, Masaaki; Hosoya, Mitsuaki; Nakano, Takashi; Tanabe, Takuya; Yamaguchi, Naoto; Suzuki, Hiroshi; Mori, Mitsuru; Hatayama, Hideaki; Ochiai, Hirotaka; Kondo, Kyoko; Ito, Kazuya; Ohfuji, Satoko; Nakamura, Yosikazu; Hirota, Yoshio

2017-08-24

Since the 1990s, self-controlled designs including self-controlled case series (SCCS) studies have been occasionally used in post-marketing evaluation of drug or vaccine safety. An SCCS study was tentatively applied to evaluate the relationship between oseltamivir use and abnormal behavior Type A (serious abnormal behavior potentially leading to an accident or harm to another person) in influenza patients. From the original prospective cohort study with approximately 10,000 Japanese children and adolescents with influenza (aged <18years), 28 subjects (mean age: 7.3years) who developed abnormal behavior Type A after the first visit to the collaborating hospitals/clinics were analyzed. We hypothesized four combination patterns of the effect period (i.e., the period that effect of oseltamivir on occurrence of abnormal behavior Type A is likely) and the control period. Mantel-Haenszel rate ratio (M-H RR) and its 95% confidence interval (CI) were calculated as the relative risk estimate. Among 28 subjects in the SCCS study, 24 subjects (86%) were administered oseltamivir and 4 subjects (14%) were not. Abnormal behavior Type A was more likely to occur in the effect period than the control period in every pattern (M-H RR: 1.90-29.1). We observed the highest estimate when the effect period was set between the initial intake of oseltamivir and T max (M-H RR: 29.1, 95% CI: 4.21-201). Abnormal behavior Type A was more likely to develop up to approximately 30 times during the period between the initial intake of oseltamivir and T max . However, this period overlapped with the early period of influenza where high fever was observed. Since useful approaches to control the influence of the natural disease course of influenza were not available in this study, we could not deny the possibility that abnormal behavior was induced by influenza itself. The SCCS study was not an optimal method to evaluate the relationship between oseltamivir use and abnormal behavior. Copyright © 2017 Elsevier Ltd. All rights reserved.

Lithium attenuated the depressant and anxiogenic effect of juvenile social stress through mitigating the negative impact of interlukin-1β and nitric oxide on hypothalamic-pituitary-adrenal axis function.

PubMed

Haj-Mirzaian, A; Amiri, S; Kordjazy, N; Momeny, M; Razmi, A; Rahimi-Balaei, M; Amini-Khoei, H; Haj-Mirzaian, A; Marzban, H; Mehr, S E; Ghaffari, S H; Dehpour, A R

2016-02-19

The neuroimmune-endocrine dysfunction has been accepted as one of fundamental mechanisms contributing to the pathophysiology of psychiatric disorders including depression and anxiety. In this study, we aimed to evaluate the involvement of hypothalamic-pituitary-adrenal (HPA) axis, interleukin-1β, and nitrergic system in mediating the negative behavioral impacts of juvenile social isolation stress (SIS) in male mice. We also investigated the possible protective effects of lithium on behavioral and neurochemical changes in socially isolated animals. Results showed that experiencing 4-weeks of juvenile SIS provoked depressive and anxiety-like behaviors that were associated with hyper responsiveness of HPA axis, upregulation of interleukin-1β, and nitric oxide (NO) overproduction in the pre-frontal cortex and hippocampus. Administration of lithium (10 mg/kg) significantly attenuated the depressant and anxiogenic effects of SIS in behavioral tests. Lithium also restored the negative effects of SIS on cortical and hippocampal interleukin-1β and NO as well as HPA axis deregulation. Unlike the neutralizing effects of l-arginine (NO precursor), administration of l-NAME (3 mg/kg) and aminoguanidine (20 mg/kg) potentiated the positive effects of lithium on the behavioral and neurochemical profile of isolated mice. In conclusion, our results revealed that juvenile SIS-induced behavioral deficits are associated with abnormalities in HPA-immune function. Also, we suggest that alleviating effects of lithium on behavioral profile of isolated mice may be partly mediated by mitigating the negative impact of NO on HPA-immune function. Copyright © 2015 IBRO. Published by Elsevier Ltd. All rights reserved.

Effect of one anesthetic exposure on long-term behavioral changes in children.

PubMed

Chemaly, Maen; El-Rajab, Mariam A; Ziade, Fouad M; Naja, Zoher M

2014-11-01

To determine the association between one anesthetic exposure and behavioral outcome at age 10 to 12 years. Retrospective comparative study. University-affiliated pediatrics department. The medical records of children who underwent anesthesia between January 2004 and December 2005 at our institution were reviewed. The records of 292 children were included in the study group and 300 children in the control group. The study group involved children who had one anesthetic exposure before age of 4 years and the control group had children who were not exposed to anesthesia. The primary outcome was behavioral change as assessed by the Eyberg Child Behavior Inventory (ECBI) questionnaire. The rate of behavioral abnormalities before the age of 11 years was 28.4% in the study group (P<0.001) and 5.7% in the control group. The risk of developing behavioral abnormalities was prominent in children being exposed to surgery versus those exposed during a diagnostic procedure (32.4% vs 4.8%; P<0.0001). Eighty-three point nine percent of the children who were exposed to longer duration anesthesia (more than 3 hrs) had behavioral abnormalities (P<0.0001), while 48.8% of children who received anesthesia at younger ages (0 - 6 mos) had behavioral abnormalities (P<0.0001). Exposure to multiple anesthetic agents versus one anesthetic agent was a significant risk factor for development of behavioral abnormalities (P<0.0001). The incidence of behavioral abnormalities increased when anesthesia and surgery were accompanied by younger age, longer duration of surgery, and use of multiple anesthetic agents. Copyright © 2014 Elsevier Inc. All rights reserved.

Role of Prefrontal Serotonergic and Dopaminergic Systems in Encounter-Induced Hyperactivity in Methamphetamine-Sensitized Mice.

PubMed

Tanaka, Tatsunori; Ago, Yukio; Umehara, Chiaki; Imoto, Emina; Hasebe, Shigeru; Hashimoto, Hitoshi; Takuma, Kazuhiro; Matsuda, Toshio

2017-05-01

Isolation-reared mice show social encounter-induced hyperactivity with activation of prefrontal serotonergic and dopaminergic systems, but it is not known whether this stress response is observed in other pathological conditions. Here we examined whether the social encounter stimulation induces abnormal behavior during withdrawal in chronic methamphetamine-treated mice. To induce methamphetamine-induced behavioral sensitization, male mice were injected with methamphetamine (1 mg/kg) once daily for 7 days. The encounter with an intruder elicited hyperactivity 24 h after the last injection of methamphetamine in methamphetamine-sensitized mice. This response was observed even as long as 2 weeks after withdrawal of methamphetamine. The encounter increased c-Fos expression in the prefrontal cortex, dorsal raphe nucleus and ventral tegmental area in methamphetamine-sensitized mice, while it did not in control mice. Furthermore, the encounter increased extracellular serotonin (5-HT) and dopamine, but not noradrenaline, levels in the prefrontal cortex in methamphetamine-sensitized mice. Local injection of 5,7-dihydroxytryptamine and 6-hydroxydopamine into the prefrontal cortex attenuated encounter-induced hyperactivity in methamphetamine-sensitized mice and it markedly decreased prefrontal 5-HT and dopamine levels, respectively. Pharmacological analysis showed that the encounter-induced hyperactivity is mediated by dopamine D1 receptors and 5-HT2A receptors and attenuated by anxiolytics and antidepressants such as diazepam, osemozotan and selective 5-HT reuptake inhibitors. The effect of paroxetine was blocked by the 5-HT3 receptor antagonist azasetron. The present study shows that psychological stress elicits hyperactivity with activation of prefrontal 5-HT and dopamine systems in methamphetamine-dependent mice and suggests that the abnormal behavior is associated with anxiety and depression. © The Author 2016. Published by Oxford University Press on behalf of CINP.

Promoting social plasticity in developmental disorders with non-invasive brain stimulation techniques

PubMed Central

Boggio, Paulo S.; Asthana, Manish K.; Costa, Thiago L.; Valasek, Cláudia A.; Osório, Ana A. C.

2015-01-01

Being socially connected directly impacts our basic needs and survival. People with deficits in social cognition might exhibit abnormal behaviors and face many challenges in our highly social-dependent world. These challenges and limitations are associated with a substantial economical and subjective impact. As many conditions where social cognition is affected are highly prevalent, more treatments have to be developed. Based on recent research, we review studies where non-invasive neuromodulatory techniques have been used to promote Social Plasticity in developmental disorders. We focused on three populations where non-invasive brain stimulation seems to be a promising approach in inducing social plasticity: Schizophrenia, Autism Spectrum Disorder (ASD) and Williams Syndrome (WS). There are still very few studies directly evaluating the effects of transcranial direct current stimulation (tDCS) and transcranial magnetic stimulation (TMS) in the social cognition of these populations. However, when considering the promising preliminary evidences presented in this review and the limited amount of clinical interventions available for treating social cognition deficits in these populations today, it is clear that the social neuroscientist arsenal may profit from non-invasive brain stimulation techniques for rehabilitation and promotion of social plasticity. PMID:26388712

Impaired self-awareness in human addiction: deficient attribution of personal relevance.

PubMed

Moeller, Scott J; Goldstein, Rita Z

2014-12-01

Compromised self-awareness of illness-related deficits and behaviors in psychopathology (e.g., schizophrenia) has been associated with deficient functioning of cortical midline regions including the ventromedial prefrontal cortex (vmPFC), implicated in personal relevance. Here, we review and critically analyze recent evidence to suggest that vmPFC abnormalities could similarly underlie deficient tagging of personal relevance in drug addiction, evidenced by a constellation of behaviors encompassing drug-biased attention, negative outcome insensitivity, self-report/behavior dissociation, and social inappropriateness. This novel framework might clarify, for example, why drug-addicted individuals often ruin long-standing relationships or forego important job opportunities while continuing to engage in uncontrolled drug-taking. Therapeutic interventions targeting personal relevance and associated vmPFC functioning could enhance self-awareness and facilitate more adaptive behavior in this chronically relapsing psychopathology. Copyright © 2014 Elsevier Ltd. All rights reserved.

Cognitive behavioral approach to understanding irritable bowel syndrome

PubMed Central

Hauser, Goran; Pletikosic, Sanda; Tkalcic, Mladenka

2014-01-01

Irritable bowel syndrome (IBS) is considered a biopsychosocial disorder, whose onset and precipitation are a consequence of interaction among multiple factors which include motility disturbances, abnormalities of gastrointestinal sensation, gut inflammation and infection, altered processing of afferent sensory information, psychological distress, and affective disturbances. Several models have been proposed in order to describe and explain IBS, each of them focusing on specific aspects or mechanisms of the disorder. This review attempts to present and discuss different determinants of IBS and its symptoms, from a cognitive behavioral therapy framework, distinguishing between the developmental predispositions and precipitants of the disorder, and its perpetuating cognitive, behavioral, affective and physiological factors. The main focus in understanding IBS will be placed on the numerous psychosocial factors, such as personality traits, early experiences, affective disturbances, altered attention and cognitions, avoidance behavior, stress, coping and social support. In conclusion, a symptom perpetuation model is proposed. PMID:24944466

Anatomical differences in the mirror neuron system and social cognition network in autism.

PubMed

Hadjikhani, Nouchine; Joseph, Robert M; Snyder, Josh; Tager-Flusberg, Helen

2006-09-01

Autism spectrum disorder (ASD) is a neurodevelopmental disorder associated with impaired social and emotional skills, the anatomical substrate of which is still unknown. In this study, we compared a group of 14 high-functioning ASD adults with a group of controls matched for sex, age, intelligence quotient, and handedness. We used an automated technique of analysis that accurately measures the thickness of the cerebral cortex and generates cross-subject statistics in a coordinate system based on cortical anatomy. We found local decreases of gray matter in the ASD group in areas belonging to the mirror neuron system (MNS), argued to be the basis of empathic behavior. Cortical thinning of the MNS was correlated with ASD symptom severity. Cortical thinning was also observed in areas involved in emotion recognition and social cognition. These findings suggest that the social and emotional deficits characteristic of autism may reflect abnormal thinning of the MNS and the broader network of cortical areas subserving social cognition.

Neural bases of eye and gaze processing: The core of social cognition

PubMed Central

Itier, Roxane J.; Batty, Magali

2014-01-01

Eyes and gaze are very important stimuli for human social interactions. Recent studies suggest that impairments in recognizing face identity, facial emotions or in inferring attention and intentions of others could be linked to difficulties in extracting the relevant information from the eye region including gaze direction. In this review, we address the central role of eyes and gaze in social cognition. We start with behavioral data demonstrating the importance of the eye region and the impact of gaze on the most significant aspects of face processing. We review neuropsychological cases and data from various imaging techniques such as fMRI/PET and ERP/MEG, in an attempt to best describe the spatio-temporal networks underlying these processes. The existence of a neuronal eye detector mechanism is discussed as well as the links between eye gaze and social cognition impairments in autism. We suggest impairments in processing eyes and gaze may represent a core deficiency in several other brain pathologies and may be central to abnormal social cognition. PMID:19428496

Gamma-band activity in the human superior temporal sulcus during mentalizing from nonverbal social cues.

PubMed

Cohen, Michael X; David, Nicole; Vogeley, Kai; Elger, Christian E

2009-01-01

The posterior superior temporal sulcus (pSTS) is a key structure for our ability to infer others' mental states based on social cues including facial expressions, body posture, and gestures ("mentalizing"), but the neural mechanisms of this ability remain largely unknown. We recorded electrocorticogram directly from the pSTS in humans to show that enhanced neural oscillations in the gamma frequency range (35-55 Hz) accompany mentalizing. One patient with a lesion in pSTS was tested behaviorally on this task; he was unable to infer a virtual character's preferences from nonverbal social cues. Enhanced coherent gamma oscillations in the patients with intact pSTS may reflect a process by which social signals are bound into a unified representation to support mentalizing. This may be relevant for other social cognitive processes, as well as to the study of autism spectrum disorders, for which both mentalizing deficits and abnormal gamma activity have been reported.

NMDA receptor agonists reverse impaired psychomotor and cognitive functions associated with hippocampal Hbegf-deficiency in mice.

PubMed

Sasaki, Keita; Omotuyi, Olaposi Idowu; Ueda, Mutsumi; Shinohara, Kazuyuki; Ueda, Hiroshi

2015-12-04

Structural and functional changes of the hippocampus are correlated with psychiatric disorders and cognitive dysfunctions. Genetic deletion of heparin-binding epidermal growth factor-like growth factor (HB-EGF), which is predominantly expressed in cortex and hippocampus, also causes similar psychiatric and cognitive dysfunctions, accompanying down-regulated NMDA receptor signaling. However, little is known of such dysfunctions in hippocampus-specific Hbegf cKO mice. We successfully developed hippocampus-specific cKO mice by crossbreeding floxed Hbegf and Gng7-Cre knock-in mice, as Gng7 promoter-driven Cre is highly expressed in hippocampal neurons as well as striatal medium spiny neurons. In mice lacking hippocampus Hbegf gene, there was a decreased neurogenesis in the subgranular zone (SGZ) of the dentate gyrus as well as down-regulation of PSD-95/NMDA-receptor-NR1/NR2B subunits and related NMDA receptor signaling. Psychiatric, social-behavioral and cognitive abnormalities were also observed in hippocampal cKO mice. Interestingly, D-cycloserine and nefiracetam, positive allosteric modulators (PAMs) of NMDA receptor reversed the apparent reduction in NMDA receptor signaling and most behavioral abnormalities. Furthermore, decreased SGZ neurogenesis in hippocampal cKO mice was reversed by nefiracetam. The present study demonstrates that PAMs of NMDA receptor have pharmacotherapeutic potentials to reverse down-regulated NMDA receptor signaling, neuro-socio-cognitive abnormalities and decreased neurogenesis in hippocampal cKO mice.

Periodic Limb Movements During Sleep Mimicking REM Sleep Behavior Disorder: A New Form of Periodic Limb Movement Disorder.

PubMed

Gaig, Carles; Iranzo, Alex; Pujol, Montserrat; Perez, Hernando; Santamaria, Joan

2017-03-01

To describe a group of patients referred because of abnormal sleep behaviors that were suggestive of rapid eye movement (REM) sleep behavior disorder (RBD) in whom video-polysomnography ruled out RBD and showed the reported behaviors associated with vigorous periodic limb movements during sleep (PLMS). Clinical history and video-polysomnography review of patients identified during routine visits in a sleep center. Patients were 15 men and 2 women with a median age of 66 (range: 48-77) years. Reported sleep behaviors were kicking (n = 17), punching (n = 16), gesticulating (n = 8), falling out of bed (n = 5), assaulting the bed partner (n = 2), talking (n = 15), and shouting (n = 10). Behaviors resulted in injuries in 3 bed partners and 1 patient. Twelve (70.6%) patients were not aware of displaying abnormal sleep behaviors that were only noticed by their bed partners. Ten (58.8%) patients recalled unpleasant dreams such as being attacked or chased. Video-polysomnography showed (1) frequent and vigorous stereotyped PLMS involving the lower limbs, upper limbs, and trunk (median PLMS index 61.2; median PLMS index in NREM sleep 61.9; during REM sleep only 8 patients had PLMS and their median PLMS index in REM sleep was 39.5); (2) abnormal behaviors (e.g., punching, groaning) during some of the arousals that immediately followed PLMS in NREM sleep; and (3) ruled out RBD and other sleep disorders such as obstructive sleep apnea. Dopaminergic agents were prescribed in 14 out of the 17 patients and resulted in improvement of abnormal sleep behaviors and unpleasant dreams in all of them. After dopaminergic treatment, follow-up video-polysomnography in 7 patients showed a decrease in the median PLMS index from baseline (108.9 vs. 19.2, p = .002) and absence of abnormal behaviors during the arousals. Abnormal sleep behaviors and unpleasant dreams simulating RBD symptomatology may occur in patients with severe PLMS. In these cases, video-polysomnography ruled out RBD and identified prominent PLMS followed by arousals containing abnormal behaviors. Our cases represent an objectively documented subtype of periodic limb movement disorder causing abnormal sleep behaviors. © Sleep Research Society 2016. Published by Oxford University Press on behalf of the Sleep Research Society. All rights reserved. For permissions, please e-mail journals.permissions@oup.com.

A clinical study of the effects of lead poisoning on the intelligence and neurobehavioral abilities of children.

PubMed

Hou, Shuangxing; Yuan, Lianfang; Jin, Pengpeng; Ding, Bojun; Qin, Na; Li, Li; Liu, Xuedong; Wu, Zhongliang; Zhao, Gang; Deng, Yanchun

2013-02-18

Lead is a heavy metal and important environmental toxicant and nerve poison that can destruction many functions of the nervous system. Lead poisoning is a medical condition caused by increased levels of lead in the body. Lead interferes with a variety of body processes and is toxic to many organs and issues, including the central nervous system. It interferes with the development of the nervous system, and is therefore particularly toxic to children, causing potentially permanent neural and cognitive impairments. In this study, we investigated the relationship between lead poisoning and the intellectual and neurobehavioral capabilities of children. The background characteristics of the research subjects were collected by questionnaire survey. Blood lead levels were detected by differential potentiometric stripping analysis (DPSA). Intelligence was assessed using the Gesell Developmental Scale. The Achenbach Child Behavior Checklist (CBCL) was used to evaluate each child's behavior. Blood lead levels were significantly negatively correlated with the developmental quotients of adaptive behavior, gross motor performance, fine motor performance, language development, and individual social behavior (P < 0.01). Compared with healthy children, more children with lead poisoning had abnormal behaviors, especially social withdrawal, depression, and atypical body movements, aggressions and destruction. Lead poisoning has adverse effects on the behavior and mental development of 2-4-year-old children, prescribing positive and effective precautionary measures.

Comprehensive Behavioral Phenotyping of Ts65Dn Mouse Model of Down Syndrome: Activation of β1-Adrenergic Receptor by Xamoterol as a Potential Cognitive Enhancer

PubMed Central

Faizi, Mehrdad; Bader, Patrick L.; Tun, Christine; Encarnacion, Angelo; Kleschevnikov, Alexander; Belichenko, Pavel; Saw, Nay; Priestley, Matthew; Tsien, Richard W; Mobley, William C; Shamloo, Mehrdad

2012-01-01

Down Syndrome (DS) is the most prevalent form of mental retardation caused by genetic abnormalities in humans. This has been successfully modeled in mice to generate the Ts65Dn mouse, a genetic model of DS. This transgenic mouse model shares a number of physical and functional abnormalities with people with DS, including changes in the structure and function of neuronal circuits. Significant abnormalities in noradrenergic (NE-ergic) afferents from the locus coeruleus to the hippocampus, as well as deficits in NE-ergic neurotransmission are detected in these animals. In the current study we characterized in detail the behavioral phenotype of Ts65Dn mice, in addition to using pharmacological tools for identification of target receptors mediating the learning and memory deficits observed in this model of DS. We undertook a comprehensive approach to mouse phenotyping using a battery of standard and novel tests encompassing: i) locomotion (Activity Chamber, PhenoTyper, and CatWalk), ii) learning and memory (spontaneous alternation, delayed matching-to-place water maze, fear conditioning, and Intellicage), and iii) social behavior. Ts65Dn mice showed increased locomotor activity in novel and home cage environments. There were significant and reproducible deficits in learning and memory tests including spontaneous alternation, delayed matching-to-place water maze, Intellicage place avoidance and contextual fear conditioning. Although Ts65Dn mice showed no deficit in sociability in the 3-chamber test, a marked impairment in social memory was detected. Xamoterol, a β1-adrenergic receptor (β1-ADR) agonist, effectively restored the memory deficit in contextual fear conditioning, spontaneous alternation and novel object recognition. These behavioral improvements were reversed by betaxolol, a selective β1-ADR antagonist. In conclusion, our results demonstrate that this mouse model of Down Syndrome display cognitive deficits which is mediated by imbalance in noradrenergic system. In this experimental model of Down Syndrome a selective activation of β1-ADR does restore some of these behavioral deficits. Further mechanistic studies will be needed to investigate the failure of noradrenergic system and the role of β1-ADR in cognitive deficit and pathogenesis of DS in people. Restoring NE neurotransmission or a selective activation of β1-ADR need to be further investigated for development of any potential therapeutic strategies for symptomatic relieve of memory deficit in DS. Furthermore, due to the significant involvement of noradrenergic system in the cardiovascular function further safety and translational studies will be needed to ensure the safety and efficacy of this approach. PMID:21527343

Neural abnormalities in early-onset and adolescence-onset conduct disorder.

PubMed

Passamonti, Luca; Fairchild, Graeme; Goodyer, Ian M; Hurford, Georgina; Hagan, Cindy C; Rowe, James B; Calder, Andrew J

2010-07-01

Conduct disorder (CD) is characterized by severe antisocial behavior that emerges in childhood (early-onset CD [EO-CD]) or adolescence (adolescence-onset CD [AO-CD]). Early-onset CD is proposed to have a neurodevelopmental basis, whereas AO-CD is thought to emerge owing to social mimicry of deviant peers. However, this developmental taxonomic theory is debated after reports of neuropsychological impairments in both CD subtypes. A critical, although unaddressed, issue is whether these subtypes present similar or distinct neurophysiological profiles. Hence, we investigated neurophysiological responses to emotional and neutral faces in regions associated with antisocial behavior (ie, the amygdala, ventromedial prefrontal cortex, insula, and orbitofrontal cortex) in individuals with EO-CD and AO-CD and in healthy control subjects. To investigate whether EO-CD and AO-CD subjects show neurophysiological abnormalities. Case-control study. Government research institute, university department. Seventy-five male adolescents and young adults aged 16 to 21 years, including 27 with EO-CD, 25 with AO-CD, and 23 healthy controls. Main Outcome Measure Neural activations measured by functional magnetic resonance imaging while participants viewed angry, sad, and neutral faces. Comparing angry vs neutral faces, participants with both CD subtypes displayed reduced responses in regions associated with antisocial behavior compared with controls; differences between the CD subtypes were not significant. Comparing each expression with fixation baseline revealed an abnormal (increased) amygdala response to neutral but not angry faces in both groups of CD relative to controls. For sad vs neutral faces, reduced amygdala activation was observed in EO-CD relative to AO-CD and control participants. Comparing each expression with fixation revealed hypoactive amygdala responses to sadness in individuals with EO-CD relative to AO-CD participants and controls. These findings were not accounted for by attention-deficit/hyperactivity disorder symptoms. Neurophysiological abnormalities are observed in both CD subtypes, contrary to the developmental taxonomic theory of CD. Additional amygdala hypofunction in relation to sad expressions might indicate why EO-CD is more severe and persistent than AO-CD.

Dysregulation of synaptic plasticity precedes appearance of morphological defects in a Pten conditional knockout mouse model of autism.

PubMed

Takeuchi, Koichi; Gertner, Michael J; Zhou, Jing; Parada, Luis F; Bennett, Michael V L; Zukin, R Suzanne

2013-03-19

The phosphoinositide signaling system is a crucial regulator of neural development, cell survival, and plasticity. Phosphatase and tensin homolog deleted on chromosome 10 (PTEN) negatively regulates phosphatidylinositol 3-kinase signaling and downstream targets. Nse-Cre Pten conditional knockout mice, in which Pten is ablated in granule cells of the dentate gyrus and pyramidal neurons of the hippocampal CA3, but not CA1, recapitulate many of the symptoms of humans with inactivating PTEN mutations, including progressive hypertrophy of the dentate gyrus and deficits in hippocampus-based social and cognitive behaviors. However, the impact of Pten loss on activity-dependent synaptic plasticity in this clinically relevant mouse model of Pten inactivation remains unclear. Here, we show that two phosphatidylinositol 3-kinase- and protein synthesis-dependent forms of synaptic plasticity, theta burst-induced long-term potentiation and metabotropic glutamate receptor (mGluR)-dependent long-term depression, are dysregulated at medial perforant path-to-dentate gyrus synapses of young Nse-Cre Pten conditional knockout mice before the onset of visible morphological abnormalities. In contrast, long-term potentiation and mGluR-dependent long-term depression are normal at CA3-CA1 pyramidal cell synapses at this age. Our results reveal that deletion of Pten in dentate granule cells dysregulates synaptic plasticity, a defect that may underlie abnormal social and cognitive behaviors observed in humans with Pten inactivating mutations and potentially other autism spectrum disorders.

A synaptic trek to autism.

PubMed

Bourgeron, Thomas

2009-04-01

Autism spectrum disorders (ASD) are diagnosed on the basis of three behavioral features namely deficits in social communication, absence or delay in language, and stereotypy. The susceptibility genes to ASD remain largely unknown, but two major pathways are emerging. Mutations in TSC1/TSC2, NF1, or PTEN activate the mTOR/PI3K pathway and lead to syndromic ASD with tuberous sclerosis, neurofibromatosis, or macrocephaly. Mutations in NLGN3/4, SHANK3, or NRXN1 alter synaptic function and lead to mental retardation, typical autism, or Asperger syndrome. The mTOR/PI3K pathway is associated with abnormal cellular/synaptic growth rate, whereas the NRXN-NLGN-SHANK pathway is associated with synaptogenesis and imbalance between excitatory and inhibitory currents. Taken together, these data strongly suggest that abnormal synaptic homeostasis represent a risk factor to ASD.

Communication, Interventions, and Scientific Advances in Autism: A Commentary

PubMed Central

Llaneza, Danielle C.; DeLuke, Susan V.; Batista, Myra; Crawley, Jacqueline N.; Christodulu, Kristin V.; Frye, Cheryl A.

2010-01-01

Autism spectrum disorders (ASD) affect approximately 1 in 150 children across the U.S., and are characterized by abnormal social actions, language difficulties, repetitive or restrictive behaviors, and special interests. ASD include autism (autistic disorder), Asperger syndrome, and Pervasive Developmental Disorder not otherwise specified (PDD-NOS or atypical autism). High-functioning individuals may communicate with moderate-to-high language skills, although difficulties in social skills may result in communication deficits. Low-functioning individuals may have severe deficiencies in language, resulting in poor communication between the individual and others. Behavioral intervention programs have been developed for ASD, and are frequently adjusted to accommodate specific individual needs. Many of these programs are school-based and aim to support the child in the development of their skills, for use outside the classroom with family and friends. Strides are being made in understanding the factors contributing to the development of ASD, particularly the genetic contributions that may underlie these disorders. Mutant mouse models provide powerful research tools to investigate the genetic factors associated with ASD and its co-morbid disorders. In support, the BTBR T+tf/J mouse strain incorporates ASD-like social and communication deficits and high levels of repetitive behaviors. This commentary briefly reviews the reciprocal relationship between observations made during evidence-based behavioral interventions of high- versus low-functioning children with ASD and the accumulating body of research in autism, including animal studies and basic research models. This reciprocity is one of the hallmarks of the scientific method, such that research may inform behavioral treatments, and observations made during treatment may inform subsequent research. PMID:20093134

Communication, interventions, and scientific advances in autism: a commentary.

PubMed

Llaneza, Danielle C; DeLuke, Susan V; Batista, Myra; Crawley, Jacqueline N; Christodulu, Kristin V; Frye, Cheryl A

2010-06-01

Autism spectrum disorders (ASD) affect approximately 1 in 150 children across the U.S., and are characterized by abnormal social actions, language difficulties, repetitive or restrictive behaviors, and special interests. ASD include autism (autistic disorder), Asperger Syndrome, and Pervasive Developmental Disorder not otherwise specified (PDD-NOS or atypical autism). High-functioning individuals may communicate with moderate-to-high language skills, although difficulties in social skills may result in communication deficits. Low-functioning individuals may have severe deficiencies in language, resulting in poor communication between the individual and others. Behavioral intervention programs have been developed for ASD, and are frequently adjusted to accommodate specific individual needs. Many of these programs are school-based and aim to support the child in the development of their skills, for use outside the classroom with family and friends. Strides are being made in understanding the factors contributing to the development of ASD, particularly the genetic contributions that may underlie these disorders. Mutant mouse models provide powerful research tools to investigate the genetic factors associated with ASD and its co-morbid disorders. In support, the BTBR T+tf/J mouse strain incorporates ASD-like social and communication deficits and high levels of repetitive behaviors. This commentary briefly reviews the reciprocal relationship between observations made during evidence-based behavioral interventions of high- versus low-functioning children with ASD and the accumulating body of research in autism, including animal studies and basic research models. This reciprocity is one of the hallmarks of the scientific method, such that research may inform behavioral treatments, and observations made during treatment may inform subsequent research. Copyright 2010 Elsevier Inc. All rights reserved.

Neonatal Exposure of Rats to Antidepressants Affects Behavioral Reactions to Novelty and Social Interactions in a Manner Analogous to Autistic Spectrum Disorders

PubMed Central

Rodriguez-Porcel, Federico; Green, Donald; Khatri, Nidhi; Harris, Sharonda Swilley; May, Warren L.; Lin, Rick C. S.; Paul, Ian A.

2011-01-01

We have demonstrated that neonatal exposure to selective serotonin reuptake inhibitors has lasting effects on behavior and serotonergic neurons in Long Evans rats. Hyperserotoninemia and altered sensory processing are reported in autistic spectrum disorders (ASD). We hypothesized that early life exposure to SSRIs alters sensory processing, disrupts responses to novelty and impairs social interactions in a manner similar to that observed in ASD. Male and female Long-Evans rat pups were administered citalopram, buproprion, fluoxetine, or saline from postnatal day (P) 8 to 21. Rats were tested for response to a novel tone before weaning (P25). Later, rats were tested 2× for response to a novel object (P39), and to a novel conspecific (P78, P101). In addition, rats were assessed for juvenile play behaviors (P32–P34) and later, we assessed sexual response to an estrus female in male rats (P153–184). Antidepressant exposure increased freezing after tone, diminished novel object exploration and reduced conspecific interaction up to 3× compared to saline exposed rats. Juvenile play was profoundly reduced in antidepressant-exposed males when compared to saline exposed groups. Exposure to the SSRIs, but not bupropion disrupted male sexual behaviors. Moreover, specific male responses to female proceptive behaviors were disrupted in SSRI, but not bupropion exposed rats. We conclude that neonatal exposure to antidepressants in rats results in sensory and social abnormalities that parallel many of those reported in ASD. PMID:21905242

[Neuropsychological models of autism spectrum disorders - behavioral evidence and functional imaging].

PubMed

Dziobek, Isabel; Bölte, Sven

2011-03-01

To review neuropsychological models of theory of mind (ToM), executive functions (EF), and central coherence (CC) as framework for cognitive abnormalities in autism spectrum disorders (ASD). Behavioral and functional imaging studies are described that assess social-cognitive, emotional, and executive functions as well as locally oriented perception in ASD. Impairments in ToM and EF as well as alterations in CC are frequently replicated phenomena in ASD. Especially problems concerning social perception and ToM have high explanatory value for clinical symptomatology. Brain activation patterns differ between individuals with and without ASD for ToM, EF, und CC functions. An approach focussing on reduced cortical connectivity seems to be increasingly favored over explanations focussing on single affected brain sites. A better understanding of the complexities of ASD in future research demands the integration of clinical, neuropsychological, functional imaging, and molecular genetics evidence. Weaknesses in ToM and EF as well as strengths in detail-focussed perception should be used for individual intervention planning.

Ambra1 Shapes Hippocampal Inhibition/Excitation Balance: Role in Neurodevelopmental Disorders.

PubMed

Nobili, Annalisa; Krashia, Paraskevi; Cordella, Alberto; La Barbera, Livia; Dell'Acqua, Maria Concetta; Caruso, Angela; Pignataro, Annabella; Marino, Ramona; Sciarra, Francesca; Biamonte, Filippo; Scattoni, Maria Luisa; Ammassari-Teule, Martine; Cecconi, Francesco; Berretta, Nicola; Keller, Flavio; Mercuri, Nicola Biagio; D'Amelio, Marcello

2018-02-27

Imbalances between excitatory and inhibitory synaptic transmission cause brain network dysfunction and are central to the pathogenesis of neurodevelopmental disorders. Parvalbumin interneurons are highly implicated in this imbalance. Here, we probed the social behavior and hippocampal function of mice carrying a haploinsufficiency for Ambra1, a pro-autophagic gene crucial for brain development. We show that heterozygous Ambra1 mice (Ambra +/- ) are characterized by loss of hippocampal parvalbumin interneurons, decreases in the inhibition/excitation ratio, and altered social behaviors that are solely restricted to the female gender. Loss of parvalbumin interneurons in Ambra1 +/- females is further linked to reductions of the inhibitory drive onto principal neurons and alterations in network oscillatory activity, CA1 synaptic plasticity, and pyramidal neuron spine density. Parvalbumin interneuron loss is underlined by increased apoptosis during the embryonic development of progenitor neurons in the medial ganglionic eminence. Together, these findings identify an Ambra1-dependent mechanism that drives inhibition/excitation imbalance in the hippocampus, contributing to abnormal brain activity reminiscent of neurodevelopmental disorders.

Oxytocin, vasopressin, and autism: is there a connection?

PubMed

Insel, T R; O'Brien, D J; Leckman, J F

1999-01-15

Autism is a poorly understood developmental disorder characterized by social impairment, communication deficits, and compulsive behavior. The authors review evidence from animal studies demonstrating that the nonapeptides, oxytocin and vasopressin, have unique effects on the normal expression of species-typical social behavior, communication, and rituals. Based on this evidence, they hypothesize that an abnormality in oxytocin or vasopressin neurotransmission may account for several features of autism. As autism appears to be a genetic disorder, mutations in the various peptide, peptide receptor, or lineage-specific developmental genes could lead to altered oxytocin or vasopressin neurotransmission. Many of these genes have been cloned and sequenced, and several polymorphisms have been identified. Recent gene targeting studies that alter expression of either the peptides or their receptors in the rodent brain partially support the autism hypothesis. While previous experience suggests caution in hypothesizing a cause or suggesting a treatment for autism, the available preclinical evidence with oxytocin and vasopressin recommends the need for clinical studies using gene scanning, pharmacological and neurobiological approaches.

Diagnosis and Management of Behavioral Variant Frontotemporal Dementia

PubMed Central

Pressman, Peter; Miller, Bruce L

2014-01-01

Frontotemporal dementia (FTD) was documented over a century ago. The last decade, however, has seen substantial changes in our conceptions of this increasingly recognized disorder. Different clinical variants have been delineated, the most common of which is the behavioral variant (bvFTD). Updated diagnostic criteria have been established. New histopathological findings and genetic etiologies have been discovered. Research continues to uncover molecular mechanisms by which abnormal proteins accumulate in degenerating brain tissue. Novel neuroimaging techniques suggest that functional networks are diminished in bvFTD that may be relevant to empathy and social behavior. Despite rapid advances in our understanding of bvFTD, the disease is still under-recognized and commonly misdiagnosed. The result is inappropriate patient care. Recognizing the various presentations of bvFTD and its histological and genetic subtypes may further diagnosis, treatment and research. PMID:24315411

Development of emotional and behavioral regulation in children born extremely preterm and very preterm: biological and social influences.

PubMed

Clark, Caron A C; Woodward, Lianne J; Horwood, L John; Moor, Stephanie

2008-01-01

This study describes the development of emotional and behavioral regulation in a regional cohort of children born extremely preterm (<28 weeks gestational age, n = 39), very preterm (<34 weeks gestational age, n = 56), and full term (n = 103). At 2 and 4 years, children born at younger gestational ages demonstrated poorer self-regulation across multiple contexts spanning observed interactions, formal cognitive testing, and parental report of child behavior at home. Among children born preterm, the 2 strongest predictors of impairments in self-regulation were the presence of moderate-to-severe cerebral white matter abnormalities on neonatal magnetic resonance and a less sensitive parenting style when children were aged 2 years. Findings support the importance of early neurological development and parenting for developing regulation in children born very preterm.

Social and Abnormal Psychology Textbooks: An Objective Analysis.

ERIC Educational Resources Information Center

Christopher, Andrew N.; Griggs, Richard A.; Hagans, Chad L.

2000-01-01

Provides feature and content analyses of 14 social and 17 abnormal psychology full-length textbooks from 1995-98 that are available for undergraduate psychology courses. Provides instructors of these courses a means for more informed text selection. (CMK)

Administration of thimerosal-containing vaccines to infant rhesus macaques does not result in autism-like behavior or neuropathology.

PubMed

Gadad, Bharathi S; Li, Wenhao; Yazdani, Umar; Grady, Stephen; Johnson, Trevor; Hammond, Jacob; Gunn, Howard; Curtis, Britni; English, Chris; Yutuc, Vernon; Ferrier, Clayton; Sackett, Gene P; Marti, C Nathan; Young, Keith; Hewitson, Laura; German, Dwight C

2015-10-06

Autism spectrum disorder (ASD) is a complex neurodevelopmental disorder. Some anecdotal reports suggest that ASD is related to exposure to ethyl mercury, in the form of the vaccine preservative, thimerosal, and/or receiving the measles, mumps, rubella (MMR) vaccine. Using infant rhesus macaques receiving thimerosal-containing vaccines (TCVs) following the recommended pediatric vaccine schedules from the 1990s and 2008, we examined behavior, and neuropathology in three brain regions found to exhibit neuropathology in postmortem ASD brains. No neuronal cellular or protein changes in the cerebellum, hippocampus, or amygdala were observed in animals following the 1990s or 2008 vaccine schedules. Analysis of social behavior in juvenile animals indicated that there were no significant differences in negative behaviors between animals in the control and experimental groups. These data indicate that administration of TCVs and/or the MMR vaccine to rhesus macaques does not result in neuropathological abnormalities, or aberrant behaviors, like those observed in ASD.

Administration of thimerosal-containing vaccines to infant rhesus macaques does not result in autism-like behavior or neuropathology

PubMed Central

Gadad, Bharathi S.; Li, Wenhao; Yazdani, Umar; Grady, Stephen; Johnson, Trevor; Hammond, Jacob; Gunn, Howard; Curtis, Britni; English, Chris; Yutuc, Vernon; Ferrier, Clayton; Sackett, Gene P.; Marti, C. Nathan; Young, Keith; Hewitson, Laura; German, Dwight C.

2015-01-01

Autism spectrum disorder (ASD) is a complex neurodevelopmental disorder. Some anecdotal reports suggest that ASD is related to exposure to ethyl mercury, in the form of the vaccine preservative, thimerosal, and/or receiving the measles, mumps, rubella (MMR) vaccine. Using infant rhesus macaques receiving thimerosal-containing vaccines (TCVs) following the recommended pediatric vaccine schedules from the 1990s and 2008, we examined behavior, and neuropathology in three brain regions found to exhibit neuropathology in postmortem ASD brains. No neuronal cellular or protein changes in the cerebellum, hippocampus, or amygdala were observed in animals following the 1990s or 2008 vaccine schedules. Analysis of social behavior in juvenile animals indicated that there were no significant differences in negative behaviors between animals in the control and experimental groups. These data indicate that administration of TCVs and/or the MMR vaccine to rhesus macaques does not result in neuropathological abnormalities, or aberrant behaviors, like those observed in ASD. PMID:26417083

Epigenetic modification of OXT and human sociability.

