Population attributable risk of factors associated with the repetition of self-harm behaviour in young people presenting to clinical services: a systematic review and meta-analysis.

PubMed

Witt, Katrina; Milner, Allison; Spittal, Matthew J; Hetrick, Sarah; Robinson, Jo; Pirkis, Jane; Carter, Gregory

2018-02-03

The repetition of hospital-treated self-harm by young people is common. However, little work has summarised the modifiable factors associated with this. A thorough understanding of those factors most strongly associated with repetition could guide the development of relevant clinical interventions. We systematically reviewed four databases (EMBASE, Medline, PubMed and PsycINFO) until 15 April 2016 to identify all observational studies of factors for the repetition of self-harm or suicide reattempts (together referred to as 'self-harm behaviour') in young people. We quantified the magnitude of association with odds ratios (OR) and 95% confidence intervals (CIs) and calculated the population attributable risk (PAR) and population preventable fraction (PPF) for modifiable factors to provide an indication of the potential impact in reducing subsequent self-harm behaviour in this population. Seventeen studies were included comprising 10,726 participants. Borderline personality disorder (OR 3.47, 95% CI 1.84-6.53; PAR 42.4%), any personality disorder (OR 2.54, 95% CI 1.71-3.78; PAR 16.3%), and any mood disorder (OR 2.16, 95% CI 1.09-4.29; PAR 42.2%) are important modifiable risk factors. Severity of hopelessness (OR 2.95, 95% CI 1.74-5.01), suicidal ideation (OR 2.01, 95% CI 1.43-2.81), and previous sexual abuse (OR 1.52, 95% CI 1.02-2.28; PAR 12.8%) are also associated with repetition of self-harm. We recommend that clinical services should focus on identifying key modifiable risk factors at the individual patient level, whilst the reduction of exposure to child and adolescent sexual abuse would also be a useful goal for public health interventions.

Update on Huntington's disease: advances in care and emerging therapeutic options.

PubMed

Zielonka, Daniel; Mielcarek, Michal; Landwehrmeyer, G Bernhard

2015-03-01

Huntington's disease (HD) is the most common hereditary neurodegenerative disorder. Despite the fact that both the gene and the mutation causing this monogenetic disorder were identified more than 20 years ago, disease-modifying therapies for HD have not yet been established. While intense preclinical research and large cohort studies in HD have laid foundations for tangible improvements in understanding HD and caring for HD patients, identifying targets for therapeutic interventions and developing novel therapeutic modalities (new chemical entities and advanced therapies using DNA and RNA molecules as therapeutic agents) continues to be an ongoing process. The authors review recent achievements in HD research and focus on approaches towards disease-modifying therapies, ranging from huntingtin-lowering strategies to improving huntingtin clearance that may be promoted by posttranslational HTT modifications. The nature and number of upcoming clinical studies/trials in HD is a reason for hope for HD patients and their families. Copyright © 2014 Elsevier Ltd. All rights reserved.

DNA sequence-level analyses reveal potential phenotypic modifiers in a large family with psychiatric disorders.

PubMed

Ryan, Niamh M; Lihm, Jayon; Kramer, Melissa; McCarthy, Shane; Morris, Stewart W; Arnau-Soler, Aleix; Davies, Gail; Duff, Barbara; Ghiban, Elena; Hayward, Caroline; Deary, Ian J; Blackwood, Douglas H R; Lawrie, Stephen M; McIntosh, Andrew M; Evans, Kathryn L; Porteous, David J; McCombie, W Richard; Thomson, Pippa A

2018-06-07

Psychiatric disorders are a group of genetically related diseases with highly polygenic architectures. Genome-wide association analyses have made substantial progress towards understanding the genetic architecture of these disorders. More recently, exome- and whole-genome sequencing of cases and families have identified rare, high penetrant variants that provide direct functional insight. There remains, however, a gap in the heritability explained by these complementary approaches. To understand how multiple genetic variants combine to modify both severity and penetrance of a highly penetrant variant, we sequenced 48 whole genomes from a family with a high loading of psychiatric disorder linked to a balanced chromosomal translocation. The (1;11)(q42;q14.3) translocation directly disrupts three genes: DISC1, DISC2, DISC1FP and has been linked to multiple brain imaging and neurocognitive outcomes in the family. Using DNA sequence-level linkage analysis, functional annotation and population-based association, we identified common and rare variants in GRM5 (minor allele frequency (MAF) > 0.05), PDE4D (MAF > 0.2) and CNTN5 (MAF < 0.01) that may help explain the individual differences in phenotypic expression in the family. We suggest that whole-genome sequencing in large families will improve the understanding of the combined effects of the rare and common sequence variation underlying psychiatric phenotypes.

Genetic modifiers of Huntington's disease.

PubMed

Gusella, James F; MacDonald, Marcy E; Lee, Jong-Min

2014-09-15

Huntington's disease (HD) is a devastating neurodegenerative disorder that directly affects more than 1 in 10,000 persons in Western societies but, as a family disorder with a long, costly, debilitating course, it has an indirect impact on a far greater proportion of the population. Although some palliative treatments are used, no effective treatment exists for preventing clinical onset of the disorder or for delaying its inevitable progression toward premature death, approximately 15 years after diagnosis. Huntington's disease involves a movement disorder characterized by chorea, as well as a variety of psychiatric disturbances and intellectual decline, with a gradual loss of independence. A dire need exists for effective HD therapies to alleviate the suffering and costs to the individual, family, and health care system. In past decades, genetics, the study of DNA sequence variation and its consequences, provided the tools to map the HD gene to chromosome 4 and ultimately to identify its mutation as an expanded CAG trinucleotide repeat in the coding sequence of a large protein, dubbed huntingtin. Now, advances in genetic technology offer an unbiased route to the identification of genetic factors that are disease-modifying agents in human patients. Such genetic modifiers are expected to highlight processes capable of altering the course of HD and therefore to provide new, human-validated targets for traditional drug development, with the goal of developing rational treatments to delay or prevent onset of HD clinical signs. © 2014 International Parkinson and Movement Disorder Society.

Results of the psychiatric, select-out evaluation of US astronaut applications

NASA Technical Reports Server (NTRS)

Faulk, D. M.; Santy, P. A.; Holland, A. W.; Marsh, R.

1992-01-01

The psychiatric exclusion criteria for astronauts are based on NASA Medical Psychiatric Standards for space flight. Until recently, there were no standardized methods to evaluate disqualifying psychopathology in astronaut applicants. Method: One hundred and six astronaut applicants who had passed the intitial screening were evaluated for Axis 1 and Axis 2 DSM-3-R diagnoses using the NASA structured psychiatric interview. The interview consisted of three parts: (1) an unstructured portion for obtaining biographical and historical information, (2) the schedule for effective disorders-lifetime version (SASDL), specially modified to include all disqualifying Axis 1 mental disorders; and, (3) the personality assessment schedule (PAS) also modified to evaluate for Axis 2 disorders. Results: Nine of 106 candidates (8.5 percent) met diagnostic criteria for six Axis 1 disorders (including V code) or Axis 2 disorders. Two of these disorders were disqualifying for the applicants. 'Near' diagnoses (where applicants met at least 50 percent of the listed criteria) were assessed to demonstrate that clinicians using the interview were able to overcome applicants' reluctance to report symptomatomatology. Conclusion: The use of the NASA structured interview was effective in identifying past and present psychopathology in a group of highly motivated astronaut applicants. This was the first time a structured psychiatric interview had been used in such a setting for this purpose.

Identifying novel genetic determinants of hemostatic balance.

PubMed

Ginsburg, D

2005-08-01

Incomplete penetrance and variable expressivity confound the diagnosis and therapy of most inherited thrombotic and hemorrhagic disorders. For many of these diseases, some or most of this variability is determined by genetic modifiers distinct from the primary disease gene itself. Clues toward identifying such modifier genes may come from studying rare Mendelian disorders of hemostasis. Examples include identification of the cause of combined factor V and VIII deficiency as mutations in the ER Golgi intermediate compartment proteins LMAN1 and MCFD2. These proteins form a cargo receptor that facilitates the transport of factors V and VIII, and presumably other proteins, from the ER to the Golgi. A similar positional cloning approach identified ADAMTS-13 as the gene responsible for familial TTP. Along with the work of many other groups, these findings identified VWF proteolysis by ADAMTS-13 as a key regulatory pathway for hemostasis. Recent advances in mouse genetics also provide powerful tools for the identification of novel genes contributing to hemostatic balance. Genetic studies of inbred mouse lines with unusually high and unusually low plasma VWF levels identified polymorphic variation in the expression of a glycosyltransferase gene, Galgt2, as an important determinant of plasma VWF levels in the mouse. Ongoing studies in mice genetically engineered to carry the factor V Leiden mutation may similarly identify novel genes contributing to thrombosis risk in humans.

Genetic Modifiers and Oligogenic Inheritance

PubMed Central

Kousi, Maria; Katsanis, Nicholas

2015-01-01

Despite remarkable progress in the identification of mutations that drive genetic disorders, progress in understanding the effect of genetic background on the penetrance and expressivity of causal alleles has been modest, in part because of the methodological challenges in identifying genetic modifiers. Nonetheless, the progressive discovery of modifier alleles has improved both our interpretative ability and our analytical tools to dissect such phenomena. In this review, we analyze the genetic properties and behaviors of modifiers as derived from studies in patient populations and model organisms and we highlight conceptual and technological tools used to overcome some of the challenges inherent in modifier mapping and cloning. Finally, we discuss how the identification of these modifiers has facilitated the elucidation of biological pathways and holds the potential to improve the clinical predictive value of primary causal mutations and to develop novel drug targets. PMID:26033081

The Efficacy of Optometric Vision Therapy.

ERIC Educational Resources Information Center

Journal of the American Optometric Association, 1988

1988-01-01

This review aims to document the efficacy and validity of vision therapy for modifying and improving vision functioning. The paper describes the essential components of the visual system and disorders which can be physiologically and clinically identified. Vision therapy is defined as a clinical approach for correcting and ameliorating the effects…

Effects of Bias Modification Training in Binge Eating Disorder.

PubMed

Schmitz, Florian; Svaldi, Jennifer

2017-09-01

Food-related attentional biases have been identified as maintaining factors in binge eating disorder (BED) as they can trigger a binge episode. Bias modification training may reduce symptoms, as it has been shown to be successful in other appetitive disorders. The aim of this study was to assess and modify food-related biases in BED. It was tested whether biases could be increased and decreased by means of a modified dot-probe paradigm, how long such bias modification persisted, and whether this affected subjective food craving. Participants were randomly assigned to a bias enhancement (attend to food stimulus) group or to a bias reduction (avoid food stimulus) group. Food-related attentional bias was found to be successfully reduced in the bias-reduction group, and effects persisted briefly. Additionally, subjective craving for food was influenced by the intervention, and possible mechanisms are discussed. Given these promising initial results, future research should investigate boundary conditions of the experimental intervention to understand how it could complement treatment of BED. Copyright © 2017. Published by Elsevier Ltd.

Genetic Modifiers of Sickle Cell Disease

PubMed Central

Steinberg, Martin H.; Sebastiani, Paola

2015-01-01

Sickle cell anemia is associated with unusual clinical heterogeneity for a Mendelian disorder. Fetal hemoglobin concentration and coincident ∝ thalassemia, both which directly affect the sickle erythrocyte, are the major modulators of the phenotype of disease. Understanding the genetics underlying the heritable subphenotypes of sickle cell anemia would be prognostically useful, could inform personalized therapeutics, and might help the discovery of new “druggable” pathophysiologic targets. Genotype-phenotype association studies have been used to identify novel genetic modifiers. In the future, whole genome sequencing with its promise of discovering hitherto unsuspected variants could add to our understanding of the genetic modifiers of this disease. PMID:22641398

Targeted delivery of non-viral vectors to cartilage in vivo using a chondrocyte-homing peptide identified by phage display.

PubMed

Pi, Yanbin; Zhang, Xin; Shi, Junjun; Zhu, Jinxian; Chen, Wenqing; Zhang, Chenguang; Gao, Weiwei; Zhou, Chunyan; Ao, Yingfang

2011-09-01

Gene therapy is a promising method for osteoarthritis and cartilage injury. However, specifically delivering target genes into chondrocytes is a great challenge because of their non-vascularity and the dense extracellular matrix of cartilage. In our study, we identified a chondrocyte-affinity peptide (CAP, DWRVIIPPRPSA) by phage display technology. Subsequent analysis suggests that the peptide can efficiently interact specifically with chondrocytes without any species specificity. Polyethylenimine (PEI) was covalently modified with CAP to construct a non-viral vector for cartilage-targeted therapy. To investigate the cartilage-targeting property of the CAP-modified vector, FITC-labeled CAP conjugated PEI/DNA particles were injected into rabbit knee joints, and visualized under confocal microscope. Higher concentrations of CAP-modified vector were detected in the cartilage and specifically taken up by chondrocytes compared with a randomly scrambled peptide (SP)-modified vector. To evaluate cartilage-targeting transfection efficiency, the GFP and luciferase genes were delivered into knee joints using CAP- and SP-modified PEI. Cartilage transfections mediated by CAP-modified PEI were much more efficient and specific than those by SP-modified PEI. This result suggests that CAP-modified PEI could be used as a specific cartilage-targeting vector for cartilage disorders. Copyright © 2011 Elsevier Ltd. All rights reserved.

A genome-wide RNAi screen identifies potential drug targets in a C. elegans model of α1-antitrypsin deficiency.

PubMed

O'Reilly, Linda P; Long, Olivia S; Cobanoglu, Murat C; Benson, Joshua A; Luke, Cliff J; Miedel, Mark T; Hale, Pamela; Perlmutter, David H; Bahar, Ivet; Silverman, Gary A; Pak, Stephen C

2014-10-01

α1-Antitrypsin deficiency (ATD) is a common genetic disorder that can lead to end-stage liver and lung disease. Although liver transplantation remains the only therapy currently available, manipulation of the proteostasis network (PN) by small molecule therapeutics offers great promise. To accelerate the drug-discovery process for this disease, we first developed a semi-automated high-throughput/content-genome-wide RNAi screen to identify PN modifiers affecting the accumulation of the α1-antitrypsin Z mutant (ATZ) in a Caenorhabditis elegans model of ATD. We identified 104 PN modifiers, and these genes were used in a computational strategy to identify human ortholog-ligand pairs. Based on rigorous selection criteria, we identified four FDA-approved drugs directed against four different PN targets that decreased the accumulation of ATZ in C. elegans. We also tested one of the compounds in a mammalian cell line with similar results. This methodology also proved useful in confirming drug targets in vivo, and predicting the success of combination therapy. We propose that small animal models of genetic disorders combined with genome-wide RNAi screening and computational methods can be used to rapidly, economically and strategically prime the preclinical discovery pipeline for rare and neglected diseases with limited therapeutic options. © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Interventions for comorbid problem gambling and psychiatric disorders: Advancing a developing field of research.

PubMed

Dowling, N A; Merkouris, S S; Lorains, F K

2016-07-01

Despite significant psychiatric comorbidity in problem gambling, there is little evidence on which to base treatment recommendations for subpopulations of problem gamblers with comorbid psychiatric disorders. This mini-review draws on two separate systematic searches to identify possible interventions for comorbid problem gambling and psychiatric disorders, highlight the gaps in the currently available evidence base, and stimulate further research in this area. In this mini-review, only 21 studies that have conducted post-hoc analyses to explore the influence of psychiatric disorders or problem gambling subtypes on gambling outcomes from different types of treatment were identified. The findings of these studies suggest that most gambling treatments are not contraindicated by psychiatric disorders. Moreover, only 6 randomized studies comparing the efficacy of interventions targeted towards specific comorbidity subgroups with a control/comparison group were identified. The results of these studies provide preliminary evidence for modified dialectical behavior therapy for comorbid substance use, the addition of naltrexone to cognitive-behavioral therapy (CBT) for comorbid alcohol use problems, and the addition of N-acetylcysteine to tobacco support programs and imaginal desensitisation/motivational interviewing for comorbid nicotine dependence. They also suggest that lithium for comorbid bipolar disorder, escitalopram for comorbid anxiety disorders, and the addition of CBT to standard drug treatment for comorbid schizophrenia may be effective. Future research evaluating interventions sequenced according to disorder severity or the functional relationship between the gambling behavior and comorbid symptomatology, identifying psychiatric disorders as moderators of the efficacy of problem gambling interventions, and evaluating interventions matched to client comorbidity could advance this immature field of study. Copyright © 2016 Elsevier Ltd. All rights reserved.

Facial discrimination in body dysmorphic, obsessive-compulsive and social anxiety disorders.

PubMed

Hübner, Claudia; Wiesendahl, Wiebke; Kleinstäuber, Maria; Stangier, Ulrich; Kathmann, Norbert; Buhlmann, Ulrike

2016-02-28

Body dysmorphic disorder (BDD) is characterized by preoccupation with perceived flaws in one's own appearance. Several risk factors such as aesthetic perceptual sensitivity have been proposed to explain BDD's unique symptomatology. Although research on facial discrimination is limited so far, the few existing studies have produced mixed results. Thus, the purpose of this study was to further examine facial discrimination in BDD. We administered a facial discrimination paradigm, which allows to assess the ability to identify slight to strong facial changes (e.g., hair loss, acne) when presented with an original (unmodified) facial image, relative to a changed (modified) facial image. The experiment was administered in individuals with BDD, social anxiety disorder, obsessive-compulsive disorder, and mentally healthy controls (32 per group, respectively). Overall, groups did not differ with respect to their ability to correctly identify facial aberrations when presented with other people's faces. Our findings do not support the hypothesis of enhanced general aesthetic perceptual sensitivity in individuals with (vs. without) BDD. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Genetic association studies in β-hemoglobinopathies.

PubMed

Thein, Swee Lay

2013-01-01

Characterization of the molecular basis of the β-thalassemias and sickle cell disease (SCD) clearly showed that individuals with the same β-globin genotypes can have extremely diverse clinical severity. Two key modifiers, an innate ability to produce fetal hemoglobin and coinheritance of α-thalassemia, both derived from family and population studies, affect the pathophysiology of both disorders at the primary level. In the past 2 decades, scientific research had applied genetic approaches to identify additional genetic modifiers. The review summarizes recent genetic studies and key genetic modifiers identified and traces the story of fetal hemoglobin genetics, which has led to an emerging network of globin gene regulation. The discoveries have provided insights on new targets for therapeutic intervention and raise possibilities of developing fetal hemoglobin predictive diagnostics for predicting disease severity in the newborn and for integration into prenatal diagnosis to better inform genetic counseling.

Current Issues in the Diagnosis of Attention Deficit Hyperactivity Disorder, Oppositional Defiant Disorder, and Conduct Disorder

PubMed Central

Frick, Paul J.; Nigg, Joel T.

2015-01-01

This review evaluates the diagnostic criteria for three of the most common disorders for which children and adolescents are referred for mental health treatment: attention deficit hyperactivity disorder (ADHD), oppositional defiant disorder (ODD), and conduct disorder (CD). Although research supports the validity and clinical utility of these disorders, several issues are highlighted that could enhance the current diagnostic criteria. For ADHD, defining the core features of the disorder and its fit with other disorders, enhancing the validity of the criteria through the lifespan, considering alternative ways to form subtypes of the disorder, and modifying the age-of-onset criterion are discussed relative to the current diagnostic criteria. For ODD, eliminating the exclusionary criteria of CD, recognizing important symptom domains within the disorder, and using the cross-situational pervasiveness of the disorder as an index of severity are highlighted as important issues for improving classification. Finally, for CD, enhancing the current subtypes related to age of onset and integrating callous-unemotional traits into the diagnostic criteria are identified as key issues for improving classification. PMID:22035245

Development of Antisocial Personality Disorder in Detained Youth: The Predictive Value of Mental Disorders

PubMed Central

Washburn, Jason J.; Romero, Erin Gregory; Welty, Leah J.; Abram, Karen M.; Teplin, Linda A.; McClelland, Gary M.; Paskar, Leah D.

2009-01-01

Antisocial personality disorder (APD) is a serious public and mental health concern. Understanding how well conduct disorder (CD) and other mental disorders predict the development of APD among youth involved in the juvenile justice system is critical for prevention. This study used a stratified random sample of 1112 detained youth to examine the development of APD at a three-year follow-up interview. Nearly one fifth of male juvenile detainees later developed APD; approximately one quarter of male juvenile detainees with CD at baseline later developed APD. Significantly more males than females developed APD; no differences were found by race/ethnicity. Having five or more symptoms of CD, dysthymia, alcohol use disorder, or generalized anxiety disorder was significantly associated with developing modified APD (M-APD; APD without the CD requirement). Some disorders were strong predictors of APD; however, none were adequate screeners for identifying which detainees would later develop M-APD. The findings of this study have implications for interventions and further research in developmental psychopathology. PMID:17469880

The natural history of substance use disorders.

PubMed

Sarvet, Aaron L; Hasin, Deborah

2016-07-01

Illicit drugs, alcohol, and tobacco use disorders contribute substantially to the global burden of disease. Knowledge about the major elements of the natural history of substance use disorders (incidence, remission, persistence, and relapse) is crucial to a broader understanding of the course and outcomes of substance use disorders. Prospective cohort studies in nonclinical samples indicate that externalizing psychopathology in earlier life, including early disordered substance use, delinquency, and personality disorders, are related to substance use disorders later in life and chronic course. Externalizing psychopathology may be initiated by early adverse experiences, for example, childhood maltreatment and stressful life events. After controlling for confounders, 'age at first use' as a causal factor for alcohol use disorder later in life and the 'drug substitution' hypothesis are not supported in general population data. Future research should focus on elaborating the causal framework that leads to the development and persistence of severe substance use disorders, with an emphasis on identifying modifiable factors for intervention by policy makers or health professionals. More research is needed on the natural history of substance use disorders in low-income and middle-income countries.

Neurocognitive Treatments for Eating Disorders and Obesity.

PubMed

Eichen, Dawn M; Matheson, Brittany E; Appleton-Knapp, Sara L; Boutelle, Kerri N

2017-09-01

Recent research has highlighted executive function and neurocognitive deficits among individuals with eating and weight disorders, identifying a potential target for treatment. Treatments targeting executive function for eating and weight disorders are emerging. This review aims to summarize the recent literature evaluating neurocognitive/executive function-oriented treatments for eating and weight disorders and highlights additional work needed in this area. Cognitive remediation therapy (CRT) for anorexia nervosa has been the most extensively studied neurocognitive treatment for eating disorders. Results demonstrate that CRT improves executive function and may aid in the reduction of eating disorder symptomatology. Computer training programs targeting modifying attention and increasing inhibition are targeting reduction of binge eating and weight loss with modest success. Neurocognitive treatments are emerging and show initial promise for eating and weight disorders. Further research is necessary to determine whether these treatments can be used as stand-alone treatments or whether they need to be used as an adjunct to or in conjunction with other evidence-based treatments to improve outcomes.

Minor mental disorders in Taiwanese healthcare workers and the associations with psychosocial work conditions.

PubMed

Cheng, Wan-Ju; Cheng, Yawen

2017-04-01

Healthcare workers face multiple psychosocial work hazards intrinsic to their work, including heavy workloads and shift work. However, how contemporary adverse psychosocial work conditions, such as workplace justice and insecurity, may contribute to increased mental health risks has rarely been studied. This study aimed to search for modifiable psychosocial work factors associated with mental health disorders in Taiwanese healthcare workers. A total of 349 healthcare workers were identified from 19,641 employees who participated in a national survey of Taiwan. Minor mental disorder was assessed using the five-item brief symptom rating scale. We compared psychosocial work characteristics and the prevalence of minor mental disorder in healthcare workers with that in a sociodemographically matched sample, and examined the associations of psychosocial work conditions with mental health status. Healthcare workers were found to have a higher prevalence of minor mental disorder than general workers, and they were more likely to have longer working hours, heavier psychological job demands, higher job control, more workplace violence, and a higher prevalence of shift work. Among healthcare workers, experiences of workplace violence, lower workplace justice, heavier psychological job demands, and job insecurity were associated with a higher risk for minor mental disorder, even after controlling for working hours and shift work. Despite the fact that healthcare workers work longer hours and shift work, there were several modifiable psychosocial work conditions that should be targeted to improve their mental health. Copyright © 2016. Published by Elsevier B.V.

Developmental pathways to autism: A review of prospective studies of infants at risk☆

PubMed Central

Jones, Emily J.H.; Gliga, Teodora; Bedford, Rachael; Charman, Tony; Johnson, Mark H.

2014-01-01

Autism Spectrum Disorders (ASDs) are neurodevelopmental disorders characterized by impairments in social interaction and communication, and the presence of restrictive and repetitive behaviors. Symptoms of ASD likely emerge from a complex interaction between pre-existing neurodevelopmental vulnerabilities and the child's environment, modified by compensatory skills and protective factors. Prospective studies of infants at high familial risk for ASD (who have an older sibling with a diagnosis) are beginning to characterize these developmental pathways to the emergence of clinical symptoms. Here, we review the range of behavioral and neurocognitive markers for later ASD that have been identified in high-risk infants in the first years of life. We discuss theoretical implications of emerging patterns, and identify key directions for future work, including potential resolutions to several methodological challenges for the field. Mapping how ASD unfolds from birth is critical to our understanding of the developmental mechanisms underlying this disorder. A more nuanced understanding of developmental pathways to ASD will help us not only to identify children who need early intervention, but also to improve the range of interventions available to them. PMID:24361967

Applicability of digital PCR to the investigation of pediatric-onset genetic disorders.

PubMed

Butchbach, Matthew E R

2016-12-01

Early-onset rare diseases have a strong impact on child healthcare even though the incidence of each of these diseases is relatively low. In order to better manage the care of these children, it is imperative to quickly diagnose the molecular bases for these disorders as well as to develop technologies with prognostic potential. Digital PCR (dPCR) is well suited for this role by providing an absolute quantification of the target DNA within a sample. This review illustrates how dPCR can be used to identify genes associated with pediatric-onset disorders, to identify copy number status of important disease-causing genes and variants and to quantify modifier genes. It is also a powerful technology to track changes in genomic biomarkers with disease progression. Based on its capability to accurately and reliably detect genomic alterations with high sensitivity and a large dynamic detection range, dPCR has the potential to become the tool of choice for the verification of pediatric disease-associated mutations identified by next generation sequencing, copy number determination and noninvasive prenatal screening.

The language-related transcription factor FOXP2 is post-translationally modified with small ubiquitin-like modifiers.

PubMed

Estruch, Sara B; Graham, Sarah A; Deriziotis, Pelagia; Fisher, Simon E

2016-02-12

Mutations affecting the transcription factor FOXP2 cause a rare form of severe speech and language disorder. Although it is clear that sufficient FOXP2 expression is crucial for normal brain development, little is known about how this transcription factor is regulated. To investigate post-translational mechanisms for FOXP2 regulation, we searched for protein interaction partners of FOXP2, and identified members of the PIAS family as novel FOXP2 interactors. PIAS proteins mediate post-translational modification of a range of target proteins with small ubiquitin-like modifiers (SUMOs). We found that FOXP2 can be modified with all three human SUMO proteins and that PIAS1 promotes this process. An aetiological FOXP2 mutation found in a family with speech and language disorder markedly reduced FOXP2 SUMOylation. We demonstrate that FOXP2 is SUMOylated at a single major site, which is conserved in all FOXP2 vertebrate orthologues and in the paralogues FOXP1 and FOXP4. Abolishing this site did not lead to detectable changes in FOXP2 subcellular localization, stability, dimerization or transcriptional repression in cellular assays, but the conservation of this site suggests a potential role for SUMOylation in regulating FOXP2 activity in vivo.

The language-related transcription factor FOXP2 is post-translationally modified with small ubiquitin-like modifiers

PubMed Central

Estruch, Sara B.; Graham, Sarah A.; Deriziotis, Pelagia; Fisher, Simon E.

2016-01-01

Mutations affecting the transcription factor FOXP2 cause a rare form of severe speech and language disorder. Although it is clear that sufficient FOXP2 expression is crucial for normal brain development, little is known about how this transcription factor is regulated. To investigate post-translational mechanisms for FOXP2 regulation, we searched for protein interaction partners of FOXP2, and identified members of the PIAS family as novel FOXP2 interactors. PIAS proteins mediate post-translational modification of a range of target proteins with small ubiquitin-like modifiers (SUMOs). We found that FOXP2 can be modified with all three human SUMO proteins and that PIAS1 promotes this process. An aetiological FOXP2 mutation found in a family with speech and language disorder markedly reduced FOXP2 SUMOylation. We demonstrate that FOXP2 is SUMOylated at a single major site, which is conserved in all FOXP2 vertebrate orthologues and in the paralogues FOXP1 and FOXP4. Abolishing this site did not lead to detectable changes in FOXP2 subcellular localization, stability, dimerization or transcriptional repression in cellular assays, but the conservation of this site suggests a potential role for SUMOylation in regulating FOXP2 activity in vivo. PMID:26867680

A case report of schizoaffective disorder with ritualistic behaviors and catatonic stupor: successful treatment by risperidone and modified electroconvulsive therapy.

PubMed

Bai, Yuanhan; Yang, Xi; Zeng, Zhiqiang; Yang, Haichen

2018-03-13

Ritualistic behaviors are common in obsessive compulsive disorder (OCD), while catatonic stupor occasionally occurs in psychotic or mood disorders. Schizoaffective disorder is a specific mental disorder involving both psychotic and affective symptoms. The syndrome usually represents a specific diagnosis, as in the case of the 10th edition of the International Classification of Diseases (ICD-10) or the 5th edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5). However, symptom-based diagnosis can result in misdiagnosis and hinder effective treatment. Few cases of ritualistic behaviors and catatonic stupor associated with schizoaffective disorder have been reported. Risperidone and modified electroconvulsive therapy (MECT) were effective in our case. A 35-year-old man with schizoaffective disorder-depression was admitted to the hospital because of ritualistic behaviors, depression, and distrust. At the time of admission, prominent ritualistic behaviors and depression misled us to make the diagnosis of OCD. Sertraline add-on treatment exacerbated the psychotic symptoms, such as pressure of thoughts and delusion of control. In the presence of obvious psychotic symptoms and depression, schizoaffective disorder-depression was diagnosed according to ICD-10. Meanwhile, the patient unfortunately developed catatonic stupor and respiratory infection, which was identified by respiratory symptoms, blood tests, and a chest X-ray. To treat psychotic symptoms, catatonic stupor, and respiratory infection, risperidone, MECT, and ceftriaxone were administered. As a result, we successfully cured the patient with the abovementioned treatment strategies. Eventually, the patient was diagnosed with schizoaffective disorder-depression with ritualistic behaviors and catatonia. Risperidone and MECT therapies were dramatically effective. Making a differential diagnosis of mental disorders is a key step in treating disease. Sertraline was not recommended for treating schizoaffective disorder-depression according to our case because it could exacerbate positive symptoms. Controversy remains about whether antipsychotics should be administered for catatonic stupor. However, more case studies will be needed. Risperidone with MECT was beneficial for the patient in our case.

The Future of Genetics in Psychology and Psychiatry: Microarrays, Genome-Wide Association, and Non-Coding RNA

ERIC Educational Resources Information Center

Plomin, Robert; Davis, Oliver S. P.

2009-01-01

Background: Much of what we thought we knew about genetics needs to be modified in light of recent discoveries. What are the implications of these advances for identifying genes responsible for the high heritability of many behavioural disorders and dimensions in childhood? Methods: Although quantitative genetics such as twin studies will continue…

Risk Factors Associated With Antidepressant Exposure and History of Antidepressant-Induced Mania in Bipolar Disorder.