PubMed

Haas, Brian W; Filkowski, Megan M; Cochran, R Nick; Denison, Lydia; Ishak, Alexandra; Nishitani, Shota; Smith, Alicia K

2016-07-05

Across many mammalian species there exist genetic and biological systems that facilitate the tendency to be social. Oxytocin is a neuropeptide involved in social-approach behaviors in humans and others mammals. Although there exists a large, mounting body of evidence showing that oxytocin signaling genes are associated with human sociability, very little is currently known regarding the way the structural gene for oxytocin (OXT) confers individual differences in human sociability. In this study, we undertook a comprehensive approach to investigate the association between epigenetic modification of OXT via DNA methylation, and overt measures of social processing, including self-report, behavior, and brain function and structure. Genetic data were collected via saliva samples and analyzed to target and quantify DNA methylation across the promoter region of OXT We observed a consistent pattern of results across sociability measures. People that exhibit lower OXT DNA methylation (presumably linked to higher OXT expression) display more secure attachment styles, improved ability to recognize emotional facial expressions, greater superior temporal sulcus activity during two social-cognitive functional MRI tasks, and larger fusiform gyrus gray matter volume than people that exhibit higher OXT DNA methylation. These findings provide empirical evidence that epigenetic modification of OXT is linked to several overt measures of sociability in humans and serve to advance progress in translational social neuroscience research toward a better understanding of the evolutionary and genetic basis of normal and abnormal human sociability.

Adolescents with a history of specific language impairment (SLI): strengths and difficulties in social, emotional and behavioral functioning.

PubMed

Conti-Ramsden, Gina; Mok, Pearl L H; Pickles, Andrew; Durkin, Kevin

2013-11-01

Adolescents with specific language impairment (SLI) are at a greater risk of emotional and behavioral problems compared to their typically developing (TD) peers, but little is known about their self-perceived strengths and difficulties. In this study, the self-reported social, emotional and behavioral functioning of 139 adolescents with a history of SLI and 124 TD individuals at age 16 was examined. The self-report version of the Strengths and Difficulties Questionnaire (SDQ) was used to assess their prosocial behavior and levels of peer, emotional and behavioral difficulties. Associations of these areas of functioning with gender, verbal and non-verbal skills were also investigated. Adolescents with a history of SLI were more likely than their TD peers to report higher levels of peer problems, emotional symptoms, hyperactivity and conduct problems. The majority of adolescents in both groups (87% SLI and 96% TD), however, reported prosocial behavior within the typical range. Difficulty with peer relations was the strongest differentiator between the groups, with the odds of reporting borderline or abnormally high levels of peer problems being 12 times higher for individuals with a history of SLI. Adolescents with poorer receptive language skills were also more likely to report higher levels of emotional and behavioral difficulties. The findings of this study identify likely traits that may lead to referral to services. Copyright © 2013 The Authors. Published by Elsevier Ltd.. All rights reserved.

Detection of Structural Abnormalities Using Neural Nets

NASA Technical Reports Server (NTRS)

Zak, M.; Maccalla, A.; Daggumati, V.; Gulati, S.; Toomarian, N.

1996-01-01

This paper describes a feed-forward neural net approach for detection of abnormal system behavior based upon sensor data analyses. A new dynamical invariant representing structural parameters of the system is introduced in such a way that any structural abnormalities in the system behavior are detected from the corresponding changes to the invariant.

Freud Was Right. . . about the Origins of Abnormal Behavior

ERIC Educational Resources Information Center

Muris, Peter

2006-01-01

Freud's psychodynamic theory is predominantly based on case histories of patients who displayed abnormal behavior. From a scientific point of view, Freud's analyses of these cases are unacceptable because the key concepts of his theory cannot be tested empirically. However, in one respect, Freud was totally right: most forms of abnormal behavior…

Serotonin Neuron Abnormalities in the BTBR Mouse Model of Autism

PubMed Central

Guo, Yue-Ping; Commons, Kathryn G.

2017-01-01

The inbred mouse strain BTBR T+ Itpr3tf/J (BTBR) i studied as a model of idiopathic autism because they are less social and more resistant to change than other strains. Forebrain serotonin receptors and the response to serotonin drugs are altered in BTBR mice, yet it remains unknown if serotonin neurons themselves are abnormal. In this study, we found that serotonin tissue content and the density of serotonin axons is reduced in the hippocampus of BTBR mice in comparison to C57BL/6J (C57) mice. This was accompanied by possible compensatory changes in serotonin neurons that were most pronounced in regions known to provide innervation to the hippocampus: the caudal dorsal raphe (B6) and the median raphe. These changes included increased numbers of serotonin neurons and hyperactivation of Fos expression. Metrics of serotonin neurons in the rostral 2/3 of the dorsal raphe and serotonin content of the prefrontal cortex were less impacted. Thus, serotonin neurons exhibit region-dependent abnormalities in the BTBR mouse that may contribute to their altered behavioral profile. PMID:27478061

Mixed Pattern Matching-Based Traffic Abnormal Behavior Recognition

PubMed Central

Cui, Zhiming; Zhao, Pengpeng

2014-01-01

A motion trajectory is an intuitive representation form in time-space domain for a micromotion behavior of moving target. Trajectory analysis is an important approach to recognize abnormal behaviors of moving targets. Against the complexity of vehicle trajectories, this paper first proposed a trajectory pattern learning method based on dynamic time warping (DTW) and spectral clustering. It introduced the DTW distance to measure the distances between vehicle trajectories and determined the number of clusters automatically by a spectral clustering algorithm based on the distance matrix. Then, it clusters sample data points into different clusters. After the spatial patterns and direction patterns learned from the clusters, a recognition method for detecting vehicle abnormal behaviors based on mixed pattern matching was proposed. The experimental results show that the proposed technical scheme can recognize main types of traffic abnormal behaviors effectively and has good robustness. The real-world application verified its feasibility and the validity. PMID:24605045

Psychological distress, social withdrawal, and coping following receipt of an abnormal mammogram among different ethnicities: a mediation model.

PubMed

Molina, Yamile; Beresford, Shirley A A; Espinoza, Noah; Thompson, Beti

2014-09-01

To explore ethnic differences in psychological distress and social withdrawal after receiving an abnormal mammogram result and to assess if coping strategies mediate ethnic differences. Descriptive correlational. Two urban mobile mammography units and a rural community hospital in the state of Washington. 41 Latina and 41 non-Latina Caucasian (NLC) women who had received an abnormal mammogram result. Women completed standard sociodemographic questions, Impact of Event Scale-Revised, the social dimension of the Psychological Consequences Questionnaire, and the Brief COPE. Ethnicity, psychological distress, social withdrawal, and coping. Latinas experienced greater psychological distress and social withdrawal compared to NLC counterparts. Denial as a coping strategy mediated ethnic differences in psychological distress. Religious coping mediated ethnic differences in social withdrawal. Larger population-based studies are necessary to understand how ethnic differences in coping strategies can influence psychological outcomes. This is an important finding that warrants additional study among women who are and are not diagnosed with breast cancer following an abnormal mammogram. Nurses may be able to work with Latina patients to diminish denial coping and consequent distress. Nurses may be particularly effective, given cultural values concerning strong interpersonal relationships and respect for authority figures.

Dissemination of an evidence-based intervention to parents of children with behavioral problems in a developing country.

PubMed

Fayyad, John A; Farah, Lynn; Cassir, Youmna; Salamoun, Mariana M; Karam, Elie G

2010-08-01

This project describes the dissemination of an evidence-based parenting skills intervention by training social and health workers with little or no mental health background so that they themselves train mothers of children with behavioral problems in impoverished communities in a developing country. The Strengths and Difficulties Questionnaire was completed by mothers to screen for children with behavioral problems and was repeated at the end of the intervention. Pre- and post-tests of knowledge and parenting attitudes were administered to mothers. Mental health workers trained social and health workers in social development centers and dispensaries. Each social and health worker trained mothers of children with behavioral problems under supervision utilizing an Arabic adaptation of the treatment manual for externalizing disorders "Helping Challenging Children" developed by the Integrated Services Taskforce of the World Psychiatric Association Child Mental Health Presidential Programme. A total of 20 workers and 87 mothers participated in the training. The proportion of children who obtained an SDQ total difficulties score in the abnormal range decreased from 54.4 to 19.7% after the training. Whereas 40.2% of mothers used severe corporal punishment with their children before the intervention, this decreased to 6.1% post-intervention. Three-fourths of mothers related that the program helped them develop new parenting skills. This pilot project demonstrated the feasibility of dissemination of a manual-based intervention and training of workers who have little background in mental health to offer effective services to families in impoverished communities who otherwise would have not received them. Successful replication in other developing countries would pave the way to incorporating such programs in national policies given their potential sustainability and cost-effectiveness.

Neurobehavioral Abnormalities in First-Degree Relatives of Individuals With Autism

PubMed Central

Mosconi, Matthew W.; Kay, Margaret; D’Cruz, Anna-Maria; Guter, Stephen; Kapur, Kush; Macmillan, Carol; Stanford, Lisa D.; Sweeney, John A.

2011-01-01

Context Studying sensorimotor and neurocognitive impairments in unaffected family members of individuals with autism may help identify familial pathophysiological mechanisms associated with the disorder. Objective To determine whether atypical sensorimotor or neurocognitive characteristics associated with autism are present in first-degree relatives of individuals with autism. Design Case-control comparison of neurobehavioral functions. Setting University medical center. Participants Fifty-seven first-degree relatives of individuals with autism and 40 age-, sex-, and IQ-matched healthy control participants (aged 8–54 years). Main Outcome Measures Oculomotor tests of sensorimotor responses (saccades and smooth pursuit); procedural learning and response inhibition; neuropsychological tests of motor, memory, and executive functions; and psychological measures of social behavior, communication skills, and obsessive-compulsive behaviors. Results On eye movement testing, family members demonstrated saccadic hypometria, reduced steady-state pursuit gain, and a higher rate of voluntary response inhibition errors relative to controls. They also showed lateralized deficits in procedural learning and open-loop pursuit gain (initial 100 milliseconds of pursuit) and increased variability in the accuracy of large-amplitude saccades that were confined to rightward movements. In neuropsychological studies, only executive functions were impaired relative to those of controls. Family members reported more communication abnormalities and obsessive-compulsive behaviors than controls. Deficits across oculomotor, neuropsychological, and psychological domains were relatively independent from one another. Conclusions Family members of individuals with autism demonstrate oculomotor abnormalities implicating pontocerebellar and frontostriatal circuits and left-lateralized alterations of frontotemporal circuitry and striatum. The left-lateralized alterations have not been identified in other neuropsychiatric disorders and are of interest given atypical brain lateralization and language development associated with the disorder. Similar oculomotor deficits have been reported in individuals with autism, suggesting that they may be familial and useful for studies of neurophysiological and genetic mechanisms in autism. PMID:20679591

Affective mentalizing and brain activity at rest in the behavioral variant of frontotemporal dementia.

PubMed

Caminiti, Silvia P; Canessa, Nicola; Cerami, Chiara; Dodich, Alessandra; Crespi, Chiara; Iannaccone, Sandro; Marcone, Alessandra; Falini, Andrea; Cappa, Stefano F

2015-01-01

bvFTD patients display an impairment in the attribution of cognitive and affective states to others, reflecting GM atrophy in brain regions associated with social cognition, such as amygdala, superior temporal cortex and posterior insula. Distinctive patterns of abnormal brain functioning at rest have been reported in bvFTD, but their relationship with defective attribution of affective states has not been investigated. To investigate the relationship among resting-state brain activity, gray matter (GM) atrophy and the attribution of mental states in the behavioral variant of fronto-temporal degeneration (bvFTD). We compared 12 bvFTD patients with 30 age- and education-matched healthy controls on a) performance in a task requiring the attribution of affective vs. cognitive mental states; b) metrics of resting-state activity in known functional networks; and c) the relationship between task-performances and resting-state metrics. In addition, we assessed a connection between abnormal resting-state metrics and GM atrophy. Compared with controls, bvFTD patients showed a reduction of intra-network coherent activity in several components, as well as decreased strength of activation in networks related to attentional processing. Anomalous resting-state activity involved networks which also displayed a significant reduction of GM density. In patients, compared with controls, higher affective mentalizing performance correlated with stronger functional connectivity between medial prefrontal sectors of the default-mode and attentional/performance monitoring networks, as well as with increased coherent activity in components of the executive, sensorimotor and fronto-limbic networks. Some of the observed effects may reflect specific compensatory mechanisms for the atrophic changes involving regions in charge of affective mentalizing. The analysis of specific resting-state networks thus highlights an intermediate level of analysis between abnormal brain structure and impaired behavioral performance in bvFTD, reflecting both dysfunction and compensation mechanisms.

Abnormal transsulfuration metabolism and reduced antioxidant capacity in Chinese children with autism spectrum disorders.

PubMed

Han, Yu; Xi, Qian-qian; Dai, Wei; Yang, Shu-han; Gao, Lei; Su, Yuan-yuan; Zhang, Xin

2015-11-01

Autism spectrum disorder (ASD) is a neurological disorder that presents a spectrum of qualitative impairments in social interaction, communication, as well as restricted and stereotyped behavioral patterns, interests, and activities. Several studies have suggested that the etiology of ASD can be partly explained by oxidative stress. However, the implications of abnormal transsulfuration metabolism and oxidative stress, and their relation with ASD are still unclear. The purpose of this study was to evaluate several transsulfuration pathway metabolites in Chinese participants diagnosed with ASD, to better understand their role in the etiology of this disorder. Fifty children (39 male, 11 female) diagnosed with ASD and 50 age- and gender-matched non-ASD children (i.e., control group) were included in this study. This prospective blinded study was undertaken to assess transsulfuration and oxidative metabolites, including levels of homocysteine (Hcy), cysteine (Cys), total glutathione (tGSH), reduced glutathione (GSH), oxidized glutathione (GSSG), and glutathione ratio (GSH/GSSG). The clinical severity of ASD was evaluated with the Childhood Autism Rating Scale (CARS), and the autistic children's present behavior was measured by the Autism Behavior Checklist (ABC). The results indicated that Hcy and GSSG levels were significantly higher in children diagnosed with ASD, Cys, tGSH and GSH levels as well as the GSH/GSSG ratio showed remarkably lower values in ASD children compared to control subjects. Hcy levels correlated significantly with increasing CARS scores and GSSG levels in children with ASD. Our results suggest that an abnormal transsulfuration metabolism and reduced antioxidant capacity (i.e., hyperhomocysteinemia and increased oxidative stress), and Hcy level appears to have a potentially negative impact on clinical severity of autistic disorder. Copyright © 2015 Elsevier Ltd. All rights reserved.

Neurobehavioral abnormalities in first-degree relatives of individuals with autism.

PubMed

Mosconi, Matthew W; Kay, Margaret; D'Cruz, Anna-Maria; Guter, Stephen; Kapur, Kush; Macmillan, Carol; Stanford, Lisa D; Sweeney, John A

2010-08-01

Studying sensorimotor and neurocognitive impairments in unaffected family members of individuals with autism may help identify familial pathophysiological mechanisms associated with the disorder. To determine whether atypical sensorimotor or neurocognitive characteristics associated with autism are present in first-degree relatives of individuals with autism. Case-control comparison of neurobehavioral functions. University medical center. Fifty-seven first-degree relatives of individuals with autism and 40 age-, sex-, and IQ-matched healthy control participants (aged 8-54 years). Oculomotor tests of sensorimotor responses (saccades and smooth pursuit); procedural learning and response inhibition; neuropsychological tests of motor, memory, and executive functions; and psychological measures of social behavior, communication skills, and obsessive-compulsive behaviors. On eye movement testing, family members demonstrated saccadic hypometria, reduced steady-state pursuit gain, and a higher rate of voluntary response inhibition errors relative to controls. They also showed lateralized deficits in procedural learning and open-loop pursuit gain (initial 100 milliseconds of pursuit) and increased variability in the accuracy of large-amplitude saccades that were confined to rightward movements. In neuropsychological studies, only executive functions were impaired relative to those of controls. Family members reported more communication abnormalities and obsessive-compulsive behaviors than controls. Deficits across oculomotor, neuropsychological, and psychological domains were relatively independent from one another. Family members of individuals with autism demonstrate oculomotor abnormalities implicating pontocerebellar and frontostriatal circuits and left-lateralized alterations of frontotemporal circuitry and striatum. The left-lateralized alterations have not been identified in other neuropsychiatric disorders and are of interest given atypical brain lateralization and language development associated with the disorder. Similar oculomotor deficits have been reported in individuals with autism, suggesting that they may be familial and useful for studies of neurophysiological and genetic mechanisms in autism.

Negative visuospatial priming in isolation-reared rats: Evidence of resistance to the disruptive effects of amphetamine

PubMed Central

Amitai, Nurith; Powell, Susan; Weber, Martin; Swerdlow, Neal R.

2015-01-01

Negative visuospatial priming (NP) represents a quantifiable measure of inhibitory information processing that is disrupted in several neurodevelopmental and psychiatric disorders, including schizophrenia. We developed a novel rodent NP task to investigate mechanisms underlying NP and its role in various disorders, and to test potential therapeutics. In the present studies, we further characterized this novel paradigm by investigating whether NP is disrupted in rats reared in isolation, a developmental manipulation that produces a range of abnormalities in behavior, neurochemistry, and brain structure that mirror aspects of schizophrenia pathology. We also further explored the role of monoaminergic signaling in NP and the effects of isolation rearing by challenging both socially reared and isolation-reared rats with D-amphetamine during the NP task. Although fewer isolation-reared animals learned the complex NP task, those that learned exhibited unaffected NP compared with socially reared rats. Consistent with previous reports, D-amphetamine impaired NP and increased motor impulsivity in socially reared rats. In contrast, D-amphetamine did not affect NP or motor impulsivity in isolation-reared rats. These data confirm a monoaminergic influence on NP behavior and indicate that rats reared in isolation have altered dopaminergic sensitivity. PMID:26220402

Rescue of fragile X syndrome phenotypes in Fmr1 KO mice by a BKCa channel opener molecule

PubMed Central

2014-01-01

Background Fragile X Syndrome (FXS) is the most common form of inherited intellectual disability and is also associated with autism spectrum disorders. Previous studies implicated BKCa channels in the neuropathogenesis of FXS, but the main question was whether pharmacological BKCa stimulation would be able to rescue FXS neurobehavioral phenotypes. Methods and results We used a selective BKCa channel opener molecule (BMS-204352) to address this issue in Fmr1 KO mice, modeling the FXS pathophysiology. In vitro, acute BMS-204352 treatment (10 μM) restored the abnormal dendritic spine phenotype. In vivo, a single injection of BMS-204352 (2 mg/kg) rescued the hippocampal glutamate homeostasis and the behavioral phenotype. Indeed, disturbances in social recognition and interaction, non-social anxiety, and spatial memory were corrected by BMS-204352 in Fmr1 KO mice. Conclusion These results demonstrate that the BKCa channel is a new therapeutic target for FXS. We show that BMS-204352 rescues a broad spectrum of behavioral impairments (social, emotional and cognitive) in an animal model of FXS. This pharmacological molecule might open new ways for FXS therapy. PMID:25079250

Effects of Acute Prenatal Exposure to Ethanol on microRNA Expression are Ameliorated by Social Enrichment

PubMed Central

Ignacio, Cherry; Mooney, Sandra M.; Middleton, Frank A.

2014-01-01

Fetal alcohol spectrum disorders (FASDs) are associated with abnormal social behavior. These behavioral changes may resemble those seen in autism. Rats acutely exposed to ethanol on gestational day 12 show decreased social motivation at postnatal day 42. We previously showed that housing these ethanol-exposed rats with non-exposed controls normalized this deficit. The amygdala is critical for social behavior and regulates it, in part, through connections with the basal ganglia, particularly the ventral striatum. MicroRNAs (miRNAs) are short, hairpin-derived RNAs that repress mRNA expression. Many brain disorders, including FASD, show dysregulation of miRNAs. In this study, we tested if miRNA and mRNA networks are altered in the amygdala and ventral striatum as a consequence of prenatal ethanol exposure and show any evidence of reversal as a result of social enrichment. RNA samples from two different brain regions in 72 male and female adolescent rats were analyzed by RNA-Seq and microarray analysis. Several miRNAs showed significant changes due to prenatal ethanol exposure and/or social enrichment in one or both brain regions. The top predicted gene targets of these miRNAs were mapped and subjected to pathway enrichment analysis. Several miRNA changes caused by ethanol were reversed by social enrichment, including mir-204, mir-299a, miR-384-5p, miR-222-3p, miR-301b-3p, and mir-6239. Moreover, enriched gene networks incorporating the targets of these miRNAs also showed reversal. We also extended our previously published mRNA expression analysis by directly examining all annotated brain-related canonical pathways. The additional pathways that were most strongly affected at the mRNA level included p53, CREB, glutamate, and GABA signaling. Together, our data suggest a number of novel epigenetic mechanisms for social enrichment to reverse the effects of ethanol exposure through widespread influences on gene expression. PMID:25309888

Studying the neurobiology of human social interaction: Making the case for ecological validity.

PubMed

Hogenelst, Koen; Schoevers, Robert A; aan het Rot, Marije

2015-01-01

With this commentary we make the case for an increased focus on the ecological validity of the measures used to assess aspects of human social functioning. Impairments in social functioning are seen in many types of psychopathology, negatively affecting the lives of psychiatric patients and those around them. Yet the neurobiology underlying abnormal social interaction remains unclear. As an example of human social neuroscience research with relevance to biological psychiatry and clinical psychopharmacology, this commentary discusses published experimental studies involving manipulation of the human brain serotonin system that included assessments of social behavior. To date, these studies have mostly been laboratory-based and included computer tasks, observations by others, or single-administration self-report measures. Most laboratory measures used so far inform about the role of serotonin in aspects of social interaction, but the relevance for real-life interaction is often unclear. Few studies have used naturalistic assessments in real life. We suggest several laboratory methods with high ecological validity as well as ecological momentary assessment, which involves intensive repeated measures in naturalistic settings. In sum, this commentary intends to stimulate experimental research on the neurobiology of human social interaction as it occurs in real life.

Can Decision Making Research Provide a Better Understanding of Chemical and Behavioral Addictions?

PubMed

Engel, Anzhelika; Cáceda, Ricardo

2015-01-01

We reviewed the cognitive and neurobiological commonalities between chemical and behavioral addictions. Poor impulse control, limited executive function and abnormalities in reward processing are seen in both group of entities. Brain imaging shows consistent abnormalities in frontoparietal regions and the limbic system. In drug addiction, exaggerated risk taking behavior and temporal discounting may reflect an imbalance between a hyperactive mesolimbic and hypoactive executive systems. Several cognitive distortions are found in pathological gambling that seems to harness the brain reward system that has evolved to face situations related to skill, not random chance. Abnormalities in risk assessment and impulsivity are found in variety of eating disorders, in particularly related to eating behavior. Corresponding findings in eating disorder patients include abnormalities in the limbic system, i.e. orbitofrontal cortex (OFC), striatum and insula. Similarly, internet addiction disorder is associated with risky decision making and increased choice impulsivity with corresponding discrepant activation in the dorsolateral prefrontal cortex, OFC, anterior cingulate cortex, caudate and insula. Sexual addictions are in turn associated with exaggerated impulsive choice and suggestive evidence of abnormalities in reward processing. In sum, exploration of executive function and decision making abnormalities in chemical and behavioral addictions may increase understanding in their psychopathology and yield valuable targets for therapeutic interventions.

The right cerebral hemisphere: emotion, music, visual-spatial skills, body-image, dreams, and awareness.

PubMed

Joseph, R

1988-09-01

Based on a review of numerous studies conducted on normal, neurosurgical and brain-injured individuals, the right cerebral hemisphere appears to be dominant in the perception and identification of environmental and nonverbal sounds; the analysis of geometric and visual space (e.g., depth perception, visual closure); somesthesis, stereognosis, the maintenance of the body image; the production of dreams during REM sleep; the perception of most aspects of musical stimuli; and the comprehension and expression of prosodic, melodic, visual, facial, and verbal emotion. When the right hemisphere is damaged a variety of cognitive abnormalities may result, including hemi-inattention and neglect, prosopagnosia, constructional apraxia, visual-perceptual disturbances, and agnosia for environmental, musical, and emotional sounds. Similarly, a myriad of affective abnormalities may occur, including indifference, depression, hysteria, gross social-emotional disinhibition, florid manic excitement, childishness, euphoria, impulsivity, and abnormal sexual behavior. Patients may become delusional, engage in the production of bizzare confabulations and experience a host of somatic disturbances such as pain and body-perceptual distortions. Based on studies of normal and "split-brain" functioning, it also appears that the right hemisphere maintains a highly developed social-emotional mental system and can independently perceive, recall and act on certain memories and experiences without the aid or active reflective participation of the left. This leads to situations in which the right and left halves of the brain sometime act in an uncooperative fashion, which gives rise to inter-manual and intra-psychic conflicts.

Feedforward and feedback motor control abnormalities implicate cerebellar dysfunctions in autism spectrum disorder.

PubMed

Mosconi, Matthew W; Mohanty, Suman; Greene, Rachel K; Cook, Edwin H; Vaillancourt, David E; Sweeney, John A

2015-02-04

Sensorimotor abnormalities are common in autism spectrum disorder (ASD) and among the earliest manifestations of the disorder. They have been studied far less than the social-communication and cognitive deficits that define ASD, but a mechanistic understanding of sensorimotor abnormalities in ASD may provide key insights into the neural underpinnings of the disorder. In this human study, we examined rapid, precision grip force contractions to determine whether feedforward mechanisms supporting initial motor output before sensory feedback can be processed are disrupted in ASD. Sustained force contractions also were examined to determine whether reactive adjustments to ongoing motor behavior based on visual feedback are altered. Sustained force was studied across multiple force levels and visual gains to assess motor and visuomotor mechanisms, respectively. Primary force contractions of individuals with ASD showed greater peak rate of force increases and large transient overshoots. Individuals with ASD also showed increased sustained force variability that scaled with force level and was more severe when visual gain was highly amplified or highly degraded. When sustaining a constant force level, their reactive adjustments were more periodic than controls, and they showed increased reliance on slower feedback mechanisms. Feedforward and feedback mechanism alterations each were associated with more severe social-communication impairments in ASD. These findings implicate anterior cerebellar circuits involved in feedforward motor control and posterior cerebellar circuits involved in transforming visual feedback into precise motor adjustments in ASD. Copyright © 2015 the authors 0270-6474/15/352015-11$15.00/0.

Autism-relevant social abnormalities in mice exposed perinatally to extremely low frequency electromagnetic fields.

PubMed

Alsaeed, Ibrahim; Al-Somali, Faisal; Sakhnini, Lama; Aljarallah, Omar S; Hamdan, Rayan M M; Bubishate, Saleh A; Sarfaraz, Ziyab Khan; Kamal, Amer

2014-10-01

The incidence of autism spectrum disorders (ASD) has been rising, but the causes of ASD remain largely unidentified. Collective data have implicated the increased human exposure to electromagnetic fields (EMF) in the increasing incidence of ASD. There are established biological effects of extremely low-frequency (ELF) EMF, but the relation to ASD is not investigated enough. In this study we examined the effects of perinatal exposure to ELF EMF on some ASD-relevant behavioral parameters in mice. The EMF was delivered via a Helmholtz coil pair. Male BALB/C mice were used and divided into exposed and control groups (n=8 and n=9, respectively). Tests were used to assess sociability, preference for social novelty, locomotion, anxiety, exploratory behavior, motor coordination, and olfaction. The examined mice were all males and exposed to EMF during the last week of gestation and for 7 days after delivery. The exposed mice demonstrated a lack of normal sociability and preference for social novelty while maintaining normal anxiety-like behavior, locomotion, motor coordination, and olfaction. Exposed mice also demonstrated decreased exploratory activity. We concluded that these results are supportive of the hypothesis of a causal link between exposure to ELF-EMF and ASD; however, replications of the study with further tests are recommended. Copyright © 2014 ISDN. Published by Elsevier Ltd. All rights reserved.

Abnormalities in early visual processes are linked to hypersociability and atypical evaluation of facial trustworthiness: An ERP study with Williams syndrome.

PubMed

Shore, Danielle M; Ng, Rowena; Bellugi, Ursula; Mills, Debra L

2017-10-01

Accurate assessment of trustworthiness is fundamental to successful and adaptive social behavior. Initially, people assess trustworthiness from facial appearance alone. These assessments then inform critical approach or avoid decisions. Individuals with Williams syndrome (WS) exhibit a heightened social drive, especially toward strangers. This study investigated the temporal dynamics of facial trustworthiness evaluation in neurotypic adults (TD) and individuals with WS. We examined whether differences in neural activity during trustworthiness evaluation may explain increased approach motivation in WS compared to TD individuals. Event-related potentials were recorded while participants appraised faces previously rated as trustworthy or untrustworthy. TD participants showed increased sensitivity to untrustworthy faces within the first 65-90 ms, indexed by the negative-going rise of the P1 onset (oP1). The amplitude of the oP1 difference to untrustworthy minus trustworthy faces was correlated with lower approachability scores. In contrast, participants with WS showed increased N170 amplitudes to trustworthy faces. The N170 difference to low-high-trust faces was correlated with low approachability in TD and high approachability in WS. The findings suggest that hypersociability associated with WS may arise from abnormalities in the timing and organization of early visual brain activity during trustworthiness evaluation. More generally, the study provides support for the hypothesis that impairments in low-level perceptual processes can have a cascading effect on social cognition.

Adult Restoration of Shank3 Expression Rescues Selective Autistic-Like Phenotypes

PubMed Central

Mei, Yuan; Monteiro, Patricia; Zhou, Yang; Kim, Jin-Ah; Gao, Xian; Fu, Zhanyan; Feng, Guoping

2016-01-01

Because ASD is a neurodevelopmental disorder and patients typically display symptoms before the age of three1, one of the key questions in autism research is whether the pathology is reversible in adults. Here we investigated the developmental requirement of Shank3, one of the most prominent monogenic ASD genes that is estimated to contribute to ~1% of all ASD cases2–6. SHANK3 is a postsynaptic scaffold protein that regulates synaptic development, function and plasticity by orchestrating the assembly of postsynaptic density (PSD) macromolecular signaling complex7–9. Disruptions of the Shank3 gene in mouse models have resulted in synaptic defects and autistic-like behaviors including anxiety, social interaction deficits, and repetitive behavior10–13. We generated a novel Shank3 conditional knock-in mouse model and used it to demonstrate that re-expression of the Shank3 gene in adult led to improvements in synaptic protein composition, spine density and neural function in the striatum. We also provided behavioral evidence that certain behavioral abnormalities including social interaction deficit and repetitive grooming behavior could be rescued, while anxiety and motor coordination deficit could not be recovered in adulthood. Together, these results elucidate the profound impact of post-developmental activation of Shank3 expression on neural function and demonstrate certain degree of continued plasticity in the adult diseased brain. PMID:26886798

The role of immune dysfunction in the pathophysiology of autism

PubMed Central

Onore, Charity; Careaga, Milo; Ashwood, Paul

2012-01-01

Autism spectrum disorders (ASD) are a complex group of neurodevelopmental disorders encompassing impairments in communication, social interactions and restricted stereotypical behaviors. Although a link between altered immune responses and ASD was first recognized nearly 40 years ago, only recently has new evidence started to shed light on the complex multifaceted relationship between immune dysfunction and behavior in ASD. Neurobiological research in ASD has highlighted pathways involved in neural development, synapse plasticity, structural brain abnormalities, cognition and behavior. At the same time, several lines of evidence point to altered immune dysfunction in ASD that directly impacts some or all these neurological processes. Extensive alterations in immune function have now been described in both children and adults with ASD, including ongoing inflammation in brain specimens, elevated pro-inflammatory cytokine profiles in the CSF and blood, increased presence of brain-specific auto-antibodies and altered immune cell function. Furthermore, these dysfunctional immune responses are associated with increased impairments in behaviors characteristic of core features of ASD, in particular, deficits in social interactions and communication. This accumulating evidence suggests that immune processes play a key role in the pathophysiology of ASD. This review will discuss the current state of our knowledge of immune dysfunction in ASD, how these findings may impact on underlying neuro-immune mechanisms and implicate potential areas where the manipulation of the immune response could have an impact on behavior and immunity in ASD. PMID:21906670

Changes in emotional empathy, affective responsivity, and behavior following severe traumatic brain injury.

PubMed

de Sousa, Arielle; McDonald, Skye; Rushby, Jacqueline

2012-01-01

This study was designed to examine the relationship between deficits in empathy, emotional responsivity, and social behavior in adults with severe traumatic brain injury (TBI). A total of 21 patients with severe TBI and 25 control participants viewed six film clips containing pleasant, unpleasant, and neutral content whilst facial muscle responses, skin conductance, and valence and arousal ratings were measured. Emotional empathy (the Balanced Emotional Empathy Scale, BEES: self-report) and changes in drive and control in social situations (The Current Behaviour Scale, CBS: relative report) were also assessed. In comparison to control participants, those in the TBI group reported less ability to empathize emotionally and had reduced facial responding to both pleasant and unpleasant films. They also exhibited lowered autonomic arousal, as well as abnormal ratings of valence and arousal, particularly to unpleasant films. Relative reported loss of emotional control was significantly associated with heightened empathy, while there was a trend to suggest that impaired drive (or motivation) may be related to lower levels of emotional empathy. The results represent the first to suggest that level of emotional empathy post traumatic brain injury may be associated with behavioral manifestations of disorders of drive and control.

Questioning our Questions: Do frequently asked questions adequately cover the aspects of women's lives most affected by abnormal uterine bleeding? Opinions of women with abnormal uterine bleeding participating in focus group discussions

PubMed Central

Matteson, Kristen A.; Clark, Melissa A.

2010-01-01

Objectives: (1) To explore the effects on women's lives by heavy or irregular menstrual bleeding; (2) To examine whether aspects of women's lives most affected by heavy or irregular menstrual bleeding were adequately addressed by questions that are frequently used in clinical encounters and available questionnaires. Methods: We conducted four focus group sessions with a total of 25 English-speaking women who had reported abnormal uterine bleeding. Discussions included open-ended questions that pertained to bleeding, aspects of life affected by bleeding, and questions frequently used in clinical settings about bleeding and quality of life. Results: We identified five themes that reflected how women's lives were affected by heavy or irregular menstrual bleeding: irritation/inconvenience, bleeding-associated pain, self-consciousness about odor, social embarrassment, and ritual like behavior. Although women responded that the frequently used questions about bleeding and quality of life were important, they felt that the questions failed to go into enough depth to adequately characterize their experiences. Conclusions: Based on the themes identified in our focus group sessions, clinicians and researchers may need to change the questions used to capture “patient experience” with abnormal uterine bleeding more accurately. PMID:20437305

Integrative nonpharmacologic behavioral interventions for the management of cancer-related fatigue.

PubMed

Mustian, Karen M; Morrow, Gary R; Carroll, Jennifer K; Figueroa-Moseley, Colmar D; Jean-Pierre, Pascal; Williams, Geoffrey C

2007-01-01

Cancer-related fatigue (CRF) is a debilitating, multi-faceted biopsychosocial symptom experienced by the majority of cancer survivors during and after treatment. CRF begins after diagnosis and frequently persists long after treatments end, even when the cancer is in remission. The etiological pathopsychophysiology underlying CRF is multifactorial and not well delineated. Mechanisms may include abnormal accumulation of muscle metabolites, dysregulation of the homeostatic status of cytokines, irregularities in neuromuscular function, abnormal gene expression, inadequate ATP synthesis, serotonin dysregulation, abnormal vagal afferent nerve activation, as well as an array of psychosocial mechanisms, including self-efficacy, causal attributions, expectancy, coping, and social support. An important first step in the management of CRF is the identification and treatment of associated comorbidities, such as anemia, hypothyroidism, pain, emotional distress, insomnia, malnutrition, and other comorbid conditions. However, even effective clinical management of these conditions will not necessarily alleviate CRF for a significant proportion of cancer survivors. For these individuals, intervention with additional therapeutic modalities may be required. The National Comprehensive Cancer Network guidelines recommend that integrative nonpharmacologic behavioral interventions be implemented for the effective management of CRF. These types of interventions may include exercise, psychosocial support, stress management, energy conservation, nutritional therapy, sleep therapy, and restorative therapy. A growing body of scientific evidence supports the use of exercise and psychosocial interventions for the management of CRF. Research on these interventions has yielded positive outcomes in cancer survivors with different diagnoses undergoing a variety of cancer treatments. The data from trials investigating the efficacy of other types of integrative nonpharmacologic behavioral therapies for the management of CRF, though limited, are also encouraging. This article provides an overview of current research on the relative merits of integrative nonpharmacologic behavioral interventions for the effective clinical management of CRF and makes recommendations for future research. Disclosure of potential conflicts of interest is found at the end of this article.

A quantitative estimate of schema abnormality in socially anxious and non-anxious individuals.

PubMed

Wenzel, Amy; Brendle, Jennifer R; Kerr, Patrick L; Purath, Donna; Ferraro, F Richard

2007-01-01

Although cognitive theories of anxiety suggest that anxious individuals are characterized by abnormal threat-relevant schemas, few empirical studies have estimated the nature of these cognitive structures using quantitative methods that lend themselves to inferential statistical analysis. In the present study, socially anxious (n = 55) and non-anxious (n = 62) participants completed 3 Q-Sort tasks to assess their knowledge of events that commonly occur in social or evaluative scenarios. Participants either sorted events according to how commonly they personally believe the events occur (i.e. "self" condition), or to how commonly they estimate that most people believe they occur (i.e. "other" condition). Participants' individual Q-Sorts were correlated with mean sorts obtained from a normative sample to obtain an estimate of schema abnormality, with lower correlations representing greater levels of abnormality. Relative to non-anxious participants, socially anxious participants' sorts were less strongly associated with sorts of the normative sample, particularly in the "self" condition, although secondary analyses suggest that some significant results might be explained, in part, by depression and experience with the scenarios. These results provide empirical support for the theoretical notion that threat-relevant self-schemas of anxious individuals are characterized by some degree of abnormality.

Neuronal glucose transporter isoform 3 deficient mice demonstrate features of autism spectrum disorders.

PubMed

Zhao, Y; Fung, C; Shin, D; Shin, B-C; Thamotharan, S; Sankar, R; Ehninger, D; Silva, A; Devaskar, S U

2010-03-01

Neuronal glucose transporter (GLUT) isoform 3 deficiency in null heterozygous mice led to abnormal spatial learning and working memory but normal acquisition and retrieval during contextual conditioning, abnormal cognitive flexibility with intact gross motor ability, electroencephalographic seizures, perturbed social behavior with reduced vocalization and stereotypies at low frequency. This phenotypic expression is unique as it combines the neurobehavioral with the epileptiform characteristics of autism spectrum disorders. This clinical presentation occurred despite metabolic adaptations consisting of an increase in microvascular/glial GLUT1, neuronal GLUT8 and monocarboxylate transporter isoform 2 concentrations, with minimal to no change in brain glucose uptake but an increase in lactate uptake. Neuron-specific glucose deficiency has a negative impact on neurodevelopment interfering with functional competence. This is the first description of GLUT3 deficiency that forms a possible novel genetic mechanism for pervasive developmental disorders, such as the neuropsychiatric autism spectrum disorders, requiring further investigation in humans.

A Dopamine Hypothesis of Autism Spectrum Disorder.

PubMed

Pavăl, Denis

2017-01-01

Autism spectrum disorder (ASD) comprises a group of neurodevelopmental disorders characterized by social deficits and stereotyped behaviors. While several theories have emerged, the pathogenesis of ASD remains unknown. Although studies report dopamine signaling abnormalities in autistic patients, a coherent dopamine hypothesis which could link neurobiology to behavior in ASD is currently lacking. In this paper, we present such a hypothesis by proposing that autistic behavior arises from dysfunctions in the midbrain dopaminergic system. We hypothesize that a dysfunction of the mesocorticolimbic circuit leads to social deficits, while a dysfunction of the nigrostriatal circuit leads to stereotyped behaviors. Furthermore, we discuss 2 key predictions of our hypothesis, with emphasis on clinical and therapeutic aspects. First, we argue that dopaminergic dysfunctions in the same circuits should associate with autistic-like behavior in nonautistic subjects. Concerning this, we discuss the case of PANDAS (pediatric autoimmune neuropsychiatric disorder associated with streptococcal infections) which displays behaviors similar to those of ASD, presumed to arise from dopaminergic dysfunctions. Second, we argue that providing dopamine modulators to autistic subjects should lead to a behavioral improvement. Regarding this, we present clinical studies of dopamine antagonists which seem to have improving effects on autistic behavior. Furthermore, we explore the means of testing our hypothesis by using neuroreceptor imaging, which could provide comprehensive evidence for dopamine signaling dysfunctions in autistic subjects. Lastly, we discuss the limitations of our hypothesis. Along these lines, we aim to provide a dopaminergic model of ASD which might lead to a better understanding of the ASD pathogenesis. © 2017 S. Karger AG, Basel.