PubMed

Williams, Aislinn J; Lai, Zongshan; Knight, Seth; Kamali, Masoud; Assari, Shervin; McInnis, Melvin G

2018-05-15

Despite their widespread use in bipolar disorder, there is controversy surrounding the inclusion of antidepressant medications in the disorder's management. We sought to identify which demographic, socioeconomic, and clinical factors are associated with antidepressant exposure in bipolar disorder and which bipolar disorder patients are most likely to report a history of antidepressant-induced mania (AIM) when exposed to antidepressants. Our study included subjects with bipolar I disorder (n = 309), bipolar II disorder (n = 66), and bipolar disorder not otherwise specified (n = 27) and schizoaffective disorder, bipolar type (n = 14), from a longitudinal, community-based study. Subjects were evaluated using the Diagnostic Interview for Genetic Studies, modified for DSM-IV criteria. We applied multivariate logistical regression modeling to investigate which factors contribute to antidepressant exposure in bipolar disorder patients. We also used a logistic regression modeling approach to determine which clinical factors in bipolar disorder patients are associated with a history of AIM. Data were gathered from February 2006 through December 2010. Our results suggest that the risk factors most strongly associated with antidepressant exposure are female sex (OR = 2.73, P = .005), older age (OR = 1.03, P = .04), greater chronicity of illness (OR = 2.29, P = .04), and, to a lesser extent, white race (OR = 0.44, P = .051). Factors associated with reduced antidepressant exposure include history of affective psychosis (OR = 0.36, P = .01) and a greater number of previous manic episodes (OR = 0.98, P = .03). In subjects who reported a history of AIM, regression analysis revealed that the only statistically significant factor associated with AIM history was female sex (OR = 3.74, P = .02). These data suggest that there are certain identifiable factors associated with antidepressant exposure in bipolar disorder patients, and some of these, specifically female sex, are also associated with a history of AIM. These data may be useful in designing prospective trials to identify interventions that can reduce the risk of this adverse outcome. © Copyright 2018 Physicians Postgraduate Press, Inc.

Development of antisocial personality disorder in detained youths: the predictive value of mental disorders.

PubMed

Washburn, Jason J; Romero, Erin Gregory; Welty, Leah J; Abram, Karen M; Teplin, Linda A; McClelland, Gary M; Paskar, Leah D

2007-04-01

Antisocial personality disorder (APD) is a serious public and mental health concern. Understanding how well conduct disorder (CD) and other mental disorders predict the development of APD among youths involved in the juvenile justice system is critical for prevention. The authors used a stratified random sample of 1,112 detained youths to examine the development of APD at a 3-year follow-up interview. Nearly one fifth of male juvenile detainees later developed APD; approximately one quarter of male juvenile detainees with CD at baseline later developed APD. Significantly more males than females developed APD; no differences were found by race/ethnicity. Having 5 or more symptoms of CD, dysthymia, alcohol use disorder, or generalized anxiety disorder was significantly associated with developing modified APD (M-APD; APD without the CD requirement). Some disorders were strong predictors of APD; however, none were adequate screeners for identifying which detainees would later develop M-APD. The findings of this study have implications for interventions and further research in developmental psychopathology. Copyright 2007 APA, all rights reserved.

Child and parent perceived food-induced gastrointestinal symptoms and quality of life in children with functional gastrointestinal disorders.

PubMed

Carlson, Michelle J; Moore, Carolyn E; Tsai, Cynthia M; Shulman, Robert J; Chumpitazi, Bruno P

2014-03-01

It is unknown whether children with functional gastrointestinal (GI) disorders identify specific foods that exacerbate their GI symptoms. The objectives of this study were to determine the perceived role of food on GI symptoms and to determine the impact of food-induced symptoms on quality of life (QOL) in children with functional GI disorders. Between August and November 2010, 25 children ages 11 to 17 years old with functional GI disorders and a parent completed a food symptom association questionnaire and validated questionnaires assessing FGID symptoms and QOL. In addition, children completed a 24-hour food recall, participated in focus groups to identify problematic foods and any coping strategies, and discussed how their QOL was affected. Statistical analyses were conducted using χ2, t test, Mann-Whitney U test, Wilcoxon signed rank, and Spearman's ρ. Children identified a median of 11 (range=2 to 25) foods as exacerbating a GI symptom, with the most commonly identified foods being spicy foods, cow's milk, and pizza. Several coping strategies were identified, including consuming smaller portions, modifying foods, and avoiding a median of 8 (range=1 to 20) foods. Children reported that food-induced symptoms interfered with school performance, sports, and social activities. Although the parent's assessment of their child's QOL negatively correlated with the number of perceived symptom-inducing foods in their child, this relationship was not found in the children. Findings suggest that specific foods are perceived to exacerbate GI symptoms in children with functional GI disorders. In addition, despite use of several coping strategies, food-induced symptoms can adversely impact children's QOL in several important areas. Copyright © 2014 Academy of Nutrition and Dietetics. Published by Elsevier Inc. All rights reserved.

Whole-Exome Sequencing and Whole-Genome Sequencing in Critically Ill Neonates Suspected to Have Single-Gene Disorders

PubMed Central

Smith, Laurie D.; Willig, Laurel K.; Kingsmore, Stephen F.

2016-01-01

As the ability to identify the contribution of genetic background to human disease continues to advance, there is no discipline of medicine in which this may have a larger impact than in the care of the ill neonate. Newborns with congenital malformations, syndromic conditions, and inherited disorders often undergo an extensive, expensive, and long diagnostic process, often without a final diagnosis resulting in significant health care, societal, and personal costs. Although ethical concerns have been raised about the use of whole-genome sequencing in medical practice, its role in the diagnosis of rare disorders in ill neonates in tertiary care neonatal intensive care units has the potential to augment or modify the care of this vulnerable population of patients. PMID:26684335

Predictors of Long-Term School-Based Behavioral Outcomes in the Multimodal Treatment Study of Children with Attention-Deficit/Hyperactivity Disorder

PubMed Central

Reed, Margot O.; Jakubovski, Ewgeni; Johnson, Jessica A.

2017-01-01

Abstract Objective: To explore predictors of 8-year school-based behavioral outcomes in attention-deficit/hyperactivity disorder (ADHD). Methods: We examined potential baseline predictors of school-based behavioral outcomes in children who completed the 8-year follow-up in the multimodal treatment study of children with ADHD. Stepwise logistic regression and receiver operating characteristic (ROC) analysis identified baseline predictors that were associated with a higher risk of truancy, school discipline, and in-school fights. Results: Stepwise regression analysis explained between 8.1% (in-school fights) and 12.0% (school discipline) of the total variance in school-based behavioral outcomes. Logistic regression identified several baseline characteristics that were associated with school-based behavioral difficulties 8 years later, including being male (associated with truancy and school discipline), African American (school discipline, in-school fights), increased conduct disorder (CD) symptoms (truancy), decreased affection from parents (school discipline), ADHD severity (in-school fights), and study site (truancy and school discipline). ROC analyses identified the most discriminative predictors of truancy, school discipline, and in-school fights, which were Aggression and Conduct Problem Scale Total score, family income, and race, respectively. Conclusions: A modest, but nontrivial portion of school-based behavioral outcomes, was predicted by baseline childhood characteristics. Exploratory analyses identified modifiable (lack of paternal involvement, lower parental knowledge of behavioral principles, and parental use of physical punishment), somewhat modifiable (income and having comorbid CD), and nonmodifiable (African American and male) factors that were associated with school-based behavioral difficulties. Future research should confirm that the associations between earlier specific parenting behaviors and poor subsequent school-based behavioral outcomes are, indeed, causally related and independent cooccurring childhood psychopathology. Future research might target increasing paternal involvement and parental knowledge of behavioral principles and reducing use of physical punishment to improve school-based behavioral outcomes in children with ADHD. PMID:28253029

Predictors of Long-Term School-Based Behavioral Outcomes in the Multimodal Treatment Study of Children with Attention-Deficit/Hyperactivity Disorder.

PubMed

Reed, Margot O; Jakubovski, Ewgeni; Johnson, Jessica A; Bloch, Michael H

2017-05-01

To explore predictors of 8-year school-based behavioral outcomes in attention-deficit/hyperactivity disorder (ADHD). We examined potential baseline predictors of school-based behavioral outcomes in children who completed the 8-year follow-up in the multimodal treatment study of children with ADHD. Stepwise logistic regression and receiver operating characteristic (ROC) analysis identified baseline predictors that were associated with a higher risk of truancy, school discipline, and in-school fights. Stepwise regression analysis explained between 8.1% (in-school fights) and 12.0% (school discipline) of the total variance in school-based behavioral outcomes. Logistic regression identified several baseline characteristics that were associated with school-based behavioral difficulties 8 years later, including being male (associated with truancy and school discipline), African American (school discipline, in-school fights), increased conduct disorder (CD) symptoms (truancy), decreased affection from parents (school discipline), ADHD severity (in-school fights), and study site (truancy and school discipline). ROC analyses identified the most discriminative predictors of truancy, school discipline, and in-school fights, which were Aggression and Conduct Problem Scale Total score, family income, and race, respectively. A modest, but nontrivial portion of school-based behavioral outcomes, was predicted by baseline childhood characteristics. Exploratory analyses identified modifiable (lack of paternal involvement, lower parental knowledge of behavioral principles, and parental use of physical punishment), somewhat modifiable (income and having comorbid CD), and nonmodifiable (African American and male) factors that were associated with school-based behavioral difficulties. Future research should confirm that the associations between earlier specific parenting behaviors and poor subsequent school-based behavioral outcomes are, indeed, causally related and independent cooccurring childhood psychopathology. Future research might target increasing paternal involvement and parental knowledge of behavioral principles and reducing use of physical punishment to improve school-based behavioral outcomes in children with ADHD.

Construct validity and parent-child agreement of the six new or modified disorders included in the Spanish version of the Kiddie Schedule for Affective Disorders and Schizophrenia present and Lifetime Version DSM-5 (K-SADS-PL-5).

PubMed

de la Peña, Francisco R; Rosetti, Marcos F; Rodríguez-Delgado, Andrés; Villavicencio, Lino R; Palacio, Juan D; Montiel, Cecilia; Mayer, Pablo A; Félix, Fernando J; Larraguibel, Marcela; Viola, Laura; Ortiz, Silvia; Fernández, Sofía; Jaímes, Aurora; Feria, Miriam; Sosa, Liz; Palacios-Cruz, Lino; Ulloa, Rosa E

2018-06-01

Changes to the Diagnostic and Statistical Manual of Mental Disorders fifth edition (DSM-5) incorporate the inclusion or modification of six disorders: Autism Spectrum Disorder, Social Anxiety Disorder, Intermittent Explosive Disorder, Disruptive Mood Dysregulation Disorder, Avoidant/Restrictive Food Intake Disorder and Binge Eating Disorder. The objectives of this study were to assess the construct validity and parent-child agreement of these six disorders in the Spanish language Schedule for Affective Disorders and Schizophrenia for School Age Children Present and Lifetime Version (K-SADS-PL-5) in a clinical population of children and adolescents from Latin America. The Spanish version of the K-SADS-PL was modified to integrate changes made to the DSM-5. Clinicians received training in the K-SADS-PL-5 and 90% agreement between raters was obtained. A total of 80 patients were recruited in four different countries in Latin America. All items from each of the six disorders were included in a factor analysis. Parent-child agreement was calculated for every item of the six disorders, including the effect of sex and age. The factor analysis revealed 6 factors separately grouping the items defining each of the new or modified disorders, with Eigenvalues greater than 2. Very good parent-child agreements (r>0.8) were found for the large majority of the items (93%), even when considering the sex or age of the patient. This independent grouping of disorders suggests that the manner in which the disorders were included into the K-SADS-PL-5 reflects robustly the DSM-5 constructs and displayed a significant inter-informant reliability. These findings support the use of K-SADS-PL-5 as a clinical and research tool to evaluate these new or modified diagnoses. Copyright © 2018. Published by Elsevier Ltd.

Dysregulated fibroblast growth factor (FGF) signaling in neurological and psychiatric disorders.

PubMed

Turner, Cortney A; Eren-Koçak, Emine; Inui, Edny G; Watson, Stanley J; Akil, Huda

2016-05-01

The role of the fibroblast growth factor (FGF) system in brain-related disorders has received considerable attention in recent years. To understand the role of this system in neurological and psychiatric disorders, it is important to identify the specific members of the FGF family that are implicated, their location and the various mechanisms they can be modulated. Each disorder appears to impact specific molecular players in unique anatomical locations, and all of these could conceivably become targets for treatment. In the last several years, the issue of how to target this system directly has become an area of increasing interest. To date, the most promising therapeutics are small molecule inhibitors and antibodies that modulate FGF receptor (FGFR) function. Beyond attempting to modify the primary players affected by a given brain disorder, it may prove useful to target molecules, such as membrane-bound or extracellular proteins that interact with FGF ligands or FGFRs to modulate signaling. Published by Elsevier Ltd.

Accuracy of "Modified Checklist for Autism in Toddlers" ("M-CHAT") in Detecting Autism and Other Developmental Disorders in Community Clinics

ERIC Educational Resources Information Center

Toh, Teck-Hock; Tan, Vivian Wee-Yen; Lau, Peter Sie-Teck; Kiyu, Andrew

2018-01-01

This study determined the accuracy of "Modified Checklist for Autism in Toddlers" ("M-CHAT") in detecting toddlers with autism spectrum disorder (ASD) and other developmental disorders (DD) in community mother and child health clinics. We analysed 19,297 eligible toddlers (15-36 months) who had "M-CHAT" performed in…

Mental Health Disorder Therapeutic Modalities Modified for the GMS.

PubMed

Sumneangsanor, Tipsuda; Vuthiarpa, Sararud; Somprasert, Chomchueun

2017-12-01

Mental health disorders can affect physical and psychological behaviors. The people of the Greater Mekong Subregion (GMS) have a high risk of mental health disorders, such as depression, stress, and substance abuse be-cause the people in this region are trafficked for forced sex work and various forms of forced labor. In these situations, vic-tims often endure violence and abuse from trafficking recruiters, employers, and other individuals. The purposes of this study were to identify the elements characterizing mental health disorders, especially in terms of depression, stress, and sub-stance abuse, and to identify the treatment modalities for mental health disorders in the GMS. The researcher undertook a comparative analysis of the literature, reviews of epidemiological studies and mental disorder therapies, and overviews of previous research studies, were used to generate a synthesis of the existing knowledge of the mental disorder therapeutic modalities. Regarding the search methods, the data from the electronic databases PubMed, PsycINFO, Dynamed and ScienceDirect were supplemented with a manual reference search covering relevant studies from 2005 to 2016. Thirty-one papers were included in the review of elements characterizing mental health disorders, especially in terms of depression, stress, and substance abuse, and to identify the treatment modalities for mental health disorders in the GMS. Nine papers defined characterizing mental health disorders, in terms of depression, stress, and substance abuse. Twenty-two papers showed the treatment modalities for mental health disorders that the treatment was effective, these in-cluded pharmacological treatments and psychological treatments, such as mindfulness-based cognitive therapy, biofeedback, and music therapy. Useful guidance can be provided for the prevention and treatment of mental health disorders, and for the care of people in the Greater Mekong Subregion. The finding of this review confirms the therapeutic modalities can provide useful guidance for the prevention and treatment of mental health disorders and the care of the people in the Greater Mekong Sub-region. In addition, the effective interventions should be tested regarding their suitability for the socio-cultural context in the Greater Mekong Subregion.

Mental Health Disorder Therapeutic Modalities Modified for the GMS

PubMed Central

Sumneangsanor, Tipsuda; Vuthiarpa, Sararud; Somprasert, Chomchueun

2017-01-01

Background: Mental health disorders can affect physical and psychological behaviors. The people of the Greater Mekong Subregion (GMS) have a high risk of mental health disorders, such as depression, stress, and substance abuse be-cause the people in this region are trafficked for forced sex work and various forms of forced labor. In these situations, vic-tims often endure violence and abuse from trafficking recruiters, employers, and other individuals. The purposes of this study were to identify the elements characterizing mental health disorders, especially in terms of depression, stress, and sub-stance abuse, and to identify the treatment modalities for mental health disorders in the GMS. Methods: The researcher undertook a comparative analysis of the literature, reviews of epidemiological studies and mental disorder therapies, and overviews of previous research studies, were used to generate a synthesis of the existing knowledge of the mental disorder therapeutic modalities. Regarding the search methods, the data from the electronic databases PubMed, PsycINFO, Dynamed and ScienceDirect were supplemented with a manual reference search covering relevant studies from 2005 to 2016. Results: Thirty-one papers were included in the review of elements characterizing mental health disorders, especially in terms of depression, stress, and substance abuse, and to identify the treatment modalities for mental health disorders in the GMS. Nine papers defined characterizing mental health disorders, in terms of depression, stress, and substance abuse. Twenty-two papers showed the treatment modalities for mental health disorders that the treatment was effective, these in-cluded pharmacological treatments and psychological treatments, such as mindfulness-based cognitive therapy, biofeedback, and music therapy. Useful guidance can be provided for the prevention and treatment of mental health disorders, and for the care of people in the Greater Mekong Subregion. Conclusion: The finding of this review confirms the therapeutic modalities can provide useful guidance for the prevention and treatment of mental health disorders and the care of the people in the Greater Mekong Sub-region. In addition, the effective interventions should be tested regarding their suitability for the socio-cultural context in the Greater Mekong Subregion. PMID:29657562

Critical exploration of co-occurring Attention-Deficit/Hyperactivity Disorder, mood disorder and Substance Use Disorder.

PubMed

Regnart, Judith; Truter, Ilse; Meyer, Anneke

2017-06-01

Co-occurring disorders (CODs) describe a Substance Use Disorder (SUD) accompanied by a comorbid psychiatric disorder. Attention-Deficit/Hyperactivity Disorder (ADHD) and mood disorders are common CODs with high prevalence rates in SUD populations. It is proposed that literature on a tri-condition presentation of ADHD, mood disorder and SUD is limited. Areas covered: A literature search was conducted using a keyword search on EBSCOhost. Initially 2 799 records were identified, however, only two articles included all three conditions occurring concurrently in individuals. CODs constitute a major concern due to their overarching burden on society as a whole. Diagnosis and treatment of such patients is challenging. There is evidence that dysfunction of dopamine in the brain reward circuitry impacts the development or symptomology of all three disorders. Disparity exists regarding whether ADHD or mood disorders are greater modifiers for increased SUD severity. However, it has been reported that poor functional capacity may have a greater influence than comorbidities on SUD development. Expert commentary: Challenges exist which confound the clear distinction of CODs, however, with greater emergence of adult ADHD its screening in SUD populations should become standard practice to establish data on multi-condition presentations with the ultimate goal of improving clinical outcomes.

EPIGENETIC MECHANISMS OF ALCOHOLISM AND STRESS-RELATED DISORDERS

PubMed Central

Palmisano, Martina; Pandey, Subhash C.

2017-01-01

Stress-related disorders, such as anxiety, early life stress and posttraumatic stress disorder appear to be important factors in promoting alcoholism, as alcohol consumption can temporarily attenuate the negative affective symptoms of these disorders. Several molecules involved in signaling pathways may contribute to the neuroadaptation induced during alcohol dependence and stress disorders, and among these, brain-derived neurotrophic factor (BDNF), corticotropin releasing factor (CRF), neuropeptide Y (NPY) and opioid peptides (i.e. nociceptin and dynorphin) are involved in the interaction of stress and alcohol. In fact, alterations in the expression and function of these molecules have been associated with the pathophysiology of stress-related disorders and alcoholism. In recent years, various studies have focused on the epigenetic mechanisms that regulate chromatin architecture thereby modifying gene expression. Interestingly, epigenetic modifications in specific brain regions have been shown to be associated with the neurobiology of psychiatric disorders, including alcoholism and stress. In particular, the enzymes responsible for chromatin remodeling (i.e. histone deacetylases and methyltransferases, DNA methyltransferases) have been identified as common molecular mechanisms for the interaction of stress and alcohol and have become promising therapeutic targets to treat or prevent alcoholism and associated emotional disorders. PMID:28477725

Epigenetic mechanisms of alcoholism and stress-related disorders.

PubMed

Palmisano, Martina; Pandey, Subhash C

2017-05-01

Stress-related disorders, such as anxiety, early life stress, and posttraumatic stress disorder appear to be important factors in promoting alcoholism, as alcohol consumption can temporarily attenuate the negative affective symptoms of these disorders. Several molecules involved in signaling pathways may contribute to the neuroadaptation induced during alcohol dependence and stress disorders, and among these, brain-derived neurotrophic factor (BDNF), corticotropin releasing factor (CRF), neuropeptide Y (NPY) and opioid peptides (i.e., nociceptin and dynorphin) are involved in the interaction of stress and alcohol. In fact, alterations in the expression and function of these molecules have been associated with the pathophysiology of stress-related disorders and alcoholism. In recent years, various studies have focused on the epigenetic mechanisms that regulate chromatin architecture, thereby modifying gene expression. Interestingly, epigenetic modifications in specific brain regions have been shown to be associated with the neurobiology of psychiatric disorders, including alcoholism and stress. In particular, the enzymes responsible for chromatin remodeling (i.e., histone deacetylases and methyltransferases, DNA methyltransferases) have been identified as common molecular mechanisms for the interaction of stress and alcohol and have become promising therapeutic targets to treat or prevent alcoholism and associated emotional disorders. Published by Elsevier Inc.

[Work accommodation at the time of Return-to-Work for workers on sick leave: a qualitative systematic review with recommendations for Return-to-work Guidance 2017].

PubMed

Nogawa, Kazuhiro; Kojimahara, Noriko

2018-05-31

We conducted a systematic review to determine whether work accommodation at the time of return-to-work (RTW) following a period of sick leave would improve work-related outcomes. Using a Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach, we developed recommendations applicable to the field of occupational health in Japan. We approached our review question for "Evidence-based Return-to-work Guidance in Occupational Health 2017 (RTW 2017) " using a PICO framework (P: workers on sick leave; I: work accommodation; C: usual care; O: improvement of work-related outcomes, such as shortened sick leave period or lower rate of sick leave recurrence). To identify relevant intervention studies about work accommodation at the time of RTW, for example, modified work or partial RTW, we searched Cochrane Library, PubMed, and ICHUSHI Web using keywords/phrases such as workplace accommodation, partial RTW, rehabilitation, and modified work. Although we found no systematic reviews, we did identify 632 randomized controlled trials and cohort studies. Two researchers screened them independently using selection and exclusion criteria defined by the RTW guidance committee in the scope. For intervention studies, we extracted PICO and evaluated risk of bias using RevMan 5.3. For cohort studies, we applied the Newcastle-Ottawa scale for evaluation of risk of bias. We then evaluated the body of evidence based on risk of bias, indirectness, inconsistency, imprecision, and publication bias using GRADEPro GDT. Finally, we adopted Evidence to Decision from GRADE and developed recommendations based on anonymous panels' votes. We identified three relevant studies, which were one randomized controlled trial and two cohort studies, on Partial RTW or modified work for musculoskeletal disorders. Although we could not conduct a meta-analysis, our qualitative systematic review of these studies led us to conclude that partial RTW could shorten the period of sick leave and modified work could lower the recurrence rates of sick leave. Therefore, "Work accommodation at the time of RTW could be provided for workers on sick leave for musculoskeletal disorders" was weakly recommended on the basis of low evidence. Our recommendation, though plausible, is weak, as it is based on evidence from a small number of studies of foreign occupational health systems. Development of robust recommendations will require accumulation of additional information on diverse factors, such as cost-effectiveness, and on other diseases, for example, mental health disorders or malignant diseases, in Japan.

Comparison of a Broad-Based Screen versus Disorder-Specific Screen in Detecting Young Children with an Autism Spectrum Disorder

ERIC Educational Resources Information Center

Wiggins, Lisa D; Piazza, Vivian; Robins, Diana L

2014-01-01

The goals of our study were to (a) compare agreement between autism spectrum disorder diagnosis and outcome of the Modified Checklist for Autism in Toddlers and Parents Evaluation of Developmental Status in a sample of toddlers and (b) examine specific concerns noted for toddlers who screened negative on the Modified Checklist for Autism in…

S219. RISK FACTORS FOR LOW BONE MINERAL DENSITY IN PATIENTS TAKING ANTIPSYCHOTICS

PubMed Central

Jhon, Min; Hong, Ji-Eun; Park, Cheol; Lee, Ju-Yeon; Jo, Anna; Kim, Jae-Min; Shin, Il-Seon; Williams, Lana; Berk, Michael; Yoon, Jin-Sang; Kim, Sung-Wan

2018-01-01

Abstract Background The aim of this study is to explore potentially modifiable risk factors for low bone mineral density (BMD) in adults with psychotic disorders. Furthermore, we sought to identify gender-specific risk factors. Methods The study included 285 community-dwelling patients with psychotic disorders. Dual-energy x-ray absorptiometry was used to measure BMD. Laboratory examinations included vitamin D and prolactin levels. Low BMD was defined as<1 standard deviation below the mean for young adults. Clinical characteristics associated with low BMD were identified with logistic regression analysis in total population and each gender. Results Fifty-eight (20.4%) subjects had low BMD. Low BMD was more common in men and in patients with low body mass indices (BMIs), as well as in those with shorter treatment durations, those on Medicaid, and patients using serotonergic antidepressants. Logistic regression analysis revealed that low BMD was negatively associated with BMI and treatment duration and positively with gender (male) and serotonergic antidepressants use in the overall population. In men, low BMD was associated with treatment duration and BMI; in women, low BMD was associated with BMI, prolactin level, vitamin D, and serotonergic antidepressant use. Discussion Low BMI was risk factor for reduced BMD in both genders. Shorter treatment duration was associated with low BMD in men, whereas higher prolactin levels, lower vitamin D, and the use of serotonergic antidepressants were associated with low BMD in women. Psychotropic agents should be prescribed mindful of their effects on bone, as use of these medications is a modifiable risk factor for osteoporosis in women with psychotic disorders.

Combination of pharmacotherapy and psychotherapy in the treatment of chronic depression: A systematic review and meta-analysis

PubMed Central

2012-01-01

Background Chronic depression represents a substantial portion of depressive disorders and is associated with severe consequences. This review examined whether the combination of pharmacological treatments and psychotherapy is associated with higher effectiveness than pharmacotherapy alone via meta-analysis; and identified possible treatment effect modifiers via meta-regression-analysis. Methods A systematic search was conducted in the following databases: Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, ISI Web of Science, BIOSIS, PsycINFO, and CINAHL. Primary efficacy outcome was a response to treatment; primary acceptance outcome was dropping out of the study. Only randomized controlled trials were considered. Results We identified 8 studies with a total of 9 relevant comparisons. Our analysis revealed small, but statistically not significant effects of combined therapies on outcomes directly related to depression (BR = 1.20) with substantial heterogeneity between studies (I² = 67%). Three treatment effect modifiers were identified: target disorders, the type of psychotherapy and the type of pharmacotherapy. Small but statistically significant effects of combined therapies on quality of life (SMD = 0.18) were revealed. No differences in acceptance rates and the long-term effects between combined treatments and pure pharmacological interventions were observed. Conclusions This systematic review could not provide clear evidence for the combination of pharmacotherapy and psychotherapy. However, due to the small amount of primary studies further research is needed for a conclusive decision. PMID:22694751

Work-related musculoskeletal disorders (WMDs) risk assessment at core assembly production of electronic components manufacturing company

NASA Astrophysics Data System (ADS)

Yahya, N. M.; Zahid, M. N. O.

2018-03-01

This study conducted to assess the work-related musculoskeletal disorders (WMDs) among the workers at core assembly production in an electronic components manufacturing company located in Pekan, Pahang, Malaysia. The study is to identify the WMDs risk factor and risk level. A set of questionnaires survey based on modified Nordic Musculoskeletal Disorder Questionnaires have been distributed to respective workers to acquire the WMDs risk factor identification. Then, postural analysis was conducted in order to measure the respective WMDs risk level. The analysis were based on two ergonomics assessment tools; Rapid Upper Limb Assessment (RULA) and Rapid Entire Body Assessment (REBA). The study found that 30 respondents out of 36 respondents suffered from WMDs especially at shoulder, wrists and lower back. The WMDs risk have been identified from unloading process, pressing process and winding process. In term of the WMDs risk level, REBA and RULA assessment tools have indicated high risk level to unloading and pressing process. Thus, this study had established the WMDs risk factor and risk level of core assembly production in an electronic components manufacturing company at Malaysia environment.

Isolation of circulating plasma cells from blood of patients diagnosed with clonal plasma cell disorders using cell selection microfluidics.

PubMed

Kamande, Joyce W; Lindell, Maria A M; Witek, Małgorzata A; Voorhees, Peter M; Soper, Steven A

2018-02-19

Blood samples from patients with plasma cell disorders were analysed for the presence of circulating plasma cells (CPCs) using a microfluidic device modified with monoclonal anti-CD138 antibodies. CPCs were immuno-phenotyped using a CD38/CD56/CD45 panel and identified in 78% of patients with monoclonal gammopathy of undetermined significance (MGUS), all patients with smouldering and symptomatic multiple myeloma (MM), and none in the controls. The burden of CPCs was higher in patients with symptomatic MM compared with MGUS and smouldering MM (p < 0.05). FISH analysis revealed the presence of chromosome 13 deletions in CPCs that correlated with bone marrow results. Point mutations in KRAS were identified, including different mutations from sub-clones derived from the same patient. The microfluidic assay represents a highly sensitive method for enumerating CPCs and allows for the cytogenetic and molecular characterization of CPCs.

Modeling space-charge-limited current transport in spatially disordered organic semiconductors

NASA Astrophysics Data System (ADS)

Zubair, M.; Ang, Y. S.; Ang, L. K.

Charge transport properties in organic semiconductors are determined by two kinds of microscopic disorder, namely energetic disorder and the spatial disorder. It is demonstrated that the thickness dependence of space-charge limited current (SCLC) can be related to spatial disorder within the framework of fractional-dimensional space. We present a modified Mott-Gurney (MG) law in different regimes to model the varying thickness dependence in such spatially disordered materials. We analyze multiple experimental results from literature where thickness dependence of SCLC shows that the classical MG law might lead to less accurate extraction of mobility parameter, whereas the modified MG law would be a better choice in such devices. Experimental SCLC measurement in a PPV-based structure was previously modeled using a carrier-density dependent model which contradicts with a recent experiment that confirms a carrier-density independent mobility originating from the disordered morphology of the polymer. Here, this is reconciled by the modified MG law which intrinsically takes into account the effect of spatial disorder without the need of using a carrier-density dependent model. This work is supported by Singapore Temasek Laboratories (TL) Seed Grant (IGDS S16 02 05 1).

Effects of Age on the Types and Severity of Excessive Fear or the Absence of Fear in Children and Young Adults with Autism

ERIC Educational Resources Information Center

Richman, David M.; Dotson, Wesley H.; Rose, Chad A.; Thompson, Samuel; Abby, Layla

2012-01-01

This study identified (a) patterns of fearful stimuli for children and young adults with autism spectrum disorder (ASD), (b) the severity of the fear, and (c) whether excessive fear or the absence of fear negatively affected the participant's quality of life. A web-based survey was used to distribute a modified and extended version of the Fear…

Disease progression and neuroscience.

PubMed

Holford, Nick

2013-06-01

The concepts of disease progression are discussed in the context of neurological disorders. The importance of understanding the time course of the response to inactive (placebo) treatment is discussed. Disease progression and response to placebo treatment both need to be considered before drug effects can be reliably identified. Criteria for distinguishing between symptomatic and disease modifying drug effects are proposed and used to interpret the results of clinical trials in pain, depression, schizophrenia, stroke, Alzheimer's disease and Parkinson's disease.

A prospective study of pre-trauma risk factors for post-traumatic stress disorder and depression.