Toll-Like Receptor 4 Deficiency Causes Reduced Exploratory Behavior in Mice Under Approach-Avoidance Conflict.

PubMed

Li, Chunlu; Yan, Yixiu; Cheng, Jingjing; Xiao, Gang; Gu, Jueqing; Zhang, Luqi; Yuan, Siyu; Wang, Junlu; Shen, Yi; Zhou, Yu-Dong

2016-04-01

Abnormal approach-avoidance behavior has been linked to deficits in the mesolimbic dopamine (DA) system of the brain. Recently, increasing evidence has indicated that toll-like receptor 4 (TLR4), an important pattern-recognition receptor in the innate immune system, can be directly activated by substances of abuse, resulting in an increase of the extracellular DA level in the nucleus accumbens. We thus hypothesized that TLR4-dependent signaling might regulate approach-avoidance behavior. To test this hypothesis, we compared the novelty-seeking and social interaction behaviors of TLR4-deficient (TLR4(-/-)) and wild-type (WT) mice in an approach-avoidance conflict situation in which the positive motivation to explore a novel object or interact with an unfamiliar mouse was counteracted by the negative motivation to hide in exposed, large spaces. We found that TLR4(-/-) mice exhibited reduced novelty-seeking and social interaction in the large open spaces. In less stressful test apparatuses similar in size to the mouse cage, however, TLR4(-/-) mice performed normally in both novelty-seeking and social interaction tests. The reduced exploratory behaviors under approach-avoidance conflict were not due to a high anxiety level or an enhanced fear response in the TLR4(-/-) mice, as these mice showed normal anxiety and fear responses in the open field and passive avoidance tests, respectively. Importantly, the novelty-seeking behavior in the large open field induced a higher level of c-Fos activation in the nucleus accumbens shell (NAcSh) in TLR4(-/-) mice than in WT mice. Partially inactivating the NAcSh via infusion of GABA receptor agonists restored the novelty-seeking behavior of TLR4(-/-) mice. These data suggested that TLR4 is crucial for positive motivational behavior under approach-avoidance conflict. TLR4-dependent activation of neurons in the NAcSh may contribute to this phenomenon.

Early Life Stress Increases Metabolic Risk, HPA Axis Reactivity, and Depressive-Like Behavior When Combined with Postweaning Social Isolation in Rats.

PubMed

Vargas, Javier; Junco, Mariana; Gomez, Carlos; Lajud, Naima

2016-01-01

Early-life stress is associated with depression and metabolic abnormalities that increase the risk of cardiovascular disease and diabetes. Such associations could be due to increased glucocorticoid levels. Periodic maternal separation in the neonate and rearing in social isolation are potent stressors that increase hypothalamus-pituitary-adrenal axis activity. Moreover, social isolation promotes feed intake and body weight gain in rats subjected to periodic maternal separation; however, its effects on metabolic risks have not been described. In the present study, we evaluated whether periodic maternal separation, social isolation rearing, and a combination of these two stressors (periodic maternal separation + social isolation rearing) impair glucose homeostasis and its relation to the hypothalamus-pituitary-adrenal axis and depressive-like behavior. Periodic maternal separation increased basal corticosterone levels, induced a passive coping strategy in the forced swimming test, and was associated with a mild (24%) increase in fasting glucose, insulin resistance, and dyslipidemia. Rearing in social isolation increased stress reactivity in comparison to both controls and in combination with periodic maternal separation, without affecting the coping strategy associated with the forced swimming test. However, social isolation also increased body weight gain, fasting glucose (120%), and insulin levels in rats subjected to periodic maternal separation. Correlation analyses showed that stress-induced effects on coping strategy on the forced swimming test (but not on metabolic risk markers) are associated with basal corticosterone levels. These findings suggest that maternal separation and postweaning social isolation affect stress and metabolic vulnerability differentially and that early-life stress-related effects on metabolism are not directly dependent on glucocorticoid levels. In conclusion, our study supports the cumulative stress hypothesis, which suggests that metabolic risk markers arise when vulnerable individuals are exposed to social challenges later in life.

The Tennessee Mouse Genome Consortium: Identification of ocular mutants

DOE Office of Scientific and Technical Information (OSTI.GOV)

Jablonski, Monica M.; Wang, Xiaofei; Lu, Lu

2005-06-01

The Tennessee Mouse Genome Consortium (TMGC) is in its fifth year of a ethylnitrosourea (ENU)-based mutagenesis screen to detect recessive mutations that affect the eye and brain. Each pedigree is tested by various phenotyping domains including the eye, neurohistology, behavior, aging, ethanol, drug, social behavior, auditory, and epilepsy domains. The utilization of a highly efficient breeding protocol and coordination of various universities across Tennessee makes it possible for mice with ENU-induced mutations to be evaluated by nine distinct phenotyping domains within this large-scale project known as the TMGC. Our goal is to create mutant lines that model human diseases andmore » disease syndromes and to make the mutant mice available to the scientific research community. Within the eye domain, mice are screened for anterior and posterior segment abnormalities using slit-lamp biomicroscopy, indirect ophthalmoscopy, fundus photography, eye weight, histology, and immunohistochemistry. As of January 2005, we have screened 958 pedigrees and 4800 mice, excluding those used in mapping studies. We have thus far identified seven pedigrees with primary ocular abnormalities. Six of the mutant pedigrees have retinal or subretinal aberrations, while the remaining pedigree presents with an abnormal eye size. Continued characterization of these mutant mice should in most cases lead to the identification of the mutated gene, as well as provide insight into the function of each gene. Mice from each of these pedigrees of mutant mice are available for distribution to researchers for independent study.« less

Excessive activation of AhR signaling disrupts neuronal migration in the hippocampal CA1 region in the developing mouse.

PubMed

Kimura, Eiki; Kubo, Ken-Ichiro; Endo, Toshihiro; Nakajima, Kazunori; Kakeyama, Masaki; Tohyama, Chiharu

2017-01-01

The aryl hydrocarbon receptor (AhR) avidly binds dioxin, a ubiquitous environmental contaminant. Disruption of downstream AhR signaling has been reported to alter neuronal development, and rodent offspring exposed to dioxin during gestation and lactation showed abnormalities in learning and memory, emotion, and social behavior. However, the mechanism behind the disrupted AhR signaling and developmental neurotoxicity induced by xenobiotic ligands remains elusive. Therefore, we studied how excessive AhR activation affects neuronal migration in the hippocampal CA1 region of the developing mouse brain. We transfected constitutively active (CA)-AhR, AhR, or control vector plasmids into neurons via in utero electroporation on gestational day 14 and analyzed neuronal positioning in the hippocampal CA1 region of offspring on postnatal day 14. CA-AhR transfection affected neuronal positioning, whereas no change was observed in AhR-transfected or control hippocampus. These results suggest that constitutively activated AhR signaling disrupts neuronal migration during hippocampal development. Further studies are needed to investigate whether such developmental disruption in the hippocampus leads to the abnormal cognition and behavior of rodent offspring upon maternal exposure to AhR xenobiotic ligands.

Abnormal emotion processing, but intact fairness and intentionality considerations during social decision-making in schizophrenia.

PubMed

de la Asuncion, Javier; Docx, Lise; Sabbe, Bernard; Morrens, Manuel; de Bruijn, Ellen R A

2015-01-01

Schizophrenia is a severe mental disorder that is highly characterized by social cognitive impairments. Most studies investigating these impairments focus on one specific social domain such as emotion recognition. However, in daily life, processing complex social situations relies on the combination of several social cognitive and affective processes simultaneously rather than one process alone. A modified version of the economically based Ultimatum Game was used to measure the interplay between fairness, intentionality, and emotion considerations during social decision-making. In this task, participants accept or reject fair and unfair monetary offers proposed intentionally or unintentionally by either angry, happy, neutral, or sad proposers. Behavioral data was collected from a group of schizophrenia patients (N = 35) and a group of healthy individuals (N = 30). Like healthy participants, schizophrenia patients differentiated between fair and unfair offers by rejecting unfair offers more compared to fair offers. However, overall patients did reject more fair offers, indicating that their construct of fairness operates within different margins. In both groups, intentional unfair offers were rejected more compared to unintentional ones, indicating a normal integration of intentionality considerations in schizophrenia. Importantly, healthy subjects also differentiated between proposers' emotion when rejecting unfair offers (more rejections from proposers depicting angry faces compared to proposers depicting, happy, neutral, or sad faces). Schizophrenia patients' decision behavior on the other hand, was not affected by the proposers' emotions. The current study thus shows that schizophrenia patients have specific problems with processing and integrating emotional information. Importantly, the finding that patients display normal fairness and intentionality considerations emphasizes preservation of central social cognitive processes in schizophrenia.

Social isolation induces deficit of latent learning performance in mice: a putative animal model of attention deficit/hyperactivity disorder.

PubMed

Ouchi, Hirofumi; Ono, Kazuya; Murakami, Yukihisa; Matsumoto, Kinzo

2013-02-01

Social isolation of rodents (SI) elicits a variety of stress responses such as increased aggressiveness, hyper-locomotion, and reduced susceptibility to pentobarbital. To obtain a better understanding of the relevance of SI-induced behavioral abnormalities to psychiatric disorders, we examined the effect of SI on latent learning as an index of spatial attention, and discussed the availability of SI as an epigenetic model of attention deficit hyperactivity disorder (ADHD). Except in specially stated cases, 4-week-old male mice were housed in a group or socially isolated for 3-70 days before experiments. The animals socially isolated for 1 week or more exhibited spatial attention deficit in the water-finding test. Re-socialized rearing for 5 weeks after 1-week SI failed to attenuate the spatial attention deficit. The effect of SI on spatial attention showed no gender difference or correlation with increased aggressive behavior. Moreover, SI had no effect on cognitive performance elucidated in a modified Y-maze or an object recognition test, but it significantly impaired contextual and conditional fear memory elucidated in the fear-conditioning test. Drugs used for ADHD therapy, methylphenidate (1-10 mg/kg, i.p.) and caffeine (0.5-1 mg/kg, i.p.), improved SI-induced latent learning deficit in a manner reversible with cholinergic but not dopaminergic antagonists. Considering the behavioral features of SI mice together with their susceptibility to ADHD drugs, the present findings suggest that SI provides an epigenetic animal model of ADHD and that central cholinergic systems play a role in the effect of methylphenidate on SI-induced spatial attention deficit. Copyright © 2012 Elsevier B.V. All rights reserved.

Effects of striatal ΔFosB overexpression and ketamine on social defeat stress-induced anhedonia in mice.

PubMed

Donahue, Rachel J; Muschamp, John W; Russo, Scott J; Nestler, Eric J; Carlezon, William A

2014-10-01

Chronic social defeat stress (CSDS) produces persistent behavioral adaptations in mice. In many behavioral assays, it can be difficult to determine if these adaptations reflect core signs of depression. We designed studies to characterize the effects of CSDS on sensitivity to reward because anhedonia (reduced sensitivity to reward) is a defining characteristic of depressive disorders in humans. We also examined the effects of striatal ΔFosB overexpression and the N-methyl-D-aspartate receptor antagonist ketamine, both of which promote resilience, on CSDS-induced alterations in reward function and social interaction. Intracranial self-stimulation (ICSS) was used to quantify CSDS-induced changes in reward function. Mice were implanted with lateral hypothalamic electrodes, and ICSS thresholds were measured after each of 10 daily CSDS sessions and during a 5-day recovery period. We also examined if acute intraperitoneal administration of ketamine (2.5-20 mg/kg) reverses CSDS-induced effects on reward or, in separate mice, social interaction. ICSS thresholds were increased by CSDS, indicating decreases in the rewarding impact of lateral hypothalamic stimulation (anhedonia). This effect was attenuated in mice overexpressing ∆FosB in striatum, consistent with pro-resilient actions of this transcription factor. High, but not low, doses of ketamine administered after completion of the CSDS regimen attenuated social avoidance in defeated mice, although this effect was transient. Ketamine did not block CSDS-induced anhedonia in the ICSS test. This study found that CSDS triggers persistent anhedonia and confirms that ΔFosB overexpression produces stress resilience. The findings of this study also indicate that acute administration of ketamine fails to attenuate CSDS-induced anhedonia despite reducing other depression-related behavioral abnormalities. Copyright © 2014 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

GPR40/FFAR1 deficient mice increase noradrenaline levels in the brain and exhibit abnormal behavior.

PubMed

Aizawa, Fuka; Nishinaka, Takashi; Yamashita, Takuya; Nakamoto, Kazuo; Kurihara, Takashi; Hirasawa, Akira; Kasuya, Fumiyo; Miyata, Atsuro; Tokuyama, Shogo

2016-12-01

The free fatty acid receptor 1 (GPR40/FFAR1) is a G protein-coupled receptor, which is activated by long chain fatty acids. We have previously demonstrated that activation of brain GPR40/FFAR1 exerts an antinociceptive effect that is mediated by the modulation of the descending pain control system. However, it is unclear whether brain GPR40/FFAR1 contributes to emotional function. In this study, we investigated the involvement of GPR40/FFAR1 in emotional behavior using GPR40/FFAR1 deficient (knockout, KO) mice. The emotional behavior in wild and KO male mice was evaluated at 9-10 weeks of age by the elevated plus-maze test, open field test, social interaction test, and sucrose preference test. Brain monoamines levels were measured using LC-MS/MS. The elevated plus-maze test and open field tests revealed that the KO mice reduced anxiety-like behavior. There were no differences in locomotor activity or social behavior between the wild and KO mice. In the sucrose preference test, the KO mice showed reduction in sucrose preference and intake. The level of noradrenaline was higher in the hippocampus, medulla oblongata, hypothalamus and midbrain of KO mice. Therefore, these results suggest that brain GPR40/FFAR1 is associated with anxiety- and depression-related behavior regulated by the increment of noradrenaline in the brain. Copyright © 2016 The Authors. Production and hosting by Elsevier B.V. All rights reserved.

Basal ganglia systems in ritualistic social displays: reptiles and humans; function and illness.

PubMed

Baxter, Lewis R

2003-08-01

Complex, situation-specific territorial maintenance routines are similar across living terrestrial vertebrates (=amniotes). Decades ago, Paul MacLean et al., at the Laboratory of Brain Evolution and Behavior of the National Institute of Mental Health, postulated that these are evolutionarily conserved behaviors whose expression is mediated by the similarly conserved amniote basal ganglia and related brain systems (BG systems). Therefore, they undertook studies in nonhuman primates and in small social lizards (the common green anole, Anolis carolinensis) to examine this idea. MacLean et al. also postulated that when BG systems misfunction in humans, behavioral abnormalities result, some of them under the rubric of psychiatric illnesses. Obsessive-compulsive disorder (OCD) was singled out as one likely candidate. In the last dozen years, functional brain imaging studies of OCD patients have validated the contention that this is, in fact, a condition involving dysfunctioning BG systems. Inspired by the MacLean group's original investigations, my colleagues and I have now applied related functional imaging techniques in naturalistic experiments using Anolis to better understand BG systems' roles in the mediation of complex behavioral routines in healthy amniotes. Here, I will review this functional imaging work in primates (man, and a little in monkey) and in lizards. I believe the literature not only supports MacLean et al.'s contentions about BG systems and behavior in general, but also validates Paul MacLean's life-long contention that human behavioral medicine can profit from a broad comparative approach.

Diagnosis and management of behavioral variant frontotemporal dementia.

PubMed

Pressman, Peter S; Miller, Bruce L

2014-04-01

Frontotemporal dementia was documented over a century ago. The last decade, however, has seen substantial changes in our conceptions of this increasingly recognized disorder. Different clinical variants have been delineated, the most common of which is the behavioral variant (bvFTD). Updated diagnostic criteria have been established. New histopathological findings and genetic etiologies have been discovered. Research continues to uncover molecular mechanisms by which abnormal proteins accumulate in degenerating brain tissue. Novel neuroimaging techniques suggest that functional networks are diminished in bvFTD that might be relevant to empathy and social behavior. Despite rapid advances in our understanding of bvFTD, the disease is still under-recognized and commonly misdiagnosed. The result is inappropriate patient care. Recognizing the various presentations of bvFTD and its histological and genetic subtypes might further diagnosis, treatment, and research. © 2013 Society of Biological Psychiatry Published by Society of Biological Psychiatry All rights reserved.

Nervous system disruption and concomitant behavioral abnormality in early hatched pufferfish larvae exposed to heavy oil.

PubMed

Kawaguchi, Masahumi; Sugahara, Yuki; Watanabe, Tomoe; Irie, Kouta; Ishida, Minoru; Kurokawa, Daisuke; Kitamura, Shin-Ichi; Takata, Hiromi; Handoh, Itsuki C; Nakayama, Kei; Murakami, Yasunori

2011-08-01

Spills of heavy oil (HO) over the oceans have been proven to have an adverse effect on marine life. It has been hypothesized that exposure of early larvae of sinking eggs to HO leads largely to normal morphology, whereas abnormal organization of the developing neural scaffold is likely to be found. HO-induced disruption of the nervous system, which controls animal behavior, may in turn cause abnormalities in the swimming behavior of hatched larvae. To clarify the toxicological effects of HO, we performed exposure experiments and morphological and behavioral analyses in pufferfish (Takifugu rubripes) larvae. Fertilized eggs of pufferfish were exposed to 50 mg/L of HO for 8 days and transferred to fresh seawater before hatching. The hatched larvae were observed for their swimming behavior, morphological appearance, and construction of muscles and nervous system. In HO-exposed larvae, we did not detect any anomaly of body morphology. However, they showed an abnormal swimming pattern and disorganized midbrain, a higher center controlling movement. Our results suggest that HO-exposed fishes suffer developmental disorder of the brain that triggers an abnormal swimming behavior and that HO may be selectively toxic to the brain and cause physical disability throughout the life span of these fishes.

Changes in food intake and abnormal behavior using a puzzle feeder in newly acquired sub-adult rhesus monkeys (Macaca mulatta): a short term study.

PubMed

Lee, Jae-Il; Lee, Chi-Woo; Kwon, Hyouk-Sang; Kim, Young-Tae; Park, Chung-Gyu; Kim, Sang-Joon; Kang, Byeong-Cheol

2008-10-01

The majority of newly acquired nonhuman primates encounter serious problems adapting themselves to new environments or facilities. In particular, loss of appetite and abnormal behavior can occur in response to environmental stresses. These adaptation abnormalities can ultimately have an affect on the animal's growth and well-being. In this study, we evaluated the affects of a puzzle feeder on the food intake and abnormal behavior of newly acquired rhesus monkeys for a short period. The puzzle feeder was applied to 47- to 58-month-old animals that had never previously encountered one. We found that there was no difference in the change of food intake between the bucket condition and the puzzle feeder condition. In contrast, the time spent for consumption of food was three times longer in the puzzle feeder condition than in the bucket condition. Two monkeys initially exhibited stereotypic behavior. One showed a decreasing, and the other an increasing pattern of abnormal behavior after introduction of the puzzle feeder. In conclusion, this result suggests that over a short period, the puzzle feeder can only affect the time for food consumption since it failed to affect the food intake and did not consistently influence stereotypic behaviors in newly acquired rhesus monkeys.

Individual differences in maternal response to immune challenge predict offspring behavior: Contribution of environmental factors

PubMed Central

Bronson, Stefanie L.; Ahlbrand, Rebecca; Horn, Paul S.; Kern, Joseph R.; Richtand, Neil M.

2011-01-01

Maternal infection during pregnancy elevates risk for schizophrenia and related disorders in offspring. Converging evidence suggests the maternal inflammatory response mediates the interaction between maternal infection, altered brain development, and behavioral outcome. The extent to which individual differences in the maternal response to immune challenge influence the development of these abnormalities is unknown. The present study investigated the impact of individual differences in maternal response to the viral mimic polyinosinic:polycytidylic acid (poly I:C) on offspring behavior. We observed significant variability in body weight alterations of pregnant rats induced by administration of poly I:C on gestational day 14. Furthermore, the presence or absence of maternal weight loss predicted MK-801 and amphetamine stimulated locomotor abnormalities in offspring. MK-801 stimulated locomotion was altered in offspring of all poly I:C treated dams; however, the presence or absence of maternal weight loss resulted in decreased and modestly increased locomotion, respectively. Adult offspring of poly I:C treated dams that lost weight exhibited significantly decreased amphetamine stimulated locomotion, while offspring of poly I:C treated dams without weight loss performed similarly to vehicle controls. Social isolation and increased maternal age predicted weight loss in response to poly I:C but not vehicle injection. In combination, these data identify environmental factors associated with the maternal response to immune challenge and functional outcome of offspring exposed to maternal immune activation. PMID:21255612

Prevalence and characteristics of hair plucking in captive bonobos (Pan paniscus) in North American zoos.

PubMed

Brand, Colin M; Marchant, Linda F

2018-04-01

When primates exhibit hair loss and are observed to engage in self or social hair plucking (a rapid jerking away of the hair shaft and follicle by the hand or mouth, often accompanied by inspection, and consumption) the altered appearance, and behavior patterns are thought to reflect individual physiological, and psychological well-being. Hair loss and hair plucking occur in many captive primate species, including all of the great apes. We present the first survey of this behavior among captive bonobos (N = 88; 50 females and 38 males) in seven zoos in the United States. We found that 43% of the population engaged in this behavior pattern and discounting youngsters (who are not observed to hair pluck until the age of five), 58% of individuals hair plucked. Of the individuals who hair plucked, 97% engaged in social plucking, whereas 46% engaged in self-directed plucking. We regressed the occurrence of hair plucking with multiple predictor variables using binary logistic regression and multimodel inference to determine which predictors best explained the prevalence of self-directed and social plucking. We also analyzed publicly available data on hair plucking in captive chimpanzees. We found that the occurrence of another abnormal behavior, age, origin, and pelage condition best explained self-directed plucking in bonobos. Social plucking was explained by age, origin, pelage, and sex. Our analysis of chimpanzee hair plucking revealed that plucking is strongly influenced by rearing and sex. This study demonstrates that hair plucking is more prevalent in captive bonobos compared to captive chimpanzees and gorillas, however, the covariates associated with hair plucking for each species are different. Our data suggest a potential link between self-directed plucking and well-being. However, the higher prevalence and etiology of social hair plucking is more difficult to explain. © 2018 Wiley Periodicals, Inc.

Genetic deletion of regulator of G-protein signaling 4 (RGS4) rescues a subset of fragile X related phenotypes in the FMR1 knockout mouse.

PubMed

Pacey, Laura K K; Doss, Lilian; Cifelli, Carlo; van der Kooy, Derek; Heximer, Scott P; Hampson, David R

2011-03-01

Fragile X syndrome (FXS), the most common cause of inherited mental retardation, is caused by the loss of the mRNA binding protein, FMRP. Persons with FXS also display epileptic seizures, social anxiety, hyperactivity, and autistic behaviors. The metabotropic glutamate receptor theory of FXS postulates that in the absence of FMRP, enhanced signaling though G-protein coupled group I metabotropic glutamate receptors in the brain contributes to many of the abnormalities observed in the disorder. However, recent evidence suggests that alterations in cellular signaling through additional G-protein coupled receptors may also be involved in the pathogenesis of FXS, thus providing impetus for examining downstream molecules. One group of signaling molecules situated downstream of the receptors is the regulator of G-protein signaling (RGS) proteins. Notably, RGS4 is highly expressed in brain and has been shown to negatively regulate signaling through Group I mGluRs and GABA(B) receptors. To examine the potential role for RGS4 in the pathogenesis of FXS, we generated FXS/RGS4 double knockout mice. Characterization of these mice revealed that a subset of FXS related phenotypes, including increased body weight, altered synaptic protein expression, and abnormal social behaviors, were rescued in the double knockout mice. Other phenotypes, such as hyperactivity and macroorchidism, were not affected by the loss of RGS4. These findings suggest that tissue and cell-type specific differences in GPCR signaling and RGS function may contribute to the spectrum of phenotypic differences observed in FXS. Copyright © 2010 Elsevier Inc. All rights reserved.

The neural basis of social risky decision making in females with major depressive disorder.

PubMed

Shao, Robin; Zhang, Hui-jun; Lee, Tatia M C

2015-01-01

Recent evidence indicates that Major Depressive Disorder (MDD) may be associated with reduced tendency of committing noncompliant actions during social decision-making even when the risk of being punished is low. The neural underpinnings of this behavioral pattern are unknown, although it likely relates to compromised functioning of the lateral prefrontal-striatal/limbic networks implicated in executive control, emotion regulation and risk/value-based instrumental behaviors. We employed a modified trust game (TG) that provided explicit information on the risk levels of cheating behaviors being detected and punished. Behavioral and neuro-image data were acquired and analyzed from 14 first-episode female MDD patients and 15 age- and gender-matched controls performing the role of trustee in the TG. Relative to controls, MDD patients exhibited less behavioral switching to making cheating choices under low risk, and reduced activity in the dorsal putamen, anterior insula and dorsolateral prefrontal cortex (DLPFC) during making low-risk cheating versus benevolent choices, with limited evidence indicating abnormal bilateral inferior frontal gyrus activities of patients when making high-risk cheating versus benevolent choices. Patients' left dorsal putamen/anterior insular signals correlated positively with their frequency of low-risk cheating. MDD patients' symptom severity correlated positively with their signals in the lateral prefrontal networks during decision-making. A psycho-physiological interaction analysis provided tentative evidence for the recruitment of IFG-striatal/limbic circuitry among the control participants, but greater frontopolar-striatal/limbic connectivity among the MDD patients, during low-risk decision-making. We propose that making risky social decisions based on the balancing of self-gain and other's welfare relies on the functioning of the integrated lateral prefrontal-striatal/limbic networks, which are less efficient and dysregulated among MDD patients compared with controls, impacting negatively on the patients' social capacity and highlighting a key therapeutic target for MDD. Copyright © 2014 Elsevier Ltd. All rights reserved.

A clinical interpretation of attitudes and behaviors associated with celebrity worship.

PubMed

Maltby, John; Houran, James; McCutcheon, Lynn E

2003-01-01

The phenomenon of celebrity worship is currently conceptualized as an abnormal type of parasocial relationship, driven by absorption and addictive elements and which potentially has significant clinical sequelae. The authors hypothesize that the three increasingly extreme sets of attitudes and behaviors associated with celebrity worship also partly reflect the three domains of personality discussed in Eysenckian theory. Specifically, celebrity worship for entertainment-social reasons may reflect extraversion personality traits; intense-personal attitudes and behaviors toward celebrities may reflect neuroticism traits; and celebrity worship of a borderline-pathological nature may reflect psychoticism traits. To test this idea, the authors administered the Celebrity Attitude Scale and the Abbreviated Form of the Revised Eysenck Personality Questionnaire to large convenience samples of students (N = 317) and community (N = 290) respondents. Results indicate that celebrity worship is not an uncommon phenomenon. Further, correlational analyses supported predictions and suggest that Eysenckian domains of personality may promote or hinder a person's progression along the continuum of behaviors associated with celebrity worship.

5-HT1A-receptor agonist modified amygdala activity and amygdala-associated social behavior in a valproate-induced rat autism model.

PubMed

Wang, Chao-Chuan; Lin, Hui-Ching; Chan, Yun-Han; Gean, Po-Wu; Yang, Yen Kung; Chen, Po See

2013-10-01

Accumulating evidence suggests that dysfunction of the amygdala is related to abnormal fear processing, anxiety, and social behaviors noted in autistic spectrum disorders (ASDs). In addition, studies have shown that disrupted brain serotonin homeostasis is linked to ASD. With a valproate (VPA)-induced rat ASD model, we investigated the possible role of amygdala serotonin homeostasis in autistic phenotypes and further explored the underlying mechanism. We first discovered that the distribution of tryptophan hydroxylase immunoreactivity in the caudal raphe system was modulated on postnatal day (PD) 28 of the VPA-exposed offspring. Then, we found a significantly higher serotonin transporter availability in the amygdala of the VPA-exposed offspring on PD 56 by using single photon emission computed tomography and computed tomography co-registration following injection of (123)I-labeled 2-((2-(dimethylamino)methyl)phenyl)thio)-5-iodophenylamine((123)I[ADAM]). Furthermore, treatment with 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT), a 5-HT1A receptor agonist, increased social interaction and improved fear memory extinction in the VPA-exposed offspring. 8-OH-DPAT treatment also reversed the characteristics of miniature excitatory post-synaptic currents as well as paired pulse facilitation observed in lateral amygdala slices. These results provided further evidence to support the role of the amygdala in characteristic behavioral changes in the rat ASD model. The serotonergic projections that modulate the amygdala function might play a certain role in the development and treatment of behavioral symptoms exhibited in individuals with ASD.

Preliminary evidence of white matter abnormality in the uncinate fasciculus in generalized social anxiety disorder.

PubMed

Phan, K Luan; Orlichenko, Anton; Boyd, Erin; Angstadt, Mike; Coccaro, Emil F; Liberzon, Israel; Arfanakis, Konstantinos

2009-10-01

Individuals with generalized social anxiety disorder (GSAD) exhibit exaggerated amygdala reactivity to aversive social stimuli. These findings could be explained by microstructural abnormalities in white matter (WM) tracts that connect the amygdala and prefrontal cortex, which is known to modulate the amygdala's response to threat. The goal of this study was to investigate brain frontal WM abnormalities using diffusion tensor imaging (DTI) in patients with social anxiety disorder. A Turboprop DTI sequence was used to acquire diffusion tensor images in 30 patients with GSAD and 30 matched healthy control subjects. Fractional anisotropy, an index of axonal organization, within WM was quantified in individual subjects, and an automated voxel-based, whole-brain method was used to analyze group differences. Compared with healthy control subjects, patients had significantly lower fractional anisotropy localized to the right uncinate fasciculus WM near the orbitofrontal cortex. There were no areas of higher fractional anisotropy in patients than controls. These findings point to an abnormality in the uncinate fasciculus, the major WM tract connecting the frontal cortex to the amygdala and other limbic temporal regions, in GSAD, which could underlie the aberrant amygdala-prefrontal interactions resulting in dysfunctional social threat processing in this illness.

Military Suicide Research Consortium: Extension to New Opportunities and Challenges

DTIC Science & Technology

2017-04-01

Abnormal Psychology . 56. Tucker, R., Michaels, M., Rogers, M., Wingate, L., & Joiner, T. (2016). Construct validity of a proposed new diagnostic entity...analysis with implications for understanding suicidal behavior. Journal of Abnormal Psychology , 123, 835-840. 2. Anestis, M., Soberay, K., Gutierrez, P...predictions of the interpersonal- psychological theory of suicidal behavior: Empirical tests in two samples of young adults. Journal of Abnormal

Military Suicide Research Consortium

DTIC Science & Technology

2016-10-01

just prior to the time of death: An analysis with implications for understanding suicidal behavior. Journal of Abnormal Psychology , 124(2), 460-461...suicidal behavior. Journal of Abnormal Psychology , 123(4), 835-840. doi: 10.1037/a0037480 Johnson, L. L., O’Connor, S.S., Kaminer, B., Jobes, D. A...Journal of Clinical and Consulting Psychology ; Journal of Abnormal Psychology ; International Journal of Psychology ; Archives of Suicide Research

Attenuation of the Type IV Pilus Retraction Motor Influences Neisseria gonorrhoeae Social and Infection Behavior.

PubMed

Hockenberry, Alyson M; Hutchens, Danielle M; Agellon, Al; So, Magdalene

2016-12-06

Retraction of the type IV pilus (Tfp) mediates DNA uptake, motility, and social and infection behavior in a wide variety of prokaryotes. To date, investigations into Tfp retraction-dependent activities have used a mutant deleted of PilT, the ATPase motor protein that causes the pilus fiber to retract. ΔpilT cells are nontransformable, nonmotile, and cannot aggregate into microcolonies. We tested the hypothesis that these retraction-dependent activities are sensitive to the strength of PilT enzymatic activity by using the pathogen Neisseria gonorrhoeae as a model. We constructed an N. gonorrhoeae mutant with an amino acid substitution in the PilT Walker B box (a substitution of cysteine for leucine at position 201, encoded by pilT L201C ). Purified PilT L201C forms a native hexamer, but mutant hexamers hydrolyze ATP at half the maximal rate. N. gonorrhoeae pilT L201C cells produce Tfp fibers, crawl at the same speed as the wild-type (wt) parent, and are equally transformable. However, the social behavior of pilT L201C cells is intermediate between the behaviors of wt and ΔpilT cells. The infection behavior of pilT L201C is also defective, due to its failure to activate the epidermal growth factor receptor (EGFR)-heparin-binding EGF-like growth factor (HB-EGF) pathway. Our study indicates that pilus retraction, per se, is not sufficient for N. gonorrhoeae microcolony formation or infectivity; rather, these activities are sensitive to the strength of PilT enzymatic activity. We discuss the implications of these findings for Neisseria pathogenesis in the context of mechanobiology. Type IV pili are fibers expressed on the surface of many bacteria. Neisseria gonorrhoeae cells crawl, take up DNA, and communicate with each other and with human cells by retracting these fibers. Here, we show that an N. gonorrhoeae mutant expressing an enzymatically weakened type IV pilus retraction motor still crawls and takes up DNA normally. However, mutant cells exhibit abnormal social behavior, and they are less infective because they fail to activate the epidermal growth factor receptor. Our study shows that N. gonorrhoeae social and infection behaviors are sensitive to the strength of the retraction motor enzyme. Copyright © 2016 Hockenberry et al.

Social development of children born very preterm: a systematic review.

PubMed

Ritchie, Kirsten; Bora, Samudragupta; Woodward, Lianne J

2015-10-01

To review systematically studies examining the development of social competence in children born very preterm (VPT) (gestation <33 wks) and identify neonatal and family predictors. Peer-reviewed original articles were extracted from PubMed and PsycINFO following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Selection criteria included children born VPT and comparison children born at term, sample born after 1990, and children assessed between 0 and 17 years on at least one measure of social competence spanning social adjustment, performance, and/or social skills. Twenty-three studies were included. Seven focused on social competence and another 16 examined social competence within a range of outcomes. Study quality was low. Limitations included reliance on single informant data, cross-sectional measurement, use of brief screening tools, absence of child or peer report, and no conceptual model. In terms of social adjustment, 16 out of 21 studies found children born VPT had more peer problems and social withdrawal. Findings of social performance were mixed, with some studies suggesting differences in prosocial behavior (4/14) and others not. Social skills were assessed in four studies and showed children born VPT had poorer skills than children born at term. Predictors of social competence included gestational age, neonatal brain abnormalities, and family socio-economic status. Children born VPT have poorer social competence. These difficulties emerge early and persist throughout childhood. © 2015 Mac Keith Press.

[Importance for Cancer Education for Schoolchildren].

PubMed

Tanaka, Hideo

2015-08-01

Since the cancer incidence rate is generally very low in individuals aged 10 to 40 years, social concern for cancer prevention education for schoolchildren is likely to be insufficient in Japan.This paper presents epidemiological evidence to stress the importance of preferable health perceptions and behaviors in schoolchildren for the prevention of tobacco-related cancer, abnormal body mass index-related cancer, and cervical cancer.To improve the effectiveness of cancer education for schoolchildren, it is important to monitor their health perceptions and behaviors at least until junior high school.When a goal is set for the reduction of cancer incidence, it takes a very long time (at least 50 years).Therefore, the vision regarding cancer education for schoolchildren should not be changed for at least 50 years, whereas the methods and contents should be revised appropriately.

Comprehensive behavioral analysis of mice deficient in Rapgef2 and Rapgef6, a subfamily of guanine nucleotide exchange factors for Rap small GTPases possessing the Ras/Rap-associating domain.

PubMed

Maeta, Kazuhiro; Hattori, Satoko; Ikutomo, Junji; Edamatsu, Hironori; Bilasy, Shymaa E; Miyakawa, Tsuyoshi; Kataoka, Tohru

2018-05-10

Rapgef2 and Rapgef6 define a subfamily of guanine nucleotide exchange factors for Rap small GTPases, characterized by the possession of the Ras/Rap-associating domain. Previous genomic analyses suggested their possible involvement in the etiology of schizophrenia. We recently demonstrated the development of an ectopic cortical mass (ECM), which resembles the human subcortical band heterotopia, in the dorsal telencephalon-specific Rapgef2 conditional knockout (Rapgef2-cKO) brains. Additional knockout of Rapgef6 in Rapgef2-cKO mice resulted in gross enlargement of the ECM whereas knockout of Rapgef6 alone (Rapgef6-KO) had no discernible effect on the brain morphology. Here, we performed a battery of behavioral tests to examine the effects of Rapgef2 or Rapgef6 deficiency on higher brain functions. Rapgef2-cKO mice exhibited hyperlocomotion phenotypes. They showed decreased anxiety-like behavior in the elevated plus maze and the open-field tests as well as increased depression-like behavior in the Porsolt forced swim and tail suspension tests. They also exhibited increased sociability especially in novel environments. They showed defects in cognitive function as evidenced by reduced learning ability in the Barnes circular maze test and by impaired working memory in the T maze tests. In contrast, although Rapgef6 and Rapgef2 share similarities in biochemical roles, Rapgef6-KO mice exhibited mild behavioral abnormalities detected with a number of behavioral tests, such as hyperlocomotion phenotype in the open-field test and the social interaction test with a novel environment and working-memory defects in the T-maze test. In conclusion, although there were differences in their brain morphology and the magnitude of the behavioral abnormalities, Rapgef2-cKO mice and Rapgef6-KO mice exhibited hyperlocomotion phenotype and working-memory defect, both of which could be recognized as schizophrenia-like behavior.

Diagnosis of Chronic Pancreatitis Incorporating Endosonographic Features, Demographics, and Behavioral Risk.

PubMed

Lee, Linda S; Tabak, Ying P; Kadiyala, Vivek; Sun, Xiaowu; Suleiman, Shadeah; Johannes, Richard S; Banks, Peter A; Conwell, Darwin L

2017-03-01

Diagnosing chronic pancreatitis remains challenging. Endoscopic ultrasound (EUS) is utilized to evaluate pancreatic disease. Abnormal pancreas function test is considered the "nonhistologic" criterion standard for chronic pancreatitis. We derived a prediction model for abnormal endoscopic pancreatic function test (ePFT) by enriching EUS findings with patient demographic and pancreatitis behavioral risk characteristics. Demographics, behavioral risk characteristics, EUS findings, and peak bicarbonate results were collected from patients evaluated for pancreatic disease. Abnormal ePFT was defined as peak bicarbonate of less than 75 mEq/L. We fit a logistic regression model and converted it to a risk score system. The risk score was validated using 1000 bootstrap simulations. A total of 176 patients were included; 61% were female with median age of 48 years (interquartile range, 38-57 years). Abnormal ePFT rate was 39.2% (69/176). Four variables formulated the risk score: alcohol or smoking status, number of parenchymal abnormalities, number of ductal abnormalities, and calcifications. Abnormal ePFT occurred in 10.7% with scores 4 or less versus 92.0% scoring 20 or greater. The model C-statistic was 0.78 (95% confidence interval, 0.71-0.85). Number of EUS pancreatic duct and parenchymal abnormalities, presence of calcification, and smoking/alcohol status were predictive of abnormal ePFT. This simple model has good discrimination for ePFT results.

Independent Review Of Social And Population Variation In Mental Health Could Improve Diagnosis In DSM Revisions

PubMed Central

Hansen, Helena B.; Donaldson, Zoe; Link, Bruce G.; Bearman, Peter S.; Hopper, Kim; Bates, Lisa M.; Cheslack-Postava, Keely; Harper, Kristin; Holmes, Seth M.; Lovasi, Gina; Springer, Kristen W.; Teitler, Julien O.

2013-01-01

At stake in the May 2013 publication of the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5), are billions of dollars in insurance payments and government resources, as well as the diagnoses and treatment of millions of patients. We argue that the most recent revision process has missed social determinants of mental health disorders and their diagnosis: environmental factors triggering biological responses that manifest themselves in behavior; differing cultural perceptions about what is normal and what is abnormal behavior; and institutional pressures related to such matters as insurance reimbursements, disability benefits, and pharmaceutical marketing. In addition, the experts charged with revising the DSM lack a systematic way to take population-level variations in diagnoses into account. To address these problems, we propose the creation of an independent research review body that would monitor variations in diagnostic patterns, inform future DSM revisions, identify needed changes in mental health policy and practice, and recommend new avenues of research. Drawing on the best available knowledge, the review body would make possible more precise and equitable psychiatric diagnoses and interventions. PMID:23614899

[Knowledge and practices of the community health agent in the universe of mental disorder].