PubMed

Wild, J; Smith, K V; Thompson, E; Béar, F; Lommen, M J J; Ehlers, A

2016-09-01

It is unclear which potentially modifiable risk factors best predict post-trauma psychiatric disorders. We aimed to identify pre-trauma risk factors for post-traumatic stress disorder (PTSD) or major depression (MD) that could be targeted with resilience interventions. Newly recruited paramedics (n = 453) were assessed for history of mental disorders with structured clinical interviews within the first week of their paramedic training and completed self-report measures to assess hypothesized predictors. Participants were assessed every 4 months for 2 years to identify any episodes of PTSD and MD; 386 paramedics (85.2%) participated in the follow-up interviews. In all, 32 participants (8.3%) developed an episode of PTSD and 41 (10.6%) an episode of MD during follow-up. In all but nine cases (2.3%), episodes had remitted by the next assessment 4 months later. At 2 years, those with episodes of PTSD or MD during follow-up reported more days off work, poorer sleep, poorer quality of life, greater burn-out; and greater weight-gain for those with PTSD. In line with theories of PTSD and depression, analyses controlling for psychiatric and trauma history identified several pre-trauma predictors (cognitive styles, coping styles and psychological traits). Logistic regressions showed that rumination about memories of stressful events at the start of training uniquely predicted an episode of PTSD. Perceived resilience uniquely predicted an episode of MD. Participants at risk of developing episodes of PTSD or depression could be identified within the first week of paramedic training. Cognitive predictors of episodes of PTSD and MD are promising targets for resilience interventions.

CRITICAL REVIEW OF OUTCOME RESEARCH ON INTERPERSONAL PSYCHOTHERAPY FOR ANXIETY DISORDERS

PubMed Central

Markowitz, John C.; Lipsitz, Joshua; Milrod, Barbara L.

2014-01-01

Background Interpersonal psychotherapy (IPT) has demonstrated efficacy in treating mood and eating disorders. This article critically reviews outcome research testing IPT for anxiety disorders, a diagnostic area where cognitive behavioral therapy (CBT) has dominated research and treatment. Methods A literature search identified six open and five controlled trials of IPT for social anxiety disorder (SAD), panic disorder, and posttraumatic stress disorder. Results Studies were generally small, underpowered, and sometimes methodologically compromised. Nonetheless, minimally adapted from its standard depression strategies, IPT for anxiety disorders yielded positive results in open trials for the three diagnoses. In controlled trials, IPT fared better than waiting list (N = 2), was equipotent to supportive psychodynamic psychotherapy (N = 1), but less efficacious than CBT for SAD (N = 1), and CBT for panic disorder (N = 1) in a methodologically complicated study. IPT equaled CBT in a group residential format (N = 1). Conclusions IPT shows some promise for anxiety disorders but has thus far shown no advantages in controlled trials relative to other therapies. Methodological and ecological issues have complicated testing of IPT for anxiety disorders, clouding some findings. The authors discuss difficulties of conducting non-CBT research in a CBT-dominated area, investigator bias, and the probable need to further modify IPT for anxiety disorders. Untested therapies deserve the fairest possible testing. Depression and Anxiety 00:1–10, 2014. PMID:24493661

Phase Transitions on Random Lattices: How Random is Topological Disorder?

NASA Astrophysics Data System (ADS)

Barghathi, Hatem; Vojta, Thomas

2015-03-01

We study the effects of topological (connectivity) disorder on phase transitions. We identify a broad class of random lattices whose disorder fluctuations decay much faster with increasing length scale than those of generic random systems, yielding a wandering exponent of ω = (d - 1) / (2 d) in d dimensions. The stability of clean critical points is thus governed by the criterion (d + 1) ν > 2 rather than the usual Harris criterion dν > 2 , making topological disorder less relevant than generic randomness. The Imry-Ma criterion is also modified, allowing first-order transitions to survive in all dimensions d > 1 . These results explain a host of puzzling violations of the original criteria for equilibrium and nonequilibrium phase transitions on random lattices. We discuss applications, and we illustrate our theory by computer simulations of random Voronoi and other lattices. This work was supported by the NSF under Grant Nos. DMR-1205803 and PHYS-1066293. We acknowledge the hospitality of the Aspen Center for Physics.

Rare deleterious mutations are associated with disease in bipolar disorder families.

PubMed

Rao, A R; Yourshaw, M; Christensen, B; Nelson, S F; Kerner, B

2017-07-01

Bipolar disorder (BD) is a common, complex and heritable psychiatric disorder characterized by episodes of severe mood swings. The identification of rare, damaging genomic mutations in families with BD could inform about disease mechanisms and lead to new therapeutic interventions. To determine whether rare, damaging mutations shared identity-by-descent in families with BD could be associated with disease, exome sequencing was performed in multigenerational families of the NIMH BD Family Study followed by in silico functional prediction. Disease association and disease specificity was determined using 5090 exomes from the Sweden-Schizophrenia (SZ) Population-Based Case-Control Exome Sequencing study. We identified 14 rare and likely deleterious mutations in 14 genes that were shared identity-by-descent among affected family members. The variants were associated with BD (P<0.05 after Bonferroni's correction) and disease specificity was supported by the absence of the mutations in patients with SZ. In addition, we found rare, functional mutations in known causal genes for neuropsychiatric disorders including holoprosencephaly and epilepsy. Our results demonstrate that exome sequencing in multigenerational families with BD is effective in identifying rare genomic variants of potential clinical relevance and also disease modifiers related to coexisting medical conditions. Replication of our results and experimental validation are required before disease causation could be assumed.

Early Intervention in Bipolar Disorder.

PubMed

Vieta, Eduard; Salagre, Estela; Grande, Iria; Carvalho, André F; Fernandes, Brisa S; Berk, Michael; Birmaher, Boris; Tohen, Mauricio; Suppes, Trisha

2018-05-01

Bipolar disorder is a recurrent disorder that affects more than 1% of the world population and usually has its onset during youth. Its chronic course is associated with high rates of morbidity and mortality, making bipolar disorder one of the main causes of disability among young and working-age people. The implementation of early intervention strategies may help to change the outcome of the illness and avert potentially irreversible harm to patients with bipolar disorder, as early phases may be more responsive to treatment and may need less aggressive therapies. Early intervention in bipolar disorder is gaining momentum. Current evidence emerging from longitudinal studies indicates that parental early-onset bipolar disorder is the most consistent risk factor for bipolar disorder. Longitudinal studies also indicate that a full-blown manic episode is often preceded by a variety of prodromal symptoms, particularly subsyndromal manic symptoms, therefore supporting the existence of an at-risk state in bipolar disorder that could be targeted through early intervention. There are also identifiable risk factors that influence the course of bipolar disorder, some of them potentially modifiable. Valid biomarkers or diagnosis tools to help clinicians identify individuals at high risk of conversion to bipolar disorder are still lacking, although there are some promising early results. Pending more solid evidence on the best treatment strategy in early phases of bipolar disorder, physicians should carefully weigh the risks and benefits of each intervention. Further studies will provide the evidence needed to finish shaping the concept of early intervention. AJP AT 175 Remembering Our Past As We Envision Our Future April 1925: Interpretations of Manic-Depressive Phases Earl Bond and G.E. Partridge reviewed a number of patients with manic-depressive illness in search of a unifying endo-psychic conflict. They concluded that understanding either phase of illness was "elusive" and "tantalizing beyond reach." (Am J Psychiatry 1925: 81: 643-662 ).

Mental health treatment among soldiers with current mental disorders in the Army Study to Assess Risk and Resilience in Servicemembers (Army STARRS)

PubMed Central

Colpe, Lisa J.; Naifeh, James A.; Aliaga, Pablo; Sampson, Nancy A.; Heeringa, Steven G.; Stein, Murray B.; Ursano, Robert J.; Fullerton, Carol S.; Nock, Matthew K.; Schoenbaum, Michael L.; Zaslavsky, Alan M.; Kessler, Ronald C.

2015-01-01

A representative sample of 5,428 non-deployed Regular Army soldiers completed a self-administered questionnaire (SAQ) and consented to linking SAQ data with administrative records as part of the Army Study to Assess Risk and Resilience in Servicemembers (Army STARRS). The SAQ included information about prevalence and treatment of mental disorders among respondents with current DSM-IV internalizing (anxiety, mood) and externalizing (disruptive behavior, substance) disorders. 21.3% of soldiers with any current disorder reported current treatment. Seven significant predictors of being in treatment rates were identified. Four of these 7 were indicators of psychopathology (bipolar disorder, panic disorder, PTSD, 8+ months duration of disorder). Two were socio-demographics (history of marriage, not being Non-Hispanic Black). The final predictor was history of deployment. Treatment rates varied between 4.7 and 71.5% depending on how many positive predictors the soldier had. The vast majority of soldiers had a low number of these predictors. These results document that most non-deployed soldiers with mental disorders are not in treatment and that untreated soldiers are not concentrated in a particular segment of the population that might be targeted for special outreach efforts. Analysis of modifiable barriers to treatment is needed to help strengthen outreach efforts. PMID:26444466

[Cardiovascular risk factors in users with severe mental disorder].

PubMed

Paños-Martínez, Montserrat; Patró-Moncunill, Ester; Santiago-Barragán, Ángel-María; Marti-Mestre, Marc; Torralbas-Ortega, Jordi; Escayola-Maranges, Anna; Granero-Lázaro, Alberto

2016-01-01

To identify the prevalence of the cardiovascular risk (RCV) in users with a Severe Mental Disorder (SMD) attended in mental health service in ParcTaulí (Sabadell - Barcelona). This is an observational, descriptive and transversal study of the factors of cardiovascular risk in 789 users with SMD. The instrument used was the scale of assessment of the Registre Gironí del Cor, which estimates the risk of cardiovascular disease. 26.6% of the sample has RCV (22.5% moderate, 3.8% high and 0.3% very high). The analysis of the modifiable risk factors shows that 16.5% of the patients are hypertensive, 55.2% are smokers, 19.77% have hyperglycaemia (8.2% of whom are diagnosed of diabetes mellitus), 40.2% have obesity, 36.2% overweight and 47.27% hypercholesterolemia. The study confirms that the prevalence of the RVC in SMD users is greater than the RCV in general population and it's associated to the presence of modifiable risk factors. Health education carried out by nurses is the best to prevent the RCV in SMD users. Copyright © 2016 Elsevier España, S.L.U. All rights reserved.

Modification of the Clinical Global Impressions (CGI) Scale for use in bipolar illness (BP): the CGI-BP.

PubMed

Spearing, M K; Post, R M; Leverich, G S; Brandt, D; Nolen, W

1997-12-05

The Clinical Global Impressions Scale (CGI) was modified specifically for use in assessing global illness severity and change in patients with bipolar disorder. Criticisms of the original CGI were addressed by correcting inconsistencies in scaling, identifying time frames for comparison, clarifying definitions of illness severity and change, and separating out assessment of treatment side effects from illness improvement during treatment. A Detailed User's Guide was developed to train clinicians in the use of the new CGI-Bipolar Version (CGI-BP) for rating severity of manic and depressive episodes and the degree of change from the immediately preceding phase and from the worst phase of illness. The revised scale and manual provide a focused set of instructions to facilitate the reliability of these ratings of mania, depression, and overall bipolar illness during treatment of an acute episode or in longer-term illness prophylaxis. Interrater reliability of the scale was demonstrated in preliminary analyses. Thus, the modified CGI-BP is anticipated to be more useful than the original CGI in studies of bipolar disorder.

Development and validation of a prediction algorithm for the onset of common mental disorders in a working population.

PubMed

Fernandez, Ana; Salvador-Carulla, Luis; Choi, Isabella; Calvo, Rafael; Harvey, Samuel B; Glozier, Nicholas

2018-01-01

Common mental disorders are the most common reason for long-term sickness absence in most developed countries. Prediction algorithms for the onset of common mental disorders may help target indicated work-based prevention interventions. We aimed to develop and validate a risk algorithm to predict the onset of common mental disorders at 12 months in a working population. We conducted a secondary analysis of the Household, Income and Labour Dynamics in Australia Survey, a longitudinal, nationally representative household panel in Australia. Data from the 6189 working participants who did not meet the criteria for a common mental disorders at baseline were non-randomly split into training and validation databases, based on state of residence. Common mental disorders were assessed with the mental component score of 36-Item Short Form Health Survey questionnaire (score ⩽45). Risk algorithms were constructed following recommendations made by the Transparent Reporting of a multivariable prediction model for Prevention Or Diagnosis statement. Different risk factors were identified among women and men for the final risk algorithms. In the training data, the model for women had a C-index of 0.73 and effect size (Hedges' g) of 0.91. In men, the C-index was 0.76 and the effect size was 1.06. In the validation data, the C-index was 0.66 for women and 0.73 for men, with positive predictive values of 0.28 and 0.26, respectively Conclusion: It is possible to develop an algorithm with good discrimination for the onset identifying overall and modifiable risks of common mental disorders among working men. Such models have the potential to change the way that prevention of common mental disorders at the workplace is conducted, but different models may be required for women.

Metabolic signature of breast cancer cell line MCF-7: profiling of modified nucleosides via LC-IT MS coupling.

PubMed

Bullinger, Dino; Neubauer, Hans; Fehm, Tanja; Laufer, Stefan; Gleiter, Christoph H; Kammerer, Bernd

2007-11-29

Cancer, like other diseases accompanied by strong metabolic disorders, shows characteristic effects on cell turnover rate, activity of modifying enzymes and DNA/RNA modifications, resulting also in elevated amounts of excreted modified nucleosides. For a better understanding of the impaired RNA metabolism in breast cancer cells, we screened these metabolites in the cell culture supernatants of the breast cancer cell line MCF-7 and compared it to the human mammary epithelial cells MCF-10A. The nucleosides were isolated and analyzed via 2D-chromatographic techniques: In the first dimension by cis-diol specific boronate affinity extraction and subsequently by reversed phase chromatography coupled to an ion trap mass spectrometer. Besides the determination of ribonucleosides, additional compounds with cis-diol structure, deriving from cross-linked biochemical pathways, like purine-, histidine- and polyamine metabolism were detected. In total, 36 metabolites were identified by comparison of fragmentation patterns and retention time. Relation to the internal standard isoguanosine yielded normalized area ratios for each identified compound and enabled a semi-quantitative metabolic signature of both analyzed cell lines.13 of the identified 26 modified ribonucleosides were elevated in the cell culture supernatants of MCF-7 cells, with 5-methyluridine, N2,N2,7-trimethylguanosine, N6-methyl-N6-threonylcarbamoyladenosine and 3-(3-aminocarboxypropyl)-uridine showing the most significant differences. 1-ribosylimidazole-4-acetic acid, a histamine metabolite, was solely found in the supernatants of MCF-10A cells, whereas 1-ribosyl-4-carboxamido-5-aminoimidazole and S-adenosylmethionine occurred only in supernatants of MCF-7 cells. The obtained results are discussed against the background of pathological changes in cell metabolism, resulting in new perspectives for modified nucleosides and related metabolites as possible biomedical markers for breast carcinoma in vivo.

Adult Attention Deficit Hyperactivity Disorder Symptoms, Perceived Stress, and Well-Being: The Role of Early Maladaptive Schemata.

PubMed

Miklósi, Mónika; Máté, Orsolya; Somogyi, Klára; Szabó, Marianna

2016-05-01

Attention deficit hyperactivity disorder (ADHD) is one of the most prevalent chronic neuropsychiatric disorders, severely affecting the emotional well-being of children as well as of adults. It has been suggested that individuals who experience symptoms of ADHD develop maladaptive schemata of failure, impaired self-discipline, social isolation, and shame. These schemata may then contribute to impaired emotional well-being by increasing unhelpful responses to stressful life events. However, to date, no empirical research has tested this theoretical proposition. In a sample of 204 nonclinical adults, we conducted a serial multiple mediator analysis, which supported the proposed model. More severe ADHD symptoms were associated with higher levels of perceived stress both directly and indirectly through stronger maladaptive schemata, which, in turn, were related to lower levels of emotional well-being. Results suggest that identifying and modifying maladaptive schemata may be an important addition to psychotherapy for adult ADHD patients.

Mental Health Treatment Among Soldiers With Current Mental Disorders in the Army Study to Assess Risk and Resilience in Service Members (Army STARRS).

PubMed

Colpe, Lisa J; Naifeh, James A; Aliaga, Pablo A; Sampson, Nancy A; Heeringa, Steven G; Stein, Murray B; Ursano, Robert J; Fullerton, Carol S; Nock, Matthew K; Schoenbaum, Michael L; Zaslavsky, Alan M; Kessler, Ronald C

2015-10-01

A representative sample of 5,428 nondeployed Regular Army soldiers completed a self-administered questionnaire (SAQ) and consented to linking SAQ data with administrative records as part of the Army Study to Assess Risk and Resilience in Service members. The SAQ included information about prevalence and treatment of mental disorders among respondents with current Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) internalizing (anxiety, mood) and externalizing (disruptive behavior, substance) disorders. 21.3% of soldiers with any current disorder reported current treatment. Seven significant predictors of being in treatment were identified. Four of these 7 were indicators of psychopathology (bipolar disorder, panic disorder, post-traumatic stress disorder, 8+ months duration of disorder). Two were sociodemographics (history of marriage, not being non-Hispanic Black). The final predictor was history of deployment. Treatment rates varied between 4.7 and 71.5% depending on how many positive predictors the soldier had. The vast majority of soldiers had a low number of these predictors. These results document that most nondeployed soldiers with mental disorders are not in treatment and that untreated soldiers are not concentrated in a particular segment of the population that might be targeted for special outreach efforts. Analysis of modifiable barriers to treatment is needed to help strengthen outreach efforts. Reprint & Copyright © 2015 Association of Military Surgeons of the U.S.

Delayed Psychological Morbidity Associated with Snakebite Envenoming

PubMed Central

Williams, Shehan S.; Wijesinghe, Chamara A.; Jayamanne, Shaluka F.; Buckley, Nicholas A.; Dawson, Andrew H.; Lalloo, David G.; de Silva, H. Janaka

2011-01-01

Introduction The psychological impact of snakebite on its victims, especially possible late effects, has not been systematically studied. Objectives To assess delayed somatic symptoms, depressive disorder, post-traumatic stress disorder (PTSD), and impairment in functioning, among snakebite victims. Methods The study had qualitative and quantitative arms. In the quantitative arm, 88 persons who had systemic envenoming following snakebite from the North Central Province of Sri Lanka were randomly identified from an established research database and interviewed 12 to 48 months (mean 30) after the incident. Persons with no history of snakebite, matched for age, sex, geograpical location and occupation, acted as controls. A modified version of the Beck Depression Inventory, Post-Traumatic Stress Symptom Scale, Hopkins Somatic Symptoms Checklist, Sheehan Disability Inventory and a structured questionnaire were administered. In the qualitative arm, focus group discussions among snakebite victims explored common somatic symptoms attributed to envenoming. Results Previous snakebite victims (cases) had more symptoms than controls as measured by the modified Beck Depression Scale (mean 19.1 Vs 14.4; p<0.001) and Hopkins Symptoms Checklist (38.9 vs. 28.2; p<0.001). 48 (54%) cases met criteria for depressive disorder compared to 13 (15%) controls. 19 (21.6%) cases also met criteria for PTSD. 24 (27%) claimed that the snakebite caused a negative change in their employment; nine (10.2%) had stopped working and 15 (17%) claimed residual physical disability. The themes identified in the qualitative arm included blindness, tooth decay, body aches, headaches, tiredness and weakness. Conclusions Snakebite causes significant ongoing psychological morbidity, a complication not previously documented. The economic and social impacts of this problem need further investigation. PMID:21829741

Modified Therapeutic Community Treatment for Offenders with Co-Occurring Disorders: Mental Health Outcomes

ERIC Educational Resources Information Center

Sullivan, Christopher J.; Sacks, Stanley; McKendrick, Karen; Banks, Steven; Sacks, Joann Y.; Stommel, Joseph

2007-01-01

This paper examines outcomes 12 months post-prison release for offenders with co-occurring disorders (n = 185) randomly assigned to either a mental health control treatment (C) or a modified therapeutic community (E). Significant between-group differences were not found for mental health measures, although improvements were observed for each…

A Modified Dialogic Reading Intervention for Preschool Children with Autism Spectrum Disorder

ERIC Educational Resources Information Center

Fleury, Veronica P.; Schwartz, Ilene S.

2017-01-01

We examined the effect of a modified dialogic reading intervention on levels of verbal participation and vocabulary growth in nine preschool children with autism spectrum disorder (ASD) using single-case design methodology. Baseline book reading resulted in consistently low levels of verbal participation followed by an immediate increase in verbal…

Functional measures developed for clinical populations identified impairment among active workers with upper extremity disorders

PubMed Central

Gardner, Bethany T.; Dale, Ann Marie; Buckner-Petty, Skye; Rachford, Robert; Strickland, Jaime; Kaskutas, Vicki; Evanoff, Bradley

2017-01-01

Purpose Few studies have explored measures of function across a range of health outcomes in a general working population. Using four upper extremity (UE) case definitions from the scientific literature, we described the performance of functional measures of work, activities of daily living, and overall health. Methods A sample of 573 workers completed several functional measures: modified recall versions of the QuickDASH, Levine Functional Status Scale (FSS), DASH Work module (DASH-W), and standard SF-8 physical component score. We determined case status based on four UE case definitions: 1) UE symptoms, 2) UE musculoskeletal disorders (MSD), 3) carpal tunnel syndrome (CTS), and 4) work limitations due to UE symptoms. We calculated effect sizes for each case definition to show the magnitude of the differences that were detected between cases and non-cases for each case definition on each functional measure. Sensitivity and specificity analyses showed how well each measure identified functional impairments across the UE case definitions. Results All measures discriminated between cases and non-cases for each case definition with the largest effect sizes for CTS and work limitations, particularly for the modified FSS and DASH-W measures. Specificity was high and sensitivity was low for outcomes of UE symptoms and UE MSD in all measures. Sensitivity was high for CTS and work limitations. Conclusions Functional measures developed specifically for use in clinical, treatment-seeking populations may identify mild levels of impairment in relatively healthy, active working populations, but measures performed better among workers with CTS or those reporting limitations at work. PMID:26091980

Identification of genetic factors that modify motor performance and body weight using Collaborative Cross mice

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

Mao, Jian -Hua; Langley, Sasha A.; Huang, Yurong

Evidence has emerged that suggests a link between motor deficits, obesity and many neurological disorders. However, the contributing genetic risk factors are poorly understood. Here we used the Collaborative Cross (CC), a large panel of newly inbred mice that captures 90% of the known variation among laboratory mice, to identify the genetic loci controlling rotarod performance and its relationship with body weight in a cohort of 365 mice across 16 CC strains. Body weight and rotarod performance varied widely across CC strains and were significantly negatively correlated. Genetic linkage analysis identified 14 loci that were associated with body weight. However,more » 45 loci affected rotarod performance, seven of which were also associated with body weight, suggesting a strong link at the genetic level. As a result, we show that genes identified in this study overlap significantly with those related to neurological disorders and obesity found in human GWA studies. In conclusion, our results provide a genetic framework for studies of the connection between body weight, the central nervous system and behavior.« less

Identification of genetic factors that modify motor performance and body weight using Collaborative Cross mice

DOE PAGES

Mao, Jian -Hua; Langley, Sasha A.; Huang, Yurong; ...

2015-11-09

Evidence has emerged that suggests a link between motor deficits, obesity and many neurological disorders. However, the contributing genetic risk factors are poorly understood. Here we used the Collaborative Cross (CC), a large panel of newly inbred mice that captures 90% of the known variation among laboratory mice, to identify the genetic loci controlling rotarod performance and its relationship with body weight in a cohort of 365 mice across 16 CC strains. Body weight and rotarod performance varied widely across CC strains and were significantly negatively correlated. Genetic linkage analysis identified 14 loci that were associated with body weight. However,more » 45 loci affected rotarod performance, seven of which were also associated with body weight, suggesting a strong link at the genetic level. As a result, we show that genes identified in this study overlap significantly with those related to neurological disorders and obesity found in human GWA studies. In conclusion, our results provide a genetic framework for studies of the connection between body weight, the central nervous system and behavior.« less

Genetic disorders of vitamin B12 metabolism: eight complementation groups – eight genes

PubMed Central

Froese, D. Sean; Gravel, Roy A.

2010-01-01

Vitamin B12 (cobalamin, Cbl) is an essential nutrient in human metabolism. Genetic diseases of vitamin B12 utilisation constitute an important fraction of inherited newborn disease. Functionally, B12 is the cofactor for methionine synthase and methylmalonyl CoA mutase. To function as a cofactor, B12 must be metabolised through a complex pathway that modifies its structure and takes it through subcellular compartments of the cell. Through the study of inherited disorders of vitamin B12 utilisation, the genes for eight complementation groups have been identified, leading to the determination of the general structure of vitamin B12 processing and providing methods for carrier testing, prenatal diagnosis and approaches to treatment. PMID:21114891

Mechanisms to medicines: elucidating neural and molecular substrates of fear extinction to identify novel treatments for anxiety disorders.

PubMed

Bukalo, Olena; Pinard, Courtney R; Holmes, Andrew

2014-10-01

The burden of anxiety disorders is growing, but the efficacy of available anxiolytic treatments remains inadequate. Cognitive behavioural therapy for anxiety disorders focuses on identifying and modifying maladaptive patterns of thinking and behaving, and has a testable analogue in rodents in the form of fear extinction. A large preclinical literature has amassed in recent years describing the neural and molecular basis of fear extinction in rodents. In this review, we discuss how this work is being harnessed to foster translational research on anxiety disorders and facilitate the search for new anxiolytic treatments. We begin by summarizing the anatomical and functional connectivity of a medial prefrontal cortex (mPFC)-amygdala circuit that subserves fear extinction, including new insights from optogenetics. We then cover some of the approaches that have been taken to model impaired fear extinction and associated impairments with mPFC-amygdala dysfunction. The principal goal of the review is to evaluate evidence that various neurotransmitter and neuromodulator systems mediate fear extinction by modulating the mPFC-amygdala circuitry. To that end, we describe studies that have tested how fear extinction is impaired or facilitated by pharmacological manipulations of dopamine, noradrenaline, 5-HT, GABA, glutamate, neuropeptides, endocannabinoids and various other systems, which either directly target the mPFC-amygdala circuit, or produce behavioural effects that are coincident with functional changes in the circuit. We conclude that there are good grounds to be optimistic that the progress in defining the molecular substrates of mPFC-amygdala circuit function can be effectively leveraged to identify plausible candidates for extinction-promoting therapies for anxiety disorders. © 2014 The British Pharmacological Society.

Why good placements matter: Pre-placement and placement risk factors associated with mental health disorders in pre-school children in foster care.

PubMed

Hillen, Thomas; Gafson, Leonie

2015-07-01

Pre-school children placed in local authority care show elevated rates of mental health disorders when compared to the general population. This study investigated risk factors for mental health disorders relating to the period prior to entering care and while in care. A representative sample of 43 children in care aged 0-72 months in an inner London borough underwent comprehensive multidimensional assessments. Presence of emotional, behavioural, attachment and adaptive disorders was ascertained. Exposure to two pre-placement risk factors and six placement risk factors was compared between children with and without a disorder. A total of 26 children (60.5%) had at least one mental health disorder. The two pre-placement risk factors, multiple types of maltreatment and entry into care after the age of 6 months, were both significantly associated with mental health disorders. The three placement risk factors of sudden placement moves, multiple placement moves and child-carer alienation showed a significant association with mental health disorders. There was a strong correlation between the number of risk factors and the number of co-morbid mental health disorders per child (r = .67, p < .001). In conclusion, this study identified five modifiable risk factors related to the quality of safeguarding and fostering services which showed a significant association with pre-school mental health. © The Author(s) 2014.

Physical activity and exercise attenuate neuroinflammation in neurological diseases.

PubMed

Spielman, Lindsay Joy; Little, Jonathan Peter; Klegeris, Andis

2016-07-01

Major depressive disorder (MDD), schizophrenia (SCH), Alzheimer's disease (AD), and Parkinson's disease (PD) are devastating neurological disorders, which increasingly contribute to global morbidity and mortality. Although the pathogenic mechanisms of these conditions are quite diverse, chronic neuroinflammation is one underlying feature shared by all these diseases. Even though the specific root causes of these diseases remain to be identified, evidence indicates that the observed neuroinflammation is initiated by unique pathological features associated with each specific disease. If the initial acute inflammation is not resolved, a chronic neuroinflammatory state develops and ultimately contributes to disease progression. Chronic neuroinflammation is characterized by adverse and non-specific activation of glial cells, which can lead to collateral damage of nearby neurons and other glia. This misdirected neuroinflammatory response is hypothesized to contribute to neuropathology in MDD, SCH, AD, and PD. Physical activity (PA), which is critical for maintenance of whole body and brain health, may also beneficially modify neuroimmune responses. Since PA has neuroimmune-modifying properties, and the common underlying feature of MDD, SCH, AD, and PD is chronic neuroinflammation, we hypothesize that PA could minimize brain diseases by modifying glia-mediated neuroinflammation. This review highlights current evidence supporting the disease-altering potential of PA and exercise through modifications of neuroimmune responses, specifically in MDD, SCH, AD and PD. Copyright © 2016 Elsevier Inc. All rights reserved.

Public attitudes toward-and identification of-cluttering and stuttering in Norway and Puerto Rico.

PubMed

St Louis, Kenneth O; Sønsterud, Hilda; Carlo, Edna J; Heitmann, Ragnhild R; Kvenseth, Helene

2014-12-01

The study sought to compare public attitudes toward cluttering versus stuttering in Norway and Puerto Rico and to compare respondents' identification of persons known with these fluency disorders. After reading lay definitions of cluttering and stuttering, three samples of adults from Norway and three from Puerto Rico rated their attitudes toward cluttering and/or stuttering on modified versions of the POSHA-Cl (for cluttering) and POSHA-S (for stuttering). They also identified children and adults whom they knew who either or both manifested cluttering or stuttering. Attitudes toward cluttering were essentially unaffected by rating either cluttering only or combined cluttering and stuttering on the same questionnaire in both countries. The same was also true of stuttering. Attitudes were very similar toward both disorders although slightly less positive for cluttering. Norwegian attitudes toward both disorders were generally more positive than Puerto Rican attitudes. The average respondent identified slightly more than one fluency disorder, a higher percentage for stuttering than cluttering and higher for adults than children. Cluttering-stuttering was rarely identified. Given a lay definition, this study confirmed that adults from diverse cultures hold attitudes toward cluttering that are similar to-but somewhat less positive than-their attitudes toward stuttering. It also confirmed that adults can identify cluttering among people they know, although less commonly than stuttering. Design controls in this study assured that consideration of stuttering did not affect either the attitudes or identification results for cluttering. The reader will be able to: (a) describe the effects-or lack thereof-of considerations of stuttering on attitudes toward cluttering; (b) describe differences in public identification of children and adults who either clutter or stutter; (c) describe differences between attitudes toward cluttering and stuttering in Norway and Puerto Rico. Copyright © 2014 Elsevier Inc. All rights reserved.

Back and upper extremity disorders among enlisted U.S. Marines: burden and individual risk factors.

PubMed

Huang, G D; Feuerstein, M; Arroyo, F

2001-11-01

Although musculoskeletal disorders of the low back and upper extremities can affect military readiness, little is known about their extent and risk factors in the U.S. Marine Corps. Using the Defense Medical Epidemiology and Defense Medical Surveillance System databases, back and upper extremity diagnostic categories were among the top four sources of outpatient visits and duty limitation among enlisted Marines. Back disorders were also found to be the fifth most common cause for lost time. Subsequently, high-risk occupations were identified, age-related trends for clinic visit rates were determined, and rate ratios were computed for the top 15 low back and upper extremity diagnoses among enlisted Marines from 1997 through 1998. Occupational categories with the highest rates of musculoskeletal-related outpatient visits included image interpretation, auditing and accounting, disturbsing, surveillance/target acquisition, and aircraft launch equipment. Significantly increasing linear trends in rates across age groups were found for most diagnoses. For 1998, age-specific rate ratios indicated significantly higher rates for most low back and upper extremity disorders for females; lower rank (i.e., E1-E4) was also a risk, but for fewer diagnoses. The findings emphasize the need to identify modifiable (e.g., work-related, individual) risk factors and to develop focused primary and secondary prevention programs for musculoskeletal disorders in the Marine Corps. Subsequently, these efforts can assist in reducing associated effects, maximizing resource utilization, and enhancing operational readiness.