PubMed

de Barros, Márcia Maria Mont'alverne; Chagas, Maristela Inês Osawa; Dias, Maria Socorro de Araújo

2009-01-01

This qualitative investigation aimed at collecting information about the knowledge and practices of the community health agents related to the universe of mental disorders. Fourteen agents working in the Family Health Program in Sobral, Ceará were interviewed. We deduced that the concepts of mental disorder are constructed in a process influenced by subjective and socio-cultural aspects and in connection with concrete experiences. The community health agents judge mentally disturbed persons on the basis of different criteria such as normal or abnormal behavior standards and the capacity to make judgments. Social isolation emerged as an important factor, considered by the different research subjects as the cause, the consequence and even as the mental disorder itself. Fear, as a consequence of the strange behavior of people with mental disorders, was identified as an important obstacle for the performance of the community health agents. The strategies adopted by these professionals, fundamentally based on dialogue, reveal concern with social inclusion and the need to involve the families in the care of people with mental disorders.

Examination of AVPR1a as an autism susceptibility gene.

PubMed

Wassink, T H; Piven, J; Vieland, V J; Pietila, J; Goedken, R J; Folstein, S E; Sheffield, V C

2004-10-01

Impaired reciprocal social interaction is one of the core features of autism. While its determinants are complex, one biomolecular pathway that clearly influences social behavior is the arginine-vasopressin (AVP) system. The behavioral effects of AVP are mediated through the AVP receptor 1a (AVPR1a), making the AVPR1a gene a reasonable candidate for autism susceptibility. We tested the gene's contribution to autism by screening its exons in 125 independent autistic probands and genotyping two promoter polymorphisms in 65 autism affected sibling pair (ASP) families. While we found no nonconservative coding sequence changes, we did identify evidence of linkage and of linkage disequilibrium. These results were most pronounced in a subset of the ASP families with relatively less severe impairment of language. Thus, though we did not demonstrate a disease-causing variant in the coding sequence, numerous nontraditional disease-causing genetic abnormalities are known to exist that would escape detection by traditional gene screening methods. Given the emerging biological, animal model, and now genetic data, AVPR1a and genes in the AVP system remain strong candidates for involvement in autism susceptibility and deserve continued scrutiny.

An implicit test of the associations between children and sex in pedophiles.

PubMed

Gray, Nicola S; Brown, Anthony S; MacCulloch, Malcolm J; Smith, Jennifer; Snowden, Robert J

2005-05-01

Pedophiles are motivated to disguise their thoughts and feelings about their sexual beliefs and attraction toward children. New developments using implicit measures of associations have been successful in accessing socially stigmatic beliefs, even in cases in which the participant is resistant to this disclosure. Using an implicit measure, the authors show that pedophiles have an association between children and sex, whereas nonpedophilic offenders have an association between adults and sex. The task can therefore identify a core cognitive abnormality that may underpin some pedophilic deviant sexual behavior. Copyright 2005 APA, all rights reserved.

Phencyclidine increased while isolation rearing did not affect progressive ratio responding in rats: Investigating potential models of amotivation in schizophrenia.

PubMed

Amitai, Nurith; Powell, Susan B; Young, Jared W

2017-11-22

Schizophrenia is a debilitating neurodevelopmental disorder affecting 1% of the global population with heterogeneous symptoms including positive, negative, and cognitive. While treatment for positive symptoms exists, none have been developed to treat negative symptoms. Animal models of schizophrenia are required to test targeted treatments and since patients exhibit reduced effort (breakpoints) for reward in a progressive ratio (PR) task, we examined the PR breakpoints of rats treated with the NMDA receptor antagonist phencyclidine or those reared in isolation - two common manipulations used to induce schizophrenia-relevant behaviors in rodents. In two cohorts, the PR breakpoint for a palatable food reward was examined in Long Evans rats after: 1) a repeated phencyclidine regimen; 2) A subchronic phencyclidine regimen followed by drug washout; and 3) post-weaning social isolation. Rats treated with repeated phencyclidine and those following washout from phencyclidine exhibited higher PR breakpoints than vehicle-treated rats. The breakpoint of isolation reared rats did not differ from those socially reared, despite abnormalities of these rats in other schizophrenia-relevant behaviors. Despite their common use for modeling other schizophrenia-relevant behaviors neither phencyclidine treatment nor isolation rearing recreated the motivational deficits observed in patients with schizophrenia, as measured by PR breakpoint. Other manipulations, and negative symptom-relevant behaviors, require investigation prior to testing putative therapeutics. Copyright © 2017 Elsevier B.V. All rights reserved.

Persistent behavioral effects following early life exposure to retinoic acid or valproic acid in zebrafish

PubMed Central

Bailey, Jordan M.; Oliveri, Anthony N.; Karbhari, Nishika; Brooks, Roy A.J.; De La Rocha, Amberlene J.; Janardhan, Sheila; Levin, Edward D.

2015-01-01

BACKGROUND Moderate to severe dysregulation in retinoid signaling during early development is associated with a constellation of physical malformations and/or neural tube defects, including spina bifida. It is thought that more subtle dysregulation of this system, which might be achievable via dietary (i.e. hypervitaminosis A) or pharmacological (i.e. valproic acid) exposure in humans, will manifest on behavioral domains including sociability, without overt physical abnormalities. METHODS During early life, zebrafish were exposed to low doses of two chemicals that disrupt retinoid signaling. From 0-5 dpf, larvae were reared in aqueous solutions containing retinoic acid (0, 0.02, 0.2 or 2 nM) or valproic acid (0, 0.5, 5.0 or 50 uM). One cohort of zebrafish was assessed using a locomotor activity screen at 6-dpf; another was reared to adulthood and assessed using a neurobehavioral test battery (startle habituation, novel tank exploration, shoaling, and predator escape/avoidance). RESULTS There was no significant increase in the incidence of physical malformation among exposed fish compared to controls. Both retinoic acid and valproic acid exposures during development disrupted larval activity with persisting behavioral alterations later in life, primarily manifesting as decreased social affiliation. CONCLUSIONS Social behavior and some aspects of motor function were altered in exposed fish; the importance of examining emotional or psychological consequences of early life exposure to retinoid acting chemicals is discussed. PMID:26439099

[Effect of sodium valproate on aggressive behavior of male mice with various aggression experience].

PubMed

Smagin, D A; Bondar', N P; Kudriavtseva, N N

2010-01-01

Sector of Social Behavior Neurogenetics, Institute of Cytology and Genetics, Siberian Branch, Effects of sodium valproate on the aggressive behavior of male mice with 2- and 20-day positive fighting experience have been studied. It is established that valproate administered in a singe dose of 100 mg/kg has no effect on the behavior of male mice with a 2-day experience of aggression. The treatment of mice with 300 mg/kg of valproate significantly decreased the level of aggressive motivation and the percentage of animals demonstrating attacks and threats. In male mice with a 20-day experience of aggression, valproate decreased the time of hostile behavior in a dose-dependent manner. Valproate in a single dose of 300 mg/kg significantly decreased the level of aggressive motivation, but also produced a toxic effect, whereby 73% of aggressive males demonstrated long-term immobility and 45% exhibited movement abnormalities (falls) upon the treatment. It is suggested that changes in the brain neurochemical activity, which are caused by a prolonged experience of aggression, modify the effects of sodium valproate.

Neuropathology and Animal Models of Autism: Genetic and Environmental Factors

PubMed Central

Gadad, Bharathi S.; Young, Keith A.; German, Dwight C.

2013-01-01

Autism is a heterogeneous behaviorally defined neurodevelopmental disorder. It is defined by the presence of marked social deficits, specific language abnormalities, and stereotyped repetitive patterns of behavior. Because of the variability in the behavioral phenotype of the disorder among patients, the term autism spectrum disorder has been established. In the first part of this review, we provide an overview of neuropathological findings from studies of autism postmortem brains and identify the cerebellum as one of the key brain regions that can play a role in the autism phenotype. We review research findings that indicate possible links between the environment and autism including the role of mercury and immune-related factors. Because both genes and environment can alter the structure of the developing brain in different ways, it is not surprising that there is heterogeneity in the behavioral and neuropathological phenotypes of autism spectrum disorders. Finally, we describe animal models of autism that occur following insertion of different autism-related genes and exposure to environmental factors, highlighting those models which exhibit both autism-like behavior and neuropathology. PMID:24151553

Serotonin neuron abnormalities in the BTBR mouse model of autism.

PubMed

Guo, Yue-Ping; Commons, Kathryn G

2017-01-01

The inbred mouse strain BTBR T + Itpr3 tf /J (BTBR) is studied as a model of idiopathic autism because they are less social and more resistant to change than other strains. Forebrain serotonin receptors and the response to serotonin drugs are altered in BTBR mice, yet it remains unknown if serotonin neurons themselves are abnormal. In this study, we found that serotonin tissue content and the density of serotonin axons is reduced in the hippocampus of BTBR mice in comparison to C57BL/6J (C57) mice. This was accompanied by possible compensatory changes in serotonin neurons that were most pronounced in regions known to provide innervation to the hippocampus: the caudal dorsal raphe (B6) and the median raphe. These changes included increased numbers of serotonin neurons and hyperactivation of Fos expression. Metrics of serotonin neurons in the rostral 2/3 of the dorsal raphe and serotonin content of the prefrontal cortex were less impacted. Thus, serotonin neurons exhibit region-dependent abnormalities in the BTBR mouse that may contribute to their altered behavioral profile. Autism Res 2017, 10: 66-77. © 2016 International Society for Autism Research, Wiley Periodicals, Inc. © 2016 International Society for Autism Research, Wiley Periodicals, Inc.

Prenatal minocycline treatment alters synaptic protein expression, and rescues reduced mother call rate in oxytocin receptor-knockout mice.

PubMed

Miyazaki, Shinji; Hiraoka, Yuichi; Hidema, Shizu; Nishimori, Katsuhiko

2016-04-01

Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by impaired communication, difficulty in companionship, repetitive behaviors and restricted interests. Recent studies have shown amelioration of ASD symptoms by intranasal administration of oxytocin and demonstrated the association of polymorphisms in the oxytocin receptor (Oxtr) gene with ASD patients. Deficient pruning of synapses by microglial cells in the brain has been proposed as potential mechanism of ASD. Other researchers have shown specific activation of microglial cells in brain regions related to sociality in patients with ASD. Although the roles of Oxtr and microglia in ASD are in the spotlight, the relationship between them remains to be elucidated. In this study, we found abnormal activation of microglial cells and a reduction of postsynaptic density protein PSD95 expression in the Oxtr-deficient brain. Moreover, pharmacological inhibition of microglia during development can alter the expression of PSD95 and ameliorate abnormal mother-infant communication in Oxtr-deficient mice. Our results suggest that microglial abnormality is a potential mechanism of the development of Oxt/Oxtr mediated ASD-like phenotypes. Copyright © 2016 Elsevier Inc. All rights reserved.

76 FR 22925 - Assumption Buster Workshop: Abnormal Behavior Detection Finds Malicious Actors

Federal Register 2010, 2011, 2012, 2013, 2014

2011-04-25

... Technology Research and Development (NITRD) Program, National Science Foundation. ACTION: Call for... NATIONAL SCIENCE FOUNDATION Assumption Buster Workshop: Abnormal Behavior Detection Finds...: The NCO, on behalf of the Special Cyber Operations Research and Engineering (SCORE) Committee, an...

Olfaction in eating disorders and abnormal eating behavior: a systematic review

PubMed Central

Islam, Mohammed A.; Fagundo, Ana B.; Arcelus, Jon; Agüera, Zaida; Jiménez-Murcia, Susana; Fernández-Real, José M.; Tinahones, Francisco J.; de la Torre, Rafael; Botella, Cristina; Frühbeck, Gema; Casanueva, Felipe F.; Menchón, José M.; Fernandez-Aranda, Fernando

2015-01-01

The study provides a systematic review that explores the current literature on olfactory capacity in abnormal eating behavior. The objective is to present a basis for discussion on whether research in olfaction in eating disorders may offer additional insight with regard to the complex etiopathology of eating disorders (ED) and abnormal eating behaviors. Electronic databases (Medline, PsycINFO, PubMed, Science Direct, and Web of Science) were searched using the components in relation to olfaction and combining them with the components related to abnormal eating behavior. Out of 1352 articles, titles were first excluded by title (n = 64) and then by abstract and fulltext resulting in a final selection of 14 articles (820 patients and 385 control participants) for this review. The highest number of existing literature on olfaction in ED were carried out with AN patients (78.6%) followed by BN patients (35.7%) and obese individuals (14.3%). Most studies were only conducted on females. The general findings support that olfaction is altered in AN and in obesity and indicates toward there being little to no difference in olfactory capacity between BN patients and the general population. Due to the limited number of studies and heterogeneity this review stresses on the importance of more research on olfaction and abnormal eating behavior. PMID:26483708

Olfaction in eating disorders and abnormal eating behavior: a systematic review.

PubMed

Islam, Mohammed A; Fagundo, Ana B; Arcelus, Jon; Agüera, Zaida; Jiménez-Murcia, Susana; Fernández-Real, José M; Tinahones, Francisco J; de la Torre, Rafael; Botella, Cristina; Frühbeck, Gema; Casanueva, Felipe F; Menchón, José M; Fernandez-Aranda, Fernando

2015-01-01

The study provides a systematic review that explores the current literature on olfactory capacity in abnormal eating behavior. The objective is to present a basis for discussion on whether research in olfaction in eating disorders may offer additional insight with regard to the complex etiopathology of eating disorders (ED) and abnormal eating behaviors. Electronic databases (Medline, PsycINFO, PubMed, Science Direct, and Web of Science) were searched using the components in relation to olfaction and combining them with the components related to abnormal eating behavior. Out of 1352 articles, titles were first excluded by title (n = 64) and then by abstract and fulltext resulting in a final selection of 14 articles (820 patients and 385 control participants) for this review. The highest number of existing literature on olfaction in ED were carried out with AN patients (78.6%) followed by BN patients (35.7%) and obese individuals (14.3%). Most studies were only conducted on females. The general findings support that olfaction is altered in AN and in obesity and indicates toward there being little to no difference in olfactory capacity between BN patients and the general population. Due to the limited number of studies and heterogeneity this review stresses on the importance of more research on olfaction and abnormal eating behavior.

Predictive factors and psychosocial effects of Internet addictive behaviors in Cypriot adolescents.

PubMed

Critselis, Elena; Janikian, Mari; Paleomilitou, Noni; Oikonomou, Despoina; Kassinopoulos, Marios; Kormas, George; Tsitsika, Artemis

2014-01-01

Internet addictive behaviors are associated with a plethora of psychosocial adversities. The study objectives were to assess the determinants and psychosocial correlates associated with Internet addictive behaviors among adolescents. A cross-sectional study design was applied among a random sample (n=805) of Cypriot adolescents (mean age: 14.7 years). Self-completed questionnaires, including Internet use characteristics, Young Internet Addiction Test, and Strengths and Difficulties Questionnaire, were utilized. Among the study population, the prevalence rates of borderline addictive Internet use (BIU) and addictive Internet use (AIU) were 18.4% and 2%, respectively. Adolescents with BIU had an increased likelihood of concomitantly presenting with abnormal peer relations (AOR: 5.28; 95% confidence interval, CI: 3.37-23.38), conduct problems (AOR: 4.77; 95% CI: 2.82-8.08), hyperactivity (AOR: 5.58; 95% CI: 2.58-12.10) and emotional symptoms (AOR: 2.85; 95% CI: 1.53-5.32). Adolescent AIU was significantly associated with abnormal conduct (AOR: 22.31; 95% CI: 6.90-72.19), peer problems (AOR: 7.14; 95% CI: 1.36-37.50), emotional symptoms (AOR: 19.06; 95% 6.06-60.61), and hyperactivity (AOR: 9.49, 95% CI: 1.87-48.19). The determinants of BIU and AIU included accessing the Internet for the purposes of retrieving sexual information (AOR: 1.17; 95% CI: 1.17-3.23) and participating in games with monetary awards (AOR: 1.90; 95% CI: 1.15-3.14). Both BIU and AIU were adversely associated with notable behavioral and social maladjustment among adolescents.

Diurnal cortisol rhythms, fatigue and psychosocial factors in five-year survivors of ovarian cancer.

PubMed

Cuneo, Michaela G; Schrepf, Andrew; Slavich, George M; Thaker, Premal H; Goodheart, Michael; Bender, David; Cole, Steve W; Sood, Anil K; Lutgendorf, Susan K

2017-10-01

Fatigue is a challenge in ovarian cancer survivorship and greatly impacts quality of life. In other cancer populations, fatigue has been associated with abnormal diurnal cortisol patterns. However, little is known about biological and behavioral factors in 5+-year ovarian cancer survivors and potential mechanisms underlying persistent fatigue have not been investigated in this population. Moreover, relationships between neuroendocrine and psychosocial factors in 5+-year ovarian cancer survivors have not been studied. We addressed these issues by examining relationships between diurnal cortisol rhythms, fatigue, life stress, and social support in 30 survivors of ovarian cancer who were assessed at least 5 years (mean=6.20years) following their primary diagnosis. Flatter diurnal cortisol slopes were associated with higher levels of fatigue, suggesting a role for HPA-axis dysregulation in sustained fatigue experienced by survivors. Moreover, greater cumulative lifetime stressor exposure (p=0.023) and stressor severity (p=0.004) were associated with flatter diurnal cortisol slopes, while higher social attachment (p=0.001) was associated with steeper diurnal cortisol slopes. These findings suggest that ovarian cancer survivors with greater lifetime stress exposure or lower social attachment may be at increased risk for circadian rhythm disruption, which in turn is associated with fatigue. Future research should examine relationships of clinical stage and inflammatory cytokines to cortisol rhythms and fatigue in long-term ovarian cancer survivors, as well as investigating the clinical significance of abnormal diurnal cortisol profiles in this population. Copyright © 2017 Elsevier Ltd. All rights reserved.

Ethnic differences in social support after initial receipt of an abnormal mammogram.

PubMed

Molina, Yamile; Hohl, Sarah D; Nguyen, Michelle; Hempstead, Bridgette H; Weatherby, Shauna Rae; Dunbar, Claire; Beresford, Shirley A A; Ceballos, Rachel M

2016-10-01

We examine access to and type of social support after initial receipt of an abnormal mammogram across non-Latina White (NLW), African American, and Latina women. This cross-sectional study used a mixed method design, with quantitative and qualitative measures. Women were recruited through 2 community advocates and 3 breast-health-related care organizations. With regard to access, African American women were less likely to access social support relative to NLW counterparts. Similar nonsignificant differences were found for Latinas. Women did not discuss results with family and friends to avoid burdening social networks and negative reactions. Networks' geographic constraints and medical mistrust influenced Latina and African American women's decisions to discuss results. With regard to type of social support, women reported emotional support across ethnicity. Latina and African American women reported more instrumental support, whereas NLW women reported more informational support in the context of their well-being. There are shared and culturally unique aspects of women's experiences with social support after initially receiving an abnormal mammogram. Latina and African American women may particularly benefit from informational support from health care professionals. Communitywide efforts to mitigate mistrust and encourage active communication about cancer may improve ethnic disparities in emotional well-being and diagnostic resolution during initial receipt of an abnormal mammogram. (PsycINFO Database Record (c) 2016 APA, all rights reserved).

Autistic spectrum disorder: evaluating a possible contributing or causal role of epilepsy.

PubMed

Deonna, Thierry; Roulet, Eliane

2006-01-01

The onset of epilepsy in brain systems involved in social communication and/or recognition of emotions can occasionally be the cause of autistic symptoms or may aggravate preexisting autistic symptoms. Knowing that cognitive and/or behavioral abnormalities can be the presenting and sometimes the only symptom of an epileptic disorder or can even be caused by paroxysmal EEG abnormalities without recognized seizures, the possibility that this may apply to autism has given rise to much debate. Epilepsy and/or epileptic EEG abnormalities are frequently associated with autistic disorders in children but this does not necessarily imply that they are the cause; great caution needs to be exercised before drawing any such conclusions. So far, there is no evidence that typical autism can be attributed to an epileptic disorder, even in those children with a history of regression after normal early development. Nevertheless, there are several early epilepsies (late infantile spasms, partial complex epilepsies, epilepsies with CSWS, early forms of Landau-Kleffner syndrome) and with different etiologies (tuberous sclerosis is an important model of these situations) in which a direct relationship between epilepsy and some features of autism may be suspected. In young children who primarily have language regression (and who may have autistic features) without evident cause, and in whom paroxysmal focal EEG abnormalities are also found, the possible direct role of epilepsy can only be evaluated in longitudinal studies.

Abnormal emotion processing, but intact fairness and intentionality considerations during social decision-making in schizophrenia

PubMed Central

de la Asuncion, Javier; Docx, Lise; Sabbe, Bernard; Morrens, Manuel; de Bruijn, Ellen R. A.

2015-01-01

Schizophrenia is a severe mental disorder that is highly characterized by social cognitive impairments. Most studies investigating these impairments focus on one specific social domain such as emotion recognition. However, in daily life, processing complex social situations relies on the combination of several social cognitive and affective processes simultaneously rather than one process alone. A modified version of the economically based Ultimatum Game was used to measure the interplay between fairness, intentionality, and emotion considerations during social decision-making. In this task, participants accept or reject fair and unfair monetary offers proposed intentionally or unintentionally by either angry, happy, neutral, or sad proposers. Behavioral data was collected from a group of schizophrenia patients (N = 35) and a group of healthy individuals (N = 30). Like healthy participants, schizophrenia patients differentiated between fair and unfair offers by rejecting unfair offers more compared to fair offers. However, overall patients did reject more fair offers, indicating that their construct of fairness operates within different margins. In both groups, intentional unfair offers were rejected more compared to unintentional ones, indicating a normal integration of intentionality considerations in schizophrenia. Importantly, healthy subjects also differentiated between proposers’ emotion when rejecting unfair offers (more rejections from proposers depicting angry faces compared to proposers depicting, happy, neutral, or sad faces). Schizophrenia patients’ decision behavior on the other hand, was not affected by the proposers’ emotions. The current study thus shows that schizophrenia patients have specific problems with processing and integrating emotional information. Importantly, the finding that patients display normal fairness and intentionality considerations emphasizes preservation of central social cognitive processes in schizophrenia. PMID:26257699

Possible Electromagnetic Effects on Abnormal Animal Behavior Before an Earthquake

PubMed Central

Hayakawa, Masashi

2013-01-01

Simple Summary Possible electromagnetic effects on abnormal animal behavior before earthquakes. Abstract The former statistical properties summarized by Rikitake (1998) on unusual animal behavior before an earthquake (EQ) have first been presented by using two parameters (epicentral distance (D) of an anomaly and its precursor (or lead) time (T)). Three plots are utilized to characterize the unusual animal behavior; (i) EQ magnitude (M) versus D, (ii) log T versus M, and (iii) occurrence histogram of log T. These plots are compared with the corresponding plots for different seismo-electromagnetic effects (radio emissions in different frequency ranges, seismo-atmospheric and -ionospheric perturbations) extensively obtained during the last 15–20 years. From the results of comparisons in terms of three plots, it is likely that lower frequency (ULF (ultra-low-frequency, f ≤ 1 Hz) and ELF (extremely-low-frequency, f ≤ a few hundreds Hz)) electromagnetic emissions exhibit a very similar temporal evolution with that of abnormal animal behavior. It is also suggested that a quantity of field intensity multiplied by the persistent time (or duration) of noise would play the primary role in abnormal animal behavior before an EQ. PMID:26487307

Preliminary Evidence of White Matter Abnormality in the Uncinate Fasciculus in Generalized Social Anxiety Disorder

PubMed Central

Phan, K. Luan; Orlichenko, Anton; Boyd, Erin; Angstadt, Mike; Coccaro, Emil F.; Liberzon, Israel; Arfanakis, Konstantinos

2009-01-01

Background Individuals with generalized social anxiety disorder (GSAD) exhibit exaggerated amygdala reactivity to aversive social stimuli. These findings could be explained by microstructural abnormalities in white matter (WM) tracts that connect the amygdala and prefrontal cortex, which is known to modulate the amygdala’s response to threat. The goal of this study was to investigate brain frontal WM abnormalities by using diffusion tensor imaging (DTI) in patients with social anxiety disorder. Method A Turboprop DTI sequence was used to acquire diffusion tensor images in thirty patients with GSAD and thirty matched healthy controls. Fractional anisotropy, an index of axonal organization, within WM was quantified in individual subjects and an automated voxel-based, whole-brain method was used to analyze group differences. Results Compared to healthy controls, patients had significantly lower fractional anisotropy localized to the right uncinate fasciculus WM near the orbitofrontal cortex. There were no areas of higher fractional anisotropy in patients than controls. Conclusions These findings point to an abnormality in the uncinate fasciculus, the major WM tract connecting the frontal cortex to the amygdala and other limbic temporal regions, in GSAD which could underlie the aberrant amygdala-prefrontal interactions resulting in dysfunctional social threat processing in this illness. PMID:19362707

Behavioral characterization of escalated aggression induced by GABAB receptor activation in the dorsal raphé nucleus

PubMed Central

Takahashi, Aki; Schilit, Arielle N.; Kim, Jisoo; DeBold, Joseph F.; Koide, Tsuyoshi; Miczek, Klaus A.

2013-01-01

Rationale Pharmacological activation of GABAB receptors in the dorsal raphé nucleus (DRN) can escalate territorial aggression in male mice. Objectives We characterized this escalated aggression in terms of its behavioral and environmental determinants. Methods Aggressive behavior of resident male (CFW or ICR mouse) was assessed in confrontations with a group-housed intruder. Either baclofen (0.06 nmol/0.2 μl) or vehicle (saline) was microinjected into the DRN ten minutes before the confrontation. We examined baclofen-heightened aggression in five situations: aggression in a neutral arena and after social instigation (experiment 1), aggression during the light phase of the cycle (experiment 2), aggression without prior fighting experience (experiment 3), aggression toward a female (experiment 4), and aggression after defeat experiences (experiment 5). In addition, we examined the body targets towards which bites are directed and the duration of aggressive bursts after baclofen treatment. Results Regardless of the past social experience, baclofen escalated aggressive behaviors. Even in the neutral arena and after defeat experiences, where aggressive behaviors were inhibited, baclofen significantly increased aggression. Baclofen increased attack bites directed at vulnerable body areas of male intruders but not toward a female and only in the dark. Also, baclofen prolonged the duration of aggressive bursts. Conclusions For baclofen to escalate aggression, specific stimulation (male intruder) and tonic level of serotonin (dark cycle) are required. Once aggressive behavior is triggered, intra-DRN baclofen escalates the level of aggression to abnormal levels and renders it difficult to terminate. Also, baclofen counteracts the effects of novelty or past experiences of defeat. PMID:22395428

A partial loss of function allele of Methyl-CpG-binding protein 2 predicts a human neurodevelopmental syndrome

PubMed Central

Samaco, Rodney C.; Fryer, John D.; Ren, Jun; Fyffe, Sharyl; Chao, Hsiao-Tuan; Sun, Yaling; Greer, John J.; Zoghbi, Huda Y.; Neul, Jeffrey L.

2008-01-01

Rett Syndrome, an X-linked dominant neurodevelopmental disorder characterized by regression of language and hand use, is primarily caused by mutations in methyl-CpG-binding protein 2 (MECP2). Loss of function mutations in MECP2 are also found in other neurodevelopmental disorders such as autism, Angelman-like syndrome and non-specific mental retardation. Furthermore, duplication of the MECP2 genomic region results in mental retardation with speech and social problems. The common features of human neurodevelopmental disorders caused by the loss or increase of MeCP2 function suggest that even modest alterations of MeCP2 protein levels result in neurodevelopmental problems. To determine whether a small reduction in MeCP2 level has phenotypic consequences, we characterized a conditional mouse allele of Mecp2 that expresses 50% of the wild-type level of MeCP2. Upon careful behavioral analysis, mice that harbor this allele display a spectrum of abnormalities such as learning and motor deficits, decreased anxiety, altered social behavior and nest building, decreased pain recognition and disrupted breathing patterns. These results indicate that precise control of MeCP2 is critical for normal behavior and predict that human neurodevelopmental disorders will result from a subtle reduction in MeCP2 expression. PMID:18321864

Reduced Glutamate Release in Adult BTBR Mouse Model of Autism Spectrum Disorder.

PubMed

Wei, Hongen; Ma, Yuehong; Ding, Caiyun; Jin, Guorong; Liu, Jianrong; Chang, Qiaoqiao; Hu, Fengyun; Yu, Li

2016-11-01

Autism spectrum disorder (ASD) is a developmental disorder characterized by impairments in social and communication abilities, as well as by restricted and repetitive behaviors. The BTBR T + Itpr3 tf (BTBR) mice have emerged as a well characterized and widely used mouse model of a range of ASD-like phenotype, showing deficiencies in social behaviors and unusual ultrasonic vocalizations as well as increased repetitive self-grooming. However, the inherited neurobiological changes that lead to ASD-like behaviors in these mice are incompletely known and still under active investigation. The aim of this study was to further evaluate the structure and neurotransmitter release of the glutamatergic synapse in BTBR mice. C57BL/6J (B6) mice were used as a control strain because of their high level of sociability. The important results showed that the evoked glutamate release in the cerebral cortex of BTBR mice was significantly lower than in B6 mice. And the level of vesicle docking-related protein Syntaxin-1A was reduced in BTBR mice. However, no significant changes were observed in the number of glutamatergic synapse, level of synaptic proteins, density of dendritic spine and postsynaptic density between BTBR mice and B6 mice. Overall, our results suggest that abnormal vesicular glutamate activity may underlie the ASD relevant pathology in the BTBR mice.

Trait-level temporal lobe hypoactivation to social exclusion in unaffected siblings of children and adolescents with autism spectrum disorders

PubMed Central

Bolling, Danielle Z.; Pelphrey, Kevin A.; Vander Wyk, Brent C.

2015-01-01

Social exclusion elicits powerful feelings of negative affect associated with rejection. Additionally, experiencing social exclusion reliably recruits neural circuitry associated with emotion processing. Recent work has demonstrated abnormal neural responses to social exclusion in children and adolescents with autism spectrum disorders (ASD). However, it remains unknown to what extent these abnormalities are due to atypical social experiences versus genetic predispositions to atypical neural processing. To address this question, the current study investigated brain responses to social exclusion compared to a baseline condition of fair play in unaffected siblings of youth with ASD using functional magnetic resonance imaging. We identified common deviations between unaffected siblings and ASD probands that might represent trait-level abnormalities in processing social exclusion versus fair play, specifically in the right anterior temporoparietal junction extending into posterior superior temporal sulcus. Thus, hypoactivation to social exclusion versus fair play in this region may represent a shared genetic vulnerability to developing autism. In addition, we present evidence supporting the idea that one’s status as an unaffected sibling moderates the relationship between IQ and neural activation to social exclusion versus fair play in anterior cingulate cortex. These results are discussed in the context of previous literature on neural endophenotypes of autism. PMID:26011751

Walk like me, talk like me

PubMed Central

Saffin, Jillian M.; Tohid, Hassaan

2016-01-01

Understanding social cognition has become a hallmark in deciphering autism spectrum disorder. Neurobiological theories are taking precedence in causation studies as researchers look to abnormalities in brain development as the cause of deficits in social behavior, cognitive processes, and language. Following their discovery in the 1990s, mirror neurons have become a dominant theory for that the mirror neuron system may play a critical role in the pathophysiology of various symptoms of autism. Over the decades, the theory has evolved from the suggestion of a broken mirror neuron system to impairments in mirror neuron circuitry. The mirror neuron system has not gained total support due to inconsistent findings; a comprehensive analysis of the growing body of research could shed light on the benefits, or the disadvantage of continuing to study mirror neurons and their connection to autism. PMID:27094520

Chromosomal abnormalities, meiotic behavior and fertility in domestic animals.

PubMed

Villagómez, D A F; Pinton, A

2008-01-01

Since the advent of the surface microspreading technique for synaptonemal complex analysis, increasing interest in describing the synapsis patterns of chromosome abnormalities associated with fertility of domestic animals has been noticed during the past three decades. In spite of the number of scientific reports describing the occurrence of structural chromosome abnormalities, their meiotic behavior and gametic products, little is known in domestic animal species about the functional effects of such chromosome aberrations in the germ cell line of carriers. However, some interesting facts gained from recent and previous studies on the meiotic behavior of chromosome abnormalities of domestic animals permit us to discuss, in the frame of recent knowledge emerging from mouse and human investigations, the possible mechanism implicated in the well known association between meiotic disruption and chromosome pairing failure. New cytogenetic techniques, based on molecular and immunofluorescent analyses, are allowing a better description of meiotic processes, including gamete production. The present communication reviews the knowledge of the meiotic consequences of chromosome abnormalities in domestic animals. Copyright 2008 S. Karger AG, Basel.

The Utility of Chromosomal Microarray Analysis in Developmental and Behavioral Pediatrics

ERIC Educational Resources Information Center

Beaudet, Arthur L.

2013-01-01

Chromosomal microarray analysis (CMA) has emerged as a powerful new tool to identify genomic abnormalities associated with a wide range of developmental disabilities including congenital malformations, cognitive impairment, and behavioral abnormalities. CMA includes array comparative genomic hybridization (CGH) and single nucleotide polymorphism…

Theoretical perspectives accounting for adolescent homosexuality.

PubMed

Savin-Williams, R C

1988-03-01

Few topics in sexology elicit such a diversity of opinions and emotions as the question of etiology of homosexuality. Views frequently carry with them implicit or explicit messages concerning the psychologic health of this sexual orientation. Theories of sexual development usually portray adolescence as a critical time in the life course because of changes in: 1) anatomy and physiology; 2) psychologic functioning: the reawakening, renewal, and reliving of previously established sexual relations and drives; and/or 3) social conditions: an increased exposure and adherence to societal messages concerning appropriate and inappropriate social and sexual behaviors and relationships. This paper provides a brief overview of several major theories--evolutionary biology, psychoanalysis, and social processes--as they relate to the development of sexual orientation. In addition, an ethologic perspective that synthesizes various etiologic theories, as they relate to homosexuality during adolescence, is briefly reviewed. In these discussions, the issue of whether homosexuality is a normal or abnormal developmental state during adolescence is also addressed.

AN OBSERVATIONAL STUDY OF SOCIAL CONTROL, MOOD, AND SELF-EFFICACY IN COUPLES DURING TREATMENT FOR HEAD AND NECK CANCER

PubMed Central

BADR, HODA; YEUNG, CHI; LEWIS, MEGAN A.; MILBURY, KATHRIN; REDD, WILLIAM H.

2014-01-01

OBJECTIVE Head and neck cancer (HNC) patients experience debilitating side effects, including abnormally reduced salivation and difficulty swallowing. Intensive self-care protocols are prescribed to control side effects and minimize discomfort, but non-adherence rates are high. Although spouses are in a prime position to encourage adherence, studies have yet to examine how spouse social control (i.e., attempts to influence patient behavior to support adherence) affects HNC patient mood and self-efficacy for engaging in these self-care routines. METHODS One-hundred twenty-five HNC couples where the patient (86% male) was undergoing radiotherapy were recorded in the laboratory as they discussed a cancer-related issue that the patient identified as being a topic of concern. RESULTS Sixty-eight couples discussed side-effects and spouses engaged in social control in 61 of these discussions. Although oral complications and pain were frequently identified by patients as being topics of concern, dental/oral care and pain management were some of the least likely self-care behaviors to be targeted by spouses, who focused primarily on encouraging patients to maintain their weight and hydration. Although spouses engaged in an almost equal number of positive and negative control attempts, only positive control was significantly (p<.05) associated with patient positive mood and self-efficacy. CONCLUSION HNC couples may benefit from programs that emphasize the regular practice of self-care routines to control oral side effects, pain, and nutrition/hydration problems. Likewise, programs that encourage spouses to maximize their use of positive social control may also boost patients’ mood during treatment and empower them to engage in recommended self-care behaviors. PMID:25471820

Evaluation of early childhood social-communication difficulties in children born preterm using the Quantitative Checklist for Autism in Toddlers.

PubMed

Wong, Hilary S; Huertas-Ceballos, Angela; Cowan, Frances M; Modi, Neena

2014-01-01

To characterize early childhood social-communication skills and autistic traits in children born very preterm using the Quantitative Checklist for Autism in Toddlers (Q-CHAT) and explore neonatal and sociodemographic factors associated with Q-CHAT scores. Parents of children born before 30 weeks gestation and enrolled in a study evaluating routinely collected neurodevelopmental data between the post-menstrual ages of 20 and 28 months were invited to complete the Q-CHAT questionnaire. Children with severe neurosensory disabilities and cerebral palsy were excluded. Participants received neurodevelopmental assessments using the Bayley Scales of Infant and Toddler Development, 3rd edition (Bayley-III). Q-CHAT scores of this preterm cohort were compared with published general population scores. The association between Bayley-III cognitive and language scores and neonatal and sociodemographic factors with Q-CHAT scores were examined. Q-CHAT questionnaires were completed from 141 participants. At a mean post-menstrual age of 24 months, the Q-CHAT scores of the preterm cohort (mean 33.7, SD 8.3) were significantly higher than published general population scores (mean 26.7; SD 7.8), indicating greater social-communication difficulty and autistic behavior. Preterm children received higher scores, particularly in the categories of restricted, repetitive, stereotyped behavior, communication, and sensory abnormalities. Lower Bayley-III language scores and non-white ethnicity were associated with higher Q-CHAT scores. Preterm children display greater social-communication difficulty and autistic behavior than the general population in early childhood as assessed by the Q-CHAT. The implications for longer-term outcome will be important to assess. Copyright © 2014 Mosby, Inc. All rights reserved.

[Abnormal cervicovaginal cytology in women with rheumatoid arthritis].

PubMed

Mercado, Ulises

2010-02-01

Patients with rheumatoid arthritis (RA) are at increased risk of infections and cancer. A link between RA and abnormal cervicovaginal cytology has rarely been reported. The aim of this study was to review cervicovaginal cytology results in women with RA and compare them with a control population. Sexual behavior also was investigated. Cervicovaginal cytology results of 95 women with RA were compared to those of a control population of 1,719 women attending at the same hospital and followed until June 2009. Records of RA patients were reviewed to obtain clinical data, particularly sexual behavior. Of 95 RA patients, 13/95 had an abnormal cervicovaginal cytology result, compared with 120/1,719 controls. Twelve/13 had squamous intraepithelial lesions (SIL), compared with 27/120 controls. There was no significant difference in sexual partners between women with RA and controls. Women with RA without abnormal cervicovaginal cytology had less sexual partners than those with RA and abnormal cytology. Two women with RA and abnormal cervicovaginal cytology had a history of condylomata and herpes genital. Three/13 women with RA developed abnormal cervicovaginal cytology after 12 to 36 months initiating their illness. None from them had ever received immunosuppressants. Women with RA have an increased prevalence of abnormal cervical cytology, compared with a control population. It may be related to chronic inflammatory disease and sexual behavior.

Dissociable patterns of medial prefrontal and amygdala activity to face identity versus emotion in bipolar disorder.

PubMed

Keener, M T; Fournier, J C; Mullin, B C; Kronhaus, D; Perlman, S B; LaBarbara, E; Almeida, J C; Phillips, M L

2012-09-01

Individuals with bipolar disorder demonstrate abnormal social function. Neuroimaging studies in bipolar disorder have shown functional abnormalities in neural circuitry supporting face emotion processing, but have not examined face identity processing, a key component of social function. We aimed to elucidate functional abnormalities in neural circuitry supporting face emotion and face identity processing in bipolar disorder. Twenty-seven individuals with bipolar disorder I currently euthymic and 27 healthy controls participated in an implicit face processing, block-design paradigm. Participants labeled color flashes that were superimposed on dynamically changing background faces comprising morphs either from neutral to prototypical emotion (happy, sad, angry and fearful) or from one identity to another identity depicting a neutral face. Whole-brain and amygdala region-of-interest (ROI) activities were compared between groups. There was no significant between-group difference looking across both emerging face emotion and identity. During processing of all emerging emotions, euthymic individuals with bipolar disorder showed significantly greater amygdala activity. During facial identity and also happy face processing, euthymic individuals with bipolar disorder showed significantly greater amygdala and medial prefrontal cortical activity compared with controls. This is the first study to examine neural circuitry supporting face identity and face emotion processing in bipolar disorder. Our findings of abnormally elevated activity in amygdala and medial prefrontal cortex (mPFC) during face identity and happy face emotion processing suggest functional abnormalities in key regions previously implicated in social processing. This may be of future importance toward examining the abnormal self-related processing, grandiosity and social dysfunction seen in bipolar disorder.

Decreased functional connectivity in schizophrenia: The relationship between social functioning, social cognition and graph theoretical network measures.

PubMed

Erdeniz, Burak; Serin, Emin; İbadi, Yelda; Taş, Cumhur

2017-12-30

Schizophrenia is a complex disorder in which abnormalities in brain connectivity and social functioning play a central role. The aim of this study is to explore small-world network properties, and understand their relationship with social functioning and social cognition in the context of schizophrenia, by testing functional connectivity differences in network properties and its relation to clinical behavioral measures. Resting-state fMRI time series data were acquired from 23 patients diagnosed with schizophrenia and 23 healthy volunteers. The results revealed that patients with schizophrenia show significantly decreased connectivity between a range of brain regions, particularly involving connections among the right orbitofrontal cortex, bilateral putamen and left amygdala. Furthermore, topological properties of functional brain networks in patients with schizophrenia were characterized by reduced path length compared to healthy controls; however, no significant difference was found for clustering coefficient, local efficiency or global efficiency. Additionally, we found that nodal efficiency of the amygdala and the putamen were significantly correlated with the independence-performance subscale of social functioning scale (SFC), and Reading the Mind in the Eyes test; however, the correlations do not survive correction for multiple comparison. The current results help to clarify the relationship between social functioning deficits and topological brain measures in schizophrenia. Copyright © 2017 Elsevier B.V. All rights reserved.

Other Persons: On the Phenomenology of Interpersonal Experience in Schizophrenia (Ancillary Article to EAWE Domain 3).

PubMed

Stanghellini, Giovanni; Ballerini, Massimo; Mancini, Milena

2017-01-01

In this paper, we discuss the philosophical and psychopathological background of Domain 3, Other persons, of the Examination of Anomalous World Experiences (EAWE). The EAWE interview aims to describe the manifold phenomena of the schizophrenic lifeworld in all of their concrete and distinctive features, thus complementing a more abstract, symptom-focused approach. Domain 3, Other persons, focuses specifically on subjectively experienced interpersonal disturbances that may be especially common in schizophrenia. The aim of this domain, as with the rest of the EAWE, is to provide clinicians and researchers with a systematic orientation toward, or knowledge of, patients' experiences, so that the experiential universe of schizophrenia can be clarified in terms of the particular feel, meaning, and value it has for the patient. To help provide a context for EAWE Domain 3, Other persons, we propose a definition of "intersubjectivity" (IS) and "dissociality." The former is the ability to understand other persons, that is, the basis of our capacity to experience people and social situations as meaningful. IS relies both on perceptive- intuitive as well as cognitive-computational resources. Dissociality addresses the core psychopathological nucleus characterizing the quality of abnormal IS in persons with schizophrenia and covers several dimensions, including disturbances of both perceptive-intuitive and cognitive-computational capacities. The most typical perceptive-intuitive abnormality is hypoattunement, that is, the lack of interpersonal resonance and difficulties in grasping or immediately understanding others' mental states. The most characteristic cognitive-computational anomaly is social hyperreflexivity, especially an algorithmic conception of sociality (an observational/ethological attitude aimed to develop an explicit, often rule-based personal method for participating in social transactions). Other anomalous interpersonal experiences, such as emotional and behavioral responses to others, are also discussed in relation to this core of dissociality. © 2017 S. Karger AG, Basel.

Callous-unemotional traits drive reduced white-matter integrity in youths with conduct problems.

PubMed

Breeden, A L; Cardinale, E M; Lozier, L M; VanMeter, J W; Marsh, A A

2015-10-01

Callous-unemotional (CU) traits represent a significant risk factor for severe and persistent conduct problems in children and adolescents. Extensive neuroimaging research links CU traits to structural and functional abnormalities in the amygdala and ventromedial prefrontal cortex. In addition, adults with psychopathy (a disorder for which CU traits are a developmental precursor) exhibit reduced integrity in uncinate fasciculus, a white-matter (WM) tract that connects prefrontal and temporal regions. However, research in adolescents has not yet yielded similarly consistent findings. We simultaneously modeled CU traits and externalizing behaviors as continuous traits, while controlling for age and IQ, in order to identify the unique relationship of each variable with WM microstructural integrity, assessed using diffusion tensor imaging. We used tract-based spatial statistics to evaluate fractional anisotropy, an index of WM integrity, in uncinate fasciculus and stria terminalis in 47 youths aged 10-17 years, of whom 26 exhibited conduct problems and varying levels of CU traits. Whereas both CU traits and externalizing behaviors were negatively correlated with WM integrity in bilateral uncinate fasciculus and stria terminalis/fornix, simultaneously modeling both variables revealed that these effects were driven by CU traits; the severity of externalizing behavior was not related to WM integrity after controlling for CU traits. These results indicate that WM abnormalities similar to those observed in adult populations with psychopathy may emerge in late childhood or early adolescence, and may be critical to understanding the social and affective deficits observed in this population.

Sleep in children with autistic spectrum disorder.

PubMed

Cortesi, Flavia; Giannotti, Flavia; Ivanenko, Anna; Johnson, Kyle

2010-08-01

Children and adolescents with autistic spectrum disorders (ASD) suffer from sleep problems, particularly insomnia, at a higher rate than typically developing children, ranging from 40% to 80%. Sleep problems in ASD might occur as a result of complex interactions between biological, psychological, social/environmental, and family factors, including child rearing practices that are not conducive to good sleep. Interestingly, children with a history of developmental regression have a more disturbed sleep pattern than children without regression. Even though regulation of sleep in children with ASD is still poorly understood, circadian abnormalities in autism might be the result of genetic abnormalities related to melatonin synthesis and melatonin's role in modulating synaptic transmission. Recently a bifurcation of the sleep/wake cycle with increased sensitivity to external noise and short sleep duration causing irregular sleep onset and wake up times has been suggested. Identifying and treating sleep disorders may result not only in improved sleep, but also impact favorably on daytime behavior and family functioning. Several studies have also demonstrated effectiveness of behavioral interventions for sleep onset and maintenance problems in these populations. When behavioral interventions are not effective or lead only to a partial response, pharmacological treatment options should be considered. Studies of melatonin use in children with ASD provide evidence for its effectiveness and safety in the long run. The clinician assessing a child with an ASD should screen carefully for sleep disorders and make referrals as indicated. Copyright 2010 Elsevier B.V. All rights reserved.

Understanding Lay Assessments of Alcohol Use Disorder: Need for Treatment and Associated Stigma.

PubMed

Weine, Erienne R; Kim, Nancy S; Lincoln, Alisa K

2016-01-01

Three-quarters of people with an alcohol use disorder in the USA never receive treatment. Our understandings of who receives care are informed by sociological perspectives, theories and models, each of which discuss the role of lay people's understanding of illness. However, comparatively little work has been done to unpack the cognitive processes underlying lay assessment. In the context of the Framework Integrating Normative Influences on Stigma (FINIS), we aim to understand key factors guiding lay people's stigmatizing attitudes, perceptions and assessments of alcohol use disorder behaviors. Lay people read a vignette depicting a male or female adult with a diagnosable alcohol use disorder, along with either a causal life-event explanation for the alcohol use disorder behaviors or no explanation. They then made judgments of the need for treatment, psychological abnormality and the stigma they felt toward the person depicted. Causal life-event explanations decreased lay judgments of the need for treatment, psychological abnormality and stigma. The results suggest that the availability of a causal life-event explanation may have a complex effect on lay judgments, decreasing the likelihood of recommending treatment for alcohol use disorders, yet simultaneously reducing stigmatizing perceptions (and presumably social distance). © The Author 2015. Medical Council on Alcohol and Oxford University Press. All rights reserved.

Arid1b haploinsufficient mice reveal neuropsychiatric phenotypes and reversible causes of growth impairment

PubMed Central

Celen, Cemre; Chuang, Jen-Chieh; Luo, Xin; Nijem, Nadine; Walker, Angela K; Chen, Fei; Zhang, Shuyuan; Chung, Andrew S; Nguyen, Liem H; Nassour, Ibrahim; Budhipramono, Albert; Sun, Xuxu; Bok, Levinus A; McEntagart, Meriel; Gevers, Evelien F; Birnbaum, Shari G; Eisch, Amelia J; Powell, Craig M; Ge, Woo-Ping; Santen, Gijs WE; Chahrour, Maria; Zhu, Hao

2017-01-01

Sequencing studies have implicated haploinsufficiency of ARID1B, a SWI/SNF chromatin-remodeling subunit, in short stature (Yu et al., 2015), autism spectrum disorder (O'Roak et al., 2012), intellectual disability (Deciphering Developmental Disorders Study, 2015), and corpus callosum agenesis (Halgren et al., 2012). In addition, ARID1B is the most common cause of Coffin-Siris syndrome, a developmental delay syndrome characterized by some of the above abnormalities (Santen et al., 2012; Tsurusaki et al., 2012; Wieczorek et al., 2013). We generated Arid1b heterozygous mice, which showed social behavior impairment, altered vocalization, anxiety-like behavior, neuroanatomical abnormalities, and growth impairment. In the brain, Arid1b haploinsufficiency resulted in changes in the expression of SWI/SNF-regulated genes implicated in neuropsychiatric disorders. A focus on reversible mechanisms identified Insulin-like growth factor (IGF1) deficiency with inadequate compensation by Growth hormone-releasing hormone (GHRH) and Growth hormone (GH), underappreciated findings in ARID1B patients. Therapeutically, GH supplementation was able to correct growth retardation and muscle weakness. This model functionally validates the involvement of ARID1B in human disorders, and allows mechanistic dissection of neurodevelopmental diseases linked to chromatin-remodeling. DOI: http://dx.doi.org/10.7554/eLife.25730.001 PMID:28695822

Caspr2-reactive antibody cloned from a mother of an ASD child mediates an ASD-like phenotype in mice.

PubMed

Brimberg, L; Mader, S; Jeganathan, V; Berlin, R; Coleman, T R; Gregersen, P K; Huerta, P T; Volpe, B T; Diamond, B

2016-12-01

Autism spectrum disorder (ASD) occurs in 1 in 68 births, preferentially affecting males. It encompasses a group of neurodevelopmental abnormalities characterized by impaired social interaction and communication, stereotypic behaviors and motor dysfunction. Although recent advances implicate maternal brain-reactive antibodies in a causative role in ASD, a definitive assessment of their pathogenic potential requires cloning of such antibodies. Here, we describe the isolation and characterization of monoclonal brain-reactive antibodies from blood of women with brain-reactive serology and a child with ASD. We further demonstrate that male but not female mice exposed in utero to the C6 monoclonal antibody, binding to contactin-associated protein-like 2 (Caspr2), display abnormal cortical development, decreased dendritic complexity of excitatory neurons and reduced numbers of inhibitory neurons in the hippocampus, as well as impairments in sociability, flexible learning and repetitive behavior. Anti-Caspr2 antibodies are frequent in women with brain-reactive serology and a child with ASD. Together these studies provide a methodology for obtaining monclonal brain-reactive antibodies from blood B cells, demonstrate that ASD can result from in utero exposure to maternal brain-reactive antibodies of single specificity and point toward the exciting possibility of prognostic and protective strategies.

Rines E3 ubiquitin ligase regulates MAO-A levels and emotional responses.

PubMed

Kabayama, Miyuki; Sakoori, Kazuto; Yamada, Kazuyuki; Ornthanalai, Veravej G; Ota, Maya; Morimura, Naoko; Katayama, Kei-ichi; Murphy, Niall P; Aruga, Jun

2013-08-07

Monoamine oxidase A (MAO-A), the catabolic enzyme of norepinephrine and serotonin, plays a critical role in emotional and social behavior. However, the control and impact of endogenous MAO-A levels in the brain remains unknown. Here we show that the RING finger-type E3 ubiquitin ligase Rines/RNF180 regulates brain MAO-A subset, monoamine levels, and emotional behavior. Rines interacted with MAO-A and promoted its ubiquitination and degradation. Rines knock-out mice displayed impaired stress responses, enhanced anxiety, and affiliative behavior. Norepinephrine and serotonin levels were altered in the locus ceruleus, prefrontal cortex, and amygdala in either stressed or resting conditions, and MAO-A enzymatic activity was enhanced in the locus ceruleus in Rines knock-out mice. Treatment of Rines knock-out mice with MAO inhibitors showed genotype-specific effects on some of the abnormal affective behaviors. These results indicated that the control of emotional behavior by Rines is partly due to the regulation of MAO-A levels. These findings verify that Rines is a critical regulator of the monoaminergic system and emotional behavior and identify a promising candidate drug target for treating diseases associated with emotion.

Frontal Hyperconnectivity Related to Discounting and Reversal Learning in Cocaine Subjects

PubMed Central

Camchong, Jazmin; MacDonald, Angus W; Nelson, Brent; Bell, Christopher; Mueller, Bryon A; Specker, Sheila; Lim, Kelvin O

2011-01-01

BACKGROUND Functional neuroimaging studies suggest that chronic cocaine use is associated with frontal lobe abnormalities. Functional connectivity (FC) alterations of cocaine dependent individuals (CD), however, are not yet clear. This is the first study to our knowledge that examines resting FC of anterior cingulate cortex (ACC) in CD. Because ACC is known to integrate inputs from different brain regions to regulate behavior, we hypothesize that CD will have connectivity abnormalities in ACC networks. In addition, we hypothesized that abnormalities would be associated with poor performance in delayed discounting and reversal learning tasks. METHODS Resting functional magnetic resonance imaging data were collected to look for FC differences between twenty-seven cocaine dependent individuals (CD) (5 females, age: M=39.73, SD=6.14) and twenty-four controls (5 females, age: M=39.76, SD = 7.09). Participants were assessed with delayed discounting and reversal learning tasks. Using seed-based FC measures, we examined FC in CD and controls within five ACC connectivity networks with seeds in subgenual, caudal, dorsal, rostral, and perigenual ACC. RESULTS CD showed increased FC within the perigenual ACC network in left middle frontal gyrus, ACC and middle temporal gyrus when compared to controls. FC abnormalities were significantly positively correlated with task performance in delayed discounting and reversal learning tasks in CD. CONCLUSIONS The present study shows that participants with chronic cocaine-dependency have hyperconnectivity within an ACC network known to be involved in social processing and mentalizing. In addition, FC abnormalities found in CD were associated with difficulties with delay rewards and slower adaptive learning. PMID:21371689

Long-Term Provision of Environmental Resources Alters Behavior but not Physiology or Neuroanatomy of Male and Female BALB/c and C57BL/6 Mice

PubMed Central

Clipperton-Allen, Amy E; Ingrao, Joelle C; Ruggiero, Laura; Batista, Lucas; Ovari, Jelena; Hammermueller, Jutta; Armstrong, John N; Bienzle, Dorothee; Choleris, Elena; Turner, Patricia V

2015-01-01

Few studies have evaluated the long-term effects of providing environmental resources to mice. This consideration is important given that mice are often maintained in vivaria for months. We evaluated the effects of providing simple cage resources (wood wool, cotton nesting material, a plastic tunnel, and oat cereal) compared with standard housing (solid-bottom cage with hardwood chips) to group-housed adult male and female C57BL/6 and BALB/c mice (n = 20/sex/strain/group) over 6 mo to determine whether these resources had a lasting effect on animal physiology, anatomy, and behavior. Body weights increased in all groups over time but were proportionately higher in male and female BALB/c mice housed in resource-supplemented environments. Throughout the study, adding environmental resources had no effect on hematology and lymphocyte subsets, fecal corticoid metabolite levels, response to LPS injection, or dendritic spine length or density. Strain- or sex×environment-specific changes occurred in dark–light activity and thermal nociceptive responses. Dominant agonistic behaviors, abnormal conspecific sexual behaviors, and social nonagonistic behaviors demonstrated sex and strain×environment interactions such that fewer maladaptive social behaviors were noted in mice that were provided with environmental resources. This association was particularly evident in male mice of both strains in resource-supplemented environments. A small but significant increase in brain weight:body weight ratios occurred in mice in resource-supplemented environments. Under the conditions evaluated here, consistent use of simple environmental resources had a positive long-term effect on the behavioral wellbeing of male and female BALB/c and C57BL/6 mice yet minimally affected other aspects of murine physiology and neuroanatomy. PMID:26632781

Assembling the Puzzle: Pathways of Oxytocin Signaling in the Brain.

PubMed

Grinevich, Valery; Knobloch-Bollmann, H Sophie; Eliava, Marina; Busnelli, Marta; Chini, Bice

2016-02-01

Oxytocin (OT) is a neuropeptide, which can be seen to be one of the molecules of the decade due to its profound prosocial effects in nonvertebrate and vertebrate species, including humans. Although OT can be detected in various physiological fluids (blood, saliva, urine, cerebrospinal fluid) and brain tissue, it is unclear whether peripheral and central OT releases match and synergize. Moreover, the pathways of OT delivery to brain regions involved in specific behaviors are far from clear. Here, we discuss the evolutionarily and ontogenetically determined pathways of OT delivery and OT signaling, which orchestrate activity of the mesolimbic social decision-making network. Furthermore, we speculate that both the alteration in OT delivery and OT receptor expression may cause behavioral abnormalities in patients afflicted with psychosocial diseases. Copyright © 2016 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

Autism: A “Critical Period” Disorder?

PubMed Central

LeBlanc, Jocelyn J.; Fagiolini, Michela

2011-01-01

Cortical circuits in the brain are refined by experience during critical periods early in postnatal life. Critical periods are regulated by the balance of excitatory and inhibitory (E/I) neurotransmission in the brain during development. There is now increasing evidence of E/I imbalance in autism, a complex genetic neurodevelopmental disorder diagnosed by abnormal socialization, impaired communication, and repetitive behaviors or restricted interests. The underlying cause is still largely unknown and there is no fully effective treatment or cure. We propose that alteration of the expression and/or timing of critical period circuit refinement in primary sensory brain areas may significantly contribute to autistic phenotypes, including cognitive and behavioral impairments. Dissection of the cellular and molecular mechanisms governing well-established critical periods represents a powerful tool to identify new potential therapeutic targets to restore normal plasticity and function in affected neuronal circuits. PMID:21826280

Early Cognitive/Social Deficits and Late Motor Phenotype in Conditional Wild-Type TDP-43 Transgenic Mice.

PubMed

Alfieri, Julio A; Silva, Pablo R; Igaz, Lionel M

2016-01-01

Frontotemporal Dementia (FTD) and amyotrophic lateral sclerosis (ALS) are two neurodegenerative diseases associated to mislocalization and aggregation of TAR DNA-binding protein 43 (TDP-43). To investigate in depth the behavioral phenotype associated with this proteinopathy, we used as a model transgenic (Tg) mice conditionally overexpressing human wild-type TDP 43 protein (hTDP-43-WT) in forebrain neurons. We previously characterized these mice at the neuropathological level and found progressive neurodegeneration and other features that evoke human TDP-43 proteinopathies of the FTD/ALS spectrum. In the present study we analyzed the behavior of mice at multiple domains, including motor, social and cognitive performance. Our results indicate that young hTDP-43-WT Tg mice (1 month after post-weaning transgene induction) present a normal motor phenotype compared to control littermates, as assessed by accelerated rotarod performance, spontaneous locomotor activity in the open field test and a mild degree of spasticity shown by a clasping phenotype. Analysis of social and cognitive behavior showed a rapid installment of deficits in social interaction, working memory (Y-maze test) and recognition memory (novel object recognition test) in the absence of overt motor abnormalities. To investigate if the motor phenotype worsen with age, we analyzed the behavior of mice after long-term (up to 12 months) transgene induction. Our results reveal a decreased performance on the rotarod test and in the hanging wire test, indicating a motor phenotype that was absent in younger mice. In addition, long-term hTDP-43-WT expression led to hyperlocomotion in the open field test. In sum, these results demonstrate a time-dependent emergence of a motor phenotype in older hTDP-43-WT Tg mice, recapitulating aspects of clinical FTD presentations with motor involvement in human patients, and providing a complementary animal model for studying TDP-43 proteinopathies.

[The Role of Physician In Enhancement of Rehabilitation of Disabled Children].

PubMed

Nizova, L M; Kislisyna, I G

2017-09-01

The national and international experience of rehabilitation of disabled children was investigated. On the basis of monitoring data problem of increasing of number of children with diagnosis of infantile cerebral paralysis, including necessity of development of new methods of their rehabilitation was established. The comparative dynamics of nosology of disabled children permitted to detect diseases of nervous system and congenital abnormalities (malformations), deformations and chromosomal disorders, psychological disorders and behavioral disorders mostly specific for urban and rural area. The model of institutional environment of rehabilitation of disabled children was developed including system of formal (state, legislative acts, health institutions, organizations of social support of population)and non-formal (public, non-commercial and social psychological organizations) institutions impacted by economic, social,legal and demographic factors. The role of physician is substantiated concerning increasing of quality of rehabilitation services: diagnostic of disordered functions, detection of optimal volume of medical, psychological and pedagogue activities in patients with severe speech disorders, motoric and and neuro-censorial disorders developed as a result of early organic damage of brain, neuro-infections, strokes, and other affection of brain. The adequate curative rehabilitative complex programs were developed of social everyday and social labor rehabilitation.

Altered Cerebellar Organization and Function in Monoamine Oxidase A Hypomorphic Mice

PubMed Central

Alzghoul, Loai; Bortolato, Marco; Delis, Foteini; Thanos, Panayotis K.; Darling, Ryan D.; Godar, Sean C; Zhang, Junlin; Grant, Samuel; Wang, Gene-Jack; Simpson, Kimberly L.; Chen, Kevin; Volkow, Nora D.; Lin, Rick C.S.; Shih, Jean C.

2012-01-01

Monoamine oxidase A (MAO-A) is the key enzyme for the degradation of brain serotonin (5-hydroxytryptamine, 5-HT), norepinephrine (NE) and dopamine (DA). We recently generated and characterized a novel line of MAO-A hypormorphic mice (MAO-ANeo), featuring elevated monoamine levels, social deficits and perseverative behaviors as well as morphological changes in the basolateral amygdala and orbitofrontal cortex. Here we showed that MAO-ANeo mice displayed deficits in motor control, manifested as subtle disturbances in gait, motor coordination, and balance. Furthermore, magnetic resonance imaging of the cerebellum revealed morphological changes and a moderate reduction in the cerebellar size of MAO- ANeo mice compared to wild type (WT) mice. Histological and immunohistochemical analyses using calbindin-D-28k (CB) expression of Purkinje cells revealed abnormal cerebellar foliation with vermal hypoplasia and decreased in Purkinje cell count and their dendritic density in MAO- ANeo mice compared to WT. Our current findings suggest that congenitally low MAO-A activity leads to abnormal development of the cerebellum. PMID:22971542

Social Isolation During Adolescence Strengthens Retention of Fear Memories and Facilitates Induction of Late-Phase Long-Term Potentiation.

PubMed

Liu, Ji-Hong; You, Qiang-Long; Wei, Mei-Dan; Wang, Qian; Luo, Zheng-Yi; Lin, Song; Huang, Lang; Li, Shu-Ji; Li, Xiao-Wen; Gao, Tian-Ming

2015-12-01

Social isolation during the vulnerable period of adolescence produces emotional dysregulation that often manifests as abnormal behavior in adulthood. The enduring consequence of isolation might be caused by a weakened ability to forget unpleasant memories. However, it remains unclear whether isolation affects unpleasant memories. To address this, we used a model of associative learning to induce the fear memories and evaluated the influence of isolation mice during adolescence on the subsequent retention of fear memories and its underlying cellular mechanisms. Following adolescent social isolation, we found that mice decreased their social interaction time and had an increase in anxiety-related behavior. Interestingly, when we assessed memory retention, we found that isolated mice were unable to forget aversive memories when tested 4 weeks after the original event. Consistent with this, we observed that a single train of high-frequency stimulation (HFS) enabled a late-phase long-term potentiation (L-LTP) in the hippocampal CA1 region of isolated mice, whereas only an early-phase LTP was observed with the same stimulation in the control mice. Social isolation during adolescence also increased brain-derived neurotrophic factor (BDNF) expression in the hippocampus, and application of a tropomyosin-related kinase B (TrkB) receptor inhibitor ameliorated the facilitated L-LTP seen after isolation. Together, our results suggest that adolescent isolation may result in mental disorders during adulthood and that this may stem from an inability to forget the unpleasant memories via BDNF-mediated synaptic plasticity. These findings may give us a new strategy to prevent mental disorders caused by persistent unpleasant memories.

Altered Striatal Synaptic Function and Abnormal Behaviour in Shank3 Exon4-9 Deletion Mouse Model of Autism.

PubMed

Jaramillo, Thomas C; Speed, Haley E; Xuan, Zhong; Reimers, Jeremy M; Liu, Shunan; Powell, Craig M

2016-03-01

Shank3 is a multi-domain, synaptic scaffolding protein that organizes proteins in the postsynaptic density of excitatory synapses. Clinical studies suggest that ∼ 0.5% of autism spectrum disorder (ASD) cases may involve SHANK3 mutation/deletion. Patients with SHANK3 mutations exhibit deficits in cognition along with delayed/impaired speech/language and repetitive and obsessive/compulsive-like (OCD-like) behaviors. To examine how mutation/deletion of SHANK3 might alter brain function leading to ASD, we have independently created mice with deletion of Shank3 exons 4-9, a region implicated in ASD patients. We find that homozygous deletion of exons 4-9 (Shank3(e4-9) KO) results in loss of the two highest molecular weight isoforms of Shank3 and a significant reduction in other isoforms. Behaviorally, both Shank3(e4-9) heterozygous (HET) and Shank3(e4-9) KO mice display increased repetitive grooming, deficits in novel and spatial object recognition learning and memory, and abnormal ultrasonic vocalizations. Shank3(e4-9) KO mice also display abnormal social interaction when paired with one another. Analysis of synaptosome fractions from striata of Shank3(e4-9) KO mice reveals decreased Homer1b/c, GluA2, and GluA3 expression. Both Shank3(e4-9) HET and KO demonstrated a significant reduction in NMDA/AMPA ratio at excitatory synapses onto striatal medium spiny neurons. Furthermore, Shank3(e4-9) KO mice displayed reduced hippocampal LTP despite normal baseline synaptic transmission. Collectively these behavioral, biochemical and physiological changes suggest Shank3 isoforms have region-specific roles in regulation of AMPAR subunit localization and NMDAR function in the Shank3(e4-9) mutant mouse model of autism. © 2015 International Society for Autism Research, Wiley Periodicals, Inc.

Affective mentalizing and brain activity at rest in the behavioral variant of frontotemporal dementia

PubMed Central

Caminiti, Silvia P.; Canessa, Nicola; Cerami, Chiara; Dodich, Alessandra; Crespi, Chiara; Iannaccone, Sandro; Marcone, Alessandra; Falini, Andrea; Cappa, Stefano F.

2015-01-01

Background bvFTD patients display an impairment in the attribution of cognitive and affective states to others, reflecting GM atrophy in brain regions associated with social cognition, such as amygdala, superior temporal cortex and posterior insula. Distinctive patterns of abnormal brain functioning at rest have been reported in bvFTD, but their relationship with defective attribution of affective states has not been investigated. Objective To investigate the relationship among resting-state brain activity, gray matter (GM) atrophy and the attribution of mental states in the behavioral variant of fronto-temporal degeneration (bvFTD). Methods We compared 12 bvFTD patients with 30 age- and education-matched healthy controls on a) performance in a task requiring the attribution of affective vs. cognitive mental states; b) metrics of resting-state activity in known functional networks; and c) the relationship between task-performances and resting-state metrics. In addition, we assessed a connection between abnormal resting-state metrics and GM atrophy. Results Compared with controls, bvFTD patients showed a reduction of intra-network coherent activity in several components, as well as decreased strength of activation in networks related to attentional processing. Anomalous resting-state activity involved networks which also displayed a significant reduction of GM density. In patients, compared with controls, higher affective mentalizing performance correlated with stronger functional connectivity between medial prefrontal sectors of the default-mode and attentional/performance monitoring networks, as well as with increased coherent activity in components of the executive, sensorimotor and fronto-limbic networks. Conclusions Some of the observed effects may reflect specific compensatory mechanisms for the atrophic changes involving regions in charge of affective mentalizing. The analysis of specific resting-state networks thus highlights an intermediate level of analysis between abnormal brain structure and impaired behavioral performance in bvFTD, reflecting both dysfunction and compensation mechanisms. PMID:26594631

Abnormal behavior with hump characteristics in current stressed a-InGaZnO thin film transistors

NASA Astrophysics Data System (ADS)

Kim, Woo-Sic; Cho, Yong-Jung; Lee, Yeol-Hyeong; Park, JeongKi; Kim, GeonTae; Kim, Ohyun

2017-11-01

We investigated the degradation mechanism of a-InGaZnO TFTs under simultaneous gate and drain bias stress. Gate and drain bias of 20 V were applied simultaneously to induce current stress, and abnormal turn-around behavior in transfer characteristics with a hump phenomenon were identified. Hump characteristics were interpreted in terms of parasitic current path, and the degradation itself was found to be caused dominantly by the electrical field and to be accelerated with current by Joule heating. The mechanism of asymmetrical degradation after current stress was also investigated. By decomposing the curves into two curves and measuring the relaxation behavior of the stressed TFTs, we also found that abnormal turn-around behavior in the transfer characteristics was related to acceptor-like states.

Anomalous rheological behavior of long glass fiber reinforced polypropylene

NASA Astrophysics Data System (ADS)

Kim, Dong Hak; Lee, Young Sil; Son, Younggon

2012-12-01

Dynamic rheological properties of PP-based long glass fiber-reinforced thermoplastics (LFT) were investigated. Weight fractions of the glass fibers investigated in the present study ranged from 0.15 to 0.5, which are higher than those of previous studies. We observed very abnormal rheological behavior. Complex viscosity (η*) of the LFT increased with the glass fiber content up to 40 wt. %. However, the η* with a weight fraction of 0.5 is observed to be lower than that of LFT with a weight fraction of 0.4 in spite of higher glass fiber content. From various experiments, we found that this abnormal behavior is analogous to the rheological behavior of a lyotropic liquid crystalline polymer solution and concluded that the abnormal rheological behavior for the LFT is attributed to the formation of a liquid crystal- like structure at high concentrations of long glass fibers.

LOBSTER BEHAVIOR AND CHEMORECEPTION: SUBLETHAL EFFECTS OF NUMBER 2 FUEL OIL

EPA Science Inventory

This research has demonstrated behavioral abnormalities and inappropriate responses in lobsters exposed to levels of 0.1-1.0 parts per million (ppm) of oil in water. Such abnormalities can lead to lack of feeding and population decline; they occur at exposure levels below those t...

A New Perspective on the Pathophysiology of Borderline Personality Disorder: A Model of the Role of Oxytocin.

PubMed

Herpertz, Sabine C; Bertsch, Katja

2015-09-01

Borderline personality disorder is characterized by three domains of dysfunction: affect dysregulation, behavioral dyscontrol, and interpersonal hypersensitivity. Interpersonal hypersensitivity is associated with a (pre)attentive bias toward negative social information and, on the level of the brain, enhanced bottom-up emotion generation, while affect dysregulation results from abnormal top-down processes. Additionally, the problems of patients with borderline personality disorder in interpersonal functioning appear to be related to alterations in the (social) reward and empathy networks. There is increasing evidence that the oxytocinergic system may be involved in these domains of dysfunction and may thus contribute to borderline psychopathology and even open new avenues for targeted pharmacotherapeutic approaches. From studies in healthy and clinical subjects (including first studies with borderline personality disorder patients), the authors provide a conceptual framework for future research in borderline personality disorder that is based on oxytocinergic modulation of the following biobehavioral mechanisms: 1) the brain salience network favoring adaptive social approach behavior, 2) the affect regulation circuit normalizing top-down processes, 3) the mesolimbic circuit improving social reward experiences, and 4) modulating brain regions involved in cognitive and emotional empathy. In addition, preliminary data point to interactions between the oxytocin and cannabinoid system, with implications for pain processing. These mechanisms, which the authors believe to be modulated by oxytocin, may not be specific for borderline personality disorder but rather may be common to a host of psychiatric disorders in which disturbed parent-infant attachment is a major etiological factor.

Frontal behavioral syndromes in Prader-Willi syndrome.

PubMed

Ogura, Kaeko; Shinohara, Mayumi; Ohno, Kousaku; Mori, Etsuro

2008-08-01

Prader-Willi syndrome (PWS) is a genetically determined neurodevelopmental disorder presenting with behavioral problems including hyperphagia, emotional aberration, and compulsion-like behaviors. This combination of behavioral problems is likely to be caused by damage to the orbitofrontal cortices and anterior temporal lobes or to circuits involving them. To investigate the prevalence of eating and non-eating behavioral disturbances in PWS by using assessment tools developed originally for patients with frontotemporal dementia and with frontal lobe injury. The questionnaire consisted of 35 questions related to three categories of behavior: eating behaviors (including four domains: appetite, food preference, eating habits, and other oral behaviors), stereotypy (including four domains: roaming, speaking, movements, and daily rhythm), and collecting behaviors. It was administered in Japan to the parents of 250 individuals aged 1-42 years with a clinical diagnosis of PWS. The prevalence rates of symptoms in all categories were high. Each domain involved in eating behaviors was significantly correlated with stereotypy and collecting behaviors. The prevalence rates and severity scores of some eating and non-eating behaviors were higher in the older groups. Abnormal eating behaviors, stereotyped behaviors, and collecting behaviors were common in the PWS subjects. There was also a potential link between abnormal eating and non-eating behaviors related to frontal behavioral syndromes. It is likely that these behavioral abnormalities reflect dysfunction of the orbitofrontal cortices and anterior temporal lobes.

[How to characterize and treat sleep complaints in bipolar disorders?

PubMed

Geoffroy, P A; Micoulaud Franchi, J-A; Lopez, R; Poirot, I; Brion, A; Royant-Parola, S; Etain, B

2017-08-01

Sleep complaints are very common in bipolar disorders (BD) both during acute phases (manic and depressive episodes) and remission (about 80 % of patients with remitted BD have poor sleep quality). Sleep complaints during remission are of particular importance since they are associated with more mood relapses and worse outcomes. In this context, this review discusses the characterization and treatment of sleep complaints in BD. We examined the international scientific literature in June 2016 and performed a literature search with PubMed electronic database using the following headings: "bipolar disorder" and ("sleep" or "insomnia" or "hypersomnia" or "circadian" or "apnoea" or "apnea" or "restless legs"). Patients with BD suffer from sleep and circadian rhythm abnormalities during major depressive episodes (insomnia or hypersomnia, nightmares, nocturnal and/or early awakenings, non-restorative sleep) and manic episodes (insomnia, decreased need for sleep without fatigue), but also some of these abnormalities may persist during remission. These remission phases are characterized by a reduced quality and quantity of sleep, with a longer sleep duration, increased sleep latency, a lengthening of the wake time after sleep onset (WASO), a decrease of sleep efficiency, and greater variability in sleep/wake rhythms. Patients also present frequent sleep comorbidities: chronic insomnia, sleepiness, sleep phase delay syndrome, obstructive sleep apnea/hypopnea syndrome (OSAHS), and restless legs syndrome (RLS). These disorders are insufficiently diagnosed and treated whereas they are associated with mood relapses, treatment resistance, affect cognitive global functioning, reduce the quality of life, and contribute to weight gain or metabolic syndrome. Sleep and circadian rhythm abnormalities have been also associated with suicidal behaviors. Therefore, a clinical exploration with characterization of these abnormalities and disorders is essential. This exploration should be helped by questionnaires and documented on sleep diaries or even actimetric objective measures. Explorations such as ventilatory polygraphy, polysomnography or a more comprehensive assessment in a sleep laboratory may be required to complete the diagnostic assessment. Treatments obviously depend on the cause identified through assessment procedures. Treatment of chronic insomnia is primarily based on non-drug techniques (by restructuring behavior and sleep patterns), on psychotherapy (cognitive behavioral therapy for insomnia [CBT-I]; relaxation; interpersonal and social rhythm therapy [IPSRT]; etc.), and if necessary with hypnotics during less than four weeks. Specific treatments are needed in phase delay syndrome, OSAHS, or other more rare sleep disorders. BD are defined by several sleep and circadian rhythm abnormalities during all phases of the disorder. These abnormalities and disorders, especially during remitted phases, should be characterized and diagnosed to reduce mood relapses, treatment resistance and improve BD outcomes. Copyright © 2016 L'Encéphale, Paris. Published by Elsevier Masson SAS. All rights reserved.

Oxytocin and Social Cognition in Affective and Psychotic Disorders

PubMed Central

Perez-Rodriguez, M. Mercedes; Mahon, Katie; Russo, Manuela; Ungar, Allison K.; Burdick, Katherine E.

2014-01-01

Impairments in social cognition are now recognized as core illness features in psychotic and affective disorders. Despite the significant disability caused by social cognitive abnormalities, treatments for this symptom dimension are lacking. Here, we describe the evidence demonstrating abnormalities in social cognition in schizophrenia, major depressive disorder, and bipolar disorder, as well as the neurobiology of social cognition including the role of oxytocin. We then review clinical trials of oxytocin administration in psychotic and affective disorders and the impact of this agent on social cognition. To date, several studies have demonstrated that oxytocin may improve social cognition in schizophrenia; too few studies have been conducted in affective disorders to determine the effect of oxytocin on social cognition in these disorders. Future work is needed to clarify which aspects of social cognition may be improved with oxytocin treatment in psychotic and affective disorders. PMID:25153535

Mice that lack the C-terminal region of Reelin exhibit behavioral abnormalities related to neuropsychiatric disorders

PubMed Central

Sakai, Kaori; Shoji, Hirotaka; Kohno, Takao; Miyakawa, Tsuyoshi; Hattori, Mitsuharu

2016-01-01

The secreted glycoprotein Reelin is believed to play critical roles in the pathogenesis of several neuropsychiatric disorders. The highly basic C-terminal region (CTR) of Reelin is necessary for efficient activation of its downstream signaling, and the brain structure of knock-in mice that lack the CTR (ΔC-KI mice) is impaired. Here, we performed a comprehensive behavioral test battery on ΔC-KI mice, in order to evaluate the effects of partial loss-of-function of Reelin on brain functions. The ΔC-KI mice were hyperactive and exhibited reduced anxiety-like and social behaviors. The working memory in ΔC-KI mice was impaired in a T-maze test. There was little difference in spatial reference memory, depression-like behavior, prepulse inhibition, or fear memory between ΔC-KI and wild-type mice. These results suggest that CTR-dependent Reelin functions are required for some specific normal brain functions and that ΔC-KI mice recapitulate some aspects of neuropsychiatric disorders, such as schizophrenia, bipolar disorder, and autism spectrum disorder. PMID:27346785

Microbiota modulate behavioral and physiological abnormalities associated with neurodevelopmental disorders.

PubMed

Hsiao, Elaine Y; McBride, Sara W; Hsien, Sophia; Sharon, Gil; Hyde, Embriette R; McCue, Tyler; Codelli, Julian A; Chow, Janet; Reisman, Sarah E; Petrosino, Joseph F; Patterson, Paul H; Mazmanian, Sarkis K

2013-12-19

Neurodevelopmental disorders, including autism spectrum disorder (ASD), are defined by core behavioral impairments; however, subsets of individuals display a spectrum of gastrointestinal (GI) abnormalities. We demonstrate GI barrier defects and microbiota alterations in the maternal immune activation (MIA) mouse model that is known to display features of ASD. Oral treatment of MIA offspring with the human commensal Bacteroides fragilis corrects gut permeability, alters microbial composition, and ameliorates defects in communicative, stereotypic, anxiety-like and sensorimotor behaviors. MIA offspring display an altered serum metabolomic profile, and B. fragilis modulates levels of several metabolites. Treating naive mice with a metabolite that is increased by MIA and restored by B. fragilis causes certain behavioral abnormalities, suggesting that gut bacterial effects on the host metabolome impact behavior. Taken together, these findings support a gut-microbiome-brain connection in a mouse model of ASD and identify a potential probiotic therapy for GI and particular behavioral symptoms in human neurodevelopmental disorders. Copyright © 2013 Elsevier Inc. All rights reserved.

Trait-level temporal lobe hypoactivation to social exclusion in unaffected siblings of children and adolescents with autism spectrum disorders.

PubMed

Bolling, Danielle Z; Pelphrey, Kevin A; Vander Wyk, Brent C

2015-06-01

Social exclusion elicits powerful feelings of negative affect associated with rejection. Additionally, experiencing social exclusion reliably recruits neural circuitry associated with emotion processing. Recent work has demonstrated abnormal neural responses to social exclusion in children and adolescents with autism spectrum disorders (ASD). However, it remains unknown to what extent these abnormalities are due to atypical social experiences versus genetic predispositions to atypical neural processing. To address this question, the current study investigated brain responses to social exclusion compared to a baseline condition of fair play in unaffected siblings of youth with ASD using functional magnetic resonance imaging. We identified common deviations between unaffected siblings and ASD probands that might represent trait-level abnormalities in processing Social Exclusion vs. Fair Play, specifically in the right anterior temporoparietal junction extending into posterior superior temporal sulcus. Thus, hypoactivation to Social Exclusion vs. Fair Play in this region may represent a shared genetic vulnerability to developing autism. In addition, we present evidence supporting the idea that one's status as an unaffected sibling moderates the relationship between IQ and neural activation to Social Exclusion vs. Fair Play in anterior cingulate cortex. These results are discussed in the context of previous literature on neural endophenotypes of autism. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

Erbb4 Deletion from Medium Spiny Neurons of the Nucleus Accumbens Core Induces Schizophrenia-Like Behaviors via Elevated GABAA Receptor α1 Subunit Expression.