[Integration of psychodynamic imaginative trauma therapy in a modified psychoanalytic concept of a inpatient psychotherapy unit].

PubMed

Beckrath-Wilking, Ulrike

2004-11-01

Results of latest neurobiological trauma-research suggest that many psychic disorders like personality disorders with complex traumatisation in patient's history and co-morbidities should better be treated as posttraumatic disorders. This is important for any therapy planning: should a modified psychoanalytic approach (like TFP by Kernberg) with emphasis on interpreting the transference-relation be preferred for patients with Borderline personality disorder or - diagnosing the same patients as complex posttraumatic stress disorder - a phase oriented trauma-specific approach. As such PITT combines psychodynamic understanding with hypnotherapeutic and imaginative methods. Crucial points are an active and supporting therapeutic relation, safety and reduction of stress, focus on all individual resources and use of imaginative ways for stabilization and later trauma-confrontation work.

Identification of five novel modifier loci of ApcMin harbored in the BXH14 recombinant inbred strain

PubMed Central

Siracusa, Linda D.

2012-01-01

Every year thousands of people in the USA are diagnosed with small intestine and colorectal cancers (CRC). Although environmental factors affect disease etiology, uncovering underlying genetic factors is imperative for risk assessment and developing preventative therapies. Familial adenomatous polyposis is a heritable genetic disorder in which individuals carry germ-line mutations in the adenomatous polyposis coli (APC) gene that predisposes them to CRC. The Apc Min mouse model carries a point mutation in the Apc gene and develops polyps along the intestinal tract. Inbred strain background influences polyp phenotypes in Apc Min mice. Several Modifier of Min (Mom) loci that alter tumor phenotypes associated with the Apc Min mutation have been identified to date. We screened BXH recombinant inbred (RI) strains by crossing BXH RI females with C57BL/6J (B6) Apc Min males and quantitating tumor phenotypes in backcross progeny. We found that the BXH14 RI strain harbors five modifier loci that decrease polyp multiplicity. Furthermore, we show that resistance is determined by varying combinations of these modifier loci. Gene interaction network analysis shows that there are multiple networks with proven gene–gene interactions, which contain genes from all five modifier loci. We discuss the implications of this result for studies that define susceptibility loci, namely that multiple networks may be acting concurrently to alter tumor phenotypes. Thus, the significance of this work resides not only with the modifier loci we identified but also with the combinations of loci needed to get maximal protection against polyposis and the impact of this finding on human disease studies. Abbreviations:APCadenomatous polyposis coliGWASgenome-wide association studiesQTLquantitative trait lociSNPsingle-nucleotide polymorphism. PMID:22637734

Intellectual Disability Modifies Gender Effects on Disruptive Behaviors

ERIC Educational Resources Information Center

Einfeld, Stewart L.; Gray, Kylie M.; Ellis, Louise A.; Taffe, John; Emerson, Eric; Tonge, Bruce J.; Horstead, Sian K.

2010-01-01

In typically developing children, boys are more commonly diagnosed than girls with disruptive behavior disorders, namely, attention-deficit/hyperactivity disorder, conduct disorder, and oppositional defiant disorder. For children with intellectual disability (ID), the evidence for this gender effect is less clear. In this report we examine gender…

Effects of Modified Schema-Based Instruction on Real-World Algebra Problem Solving of Students with Autism Spectrum Disorder and Moderate Intellectual Disability

ERIC Educational Resources Information Center

Root, Jenny Rose

2016-01-01

The current study evaluated the effects of modified schema-based instruction (SBI) on the algebra problem solving skills of three middle school students with autism spectrum disorder and moderate intellectual disability (ASD/ID). Participants learned to solve two types of group word problems: missing-whole and missing-part. The themes of the word…

A Review of Biomarkers in Mood and Psychotic Disorders: A Dissection of Clinical vs. Preclinical Correlates

PubMed Central

Brand, Sarel J.; Möller, Marisa; Harvey, Brian H.

2015-01-01

Despite significant research efforts aimed at understanding the neurobiological underpinnings of mood (depression, bipolar disorder) and psychotic disorders, the diagnosis and evaluation of treatment of these disorders are still based solely on relatively subjective assessment of symptoms as well as psychometric evaluations. Therefore, biological markers aimed at improving the current classification of psychotic and mood-related disorders, and that will enable patients to be stratified on a biological basis into more homogeneous clinically distinct subgroups, are urgently needed. The attainment of this goal can be facilitated by identifying biomarkers that accurately reflect pathophysiologic processes in these disorders. This review postulates that the field of psychotic and mood disorder research has advanced sufficiently to develop biochemical hypotheses of the etiopathology of the particular illness and to target the same for more effective disease modifying therapy. This implies that a “one-size fits all” paradigm in the treatment of psychotic and mood disorders is not a viable approach, but that a customized regime based on individual biological abnormalities would pave the way forward to more effective treatment. In reviewing the clinical and preclinical literature, this paper discusses the most highly regarded pathophysiologic processes in mood and psychotic disorders, thereby providing a scaffold for the selection of suitable biomarkers for future studies in this field, to develope biomarker panels, as well as to improve diagnosis and to customize treatment regimens for better therapeutic outcomes. PMID:26411964

Dialectical Behavior Therapy Modified for Adolescent Binge Eating Disorder: A Case Report

ERIC Educational Resources Information Center

Safer, Debra L.; Couturier, Jennifer L.; Lock, James

2007-01-01

Given the lack of empirically supported treatments available for adolescents with eating disorders, it is important to investigate the clinical utility of extending treatments for adults with eating disorders to younger populations. Dialectical behavior therapy for binge eating disorder, based on the affect-regulation model, conceptualizes binge…

Genetic polymorphisms in glutathione-S-transferases are associated with anxiety and mood disorders in nicotine dependence

PubMed Central

Pizzo de Castro, Márcia Regina; Ehara Watanabe, Maria Angelica; Losi Guembarovski, Roberta; Odebrecht Vargas, Heber; Vissoci Reiche, Edna Maria; Kaminami Morimoto, Helena; Dodd, Seetal; Berk, Michael

2014-01-01

Background Nicotine dependence is associated with an increased risk of mood and anxiety disorders and suicide. The primary hypothesis of this study was to identify whether the polymorphisms of two glutathione-S-transferase enzymes (GSTM1 and GSTT1 genes) predict an increased risk of mood and anxiety disorders in smokers with nicotine dependence. Materials and methods Smokers were recruited at the Centre of Treatment for Smokers. The instruments were a sociodemographic questionnaire, Fagerström Test for Nicotine Dependence, diagnoses of mood disorder and nicotine dependence according to DSM-IV (SCID-IV), and the Alcohol, Smoking and Substance Involvement Screening Test. Anxiety disorder was assessed based on the treatment report. Laboratory assessment included glutathione-S-transferases M1 (GSTM1) and T1 (GSTT1), which were detected by a multiplex-PCR protocol. Results Compared with individuals who had both GSTM1 and GSTT1 genes, a higher frequency of at least one deletion of the GSTM1 and GSTT1 genes was identified in anxious smokers [odds ratio (OR)=2.21, 95% confidence interval (CI)=1.05–4.65, P=0.034], but there was no association with bipolar and unipolar depression (P=0.943). Compared with nonanxious smokers, anxious smokers had a greater risk for mood disorders (OR=4.67; 95% CI=2.24–9.92, P<0.001), lung disease (OR=6.78, 95% CI=1.95–23.58, P<0.003), and suicide attempts (OR=17.01, 95% CI=2.23–129.91, P<0.006). Conclusion This study suggests that at least one deletion of the GSTM1 and GSTT1 genes represents a risk factor for anxious smokers. These two genes may modify the capacity for the detoxification potential against oxidative stress. PMID:24637631

Maternal near miss and death among women with severe hypertensive disorders: a Brazilian multicenter surveillance study.

PubMed

Zanette, Elvira; Parpinelli, Mary Angela; Surita, Fernanda Garanhani; Costa, Maria Laura; Haddad, Samira Maerrawi; Sousa, Maria Helena; E Silva, Joao Luiz Pinto; Souza, Joao Paulo; Cecatti, Jose Guilherme

2014-01-16

Hypertensive disorders represent the major cause of maternal morbidity in middle income countries. The main objective of this study was to identify the prevalence and factors associated with severe maternal outcomes in women with severe hypertensive disorders. This was a cross-sectional, multicenter study, including 6706 women with severe hypertensive disorder from 27 maternity hospitals in Brazil. A prospective surveillance of severe maternal morbidity with data collected from medical charts and entered into OpenClinica®, an online system, over a one-year period (2009 to 2010). Women with severe preeclampsia, severe hypertension, eclampsia and HELLP syndrome were included in the study. They were grouped according to outcome in near miss, maternal death and potentially life-threatening condition. Prevalence ratios and 95% confidence intervals adjusted for cluster effect for maternal and perinatal variables and delays in receiving obstetric care were calculated as risk estimates of maternal complications having a severe maternal outcome (near miss or death). Poisson multiple regression analysis was also performed. Severe hypertensive disorders were the main cause of severe maternal morbidity (6706/9555); the prevalence of near miss was 4.2 cases per 1000 live births, there were 8.3 cases of Near Miss to 1 Maternal Death and the mortality index was 10.7% (case fatality). Early onset of the disease and postpartum hemorrhage were independent variables associated with severe maternal outcomes, in addition to acute pulmonary edema, previous heart disease and delays in receiving secondary and tertiary care. In women with severe hypertensive disorders, the current study identified situations independently associated with a severe maternal outcome, which could be modified by interventions in obstetric care and in the healthcare system. Furthermore, the study showed the feasibility of a hospital system for surveillance of severe maternal morbidity.

Recent Advances in Resting-State Electroencephalography Biomarkers for Autism Spectrum Disorder-A Review of Methodological and Clinical Challenges.

PubMed

Heunis, Tosca-Marie; Aldrich, Chris; de Vries, Petrus J

2016-08-01

Electroencephalography (EEG) has been used for almost a century to identify seizure-related disorders in humans, typically through expert interpretation of multichannel recordings. Attempts have been made to quantify EEG through frequency analyses and graphic representations. These "traditional" quantitative EEG analysis methods were limited in their ability to analyze complex and multivariate data and have not been generally accepted in clinical settings. There has been growing interest in identification of novel EEG biomarkers to detect early risk of autism spectrum disorder, to identify clinically meaningful subgroups, and to monitor targeted intervention strategies. Most studies to date have, however, used quantitative EEG approaches, and little is known about the emerging multivariate analytical methods or the robustness of candidate biomarkers in the context of the variability of autism spectrum disorder. Here, we present a targeted review of methodological and clinical challenges in the search for novel resting-state EEG biomarkers for autism spectrum disorder. Three primary novel methodologies are discussed: (1) modified multiscale entropy, (2) coherence analysis, and (3) recurrence quantification analysis. Results suggest that these methods may be able to classify resting-state EEG as "autism spectrum disorder" or "typically developing", but many signal processing questions remain unanswered. We suggest that the move to novel EEG analysis methods is akin to the progress in neuroimaging from visual inspection, through region-of-interest analysis, to whole-brain computational analysis. Novel resting-state EEG biomarkers will have to evaluate a range of potential demographic, clinical, and technical confounders including age, gender, intellectual ability, comorbidity, and medication, before these approaches can be translated into the clinical setting. Copyright © 2016 Elsevier Inc. All rights reserved.

Mental Health Treatment Seeking Among Veteran and Civilian Community College Students.

PubMed

Fortney, John C; Curran, Geoffrey M; Hunt, Justin B; Lu, Liya; Eisenberg, Daniel; Valenstein, Marcia

2017-08-01

A Web-based survey examined treatment seeking among community college students to inform the design of engagement interventions. Veteran and civilian community college students (N=765) were screened for mental disorders and reported perceptions of treatment need, effectiveness, and stigma, as well as service use. Regression analysis identified predictors of pharmacotherapy and psychotherapy use. Of the 511 students who screened positive for a current mental disorder or reported a perceived need for treatment (149 veterans and 362 civilians), 30% reported past-year use of psychotropic medications. Predictors were perceived treatment need (odds ratio [OR]=7.81, p<.001) and the perception that psychotropic medications are effective (OR=3.38, p=.012). Eleven percent of participants reported past-year psychotherapy use, and predictors were a positive screen for posttraumatic stress disorder (OR=2.78, p=.04) and poorer financial status. Modifiable barriers, including perceived need for and effectiveness of treatment, were correlated with pharmacotherapy use and should be targeted by engagement interventions.

Open Trial of Modular Cognitive-Behavioral Therapy in the Treatment of Anxiety Among Late Adolescents with Autism Spectrum Disorder.

PubMed

Wise, Jillian M; Cepeda, Sandra L; Ordaz, D Luis; McBride, Nicole M; Cavitt, Mark A; Howie, Flora R; Scalli, Leanne; Ehrenreich-May, Jill; Wood, Jeffrey J; Lewin, Adam B; Storch, Eric A

2018-05-31

Given the high rates of comorbid anxiety and autism spectrum disorder (ASD) in the adolescent and young adult population, effective treatment protocols to address anxiety symptoms are of importance to help promote greater independence across settings. While research supports the use of cognitive-behavioral therapy (CBT) across younger age groups with ASD, the literature is limited on interventions benefitting adolescents and young adults with comorbid anxiety disorders and ASD. Therefore, this open trial utilized a modified CBT manual for seven participants between the ages of 16 and 20 years, consisting of a 16-week modularized CBT treatment, including psychoeducation, cognitive therapy, and exposure therapy. Measures of anxiety and depression were completed at baseline and post-treatment. Findings demonstrated significant reductions on clinician-rated measures of anxiety. While findings are encouraging, additional studies examining the efficacy of CBT for this population with ASD and clinical anxiety are necessary to further identify beneficial treatment components.

The Modified Checklist for Autism in Toddlers: A Follow-Up Study Investigating the Early Detection of Autism Spectrum Disorders

ERIC Educational Resources Information Center

Kleinman, Jamie M.; Robins, Diana L.; Ventola, Pamela E.; Pandey, Juhi; Boorstein, Hilary C.; Esser, Emma L.; Wilson, Leandra B.; Rosenthal, Michael A.; Sutera, Saasha; Verbalis, Alyssa D.; Barton, Marianne; Hodgson, Sarah; Green, James; Dumont-Mathieu, Thyde; Volkmar, Fred; Chawarska, Katarzyna; Klin, Ami; Fein, Deborah

2008-01-01

Autism spectrum disorders (ASD) often go undetected in toddlers. The Modified Checklist for Autism in Toddlers (M-CHAT) was used to screen 3,793 children aged 16-30 months from low- and high-risk sources; screen positive cases were diagnostically evaluated. Re-screening was performed on 1,416 children aged 42-54 months. Time1 Positive Predictive…

Comparison of independent screens on differentially vulnerable motor neurons reveals alpha-synuclein as a common modifier in motor neuron diseases

PubMed Central

Kaifer, Kevin A.; Osman, Erkan Y.; Carella, Francesco; Tiberi, Ariana; Ross, Jolill; Pennetta, Giuseppa; Lorson, Christian L.

2017-01-01

The term “motor neuron disease” encompasses a spectrum of disorders in which motor neurons are the primary pathological target. However, in both patients and animal models of these diseases, not all motor neurons are equally vulnerable, in that while some motor neurons are lost very early in disease, others remain comparatively intact, even at late stages. This creates a valuable system to investigate the factors that regulate motor neuron vulnerability. In this study, we aim to use this experimental paradigm to identify potential transcriptional modifiers. We have compared the transcriptome of motor neurons from healthy wild-type mice, which are differentially vulnerable in the childhood motor neuron disease Spinal Muscular Atrophy (SMA), and have identified 910 transcriptional changes. We have compared this data set with published microarray data sets on other differentially vulnerable motor neurons. These neurons were differentially vulnerable in the adult onset motor neuron disease Amyotrophic Lateral Sclerosis (ALS), but the screen was performed on the equivalent population of neurons from neurologically normal human, rat and mouse. This cross species comparison has generated a refined list of differentially expressed genes, including CELF5, Col5a2, PGEMN1, SNCA, Stmn1 and HOXa5, alongside a further enrichment for synaptic and axonal transcripts. As an in vivo validation, we demonstrate that the manipulation of a significant number of these transcripts can modify the neurodegenerative phenotype observed in a Drosophila line carrying an ALS causing mutation. Finally, we demonstrate that vector-mediated expression of alpha-synuclein (SNCA), a transcript decreased in selectively vulnerable motor neurons in all four screens, can extend life span, increase weight and decrease neuromuscular junction pathology in a mouse model of SMA. In summary, we have combined multiple data sets to identify transcripts, which are strong candidates for being phenotypic modifiers, and demonstrated SNCA is a modifier of pathology in motor neuron disease. PMID:28362802

Comparison of independent screens on differentially vulnerable motor neurons reveals alpha-synuclein as a common modifier in motor neuron diseases.

PubMed

Kline, Rachel A; Kaifer, Kevin A; Osman, Erkan Y; Carella, Francesco; Tiberi, Ariana; Ross, Jolill; Pennetta, Giuseppa; Lorson, Christian L; Murray, Lyndsay M

2017-03-01

The term "motor neuron disease" encompasses a spectrum of disorders in which motor neurons are the primary pathological target. However, in both patients and animal models of these diseases, not all motor neurons are equally vulnerable, in that while some motor neurons are lost very early in disease, others remain comparatively intact, even at late stages. This creates a valuable system to investigate the factors that regulate motor neuron vulnerability. In this study, we aim to use this experimental paradigm to identify potential transcriptional modifiers. We have compared the transcriptome of motor neurons from healthy wild-type mice, which are differentially vulnerable in the childhood motor neuron disease Spinal Muscular Atrophy (SMA), and have identified 910 transcriptional changes. We have compared this data set with published microarray data sets on other differentially vulnerable motor neurons. These neurons were differentially vulnerable in the adult onset motor neuron disease Amyotrophic Lateral Sclerosis (ALS), but the screen was performed on the equivalent population of neurons from neurologically normal human, rat and mouse. This cross species comparison has generated a refined list of differentially expressed genes, including CELF5, Col5a2, PGEMN1, SNCA, Stmn1 and HOXa5, alongside a further enrichment for synaptic and axonal transcripts. As an in vivo validation, we demonstrate that the manipulation of a significant number of these transcripts can modify the neurodegenerative phenotype observed in a Drosophila line carrying an ALS causing mutation. Finally, we demonstrate that vector-mediated expression of alpha-synuclein (SNCA), a transcript decreased in selectively vulnerable motor neurons in all four screens, can extend life span, increase weight and decrease neuromuscular junction pathology in a mouse model of SMA. In summary, we have combined multiple data sets to identify transcripts, which are strong candidates for being phenotypic modifiers, and demonstrated SNCA is a modifier of pathology in motor neuron disease.

The Menkes and Wilson disease genes counteract in copper toxicosis in Labrador retrievers: a new canine model for copper-metabolism disorders

PubMed Central

Fieten, Hille; Gill, Yadvinder; Martin, Alan J.; Concilli, Mafalda; Dirksen, Karen; van Steenbeek, Frank G.; Spee, Bart; van den Ingh, Ted S. G. A. M.; Martens, Ellen C. C. P.; Festa, Paola; Chesi, Giancarlo; van de Sluis, Bart; Houwen, Roderick H. J. H.; Watson, Adrian L.; Aulchenko, Yurii S.; Hodgkinson, Victoria L.; Zhu, Sha; Petris, Michael J.; Polishchuk, Roman S.; Leegwater, Peter A. J.; Rothuizen, Jan

2016-01-01

ABSTRACT The deleterious effects of a disrupted copper metabolism are illustrated by hereditary diseases caused by mutations in the genes coding for the copper transporters ATP7A and ATP7B. Menkes disease, involving ATP7A, is a fatal neurodegenerative disorder of copper deficiency. Mutations in ATP7B lead to Wilson disease, which is characterized by a predominantly hepatic copper accumulation. The low incidence and the phenotypic variability of human copper toxicosis hamper identification of causal genes or modifier genes involved in the disease pathogenesis. The Labrador retriever was recently characterized as a new canine model for copper toxicosis. Purebred dogs have reduced genetic variability, which facilitates identification of genes involved in complex heritable traits that might influence phenotype in both humans and dogs. We performed a genome-wide association study in 235 Labrador retrievers and identified two chromosome regions containing ATP7A and ATP7B that were associated with variation in hepatic copper levels. DNA sequence analysis identified missense mutations in each gene. The amino acid substitution ATP7B:p.Arg1453Gln was associated with copper accumulation, whereas the amino acid substitution ATP7A:p.Thr327Ile partly protected against copper accumulation. Confocal microscopy indicated that aberrant copper metabolism upon expression of the ATP7B variant occurred because of mis-localization of the protein in the endoplasmic reticulum. Dermal fibroblasts derived from ATP7A:p.Thr327Ile dogs showed copper accumulation and delayed excretion. We identified the Labrador retriever as the first natural, non-rodent model for ATP7B-associated copper toxicosis. Attenuation of copper accumulation by the ATP7A mutation sheds an interesting light on the interplay of copper transporters in body copper homeostasis and warrants a thorough investigation of ATP7A as a modifier gene in copper-metabolism disorders. The identification of two new functional variants in ATP7A and ATP7B contributes to the biological understanding of protein function, with relevance for future development of therapy. PMID:26747866

The modified gait abnormality rating scale in patients with a conversion disorder: a reliability and responsiveness study.

PubMed

Vandenberg, Justin M; George, Deanna R; O'Leary, Andrea J; Olson, Lindsay C; Strassburg, Kaitlyn R; Hollman, John H

2015-01-01

Individuals with conversion disorder have neurologic symptoms that are not identified by an underlying organic cause. Often the symptoms manifest as gait disturbances. The modified gait abnormality rating scale (GARS-M) may be useful for quantifying gait abnormalities in these individuals. The purpose of this study was to examine the reliability, responsiveness and concurrent validity of GARS-M scores in individuals with conversion disorder. Data from 27 individuals who completed a rehabilitation program were included in this study. Pre- and post-intervention videos were obtained and walking speed was measured. Five examiners independently evaluated gait performance according to the GARS-M criteria. Inter- and intrarater reliability of GARS-M scores were estimated with intraclass correlation coefficients (ICCs). Responsiveness was estimated with the minimum detectable change (MDC). Pre- to post-treatment changes in GARS-M scores were analyzed with a dependent t-test. The correlation between GARS-M scores and walking speed was analyzed to assess concurrent validity. GARS-M scores were quantified with good-to-excellent inter- (ICC = 0.878) and intrarater reliability (ICC = 0.989). The MDC was 2 points. Mean GARS-M scores decreased from 7 ± 5 at baseline to 1 ± 2 at discharge (t26 = 7.411, p < 0.001) and 85% of patients improved beyond the MDC. Furthermore, GARS-M scores and walking speed measurements were moderately correlated (r = -0.582, p = 0.004), indicating that the GARS-M has acceptable concurrent validity. Our findings provide evidence that the GARS-M scores are reliable, valid and responsive for quantifying gait abnormalities in patients with conversion disorder. GARS-M scores provide objective measures upon which treatment effects can be assessed. Copyright © 2014 Elsevier B.V. All rights reserved.

Advances in urea cycle neuroimaging: Proceedings from the 4th International Symposium on urea cycle disorders, Barcelona, Spain, September 2013.

PubMed

Pacheco-Colón, Ileana; Fricke, Stanley; VanMeter, John; Gropman, Andrea L

2014-01-01

Our previous imaging research performed as part of a Urea Cycle Rare Disorders Consortium (UCRDC) grant, has identified specific biomarkers of neurologic injury in ornithine transcarbamylase deficiency, OTCD. While characterization of mutations can be achieved in most cases, this information does not necessarily predict the severity of the underlying neurological syndrome. The biochemical consequences of any mutation may be modified additionally by a large number of factors, including contributions of other enzymes and transport systems that mediate flux through the urea cycle, diet and other environmental factors. These factors likely vary from one patient to another, and they give rise to heterogeneity of clinical severity. Affected cognitive domains include non-verbal learning, fine motor processing, reaction time, visual memory, attention, and executive function. Deficits in these capacities may be seen in symptomatic patients, as well as asymptomatic carriers with normal IQ and correlate with variances in brain structure and function in these patients. Using neuroimaging we can identify biomarkers that reflect the downstream impact of UCDs on cognition. This manuscript is a summary of the presentation from the 4th International Consortium on urea cycle disorders held in, Barcelona, Spain, September 2, 2014. Copyright © 2014 Elsevier Inc. All rights reserved.

Use of Abstracts, Orientations, and Codas in Narration by Language-Disordered and Nondisordered Children.

ERIC Educational Resources Information Center

Sleight, Christine C.; Prinz, Philip M.

1985-01-01

Forty language-disordered and nondisordered elementary children viewed a nonverbal film, wrote the story, and narrated it to language-disordered and nondisordered peers unfamiliar with the film. Language-disordered Ss made fewer references to the orientation clauses of props and activities than nondisordered Ss. Neither group modified their…

Genetic and functional analyses of SHANK2 mutations suggest a multiple hit model of autism spectrum disorders.

PubMed

Leblond, Claire S; Heinrich, Jutta; Delorme, Richard; Proepper, Christian; Betancur, Catalina; Huguet, Guillaume; Konyukh, Marina; Chaste, Pauline; Ey, Elodie; Rastam, Maria; Anckarsäter, Henrik; Nygren, Gudrun; Gillberg, I Carina; Melke, Jonas; Toro, Roberto; Regnault, Beatrice; Fauchereau, Fabien; Mercati, Oriane; Lemière, Nathalie; Skuse, David; Poot, Martin; Holt, Richard; Monaco, Anthony P; Järvelä, Irma; Kantojärvi, Katri; Vanhala, Raija; Curran, Sarah; Collier, David A; Bolton, Patrick; Chiocchetti, Andreas; Klauck, Sabine M; Poustka, Fritz; Freitag, Christine M; Waltes, Regina; Kopp, Marnie; Duketis, Eftichia; Bacchelli, Elena; Minopoli, Fiorella; Ruta, Liliana; Battaglia, Agatino; Mazzone, Luigi; Maestrini, Elena; Sequeira, Ana F; Oliveira, Barbara; Vicente, Astrid; Oliveira, Guiomar; Pinto, Dalila; Scherer, Stephen W; Zelenika, Diana; Delepine, Marc; Lathrop, Mark; Bonneau, Dominique; Guinchat, Vincent; Devillard, Françoise; Assouline, Brigitte; Mouren, Marie-Christine; Leboyer, Marion; Gillberg, Christopher; Boeckers, Tobias M; Bourgeron, Thomas

2012-02-01

Autism spectrum disorders (ASD) are a heterogeneous group of neurodevelopmental disorders with a complex inheritance pattern. While many rare variants in synaptic proteins have been identified in patients with ASD, little is known about their effects at the synapse and their interactions with other genetic variations. Here, following the discovery of two de novo SHANK2 deletions by the Autism Genome Project, we identified a novel 421 kb de novo SHANK2 deletion in a patient with autism. We then sequenced SHANK2 in 455 patients with ASD and 431 controls and integrated these results with those reported by Berkel et al. 2010 (n = 396 patients and n = 659 controls). We observed a significant enrichment of variants affecting conserved amino acids in 29 of 851 (3.4%) patients and in 16 of 1,090 (1.5%) controls (P = 0.004, OR = 2.37, 95% CI = 1.23-4.70). In neuronal cell cultures, the variants identified in patients were associated with a reduced synaptic density at dendrites compared to the variants only detected in controls (P = 0.0013). Interestingly, the three patients with de novo SHANK2 deletions also carried inherited CNVs at 15q11-q13 previously associated with neuropsychiatric disorders. In two cases, the nicotinic receptor CHRNA7 was duplicated and in one case the synaptic translation repressor CYFIP1 was deleted. These results strengthen the role of synaptic gene dysfunction in ASD but also highlight the presence of putative modifier genes, which is in keeping with the "multiple hit model" for ASD. A better knowledge of these genetic interactions will be necessary to understand the complex inheritance pattern of ASD.

Genetic and Functional Analyses of SHANK2 Mutations Suggest a Multiple Hit Model of Autism Spectrum Disorders

PubMed Central

Leblond, Claire S.; Heinrich, Jutta; Delorme, Richard; Proepper, Christian; Betancur, Catalina; Huguet, Guillaume; Konyukh, Marina; Chaste, Pauline; Ey, Elodie; Rastam, Maria; Anckarsäter, Henrik; Nygren, Gudrun; Gillberg, I. Carina; Melke, Jonas; Toro, Roberto; Regnault, Beatrice; Fauchereau, Fabien; Mercati, Oriane; Lemière, Nathalie; Skuse, David; Poot, Martin; Holt, Richard; Monaco, Anthony P.; Järvelä, Irma; Kantojärvi, Katri; Vanhala, Raija; Curran, Sarah; Collier, David A.; Bolton, Patrick; Chiocchetti, Andreas; Klauck, Sabine M.; Poustka, Fritz; Freitag, Christine M.; Waltes, Regina; Kopp, Marnie; Duketis, Eftichia; Bacchelli, Elena; Minopoli, Fiorella; Ruta, Liliana; Battaglia, Agatino; Mazzone, Luigi; Maestrini, Elena; Sequeira, Ana F.; Oliveira, Barbara; Vicente, Astrid; Oliveira, Guiomar; Pinto, Dalila; Scherer, Stephen W.; Zelenika, Diana; Delepine, Marc; Lathrop, Mark; Bonneau, Dominique; Guinchat, Vincent; Devillard, Françoise; Assouline, Brigitte; Mouren, Marie-Christine; Leboyer, Marion; Gillberg, Christopher; Boeckers, Tobias M.; Bourgeron, Thomas

2012-01-01

Autism spectrum disorders (ASD) are a heterogeneous group of neurodevelopmental disorders with a complex inheritance pattern. While many rare variants in synaptic proteins have been identified in patients with ASD, little is known about their effects at the synapse and their interactions with other genetic variations. Here, following the discovery of two de novo SHANK2 deletions by the Autism Genome Project, we identified a novel 421 kb de novo SHANK2 deletion in a patient with autism. We then sequenced SHANK2 in 455 patients with ASD and 431 controls and integrated these results with those reported by Berkel et al. 2010 (n = 396 patients and n = 659 controls). We observed a significant enrichment of variants affecting conserved amino acids in 29 of 851 (3.4%) patients and in 16 of 1,090 (1.5%) controls (P = 0.004, OR = 2.37, 95% CI = 1.23–4.70). In neuronal cell cultures, the variants identified in patients were associated with a reduced synaptic density at dendrites compared to the variants only detected in controls (P = 0.0013). Interestingly, the three patients with de novo SHANK2 deletions also carried inherited CNVs at 15q11–q13 previously associated with neuropsychiatric disorders. In two cases, the nicotinic receptor CHRNA7 was duplicated and in one case the synaptic translation repressor CYFIP1 was deleted. These results strengthen the role of synaptic gene dysfunction in ASD but also highlight the presence of putative modifier genes, which is in keeping with the “multiple hit model” for ASD. A better knowledge of these genetic interactions will be necessary to understand the complex inheritance pattern of ASD. PMID:22346768

Conducting preference assessments for youth with disorders of consciousness during rehabilitation.

PubMed

Amari, Adrianna; Suskauer, Stacy J; Paasch, Valerie; Grodin, Lauren K; Slomine, Beth S

2017-08-01

Care and rehabilitation for individuals with disorders of consciousness (DOC) can be challenging; the use of observational data collection, individualized treatment programs, and incorporation of preferred, personally meaningful and salient items may be helpful in addressing such challenges during assessment and intervention. In this article, we extend the predominantly adult literature on use of salient items to promote differential responding by describing our methodology to identify preferred items across sensory domains for application during inpatient rehabilitation with children with DOC. Details on the indirect and direct preference assessment procedures rooted in applied behavior analysis that we have tailored for this population are provided. We describe steps of the procedures, including structured caregiver interview, staff survey, item inclusion, in vivo single-item stimulus preference assessment, and treatment. Clinical case examples further illustrate implementation of our methodology, observed response topographies, individually identified preferred items, and their application for 3 children in a minimally conscious state. In addition, we introduce a new structured caregiver interview, the Preference Assessment for Youth with Disorders of Consciousness (PAYDOC), modeled on the Reinforcer Assessment for Individuals with Severe Disabilities (RAISD; Fisher, Piazza, Bowman, & Amari, 1996) and modified to be appropriate for future use as a clinical tool to enhance assessment of preferences with this pediatric brain injury population. This methodology can be used to identify highly idiosyncratic stimuli that can be incorporated in multiple ways throughout rehabilitation to optimize care for youth with DOC. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

Genome-wide association and linkage identify modifier loci of lung disease severity in cystic fibrosis at 11p13 and 20q13.2

PubMed Central

Wright, Fred A.; Strug, Lisa J.; Doshi, Vishal K.; Commander, Clayton W.; Blackman, Scott M.; Sun, Lei; Berthiaume, Yves; Cutler, David; Cojocaru, Andreea; Collaco, J. Michael; Corey, Mary; Dorfman, Ruslan; Goddard, Katrina; Green, Deanna; Kent, Jack W.; Lange, Ethan M.; Lee, Seunggeun; Li, Weili; Luo, Jingchun; Mayhew, Gregory M.; Naughton, Kathleen M.; Pace, Rhonda G.; Paré, Peter; Rommens, Johanna M.; Sandford, Andrew; Stonebraker, Jaclyn R.; Sun, Wei; Taylor, Chelsea; Vanscoy, Lori L.; Zou, Fei; Blangero, John; Zielenski, Julian; O’Neal, Wanda K.; Drumm, Mitchell L.; Durie, Peter R.; Knowles, Michael R.; Cutting, Garry R.

2012-01-01

A combined genome-wide association and linkage study was used to identify loci causing variation in CF lung disease severity. A significant association (P=3. 34 × 10-8) near EHF and APIP (chr11p13) was identified in F508del homozygotes (n=1,978). The association replicated in F508del homozygotes (P=0.006) from a separate family-based study (n=557), with P=1.49 × 10-9 for the three-study joint meta-analysis. Linkage analysis of 486 sibling pairs from the family-based study identified a significant QTL on chromosome 20q13.2 (LOD=5.03). Our findings provide insight into the causes of variation in lung disease severity in CF and suggest new therapeutic targets for this life-limiting disorder. PMID:21602797

Changes in Muscle Metabolism are Associated with Phenotypic Variability in Golden Retriever Muscular Dystrophy




PubMed Central

Nghiem, Peter P.; Bello, Luca; Stoughton, William B.; López, Sara Mata; Vidal, Alexander H.; Hernandez, Briana V.; Hulbert, Katherine N.; Gourley, Taylor R.; Bettis, Amanda K.; Balog-Alvarez, Cynthia J.; Heath-Barnett, Heather; Kornegay, Joe N.

2017-01-01

Duchenne muscular dystrophy (DMD) is an X-chromosome-linked disorder and the most common monogenic disease in people. Affected boys are diagnosed at a young age, become non-ambulatory by their early teens, and succumb to cardiorespiratory failure by their thirties. Despite being a monogenic condition resulting from mutations in the DMD gene, affected boys have noteworthy phenotypic variability. Efforts have identified genetic modifiers that could modify disease progression and be pharmacologic targets. Dogs affected with golden retriever muscular dystrophy (GRMD) have absent dystrophin and demonstrate phenotypic variability at the functional, histopathological, and molecular level. Our laboratory is particularly interested in muscle metabolism changes in dystrophin-deficient muscle. We identified several metabolic alterations, including myofiber type switching from fast (type II) to slow (type I), reduced glycolytic enzyme expression, reduced and morphologically abnormal mitochondria, and differential AMP-kinase phosphorylation (activation) between hypertrophied and wasted muscle. We hypothesize that muscle metabolism changes are, in part, responsible for phenotypic variability in GRMD. Pharmacological therapies aimed at modulating muscle metabolism can be tested in GRMD dogs for efficacy. PMID:28955176

Scavenger Receptors: Emerging Roles in Cancer Biology and Immunology

PubMed Central

Yu, Xiaofei; Guo, Chunqing; Fisher, Paul B.; Subjeck, John R.; Wang, Xiang-Yang

2015-01-01

Scavenger receptors constitute a large family of evolutionally conserved protein molecules that are structurally and functionally diverse. Although scavenger receptors were originally identified based on their capacity to scavenge modified lipoproteins, these molecules have been shown to recognize and bind to a broad spectrum of ligands, including modified and unmodified host-derived molecules or microbial components. As a major subset of innate pattern recognition receptors, scavenger receptors are mainly expressed on myeloid cells and function in a wide range of biological processes, such as endocytosis, adhesion, lipid transport, antigen presentation, and pathogen clearance. In addition to playing a crucial role in maintenance of host homeostasis, scavenger receptors have been implicated in the pathogenesis of a number of diseases, e.g., atherosclerosis, neurodegeneration, or metabolic disorders. Emerging evidence has begun to reveal these receptor molecules as important regulators of tumor behavior and host immune responses to cancer. This review summarizes our current understanding on the newly identified, distinct functions of scavenger receptors in cancer biology and immunology. The potential of scavenger receptors as diagnostic biomarkers and novel targets for therapeutic interventions to treat malignancies is also highlighted. PMID:26216637

The Autism Diagnostic Observation Schedule--Toddler Module: A New Module of a Standardized Diagnostic Measure for Autism Spectrum Disorders

ERIC Educational Resources Information Center

Luyster, Rhiannon; Gotham, Katherine; Guthrie, Whitney; Coffing, Mia; Petrak, Rachel; Pierce, Karen; Bishop, Somer; Esler, Amy; Hus, Vanessa; Oti, Rosalind; Richler, Jennifer; Risi, Susan; Lord, Catherine

2009-01-01

The Autism Diagnostic Observation Schedule (ADOS; Lord et al., J Autism Dev Disord, 30(3):205-223, 2000) is widely accepted as a "gold standard" diagnostic instrument, but it is of restricted utility with very young children. The purpose of the current project was to modify the ADOS for use in children under 30 months of age. A modified ADOS, the…

Post-traumatic stress disorder diagnosis in children: challenges and promises

PubMed Central

Cohen, Judith A.; Scheeringa, Michael S.

2009-01-01

Children and adolescents experience high rates of potentially traumatic experiences. Many children subsequently develop mental health problems, including post-traumatic stress disorder (PTSD) symptoms. Accurately diagnosing PTSD in children is challenging. This paper reviews the following important issues: (i) the specificity of the PTSD diagnosis; (ii) children who are symptomatic and impaired but do not have enough symptoms for the diagnosis of PTSD; (iii) developmental considerations for preschool and schooi-age children; and (iv) a variety of assessment challenges that reflect the difficulty and complexity of interviewing children and caregivers about these symptoms. Despite these challenges, PTSD remains the best construct for clinical and research work with trauma survivors. Pediatric PTSD criteria are valuable for identifying children at risk and in need of treatment and can be even more helpful when developmentally modified in ways that are discussed. PMID:19432391

Modified crisis intervention for personality disorder.

PubMed

Rudnick, A

1998-01-01

This study proposes that the goal of crisis intervention for persons with personality disorders should be to return them to their pre-crisis level of functioning, even though this is maladaptive. This is contrasted with standard crisis intervention, which aims to return normal or neurotic persons to their pre-crisis normal or neurotic functioning, usually by means of few and short-term therapeutic encounters. The modification proposed costs more time and resources in persons with personality disorders in crisis and fits the intervention to the personality type. This is illustrated by the case of Eve, a patient in crisis, whose pre-crisis functioning was maladaptive because of a dependent personality disorder. The goal of (modified) crisis intervention in this case was to return the patient to her dependent lifestyle, by means of pharmacotherapy combined with intensive supportive psychotherapy during 3-4 months of partial (day) hospitalization. The special nature of crisis in personality disorders is discussed.

Mechanisms to medicines: elucidating neural and molecular substrates of fear extinction to identify novel treatments for anxiety disorders

PubMed Central

Bukalo, Olena; Pinard, Courtney R; Holmes, Andrew

2014-01-01

The burden of anxiety disorders is growing, but the efficacy of available anxiolytic treatments remains inadequate. Cognitive behavioural therapy for anxiety disorders focuses on identifying and modifying maladaptive patterns of thinking and behaving, and has a testable analogue in rodents in the form of fear extinction. A large preclinical literature has amassed in recent years describing the neural and molecular basis of fear extinction in rodents. In this review, we discuss how this work is being harnessed to foster translational research on anxiety disorders and facilitate the search for new anxiolytic treatments. We begin by summarizing the anatomical and functional connectivity of a medial prefrontal cortex (mPFC)–amygdala circuit that subserves fear extinction, including new insights from optogenetics. We then cover some of the approaches that have been taken to model impaired fear extinction and associated impairments with mPFC–amygdala dysfunction. The principal goal of the review is to evaluate evidence that various neurotransmitter and neuromodulator systems mediate fear extinction by modulating the mPFC–amygdala circuitry. To that end, we describe studies that have tested how fear extinction is impaired or facilitated by pharmacological manipulations of dopamine, noradrenaline, 5-HT, GABA, glutamate, neuropeptides, endocannabinoids and various other systems, which either directly target the mPFC–amygdala circuit, or produce behavioural effects that are coincident with functional changes in the circuit. We conclude that there are good grounds to be optimistic that the progress in defining the molecular substrates of mPFC–amygdala circuit function can be effectively leveraged to identify plausible candidates for extinction-promoting therapies for anxiety disorders. Linked Articles This article is part of a themed section on Animal Models in Psychiatry Research. To view the other articles in this section visit http://dx.doi.org/10.1111/bph.2014.171.issue-20 PMID:24835117

Monogenic Mouse Models of Autism Spectrum Disorders: Common Mechanisms and Missing Links

PubMed Central

Hulbert, Samuel W.; Jiang, Yong-hui

2016-01-01

Autism Spectrum Disorders (ASDs) present unique challenges in the fields of genetics and neurobiology because of the clinical and molecular heterogeneity underlying these disorders. Genetic mutations found in ASD patients provide opportunities to dissect the molecular and circuit mechanisms underlying autistic behaviors using animal models. Ongoing studies of genetically modified models have offered critical insight into possible common mechanisms arising from different mutations, but links between molecular abnormalities and behavioral phenotypes remain elusive. The challenges encountered in modeling autism in mice demand a new analytic paradigm that integrates behavioral analysis with circuit-level analysis in genetically modified models with strong construct validity. PMID:26733386

Modified Therapeutic Community Treatment for Offenders with MICA Disorders: Antisocial Personality Disorder and Treatment Outcomes

ERIC Educational Resources Information Center

McKendrick, Karen; Sullivan, Christopher; Banks, Steven; Sacks, Stanley

2006-01-01

Treatment outcomes 1 year after release from prison were compared for two subgroups of male inmates with co-occurring serious mental illness and chemical abuse (MICA) disorders, those with a diagnosis for Antisocial Personality Disorder (APD), and those without a diagnosis of APD. The foundation study had randomly assigned inmates to either…

Mutations in the DNA methyltransferase gene DNMT3A cause an overgrowth syndrome with intellectual disability.

PubMed

Tatton-Brown, Katrina; Seal, Sheila; Ruark, Elise; Harmer, Jenny; Ramsay, Emma; Del Vecchio Duarte, Silvana; Zachariou, Anna; Hanks, Sandra; O'Brien, Eleanor; Aksglaede, Lise; Baralle, Diana; Dabir, Tabib; Gener, Blanca; Goudie, David; Homfray, Tessa; Kumar, Ajith; Pilz, Daniela T; Selicorni, Angelo; Temple, I Karen; Van Maldergem, Lionel; Yachelevich, Naomi; van Montfort, Robert; Rahman, Nazneen

2014-04-01

Overgrowth disorders are a heterogeneous group of conditions characterized by increased growth parameters and other variable clinical features such as intellectual disability and facial dysmorphism. To identify new causes of human overgrowth, we performed exome sequencing in ten proband-parent trios and detected two de novo DNMT3A mutations. We identified 11 additional de novo mutations by sequencing DNMT3A in a further 142 individuals with overgrowth. The mutations alter residues in functional DNMT3A domains, and protein modeling suggests that they interfere with domain-domain interactions and histone binding. Similar mutations were not present in 1,000 UK population controls (13/152 cases versus 0/1,000 controls; P < 0.0001). Mutation carriers had a distinctive facial appearance, intellectual disability and greater height. DNMT3A encodes a DNA methyltransferase essential for establishing methylation during embryogenesis and is commonly somatically mutated in acute myeloid leukemia. Thus, DNMT3A joins an emerging group of epigenetic DNA- and histone-modifying genes associated with both developmental growth disorders and hematological malignancies.

Mutations in the DNA methyltransferase gene, DNMT3A, cause an overgrowth syndrome with intellectual disability

PubMed Central

Tatton-Brown, Katrina; Seal, Sheila; Ruark, Elise; Harmer, Jenny; Ramsay, Emma; del Vecchio Duarte, Silvana; Zachariou, Anna; Hanks, Sandra; O’Brien, Eleanor; Aksglaede, Lise; Baralle, Diana; Dabir, Tabib; Gener, Blanca; Goudie, David; Homfray, Tessa; Kumar, Ajith; Pilz, Daniela T; Selicorni, Angelo; Temple, I Karen; Van Maldergem, Lionel; Yachelevich, Naomi; van Montfort, Robert; Rahman, Nazneen

2014-01-01

Overgrowth disorders are a heterogeneous group of conditions characterised by increased growth parameters and variable other clinical features, such as intellectual disability and facial dysmorphism1. To identify novel causes of human overgrowth we performed exome sequencing in 10 proband-parent trios and detected two de novo DNMT3A mutations. We identified 11 additional de novo mutations through DNMT3A sequencing of a further 142 individuals with overgrowth. The mutations were all located in functional DNMT3A domains and protein modelling suggests they interfere with domain-domain interactions and histone binding. No similar mutations were present in 1000 UK population controls (13/152 vs 0/1000; P<0.0001). Mutation carriers had a distinctive facial appearance, intellectual disability and increased height. DNMT3A encodes a key methyltransferase essential for establishing the methylation imprint in embryogenesis and is commonly somatically mutated in acute myeloid leukaemia2-4. Thus DNMT3A joins an emerging group of epigenetic DNA and histone modifying genes associated with both developmental growth disorders and haematological malignancies5. PMID:24614070

Current Update on Synopsis of miRNA Dysregulation in Neurological Disorders

PubMed Central

Kamal, Mohammad A.; Mushtaq, Gohar; Greig, Nigel H.

2018-01-01

Aberrant expression of microRNAs (miRNAs) has been implicated in various neurological disorders (NDs) of the central nervous system such as Alzheimer disease, Parkinson’s disease, Huntington disease, amyotrophic lateral sclerosis, schizophrenia and autism. If dysregulated miRNAs are identified in patients suffering from NDs, this may serve as a biomarker for the earlier diagnosis and monitoring of disease progression. Identifying the role of miRNAs in normal cellular processes and understanding how dysregulated miRNA expression is responsible for their neurological effects is also critical in the development of new therapeutic strategies for NDs. miRNAs hold great promise from a therapeutic point of view especially if it can be proved that a single miRNA has the ability to influence several target genes, making it possible for the researchers to potentially modify a whole disease phenotype by modulating a single miRNA molecule. Hence, better understanding of the mechanisms by which miRNA play a role in the pathogenesis of NDs may provide novel targets to scientists and researchers for innovative therapies. PMID:25714967

Conformational entropic maps of functional coupling domains in GPCR activation: A case study with beta2 adrenergic receptor

NASA Astrophysics Data System (ADS)

Liu, Fan; Abrol, Ravinder; Goddard, William, III; Dougherty, Dennis

2014-03-01

Entropic effect in GPCR activation is poorly understood. Based on the recent solved structures, researchers in the GPCR structural biology field have proposed several ``local activating switches'' that consisted of a few number of conserved residues, but have long ignored the collective dynamical effect (conformational entropy) of a domain comprised of an ensemble of residues. A new paradigm has been proposed recently that a GPCR can be viewed as a composition of several functional coupling domains, each of which undergoes order-to-disorder or disorder-to-order transitions upon activation. Here we identified and studied these functional coupling domains by comparing the local entropy changes of each residue between the inactive and active states of the β2 adrenergic receptor from computational simulation. We found that agonist and G-protein binding increases the heterogeneity of the entropy distribution in the receptor. This new activation paradigm and computational entropy analysis scheme provides novel ways to design functionally modified mutant and identify new allosteric sites for GPCRs. The authors thank NIH and Sanofi for funding this project.

Annual research review: Rare genotypes and childhood psychopathology--uncovering diverse developmental mechanisms of ADHD risk.

PubMed

Scerif, Gaia; Baker, Kate

2015-03-01

Through the increased availability and sophistication of genetic testing, it is now possible to identify causal diagnoses in a growing proportion of children with neurodevelopmental disorders. In addition to developmental delay and intellectual disability, many genetic disorders are associated with high risks of psychopathology, which curtail the wellbeing of affected individuals and their families. Beyond the identification of significant clinical needs, understanding the diverse pathways from rare genetic mutations to cognitive dysfunction and emotional-behavioural disturbance has theoretical and practical utility. We overview (based on a strategic search of the literature) the state-of-the-art on causal mechanisms leading to one of the most common childhood behavioural diagnoses - attention deficit hyperactivity disorder (ADHD) - in the context of specific genetic disorders. We focus on new insights emerging from the mapping of causal pathways from identified genetic differences to neuronal biology, brain abnormalities, cognitive processing differences and ultimately behavioural symptoms of ADHD. First, ADHD research in the context of rare genotypes highlights the complexity of multilevel mechanisms contributing to psychopathology risk. Second, comparisons between genetic disorders associated with similar psychopathology risks can elucidate convergent or distinct mechanisms at each level of analysis, which may inform therapeutic interventions and prognosis. Third, genetic disorders provide an unparalleled opportunity to observe dynamic developmental interactions between neurocognitive risk and behavioural symptoms. Fourth, variation in expression of psychopathology risk within each genetic disorder points to putative moderating and protective factors within the genome and the environment. A common imperative emerging within psychopathology research is the need to investigate mechanistically how developmental trajectories converge or diverge between and within genotype-defined groups. Crucially, as genetic predispositions modify interaction dynamics from the outset, longitudinal research is required to understand the multi-level developmental processes that mediate symptom evolution. © 2014 Association for Child and Adolescent Mental Health.

Does Gender Influence Electroconvulsive Therapy Sessions Required across Psychiatric Diagnoses? A 5-Year Experience from a Single Center

PubMed Central

Manohar, Harshini; Subramanian, Karthick; Menon, Vikas; Kattimani, Shivanand

2017-01-01

Context: There is a paucity of systematic data reflecting the practice of electroconvulsive therapy (ECT) from developing countries. Aim: We aimed to identify the number of ECT sessions required to yield response and gender diffeferences in the number of sessions across various diagnostic categories. Setting and Design: A record-based study from a teaching cum tertiary care hospital in South India. Subjects and Methods: Case records of patients who received modified ECT from January 2011 to January 2016 were reviewed. The sociodemographic details and ECT-related data were collected. Psychiatric diagnoses were ascertained as per the International Classification of Diseases, 10th Revision criteria. Statistical Analysis Used: Kruskal–Wallis test and Mann–Whitney U-test. Results: Among 148 patients, 82 (55.4%) had mood disorder (bipolar disorder and recurrent depressive disorder), 43 (29.1%) had schizophrenia, and 22 (14.9%) had other acute and transient psychotic disorders (ATPDs). Patients with mood disorders, schizophrenia, and other ATPD received 7.3 (± 3.8), 9.7 (± 6.1), and 5.4 (± 2.0) ECT sessions, respectively, to achieve response. There was no gender difference in the number of sessions received. Conclusion: Our findings show that number of ECT sessions required to yield response may be disorder-specific. Gender does not influence the ECT dose requirement. Variations in ECT parameters across settings may limit the generalizability of results. PMID:28694625

A systematic review of alcohol use and sexual risk-taking in Latin America

PubMed Central

Vagenas, Panagiotis; Lama, Javier R.; Ludford, Kaysia T.; Gonzales, Pedro; Sanchez, Jorge; Altice, Frederick L.

2014-01-01

Objective To provide an account of published literature on the association between alcohol use and sexual risk-taking, focusing on Latin America. Methods A search of MEDLINE, Embase, Web of Science, LILACS, and Cochrane databases identified 561 unique articles. After excluding those that were not directly relevant, 30 studies were retained for review. Results Twenty-seven studies showed direct or indirect associations between alcohol abuse and unprotected/risky sex. Three studies, however, showed no association between these variables, suggesting that the public health message of safer sex may have been effective. Conclusions Further research is needed to identify factors and behaviors that could be modified to reduce the association between alcohol use disorders and risky sexual behavior. PMID:24301738

Multifunctional roles of enolase in Alzheimer's disease brain: beyond altered glucose metabolism.

PubMed

Butterfield, D Allan; Lange, Miranda L Bader

2009-11-01

Enolase enzymes are abundantly expressed, cytosolic carbon-oxygen lyases known for their role in glucose metabolism. Recently, enolase has been shown to possess a variety of different regulatory functions, beyond glycolysis and gluconeogenesis, associated with hypoxia, ischemia, and Alzheimer's disease (AD). AD is an age-associated neurodegenerative disorder characterized pathologically by elevated oxidative stress and subsequent damage to proteins, lipids, and nucleic acids, appearance of neurofibrillary tangles and senile plaques, and loss of synapse and neuronal cells. It is unclear if development of a hypometabolic environment is a consequence of or contributes to AD pathology, as there is not only a significant decline in brain glucose levels in AD, but also there is an increase in proteomics identified oxidatively modified glycolytic enzymes that are rendered inactive, including enolase. Previously, our laboratory identified alpha-enolase as one the most frequently up-regulated and oxidatively modified proteins in amnestic mild cognitive impairment (MCI), early-onset AD, and AD. However, the glycolytic conversion of 2-phosphoglycerate to phosphoenolpyruvate catalyzed by enolase does not directly produce ATP or NADH; therefore it is surprising that, among all glycolytic enzymes, alpha-enolase was one of only two glycolytic enzymes consistently up-regulated from MCI to AD. These findings suggest enolase is involved with more than glucose metabolism in AD brain, but may possess other functions, normally necessary to preserve brain function. This review examines potential altered function(s) of brain enolase in MCI, early-onset AD, and AD, alterations that may contribute to the biochemical, pathological, clinical characteristics, and progression of this dementing disorder.

Insurance coverage of medical foods for treatment of inherited metabolic disorders

PubMed Central

Berry, Susan A.; Kenney, Mary Kay; Harris, Katharine B.; Singh, Rani H.; Cameron, Cynthia A.; Kraszewski, Jennifer N.; Levy-Fisch, Jill; Shuger, Jill F.; Greene, Carol L.; Lloyd-Puryear, Michele A.; Boyle, Coleen A.

2015-01-01

Purpose Treatment of inherited metabolic disorders is accomplished by use of specialized diets employing medical foods and medically necessary supplements. Families seeking insurance coverage for these products express concern that coverage is often limited; the extent of this challenge is not well defined. Methods To learn about limitations in insurance coverage, parents of 305 children with inherited metabolic disorders completed a paper survey providing information about their use of medical foods, modified low-protein foods, prescribed dietary supplements, and medical feeding equipment and supplies for treatment of their child's disorder as well as details about payment sources for these products. Results Although nearly all children with inherited metabolic dis orders had medical coverage of some type, families paid “out of pocket” for all types of products. Uncovered spending was reported for 11% of families purchasing medical foods, 26% purchasing supplements, 33% of those needing medical feeding supplies, and 59% of families requiring modified low-protein foods. Forty-two percent of families using modified low-protein foods and 21% of families using medical foods reported additional treatment-related expenses of $100 or more per month for these products. Conclusion Costs of medical foods used to treat inherited metabolic disorders are not completely covered by insurance or other resources. PMID:23598714

Exome Sequencing and the Management of Neurometabolic Disorders.

PubMed

Tarailo-Graovac, Maja; Shyr, Casper; Ross, Colin J; Horvath, Gabriella A; Salvarinova, Ramona; Ye, Xin C; Zhang, Lin-Hua; Bhavsar, Amit P; Lee, Jessica J Y; Drögemöller, Britt I; Abdelsayed, Mena; Alfadhel, Majid; Armstrong, Linlea; Baumgartner, Matthias R; Burda, Patricie; Connolly, Mary B; Cameron, Jessie; Demos, Michelle; Dewan, Tammie; Dionne, Janis; Evans, A Mark; Friedman, Jan M; Garber, Ian; Lewis, Suzanne; Ling, Jiqiang; Mandal, Rupasri; Mattman, Andre; McKinnon, Margaret; Michoulas, Aspasia; Metzger, Daniel; Ogunbayo, Oluseye A; Rakic, Bojana; Rozmus, Jacob; Ruben, Peter; Sayson, Bryan; Santra, Saikat; Schultz, Kirk R; Selby, Kathryn; Shekel, Paul; Sirrs, Sandra; Skrypnyk, Cristina; Superti-Furga, Andrea; Turvey, Stuart E; Van Allen, Margot I; Wishart, David; Wu, Jiang; Wu, John; Zafeiriou, Dimitrios; Kluijtmans, Leo; Wevers, Ron A; Eydoux, Patrice; Lehman, Anna M; Vallance, Hilary; Stockler-Ipsiroglu, Sylvia; Sinclair, Graham; Wasserman, Wyeth W; van Karnebeek, Clara D

2016-06-09

Whole-exome sequencing has transformed gene discovery and diagnosis in rare diseases. Translation into disease-modifying treatments is challenging, particularly for intellectual developmental disorder. However, the exception is inborn errors of metabolism, since many of these disorders are responsive to therapy that targets pathophysiological features at the molecular or cellular level. To uncover the genetic basis of potentially treatable inborn errors of metabolism, we combined deep clinical phenotyping (the comprehensive characterization of the discrete components of a patient's clinical and biochemical phenotype) with whole-exome sequencing analysis through a semiautomated bioinformatics pipeline in consecutively enrolled patients with intellectual developmental disorder and unexplained metabolic phenotypes. We performed whole-exome sequencing on samples obtained from 47 probands. Of these patients, 6 were excluded, including 1 who withdrew from the study. The remaining 41 probands had been born to predominantly nonconsanguineous parents of European descent. In 37 probands, we identified variants in 2 genes newly implicated in disease, 9 candidate genes, 22 known genes with newly identified phenotypes, and 9 genes with expected phenotypes; in most of the genes, the variants were classified as either pathogenic or probably pathogenic. Complex phenotypes of patients in five families were explained by coexisting monogenic conditions. We obtained a diagnosis in 28 of 41 probands (68%) who were evaluated. A test of a targeted intervention was performed in 18 patients (44%). Deep phenotyping and whole-exome sequencing in 41 probands with intellectual developmental disorder and unexplained metabolic abnormalities led to a diagnosis in 68%, the identification of 11 candidate genes newly implicated in neurometabolic disease, and a change in treatment beyond genetic counseling in 44%. (Funded by BC Children's Hospital Foundation and others.).

Exome Sequencing and the Management of Neurometabolic Disorders

PubMed Central

Tarailo-Graovac, M.; Shyr, C.; Ross, C.J.; Horvath, G.A.; Salvarinova, R.; Ye, X.C.; Zhang, L.-H.; Bhavsar, A.P.; Lee, J.J.Y.; Drögemöller, B.I.; Abdelsayed, M.; Alfadhel, M.; Armstrong, L.; Baumgartner, M.R.; Burda, P.; Connolly, M.B.; Cameron, J.; Demos, M.; Dewan, T.; Dionne, J.; Evans, A.M.; Friedman, J.M.; Garber, I.; Lewis, S.; Ling, J.; Mandal, R.; Mattman, A.; McKinnon, M.; Michoulas, A.; Metzger, D.; Ogunbayo, O.A.; Rakic, B.; Rozmus, J.; Ruben, P.; Sayson, B.; Santra, S.; Schultz, K.R.; Selby, K.; Shekel, P.; Sirrs, S.; Skrypnyk, C.; Superti-Furga, A.; Turvey, S.E.; Van Allen, M.I.; Wishart, D.; Wu, J.; Wu, J.; Zafeiriou, D.; Kluijtmans, L.; Wevers, R.A.; Eydoux, P.; Lehman, A.M.; Vallance, H.; Stockler-Ipsiroglu, S.; Sinclair, G.; Wasserman, W.W.; van Karnebeek, C.D.

2016-01-01

BACKGROUND Whole-exome sequencing has transformed gene discovery and diagnosis in rare diseases. Translation into disease-modifying treatments is challenging, particularly for intellectual developmental disorder. However, the exception is inborn errors of metabolism, since many of these disorders are responsive to therapy that targets pathophysiological features at the molecular or cellular level. METHODS To uncover the genetic basis of potentially treatable inborn errors of metabolism, we combined deep clinical phenotyping (the comprehensive characterization of the discrete components of a patient’s clinical and biochemical phenotype) with whole-exome sequencing analysis through a semiautomated bioinformatics pipeline in consecutively enrolled patients with intellectual developmental disorder and unexplained metabolic phenotypes. RESULTS We performed whole-exome sequencing on samples obtained from 47 probands. Of these patients, 6 were excluded, including 1 who withdrew from the study. The remaining 41 probands had been born to predominantly nonconsanguineous parents of European descent. In 37 probands, we identified variants in 2 genes newly implicated in disease, 9 candidate genes, 22 known genes with newly identified phenotypes, and 9 genes with expected phenotypes; in most of the genes, the variants were classified as either pathogenic or probably pathogenic. Complex phenotypes of patients in five families were explained by coexisting monogenic conditions. We obtained a diagnosis in 28 of 41 probands (68%) who were evaluated. A test of a targeted intervention was performed in 18 patients (44%). CONCLUSIONS Deep phenotyping and whole-exome sequencing in 41 probands with intellectual developmental disorder and unexplained metabolic abnormalities led to a diagnosis in 68%, the identification of 11 candidate genes newly implicated in neurometabolic disease, and a change in treatment beyond genetic counseling in 44%. (Funded by BC Children’s Hospital Foundation and others.) PMID:27276562

Why do persons with bipolar disorder stop their medication?

PubMed

Devulapalli, Kavi K; Ignacio, Rosalinda V; Weiden, Peter; Cassidy, Kristin A; Williams, Tiffany D; Safavi, Roknedin; Blow, Frederic C; Sajatovic, Martha

2010-01-01

Non-adherence to maintenance medication regimens is a major problem, limiting outcomes for many persons with bipolar disorder. The aim of this paper is to determine the most relevant aspects of adherence attitudes in a sample of bipolar patients selected for problems with adherence behavior. Among a larger sample of bipolar disorder patients participating in a prospective follow-up study (N = 140), a subsample of patients were selected for non-adherent behavior defined as missing ≥ 30% of medication during the past month (n = 27; 19.3%). Adherence attitudes were assessed with the Rating of Medication Influences scale (ROMI), a self-reported attitudinal measure assessing reasons for and against adherence. Multiple logistic regression models for non-adherence vs. adherence were estimated with each of the 19 ROMI items in the model, while controlling for sex, age, ethnicity, education, duration of illness, and substance abuse. Mean score of ROMI items corresponding to reasons for treatment adherence was greater among adherent participants, whereas the mean score of ROMI items corresponding to reasons for treatment non-adherence was greater among nonadherent participants. The ROMI item identifying that the individual believes that medications are unnecessary had the strongest influence for non-adherence (p < 0.0001). This was followed by ROMI items corresponding to no perceived daily benefit (p = 0.0008), perceived change in appearance (p = 0.0057), and perceived interference with life goals (p = 0.0033). The ROMI item identifying fear of relapse was the strongest predictor for adherence (p = 0.0017). Non-adherent patients with bipolar disorder differ from adherent patients with bipolar disorder on reasons for adherence and non-adherence. Utilization of tools that evaluate medication treatment attitudes, such as the ROMI or similar measures, may assist clinicians in the selection of interventions that are most likely to modify future treatment adherence.