PubMed

Geng, Hong-Yan; Zhang, Jing; Yang, Jian-Ming; Li, Yue; Wang, Ning; Ye, Mao; Chen, Xiao-Juan; Lian, Hong; Li, Xiao-Ming

2017-08-02

Medium spiny neurons (MSNs), the major GABAergic projection neurons in the striatum, are implicated in many neuropsychiatric diseases such as schizophrenia, but the underlying mechanisms remain unclear. We found that a deficiency in Erbb4 , a schizophrenia risk gene, in MSNs of the nucleus accumbens (NAc) core, but not the dorsomedial striatum, markedly induced schizophrenia-like behaviors such as hyperactivity, abnormal marble-burying behavior, damaged social novelty recognition, and impaired sensorimotor gating function in male mice. Using immunohistochemistry, Western blot, RNA interference, electrophysiology, and behavior test studies, we found that these phenomena were mediated by increased GABA A receptor α1 subunit (GABA A R α1) expression, which enhanced inhibitory synaptic transmission on MSNs. These results suggest that Erbb4 in MSNs of the NAc core may contribute to the pathogenesis of schizophrenia by regulating GABAergic transmission and raise the possibility that GABA A R α1 may therefore serve as a new therapeutic target for schizophrenia. SIGNIFICANCE STATEMENT Although ErbB4 is highly expressed in striatal medium spiny neurons (MSNs), its role in this type of neuron has not been reported previously. The present study demonstrates that Erbb4 deletion in nucleus accumbens (NAc) core MSNs can induce schizophrenia-like behaviors via elevated GABA A receptor α1 subunit (GABA A R α1) expression. To our knowledge, this is the first evidence that ErbB4 signaling in the MSNs is involved in the pathology of schizophrenia. Furthermore, restoration of GABA A R α1 in the NAc core, but not the dorsal medium striatum, alleviated the abnormal behaviors. Here, we highlight the role of the NAc core in the pathogenesis of schizophrenia and suggest that GABA A R α1 may be a potential pharmacological target for its treatment. Copyright © 2017 the authors 0270-6474/17/377450-15$15.00/0.

Environmental factors influencing the risk of autism

PubMed Central

Karimi, Padideh; Kamali, Elahe; Mousavi, Seyyed Mohammad; Karahmadi, Mojgan

2017-01-01

Autism is a developmental disability with age of onset in childhood (under 3 years old), which is characterized by definite impairments in social interactions, abnormalities in speech, and stereotyped pattern of behaviors. Due to the progress of autism in recent decades, a wide range of studies have been done to identify the etiological factors of autism. It has been found that genetic and environmental factors are both involved in autism pathogenesis. Hence, in this review article, a set of environmental factors involved in the occurrence of autism has been collected, and finally, some practical recommendations for reduction of the risk of this devastating disease in children are represented. PMID:28413424

The (ab)normal-social-personality catena: Exploring The Journal of Abnormal and Social Psychology during the interwar years.

PubMed

Davidson, Ian J

2018-05-01

This article is a cocitation network analysis of The Journal of Abnormal and Social Psychology ( JASP ) from 1925 to 1942. The analysis was conducted to help shed light on the historical roots of the intellectual and institutional relationships among social, personality, and abnormal psychology. JASP was a main venue for the boundary work of early- to mid-twentieth-century American psychologists. One of the main goals of these various research communities was to appropriate psychoanalytic and sociological concepts into preferred methods and approaches that favored an individualistic, quantifiable, and ultimately normal subject. Five major research communities are identified using the citations, and historically contextualized: Community #1, Measuring Social Aspects; Community #2, Psychometrics; Community #3, Operationalizing Psychoanalysis; Community #4, Introversion Studies; and Community #5, Experimental Social Psychology. This analysis demonstrates how disciplinary psychologists, at least within JASP , were united by the work of delimiting their research from closely aligned fields studying the same concepts-even while psychologists' methodological commitments to experimentalism or psychological testing might have ostensibly divided them. Possible future research incorporating post-World War II research and dynamic networking approaches is recommended. (PsycINFO Database Record (c) 2018 APA, all rights reserved).

Familial Risk for Insomnia Is Associated With Abnormal Cortisol Response to Stress.

PubMed

Drake, Christopher L; Cheng, Philip; Almeida, David M; Roth, Thomas

2017-10-01

Abnormalities in the stress system have been implicated in insomnia. However, studies examining physiological stress regulation in insomnia have not consistently detected differences in the hypothalamic-pituitary-adrenal (HPA)-axis response to stress. One explanation may be that deficits in the stress system are associated specifically with a biological vulnerability to insomnia rather than the phenotypic expression of insomnia. To examine stress response as a function of vulnerability to insomnia, this study tested response to the Trier Social Stress Test in a sample of healthy sleepers with varying familial risks for insomnia. Thirty-five healthy individuals with and without familial risk for insomnia were recruited to complete a laboratory stressor. Participants with one or both biological parents with insomnia were categorized as positive for familial risk, whereas those without biological parents with insomnia were categorized as negative for familial risk. Participants completed the Trier Social Stress Test in the laboratory, and psychological and physiological (autonomic and HPA-axis) responses were compared. Despite self-reported increases in anxiety, those positive for familial risk exhibited a blunted cortisol response relative to those without familial risk for insomnia. Individuals with blunted cortisol also reported heightened reactivity to personal life stressors, including increased sleep disturbances, elevated cognitive intrusions, and more behavioral avoidance. Findings from this study provide initial evidence that abnormal stress regulation may be a biological predisposing factor conferred via familial risk for insomnia. This deficit may also predict negative consequences over time, including insomnia and the associated psychiatric comorbidities. © Sleep Research Society 2017. Published by Oxford University Press on behalf of the Sleep Research Society. All rights reserved. For permissions, please e-mail journals.permissions@oup.com.

Ketoacidosis due to a Low-carbohydrate Diet in an Elderly Woman with Dementia and Abnormal Eating Behavior

PubMed Central

Iwata, Hitoshi; Tsuzuki, Seiichiro; Iwata, Mitsunaga; Terasawa, Teruhiko

2017-01-01

Strict restriction of carbohydrates can induce symptomatic ketoacidosis. We herein report a 76-year-old demented woman who developed ketoacidosis after 1 month of abnormal eating behavior involving selectively eating hamburger steak (estimated carbohydrate =12.7 g/day). Laboratory tests showed high-anion-gap metabolic acidosis with elevated blood ketone levels. She was successfully treated with intravenous fluids followed by oral intake of a regular diet. She remained relapse-free after correcting her eating habits. Healthcare providers should know that abnormal eating behavior in demented people can lead to an extremely-low-carbohydrate diet and cause atypical ketoacidosis unexplained by diabetes, heavy alcohol intake, or starvation conditions. PMID:28883241

Ketoacidosis due to a Low-carbohydrate Diet in an Elderly Woman with Dementia and Abnormal Eating Behavior.

PubMed

Iwata, Hitoshi; Tsuzuki, Seiichiro; Iwata, Mitsunaga; Terasawa, Teruhiko

2017-10-01

Strict restriction of carbohydrates can induce symptomatic ketoacidosis. We herein report a 76-year-old demented woman who developed ketoacidosis after 1 month of abnormal eating behavior involving selectively eating hamburger steak (estimated carbohydrate =12.7 g/day). Laboratory tests showed high-anion-gap metabolic acidosis with elevated blood ketone levels. She was successfully treated with intravenous fluids followed by oral intake of a regular diet. She remained relapse-free after correcting her eating habits. Healthcare providers should know that abnormal eating behavior in demented people can lead to an extremely-low-carbohydrate diet and cause atypical ketoacidosis unexplained by diabetes, heavy alcohol intake, or starvation conditions.

White matter correlates of sensory processing in autism spectrum disorders

PubMed Central

Pryweller, Jennifer R.; Schauder, Kimberly B.; Anderson, Adam W.; Heacock, Jessica L.; Foss-Feig, Jennifer H.; Newsom, Cassandra R.; Loring, Whitney A.; Cascio, Carissa J.

2014-01-01

Autism spectrum disorder (ASD) has been characterized by atypical socio-communicative behavior, sensorimotor impairment and abnormal neurodevelopmental trajectories. DTI has been used to determine the presence and nature of abnormality in white matter integrity that may contribute to the behavioral phenomena that characterize ASD. Although atypical patterns of sensory responding in ASD are well documented in the behavioral literature, much less is known about the neural networks associated with aberrant sensory processing. To address the roles of basic sensory, sensory association and early attentional processes in sensory responsiveness in ASD, our investigation focused on five white matter fiber tracts known to be involved in these various stages of sensory processing: superior corona radiata, centrum semiovale, inferior longitudinal fasciculus, posterior limb of the internal capsule, and splenium. We acquired high angular resolution diffusion images from 32 children with ASD and 26 typically developing children between the ages of 5 and 8. We also administered sensory assessments to examine brain-behavior relationships between white matter integrity and sensory variables. Our findings suggest a modulatory role of the inferior longitudinal fasciculus and splenium in atypical sensorimotor and early attention processes in ASD. Increased tactile defensiveness was found to be related to reduced fractional anisotropy in the inferior longitudinal fasciculus, which may reflect an aberrant connection between limbic structures in the temporal lobe and the inferior parietal cortex. Our findings also corroborate the modulatory role of the splenium in attentional orienting, but suggest the possibility of a more diffuse or separable network for social orienting in ASD. Future investigation should consider the use of whole brain analyses for a more robust assessment of white matter microstructure. PMID:25379451

Psychosocial predator-based animal model of PTSD produces physiological and behavioral sequelae and a traumatic memory four months following stress onset.

PubMed

Zoladz, Phillip R; Park, Collin R; Fleshner, Monika; Diamond, David M

2015-08-01

We have a well-established animal model of PTSD composed of predator exposure administered in conjunction with social instability that produces PTSD-like behavioral and physiological abnormalities one month after stress initiation. Here, we assessed whether the PTSD-like effects would persist for at least 4months after the initiation of the psychosocial stress regimen. Adult male Sprague-Dawley rats were exposed to either 2 or 3 predator-based fear conditioning sessions. During each session, rats were placed in a chamber for a 3-min period that terminated with a 30-s tone, followed by 1h of immobilization of the rats during cat exposure (Day 1). All rats in the stress groups received a second fear conditioning session 10days later (Day 11). Half of the stress rats received a third fear conditioning session 3weeks later (Day 32). The two cat-exposed groups were also exposed to daily unstable housing conditions for the entire duration of the psychosocial stress regimen. The control group received stable (conventional) housing conditions and an equivalent amount of chamber exposure on Days 1, 11 and 32, without cat exposure. Behavioral testing commenced for all groups on Day 116. The stress groups demonstrated increased anxiety on the elevated plus maze, impaired object recognition memory and robust contextual and cued fear conditioned memory 3months after the last conditioning session. Combined data from the two stress groups revealed lower post-stress corticosterone levels and greater diastolic blood pressure relative to the control group. These findings indicate that predator-based psychosocial stress produces persistent PTSD-like physiological and behavioral abnormalities that may provide insight into the neurobiological and endocrine sequelae in traumatized people with PTSD. Copyright © 2015 Elsevier Inc. All rights reserved.

Proportionate Responses to Life Events Influence Clinicians’ Judgments Of Psychological Abnormality

PubMed Central

Kim, Nancy S.; Paulus, Daniel J.; Gonzalez, Jeffrey S.; Khalife, Danielle

2012-01-01

Psychological abnormality is a fundamental concept in the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV-TR; APA, 2000) and in all clinical evaluations. How do practicing clinical psychologists use the context of life events to judge the abnormality of a person’s current behaviors? The appropriate role of life-event context in assessment has long been the subject of intense debate and scrutiny among clinical theorists, yet relatively little is known about clinicians’ own judgments in practice. We propose a proportionate-response hypothesis, such that judgments of abnormality are influenced by whether the behaviors are a disproportionate response to past events, rendering them difficult to understand or explain. We presented licensed, practicing clinical psychologists (N=77) with vignettes describing hypothetical people’s behaviors (disordered, mildly distressed, or unaffected) that had been preceded by either traumatic or mildly distressing events. Experts’ judgments of abnormality were strongly and systematically influenced by the degree of mismatch between the past event and current behaviors in strength and valence, such that the greater the mismatch, the more abnormal the person seemed. A separate, additional group of clinical psychologists (N=20) further confirmed that the greater the degree of mismatch, the greater the perceived difficulty in understanding the patient. These findings held true across clinicians of different theoretical orientations and in disorders for which these patterns of judgments ran contrary to formal recommendations in the DSM-IV-TR (APA, 2000). The rationality of these effects and implications for clinical decision science are discussed. PMID:22142425

Sleep and circadian rhythm disruption in social jetlag and mental illness.

PubMed

Foster, Russell G; Peirson, Stuart N; Wulff, Katharina; Winnebeck, Eva; Vetter, Céline; Roenneberg, Till

2013-01-01

Sleep and wake represent two profoundly different states of physiology that arise within the brain from a complex interaction between multiple neural circuits and neurotransmitter systems. These neural networks are, in turn, adjusted by three key drivers that collectively determine the duration, quality, and efficiency of sleep. Two of these drivers are endogenous, namely, the circadian system and a homeostatic hourglass oscillator, while the third is exogenous-our societal structure (social time). In this chapter, we outline the neuroscience of sleep and highlight the links between sleep, mood, cognition, and mental health. We emphasize that the complexity of sleep/wake generation and regulation makes this behavioral cycle very vulnerable to disruption and then explore this concept by examining sleep and circadian rhythm disruption (SCRD) when the exogenous and endogenous drivers of sleep are in conflict. SCRD can be particularly severe when social timing forces an abnormal pattern of sleep and wake upon our endogenous sleep biology. SCRD is also very common in mental illness, and although well known, this association is poorly understood or treated. Recent studies suggest that the generation of sleep and mental health shares overlapping neural mechanisms such that defects in these endogenous pathways result in pathologies to both behaviors. The evidence for this association is examined in some detail. We conclude this review by suggesting that the emerging understanding of the neurobiology of sleep/wake behavior, and of the health consequences of sleep disruption, will provide new ways to decrease the conflict between biological and societal timing in both the healthy and individuals with mental illness. © 2013, Elsevier Inc. All Rights Reserved.

Social Attention, Joint Attention and Sustained Attention in Autism Spectrum Disorder and Williams Syndrome: Convergences and Divergences.

PubMed

Vivanti, Giacomo; Fanning, Peter A J; Hocking, Darren R; Sievers, Stephanie; Dissanayake, Cheryl

2017-06-01

There is limited knowledge on shared and syndrome-specific attentional profiles in autism spectrum disorder (ASD) and Williams syndrome (WS). Using eye-tracking, we examined attentional profiles of 35 preschoolers with ASD, 22 preschoolers with WS and 20 typically developing children across social and non-social dimensions of attention. Children with ASD and those with WS presented with overlapping deficits in spontaneous visual engagement with the target of others' attention and in sustained attention. Children with ASD showed syndrome-specific abnormalities in monitoring and following a person's referential gaze, as well as a lack of preferential attention to social stimuli. Children with ASD and WS present with shared as well as syndrome-specific abnormalities across social and non-social dimensions of attention.

Walk like me, talk like me. The connection between mirror neurons and autism spectrum disorder.

PubMed

Saffin, Jillian M; Tohid, Hassaan

2016-04-01

Understanding social cognition has become a hallmark in deciphering autism spectrum disorder. Neurobiological theories are taking precedence in causation studies as researchers look to abnormalities in brain development as the cause of deficits in social behavior, cognitive processes, and language. Following their discovery in the 1990s, mirror neurons have become a dominant theory for that the mirror neuron system may play a critical role in the pathophysiology of various symptoms of autism. Over the decades, the theory has evolved from the suggestion of a broken mirror neuron system to impairments in mirror neuron circuitry. The mirror neuron system has not gained total support due to inconsistent findings; a comprehensive analysis of the growing body of research could shed light on the benefits, or the disadvantage of continuing to study mirror neurons and their connection to autism.

A Systems Engineering Survey of Artificial Intelligence and Smart Sensor Networks in a Network-Centric Environment

DTIC Science & Technology

2009-09-01

problems, to better model the problem solving of computer systems. This research brought about the intertwining of AI and cognitive psychology . Much of...where symbol sequences are sequential intelligent states of the network, and must be classified as normal, abnormal , or unknown. These symbols...is associated with abnormal behavior; and abcbc is associated with unknown behavior, as it fits no known behavior. Predicted outcomes from

Mice over-expressing BDNF in forebrain neurons develop an altered behavioral phenotype with age.

PubMed

Weidner, Kate L; Buenaventura, Diego F; Chadman, Kathryn K

2014-07-15

Evidence from clinical studies suggests that abnormal activity of brain derived neurotrophic factor (BDNF) contributes to the pathogenesis of autism spectrum disorders (ASDs). A genetically modified line of mice over-expressing a BDNF transgene in forebrain neurons was used to investigate if this mutation leads to changes in behavior consistent with ASD. The mice used in these experiments were behaviorally tested past 5 months of age when spontaneous seizures were evident. These seizures were not observed in age-matched wildtype (WT) mice or younger mice from this transgenic line. The BDNF mice in these experiments weighed less than their WT littermates. The BDNF transgenic (BDNF-tg) mice demonstrated similar levels of sociability in the social approach test. Conversely, the BDNF-tg mice demonstrated less obsessive compulsive-like behavior in the marble burying test, less anxiety-like behavior in the elevated plus maze test, and less depressive-like behavior in the forced swim test. Changes in behavior were found in these older mice that have not been observed in younger mice from this transgenic line, which may be due to the development of seizures as the mice age. These mice do not have an ASD phenotype but may be useful to study adult onset epilepsy. Copyright © 2014 Elsevier B.V. All rights reserved.

Intact perception but abnormal orientation towards face-like objects in young children with ASD

PubMed Central

Guillon, Quentin; Rogé, Bernadette; Afzali, Mohammad H.; Baduel, Sophie; Kruck, Jeanne; Hadjikhani, Nouchine

2016-01-01

There is ample behavioral evidence of diminished orientation towards faces as well as the presence of face perception impairments in autism spectrum disorder (ASD), but the underlying mechanisms of these deficits are still unclear. We used face-like object stimuli that have been shown to evoke pareidolia in typically developing (TD) individuals to test the effect of a global face-like configuration on orientation and perceptual processes in young children with ASD and age-matched TD controls. We show that TD children were more likely to look first towards upright face-like objects than children with ASD, showing that a global face-like configuration elicit a stronger orientation bias in TD children as compared to children with ASD. However, once they were looking at the stimuli, both groups spent more time exploring the upright face-like object, suggesting that they both perceived it as a face. Our results are in agreement with abnormal social orienting in ASD, possibly due to an abnormal tuning of the subcortical pathway, leading to poor orienting and attention towards faces. Our results also indicate that young children with ASD can perceive a generic face holistically, such as face-like objects, further demonstrating holistic processing of faces in ASD. PMID:26912096

Intact perception but abnormal orientation towards face-like objects in young children with ASD.

PubMed

Guillon, Quentin; Rogé, Bernadette; Afzali, Mohammad H; Baduel, Sophie; Kruck, Jeanne; Hadjikhani, Nouchine

2016-02-25

There is ample behavioral evidence of diminished orientation towards faces as well as the presence of face perception impairments in autism spectrum disorder (ASD), but the underlying mechanisms of these deficits are still unclear. We used face-like object stimuli that have been shown to evoke pareidolia in typically developing (TD) individuals to test the effect of a global face-like configuration on orientation and perceptual processes in young children with ASD and age-matched TD controls. We show that TD children were more likely to look first towards upright face-like objects than children with ASD, showing that a global face-like configuration elicit a stronger orientation bias in TD children as compared to children with ASD. However, once they were looking at the stimuli, both groups spent more time exploring the upright face-like object, suggesting that they both perceived it as a face. Our results are in agreement with abnormal social orienting in ASD, possibly due to an abnormal tuning of the subcortical pathway, leading to poor orienting and attention towards faces. Our results also indicate that young children with ASD can perceive a generic face holistically, such as face-like objects, further demonstrating holistic processing of faces in ASD.

The Effects of Twitter Sentiment on Stock Price Returns.

PubMed

Ranco, Gabriele; Aleksovski, Darko; Caldarelli, Guido; Grčar, Miha; Mozetič, Igor

2015-01-01

Social media are increasingly reflecting and influencing behavior of other complex systems. In this paper we investigate the relations between a well-known micro-blogging platform Twitter and financial markets. In particular, we consider, in a period of 15 months, the Twitter volume and sentiment about the 30 stock companies that form the Dow Jones Industrial Average (DJIA) index. We find a relatively low Pearson correlation and Granger causality between the corresponding time series over the entire time period. However, we find a significant dependence between the Twitter sentiment and abnormal returns during the peaks of Twitter volume. This is valid not only for the expected Twitter volume peaks (e.g., quarterly announcements), but also for peaks corresponding to less obvious events. We formalize the procedure by adapting the well-known "event study" from economics and finance to the analysis of Twitter data. The procedure allows to automatically identify events as Twitter volume peaks, to compute the prevailing sentiment (positive or negative) expressed in tweets at these peaks, and finally to apply the "event study" methodology to relate them to stock returns. We show that sentiment polarity of Twitter peaks implies the direction of cumulative abnormal returns. The amount of cumulative abnormal returns is relatively low (about 1-2%), but the dependence is statistically significant for several days after the events.

Transdiagnostic psychiatric symptoms related to visual evoked potential abnormalities.

PubMed

Bedwell, Jeffrey S; Butler, Pamela D; Chan, Chi C; Trachik, Benjamin J

2015-12-15

Visual processing abnormalities have been reported across a range of psychotic and mood disorders, but are typically examined within a particular disorder. The current study used a novel transdiagnostic approach to examine diagnostic classes, clinician-rated current symptoms, and self-reported personality traits in relation to visual processing abnormalities. We examined transient visual-evoked potentials (VEPs) from 48 adults (56% female), representing a wide range of psychotic and mood disorders, as well as individuals with no history of psychiatric disorder. Stimuli were low contrast check arrays presented on green and red backgrounds. Pairwise comparisons between individuals with schizophrenia-spectrum disorders (SSD), chronic mood disorders (CMD), and nonpsychiatric controls (NC) revealed no overall differences for either P1 or N1 amplitude. However, there was a significant interaction with the color background in which the NC group showed a significant increase in P1 amplitude to the red, vs. green, background, while the SSD group showed no change. This was related to an increase in social anhedonia and general negative symptoms. Stepwise regressions across the entire sample revealed that individuals with greater apathy and/or eccentric behavior had a reduced P1 amplitude. These relationships provide clues for uncovering the underlying causal pathology for these transdiagnostic symptoms. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

A single day of 5-azacytidine exposure during development induces neurodegeneration in neonatal mice and neurobehavioral deficits in adult mice.

PubMed

Subbanna, Shivakumar; Nagre, Nagaraja N; Shivakumar, Madhu; Basavarajappa, Balapal S

2016-12-01

The present study was undertaken to evaluate the immediate and long-term effects of a single-day exposure to 5-Azacytidine (5-AzaC), a DNA methyltransferase inhibitor, on neurobehavioral abnormalities in mice. Our findings suggest that the 5-AzaC treatment significantly inhibited DNA methylation, impaired extracellular signal-regulated kinase (ERK1/2) activation and reduced expression of the activity-regulated cytoskeleton-associated protein (Arc). These events lead to the activation of caspase-3 (a marker for neurodegeneration) in several brain regions, including the hippocampus and cortex, two brain areas that are essential for memory formation and memory storage, respectively. 5-AzaC treatment of P7 mice induced significant deficits in spatial memory, social recognition, and object memory in adult mice and deficits in long-term potentiation (LTP) in adult hippocampal slices. Together, these data demonstrate that the inhibition of DNA methylation by 5-AzaC treatment in P7 mice causes neurodegeneration and impairs ERK1/2 activation and Arc protein expression in neonatal mice and induces behavioral abnormalities in adult mice. DNA methylation-mediated mechanisms appear to be necessary for the proper maturation of synaptic circuits during development, and disruption of this process by 5-AzaC could lead to abnormal cognitive function. Published by Elsevier Inc.

Hypomelanosis of Ito: neurological and psychiatric pictures in developmental age.

PubMed

Parisi, L; Di Filippo, T; Roccella, M

2012-02-01

Hypomelanosis of Ito (HOI) is a multisystem neurocutaneous disorder. In the described cases, cutaneous manifestations (unilateral or bilateral streaks and swirls of hypomelanosis with regular and confluent borders) and extracutaneous abnormalities are often associated. Extracutaneous abnormalities involve the musculoskeletal system (scoliosis, vertebral anomalies, cranial-facial malformations) and other organs, as well as the central nervous system (CNS). The most significant anomalies of the CNS are psychomotor retardation and cognitive deficit. Autism, epilepsy, language disorders, cerebral malformations (neural migration disorders, cerebral hypoplasia, cortical atrophy, agenesis of the corpus callosum) are sometimes present. Numerous abnormal chromosomal patterns have been observed. HOI is usually a sporadic disorder; though autosomal dominant transmission has been suggested, recessive and X-linked inheritance patterns have also been reported. This study describes five children with HOI presenting with various features of the clinical spectrum of the syndrome. Some of these cases were referred for psychomotor therapy as part of an integrated neuropsychologic and psychomotor treatment support program. In this view, psychomotor treatment aims to promote the emotional-relational component, to overcome rigid divisions, and to integrate learning-related cognitive aspects with psychodynamic concepts. Finally, the goals of psychological and social support are to help the parents accept their child's handicap, understand the child's behavior, plan future pregnancies, and foster an environment for their child's integration.

The usefulness of body image tests in the prevention of eating disorders.

PubMed

Yamamoto, Chie; Uemoto, Masaharu; Shinfuku, Naotaka; Maeda, Kiyoshi

2007-01-01

Individual psychological factors such as mental conditions and self-esteem and family relational factors are thought to be predisposing factors in the development of eating disorders. In this study, we conducted a survey of 12-15 year-old public junior high school students to extract factors related to abnormal eating behavior and determine what information could be used by schools to prevent eating disorders. Self-descriptive surveys were distributed and collected during homeroom time at school. The survey consisted of the 26-item Eating Attitude Test (EAT-26) to measure the degree of abnormal eating behavior, Stunkard, Sorensen and Schlusinger's Body Image Scale to determine predisposing factors, the Family Adaptability and Cohesion Scale III (FACES III), General Health Questionnaire (GHQ), and Rosenberg's Self-Esteem Scale. 483 students (263 boys and 220 girls) participated in the survey. School-year height and weight data was used to calculate BMI. Approximately 7% of girls and 3% of boys showed clear indications of abnormal eating behavior. We found no direct relationship between abnormal eating behavior and family factors in this study, but an indirect relationship was suggested through other factors such as psychological complaints and self-esteem. There were relationships between abnormal eating behavior and the individual factors of psychological complaints, current and ideal body image, and low self-esteem. Furthermore, cluster analysis showed that there were students with high BMI who thought of themselves as fat, as well as students who perceived themselves as fat despite having average BMI. These students had a high frequency of abnormal eating behaviors, a great deal of psychological complaints, and low self-esteem. An understanding of BMI, along with body image, is essential for students who feel that they are overweight. Schools can practice preventative education by teaching these students about healthy body weight and by screening for the eating disorders that have become so rampant in our thin-worshiping culture.

Autism and sleep disorders.

PubMed

Devnani, Preeti A; Hegde, Anaita U

2015-01-01

"Autism Spectrum Disorders" (ASDs) are neurodevelopment disorders and are characterized by persistent impairments in reciprocal social interaction and communication. Sleep problems in ASD, are a prominent feature that have an impact on social interaction, day to day life, academic achievement, and have been correlated with increased maternal stress and parental sleep disruption. Polysomnography studies of ASD children showed most of their abnormalities related to rapid eye movement (REM) sleep which included decreased quantity, increased undifferentiated sleep, immature organization of eye movements into discrete bursts, decreased time in bed, total sleep time, REM sleep latency, and increased proportion of stage 1 sleep. Implementation of nonpharmacotherapeutic measures such as bedtime routines and sleep-wise approach is the mainstay of behavioral management. Treatment strategies along with limited regulated pharmacotherapy can help improve the quality of life in ASD children and have a beneficial impact on the family. PubMed search was performed for English language articles from January 1995 to January 2015. Following key words: Autism spectrum disorder, sleep disorders and autism, REM sleep and autism, cognitive behavioral therapy, sleep-wise approach, melatonin and ASD were used. Only articles reporting primary data relevant to the above questions were included.

An investigation of moral judgement in frontotemporal dementia.

PubMed

Mendez, Mario F; Anderson, Eric; Shapira, Jill S

2005-12-01

To investigate the basis of disturbed moral judgment in patients with frontotemporal dementia (FTD). FTD is characterized by difficulty in modulating social behavior. Patients lack social propriety and may perform sociopathic acts. In addition, FTD patients often lack empathy for others. These findings suggest alterations in the nature of morality in patients with FTD. We administered an inventory of moral knowledge and two moral dilemmas to 26 patients with the frontal variant of FTD, 26 patients with Alzheimer disease (AD), and 26 normal control subjects. The FTD patients met Consensus Criteria for FTD and had corroborative frontal abnormalities on functional neuroimaging. The FTD and AD patients were comparably impaired on dementia measures. All these groups showed the retention of knowledge for moral behavior and the ability to make "impersonal" moral judgments. In contrast, the FTD patients were impaired in their ability to make immediate, emotionally based moral judgments compared with the patients with AD and the normal control subjects. These findings are consistent with an attenuation of the automatic emotional identification with others that is part of the innate moral sense. Such a disturbance may result from neurodegenerative disease affecting the ventromedial frontal cortex.

Brain effects of chronic IBD in areas abnormal in autism and treatment by single neuropeptides secretin and oxytocin.

PubMed

Welch, Martha G; Welch-Horan, Thomas B; Anwar, Muhammad; Anwar, Nargis; Ludwig, Robert J; Ruggiero, David A

2005-01-01

Recent research points to the connection between behavioral and gut disorders. Early adverse events are associated with inflammatory bowel disease (IBD). In animal models, maternal deprivation and social isolation predispose to gastric erosion and brain pathology. This study examined (1) brain effects of chronic gastrointestinal inflammation in a rat model of acquired IBD and (2) whether such changes are resolved by individual secretin (S) or oxytocin (OT) peptide treatment. Neurological manifestations of IBD were mapped by c-fos gene expression in male Sprague-Dawley rats (n = 10) with trinitrobenzene sulfonic acid (TNBS)-induced IBD vs controls (n = 11). IBD was characterized by moderate/severe infiltration of inflammatory cells 10 d after TNBS infusion. Age-matched pairs were processed for immunocytochemical detection of Fos, expressed when neurons are stimulated. S or OT (100 mg/250 mL saline) or equivolume saline was administered iv by Alzet pump for 20 d after disease onset. Degree of resolution of colitis-induced brain activation was assessed by c-fos expression, and mean numbers of Fos-immunoreactive nuclei for each group were compared using Independent Samples T-test. Chronic IBD activated periventricular gray, hypothalamic/visceral thalamic stress axes and cortical domains, and septal/preoptic/amygdala, brain areas abnormal in autism. Single peptide treatment with S or OT did not alter the effects of inflammation on the brain. Brain areas concomitantly activated by visceral inflammation are those often abnormal in autism, suggesting that IBD could be a model for testing treatments of autism. Other single and combined peptide treatments of IBD should be tested. The clinical implications for treating autism, IBD, and concomitant sickness behaviors with peptide therapy, with or without maternal nurturing as a natural equivalent, are presented.

Neuroimaging studies of social cognition in schizophrenia.

PubMed

Fujiwara, Hironobu; Yassin, Walid; Murai, Toshiya

2015-05-01

Impaired social cognition is considered a core contributor to unfavorable psychosocial functioning in schizophrenia. Rather than being a unitary process, social cognition is a collection of multifaceted processes that recruit multiple brain structures, thus structural and functional neuroimaging techniques are ideal methodologies for revealing the underlying pathophysiology of impaired social cognition. Many neuroimaging studies have suggested that in addition to white-matter deficits, schizophrenia is associated with decreased gray-matter volume in multiple brain areas, especially fronto-temporal and limbic regions. However, few schizophrenia studies have examined associations between brain abnormalities and social cognitive disabilities. During the last decade, we have investigated structural brain abnormalities in schizophrenia using high-resolution magnetic resonance imaging, and our findings have been confirmed by us and others. By assessing different types of social cognitive abilities, structural abnormalities in multiple brain regions have been found to be associated with disabilities in social cognition, such as recognition of facial emotion, theory of mind, and empathy. These structural deficits have also been associated with alexithymia and quality of life in ways that are closely related to the social cognitive disabilities found in schizophrenia. Here, we overview a series of neuroimaging studies from our laboratory that exemplify current research into this topic, and discuss how it can be further tackled using recent advances in neuroimaging technology. © 2014 The Authors. Psychiatry and Clinical Neurosciences © 2014 Japanese Society of Psychiatry and Neurology.

Methods and systems for detecting abnormal digital traffic

DOEpatents

Goranson, Craig A [Kennewick, WA; Burnette, John R [Kennewick, WA

2011-03-22

Aspects of the present invention encompass methods and systems for detecting abnormal digital traffic by assigning characterizations of network behaviors according to knowledge nodes and calculating a confidence value based on the characterizations from at least one knowledge node and on weighting factors associated with the knowledge nodes. The knowledge nodes include a characterization model based on prior network information. At least one of the knowledge nodes should not be based on fixed thresholds or signatures. The confidence value includes a quantification of the degree of confidence that the network behaviors constitute abnormal network traffic.

Automatic event recognition and anomaly detection with attribute grammar by learning scene semantics

NASA Astrophysics Data System (ADS)

Qi, Lin; Yao, Zhenyu; Li, Li; Dong, Junyu

2007-11-01

In this paper we present a novel framework for automatic event recognition and abnormal behavior detection with attribute grammar by learning scene semantics. This framework combines learning scene semantics by trajectory analysis and constructing attribute grammar-based event representation. The scene and event information is learned automatically. Abnormal behaviors that disobey scene semantics or event grammars rules are detected. By this method, an approach to understanding video scenes is achieved. Further more, with this prior knowledge, the accuracy of abnormal event detection is increased.

Biological aspects of social bonding and the roots of human violence.

PubMed

Pedersen, Cort A

2004-12-01

The brain systems that motivate humans to form emotional bonds with others probably first evolved to mobilize the high-quality maternal care necessary for reproductive success in placental mammals. In these species, the helplessness of infants at birth and their dependence upon nutrition secreted from their mothers' bodies (milk) and parental body heat to stay warm required the evolution of a new motivational system in the brain to stimulate avid and sustained mothering behavior. Other types of social bonds that emerged subsequently in placental mammals, in particular monogamous bonds between breeding pairs, appear to have evolved from motivational brain systems that stimulate maternal behavior. This chapter focuses on aspects of the evolution and neurobiology of maternal and pair bonding and associated behavioral changes that may provide insights into the origins of human violence. The roles of the neuropeptides oxytocin and vasopressin as well as the neurotransmitter dopamine will be emphasized. Maternal and pair bonding are accompanied by increased aggressiveness toward perceived threats to the object of attachment as well as diminished fear and anxiety in stressful situations. The sustained closeness with mother required for the survival of infant mammals opened a new evolutionary niche in which aspects of the mother's care became increasingly important in regulating development in offspring. The quantity and quality of maternal care received during infancy determines adult social competence, ability to cope with stress, aggressiveness, and even preference for addictive substances. Indeed, the development of neurochemical systems within the brain that regulate mothering, aggression, and other types of social behavior, such as the oxytocin and vasopressin systems, are strongly affected by parental nurturing received during infancy. Evidence will be reviewed that the neural circuitry and neurochemistry implicated in studies of lower mammals also facilitate primate/human interpersonal bonding. It is hypothesized that neural bonding systems may also be important for the development in individuals of loyalty to the social group and its culture. Neglect and abuse during early life may cause bonding systems to develop abnormally and compromise capacity for rewarding interpersonal relationships and commitment to societal and cultural values later in life. Other means of stimulating reward pathways in the brain, such as drugs, sex, aggression, and intimidating others, could become relatively more attractive and less constrained by concern about violating trusting relationships. The ability to modify behavior based on negative experiences may be impaired. Unmet needs for social bonding and acceptance early in life might increase the emotional allure of groups (gangs, sects) with violent and authoritarian values and leadership. Social neurobiology has the potential to provide new strategies for treating and preventing violence and associated social dysfunction.

The Immune System, Cytokines, and Biomarkers in Autism Spectrum Disorder.

PubMed

Masi, Anne; Glozier, Nicholas; Dale, Russell; Guastella, Adam J

2017-04-01

Autism Spectrum Disorder (ASD) is a pervasive neurodevelopmental condition characterized by variable impairments in communication and social interaction as well as restricted interests and repetitive behaviors. Heterogeneity of presentation is a hallmark. Investigations of immune system problems in ASD, including aberrations in cytokine profiles and signaling, have been increasing in recent times and are the subject of ongoing interest. With the aim of establishing whether cytokines have utility as potential biomarkers that may define a subgroup of ASD, or function as an objective measure of response to treatment, this review summarizes the role of the immune system, discusses the relationship between the immune system, the brain, and behavior, and presents previously-identified immune system abnormalities in ASD, specifically addressing the role of cytokines in these aberrations. The roles and identification of biomarkers are also addressed, particularly with respect to cytokine profiles in ASD.

Neurobiologically based interventions for autism spectrum disorders-rationale and new directions.

PubMed

Poustka, Luise; Brandeis, Daniel; Hohmann, Sarah; Holtmann, Martin; Bölte, Sven; Banaschewski, Tobias

2014-01-01

Autism spectrum disorders (ASD) are heterogeneous, neurodevelopmental disorders with early onset, characterized by a triad of impairments in reciprocal interaction and communication as well as repetitive and restricted interests and activities. Though underlying causes still remain largely unknown, there is now evidence for abnormal growth trajectories in the early brain development in ASD during vulnerable periods and subsequent impairment of neuronal organization and differentiation of neuronal networks. A growing number of studies over the last 10 years support the efficacy of behaviorally based interventions in ASD for the improvement of social communication and behavioral functioning. In contrast, research on neurobiologically based therapies for ASD is still at its beginnings. In this article, we will provide a selective overview of novel interventions and trainings based on neurobiological principles. Directions and options for future research on treatment aiming at restoration of normal plasticity in disrupted brain circuits in ASD are discussed.

Computational Psychiatry

PubMed Central

Wang, Xiao-Jing; Krystal, John H.

2014-01-01

Psychiatric disorders such as autism and schizophrenia arise from abnormalities in brain systems that underlie cognitive, emotional and social functions. The brain is enormously complex and its abundant feedback loops on multiple scales preclude intuitive explication of circuit functions. In close interplay with experiments, theory and computational modeling are essential for understanding how, precisely, neural circuits generate flexible behaviors and their impairments give rise to psychiatric symptoms. This Perspective highlights recent progress in applying computational neuroscience to the study of mental disorders. We outline basic approaches, including identification of core deficits that cut across disease categories, biologically-realistic modeling bridging cellular and synaptic mechanisms with behavior, model-aided diagnosis. The need for new research strategies in psychiatry is urgent. Computational psychiatry potentially provides powerful tools for elucidating pathophysiology that may inform both diagnosis and treatment. To achieve this promise will require investment in cross-disciplinary training and research in this nascent field. PMID:25442941

Phencyclidine animal models of schizophrenia: approaches from abnormality of glutamatergic neurotransmission and neurodevelopment.

PubMed

Mouri, Akihiro; Noda, Yukihiro; Enomoto, Takeshi; Nabeshima, Toshitaka

2007-01-01

In humans, phencyclidine (PCP), a non-competitive N-methyl-d-aspartate (NMDA) receptor antagonist, reproduces a schizophrenia-like psychosis including positive symptoms, negative symptoms and cognitive dysfunction. Thus, the glutamatergic neuronal dysfunction hypothesis is one of the main explanatory hypotheses and PCP-treated animals have been utilized as an animal model of schizophrenia. The adult rodents treated with PCP repeatedly exhibit hyperlocomotion as an index of positive symptoms, a social behavioral deficit in a social interaction test and enhanced immobility in a forced swimming test as indices of negative symptoms. They also show a sensorimotor gating deficits and cognitive dysfunctions in several learning and memory tests. Some of these behavioral changes endure after withdrawal from repeated PCP treatment. Furthermore, repeated PCP treatment induces some neurochemical and neuroanatomical changes. On the other hand, the exposure to viral or environmental insult in the second trimester of pregnancy increases the probability of subsequently developing schizophrenia as an adult. NMDA receptor has been implicated in controlling the structure and plasticity of developing brain circuitry. Based on neurodevelopment hypothesis of schizophrenia, schizophrenia model rats treated with PCP at the perinatal stage is developed. Perinatal PCP treatment impairs neuronal development and induces long-lasting schizophrenia-like behaviors in adult period. Many findings suggest that these PCP animal models would be useful for evaluating novel therapeutic candidates and for confirming pathological mechanisms of schizophrenia.

Extinction after retrieval: effects on the associative and nonassociative components of remote contextual fear memory.

PubMed

Costanzi, Marco; Cannas, Sara; Saraulli, Daniele; Rossi-Arnaud, Clelia; Cestari, Vincenzo

2011-01-01

Long-lasting memories of adverse experiences are essential for individuals' survival but are also involved, in the form of recurrent recollections of the traumatic experience, in the aetiology of anxiety diseases (e.g., post-traumatic stress disorder [PTSD]). Extinction-based erasure of fear memories has long been pursued as a behavioral way to treat anxiety disorders; yet, such a procedure turns out to be transient, context-dependent, and ineffective unless it is applied immediately after trauma. Recent evidence indicates that, in both rats and humans, extinction training can prevent the return of fear if administered within the reconsolidation window, when memories become temporarily labile and susceptible of being updated. Here, we show that the reconsolidation-extinction procedure fails to prevent the spontaneous recovery of a remote contextual fear memory in a mouse model of PTSD, as well as the long-lasting behavioral abnormalities induced by traumatic experience on anxiety and in both social and cognitive domains (i.e., social withdrawal and spatial learning deficits). Such a failure appears to be related to the ineffectiveness of the reconsolidation-extinction procedure in targeting the pathogenic process of fear sensitization, a nonassociative component of traumatic memory that causes animals to react aberrantly to harmless stimuli. This indicates fear sensitization as a major target for treatments aimed at mitigating anxiety and the behavioral outcomes of traumatic experiences.

On the relationship between emotional state and abnormal unfairness sensitivity in alcohol dependence.

PubMed

Brevers, Damien; Noël, Xavier; Hanak, Catherine; Verbanck, Paul; Kornreich, Charles

2015-01-01

Recent empirical findings suggest that alcohol dependence is characterized by heightened sensitivity to unfairness during social transactions. The present study went a step further and aimed to ascertain whether this abnormal level of sensitivity to unfairness is underlined by an increased emotional reactivity. Twenty-six recently abstinent alcohol-dependent (AD) individuals and 32 controls performed an ultimatum game (UG), in which participants had to respond to take-it-or-leave-it offers, ranging from fair to unfair and made by a fictive proposer. Emotional state was recorded during UG offers presentation and was indexed by the amplitude of skin conductance response (SCR). Results showed that AD decided to reject unfair offers more frequently than their controls, confirming previous data. The proportion of rejected unfair UG offers was correlated with SCR, in the AD but not in the control group. This finding suggests that deciding to accept or reject unfair UG offers is influenced by arousal-affective activity in AD, but not in controls. Heightened emotional reactivity may have driven AD to punish the proposer rather than acting as a rational economic agent. An implication of present findings is that AD might have difficult to cope with unfair situations triggered by social interactions. Future studies are needed in order to examine whether-emotional and behavioral-reactivity to unfairness during the UG could impact alcohol consumption and relapse in AD.

Shape-and-behavior encoded tracking of bee dances.

PubMed

Veeraraghavan, Ashok; Chellappa, Rama; Srinivasan, Mandyam

2008-03-01

Behavior analysis of social insects has garnered impetus in recent years and has led to some advances in fields like control systems, flight navigation etc. Manual labeling of insect motions required for analyzing the behaviors of insects requires significant investment of time and effort. In this paper, we propose certain general principles that help in simultaneous automatic tracking and behavior analysis with applications in tracking bees and recognizing specific behaviors exhibited by them. The state space for tracking is defined using position, orientation and the current behavior of the insect being tracked. The position and orientation are parametrized using a shape model while the behavior is explicitly modeled using a three-tier hierarchical motion model. The first tier (dynamics) models the local motions exhibited and the models built in this tier act as a vocabulary for behavior modeling. The second tier is a Markov motion model built on top of the local motion vocabulary which serves as the behavior model. The third tier of the hierarchy models the switching between behaviors and this is also modeled as a Markov model. We address issues in learning the three-tier behavioral model, in discriminating between models, detecting and in modeling abnormal behaviors. Another important aspect of this work is that it leads to joint tracking and behavior analysis instead of the traditional track and then recognize approach. We apply these principles for tracking bees in a hive while they are executing the waggle dance and the round dance.

Frontal hyperconnectivity related to discounting and reversal learning in cocaine subjects.

PubMed

Camchong, Jazmin; MacDonald, Angus W; Nelson, Brent; Bell, Christopher; Mueller, Bryon A; Specker, Sheila; Lim, Kelvin O

2011-06-01

Functional neuroimaging studies suggest that chronic cocaine use is associated with frontal lobe abnormalities. Functional connectivity (FC) alterations of cocaine-dependent individuals (CD), however, are not yet clear. This is the first study to our knowledge that examines resting FC of anterior cingulate cortex (ACC) in CD. Because ACC is known to integrate inputs from different brain regions to regulate behavior, we hypothesized that CD will have connectivity abnormalities in ACC networks. In addition, we hypothesized that abnormalities would be associated with poor performance in delayed discounting and reversal learning tasks. Resting functional magnetic resonance imaging data were collected to look for FC differences between 27 CD (5 women, age: M = 39.73, SD = 6.14 years) and 24 control subjects (5 women, age: M = 39.76, SD = 7.09 years). Participants were assessed with delayed discounting and reversal learning tasks. With seed-based FC measures, we examined FC in CD and control subjects within five ACC connectivity networks with seeds in subgenual, caudal, dorsal, rostral, and perigenual ACC. The CD showed increased FC within the perigenual ACC network in left middle frontal gyrus, ACC, and middle temporal gyrus when compared with control subjects. The FC abnormalities were significantly positively correlated with task performance in delayed discounting and reversal learning tasks in CD. The present study shows that participants with chronic cocaine-dependency have hyperconnectivity within an ACC network known to be involved in social processing and "mentalizing." In addition, FC abnormalities found in CD were associated with difficulties with delay rewards and slower adaptive learning. Copyright © 2011 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

Teaching a Course in Abnormal Psychology and Behavior Intervention Skills for Nursing Home Aides.

ERIC Educational Resources Information Center

Glenwick, David S.; Slutzsky, Mitchel R.; Garfinkel, Eric

2001-01-01

Describes an 11-week course given at a nursing home to nursing home aides that focused on abnormal psychology and behavior intervention skills. Discusses the course goals, class composition, and course description. Addresses the problems and issues encountered with teaching this course to a nontraditional population in an unconventional setting.…

Correlation between physical anomaly and behavioral abnormalities in Down syndrome

PubMed Central

Bhattacharyya, Ranjan; Sanyal, Debasish; Roy, Krishna; Bhattacharyya, Sumita

2010-01-01

Objective: The minor physical anomaly (MPA) is believed to reflect abnormal development of the CNS. The aim is to find incidence of MPA and its behavioral correlates in Down syndrome and to compare these findings with the other causes of intellectual disability and normal population. Materials and Methods: One-hundred and forty intellectually disabled people attending a tertiary care set-up and from various NGOs are included in the study. The age-matched group from normal population was also studied for comparison. MPA are assessed by using Modified Waldrop scale and behavioral abnormality by Diagnostic assessment scale for severely handicapped (DASH II scale). Results: The Down syndrome group had significantly more MPA than other two groups and most of the MPA is situated in the global head region. There is strong correlation (P < 0.001) between the various grouped items of Modified Waldrop scale. Depression subscale is correlated with anomalies in the hands (P < 0.001), feet and Waldrop total items (P < 0.005). Mania item of DASH II scale is related with anomalies around the eyes (P < 0.001). Self-injurious behavior and total Waldrop score is negatively correlated with global head. Conclusion: Down syndrome group has significantly more MPA and a pattern of correlation between MPA and behavioral abnormalities exists which necessitates a large-scale study. PMID:21559153

Electrolyte and acid-base abnormalities associated with purging behaviors.

PubMed

Mehler, Philip S; Walsh, Kristine

2016-03-01

Eating disorders that are associated with purging behaviors are complicated by frequent blood electrolyte and acid-base abnormalities. Herein, we review the major electrolyte and acid-base abnormalities and their treatment methods. The body of rigorous, eating disorder-specific literature on this topical area is not robust enough to perform a systematic review as defined by PRISMA guidelines. Therefore, a qualitative review of mostly medical literature was conducted. Hypokalemia, hyponatremia, and sodium chloride-responsive metabolic alkalosis are the most common serum changes that occur as a result of purging behaviors. They vary depending on the mode and frequency of purging behaviors. They can all potentially cause dangerous medical complications and are in need of definitive medical treatment. Eating disorders that are associated with purging behaviors are associated with a number of electrolyte and acid-base changes which are complex in their origin, documented to be medically dangerous and this definitive treatment is necessary to help achieve a successful treatment outcome, and in need of definitive treatment as described herein. © 2016 Wiley Periodicals, Inc.

Previously unrecognized behavioral phenotype in Gaucher disease type 3

PubMed Central

Potegal, Michael; Shapiro, Elsa G.; Nestrasil, Igor

2017-01-01

Objective: To provide a comprehensive description of abnormal behaviors in patients with Gaucher disease type 3 (GD3) and relate these behaviors to demographic, neurodevelopmental, and neurologic characteristics. Methods: Thirty-four Egyptian patients with GD3 (mean age of 7.9 years) were enrolled in the study. They were selected based on parent report and/or physician observation of one or more abnormal behaviors documented in 2 settings and by 2 different individuals and/or by video recording. Behaviors were grouped into 4 categories: Crying/Withdrawal, Impatience/Overactivity, Anger/Aggression, and Repetitive Acts. Baseline and follow-up 6–12 monthly neurologic evaluations included IQ assessment and an EEG. All patients were receiving enzyme replacement therapy (30–60 IU/kg every 2 weeks) and were followed for periods of 3–10 years. Results: Supranuclear palsy of horizontal gaze, and of both horizontal and vertical gaze, bulbar symptoms, seizures, convergent strabismus, abnormal gait, and neck retroflexion were present in 97.1%, 50%, 55.9%, 29.4%, 29.4%, 20.6%, and 4.4% of patients, respectively. The most abnormal behavioral features were excessive anger (88.2%) and aggression (64.7%), and both were significantly higher in males. Anger/Aggression scores were highly correlated with IQ but not with either EEG/Seizure status or neurologic signs. Conclusions: We describe behavioral problems with a unique pattern of excessive anger and aggression in patients with GD3. Defining these components using quantitative behavioral scoring methods holds promise to provide a marker of neurologic disease progression and severity. PMID:28634598

Activation of presynaptic oxytocin receptors enhances glutamate release in the ventral hippocampus of prenatally restraint stressed rats.

PubMed

Mairesse, Jérôme; Gatta, Eleonora; Reynaert, Marie-Line; Marrocco, Jordan; Morley-Fletcher, Sara; Soichot, Marion; Deruyter, Lucie; Camp, Gilles Van; Bouwalerh, Hammou; Fagioli, Francesca; Pittaluga, Anna; Allorge, Delphine; Nicoletti, Ferdinando; Maccari, Stefania

2015-12-01

Oxytocin receptors are known to modulate synaptic transmission and network activity in the hippocampus, but their precise function has been only partially elucidated. Here, we have found that activation of presynaptic oxytocin receptor with the potent agonist, carbetocin, enhanced depolarization-evoked glutamate release in the ventral hippocampus with no effect on GABA release. This evidence paved the way for examining the effect of carbetocin treatment in "prenatally restraint stressed" (PRS) rats, i.e., the offspring of dams exposed to repeated episodes of restraint stress during pregnancy. Adult PRS rats exhibit an anxious/depressive-like phenotype associated with an abnormal glucocorticoid feedback regulation of the hypothalamus-pituitary-adrenal (HPA) axis, and, remarkably, with a reduced depolarization-evoked glutamate release in the ventral hippocampus. Chronic systemic treatment with carbetocin (1mg/kg, i.p., once a day for 2-3 weeks) in PRS rats corrected the defect in glutamate release, anxiety- and depressive-like behavior, and abnormalities in social behavior, in the HPA response to stress, and in the expression of stress-related genes in the hippocampus and amygdala. Of note, carbetocin treatment had no effect on these behavioral and neuroendocrine parameters in prenatally unstressed (control) rats, with the exception of a reduced expression of the oxytocin receptor gene in the amygdala. These findings disclose a novel function of oxytocin receptors in the hippocampus, and encourage the use of oxytocin receptor agonists in the treatment of stress-related psychiatric disorders in adult life. Copyright © 2015 Elsevier Ltd. All rights reserved.

Morphological and behavioral markers of environmentally induced retardation of brain development: an animal model

DOE Office of Scientific and Technical Information (OSTI.GOV)

Altman, J.

1987-10-01

In most neurotoxicological studies morphological assessment focuses on pathological effects, like degenerative changes in neuronal perikarya, axonopathy, demyelination, and glial and endothelial cell reactions. Similarly, the assessment of physiological and behavioral effects center on evident neurological symptoms, like EEG and EMG abnormalities, resting and intention tremor, abnormal gait, and abnormal reflexes. This paper reviews briefly another central nervous system target of harmful environmental agents, which results in behavioral abnormalities without any qualitatively evident neuropathology. This is called microneuronal hypoplasia, a retardation of brain development characterized by a quantitative reduction in the normal population of late-generated, short-axoned neurons in specific brainmore » regions. Correlated descriptive and experimental neurogenetic studies in the rat have established that all the cerebellar granule cells and a very high proportion of hippocampal granule cells are produced postnatally, and that focal, low-dose X-irradiation either of the cerebellum or of the hippocampus after birth selectively interferes with the acquisition of the full complement of granule cells (microneuronal hypoplasia). Subsequent behavioral investigations showed that cerebellar microneuronal hypoplasia results in profound hyperactivity without motor abnormalities, while hippocampal microneuronal hypoplasia results in hyperactivity, as well as attentional and learning deficits. There is much indirect clinical evidence that various harmful environmental agents affecting the pregnant mother and/or the infant lead to such childhood disorders as hyperactivity and attentional and learning disorders. 109 references.« less

Prevalence of abnormal eating behaviors in adolescents in Mexico: Mexican National Health and Nutrition Survey 2006.

PubMed

Barriguete-Meléndez, Jorge Armando; Unikel-Santoncini, Claudia; Aguilar-Salinas, Carlos; Córdoba-Villalobos, José Angel; Shamah, Teresa; Barquera, Simón; Rivera, Juan A; Hernández-Avila, Mauricio

2009-01-01

To describe the prevalence of abnormal eating behaviors in a population-based nationwide survey. A stratified, probabilistic, multistage design sampling process was used. The Brief Questionnaire for Risky Eating Behaviors was included in the Mexican Health and Nutrition Survey 2006 (ENSANUT 2006) and administered to participants 10-19 years old (n= 25 166). The study had the power to describe nationwide characteristics by age, regions and urban/rural settings. A high risk for having an eating disorder was found in 0.8% of the total participants (0.4% male adolescents and 1.0% female). Inhabitants in large cities showed higher risk for having an abnormal eating behavior compared to subjects living in other settings. The highest prevalences were found in males > 15 years old and females > 13 years old for all evaluated behaviors. Results show less prevalence of risky eating behaviors among adolescents in comparison to other populations. The female/male ratio was 3:1, far different from the 9:1 shown in a previous study in Mexico City, but similar to results from the US national eating disorders screening.

Effects of early weaning and social isolation on the expression of glucocorticoid and mineralocorticoid receptor and 11beta-hydroxysteroid dehydrogenase 1 and 2 mRNAs in the frontal cortex and hippocampus of piglets.

PubMed

Poletto, R; Steibel, J P; Siegford, J M; Zanella, A J

2006-01-05

Pigs weaned at young ages show more abnormal and aggressive behaviors and cognitive deficits compared to later weaned pigs. We investigated the effects of age, weaning and/or social isolation on the expression of genes regulating glucocorticoid response [glucocorticoid receptor (GR), mineralocorticoid receptor (MR), 11beta-hydroxysteroid dehydrogenases 1 and 2 (11beta-HSD1 and 11beta-HSD2)] in the frontal cortex and hippocampus. Early- (EW; n = 6) and conventionally-weaned (CW; n = 6) piglets were weaned at 10 and 21 days after birth, respectively. Non-weaned (NW) piglets of both ages (NW; n = 6/group) remained with their dams. Immediately before euthanasia, half of CW, EW and NW animals were socially isolated for 15 min at 12 (EW, NW) and 23 (CW, NW) days of age. Differences in amounts of 11beta-HSD1, 11beta-HSD2, GR and MR mRNA were determined by quantitative real-time RT-PCR and data subjected to multivariate linear mixed model analysis. When compared with NW piglets at 12 days of age, the hippocampi of EW piglets showed decreased gene expression (P < 0.01). Social isolation decreased gene expression (P < 0.05) in the frontal cortex of all piglets. Twelve-day-old piglets showed higher MR mRNA in the frontal cortex (P < 0.01) and lower 11beta-HSD2 and GR mRNA (P < 0.05) in the hippocampus compared to 23-day-old animals. Results indicate that EW affected the hippocampus of piglets at 12 days of age, while social isolation affected frontal cortex regardless of age. These results may be correlated with behavioral and cognitive changes reported in EW piglets.

Genetic background effects in Neuroligin-3 mutant mice: Minimal behavioral abnormalities on C57 background.

PubMed

Jaramillo, Thomas C; Escamilla, Christine Ochoa; Liu, Shunan; Peca, Lauren; Birnbaum, Shari G; Powell, Craig M

2018-02-01

Neuroligin-3 (NLGN3) is a postsynaptic cell adhesion protein that interacts with presynaptic ligands including neurexin-1 (NRXN1) [Ichtchenko et al., Journal of Biological Chemistry, 271, 2676-2682, 1996]. Mice harboring a mutation in the NLGN3 gene (NL3R451C) mimicking a mutation found in two brothers with autism spectrum disorder (ASD) were previously generated and behaviorally phenotyped for autism-related behaviors. In these NL3R451C mice generated and tested on a hybrid C57BL6J/129S2/SvPasCrl background, we observed enhanced spatial memory and reduced social interaction [Tabuchi et al., Science, 318, 71-76, 2007]. Curiously, an independently generated second line of mice harboring the same mutation on a C57BL6J background exhibited minimal aberrant behavior, thereby providing apparently discrepant results. To investigate the origin of the discrepancy, we previously replicated the original findings of Tabuchi et al. by studying the same NL3R451C mutation on a pure 129S2/SvPasCrl genetic background. Here we complete the behavioral characterization of the NL3R451C mutation on a pure C57BL6J genetic background to determine if background genetics play a role in the discrepant behavioral outcomes involving NL3R451C mice. NL3R451C mutant mice on a pure C57BL6J background did not display spatial memory enhancements or social interaction deficits. We only observed a decreased startle response and mildly increased locomotor activity in these mice suggesting that background genetics influences behavioral outcomes involving the NL3R451C mutation. Autism Res 2018, 11: 234-244. © 2017 International Society for Autism Research, Wiley Periodicals, Inc. Behavioral symptoms of autism can be highly variable, even in cases that involve identical genetic mutations. Previous studies in mice with a mutation of the Neuroligin-3 gene showed enhanced learning and social deficits. We replicated these findings on the same and different genetic backgrounds. In this study, however, the same mutation in mice on a different genetic background did not reproduce our previous findings. Our results suggest that genetic background influences behavioral symptoms of this autism-associated mutation. © 2017 International Society for Autism Research, Wiley Periodicals, Inc.

Motor and cognitive stereotypies in the BTBR T+tf/J mouse model of autism

PubMed Central

Pearson, BL; Pobbe, RLH; Defensor, EB; Oasay, L; Bolivar, VJ; Blanchard, DC; Blanchard, RJ

2010-01-01

The BTBR T+tf/J inbred mouse strain displays a variety of persistent phenotypic alterations similar to those exhibited in autism spectrum disorders. The unique genetic background of the BTBR strain is thought to underlie its lack of reciprocal social interactions, elevated repetitive self-directed grooming and restricted exploratory behaviors. In order to clarify the existence, range and mechanisms of abnormal repetitive behaviors within BTBR mice, we performed detailed analyses of the microstructure of self-grooming patterns and noted increased overall grooming, higher percentages of interruptions in grooming bouts and a concomitant decrease in the proportion of incorrect sequence transitions compared to C57BL/6J inbred mice. Analyses of active phase home cage behavior also revealed an increase in stereotypic bar-biting behavior in the BTBR strain relative to B6 mice. Finally, in a novel object investigation task, BTBR mice exhibited greater baseline preference for specific unfamiliar objects as well as more patterned sequences of sequential investigations of those items. These results suggest that the repetitive, stereotyped behavior patterns of BTBR mice are relatively pervasive and reflect both motor and cognitive mechanisms. Furthermore, other pre-clinical mouse models of autism spectrum disorders may benefit from these more detailed analyses of stereotypic behavior. PMID:21040460

Abnormal chromosome behavior in human oocytes which remained unfertilized during human in vitro fertilization.

PubMed

Spielmann, H; Krüger, C; Stauber, M; Vogel, R

1985-09-01

Chromosomal abnormalities and abnormal embryonic development have previously been observed after human in vitro fertilization (IVF). Chromosomal abnormalities may arise not only after fertilization but even earlier during meiotic maturation of human oocytes in culture. Since chromosomal analysis is simple in oocytes during meiotic maturation, the chromosomal status was analyzed in oocytes which remained unfertilized in a human in vitro fertilization program. In 50 fertilization attempts the chromosomes of 62 unfertilized oocytes could be analyzed; 45 of them were in the process of meiotic maturation. In three oocytes two small polar bodies were observed 16-18 hr after insemination in the absence of fertilization. In one oocyte abnormal chromosome behavior was found during the first meiotic division, and in four oocytes during metaphase of the second meiotic division. These data suggest that chromosomal analysis of unfertilized oocytes in human IVF may improve the understanding human oocyte maturation and fertilization.

Studies of planning behavior of aircraft pilots in normal, abnormal, and emergency situations

NASA Technical Reports Server (NTRS)

Johannsen, G.; Rouse, W. B.; Hillmann, K.

1981-01-01

A methodology for the study of human planning behavior in complex dynamic systems is presented and applied to the study of aircraft pilot behavior in normal, abnormal and emergency situations. The method measures the depth of planning, that is the level of detail employed with respect to a specific task, according to responses to a verbal questionnaire, and compares planning depth with variables relating to time, task criticality and the probability of increased task difficulty. In two series of experiments, depth of planning was measured on a five- or ten-point scale during various phases of flight in a HFB-320 simulator under normal flight conditions, abnormal scenarios involving temporary runway closure due to snow removal or temporary CAT-III conditions due to a dense fog, and emergency scenarios involving engine shut-down or hydraulic pressure loss. Results reveal a dichotomy between event-driven and time-driven planning, different effects of automation in abnormal and emergency scenarios and a low correlation between depth of planning and workload or flight performance.

Social environments and interpersonal distance regulation in psychosis: A virtual reality study.

PubMed

Geraets, Chris N W; van Beilen, Marije; Pot-Kolder, Roos; Counotte, Jacqueline; van der Gaag, Mark; Veling, Wim

2018-02-01

Experimentally studying the influence of social environments on mental health and behavior is challenging, as social context is difficult to standardize in laboratory settings. Virtual Reality (VR) enables studying social interaction in terms of interpersonal distance in a more ecologically valid manner. Regulation of interpersonal distance may be abnormal in patients with psychotic disorders and influenced by environmental stress, symptoms or distress. To investigate interpersonal distance in people with a psychotic disorder and at ultrahigh risk for psychosis (UHR) compared to siblings and controls in virtual social environments, and explore the relationship between clinical characteristics and interpersonal distance. Nineteen UHR patients, 52 patients with psychotic disorders, 40 siblings of patients with a psychotic disorder and 47 controls were exposed to virtual cafés. In five virtual café visits, participants were exposed to different levels of social stress, in terms of crowdedness, ethnicity and hostility. Measures on interpersonal distance, distress and state paranoia were obtained. Baseline measures included trait paranoia, social anxiety, depressive, positive and negative symptoms. Interpersonal distance increased when social stressors were present in the environment. No difference in interpersonal distance regulation was found between the groups. Social anxiety and distress were positively associated with interpersonal distance in the total sample. This VR paradigm indicates that interpersonal distance regulation in response to environmental social stressors is unaltered in people with psychosis or UHR. Environmental stress, social anxiety and distress trigger both people with and without psychosis to maintain larger interpersonal distances in social situations. Copyright © 2017 Elsevier B.V. All rights reserved.

The assessment of fetal brain function in fetuses with ventrikulomegaly: the role of the KANET test.

PubMed

Talic, Amira; Kurjak, Asim; Stanojevic, Milan; Honemeyer, Ulrich; Badreldeen, Ahmed; DiRenzo, Gian Carlo

2012-08-01

To assess differences in fetal behavior in both normal fetuses and fetuses with cerebral ventriculomegaly (VM). In a period of eighteen months, in a longitudinal prospective cohort study, Kurjak Antenatal NeuorogicalTest (KANET) was applied to assess fetal behavior in both normal pregnancies and pregnancies with cerebral VM using four-dimensional ultrasound (4D US). According to the degree of enlargement of the ventricles, VM was divided into three groups: mild, moderate and severe. Moreover fetuses with isolated VM were separated from those with additional abnormalities. According to the KANET, fetuses with scores ≥ 14 were considered normal, those with scores 6-13 borderline and abnormal if the score was ≤ 5. Differences between two groups were examined by Fisher's exact test. Differences within the subgroups were examined by Kruskal-Wallis test and contingency table test. KANET scores in normal pregnancies and pregnancies with VM showed statistically significant differences. Most of the abnormal KANET scores as well as most of the borderline-scores were found among the fetuses with severe VM associated with additional abnormalities. There were no statistically significant differences between the control group and the groups with isolated and mild and /or moderate VM. Evaluation of the fetal behavior in fetuses with cerebral VM using KANET test has the potential to detect fetuses with abnormal behavior, and to add the dimension of CNS function to the morphological criteria of VM. Long-term postnatal neurodevelopmental follow-up should confirm the data from prenatal investigation of fetal behavior.

Impaired visual recognition of biological motion in schizophrenia.

PubMed

Kim, Jejoong; Doop, Mikisha L; Blake, Randolph; Park, Sohee

2005-09-15

Motion perception deficits have been suggested to be an important feature of schizophrenia but the behavioral consequences of such deficits are unknown. Biological motion refers to the movements generated by living beings. The human visual system rapidly and effortlessly detects and extracts socially relevant information from biological motion. A deficit in biological motion perception may have significant consequences for detecting and interpreting social information. Schizophrenia patients and matched healthy controls were tested on two visual tasks: recognition of human activity portrayed in point-light animations (biological motion task) and a perceptual control task involving detection of a grouped figure against the background noise (global-form task). Both tasks required detection of a global form against background noise but only the biological motion task required the extraction of motion-related information. Schizophrenia patients performed as well as the controls in the global-form task, but were significantly impaired on the biological motion task. In addition, deficits in biological motion perception correlated with impaired social functioning as measured by the Zigler social competence scale [Zigler, E., Levine, J. (1981). Premorbid competence in schizophrenia: what is being measured? Journal of Consulting and Clinical Psychology, 49, 96-105.]. The deficit in biological motion processing, which may be related to the previously documented deficit in global motion processing, could contribute to abnormal social functioning in schizophrenia.

Oxytocin attenuates deficits in social interaction but not recognition memory in a prenatal valproic acid-induced mouse model of autism.

PubMed

Hara, Yuta; Ago, Yukio; Higuchi, Momoko; Hasebe, Shigeru; Nakazawa, Takanobu; Hashimoto, Hitoshi; Matsuda, Toshio; Takuma, Kazuhiro

2017-11-01

Recent studies have reported that oxytocin ameliorates behavioral abnormalities in both animal models and individuals with autism spectrum disorders (ASD). However, the mechanisms underlying the ameliorating effects of oxytocin remain unclear. In this study, we examined the effects of intranasal oxytocin on impairments in social interaction and recognition memory in an ASD mouse model in which animals are prenatally exposed to valproic acid (VPA). We found that a single intranasal administration of oxytocin restored social interaction deficits for up to 2h in mice prenatally exposed to VPA, but there was no effect on recognition memory impairments. Additionally, administration of oxytocin across 2weeks improved prenatal VPA-induced social interaction deficits for at least 24h. In contrast, there were no effects on the time spent sniffing in control mice. Immunohistochemical analysis revealed that intranasal administration of oxytocin increased c-Fos expression in the paraventricular nuclei (PVN), prefrontal cortex, and somatosensory cortex, but not the hippocampal CA1 and CA3 regions of VPA-exposed mice, suggesting the former regions may underlie the effects of oxytocin. These findings suggest that oxytocin attenuates social interaction deficits through the activation of higher cortical areas and the PVN in an ASD mouse model. Copyright © 2017 Elsevier Inc. All rights reserved.

Exogenous cortisol facilitates responses to social threat under high provocation.

PubMed

Bertsch, Katja; Böhnke, Robina; Kruk, Menno R; Richter, Steffen; Naumann, Ewald

2011-04-01

Stress is one of the most important promoters of aggression. Human and animal studies have found associations between basal and acute levels of the stress hormone cortisol and (abnormal) aggression. Irrespective of the direction of these changes--i.e., increased or decreased aggressive behavior--the results of these studies suggest dramatic alterations in the processing of threat-related social information. Therefore, the effects of cortisol and provocation on social information processing were addressed by the present study. After a placebo-controlled pharmacological manipulation of acute cortisol levels, we exposed healthy individuals to high or low levels of provocation in a competitive aggression paradigm. Influences of cortisol and provocation on emotional face processing were then investigated with reaction times and event-related potentials (ERPs) in an emotional Stroop task. In line with previous results, enhanced early and later positive, posterior ERP components indicated a provocation-induced enhanced relevance for all kinds of social information. Cortisol, however, reduced an early frontocentral bias for angry faces and--despite the provocation-enhancing relevance--led to faster reactions for all facial expressions in highly provoked participants. The results thus support the moderating role of social information processing in the 'vicious circle of stress and aggression'. Copyright © 2010 Elsevier Inc. All rights reserved.

In Vivo Test for Chemical Induction of Micronucleated Polychromatic Erythrocytes in Mouse Bone Marrow Cells. Test Article: Dimethylamine-2-2ethyl azide (DMAZ)

DTIC Science & Technology

2008-06-25

Hunched Back Unusual Body Secretions - Nasal Discharge - Lacrimation - Salivation - Bloody Stool - Dianhea Abnormal Behavior - Convulsions...WetGroin - Hunched Back Unusual Body Secretions - Nasal Discharge - Lacrimation - Salivation - Bloody Stool - Diarrhea Abnormal Behavior...Ataxia - Piloerection - WetGrain - Hunched Back Unusual Body Secretions - Nasal Discharge - Lacrimation - Salivation - Bloody Stool

Learning to trust: social feedback normalizes trust behavior in first-episode psychosis and clinical high risk.

PubMed

Lemmers-Jansen, Imke L J; Fett, Anne-Kathrin J; Hanssen, Esther; Veltman, Dick J; Krabbendam, Lydia

2018-06-13

Psychosis is characterized by problems in social functioning that exist well before illness onset, and in individuals at clinical high risk (CHR) for psychosis. Trust is an essential element for social interactions that is impaired in psychosis. In the trust game, chronic patients showed reduced baseline trust, impaired response to positive social feedback, and attenuated brain activation in reward and mentalizing areas. We investigated whether first-episode psychosis patients (FEP) and CHR show similar abnormalities in the neural and behavioral mechanisms underlying trust. Twenty-two FEP, 17 CHR, and 43 healthy controls performed two trust games, with a cooperative and an unfair partner in the fMRI scanner. Region of interest analyses were performed on mentalizing and reward processing areas, during the investment and outcome phases of the games. Compared with healthy controls, FEP and CHR showed reduced baseline trust, but like controls, learned to trust in response to cooperative and unfair feedback. Symptom severity was not associated with baseline trust, however in FEP associated with reduced response to feedback. The only group differences in brain activation were that CHR recruited the temporo-parietal junction (TPJ) more than FEP and controls during investment in the unfair condition. This hyper-activation in CHR was associated with greater symptom severity. Reduced baseline trust may be associated with risk for psychotic illness, or generally with poor mental health. Feedback learning is still intact in CHR and FEP, as opposed to chronic patients. CHR however show distinct neural activation patterns of hyper-activation of the TPJ.

Neuronal Growth and Behavioral Alterations in Mice Deficient for the Psychiatric Disease-Associated Negr1 Gene

PubMed Central

Singh, Katyayani; Loreth, Desirée; Pöttker, Bruno; Hefti, Kyra; Innos, Jürgen; Schwald, Kathrin; Hengstler, Heidi; Menzel, Lutz; Sommer, Clemens J.; Radyushkin, Konstantin; Kretz, Oliver; Philips, Mari-Anne; Haas, Carola A.; Frauenknecht, Katrin; Lilleväli, Kersti; Heimrich, Bernd; Vasar, Eero; Schäfer, Michael K. E.

2018-01-01

Neuronal growth regulator 1 (NEGR1), a member of the immunoglobulin superfamily cell adhesion molecule subgroup IgLON, has been implicated in neuronal growth and connectivity. In addition, genetic variants in or near the NEGR1 locus have been associated with obesity and more recently with learning difficulties, intellectual disability and psychiatric disorders. However, experimental evidence is lacking to support a possible link between NEGR1, neuronal growth and behavioral abnormalities. Initial expression analysis of NEGR1 mRNA in C57Bl/6 wildtype (WT) mice by in situ hybridization demonstrated marked expression in the entorhinal cortex (EC) and dentate granule cells. In co-cultures of cortical neurons and NSC-34 cells overexpressing NEGR1, neurite growth of cortical neurons was enhanced and distal axons occupied an increased area of cells overexpressing NEGR1. Conversely, in organotypic slice co-cultures, Negr1-knockout (KO) hippocampus was less permissive for axons grown from EC of β-actin-enhanced green fluorescent protein (EGFP) mice compared to WT hippocampus. Neuroanatomical analysis revealed abnormalities of EC axons in the hippocampal dentate gyrus (DG) of Negr1-KO mice including increased numbers of axonal projections to the hilus. Neurotransmitter receptor ligand binding densities, a proxy of functional neurotransmitter receptor abundance, did not show differences in the DG of Negr1-KO mice but altered ligand binding densities to NMDA receptor and muscarinic acetylcholine receptors M1 and M2 were found in CA1 and CA3. Activity behavior, anxiety-like behavior and sensorimotor gating were not different between genotypes. However, Negr1-KO mice exhibited impaired social behavior compared to WT littermates. Moreover, Negr1-KO mice showed reversal learning deficits in the Morris water maze and increased susceptibility to pentylenetetrazol (PTZ)-induced seizures. Thus, our results from neuronal growth assays, neuroanatomical analyses and behavioral assessments provide first evidence that deficiency of the psychiatric disease-associated Negr1 gene may affect neuronal growth and behavior. These findings might be relevant to further evaluate the role of NEGR1 in cognitive and psychiatric disorders. PMID:29479305

The detrimental effects of atypical nonverbal behavior on older adults' first impressions of individuals with Parkinson's disease.

PubMed

Hemmesch, Amanda R

2014-09-01

After viewing short video clips of individuals with Parkinson's disease (PD) who varied in the symptoms of facial masking (reduced expressivity) and abnormal bodily movement (ABM: including tremor and related movement disorders), older adult observers provided their first impressions of targets' social positivity. Impressions of targets with higher masking or ABM were more negative than impressions of targets with lower masking or ABM. Furthermore, masking was more detrimental for impressions of women and when observers considered emotional relationship goals, whereas ABM was more detrimental for instrumental relationship goals. This study demonstrated the stigmatizing effects of both reduced and excessive movement. PsycINFO Database Record (c) 2014 APA, all rights reserved.

Behaviour modification in the management of chronic habits of abnormal eye rubbing.

PubMed

McMonnies, Charles W

2009-04-01

To describe how and why many keratoconus patients do not comply with strong advice to control chronic habits of abnormal rubbing. To outline a behaviour modification approach for controlling chronic habits of abnormal rubbing. Common reasons for chronic habits of abnormal rubbing have been reviewed as a basis for specifying a behavioural modification approach to habit reversal. The methods described are organized into the classic behavioural modification structure of: (1) habit awareness, (2) competing responses, (3) development of motivation, and (4) social support. This structure is supported by the application of social influence principles to achieve optimum compliance. The use of take-home written information in the form of an Abnormal Rubbing Guide is the basis for the development of motivation. Family social support is based upon a widening of the responsibility for avoiding eye rubbing to all family members. Some patients will need minimal application of these principles with patient education being sufficient intervention to achieve habit reversal. For patients with strong provocation to rubbing and/or by having a well established rubbing habit, a greater exposure to the habit reversal program described is indicated. Successful habit reversal may slow the rate of ectasia progression. Prophylactic application of the methods described for patients who are at risk for developing keratoconus, or post-laser assisted in situ keratomileusis keratectasia, may show that some forms of keratectasia are preventable.

Reversal of autism-like behaviors and metabolism in adult mice with single-dose antipurinergic therapy

PubMed Central

Naviaux, J C; Schuchbauer, M A; Li, K; Wang, L; Risbrough, V B; Powell, S B; Naviaux, R K

2014-01-01

Autism spectrum disorders (ASDs) now affect 1–2% of the children born in the United States. Hundreds of genetic, metabolic and environmental factors are known to increase the risk of ASD. Similar factors are known to influence the risk of schizophrenia and bipolar disorder; however, a unifying mechanistic explanation has remained elusive. Here we used the maternal immune activation (MIA) mouse model of neurodevelopmental and neuropsychiatric disorders to study the effects of a single dose of the antipurinergic drug suramin on the behavior and metabolism of adult animals. We found that disturbances in social behavior, novelty preference and metabolism are not permanent but are treatable with antipurinergic therapy (APT) in this model of ASD and schizophrenia. A single dose of suramin (20 mg kg−1 intraperitoneally (i.p.)) given to 6-month-old adults restored normal social behavior, novelty preference and metabolism. Comprehensive metabolomic analysis identified purine metabolism as the key regulatory pathway. Correction of purine metabolism normalized 17 of 18 metabolic pathways that were disturbed in the MIA model. Two days after treatment, the suramin concentration in the plasma and brainstem was 7.64 μM pmol μl−1 (±0.50) and 5.15 pmol mg−1 (±0.49), respectively. These data show good uptake of suramin into the central nervous system at the level of the brainstem. Most of the improvements associated with APT were lost after 5 weeks of drug washout, consistent with the 1-week plasma half-life of suramin in mice. Our results show that purine metabolism is a master regulator of behavior and metabolism in the MIA model, and that single-dose APT with suramin acutely reverses these abnormalities, even in adults. PMID:24937094

Neural Connectivity Evidence for a Categorical-Dimensional Hybrid Model of Autism Spectrum Disorder.

PubMed

Elton, Amanda; Di Martino, Adriana; Hazlett, Heather Cody; Gao, Wei

2016-07-15

Autism spectrum disorder (ASD) encompasses a complex manifestation of symptoms that include deficits in social interaction and repetitive or stereotyped interests and behaviors. In keeping with the increasing recognition of the dimensional characteristics of ASD symptoms and the categorical nature of a diagnosis, we sought to delineate the neural mechanisms of ASD symptoms based on the functional connectivity of four known neural networks (i.e., default mode network, dorsal attention network, salience network, and executive control network). We leveraged an open data resource (Autism Brain Imaging Data Exchange) providing resting-state functional magnetic resonance imaging data sets from 90 boys with ASD and 95 typically developing boys. This data set also included the Social Responsiveness Scale as a dimensional measure of ASD traits. Seed-based functional connectivity was paired with linear regression to identify functional connectivity abnormalities associated with categorical effects of ASD diagnosis, dimensional effects of ASD-like behaviors, and their interaction. Our results revealed the existence of dimensional mechanisms of ASD uniquely affecting each network based on the presence of connectivity-behavioral relationships; these were independent of diagnostic category. However, we also found evidence of categorical differences (i.e., diagnostic group differences) in connectivity strength for each network as well as categorical differences in connectivity-behavioral relationships (i.e., diagnosis-by-behavior interactions), supporting the coexistence of categorical mechanisms of ASD. Our findings support a hybrid model for ASD characterization that includes a combination of categorical and dimensional brain mechanisms and provide a novel understanding of the neural underpinnings of ASD. Copyright © 2016 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

Growth restriction, leptin, and the programming of adult behavior in mice.