Glix 13, a new drug acting on glutamatergic pathways in children and animal models of autism spectrum disorders.

PubMed

Santini, Annamaria Chiara; Pierantoni, Giovanna Maria; Gerlini, Raffaele; Iorio, Rosamaria; Olabinjo, Yinka; Giovane, Alfonso; Di Domenico, Marina; Sogos, Carla

2014-01-01

Recently standardized diagnostic instruments have been developed in diagnostic and therapeutic procedures for Autism Spectrumv Disorders (ASD). According to the DSM-5 criteria, individuals with ASD must show symptoms from early childhood. These symptoms are communication deficits and restricted, repetitive patterns of behaviour. It was recently described by Bioinformatic analysis that 99 modified genes were associated with human autism. Gene expression patterns in the low-line animals show significant enrichment in autism-associated genes and the NMDA receptor gene family was identified among these. Using ultrasonic vocalizations, it was demonstrated that genetic variation has a direct impact on the expression of social interactions. It has been proposed that specific alleles interact with a social reward process in the adolescent mouse modifying their social interaction and their approach toward each other. In this review we report that the monoclonal antibody-derived tetrapeptide GLYX-13 was found to act as an N-methyl-D-aspartate receptor modulator and possesses the ability to readily cross the blood brain barrier. Treatment with the NMDAR glycine site partial agonist GLYX-13 rescued the deficit in the animal model. Thus, the NMDA receptor has been shown to play a functional role in autism, and GLYX-13 shows promise for the treatment of autism in autistic children.

Academic Achievement and Risk Factors for Adolescents with Attention-Deficit Hyperactivity Disorder in Middle School and Early High School.

PubMed

Zendarski, Nardia; Sciberras, Emma; Mensah, Fiona; Hiscock, Harriet

Examine academic achievement of students with attention-deficit hyperactivity disorder (ADHD) during the early high school period and identify potentially modifiable risk factors for low achievement. Data were collected through surveys (adolescent, parent, and teacher) and direct assessment of Australian adolescents (12-15 yr; n = 130) with ADHD in early high school (i.e., US middle and high school grades). Academic achievement outcomes were measured by linking to individual performance on the National Assessment Program-Literacy and Numeracy (NAPLAN) tests, direct assessment of reading and math, and teacher report of academic competence. Linear regression models examined associations between adolescent, parent/family, and school factors and NAPLAN domain scores. Students with ADHD had lower NAPLAN scores on all domains and fewer met minimum academic standards in comparison with state benchmarks. The poorest results were for persuasive writing. Poor achievement was associated with lower intelligence quotient across all academic domains. Adolescent inattention, bullying, poor family management, male sex, and attending a low socioeconomic status school were associated with lower achievement on specific domains. Students with ADHD are at increased academic risk during the middle school and early high school period. In addition to academic support, interventions targeting modifiable factors including inattention, bullying, and poor family management may improve academic achievement across this critical period.

A systematic review of the nutritional status of women of a childbearing age with severe mental illness.

PubMed

McColl, Helen; Dhillon, Manpreet; Howard, Louise M

2013-02-01

Little is known about the nutritional status of pregnant women with severe mental illness. We therefore carried out a systematic review to investigate whether pregnant women and childbearing aged women with severe mental illness have significantly greater nutritional deficiencies compared with pregnant women and childbearing aged women with no mental illness. We carried out a search using MEDLINE, EMBASE and PsycINFO from January 1980 to January 2011 for studies on nutritional status of childbearing aged women with psychotic disorders. Identification of papers and quality rating of papers (using a modified version of the Newcastle-Ottawa scale) was carried out by two reviewers independently. We identified and screened 4,130 potentially relevant studies from the electronic databases. Fifteen studies met the inclusion criteria (n = 587 women). There were no studies of pregnant women. There was some evidence of low serum folate and vitamin B(12) levels and elevated homocysteine levels in childbearing aged women with psychotic disorders. Further research into the nutritional status of childbearing aged women with severe mental illness is needed. Maternal nutrition has a profound impact on foetal outcome, is a modifiable risk factor and therefore needs prioritising in the care of all childbearing aged women with severe mental illness.

Replication of a Modified Factor Structure for the Eating Disorder Examination-Questionnaire: Extension to Clinical Eating Disorder and Non-clinical Samples in Portugal.

PubMed

Machado, Paulo P P; Grilo, Carlos M; Crosby, Ross D

2018-01-01

Psychometric investigations of the Eating Disorder Examination-Questionnaire (EDE-Q) have generally not supported the original scale structure. The present study tested an alternative brief factor structure in two large Portuguese samples: (1) a non-clinical sample of N = 4117 female students and (2) a treatment-seeking sample of N = 609 patients diagnosed with eating disorders. Confirmatory factor analysis revealed a poor fit for the original EDE-Q structure in both the non-clinical and the clinical samples but revealed a good fit for the alternative 7-item 3-factor structure (dietary restraint, shape/weight overvaluation and body dissatisfaction). Factor loadings were invariant across samples and across the different specific eating disorder diagnoses in the clinical sample. These confirmatory factor analysis findings, which replicate findings from studies with diverse predominately overweight/obese samples, supported a modified 7-item, 3-factor structure for the EDE-Q. The reliable findings across different non-clinical and clinical eating disorder groups provide confidence regarding the potential utility of this brief version. Copyright © 2017 John Wiley & Sons, Ltd and Eating Disorders Association. Copyright © 2017 John Wiley & Sons, Ltd and Eating Disorders Association.

An Allelic Series of Trp63 Mutations Defines TAp63 as a Modifier of EEC Syndrome

PubMed Central

Lindahl, Emma Vernersson; Garcia, Elvin L.; Mills, Alea A.

2014-01-01

Human Ectrodactyly, Ectodermal dysplasia, Clefting (EEC) syndrome is an autosomal dominant developmental disorder defined by limb deformities, skin defects, and craniofacial clefting. Although associated with heterozygous missense mutations in TP63, the genetic basis underlying the variable expressivity and incomplete penetrance of EEC is unknown. Here we show that mice heterozygous for an allele encoding the Trp63 p.Arg318His mutation, which corresponds to the human TP63 p.Arg279His mutation found in patients with EEC, have features of human EEC. Using an allelic series, we discovered that whereas clefting and skin defects are caused by loss of Trp63 function, limb anomalies are due to gain- and/or dominant-negative effects of Trp63. Furthermore, we identify TAp63 as a strong modifier of EEC-associated phenotypes with regard to both penetrance and expressivity. PMID:23775923

Online attention modification for social anxiety disorder: replication of a randomized controlled trial.

PubMed

Carleton, R Nicholas; Teale Sapach, Michelle J N; Oriet, Chris; LeBouthillier, Daniel M

2017-01-01

Social anxiety disorder (SAD) models posit vigilance for external social threat cues and exacerbated self-focused attention as key in disorder development and maintenance. Evidence indicates a modified dot-probe protocol may reduce symptoms of SAD; however, the efficacy when compared to a standard protocol and long-term maintenance of treatment gains remains unclear. Furthermore, the efficacy of such protocols on SAD-related constructs remains relatively unknown. The current investigation clarified these associations using a randomized control trial replicating and extending previous research. Participants with SAD (n = 113; 71% women) were randomized to complete a standard (i.e. control) or modified (i.e. active) dot-probe protocol consisting of 15-min sessions twice weekly for four weeks. Self-reported symptoms were measured at baseline, post-treatment, and 4-month and 8-month follow-ups. Hierarchical linear modeling indicated significant self-reported reductions in symptoms of social anxiety, fear of negative evaluation, trait anxiety, and depression, but no such reductions in fear of positive evaluation. Symptom changes did not differ based on condition and were maintained at 8-month follow-up. Attentional biases during the dot-probe task were not related to symptom change. Overall, our results replicate support for the efficacy of both protocols in reducing symptoms of SAD and specific related constructs, and suggest a role of exposure, expectancy, or practice effects, rather than attention modification, in effecting such reductions. The current results also support distinct relationships between fears of negative and positive evaluation and social anxiety. Further research focused on identifying the mechanisms of change in attention modification protocols appears warranted.

Recent neuroimaging, neurophysiological, and neuropathological advances for the understanding of NPC

PubMed Central

Benussi, Alberto; Cotelli, Maria Sofia; Padovani, Alessandro; Borroni, Barbara

2018-01-01

Niemann–Pick disease type C (NPC) is a rare autosomal recessive lysosomal storage disorder with extensive biological, molecular, and clinical heterogeneity. Recently, numerous studies have tried to shed light on the pathophysiology of the disease, highlighting possible disease pathways common to other neurodegenerative disorders, such as Alzheimer’s disease and frontotemporal dementia, and identifying possible candidate biomarkers for disease staging and response to treatment. Miglustat, which reversibly inhibits glycosphingolipid synthesis, has been licensed in the European Union and elsewhere for the treatment of NPC in both children and adults. A number of ongoing clinical trials might hold promise for the development of new treatments for NPC. The objective of the present work is to review and evaluate recent literature data in order to highlight the latest neuroimaging, neurophysiological, and neuropathological advances for the understanding of NPC pathophysiology. Furthermore, ongoing developments in disease-modifying treatments will be briefly discussed. PMID:29511534

Call for Standardized Definitions of Osteoarthritis and Risk Stratification for Clinical Trials and Clinical Use

PubMed Central

Kraus, Virginia Byers; Blanco, Francisco J.; Englund, Martin; Karsdal, Morten A.; Lohmander, L. Stefan

2015-01-01

Osteoarthritis is a heterogeneous disorder. The goals of this review are (1) To stimulate use of standardized nomenclature for osteoarthritis (OA) that could serve as building blocks for describing OA and defining OA phenotypes, in short to provide unifying disease concepts for a heterogeneous disorder; and (2) To stimulate establishment of ROAD (Risk of Osteoarthritis Development) and ROAP (Risk of Osteoarthritis Progression) tools analogous to the FRAX™ instrument for predicting risk of fracture in osteoporosis; and (3) To stimulate formulation of tools for identifying disease in its early preradiographic and/or molecular stages -- REDI (Reliable Early Disease Identification). Consensus around more sensitive and specific diagnostic criteria for OA could spur development of disease modifying therapies for this entity that has proved so recalcitrant to date. We fully acknowledge that as we move forward, we expect to develop more sophisticated definitions, terminology and tools. PMID:25865392

Anorexia nervosa and bulimia nervosa: brains, bones and breeding.

PubMed

Starr, Taylor B; Kreipe, Richard E

2014-05-01

Recent research has modified both the conceptualization and treatment of eating disorders. New diagnostic criteria reducing the "not otherwise specified" category should facilitate the early recognition and treatment of anorexia nervosa (AN) and bulimia nervosa (BN). Technology-based studies identify AN and BN as "brain circuit" disorders; epidemiologic studies reveal that the narrow racial, ethnic and income profile of individuals no longer holds true for AN. The major organs affected long term-the brain and skeletal system-both respond to improved nutrition, with maintenance of body weight the best predictor of recovery. Twin studies have revealed gene x environment interactions, including both the external (social) and internal (pubertal) environments of boys and of girls. Family-based treatment has the best evidence base for effectiveness for younger patients. Medication plays a limited role in AN, but a major role in BN. Across diagnoses, the most important medicine is food.

A Pilot Study of an Adaptive, Idiographic, and Multi-Component Attention Bias Modification Program for Social Anxiety Disorder

PubMed Central

Amir, Nader; Kuckertz, Jennie M.; Strege, Marlene V.

2016-01-01

An attentional bias toward threat may be one mechanism underlying clinical anxiety. Attention bias modification (ABM) aims to reduce symptoms of anxiety disorders by directly modifying this deficit. However, existing ABM training programs have not consistently modified attentional bias and may not reflect optimal learning needs of participants (i.e., lack of explicit instruction, training goal unclear to participants, lack of feedback, non-adaptive, inability to differentiate or target different components of attentional bias). In the current study, we introduce a new adaptive ABM program (AABM) and test its feasibility in individuals with social anxiety disorder. We report task characteristics and preliminary evidence that this task consistently modifies attentional bias and that changes in attentional bias (but not number of trials) correlate with the level of symptom reduction. These results suggest that AABM may be a targeted method for the next generation of studies examining the utility of attention training. PMID:27795598

Scientists adopt new strategy to find Huntington's disease therapies

MedlinePlus

... Disorders and Stroke, part of NIH. “It’s an example of how precision medicine may be applied to neurological disorders.” The study was conducted by the Genetic Modifiers of Huntington’s ...

Karolinska Psychodynamic Profile for Sexual Disorders: KAPP-SD. A proposal for a psychodynamic rating scale for sexual disorders.

PubMed

Soldati, Lorenzo; Köhl, John; Abraham, Georges; Bianchi Demicheli, Francesco; Wilczek, Alexander

2015-01-01

Our first objective in this paper was to review the literature on psychodynamic rating scales of sexual disorders. Our second objective, based on the findings from our review, was to develop a psychodynamic rating scale for people with sexual disorders: the KAPP-SD. We developed the KAPP-SD by modifying an existing psychodynamic rating scale, which assesses stable modes of mental functioning and character traits, the Karolinska Psychodynamic Profile (KAPP). We removed items 13 and 14 of the KAPP and replaced them with three other items-sexual fantasies, conceptions and role of gender identity, and conceptions and role of sexual orientation. These items are part of the assessment of an individual's sexuality and are used to evaluate a person with a sexual disorder psychodynamically. The KAPP-SD, a modified version of the KAPP, can be found in the Appendix. We developed the KAPP-SD in order to help sex therapists make a rigorous psychodynamic evaluation of persons with sexual disorders, which would give information on the prognosis and on the type of treatment to offer.

[Beyond depression: assessing personality disorders, alexithymia and socio-emotional alienation in patients with HIV infection].

PubMed

Masiello, Addolorata; De Guglielmo, Carmen; Giglio, Sergio; Acone, Nicola

2014-09-01

HIV infection is commonly associated with emotional and cognitive disorders that recognize both causes of an organic nature (related to the virus itself) and non-organic factors (emotional stress resulting from HIV diagnosis, social stigma and continued risk behaviour such as alcohol or drug abuse). Most of the literature has focused attention on depressive disorder, the most common mental disorder in the HIV population. In our analysis we evaluated the presence of personality disorders and alexithymia in a group of patients seropositive for HIV through appropriate psychological tests. Our data revealed a close relationship between socio-emotional alienation, distorted body perception and the difficulty in relating with each other, which is perceived as threatening and judgmental; this concept takes us back to the social stigma that modifies the emotional communication of HIV patients. The illness is experienced as an outsider that modifies the body, imprisons the emotionalism and cannot be controlled. Such personality alterations stop the emotional communication, thereby developing alexithymia.

Regulation of glycogen synthase kinase-3 during bipolar mania treatment.

PubMed

Li, Xiaohong; Liu, Min; Cai, Zhuoji; Wang, Gang; Li, Xiaohua

2010-11-01

Bipolar disorder is a debilitating psychiatric illness presenting with recurrent mania and depression. The pathophysiology of bipolar disorder is poorly understood, and molecular targets in the treatment of bipolar disorder remain to be identified. Preclinical studies have suggested that glycogen synthase kinase-3 (GSK3) is a potential therapeutic target in bipolar disorder, but evidence of abnormal GSK3 in human bipolar disorder and its response to treatment is still lacking. This study was conducted in acutely ill type I bipolar disorder subjects who were hospitalized for a manic episode. The protein level and the inhibitory serine phosphorylation of GSK3 in peripheral blood mononuclear cells of bipolar manic and healthy control subjects were compared, and the response of GSK3 to antimanic treatment was evaluated. The levels of GSK3α and GSK3β in this group of bipolar manic subjects were higher than healthy controls. Symptom improvement during an eight-week antimanic treatment with lithium, valproate, and atypical antipsychotics was accompanied by a significant increase in the inhibitory serine phosphorylation of GSK3, but not the total level of GSK3, whereas concomitant electroconvulsive therapy treatment during a manic episode appeared to dampen the response of GSK3 to pharmacological treatment. Results of this study suggest that GSK3 can be modified during the treatment of bipolar mania. This finding in human bipolar disorder is in agreement with preclinical data suggesting that inhibition of GSK3 by increasing serine phosphorylation is a response of GSK3 to psychotropics used in bipolar disorder, supporting the notion that GSK3 is a promising molecular target in the pharmacological treatment of bipolar disorder. © 2010 John Wiley and Sons A/S.

Obesity and Sex Interact in the Regulation of Alzheimer’s Disease

PubMed Central

Moser, V. Alexandra; Pike, Christian J.

2015-01-01

Alzheimer’s disease (AD) is a progressive neurodegenerative disorder, for which a number of genetic, environmental, and lifestyle risk factors have been identified. A significant modifiable risk factor is obesity in mid-life. Interestingly, both obesity and AD exhibit sex differences and are regulated by sex steroid hormones. Accumulating evidence suggests interactions between obesity and sex in regulation of AD risk, although the pathways underlying this relationship are unclear. Inflammation and the E4 allele of apolipoprotein E have been identified as independent risk factors for AD and both interact with obesity and sex steroid hormones. We review the individual and cooperative effects of obesity and sex on development of AD and examine the potential contributions of apolipoprotein E, inflammation, and their interactions to this relationship. PMID:26708713

Guidelines on the diagnosis of noise-induced hearing loss for medicolegal purposes.

PubMed

Coles, R R; Lutman, M E; Buffin, J T

2000-08-01

These guidelines aim to assist in the diagnosis of noise-induced hearing loss (NIHL) in medicolegal settings. The task is to distinguish between possibility and probability, the legal criterion being 'more probable than not'. It is argued that the amount of NIHL needed to qualify for that diagnosis is that which is reliably measurable and identifiable on the audiogram. The three main requirements for the diagnosis of NIHL are defined: R1, high-frequency hearing impairment; R2, potentially hazardous amount of noise exposure; R3, identifiable high-frequency audiometric notch or bulge. Four modifying factors also need consideration: MF1, the clinical picture; MF2, compatibility with age and noise exposure; MF3, Robinson's criteria for other causation; MF4, complications such as asymmetry, mixed disorder and conductive hearing impairment.

Craving Facebook? Behavioral addiction to online social networking and its association with emotion regulation deficits.

PubMed

Hormes, Julia M; Kearns, Brianna; Timko, C Alix

2014-12-01

To assess disordered online social networking use via modified diagnostic criteria for substance dependence, and to examine its association with difficulties with emotion regulation and substance use. Cross-sectional survey study targeting undergraduate students. Associations between disordered online social networking use, internet addiction, deficits in emotion regulation and alcohol use problems were examined using univariate and multivariate analyses of covariance. A large University in the Northeastern United States. Undergraduate students (n = 253, 62.8% female, 60.9% white, age mean = 19.68, standard deviation = 2.85), largely representative of the target population. The response rate was 100%. Disordered online social networking use, determined via modified measures of alcohol abuse and dependence, including DSM-IV-TR diagnostic criteria for alcohol dependence, the Penn Alcohol Craving Scale and the Cut-down, Annoyed, Guilt, Eye-opener (CAGE) screen, along with the Young Internet Addiction Test, Alcohol Use Disorders Identification Test, Acceptance and Action Questionnaire-II, White Bear Suppression Inventory and Difficulties in Emotion Regulation Scale. Disordered online social networking use was present in 9.7% [n = 23; 95% confidence interval (5.9, 13.4)] of the sample surveyed, and significantly and positively associated with scores on the Young Internet Addiction Test (P < 0.001), greater difficulties with emotion regulation (P = 0.003) and problem drinking (P = 0.03). The use of online social networking sites is potentially addictive. Modified measures of substance abuse and dependence are suitable in assessing disordered online social networking use. Disordered online social networking use seems to arise as part of a cluster of symptoms of poor emotion regulation skills and heightened susceptibility to both substance and non-substance addiction. © 2014 Society for the Study of Addiction.

Evidence-based guideline: Assessment and management of psychiatric disorders in individuals with MS

PubMed Central

Minden, Sarah L.; Feinstein, Anthony; Kalb, Rosalind C.; Miller, Deborah; Mohr, David C.; Patten, Scott B.; Bever, Christopher; Schiffer, Randolph B.; Gronseth, Gary S.; Narayanaswami, Pushpa

2014-01-01

Objective: To make evidence-based recommendations for screening, diagnosing, and treating psychiatric disorders in individuals with multiple sclerosis (MS). Methods: We reviewed the literature (1950 to August 2011) and evaluated the available evidence. Results and recommendations: Clinicians may consider using the Center for Neurologic Study Emotional Lability Scale to screen for pseudobulbar affect (Level C). Clinicians may consider the Beck Depression Inventory and a 2-question tool to screen for depressive disorders and the General Health Questionnaire to screen for broadly defined emotional disturbances (Level C). Evidence is insufficient to support/refute the use of other screening tools, the possibility that somatic/neurovegetative symptoms affect these tools' accuracy, or the use of diagnostic instruments or clinical evaluation procedures for identifying psychiatric disorders in MS (Level U). Clinicians may consider a telephone-administered cognitive behavioral therapy program for treating depressive symptoms (Level C). Although pharmacologic and nonpharmacologic therapies are widely used to treat depressive and anxiety disorders in individuals with MS, evidence is insufficient to support/refute the use of the antidepressants and individual and group therapies reviewed herein (Level U). For pseudobulbar affect, a combination of dextromethorphan and quinidine may be considered (Level C). Evidence is insufficient to determine the psychiatric effects in individuals with MS of disease-modifying and symptomatic therapies and corticosteroids; risk factors for suicide; and treatment of psychotic disorders (Level U). Research is needed on the effectiveness in individuals with MS of pharmacologic and nonpharmacologic treatments frequently used in the non-MS population. PMID:24376275

Does the Vigilance-Avoidance Gazing Behavior of Children with Separation Anxiety Disorder Change after Cognitive-Behavioral Therapy?

ERIC Educational Resources Information Center

In-Albon, Tina; Schneider, Silvia

2012-01-01

Cognitive biases are of interest in understanding the development of anxiety disorders. They also play a significant role during psychotherapy, where cognitive biases are modified in order to break the vicious cycle responsible for maintaining anxiety disorders. In a previous study, the vigilance-avoidance pattern was shown in children with…

Genetic Variation in Melatonin Pathway Enzymes in Children with Autism Spectrum Disorder and Comorbid Sleep Onset Delay

ERIC Educational Resources Information Center

Veatch, Olivia J.; Pendergast, Julie S.; Allen, Melissa J.; Leu, Roberta M.; Johnson, Carl Hirschie; Elsea, Sarah H.; Malow, Beth A.

2015-01-01

Sleep disruption is common in individuals with autism spectrum disorder (ASD). Genes whose products regulate endogenous melatonin modify sleep patterns and have been implicated in ASD. Genetic factors likely contribute to comorbid expression of sleep disorders in ASD. We studied a clinically unique ASD subgroup, consisting solely of children with…

The Implementation of Modified Parent-Child Interaction Therapy for Youth with Separation Anxiety Disorder

ERIC Educational Resources Information Center

Pincus, Donna B.; Santucci, Lauren C.; Ehrenreich, Jill T.; Eyberg, Sheila M.

2008-01-01

Separation Anxiety Disorder (SAD) is the most prevalent anxiety disorder experienced by children, and yet empirical treatment studies of SAD in young children are virtually nonexistent. This paper will describe the development and implementation of an innovative treatment for SAD in young children. First, we will highlight the rationale for…

Brief Report: Treating Stuttering in an Adult with Autism Spectrum Disorder

ERIC Educational Resources Information Center

Brundage, Shelley B.; Whelan, Cory J.; Burgess, Cathleen M.

2013-01-01

Stuttering and autism can co-occur and when they do it presents a significant communication challenge. This study examined the effectiveness of a modified version of the fluency rules program (FRP; Runyan and Runyan, Stuttering and related disorders of fluency, in 2007) to reduce stuttering frequency in a man with autism spectrum disorder (ASD).…

Correction to: Associations between attention-deficit/hyperactivity disorder and autoimmune diseases are modified by sex: a population-based cross-sectional study.

PubMed

Hegvik, Tor-Arne; Instanes, Johanne Telnes; Haavik, Jan; Klungsøyr, Kari; Engeland, Anders

2018-05-01

The article "Associations between attention-deficit/hyperactivity disorder and autoimmune diseases are modified by sex: a population-based cross-sectional study", written by Tor-Arne Hegvik, Johanne Telnes Instanes, Jan Haavik, Kari Klungsøyr and Anders Engeland, was originally published electronically on the publisher's internet portal (currently SpringerLink) on October 5, 2017 without open access due to an error by the Springer editorial office in the processing of this article. The authors had originally opted for open access.

Coping strategies in schizoaffective disorder and schizophrenia: Differences and similarities.

PubMed

Mingrone, Cinzia; Montemagni, Cristiana; Sandei, Luisa; Bava, Irene; Mancini, Irene; Cardillo, Simona; Rocca, Paola

2016-10-30

Aims of the current study were to explore differences in coping between 58 patients with schizoaffective disorder (SAD) and 89 with schizophrenia (SZ) and to identify factors associated with coping in both disorders. The demographic and clinical characteristics of patients with SAD and with SZ were compared using ANOVA and χ(2). Pearson's correlations were calculated between coping styles and socio-demographic and clinical variables in each group. The significant ones were subsequently analyzed using multiple regressions. Patients with SAD used emotion oriented coping more frequently than patients 2016with SZ. In patients with SAD, self-esteem contributed to task-oriented; avolition-anhedonia (AA) to emotion-oriented; duration of illness and years of education to distraction; AA to social diversion. In patients with SZ, AA, the mental component summary score of the Short Form - 36 Health Survey (SF-36) and self-esteem contributed to emotion oriented coping; the mental component summary score of SF-36 to distraction; AA to social diversion. Our results suggest that patients with SAD and SZ use diverse coping strategies. A greater attention must be given to the presence of self-esteem and AA in individuals with both disorders. These factors are potentially modifiable from specific therapeutic interventions, which can produce effects on coping strategies. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Gender-specific risk factors for low bone mineral density in patients taking antipsychotics for psychosis.

PubMed

Jhon, Min; Yoo, Taeyoung; Lee, Ju-Yeon; Kim, Seon-Young; Kim, Jae-Min; Shin, Il-Seon; Williams, Lana; Berk, Michael; Yoon, Jin-Sang; Kim, Sung-Wan

2018-01-01

This study examined clinical and gender-specific risk factors for low bone mineral density (BMD) in adult patients with psychotic disorders. The study included 285 community-dwelling patients with psychotic disorders. Dual-energy X-ray absorptiometry was used to measure BMD. Clinical characteristics associated with low BMD were identified with logistic regression analysis in total population and each gender. Fifty-eight (20.4%) subjects had low BMD. Low BMD was more common in men and in patients with low body mass indices (BMIs), as well as in those with shorter treatment durations, those on Medicaid, and patients using serotonergic antidepressants. Logistic regression analysis revealed that low BMD was negatively associated with BMI and treatment duration and positively with gender (male) and serotonergic antidepressants use in the overall population. In men, low BMD was associated with treatment duration and BMI; in women, low BMD was associated with BMI, prolactin level, vitamin D, and serotonergic antidepressant use. Managing the risk factors associated with low BMD among patients with psychotic disorder should be done gender-specifically. Psychotropic agents should be prescribed mindful of their effects on bone, as use of these medications is a modifiable risk factor for osteoporosis in women with psychotic disorders. Copyright © 2018 John Wiley & Sons, Ltd.

Cutaneous EBV-related lymphoproliferative disorders.

PubMed

Gru, Alejandro A; Jaffe, Elaine S

2017-01-01

This article will focus on the cutaneous lymphoproliferative disorders associated with EBV, with an emphasis on the upcoming changes in the revised 4th Edition of the WHO classification of tumors of the hematopoietic system, many of which deal with cutaneous disorders derived from NK-cells or T-cells. Extranodal NK/T-cell lymphoma usually presents in the upper aerodigestive tract, but can involve the skin secondarily. EBV-associated T- and NK-cell lymphoproliferative disorders (LPD) in the pediatric age group include the systemic diseases, chronic active EBV infection (CAEBV) and systemic EBV+ T-cell lymphoma of childhood. Hydroa vacciniforme (HV)-like LPD is a primarily cutaneous form of CAEBV and encompasses the lesions previously referred to as HV and HV-like lymphoma (HVLL). All the T/NK-cell-EBV-associated diseases occur with higher frequency in Asians, and indigenous populations from Central and South America and Mexico. Among the B-cell EBV-associated LPD two major changes have been introduced in the WHO. The previously designated EBV-positive diffuse large B-cell lymphoma (EBV-DLBCL) of the elderly, has been changed to EBV-DLBCL with 'not otherwise specified' as a modifier (NOS). A new addition to the WHO system is the more recently identified EBV+ mucocutaneous ulcer, which involves skin and mucosal-associated sites. Copyright © 2017 Elsevier Inc. All rights reserved.

Associations of metabolic disorder factors with the risk of uncontrolled hypertension: a follow-up cohort in rural China.

PubMed

Xiao, Jing; Hua, Tianqi; Shen, Huan; Zhang, Min; Wang, Xiao-Jian; Gao, Yue-Xia; Lu, Qinyun; Wu, Chuanli

2017-04-07

We evaluated how metabolic disorders affected antihypertension therapy. 2,912 rural Chinese patients with hypertension who provided blood samples, demographic and clinical data at baseline and after 1 year of antihypertension therapy were evaluated. At baseline, 1,515 patients (52.0%) were already receiving drug therapy and 11.4% of them had controlled blood pressure (BP). After 1 year, all 2,912 patients were receiving antihypertension therapy that was administered by community physicians, and 59.42% of them had controlled BP. Central obesity and abnormal triglyceride, high-density lipoprotein cholesterol, and glucose were associated with 15-70% higher risks of uncontrolled hypertension. Metabolic syndrome using the JIS criteria was associated with poor BP control (odds ratio: 1.71 and 1.54 for the baseline and follow-up datasets, respectively). The risk of uncontrolled hypertension increased with the number of metabolic disorders (p for trend <0.01). The presence of ≥3 metabolic disorder factors was associated with higher risks of poor BP control. The associations of metabolic factors and uncontrolled hypertension were stronger for the standard and modified ATP III criteria, compared to the IDF and JIS criteria. Metabolic factors were associated with less effective antihypertension therapy, and all definitions of metabolic syndrome helped identify patients with elevated risks of uncontrolled hypertension.

Recommendations regarding splenectomy in hereditary hemolytic anemias

PubMed Central

Iolascon, Achille; Andolfo, Immacolata; Barcellini, Wilma; Corcione, Francesco; Garçon, Loïc; De Franceschi, Lucia; Pignata, Claudio; Graziadei, Giovanna; Pospisilova, Dagmar; Rees, David C.; de Montalembert, Mariane; Rivella, Stefano; Gambale, Antonella; Russo, Roberta; Ribeiro, Leticia; Vives-Corrons, Jules; Martinez, Patricia Aguilar; Kattamis, Antonis; Gulbis, Beatrice; Cappellini, Maria Domenica; Roberts, Irene; Tamary, Hannah

2017-01-01

Hereditary hemolytic anemias are a group of disorders with a variety of causes, including red cell membrane defects, red blood cell enzyme disorders, congenital dyserythropoietic anemias, thalassemia syndromes and hemoglobinopathies. As damaged red blood cells passing through the red pulp of the spleen are removed by splenic macrophages, splenectomy is one possible therapeutic approach to the management of severely affected patients. However, except for hereditary spherocytosis for which the effectiveness of splenectomy has been well documented, the efficacy of splenectomy in other anemias within this group has yet to be determined and there are concerns regarding short- and long-term infectious and thrombotic complications. In light of the priorities identified by the European Hematology Association Roadmap we generated specific recommendations for each disorder, except thalassemia syndromes for which there are other, recent guidelines. Our recommendations are intended to enable clinicians to achieve better informed decisions on disease management by splenectomy, on the type of splenectomy and the possible consequences. As no randomized clinical trials, case control or cohort studies regarding splenectomy in these disorders were found in the literature, recommendations for each disease were based on expert opinion and were subsequently critically revised and modified by the Splenectomy in Rare Anemias Study Group, which includes hematologists caring for both adults and children. PMID:28550188

Perceptions of factors associated with weight management in obese adults with schizophrenia.

PubMed

Lundgren, Jennifer D; Rempfer, Melisa V; Lent, Michelle R; Foster, Gary D

2014-12-01

Individuals with serious mental illnesses are at increased risk of obesity, although the behavioral factors contributing to excess weight are not well understood. We report on the eating behavior, physical activity, and body image of obese adults with and without schizophrenia spectrum disorders. Twenty-two obese adults diagnosed with schizophrenia or schizoaffective disorder were compared to demographically matched obese adults without psychiatric diagnoses on their responses to a comprehensive assessment of several psychosocial and behavioral domains relevant to obesity and weight management. The schizophrenia group, compared to controls, reported more difficulty with several eating behaviors that were self-identified as contributing to increased weight. They also reported more enjoyment of physical activity and greater satisfaction with body weight and shape compared to controls. Clinically relevant group differences were identified that should be considered when designing ecologically valid weight management assessments and interventions for individuals diagnosed with serious mental illnesses. Health care providers are encouraged to assess an individual's weight management strengths and barriers through available assessment tools and home visits, as well as offer specific environmental and behavioral changes to manage hunger and modify eating patterns. (c) 2014 APA, all rights reserved.

Nanoimages show disruption of tubulin polymerization by chlorpyrifos oxon: Implications for neurotoxicity

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

Grigoryan, Hasmik; Lockridge, Oksana

2009-10-15

Organophosphorus agents cause cognitive deficits and depression in some people. We hypothesize that the mechanism by which organophosphorus agents cause these disorders is by modification of proteins in the brain. One such protein could be tubulin. Tubulin polymerizes to make the microtubules that transport cell components to nerve axons. The goal of the present work was to measure the effect of the organophosphorus agent chlorpyrifos oxon on tubulin polymerization. An additional goal was to identify the amino acids covalently modified by chlorpyrifos oxon in microtubule polymers and to compare them to the amino acids modified in unpolymerized tubulin dimers. Purifiedmore » bovine tubulin (0.1 mM) was treated with 0.005-0.1 mM chlorpyrifos oxon for 30 min at room temperature and then polymerized by addition of 1 mM GTP to generate microtubules. Microtubules were visualized by atomic force microscopy. Chlorpyrifos oxon-modified residues were identified by tandem ion trap electrospray ionization and matrix-assisted laser desorption/ionization mass spectrometry of tryptic peptides. Nanoimaging showed that low concentrations (0.005 and 0.01 mM) of chlorpyrifos oxon yielded short, thin microtubules. A concentration of 0.025 mM stimulated polymerization, while high concentrations (0.05 and 0.1 mM) caused aggregation. Of the 17 tyrosines covalently modified by chlorpyrifos oxon in unpolymerized tubulin dimers, only 2 tyrosines were labeled in polymerized microtubules. The two labeled tyrosines in polymerized tubulin were Tyr 103 in EDAANNY*R of alpha tubulin, and Tyr 281 in GSQQY*R of beta tubulin. In conclusion, chlorpyrifos oxon binding to tubulin disrupts tubulin polymerization. These results may lead to an understanding of the neurotoxicity of organophosphorus agents.« less

Nanoimages show disruption of tubulin polymerization by chlorpyrifos oxon; implications for neurotoxicity

PubMed Central

Grigoryan, Hasmik; Lockridge, Oksana

2009-01-01

Organophosphorus agents cause cognitive deficits and depression in some people. We hypothesize that the mechanism by which organophosphorus agents cause these disorders is by modification of proteins in the brain. One such protein could be tubulin. Tubulin polymerizes to make the microtubules that transport cell components to nerve axons. The goal of the present work was to measure the effect of the organophosphorus agent chlorpyrifos oxon on tubulin polymerization. An additional goal was to identify the amino acids covalently modified by chlorpyrifos oxon in microtubule polymers and to compare them to the amino acids modified in unpolymerized tubulin dimers. Purified bovine tubulin (0.1 mM) was treated with 0.005-0.1 mM chlorpyrifos oxon for 30 min at room temperature and then polymerized by addition of 1 mM GTP to generate microtubules. Microtubules were visualized by atomic force microscopy. Chlorpyrifos oxon-modified residues were identified by tandem ion trap electrospray ionization and matrix-assisted laser desorption/ionization mass spectrometry of tryptic peptides. Nanoimaging showed that low concentrations (0.005 and 0.01 mM) of chlorpyrifos oxon yielded short, thin microtubules. A concentration of 0.025 mM stimulated polymerization, while high concentrations (0.05 and 0.1 mM) caused aggregation. Of the 17 tyrosines covalently modified by chlorpyrifos oxon in unpolymerized tubulin dimers, only 2 tyrosines were labeled in polymerized microtubules. The two labeled tyrosines in polymerized tubulin were Tyr 103 in EDAANNY*R of alpha tubulin, and Tyr 281 in GSQQY*R of beta tubulin. In conclusion, chlorpyrifos oxon binding to tubulin disrupts tubulin polymerization. These results may lead to an understanding of the neurotoxicity of organophosphorus agents. PMID:19631231

Incorporation of therapeutically modified bacteria into gut microbiota inhibits obesity.

PubMed

Chen, Zhongyi; Guo, Lilu; Zhang, Yongqin; Walzem, Rosemary L; Pendergast, Julie S; Printz, Richard L; Morris, Lindsey C; Matafonova, Elena; Stien, Xavier; Kang, Li; Coulon, Denis; McGuinness, Owen P; Niswender, Kevin D; Davies, Sean S

2014-08-01

Metabolic disorders, including obesity, diabetes, and cardiovascular disease, are widespread in Westernized nations. Gut microbiota composition is a contributing factor to the susceptibility of an individual to the development of these disorders; therefore, altering a person's microbiota may ameliorate disease. One potential microbiome-altering strategy is the incorporation of modified bacteria that express therapeutic factors into the gut microbiota. For example, N-acylphosphatidylethanolamines (NAPEs) are precursors to the N-acylethanolamide (NAE) family of lipids, which are synthesized in the small intestine in response to feeding and reduce food intake and obesity. Here, we demonstrated that administration of engineered NAPE-expressing E. coli Nissle 1917 bacteria in drinking water for 8 weeks reduced the levels of obesity in mice fed a high-fat diet. Mice that received modified bacteria had dramatically lower food intake, adiposity, insulin resistance, and hepatosteatosis compared with mice receiving standard water or control bacteria. The protective effects conferred by NAPE-expressing bacteria persisted for at least 4 weeks after their removal from the drinking water. Moreover, administration of NAPE-expressing bacteria to TallyHo mice, a polygenic mouse model of obesity, inhibited weight gain. Our results demonstrate that incorporation of appropriately modified bacteria into the gut microbiota has potential as an effective strategy to inhibit the development of metabolic disorders.

Incorporation of therapeutically modified bacteria into gut microbiota inhibits obesity

PubMed Central

Chen, Zhongyi; Guo, Lilu; Zhang, Yongqin; L. Walzem, Rosemary; Pendergast, Julie S.; Printz, Richard L.; Morris, Lindsey C.; Matafonova, Elena; Stien, Xavier; Kang, Li; Coulon, Denis; McGuinness, Owen P.; Niswender, Kevin D.; Davies, Sean S.

2014-01-01

Metabolic disorders, including obesity, diabetes, and cardiovascular disease, are widespread in Westernized nations. Gut microbiota composition is a contributing factor to the susceptibility of an individual to the development of these disorders; therefore, altering a person’s microbiota may ameliorate disease. One potential microbiome-altering strategy is the incorporation of modified bacteria that express therapeutic factors into the gut microbiota. For example, N-acylphosphatidylethanolamines (NAPEs) are precursors to the N-acylethanolamide (NAE) family of lipids, which are synthesized in the small intestine in response to feeding and reduce food intake and obesity. Here, we demonstrated that administration of engineered NAPE-expressing E. coli Nissle 1917 bacteria in drinking water for 8 weeks reduced the levels of obesity in mice fed a high-fat diet. Mice that received modified bacteria had dramatically lower food intake, adiposity, insulin resistance, and hepatosteatosis compared with mice receiving standard water or control bacteria. The protective effects conferred by NAPE-expressing bacteria persisted for at least 4 weeks after their removal from the drinking water. Moreover, administration of NAPE-expressing bacteria to TallyHo mice, a polygenic mouse model of obesity, inhibited weight gain. Our results demonstrate that incorporation of appropriately modified bacteria into the gut microbiota has potential as an effective strategy to inhibit the development of metabolic disorders. PMID:24960158

Apparently enhanced magnetization of Cu(I)-modified γ-Fe2O3 based nanoparticles

NASA Astrophysics Data System (ADS)

Qiu, Xiaoyan; He, Zhenghong; Mao, Hong; Zhang, Ting; Lin, Yueqiang; Liu, Xiaodong; Li, Decai; Meng, Xiangshen; Li, Jian

2017-11-01

Using a chemically induced transition method in FeCl2 solution, γ-Fe2O3 based magnetic nanoparticles, in which γ-Fe2O3 crystallites were coated with FeCl3ṡ6H2O, were prepared. During the synthesis of the γ-Fe2O3 nanoparticles Cu(I) modification of the particles was attempted. According to the results from both magnetization measurements and structural characterization, it was judged that a magnetic silent "dead layer", which can be attributed to spin disorder in the surface of the γ-Fe2O3 crystallites due to breaking of the crystal symmetry, existed in the unmodified particles. For the Cu(I)-modified sample, the CuCl thin layer on the γ-Fe2O3 crystallites incurred the crystal symmetry to reduce the spin disorder, which "awakened" the "dead layer" on the surface of the γ-Fe2O3 crystallites, enhancing the apparent magnetization of the Cu(I)-modified nanoparticles. It was determined that the surface spin disorder of the magnetic crystallite could be related to the coating layer on the crystallite, and can be modified by altering the coating layer to enhance the effective magnetization of the magnetic nanoparticles.

Anxiety disorders and risk of stroke: A systematic review and meta-analysis.

PubMed

Pérez-Piñar, M; Ayerbe, L; González, E; Mathur, R; Foguet-Boreu, Q; Ayis, S

2017-03-01

Anxiety disorders are the most common mental health problem worldwide. However, the evidence on the association between anxiety disorders and risk of stroke is limited. This systematic review and meta-analysis presents a critical appraisal and summary of the available evidence on the association between anxiety disorders and risk of stroke. Cohort studies reporting risk of stroke among patients with anxiety disorders were searched in PubMed, Embase, PsycINFO, Scopus, and the Web of Science, from database inception to June 2016. The quality of the studies was assessed using standard criteria. A meta-analysis was undertaken to obtain pooled estimates of the risk of stroke among patients with anxiety disorders. Eight studies, including 950,759 patients, from the 11,764 references initially identified, were included in this review. A significantly increased risk of stroke for patients with anxiety disorders was observed, with an overall hazard ratio: 1.24 (1.09-1.41), P=0.001. No significant heterogeneity between studies was detected and the funnel plot suggested that publication bias was unlikely. Limited evidence suggests that the risk of stroke is increased shortly after the diagnosis of anxiety and that risk of stroke may be higher for patients with severe anxiety. Anxiety disorders are a very prevalent modifiable condition associated with risk of stroke increased by 24%. This evidence could inform the development of interventions for the management of anxiety and the prevention of stroke. Further studies on the risk of stroke in patients with anxiety, and the explanatory factors for this association, are required. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

RADAR study: protocol for an observational cohort study to identify early warning signals on the pathways to alcohol use disorder.

PubMed

Slade, Tim; Swift, Wendy; Mewton, Louise; Kypri, Kypros; Lynskey, Michael T; Butterworth, Peter; Tibbetts, Joel; McCraw, Stacey; Upton, Emily

2017-08-21

Harmful alcohol consumption, particularly alcohol use disorder (AUD), is a worldwide health priority, contributing substantially to global morbidity and mortality. The peak age of onset of AUD is 18-24, thus a deeper understanding of the young adult experience is vital if we are to identify modifiable risk factors and intervene early in the developmental course of this disabling disorder. Critical unanswered questions include: How soon after drinking initiation do AUD symptoms begin to emerge? Which symptoms come first? Do the symptoms unfold in a predictable pattern? In what ways do the emerging symptoms interact with individual, peer, family and environmental risk factors to impact on the transition to disorder? The proposed RADAR study will examine the prospective development of AUD symptoms over the young adulthood (18-24) years. We will capitalise on an existing cohort of 1911 community-based adolescents who were recruited at age 13 and have completed a baseline and five annual follow-up assessments as part of an observational cohort study. We will interview these adolescents every 6 months between the ages of 19 and 23 to derive monthly histories of both alcohol use and AUD symptomatology, along with a comprehensive battery of risk and protective factor scales hypothesised to predict the emergence and course of AUD. The results of this study will inform the natural history of AUD and will be used to identify specific targets for prevention and early intervention of AUD. Ethical approval has already been granted for the study (UNSW HREC 10144). We will disseminate the results of the study through published manuscripts, conferences and seminar presentations. Data used in published manuscripts will be made available through a suitable online repository (eg, Dryad-datadryad.org). © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Where to Go from Here? An Exploratory Meta-Analysis of the Most Promising Approaches to Depression Prevention Programs for Children and Adolescents

PubMed Central

Hetrick, Sarah E.; Cox, Georgina R.; Merry, Sally N.

2015-01-01

Objective: To examine the overall effect of individual depression prevention programs on future likelihood of depressive disorder and reduction in depressive symptoms. In addition, we have investigated whether Cognitive Behavioural Therapy (CBT), Interpersonal Therapy (IPT) and other therapeutic techniques may modify this effectiveness. Methods: This study is based on and includes the trial data from meta-analyses conducted in the Cochrane systematic review of depression prevention programs for children and adolescents by Merry et al. (2011). All trials were published or unpublished English language randomized controlled trials (RCTs) or cluster RCTs of any psychological or educational intervention compared to no intervention to prevent depression in children and adolescents aged 5–19 years. Results: There is some evidence that the therapeutic approach used in prevention programs modifies the overall effect. CBT is the most studied type of intervention for depression prevention, and there is some evidence of its effectiveness in reducing the risk of developing a depressive disorder, particularly in targeted populations. Fewer studies employed IPT, however this approach appears promising. To our knowledge, this is the first study to have explored how differences in the approach taken in the prevention programs modify the overall treatment effects of prevention programs for children and adolescents. Conclusions: More research is needed to identify the specific components of CBT that are most effective or indeed if there are other approaches that are more effective in reducing the risk of future depressive episodes. It is imperative that prevention programs are suitable for large scale roll-out, and that emerging popular modes of delivery, such as online dissemination continue to be rigorously tested. PMID:25941844

MERRF Classification: Implications for Diagnosis and Clinical Trials.

PubMed

Finsterer, Josef; Zarrouk-Mahjoub, Sinda; Shoffner, John M

2018-03-01

Given the etiologic heterogeneity of disease classification using clinical phenomenology, we employed contemporary criteria to classify variants associated with myoclonic epilepsy with ragged-red fibers (MERRF) syndrome and to assess the strength of evidence of gene-disease associations. Standardized approaches are used to clarify the definition of MERRF, which is essential for patient diagnosis, patient classification, and clinical trial design. Systematic literature and database search with application of standardized assessment of gene-disease relationships using modified Smith criteria and of variants reported to be associated with MERRF using modified Yarham criteria. Review of available evidence supports a gene-disease association for two MT-tRNAs and for POLG. Using modified Smith criteria, definitive evidence of a MERRF gene-disease association is identified for MT-TK. Strong gene-disease evidence is present for MT-TL1 and POLG. Functional assays that directly associate variants with oxidative phosphorylation impairment were critical to mtDNA variant classification. In silico analysis was of limited utility to the assessment of individual MT-tRNA variants. With the use of contemporary classification criteria, several mtDNA variants previously reported as pathogenic or possibly pathogenic are reclassified as neutral variants. MERRF is primarily an MT-TK disease, with pathogenic variants in this gene accounting for ~90% of MERRF patients. Although MERRF is phenotypically and genotypically heterogeneous, myoclonic epilepsy is the clinical feature that distinguishes MERRF from other categories of mitochondrial disorders. Given its low frequency in mitochondrial disorders, myoclonic epilepsy is not explained simply by an impairment of cellular energetics. Although MERRF phenocopies can occur in other genes, additional data are needed to establish a MERRF disease-gene association. This approach to MERRF emphasizes standardized classification rather than clinical phenomenology, thus improving patient diagnosis and clinical trial design. Copyright © 2017 Elsevier Inc. All rights reserved.

A Qualitative Assessment of the Parenting Challenges and Treatment Needs of Mothers with Borderline Personality Disorder

PubMed Central

Zalewski, Maureen; Stepp, Stephanie D.; Whalen, Diana J.; Scott, Lori N.

2014-01-01

There are currently no empirically supported interventions to target parenting among mothers who have Borderline Personality Disorder (BPD). The current study uses Consensus Qualitative Research (CQR) methodology to: I) learn about mothers’ experiences of parenting with BPD, and II) identify treatment modifications to Dialectical Behavior Therapy (DBT) as suggested by mothers with BPD who are currently engaged in DBT skills training. Twenty-three mothers were recruited from intensive outpatient and partial hospitalization programs that teach DBT skills. A total of 9 focus groups that met one time were conducted asking women a series of questions regarding their experiences of parenting with BPD and how they would modify DBT to address parenting issues. Using the CQR approach, we coded domains and categories that were discussed by mothers in the focus groups. Coding revealed that mothers with BPD wished parenting was integrated more in their current DBT skills groups. In addition, one of the most prominent themes to emerge was that parenting is particularly stressful to mothers with BPD and is associated with guilt, uncertainty, and worry. Finally, mothers offered many ideas for how to integrate parenting-focused interventions into DBT. The CQR method revealed gaps in current treatment for mothers with BPD and provided useful ideas for how to modify DBT to target parenting and integrate these modifications into other approaches for treating mothers with BPD. PMID:26257507

The Global Spine Care Initiative: a consensus process to develop and validate a stratification scheme for surgical care of spinal disorders as a guide for improved resource utilization in low- and middle-income communities.

PubMed

Acaroğlu, Emre; Mmopelwa, Tiro; Yüksel, Selcen; Ayhan, Selim; Nordin, Margareta; Randhawa, Kristi; Haldeman, Scott

2017-10-16

The purpose of this study was to develop a stratification scheme for surgical spinal care to serve as a framework for referrals and distribution of patients with spinal disorders. We used a modified Delphi process. A literature search identified experts for the consensus panel and the panel was expanded by inviting spine surgeons known to be global opinion leaders. After creating a seed document of five hierarchical levels of surgical care, a four-step modified Delphi process (question validation, collection of factors, evaluation of factors, re-evaluation of factors) was performed. Of 78 invited experts, 19 participated in round 1, and of the 19, 14 participated in 2, and 12 in 3 and 4. Consensus was fairly heterogeneous for levels of care 2-4 (moderate resources). Only simple assessment methods based on the clinical skills of the medical personnel were considered feasible and safe in low-resource settings. Diagnosis, staging, and treatment were deemed feasible and safe in a specialized spine center. Accurate diagnostic workup was deemed feasible and safe for lower levels of care complexity (from level 3 upwards) compared to non-invasive procedures (level 4) and the full range of invasive procedures (level 5). This study introduces a five-level stratification scheme for the surgical care of spinal disorders. This stratification may provide input into the Global Spine Care Initiative care pathway that will be applied in medically underserved areas and low- and middle-income countries. These slides can be retrieved under Electronic Supplementary Material.

Porcine Zygote Injection with Cas9/sgRNA Results in DMD-Modified Pig with Muscle Dystrophy.

PubMed

Yu, Hong-Hao; Zhao, Heng; Qing, Yu-Bo; Pan, Wei-Rong; Jia, Bao-Yu; Zhao, Hong-Ye; Huang, Xing-Xu; Wei, Hong-Jiang

2016-10-09

Dystrophinopathy, including Duchenne muscle dystrophy (DMD) and Becker muscle dystrophy (BMD) is an incurable X-linked hereditary muscle dystrophy caused by a mutation in the DMD gene in coding dystrophin. Advances in further understanding DMD/BMD for therapy are expected. Studies on mdx mice and dogs with muscle dystrophy provide limited insight into DMD disease mechanisms and therapeutic testing because of the different pathological manifestations. Miniature pigs share similar physiology and anatomy with humans and are thus an excellent animal model of human disease. Here, we successfully achieved precise DMD targeting in Chinese Diannan miniature pigs by co-injecting zygotes with Cas9 mRNA and sgRNA targeting DMD . Two piglets were obtained after embryo transfer, one of piglets was identified as DMD -modified individual via traditional cloning, sequencing and T7EN1 cleavage assay. An examination of targeting rates in the DMD -modified piglet revealed that sgRNA:Cas9-mediated on-target mosaic mutations were 70% and 60% of dystrophin alleles in skeletal and smooth muscle, respectively. Meanwhile, no detectable off-target mutations were found, highlighting the high specificity of genetic modification using CRISPR/Cas9. The DMD -modified piglet exhibited degenerative and disordered phenotypes in skeletal and cardiac muscle, and declining thickness of smooth muscle in the stomach and intestine. In conclusion, we successfully generated myopathy animal model by modifying the DMD via CRISPR/Cas9 system in a miniature pig.

Validation of modified forms of the PedsQL generic core scales and cancer module scales for adolescents and young adults (AYA) with cancer or a blood disorder.

PubMed

Ewing, Jane E; King, Madeleine T; Smith, Narelle F

2009-03-01

To validate two health-related quality of life (HRQOL) measures, the PedsQL Generic Core and Cancer Module adolescent forms (13-18 years), after modification for 16-25-year-old adolescents and young adults (AYA) with cancer or a blood disorder. AYA patients and nominated proxies were recruited from three Sydney hospitals. Modified forms were administered by telephone or in clinics/wards. Analyses included correlations, factor analysis, and analysis of variance of known-groups (defined by the Memorial Symptom Assessment Scale). Eighty-eight patients and 79 proxies completed questionnaires. Factor structures consistent with those of the unmodified forms confirmed construct validity. Cronbach's alpha ranged 0.81-0.98. Inter-scale correlations were as hypothesized, confirming discriminant validity. Statistically significant differences between groups with mild, moderate, and severe symptoms (P < 0.05) confirmed clinical validity. These modified forms provide reliable and valid measures of HRQOL in AYA with cancer or a blood disorder, suitable for clinical trials, research, and practice.

A Diagnostic Model for Dementia in Clinical Practice-Case Methodology Assisting Dementia Diagnosis.

PubMed

Londos, Elisabet

2015-04-02

Dementia diagnosis is important for many different reasons. Firstly, to separate dementia, or major neurocognitive disorder, from MCI (mild cognitive impairment), mild neurocognitive disorder. Secondly, to define the specific underlying brain disorder to aid treatment, prognosis and decisions regarding care needs and assistance. The diagnostic method of dementias is a puzzle of different data pieces to be fitted together in the best possible way to reach a clinical diagnosis. Using a modified case methodology concept, risk factors affecting cognitive reserve and symptoms constituting the basis of the brain damage hypothesis, can be visualized, balanced and reflected against test results as well as structural and biochemical markers. The model's origin is the case method initially described in Harvard business school, here modified to serve dementia diagnostics.

A Diagnostic Model for Dementia in Clinical Practice—Case Methodology Assisting Dementia Diagnosis

PubMed Central

Londos, Elisabet

2015-01-01

Dementia diagnosis is important for many different reasons. Firstly, to separate dementia, or major neurocognitive disorder, from MCI (mild cognitive impairment), mild neurocognitive disorder. Secondly, to define the specific underlying brain disorder to aid treatment, prognosis and decisions regarding care needs and assistance. The diagnostic method of dementias is a puzzle of different data pieces to be fitted together in the best possible way to reach a clinical diagnosis. Using a modified case methodology concept, risk factors affecting cognitive reserve and symptoms constituting the basis of the brain damage hypothesis, can be visualized, balanced and reflected against test results as well as structural and biochemical markers. The model’s origin is the case method initially described in Harvard business school, here modified to serve dementia diagnostics. PMID:26854146

Potential of chromatin modifying compounds for the treatment of Alzheimer's disease

PubMed Central

Karagiannis, Tom C.; Ververis, Katherine

2012-01-01

Alzheimer's disease is a very common progressive neurodegenerative disorder affecting the learning and memory centers in the brain. The hallmarks of disease are the accumulation of β-amyloid neuritic plaques and neurofibrillary tangles formed by abnormally phosphorylated tau protein. Alzheimer's disease is currently incurable and there is an intense interest in the development of new potential therapies. Chromatin modifying compounds such as sirtuin modulators and histone deacetylase inhibitors have been evaluated in models of Alzheimer's disease with some promising results. For example, the natural antioxidant and sirtuin 1 activator resveratrol has been shown to have beneficial effects in animal models of disease. Similarly, numerous histone deacetylase inhibitors including Trichostatin A, suberoylanilide hydroxamic acid, valproic acid and phenylbutyrate reduction have shown promising results in models of Alzheimer's disease. These beneficial effects include a reduction of β-amyloid production and stabilization of tau protein. In this review we provide an overview of the histone deacetylase enzymes, with a focus on enzymes that have been identified to have an important role in the pathobiology of Alzheimer's disease. Further, we discuss the potential for pharmacological intervention with chromatin modifying compounds that modulate histone deacetylase enzymes. PMID:22953035

Potential of chromatin modifying compounds for the treatment of Alzheimer's disease.

PubMed

Karagiannis, Tom C; Ververis, Katherine

2012-01-01

Alzheimer's disease is a very common progressive neurodegenerative disorder affecting the learning and memory centers in the brain. The hallmarks of disease are the accumulation of β-amyloid neuritic plaques and neurofibrillary tangles formed by abnormally phosphorylated tau protein. Alzheimer's disease is currently incurable and there is an intense interest in the development of new potential therapies. Chromatin modifying compounds such as sirtuin modulators and histone deacetylase inhibitors have been evaluated in models of Alzheimer's disease with some promising results. For example, the natural antioxidant and sirtuin 1 activator resveratrol has been shown to have beneficial effects in animal models of disease. Similarly, numerous histone deacetylase inhibitors including Trichostatin A, suberoylanilide hydroxamic acid, valproic acid and phenylbutyrate reduction have shown promising results in models of Alzheimer's disease. These beneficial effects include a reduction of β-amyloid production and stabilization of tau protein. In this review we provide an overview of the histone deacetylase enzymes, with a focus on enzymes that have been identified to have an important role in the pathobiology of Alzheimer's disease. Further, we discuss the potential for pharmacological intervention with chromatin modifying compounds that modulate histone deacetylase enzymes.

Lessons from obesity prevention for the prevention of mental disorders: the primordial prevention approach.

PubMed

Hayward, Joshua; Jacka, Felice N; Waters, Elizabeth; Allender, Steven

2014-09-10

Emerging evidence supports a relationship between risk factors for obesity and the genesis of the common mental disorders, depression and anxiety. This suggests common mental disorders should be considered as a form of non-communicable disease, preventable through the modification of lifestyle behaviours, particularly diet and physical activity. Obesity prevention research since the 1970's represents a considerable body of knowledge regarding strategies to modify diet and physical activity and so there may be clear lessons from obesity prevention that apply to the prevention of mental disorders. For obesity, as for common mental disorders, adolescence represents a key period of vulnerability. In this paper we briefly discuss relationships between modifiable lifestyle risk factors and mental health, lifestyle risk factor interventions in obesity prevention research, the current state of mental health prevention, and the implications of current applications of systems thinking in obesity prevention research for lifestyle interventions. We propose a potential focus for future mental health promotion interventions and emphasise the importance of lessons available from other lifestyle modification intervention programmes.

Baseline Factors Predicting Placebo Response to Treatment in Children and Adolescents With Autism Spectrum Disorders

PubMed Central

King, Bryan H.; Dukes, Kimberly; Donnelly, Craig L.; Sikich, Linmarie; McCracken, James T.; Scahill, Lawrence; Hollander, Eric; Bregman, Joel D.; Anagnostou, Evdokia; Robinson, Fay; Sullivan, Lisa; Hirtz, Deborah

2016-01-01

IMPORTANCE The finding of factors that differentially predict the likelihood of response to placebo over that of an active drug could have a significant impact on study design in this population. OBJECTIVE To identify possible nonspecific, baseline predictors of response to intervention in a large randomized clinical trial of children and adolescents with autism spectrum disorders. DESIGN, SETTING, AND PARTICIPANTS Randomized clinical trial of citalopram hydrobromide for children and adolescents with autism spectrum disorders and prominent repetitive behavior. Baseline data at study entry were examined with respect to final outcome to determine if response predictors could be identified. A total of 149 children and adolescents 5 to 17 years of age (mean [SD] age, 9.4 [3.1] years) from 6 academic centers were randomly assigned to citalopram (n = 73) or placebo (n = 76). Participants had autistic disorder, Asperger syndrome, or pervasive developmental disorder, not otherwise specified; had illness severity ratings that were moderate or more than moderate on the Clinical Global Impression–Severity scale; and scored moderate or more than moderate on compulsive behaviors measured with the modified Children’s Yale-Brown Obsessive-Compulsive Scale. INTERVENTIONS Twelve weeks of treatment with citalopram (10 mg/5 mL) or placebo. The mean (SD) maximum dose of citalopram was 16.5 (6.5) mg by mouth daily (maximum dose, 20 mg/d). MAIN OUTCOMES AND MEASURES A positive response was defined as having a score of at least much improved on the Clinical Global Impression–Improvement scale at week 12. Baseline measures included demographic (sex, age, weight, and pubertal status), clinical, and family measures. Clinical variables included baseline illness severity ratings (the Aberrant Behavior Checklist, the Child and Adolescent Symptom Inventory, the Vineland Adaptive Behavior Scales, the Repetitive Behavior Scale–Revised, and the Children’s Yale-Brown Obsessive-Compulsive Scale). Family measures included the Caregiver Strain Questionnaire. RESULTS Several baseline predictors of response were identified, and a principal component analysis yielded 3 composite measures (disruptive behavior, autism/mood, and caregiver strain) that significantly predicted response at week 12. Specifically, participants in the placebo group were significantly less likely than participants in the citalopram group to respond at week 12 if they entered the study more symptomatic on each of the 3 composite measures, and they were at least 2 times less likely to be responders. CONCLUSIONS AND RELEVANCE This analysis suggests strategies that may be useful in anticipating and potentially mitigating the nonspecific response in randomized clinical trials of children and adolescents with autism spectrum disorders. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT00086645 PMID:24061784

Neurological manifestations of influenza infection in children and adults: results of a National British Surveillance Study.