PubMed

Meyer, Lauritz R; Zhu, Vivian; Miller, Alise; Roghair, Robert D

2014-12-15

Prematurity and neonatal growth restriction (GR) are risk factors for autism and attention deficit hyperactivity disorder (ADHD). Leptin production is suppressed during periods of undernutrition, and we have shown that isolated neonatal leptin deficiency leads to adult hyperactivity while neonatal leptin supplementation normalizes the brain morphology of GR mice. We hypothesized that neonatal leptin would prevent the development of GR-associated behavioral abnormalities. From postnatal day 4-14, C57BL/6 mice were randomized to daily injections of saline or leptin (80ng/g), and GR was identified by a weanling weight below the tenth percentile. The behavioral phenotypes of GR and control mice were assessed beginning at 4 months. Within the tripartite chamber, GR mice had significantly impaired social interaction. Baseline escape times from the Barnes maze were faster for GR mice (65+/-6s vs 87+/-7s for controls, p<0.05), but GR mice exhibited regression in their escape times on days 2 and 3 (56% regressed vs 22% of control saline mice, p<0.05). Compared to controls, GR mice entered the open arms of the elevated plus maze more often and stayed there longer (72+/-10s vs 36+/-5s, p<0.01). Neonatal leptin supplementation normalized the behavior of GR mice across all behavioral assays. In conclusion, GR alters the social interactions, learning and activity of mice, and supplementation with the neurotrophic hormone leptin mitigates these effects. We speculate neonatal leptin deficiency may contribute to the adverse neurodevelopmental outcomes associated with postnatal growth restriction, and postnatal leptin therapy may be protective. Copyright © 2014 Elsevier B.V. All rights reserved.

Perceived functional impact of abnormal facial appearance.

PubMed

Rankin, Marlene; Borah, Gregory L

2003-06-01

Functional facial deformities are usually described as those that impair respiration, eating, hearing, or speech. Yet facial scars and cutaneous deformities have a significant negative effect on social functionality that has been poorly documented in the scientific literature. Insurance companies are declining payments for reconstructive surgical procedures for facial deformities caused by congenital disabilities and after cancer or trauma operations that do not affect mechanical facial activity. The purpose of this study was to establish a large, sample-based evaluation of the perceived social functioning, interpersonal characteristics, and employability indices for a range of facial appearances (normal and abnormal). Adult volunteer evaluators (n = 210) provided their subjective perceptions based on facial physical appearance, and an analysis of the consequences of facial deformity on parameters of preferential treatment was performed. A two-group comparative research design rated the differences among 10 examples of digitally altered facial photographs of actual patients among various age and ethnic groups with "normal" and "abnormal" congenital deformities or posttrauma scars. Photographs of adult patients with observable congenital and posttraumatic deformities (abnormal) were digitally retouched to eliminate the stigmatic defects (normal). The normal and abnormal photographs of identical patients were evaluated by the large sample study group on nine parameters of social functioning, such as honesty, employability, attractiveness, and effectiveness, using a visual analogue rating scale. Patients with abnormal facial characteristics were rated as significantly less honest (p = 0.007), less employable (p = 0.001), less trustworthy (p = 0.01), less optimistic (p = 0.001), less effective (p = 0.02), less capable (p = 0.002), less intelligent (p = 0.03), less popular (p = 0.001), and less attractive (p = 0.001) than were the same patients with normal facial appearances. Facial deformity caused by trauma, congenital disabilities, and postsurgical sequelae present with significant adverse functional consequences. Facial deformities have a significant negative effect on perceptions of social functionality, including employability, honesty, and trustworthiness. Adverse perceptions of patients with facial deformities occur regardless of sex, educational level, and age of evaluator.

Effectiveness of the gluten-free, casein-free diet for children diagnosed with autism spectrum disorder: based on parental report.

PubMed

Pennesi, Christine M; Klein, Laura Cousino

2012-03-01

Studies on the gluten-free and/or casein-free (GFCF) dietary intervention for children with autism spectrum disorders (ASDs) suggest that some children may positively respond to implementation of the dietary intervention. Other research suggests that children diagnosed with ASD can be classified into subpopulations based on various factors, including gastrointestinal (GI) abnormalities and immune function. This study analyzes parental report data collected using a 90-item online questionnaire from 387 parents or primary caregivers of children diagnosed with ASD on the efficacy of the GFCF diet. Parents reported on their child's GI symptoms, food allergy diagnoses, and suspected food sensitivities, as well as the degree and length of their diet implementation. Overall, diet efficacy among children whose parents reported the presence of GI symptoms, food allergy diagnoses, and suspected food sensitivities included greater improvement in ASD behaviors, physiological symptoms, and social behaviors compared with children whose parents reported none of these symptoms, diagnoses, or sensitivities (P < 0.05). Parental report of strict diet implementation, indicated by complete gluten/casein elimination and infrequent diet errors during and outside of parental care, also corresponded to improvement in ASD behaviors, physiological symptoms, and social behaviors (P < 0.05). These findings suggest that various intricacies related to diet implementation and GI and immune factors may play a role in differentiating diet responders from diet non-responders and substantiate the importance of further investigations into the various, nuanced factors that influence efficacy of the intervention among children with ASDs.

Hyporesponsive reward anticipation in the basal ganglia following severe institutional deprivation early in life.

PubMed

Mehta, Mitul A; Gore-Langton, Emma; Golembo, Nicole; Colvert, Emma; Williams, Steven C R; Sonuga-Barke, Edmund

2010-10-01

Severe deprivation in the first few years of life is associated with multiple difficulties in cognition and behavior. However, the brain basis for these difficulties is poorly understood. Structural and functional neuroimaging studies have implicated limbic system structures as dysfunctional, and one functional imaging study in a heterogeneous group of maltreated individuals has confirmed the presence of abnormalities in the basal ganglia. Based on these studies and known dopaminergic abnormalities from studies in experimental animals using social isolation, we used a task of monetary reward anticipation to examine the functional integrity of brain regions previously shown to be implicated in reward processing. Our sample included a group of adolescents (n = 12) who had experienced global deprivation early in their lives in Romania prior to adoption into UK families. In contrast to a nonadopted comparison group (n = 11), the adoptees did not recruit the striatum during reward anticipation despite comparable performance accuracy and latency. These results show, for the first time, an association between early institutional deprivation and brain reward systems in humans and highlight potential neural vulnerabilities resulting from such exposures.

Benefits of pair housing are consistent across a diverse population of rhesus macaques

PubMed Central

Baker, Kate C.; Bloomsmith, Mollie A.; Oettinger, Brooke; Neu, Kimberly; Griffis, Caroline; Schoof, Valérie; Maloney, Margaret

2015-01-01

Introducing singly housed rhesus macaques (Macaca mulatta) into isosexual pairs is widely considered to improve welfare. The population of laboratory rhesus macaques is heterogeneous on a variety of factors and there is little literature available to directly evaluate the influence of many of these factors on the benefits of pair housing. Subjects were 46 adult female and 18 adult male rhesus macaques housed at the Tulane National Primate Research Center and the Yerkes National Primate Research Center. Behavioral data totalling 859 h and serum cortisol levels derived from 312 serum samples were analyzed for main effects of housing condition, comparing single housing to pair housing. In addition, a series of analyses were performed to test for interactions between housing condition and seven independent variables: sex, age, prior duration of single housing, presence or absence of a history of self-injurious behavior, and dominance rank, levels of affiliation and agonism in the paired setting. After the collection of 4–8 h of baseline data and three serum cortisol samples, pairs of individuals were introduced to one another and data collection was repeated, no earlier than 4 weeks after introduction. In pair housing both female and male subjects showed decrease in abnormal behavior (females: 54% reduction; P = 0.001; males: 18% reduction; P = 0.0007) and anxiety-related behavior (females: 35% reduction; P = 0.0001; males: 41% reduction; P = 0.0001), and increases in locomotion (females: 41% increase; P = 0.0001; males: 76% increase: P = 0.002). In pair housing, there were no significant sex differences in social behavior. Descriptively, paired females spent 12% of samples engaged in affiliative behavior and 0.5% engaged in agonistic behavior (back-transformed arcsin square root means). The corresponding values for males were 12% and 0.3%. No interaction effects were detected with any of the independent variables tested in this study. Cortisol values varied with sex but did not differ between housing conditions; no differences were detected when any of the above variables were included in the statistical model. Results support the general consensus among those studying the welfare of captive primates that social housing is a potent means for promoting behavioral indicators of the psychological well-being of laboratory primates. These results are of considerable practical significance and include information that refutes common perceptions about the unsuitability of males as socialization candidates, perceived negative PMID:25635151

Structural and functional alterations in the prefrontal cortex after post-weaning social isolation: relationship with species-typical and deviant aggression.

PubMed

Biro, Laszlo; Toth, Mate; Sipos, Eszter; Bruzsik, Biborka; Tulogdi, Aron; Bendahan, Samuel; Sandi, Carmen; Haller, Jozsef

2017-05-01

Although the inhibitory control of aggression by the prefrontal cortex (PFC) is the cornerstone of current theories of aggression control, a number of human and laboratory studies showed that the execution of aggression increases PFC activity; moreover, enhanced activation was observed in aggression-related psychopathologies and laboratory models of abnormal aggression. Here, we investigated these apparently contradictory findings in the post-weaning social isolation paradigm (PWSI), an established laboratory model of abnormal aggression. When studied in the resident-intruder test as adults, rats submitted to PWSI showed increased attack counts, increased share of bites directed towards vulnerable body parts of opponents (head, throat, and belly) and reduced social signaling of attacks. These deviations from species-typical behavioral characteristics were associated with a specific reduction in the thickness of the right medial PFC (mPFC), a bilateral decrease in dendritic and glial density, and reduced vascularization on the right-hand side of the mPFC. Thus, the early stressor interfered with mPFC development. Despite these structural deficits, aggressive encounters enhanced the activation of the mPFC in PWSI rats as compared to controls. A voxel-like functional analysis revealed that overactivation was restricted to a circumscribed sub-region, which contributed to the activation of hypothalamic centers involved in the initiation of biting attacks as shown by structural equation modeling. These findings demonstrate that structural alterations and functional hyperactivity can coexist in the mPFC of rats exposed to early stressors, and suggest that the role of the mPFC in aggression control is more complex than suggested by the inhibitory control theory.

Low-Frequency rTMS Ameliorates Autistic-Like Behaviors in Rats Induced by Neonatal Isolation Through Regulating the Synaptic GABA Transmission

PubMed Central

Tan, Tao; Wang, Wei; Xu, Haitao; Huang, Zhilin; Wang, Yu Tian; Dong, Zhifang

2018-01-01

Patients with autism spectrum disorder (ASD) display abnormalities in neuronal development, synaptic function and neural circuits. The imbalance of excitatory and inhibitory (E/I) synaptic transmission has been proposed to cause the main behavioral characteristics of ASD. Repetitive transcranial magnetic stimulation (rTMS) can directly or indirectly induce excitability and synaptic plasticity changes in the brain noninvasively. However, whether rTMS can ameliorate autistic-like behaviors in animal model via regulating the balance of E/I synaptic transmission is unknown. By using our recent reported animal model with autistic-like behaviors induced by neonatal isolation (postnatal days 1–9), we found that low-frequency rTMS (LF-rTMS, 1 Hz) treatment for 2 weeks effectively alleviated the acquired autistic-like symptoms, as reflected by an increase in social interaction and decrease in self-grooming, anxiety- and depressive-like behaviors in young adult rats compared to those in untreated animals. Furthermore, the amelioration in autistic-like behavior was accompanied by a restoration of the balance between E/I activity, especially at the level of synaptic transmission and receptors in synaptosomes. These findings indicated that LF-rTMS may alleviate the symptoms of ASD-like behaviors caused by neonatal isolation through regulating the synaptic GABA transmission, suggesting that LF-rTMS may be a potential therapeutic technique to treat ASD. PMID:29541022

Motor and cognitive stereotypies in the BTBR T+tf/J mouse model of autism.

PubMed

Pearson, B L; Pobbe, R L H; Defensor, E B; Oasay, L; Bolivar, V J; Blanchard, D C; Blanchard, R J

2011-03-01

The BTBR T+tf/J inbred mouse strain displays a variety of persistent phenotypic alterations similar to those exhibited in autism spectrum disorders (ASDs). The unique genetic background of the BTBR strain is thought to underlie its lack of reciprocal social interactions, elevated repetitive self-directed grooming, and restricted exploratory behaviors. In order to clarify the existence, range, and mechanisms of abnormal repetitive behaviors within BTBR mice, we performed detailed analyses of the microstructure of self-grooming patterns and noted increased overall grooming, higher percentages of interruptions in grooming bouts and a concomitant decrease in the proportion of incorrect sequence transitions compared to C57BL/6J inbred mice. Analyses of active phase home-cage behavior also revealed an increase in stereotypic bar-biting behavior in the BTBR strain relative to B6 mice. Finally, in a novel object investigation task, the BTBR mice exhibited greater baseline preference for specific unfamiliar objects as well as more patterned sequences of sequential investigations of those items. These results suggest that the repetitive, stereotyped behavior patterns of BTBR mice are relatively pervasive and reflect both motor and cognitive mechanisms. Furthermore, other pre-clinical mouse models of ASDs may benefit from these more detailed analyses of stereotypic behavior. © 2010 The Authors. Genes, Brain and Behavior © 2010 Blackwell Publishing Ltd and International Behavioural and Neural Genetics Society.

Arid1b haploinsufficiency disrupts cortical interneuron development and mouse behavior.

PubMed

Jung, Eui-Man; Moffat, Jeffrey Jay; Liu, Jinxu; Dravid, Shashank Manohar; Gurumurthy, Channabasavaiah Basavaraju; Kim, Woo-Yang

2017-12-01

Haploinsufficiency of the AT-rich interactive domain 1B (ARID1B) gene causes autism spectrum disorder and intellectual disability; however, the neurobiological basis for this is unknown. Here we generated Arid1b-knockout mice and examined heterozygotes to model human patients. Arid1b-heterozygous mice showed a decreased number of cortical GABAergic interneurons and reduced proliferation of interneuron progenitors in the ganglionic eminence. Arid1b haploinsufficiency also led to an imbalance between excitatory and inhibitory synapses in the cerebral cortex. Furthermore, we found that Arid1b haploinsufficiency suppressed histone H3 lysine 9 acetylation (H3K9ac) overall and particularly reduced H3K9ac of the Pvalb promoter, resulting in decreased transcription. Arid1b-heterozygous mice exhibited abnormal cognitive and social behaviors, which were rescued by treatment with a positive allosteric GABA A receptor modulator. Our results demonstrate a critical role for Arid1b in interneuron development and behavior and provide insight into the pathogenesis of autism spectrum disorder and intellectual disability.

The genesis of cognitive and behavioral deficits in premature graduates of intensive care.

PubMed

Perlman, J M

2003-04-01

Increased survival of very low birth weight infants including those born at the cutting edge of viability is associated with substantial cognitive and behavioral deficits at follow-up that has extended into school age and adolescence. These problems have occurred as common in the presence or absence of neurosonographic abnormalities. Factors/events that may predispose to these problems include medical complications of prematurity i.e. chronic lung disease, recurrent episodes of apnea and bradycardia, transient hypothyroxinemia of prematurity, hyperbilirubinemia, nutritional deficiencies, medications used to treat such conditions i.e. glucorticoids, theophylline etc. and stress associated with prolonged hospitalization. With regard to the latter, attachment to multiple devices that limits infant provider interactions, high noise levels and constant light levels are considered to be of particular importance. Experimental evidence is presented that demonstrates the value of positive interactions between the subject and provider with regard to neurobehavioral outcome. Some suggested interventions include reducing noise levels and displacing it with music, modulating light exposure and enhancing infant parent interactions such as kangaroo care. Finally the important postnatal role of social influences on cognitive and behavioral outcomes is discussed.

Modeling Autistic Features in Animals

PubMed Central

Patterson, Paul H.

2011-01-01

A variety of features of autism can be simulated in rodents, including the core behavioral hallmarks of stereotyped and repetitive behaviors, and deficits in social interaction and communication. Other behaviors frequently found in autism spectrum disorders (ASD) such as neophobia, enhanced anxiety, abnormal pain sensitivity and eye blink conditioning, disturbed sleep patterns, seizures, and deficits in sensorimotor gating are also present in some of the animal models. Neuropathology and some characteristic neurochemical changes that are frequently seen in autism, as well as alterations in the immune status in the brain and periphery are also found in some of the models. Several known environmental risk factors for autism have been successfully established in rodents, including maternal infection and maternal valproate administration. Also under investigation are a number of mouse models based on genetic variants associated with autism or on syndromic disorders with autistic features. This review briefly summarizes recent developments in this field, highlighting models with face and/or construct validity, and noting the potential for investigation of pathogenesis and early progress towards clinical testing of potential therapeutics. Wherever possible, reference is made to reviews rather than primary articles. PMID:21289542

Proportionate Responses to Life Events Influence Clinicians' Judgments of Psychological Abnormality

ERIC Educational Resources Information Center

Kim, Nancy S.; Paulus, Daniel J.; Gonzalez, Jeffrey S.; Khalife, Danielle

2012-01-01

Psychological abnormality is a fundamental concept in the "Diagnostic and Statistical Manual of Mental Disorders" ("DSM-IV-TR"; American Psychiatric Association, 2000) and in all clinical evaluations. How do practicing clinical psychologists use the context of life events to judge the abnormality of a person's current behaviors? The appropriate…

The Double Meaning of Online Social Space: Three-Way Interactions Among Social Anxiety, Online Social Behavior, and Offline Social Behavior.

PubMed

Koo, Hoon Jung; Woo, Sungbum; Yang, Eunjoo; Kwon, Jung Hye

2015-09-01

The present study aimed to investigate how online and offline social behavior interact with each other ultimately to affect the well-being of socially anxious adolescents. Based on previous studies, it was assumed that there might be three-way interactive effects among online social behavior, offline social behavior, and social anxiety regarding the relationship with well-being. To measure social anxiety, online and offline social behavior, and mental well-being, self-report questionnaires such as the Korean-Social Avoidance and Distress Scale, Korean version of the Relational Maintenance Behavior Questionnaire, and Korean version of Mental Health Continuum Short Form were administered to 656 Korean adolescents. Hierarchical regression analysis revealed that the three-way interaction of online social behavior, offline social behavior, and social anxiety was indeed significant. First, online social behavior was associated with lower well-being of adolescents with higher social anxiety under conditions of low engagement in offline social behavior. In contrast, a higher level of online social behavior predicted greater well-being for individuals with high social anxiety under conditions of more engagement in offline social behavior. Second, online social behavior was not significantly related to well-being in youths with low social anxiety under conditions of both high and low engagement in offline social behavior. Implications and limitations of this study were discussed.

Drosophila mutants of the autism candidate gene neurobeachin (rugose) exhibit neuro-developmental disorders, aberrant synaptic properties, altered locomotion, and impaired adult social behavior and activity patterns.

PubMed

Wise, Alexandria; Tenezaca, Luis; Fernandez, Robert W; Schatoff, Emma; Flores, Julian; Ueda, Atsushi; Zhong, Xiaotian; Wu, Chun-Fang; Simon, Anne F; Venkatesh, Tadmiri

2015-01-01

Autism spectrum disorder (ASD) is a neurodevelopmental disorder in humans characterized by complex behavioral deficits, including intellectual disability, impaired social interactions, and hyperactivity. ASD exhibits a strong genetic component with underlying multigene interactions. Candidate gene studies have shown that the neurobeachin (NBEA) gene is disrupted in human patients with idiopathic autism ( Castermans et al., 2003 ). The NBEA gene spans the common fragile site FRA 13A and encodes a signal scaffold protein ( Savelyeva et al., 2006 ). In mice, NBEA has been shown to be involved in the trafficking and function of a specific subset of synaptic vesicles. ( Medrihan et al., 2009 ; Savelyeva et al., 2006 ). Rugose (rg) is the Drosophila homolog of the mammalian and human NBEA. Our previous genetic and molecular analyses have shown that rg encodes an A kinase anchor protein (DAKAP 550), which interacts with components of the epidermal growth factor receptor or EGFR and Notch-mediated signaling pathways, facilitating cross talk between these and other pathways ( Shamloula et al., 2002 ). We now present functional data from studies on the larval neuromuscular junction that reveal abnormal synaptic architecture and physiology. In addition, adult rg loss-of-function mutants exhibit defective social interactions, impaired habituation, aberrant locomotion, and hyperactivity. These results demonstrate that Drosophila NBEA (rg) mutants exhibit phenotypic characteristics reminiscent of human ASD and thus could serve as a genetic model for studying ASDs.

The Effects of Twitter Sentiment on Stock Price Returns

PubMed Central

Ranco, Gabriele; Aleksovski, Darko; Caldarelli, Guido; Grčar, Miha; Mozetič, Igor

2015-01-01

Social media are increasingly reflecting and influencing behavior of other complex systems. In this paper we investigate the relations between a well-known micro-blogging platform Twitter and financial markets. In particular, we consider, in a period of 15 months, the Twitter volume and sentiment about the 30 stock companies that form the Dow Jones Industrial Average (DJIA) index. We find a relatively low Pearson correlation and Granger causality between the corresponding time series over the entire time period. However, we find a significant dependence between the Twitter sentiment and abnormal returns during the peaks of Twitter volume. This is valid not only for the expected Twitter volume peaks (e.g., quarterly announcements), but also for peaks corresponding to less obvious events. We formalize the procedure by adapting the well-known “event study” from economics and finance to the analysis of Twitter data. The procedure allows to automatically identify events as Twitter volume peaks, to compute the prevailing sentiment (positive or negative) expressed in tweets at these peaks, and finally to apply the “event study” methodology to relate them to stock returns. We show that sentiment polarity of Twitter peaks implies the direction of cumulative abnormal returns. The amount of cumulative abnormal returns is relatively low (about 1–2%), but the dependence is statistically significant for several days after the events. PMID:26390434

How Abnormal Is the Behaviour of Captive, Zoo-Living Chimpanzees?

PubMed Central

Birkett, Lucy P.; Newton-Fisher, Nicholas E.

2011-01-01

Background Many captive chimpanzees (Pan troglodytes) show a variety of serious behavioural abnormalities, some of which have been considered as possible signs of compromised mental health. The provision of environmental enrichments aimed at reducing the performance of abnormal behaviours is increasing the norm, with the housing of individuals in (semi-)natural social groups thought to be the most successful of these. Only a few quantitative studies of abnormal behaviour have been conducted, however, particularly for the captive population held in zoological collections. Consequently, a clear picture of the level of abnormal behaviour in zoo-living chimpanzees is lacking. Methods We present preliminary findings from a detailed observational study of the behaviour of 40 socially-housed zoo-living chimpanzees from six collections in the United States of America and the United Kingdom. We determined the prevalence, diversity, frequency, and duration of abnormal behaviour from 1200 hours of continuous behavioural data collected by focal animal sampling. Results, Conclusion and Significance Our overall finding was that abnormal behaviour was present in all sampled individuals across six independent groups of zoo-living chimpanzees, despite the differences between these groups in size, composition, housing, etc. We found substantial variation between individuals in the frequency and duration of abnormal behaviour, but all individuals engaged in at least some abnormal behaviour and variation across individuals could not be explained by sex, age, rearing history or background (defined as prior housing conditions). Our data support a conclusion that, while most behaviour of zoo-living chimpanzees is ‘normal’ in that it is typical of their wild counterparts, abnormal behaviour is endemic in this population despite enrichment efforts. We suggest there is an urgent need to understand how the chimpanzee mind copes with captivity, an issue with both scientific and welfare implications. PMID:21698219

How abnormal is the behaviour of captive, zoo-living chimpanzees?

PubMed

Birkett, Lucy P; Newton-Fisher, Nicholas E

2011-01-01

Many captive chimpanzees (Pan troglodytes) show a variety of serious behavioural abnormalities, some of which have been considered as possible signs of compromised mental health. The provision of environmental enrichments aimed at reducing the performance of abnormal behaviours is increasing the norm, with the housing of individuals in (semi-)natural social groups thought to be the most successful of these. Only a few quantitative studies of abnormal behaviour have been conducted, however, particularly for the captive population held in zoological collections. Consequently, a clear picture of the level of abnormal behaviour in zoo-living chimpanzees is lacking. We present preliminary findings from a detailed observational study of the behaviour of 40 socially-housed zoo-living chimpanzees from six collections in the United States of America and the United Kingdom. We determined the prevalence, diversity, frequency, and duration of abnormal behaviour from 1200 hours of continuous behavioural data collected by focal animal sampling. Our overall finding was that abnormal behaviour was present in all sampled individuals across six independent groups of zoo-living chimpanzees, despite the differences between these groups in size, composition, housing, etc. We found substantial variation between individuals in the frequency and duration of abnormal behaviour, but all individuals engaged in at least some abnormal behaviour and variation across individuals could not be explained by sex, age, rearing history or background (defined as prior housing conditions). Our data support a conclusion that, while most behaviour of zoo-living chimpanzees is 'normal' in that it is typical of their wild counterparts, abnormal behaviour is endemic in this population despite enrichment efforts. We suggest there is an urgent need to understand how the chimpanzee mind copes with captivity, an issue with both scientific and welfare implications.

T cell deficiency leads to cognitive dysfunction: Implications for therapeutic vaccination for schizophrenia and other psychiatric conditions

PubMed Central

Kipnis, Jonathan; Cohen, Hagit; Cardon, Michal; Ziv, Yaniv; Schwartz, Michal

2004-01-01

The effects of the adaptive immune system on the cognitive performance and abnormal behaviors seen in mental disorders such as schizophrenia have never been documented. Here, we show that mice deprived of mature T cells manifested cognitive deficits and behavioral abnormalities, which were remediable by T cell restoration. T cell-based vaccination, using glatiramer acetate (copolymer-1, a weak agonist of numerous self-reactive T cells), can overcome the behavioral and cognitive abnormalities that accompany neurotransmitter imbalance induced by (+)dizocilpine maleate (MK-801) or amphetamine. The results, by suggesting that peripheral T cell deficit can lead to cognitive and behavioral impairment, highlight the importance of properly functioning adaptive immunity in the maintenance of mental activity and in coping with conditions leading to cognitive deficits. These findings point to critical factors likely to contribute to age- and AIDS-related dementias and might herald the development of a therapeutic vaccination for fighting off cognitive dysfunction and psychiatric conditions. PMID:15141078

An Abnormal Increase of Fatigue Life with Dwell Time during Creep-Fatigue Deformation for Directionally Solidified Ni-Based Superalloy DZ445

NASA Astrophysics Data System (ADS)

Ding, Biao; Ren, Weili; Deng, Kang; Li, Haitao; Liang, Yongchun

2018-03-01

The paper investigated the creep-fatigue behavior for directionally solidified nickel-based superalloy DZ445 at 900 °C. It is found that the fatigue life shows an abnormal increase when the dwell time exceeds a critical value during creep-fatigue deformation. The area of hysteresis loop and fractograph explain the phenomenon quite well. The shortest life corresponds to the maximal area of hysteresis loop, i. e. the maximum energy to be consumed during the creep-fatigue cycle. The fractographic observation of failed samples further supports the abnormal behavior of fatigue life.

Geomagnetic Navigation of Autonomous Underwater Vehicle Based on Multi-objective Evolutionary Algorithm.

PubMed

Li, Hong; Liu, Mingyong; Zhang, Feihu

2017-01-01

This paper presents a multi-objective evolutionary algorithm of bio-inspired geomagnetic navigation for Autonomous Underwater Vehicle (AUV). Inspired by the biological navigation behavior, the solution was proposed without using a priori information, simply by magnetotaxis searching. However, the existence of the geomagnetic anomalies has significant influence on the geomagnetic navigation system, which often disrupts the distribution of the geomagnetic field. An extreme value region may easily appear in abnormal regions, which makes AUV lost in the navigation phase. This paper proposes an improved bio-inspired algorithm with behavior constraints, for sake of making AUV escape from the abnormal region. First, the navigation problem is considered as the optimization problem. Second, the environmental monitoring operator is introduced, to determine whether the algorithm falls into the geomagnetic anomaly region. Then, the behavior constraint operator is employed to get out of the abnormal region. Finally, the termination condition is triggered. Compared to the state-of- the-art, the proposed approach effectively overcomes the disturbance of the geomagnetic abnormal. The simulation result demonstrates the reliability and feasibility of the proposed approach in complex environments.

Geomagnetic Navigation of Autonomous Underwater Vehicle Based on Multi-objective Evolutionary Algorithm

PubMed Central

Li, Hong; Liu, Mingyong; Zhang, Feihu

2017-01-01

This paper presents a multi-objective evolutionary algorithm of bio-inspired geomagnetic navigation for Autonomous Underwater Vehicle (AUV). Inspired by the biological navigation behavior, the solution was proposed without using a priori information, simply by magnetotaxis searching. However, the existence of the geomagnetic anomalies has significant influence on the geomagnetic navigation system, which often disrupts the distribution of the geomagnetic field. An extreme value region may easily appear in abnormal regions, which makes AUV lost in the navigation phase. This paper proposes an improved bio-inspired algorithm with behavior constraints, for sake of making AUV escape from the abnormal region. First, the navigation problem is considered as the optimization problem. Second, the environmental monitoring operator is introduced, to determine whether the algorithm falls into the geomagnetic anomaly region. Then, the behavior constraint operator is employed to get out of the abnormal region. Finally, the termination condition is triggered. Compared to the state-of- the-art, the proposed approach effectively overcomes the disturbance of the geomagnetic abnormal. The simulation result demonstrates the reliability and feasibility of the proposed approach in complex environments. PMID:28747884

Neurobehavioral Mutants Identified in an ENU Mutagenesis Project

DOE Office of Scientific and Technical Information (OSTI.GOV)

Cook, Melloni N.; Dunning, Jonathan P; Wiley, Ronald G

2007-01-01

We report on a behavioral screening test battery that successfully identified several neurobehavioral mutants among a large-scale ENU-mutagenized mouse population. Large numbers of ENU mutagenized mice were screened for abnormalities in central nervous system function based on abnormal performance in a series of behavior tasks. We developed and employed a high-throughput screen of behavioral tasks to detect behavioral outliers. Twelve mutant pedigrees, representing a broad range of behavioral phenotypes, have been identified. Specifically, we have identified two open field mutants (one displaying hyper-locomotion, the other hypo-locomotion), four tail suspension mutants (all displaying increased immobility), one nociception mutant (displaying abnormal responsivenessmore » to thermal pain), two prepulse inhibition mutants (displaying poor inhibition of the startle response), one anxiety-related mutant (displaying decreased anxiety in the light/dark test), and one learning and memory mutant (displaying reduced response to the conditioned stimulus) These findings highlight the utility of a set of behavioral tasks used in a high throughput screen to identify neurobehavioral mutants. Further analysis (i.e., behavioral and genetic mapping studies) of mutants is in progress with the ultimate goal of identification of novel genes and mouse models relevant to human disorders as well as the identification of novel therapeutic targets.« less

Are There Gender-Specific Pathways from Early Adolescence Psychological Distress Symptoms toward the Development of Substance Use and Abnormal Eating Behavior?

ERIC Educational Resources Information Center

Beato-Fernandez, Luis; Rodriguez-Cano, Teresa; Pelayo-Delgado, Esther; Calaf, Myralys

2007-01-01

The aim of the present longitudinal community study was to test whether psychological distress at 13 years of age predicted reported substance use problems in boys and abnormal eating behavior in girls 2 years later. The sample consisted of 500 male and 576 female students. The use of substances was evaluated using a semi-structured interview,…

[Autism spectrum disorder. Contemporary experimental researches review].

PubMed

Luschekina, E A; Strelets, V B

2014-01-01

Autism, like schizophrenia, are heterogeneous diseases, which are directed by both genetic factors and external influences in the early stages of development. Knowledge about the similarities and differences of these disorders can help early diagnosis and treatment. Patients with autism have specific cognitive difficulties in social relations. They are characterized by impairment of social interaction, communication and behavioral flexibility. The severity of the delay the development of autistic children, clinical and psychological indicators is correlated with an increase in the high frequency of spontaneous EEG activity. Cognitive task in autistic children, unlike normal persons, does not lead to a significant restructuring of high-frequency EEG activity, which may be a violation of the reaction mechanism to external stimuli and behavioral disorders. Abnormality in high-frequency components of EEG reactivity on cognitive task, the perception of human faces and visual illusions as well as the inadequate system of mirror neurons, can be considered common mechanisms underlying disorders of autism and schizophrenia. These general mechanisms may be considered as related to violation of the inhibition-exitation balance, controlled via GABA-transmission and NMDA-receptors. A multidimensional study of patterns of disontogenesis in autism, in addition to detailing the clinical picture of disease and rehabilitation activities, allows us to clear the fundamental understanding of the brain.

Dissociation of frontotemporal dementia-related deficits and neuroinflammation in progranulin haploinsufficient mice.

PubMed

Filiano, Anthony J; Martens, Lauren Herl; Young, Allen H; Warmus, Brian A; Zhou, Ping; Diaz-Ramirez, Grisell; Jiao, Jian; Zhang, Zhijun; Huang, Eric J; Gao, Fen-Biao; Farese, Robert V; Roberson, Erik D

2013-03-20

Frontotemporal dementia (FTD) is a neurodegenerative disease with hallmark deficits in social and emotional function. Heterozygous loss-of-function mutations in GRN, the progranulin gene, are a common genetic cause of the disorder, but the mechanisms by which progranulin haploinsufficiency causes neuronal dysfunction in FTD are unclear. Homozygous progranulin knock-out (Grn(-/-)) mice have been studied as a model of this disorder and show behavioral deficits and a neuroinflammatory phenotype with robust microglial activation. However, homozygous GRN mutations causing complete progranulin deficiency were recently shown to cause a different neurological disorder, neuronal ceroid lipofuscinosis, suggesting that the total absence of progranulin may have effects distinct from those of haploinsufficiency. Here, we studied progranulin heterozygous (Grn(+/-)) mice, which model progranulin haploinsufficiency. We found that Grn(+/-) mice developed age-dependent social and emotional deficits potentially relevant to FTD. However, unlike Grn(-/-) mice, behavioral deficits in Grn(+/-) mice occurred in the absence of gliosis or increased expression of tumor necrosis factor-α. Instead, we found neuronal abnormalities in the amygdala, an area of selective vulnerability in FTD, in Grn(+/-) mice. Our findings indicate that FTD-related deficits resulting from progranulin haploinsufficiency can develop in the absence of detectable gliosis and neuroinflammation, thereby dissociating microglial activation from functional deficits and suggesting an important effect of progranulin deficiency on neurons.

The Psycho-Neurology of Cross-Species Affective/Social Neuroscience: Understanding Animal Affective States as a Guide to Development of Novel Psychiatric Treatments.

PubMed

Panksepp, Jaak

During the past half century of research with preclinical animal models, affective neuroscience has helped identify and illuminate the functional neuroanatomies and neurochemistries of seven primary process, i.e., genetically provided emotional systems of mammalian brains. All are subcortically localized, allowing animal models to guide the needed behavioral and neuroscientific analyses at levels of detail that cannot be achieved through human research, including modern brain imaging. They consist of the following neuronal processes: SEEKING/Enthusiasm, RAGE/Anger, FEAR/Anxiety, sexual LUST/Passion, maternal CARE/Nurturance, separation-distress PANIC/Grief and PLAY/Social Joy. Several of these systems figure heavily in social bonding. I will focus here especially on the genesis of depression. Its genesis is significantly influenced by (i) sustained overactivity of the separation-distress PANIC system reflecting severed social bonds and the excessive "psychological pain" of loneliness that can, if sustained, lead to a downward cascade known as psychological despair, and (ii) the despair phase that follows the acute PANIC response, which is characterized by abnormally low activity of the SEEKING, the so-called brain reward networks, leading to amotivational states that characterize depression. Depressive affect is promoted by such brain affective mechanisms of social attachments and social loss as well as diminished arousability of the SEEKING system, leading to chronic dysphoria. To understand why depression feels so bad, we must understand the neural mechanisms that mediate such social feelings.

Streptozotocin induced oxidative stress, innate immune system responses and behavioral abnormalities in male mice.

PubMed

Amiri, Shayan; Haj-Mirzaian, Arya; Momeny, Majid; Amini-Khoei, Hossein; Rahimi-Balaei, Maryam; Poursaman, Simin; Rastegar, Mojgan; Nikoui, Vahid; Mokhtari, Tahmineh; Ghazi-Khansari, Mahmoud; Hosseini, Mir-Jamal

2017-01-06

Recent evidence indicates the involvement of inflammatory factors and mitochondrial dysfunction in the etiology of psychiatric disorders such as anxiety and depression. To investigate the possible role of mitochondrial-induced sterile inflammation in the co-occurrence of anxiety and depression, in this study, we treated adult male mice with the intracerebroventricular (i.c.v.) infusion of a single low dose of streptozotocin (STZ, 0.2mg/mouse). Using valid and qualified behavioral tests for the assessment of depressive and anxiety-like behaviors, we showed that STZ-treated mice exhibited behaviors relevant to anxiety and depression 24h following STZ treatment. We observed that the co-occurrence of anxiety and depressive-like behaviors in animals were associated with abnormal mitochondrial function, nitric oxide overproduction and, the increased activity of cytosolic phospholipase A 2 (cPLA 2 ) in the hippocampus. Further, STZ-treated mice had a significant upregulation of genes associated with the innate immune system such as toll-like receptors 2 and 4. Pathological evaluations showed no sign of neurodegeneration in the hippocampus of STZ-treated mice. Results of this study revealed that behavioral abnormalities provoked by STZ, as a cytotoxic agent that targets mitochondria and energy metabolism, are associated with abnormal mitochondrial activity and, consequently the initiation of innate-inflammatory responses in the hippocampus. Our findings highlight the role of mitochondria and innate immunity in the formation of sterile inflammation and behaviors relevant to anxiety and depression. Also, we have shown that STZ injection (i.c.v.) might be an animal model for depression and anxiety disorders based on sterile inflammation. Copyright © 2016 IBRO. Published by Elsevier Ltd. All rights reserved.

Parenting behavior at 2 years predicts school-age performance at 7 years in very preterm children.

PubMed

Treyvaud, Karli; Doyle, Lex W; Lee, Katherine J; Ure, Alexandra; Inder, Terrie E; Hunt, Rod W; Anderson, Peter J

2016-07-01

Parenting influences child development, but it is unclear whether early parenting behavior can influence school-age outcomes in very preterm (VPT) children, and/or if certain groups of VPT children may be more affected by early parenting behavior. These research questions were examined. Participants were 147 children born <30 weeks' gestation or birth weight <1250 g and their primary caregiver. At term corrected age (CA), magnetic resonance imaging (MRI) was used to determine presence and severity of brain abnormality and medical data collected. High medical risk was defined as the presence of at least one of sepsis, necrotizing enterocolitis, bronchopulmonary dysplasia, moderate to severe white matter abnormality on MRI, or postnatal corticosteroids. At 2 years CA, parent-child interaction was assessed, and at 7 years CA, general intelligence (IQ), language, executive function, academic skills, and social-emotional functioning were assessed. Higher levels of parent-child synchrony, and parent facilitation, sensitivity and positive affect at 2 years were associated with better child outcomes at 7 years, while higher levels of intrusiveness and negative affect were associated with poorer outcomes. Many of these relationships remained after controlling for early child cognitive development. Interactions between child medical risk (higher/lower) and parenting were limited to child reading, math, and executive functioning outcomes, with stronger relationships for lower medical risk children. The contribution of early parenting to VPT children's school-age performance is significant, with stronger effects for lower medical risk children in some outcomes. These findings support the premise that parenting strategies should be included in the NICU and early interventions programs for VPT infants. © 2015 Association for Child and Adolescent Mental Health.

A Case of ADHD and a Major Y Chromosome Abnormality

ERIC Educational Resources Information Center

Mulligan, Aisling; Gill, Michael; Fitzgerald, Michael

2008-01-01

Background: ADHD is a common, heritable disorder of childhood. Sex chromosome abnormalities are relatively rare conditions that are sometimes associated with behavioral disorders. Method: The authors present a male child with ADHD and a major de-novo Y chromosome abnormality consisting of deletion of the long arm and duplication of the short arm.…

Effects of physician counseling on the smoking behavior of asbestos-exposed workers

DOE Office of Scientific and Technical Information (OSTI.GOV)

Li, V.C.; Kim, Y.J.; Ewart, C.K.

Physician antismoking advice has been shown to increase smoking cessation, particularly among patients who have medical problems or perceive themselves to be at risk. The present study tested three hypotheses: (a) providing 3 to 5 min of behavioral counseling regarding a cessation strategy would be more effective than simply warning the smoker to quit smoking; (b) smokers with abnormal pulmonary function would be more likely to comply with medical advice than would smokers with normal pulmonary function; and (c) that smokers with abnormal pulmonary function who receive behavioral counseling would be the group most likely to achieve prolonged abstinence. Asbestos-exposedmore » smoking men undergoing screening in a mandated program for naval shipyard workers were categorized as having normal or abnormal pulmonary status on the basis of chest X ray and pulmonary function tests (PFT). They were then randomly assigned within PFT categories to receive either a simple warning or 3 to 5 min of behavioral cessation counseling from the physician who gave them the results of their pulmonary tests. Subjects smoking status was evaluated at 3- and 11-month intervals following the physician intervention. Smokers who received behavioral counseling were more likely to quit and remain abstinent over the 11-month period (8.4% abstinent) than were smokers given a minimal warning (3.6% abstinent). Prolonged abstinence rates among abnormal PFT subjects (3.7%) did not differ from those of normals (5.9%). The group with normal PFT who received behavioral counseling achieved the highest level of abstinence (9.5%).« less