PubMed

Goenka, Anu; Michael, Benedict D; Ledger, Elizabeth; Hart, Ian J; Absoud, Michael; Chow, Gabriel; Lilleker, James; Lunn, Michael; McKee, David; Peake, Deirdre; Pysden, Karen; Roberts, Mark; Carrol, Enitan D; Lim, Ming; Avula, Shivaram; Solomon, Tom; Kneen, Rachel

2014-03-01

The emergence of influenza A(H1N1) 2009 was met with increased reports of associated neurological manifestations. We aimed to describe neurological manifestations of influenza in adults and children in the United Kingdom that presented at this time. A 2-year surveillance study was undertaken through the British adult and pediatric neurological surveillance units from February 2011. Patients were included if they met clinical case definitions within 1 month of proven influenza infection. Twenty-five cases were identified: 21 (84%) in children and 4 (16%) in adults. Six (29%) children had preexisting neurological disorders. Polymerase chain reaction of respiratory secretions identified influenza A in 21 (81%; 20 of which [95%] were H1N1) and influenza B in 4 (15%). Twelve children had encephalopathy (1 with movement disorder), 8 had encephalitis, and 1 had meningoencephalitis. Two adults had encephalopathy with movement disorder, 1 had encephalitis, and 1 had Guillain-Barré syndrome. Seven individuals (6 children) had specific acute encephalopathy syndromes (4 acute necrotizing encephalopathy, 1 acute infantile encephalopathy predominantly affecting the frontal lobes, 1 hemorrhagic shock and encephalopathy, 1 acute hemorrhagic leukoencephalopathy). Twenty (80%) required intensive care, 17 (68%) had poor outcome, and 4 (16%) died. This surveillance study described a cohort of adults and children with neurological manifestations of influenza. The majority were due to H1N1. More children than adults were identified; many children had specific encephalopathy syndromes with poor outcomes. None had been vaccinated, although 8 (32%) had indications for this. A modified classification system is proposed based on our data and the increasing spectrum of recognized acute encephalopathy syndromes.

Performance of polygenic scores for predicting phobic anxiety.

PubMed

Walter, Stefan; Glymour, M Maria; Koenen, Karestan; Liang, Liming; Tchetgen Tchetgen, Eric J; Cornelis, Marilyn; Chang, Shun-Chiao; Rimm, Eric; Kawachi, Ichiro; Kubzansky, Laura D

2013-01-01

Anxiety disorders are common, with a lifetime prevalence of 20% in the U.S., and are responsible for substantial burdens of disability, missed work days and health care utilization. To date, no causal genetic variants have been identified for anxiety, anxiety disorders, or related traits. To investigate whether a phobic anxiety symptom score was associated with 3 alternative polygenic risk scores, derived from external genome-wide association studies of anxiety, an internally estimated agnostic polygenic score, or previously identified candidate genes. Longitudinal follow-up study. Using linear and logistic regression we investigated whether phobic anxiety was associated with polygenic risk scores derived from internal, leave-one out genome-wide association studies, from 31 candidate genes, and from out-of-sample genome-wide association weights previously shown to predict depression and anxiety in another cohort. Study participants (n = 11,127) were individuals from the Nurses' Health Study and Health Professionals Follow-up Study. Anxiety symptoms were assessed via the 8-item phobic anxiety scale of the Crown Crisp Index at two time points, from which a continuous phenotype score was derived. We found no genome-wide significant associations with phobic anxiety. Phobic anxiety was also not associated with a polygenic risk score derived from the genome-wide association study beta weights using liberal p-value thresholds; with a previously published genome-wide polygenic score; or with a candidate gene risk score based on 31 genes previously hypothesized to predict anxiety. There is a substantial gap between twin-study heritability estimates of anxiety disorders ranging between 20-40% and heritability explained by genome-wide association results. New approaches such as improved genome imputations, application of gene expression and biological pathways information, and incorporating social or environmental modifiers of genetic risks may be necessary to identify significant genetic predictors of anxiety.

Genetic Epidemiology and Insights into Interactive Genetic and Environmental Effects in Autism Spectrum Disorders

PubMed Central

Kim, Young Shin; Leventhal, Bennett L.

2014-01-01

Understanding the pathogenesis of Neurodevelopmental Disorders (NDDs) has proven to be challenging. Using Autism Spectrum Disorder (ASD) as a paradigmatic NDD, this paper reviews the existing literature on the etiologic substrates of ASD and explores how genetic epidemiology approaches including gene-environment interactions (GxE) can play roles in identifying factors associated with ASD etiology. New genetic and bioinformatics strategies have yielded important clues to ASD genetic substrates. Next steps for understanding ASD pathogenesis require significant effort to focus on how genes and environment interact with one another in typical development and its perturbations. Along with larger sample sizes, future study designs should include sample ascertainment that is epidemiologic and population-based to capture the entire ASD spectrum with both categorical and dimensional phenotypic characterization, environmental measurement with accuracy, validity and biomarkers, statistical methods to address population stratification, multiple comparisons and GxE of rare variants, animal models to test hypotheses and, new methods to broaden the capacity to search for GxE, including genome-wide and environment-wide association studies, precise estimation of heritability using dense genetic markers and consideration of GxE both as the disease cause and a disease course modifier. While examination of GxE appears to be a daunting task, tremendous recent progress in gene discovery opens new horizons for advancing our understanding the role of GxE in the pathogenesis of, and ultimately identifying the causes, treatments and even prevention for ASD and other NDDs. PMID:25483344

Developing a broad categorisation scheme to describe risk factors for mental illness, for use in prevention policy and planning.

PubMed

Furber, Gareth; Leach, Matthew; Guy, Sophie; Segal, Leonie

2017-03-01

The prevention of mental illness involves identifying and modifying those characteristics and exposures of an individual that threaten their mental health - commonly referred to as risk factors. Existing categorisations of risk factors for mental illness are either limited in their scope or oversimplified in their description. As part of a large mental health workforce and service planning project, we set out to develop a more detailed and comprehensive categorisation scheme to describe risk factors for mental illness. We conducted a rapid review of MEDLINE and Google Scholar for meta-analytic studies that examined the characteristics and exposures that typify the population with mental illness in order to identify and categorise potential risk factors. The search uncovered 1628 relevant studies, from which 10 primary and 23 secondary categories of risk factors were identified, ranging from genetic and biomedical to psychological and sociocultural. The review revealed interesting distortions in the focus of the literature, with the majority of studies focused on a few disorders (schizophrenia, depression and neurodegenerative disorders) and genetic, psychological and physiological risks. In contrast, environmental (e.g. media exposure) and occupational (e.g. employee health) were under-represented. The categorisation scheme developed in this paper is a step towards a more detailed taxonomy of risk factors for mental illness; this will be most useful in guiding clinicians, researchers and policy-makers in driving the prevention agenda forward.

The Psychosomatic Disorders Pertaining to Dental Practice with Revised Working Type Classification

PubMed Central

2014-01-01

Psychosomatic disorders are defined as disorders characterized by physiological changes that originate partially from emotional factors. This article aims to discuss the psychosomatic disorders of the oral cavity with a revised working type classification. The author has added one more subset to the existing classification, i.e., disorders caused by altered perception of dentofacial form and function, which include body dysmorphic disorder. The author has also inserted delusional halitosis under the miscellaneous disorders classification of psychosomatic disorders and revised the already existing classification proposed for the psychosomatic disorders pertaining to dental practice. After the inclusion of the subset (disorders caused by altered perception of dentofacial form and function), the terminology "psychosomatic disorders of the oral cavity" is modified to "psychosomatic disorders pertaining to dental practice". PMID:24478896

The psychosomatic disorders pertaining to dental practice with revised working type classification.

PubMed

Shamim, Thorakkal

2014-01-01

Psychosomatic disorders are defined as disorders characterized by physiological changes that originate partially from emotional factors. This article aims to discuss the psychosomatic disorders of the oral cavity with a revised working type classification. The author has added one more subset to the existing classification, i.e., disorders caused by altered perception of dentofacial form and function, which include body dysmorphic disorder. The author has also inserted delusional halitosis under the miscellaneous disorders classification of psychosomatic disorders and revised the already existing classification proposed for the psychosomatic disorders pertaining to dental practice. After the inclusion of the subset (disorders caused by altered perception of dentofacial form and function), the terminology "psychosomatic disorders of the oral cavity" is modified to "psychosomatic disorders pertaining to dental practice".

Silver Nanoparticle Modified Electrode Covered by Graphene Oxide for the Enhanced Electrochemical Detection of Dopamine

PubMed Central

Shin, Jae-Wook; Kim, Kyeong-Jun; Yoon, Jinho; Jo, Jinhee; El-Said, Waleed Ahmed; Choi, Jeong-Woo

2017-01-01

Several neurological disorders such as Alzheimer’s disease and Parkinson’s disease have become a serious impediment to aging people nowadays. One of the efficient methods used to monitor these neurological disorders is the detection of neurotransmitters such as dopamine. Metal materials, such as gold and platinum, are widely used in this electrochemical detection method; however, low sensitivity and linearity at low dopamine concentrations limit the use of these materials. To overcome these limitations, a silver nanoparticle (SNP) modified electrode covered by graphene oxide for the detection of dopamine was newly developed in this study. For the first time, the surface of an indium tin oxide (ITO) electrode was modified using SNPs and graphene oxide sequentially through the electrochemical deposition method. The developed biosensor provided electrochemical signal enhancement at low dopamine concentrations in comparison with previous biosensors. Therefore, our newly developed SNP modified electrode covered by graphene oxide can be used to monitor neurological diseases through electrochemical signal enhancement at low dopamine concentrations. PMID:29186040

Silver Nanoparticle Modified Electrode Covered by Graphene Oxide for the Enhanced Electrochemical Detection of Dopamine.

PubMed

Shin, Jae-Wook; Kim, Kyeong-Jun; Yoon, Jinho; Jo, Jinhee; El-Said, Waleed Ahmed; Choi, Jeong-Woo

2017-11-29

Several neurological disorders such as Alzheimer's disease and Parkinson's disease have become a serious impediment to aging people nowadays. One of the efficient methods used to monitor these neurological disorders is the detection of neurotransmitters such as dopamine. Metal materials, such as gold and platinum, are widely used in this electrochemical detection method; however, low sensitivity and linearity at low dopamine concentrations limit the use of these materials. To overcome these limitations, a silver nanoparticle (SNP) modified electrode covered by graphene oxide for the detection of dopamine was newly developed in this study. For the first time, the surface of an indium tin oxide (ITO) electrode was modified using SNPs and graphene oxide sequentially through the electrochemical deposition method. The developed biosensor provided electrochemical signal enhancement at low dopamine concentrations in comparison with previous biosensors. Therefore, our newly developed SNP modified electrode covered by graphene oxide can be used to monitor neurological diseases through electrochemical signal enhancement at low dopamine concentrations.

The efficacy of the modified Atkins diet in North Sea Progressive Myoclonus Epilepsy: an observational prospective open-label study.

PubMed

van Egmond, Martje E; Weijenberg, Amerins; van Rijn, Margreet E; Elting, Jan Willem J; Gelauff, Jeannette M; Zutt, Rodi; Sival, Deborah A; Lambrechts, Roald A; Tijssen, Marina A J; Brouwer, Oebele F; de Koning, Tom J

2017-03-07

North Sea Progressive Myoclonus Epilepsy is a rare and severe disorder caused by mutations in the GOSR2 gene. It is clinically characterized by progressive myoclonus, seizures, early-onset ataxia and areflexia. As in other progressive myoclonus epilepsies, the efficacy of antiepileptic drugs is disappointingly limited in North Sea Progressive Myoclonus Epilepsy. The ketogenic diet and the less restrictive modified Atkins diet have been proven to be effective in other drug-resistant epilepsy syndromes, including those with myoclonic seizures. Our aim was to evaluate the efficacy of the modified Atkins diet in patients with North Sea Progressive Myoclonus Epilepsy. Four North Sea Progressive Myoclonus Epilepsy patients (aged 7-20 years) participated in an observational, prospective, open-label study on the efficacy of the modified Atkins diet. Several clinical parameters were assessed at baseline and again after participants had been on the diet for 3 months. The primary outcome measure was health-related quality of life, with seizure frequency and blinded rated myoclonus severity as secondary outcome measures. Ketosis was achieved within 2 weeks and all patients completed the 3 months on the modified Atkins diet. The diet was well tolerated by all four patients. Health-related quality of life improved considerably in one patient and showed sustained improvement during long-term follow-up, despite the progressive nature of the disorder. Health-related quality of life remained broadly unchanged in the other three patients and they did not continue the diet. Seizure frequency remained stable and blinded rating of their myoclonus showed improvement, albeit modest, in all patients. This observational, prospective study shows that some North Sea Progressive Myoclonus Epilepsy patients may benefit from the modified Atkins diet with sustained health-related quality of life improvement. Not all our patients continued on the diet, but nonetheless we show that the modified Atkins diet might be considered as a possible treatment in this devastating disorder.

[Repetitive transcranial magnetic stimulation: A potential therapy for cognitive disorders?

PubMed

Nouhaud, C; Sherrard, R M; Belmin, J

2017-03-01

Considering the limited effectiveness of drugs treatments in cognitive disorders, the emergence of noninvasive techniques to modify brain function is very interesting. Among these techniques, repetitive transcranial magnetic stimulation (rTMS) can modulate cortical excitability and have potential therapeutic effects on cognition and behaviour. These effects are due to physiological modifications in the stimulated cortical tissue and their associated circuits, which depend on the parameters of stimulation. The objective of this article is to specify current knowledge and efficacy of rTMS in cognitive disorders. Previous studies found very encouraging results with significant improvement of higher brain functions. Nevertheless, these few studies have limits: a few patients were enrolled, the lack of control of the mechanisms of action by brain imaging, insufficiently formalized technique and variability of cognitive tests. It is therefore necessary to perform more studies, which identify statistical significant improvement and to specify underlying mechanisms of action and the parameters of use of the rTMS to offer rTMS as a routine therapy for cognitive dysfunction. Copyright © 2016 Société Nationale Française de Médecine Interne (SNFMI). Published by Elsevier SAS. All rights reserved.

Risk Assessment for Parents Who Suspect Their Child Has Autism Spectrum Disorder: Machine Learning Approach.

PubMed

Ben-Sasson, Ayelet; Robins, Diana L; Yom-Tov, Elad

2018-04-24

Parents are likely to seek Web-based communities to verify their suspicions of autism spectrum disorder markers in their child. Automated tools support human decisions in many domains and could therefore potentially support concerned parents. The objective of this study was to test the feasibility of assessing autism spectrum disorder risk in parental concerns from Web-based sources, using automated text analysis tools and minimal standard questioning. Participants were 115 parents with concerns regarding their child's social-communication development. Children were 16- to 30-months old, and 57.4% (66/115) had a family history of autism spectrum disorder. Parents reported their concerns online, and completed an autism spectrum disorder-specific screener, the Modified Checklist for Autism in Toddlers-Revised, with Follow-up (M-CHAT-R/F), and a broad developmental screener, the Ages and Stages Questionnaire (ASQ). An algorithm predicted autism spectrum disorder risk using a combination of the parent's text and a single screening question, selected by the algorithm to enhance prediction accuracy. Screening measures identified 58% (67/115) to 88% (101/115) of children at risk for autism spectrum disorder. Children with a family history of autism spectrum disorder were 3 times more likely to show autism spectrum disorder risk on screening measures. The prediction of a child's risk on the ASQ or M-CHAT-R was significantly more accurate when predicted from text combined with an M-CHAT-R question selected (automatically) than from the text alone. The frequently automatically selected M-CHAT-R questions that predicted risk were: following a point, make-believe play, and concern about deafness. The internet can be harnessed to prescreen for autism spectrum disorder using parental concerns by administering a few standardized screening questions to augment this process. ©Ayelet Ben-Sasson, Diana L Robins, Elad Yom-Tov. Originally published in the Journal of Medical Internet Research (http://www.jmir.org), 24.04.2018.

Different results on tetrachorical correlations in Mplus and Stata--Stata announces modified procedure.

PubMed

Günther, Agnes; Höfler, Michael

2006-01-01

To identify the structure of mental disorders in large-scale epidemiological data sets, investigators frequently use tetrachoric correlations as a first step for subsequent application of latent class and factor analytic methods. It has been possible to do this with Stata since 2005, whereas the corresponding Mplus routine has been on the market for some years. Using an identical data set we observed considerable differences between the results of the packages. This paper illustrates the differences with several examples from the Early Developmental Stages of Psychopathology Study data set, which consists of 3021 subjects, with diagnostic information assessed by the CIDI. Results reveal that tetrachoric correlations resulting from Mplus were often considerably smaller than those computed with Stata. The results were dramatically different, especially where there were few observation per cell or even empty cells. These findings were put to Mplus and Stata, whose responses clarified the discrepancies by describing the different mathematical assumptions and procedures used. Stata announced that it intended to launch a modified procedure.

Composition of a Vision Screen for Servicemembers With Traumatic Brain Injury: Consensus Using a Modified Nominal Group Technique

PubMed Central

Finkelstein, Marsha; Llanos, Imelda; Scheiman, Mitchell; Wagener, Sharon Gowdy

2014-01-01

Vision impairment is common in the first year after traumatic brain injury (TBI), including among service members whose brain injuries occurred during deployment in Iraq and Afghanistan. Occupational therapy practitioners provide routine vision screening to inform treatment planning and referral to vision specialists, but existing methods are lacking because many tests were developed for children and do not screen for vision dysfunction typical of TBI. An expert panel was charged with specifying the composition of a vision screening protocol for servicemembers with TBI. A modified nominal group technique fostered discussion and objective determinations of consensus. After considering 29 vision tests, the panel recommended a nine-test vision screening that examines functional performance, self-reported problems, far–near acuity, reading, accommodation, convergence, eye alignment and binocular vision, saccades, pursuits, and visual fields. Research is needed to develop reliable, valid, and clinically feasible vision screening protocols to identify TBI-related vision disorders in adults. PMID:25005505

Significance of borderline personality-spectrum symptoms among adolescents with bipolar disorder.

PubMed

Fonseka, Trehani M; Swampillai, Brenda; Timmins, Vanessa; Scavone, Antonette; Mitchell, Rachel; Collinger, Katelyn A; Goldstein, Benjamin I

2015-01-01

Little is known regarding correlates of borderline personality-spectrum symptoms (BPSS) among adolescents with bipolar disorder (BP). Participants were 90 adolescents, 13-19 years of age, who fulfilled DSM-IV-TR criteria for BP using semi-structured diagnostic interviews. BPSS status was ascertained using the Life Problems Inventory which assessed identity confusion, interpersonal problems, impulsivity, and emotional lability. Analyses compared adolescents with "high" versus "low" BPSS based on a median split. Participants with high, relative to low, BPSS were younger, and had greater current and past depressive episode severity, greater current hypo/manic episode severity, younger age of depression onset, and reduced global functioning. High BPSS participants were more likely to have BP-II, and had higher rates of social phobia, generalized anxiety disorder, conduct disorder, oppositional defiant disorder, homicidal ideation, assault of others, non-suicidal self-injury, suicidal ideation, and physical abuse. Despite greater illness burden, high BPSS participants reported lower rates of lithium use. The most robust independent predictors of high BPSS, identified in multivariate analyses, included lifetime social phobia, non-suicidal self-injury, reduced global functioning, and conduct and/or oppositional defiant disorder. The study design is cross-sectional and cannot determine causality. High BPSS were associated with greater mood symptom burden and functional impairment. Presence of high BPSS among BP adolescents may suggest the need to modify clinical monitoring and treatment practices. Future prospective studies are needed to examine the direction of observed associations, the effect of treatment on BPSS, and the effect of BPSS as a moderator or predictor of treatment response. Copyright © 2014 Elsevier B.V. All rights reserved.

Evidence-based guideline: assessment and management of psychiatric disorders in individuals with MS: report of the Guideline Development Subcommittee of the American Academy of Neurology.

PubMed

Minden, Sarah L; Feinstein, Anthony; Kalb, Rosalind C; Miller, Deborah; Mohr, David C; Patten, Scott B; Bever, Christopher; Schiffer, Randolph B; Gronseth, Gary S; Narayanaswami, Pushpa

2014-01-14

To make evidence-based recommendations for screening, diagnosing, and treating psychiatric disorders in individuals with multiple sclerosis (MS). We reviewed the literature (1950 to August 2011) and evaluated the available evidence. Clinicians may consider using the Center for Neurologic Study Emotional Lability Scale to screen for pseudobulbar affect (Level C). Clinicians may consider the Beck Depression Inventory and a 2-question tool to screen for depressive disorders and the General Health Questionnaire to screen for broadly defined emotional disturbances (Level C). Evidence is insufficient to support/refute the use of other screening tools, the possibility that somatic/neurovegetative symptoms affect these tools' accuracy, or the use of diagnostic instruments or clinical evaluation procedures for identifying psychiatric disorders in MS (Level U). Clinicians may consider a telephone-administered cognitive behavioral therapy program for treating depressive symptoms (Level C). Although pharmacologic and nonpharmacologic therapies are widely used to treat depressive and anxiety disorders in individuals with MS, evidence is insufficient to support/refute the use of the antidepressants and individual and group therapies reviewed herein (Level U). For pseudobulbar affect, a combination of dextromethorphan and quinidine may be considered (Level C). Evidence is insufficient to determine the psychiatric effects in individuals with MS of disease-modifying and symptomatic therapies and corticosteroids; risk factors for suicide; and treatment of psychotic disorders (Level U). Research is needed on the effectiveness in individuals with MS of pharmacologic and nonpharmacologic treatments frequently used in the non-MS population.

Examining the association between psychiatric illness and suicidal ideation in a sample of treatment-seeking Canadian peacekeeping and combat veterans with posttraumatic stress disorder PTSD.

PubMed

Richardson, J Don; St Cyr, Kate C M; McIntyre-Smith, Alexandra M; Haslam, David; Elhai, Jon D; Sareen, Jitender

2012-08-01

Our study examines the association between suicidal ideation and and self-reported symptoms of posttraumatic stress disorder (PTSD), major depressive disorder (MDD), generalized anxiety disorder (GAD), and alcohol use disorder (AUD) in a sample of treatment-seeking Canadian combat and peacekeeping veterans; and identifies potential predictors of suicidal ideation. Actively serving Canadian Forces and Royal Canadian Mounted Police members and veterans seeking treatment at the Parkwood Hospital Operational Stress Injury Clinic (n = 250) completed measures including the Primary Care Evaluation of Mental Disorders Patient Health Questionnaire, the Alcohol Use Disorder Identification Test, and the PTSD Checklist-Military Version (PCL-M) between January 2002 and December 2010. Regression analyses were used to determine the respective impact of PTSD, and self-reported symptoms of MDD, GAD, AUD, and anxiety on suicidal ideation. Most people met PCL-M screening criteria for PTSD (73.6%, n = 184), while 70.8% (n = 177) screened positively for a probable major depressive episode. PTSD symptom was significantly associated with suicidal ideation (β = 0.412, P < 0.001). After controlling for self-reported depressive symptom severity, AUD severity, and generalized anxiety, PTSD severity was no longer significantly associated with suicidal ideation (β = 0.043, P = 0.58). Although PTSD alone is associated with suicidal ideation, after controlling for common comorbid psychiatric illnesses, self-reported depressive symptom severity emerged as the most significant predictor of suicidal ideation. These findings support the importance of screening for comorbidities, particularly an MDD, as potentially modifiable conditions that are strongly related to suicidal ideation in military personnel's endorsing criteria for PTSD.

“Selfish spermatogonial selection”: a novel mechanism for the association between advanced paternal age and neurodevelopmental disorders

PubMed Central

Goriely, Anne; McGrath, John J.; Hultman, Christina M.; Wilkie, Andrew O.M.; Malaspina, Dolores

2014-01-01

Objectives There is robust evidence from epidemiological studies that the offspring of older fathers have an increased risk of neurodevelopmental disorders such as schizophrenia and autism. Here we present a novel mechanism that may contribute to this association. Methods Narrative review. Results Because the male germ cell undergoes many more cell divisions across the reproductive age range, copy-errors taking place in the paternal germline are associated with de novo mutations in the offspring of older men. Recently it has been recognized that somatic mutations in male germ cells that modify proliferation via dysregulation of the RAS pathway can lead to within-testis expansion of mutant clonal lines. First identified in association with rare paternal age-effect disorders (e.g. Apert syndrome, achondroplasia), this process is known as ‘selfish spermatogonial selection’. This mechanism will (a) favor propagation of germ cells carrying pathogenic mutations, (b) increasingly skew the mutational profile of sperm as men age, and (c) result in an enrichment of de novo mutations in the offspring of older fathers that preferentially impact on specific cellular signaling pathways. This mechanism offers a parsimonious explanation not only for the association between advanced paternal age and various neurodevelopmental disorders, but also provides insights into the genetic architecture (role of de novo mutations), neurobiological correlates (altered cell cycle) and some epidemiological features of these disorders. We outline hypotheses to test this model. Conclusions In light of our current understanding of the genetic networks involved in neurocognitive disorders and the principles of selfish spermatogonial selection, we speculate that some pathogenic mutations associated with these disorders are the consequence of a selfish mechanism originating in the aging testis. Given the secular changes for delayed parenthood in most societies, this hypothesis has important public health implications. PMID:23639989

Mechanism-based treatments in neurodevelopmental disorders: fragile X syndrome.

PubMed

Berry-Kravis, Elizabeth

2014-04-01

Fragile X syndrome (FXS) is the most common identifiable genetic cause of intellectual disability and autistic spectrum disorders. Recent major advances have been made in the understanding of the neurobiology and functions of fragile X mental retardation protein, the FMR1 gene product, which is absent or reduced in FXS, largely based on work in the fmr1 knockout mouse model. FXS has emerged as a disorder of synaptic plasticity associated with abnormalities of long-term depression and long-term potentiation and immature dendritic spine architecture, related to dysregulation of dendritic translation typically activated by group I mGluR and other receptors. This work has led to efforts to develop treatments for FXS with neuroactive molecules targeted to pathways dysregulated in the absence of fragile X mental retardation protein. These agents have been shown to rescue molecular, spine, and behavioral phenotypes in the FXS mouse model, and clinical trials are underway to translate findings in animal models of FXS to humans, raising complex issues about trial design and outcome measures to assess disease-modifying changes that might be associated with treatment. Genes known to be causes of autistic spectrum disorders interact with the translational pathway defective in FXS and it is likely that there will be substantial overlap in molecular pathways and mechanisms of synaptic dysfunction. Thus targeted treatment and clinical trial strategies in FXS may serve as a model for ASD and other cognitive disorders. Copyright © 2014 Elsevier Inc. All rights reserved.

The Future of D-Cycloserine and Other Cognitive Modifiers in Obsessive-Compulsive and Related Disorders

PubMed Central

Sulkowski, Michael L.; Geller, Daniel A.; Lewin, Adam B.; Murphy, Tanya K.; Mittelman, Andrew; Brown, Ashley; Storch, Eric A.

2014-01-01

Variants of exposure therapy are effective for treating obsessive-compulsive and related disorders (OCRDs). However, significant numbers of patients do not respond adequately to exposure therapy resulting in continued distress and functional impairment. Therefore, novel approaches to augmenting exposure therapy are needed to adequately treat non- and partial-responders. Emerging research suggests that interventions that augment learning and memory processes associated with exposure therapy (i.e., extinction training) may display promise in enhancing treatment response in OCRDs. As the most studied example, d-cycloserine (DCS) is a relatively safe cognitive enhancer that appears to accelerate treatment gains associated with exposure therapy. This article reviews research on the use of DCS and other putative cognitive modifiers as they relate to the treatment (or prospective treatment) of obsessive-compulsive disorder and other OCRDs. PMID:25383074

Tuning thermal conductivity in molybdenum disulfide by electrochemical intercalation

PubMed Central

Zhu, Gaohua; Liu, Jun; Zheng, Qiye; Zhang, Ruigang; Li, Dongyao; Banerjee, Debasish; Cahill, David G.

2016-01-01

Thermal conductivity of two-dimensional (2D) materials is of interest for energy storage, nanoelectronics and optoelectronics. Here, we report that the thermal conductivity of molybdenum disulfide can be modified by electrochemical intercalation. We observe distinct behaviour for thin films with vertically aligned basal planes and natural bulk crystals with basal planes aligned parallel to the surface. The thermal conductivity is measured as a function of the degree of lithiation, using time-domain thermoreflectance. The change of thermal conductivity correlates with the lithiation-induced structural and compositional disorder. We further show that the ratio of the in-plane to through-plane thermal conductivity of bulk crystal is enhanced by the disorder. These results suggest that stacking disorder and mixture of phases is an effective mechanism to modify the anisotropic thermal conductivity of 2D materials. PMID:27767030

Boundary modifications in the treatment of people with dissociative disorders: a pilot study.

PubMed

Sachs, Adah

2013-01-01

This article examines the prevalence and types of modifications to professional boundaries that occur in the treatment of people with dissociative disorders (DDs) and considers some of the implications of the findings. The study is based on the replies of 163 professionals to a 20-question survey. The survey compared the boundaries that each practitioner kept with patients/clients (P/Cs) who suffered DDs to their boundary practice with all of their other P/Cs (non-DDs). Boundaries were deemed modified when professionals treated their DDs P/Cs differently than their other P/Cs. Professionals' general boundaries were not examined. The results showed a marked tendency for the modification of professional boundaries when treating people with DDs. These results appeared to be independent of country or profession but were more pronounced among the more experienced professionals. Areas of greatest modifications were identified. The prevalence of these modifications points to their potential importance in understanding some features of DDs.

Influence of the DSM-IV Outline for Cultural Formulation on multidisciplinary case conferences in mental health.

PubMed

Dinh, Nathalie M H; Groleau, Danielle; Kirmayer, Laurence J; Rodriguez, Charo; Bibeau, Gilles

2012-01-01

The Diagnostic and Statistical Manual of Mental Disorders of the American Psychiatric Association (DSM-IV-TR) includes an Outline for Cultural Formulation (CF) that identifies cultural information that can be used to modify diagnosis, clinical assessment and treatment plan. This study examined the use of the CF by a Cultural Consultation Service in the psychiatric assessment of patients referred by primary care providers. The study uses conversation analysis of 12 clinical case conferences to explore the ways in which the CF influenced the interaction of a multidisciplinary group of mental health professionals in conceptualizing the implications of patients' cultural background and current context for diagnosis and treatment planning. The results suggest that the CF can be a useful tool for interdisciplinary collaboration and knowledge transfer by providing a framework to systematically introduce different disciplinary perspectives and levels of description that transcend the narrow frame of disorder-centred psychiatric diagnosis, assessment and care.

Alcohol use disorders among pulmonary tuberculosis patients under RNTCP in urban Pondicherry, India.

PubMed

Veerakumar, A M; Sahu, Swaroop Kumar; Sarkar, Sonali; Kattimani, Shivanand; Govindarajan, S

2015-07-01

Alcohol use is implicated in a wide variety of diseases and disorders including TB. To study the prevalence and pattern of alcohol use among the PTB patients registered under RNTCP in urban Pondicherry and the association of various socio-demographic variables with alcohol drinking during treatment. A cross-sectional study was conducted among 235 PTB patients from 6 randomly selected urban PHCs of Pondicherry from Jan 2013 to March 2014. Alcohol Use Disorder Identification Test (AUDIT) was used for screening the PTB patients for their severity of alcohol use. Data were entered in Epi-data v3.1 and was analyzed by SPSS v20. Chi-square test and multiple-logistic regression were used. Prevalence of alcohol use among PTB patients at the time of diagnosis was 59% and during treatment was 31.5%. Around 54% PTB patients had alcohol use disorders (AUD) during diagnosis, whereas the same during treatment was 26.4%. Among drinkers at the time of diagnosis (n=139), 80% modified and 20% did not modify their alcohol use even after TB diagnosis. Male gender was significantly associated with alcohol use (p≤0.001). Univariate analysis showed that lower level of education, lower SES, unemployed/unskilled/semiskilled/skilled occupational group, and Category II were significantly associated with alcohol use among male patients (p<0.05). Multivariate analysis showed that none of the variables were associated. One-third of PTB patients were drinking alcohol during the treatment. Though 80% modified alcohol use after TB diagnosis, the rest 20% did not modify. Necessary interventions need to be planned to screen for alcohol use. Copyright © 2015 Tuberculosis Association of India. Published by Elsevier B.V. All rights reserved.

ECT Has Greater Efficacy Than Fluoxetine in Alleviating the Burden of Illness for Patients with Major Depressive Disorder: A Taiwanese Pooled Analysis

PubMed Central

Huang, Chun-Jen; Chen, Cheng-Chung

2018-01-01

Abstract Background The burden of major depressive disorder includes suffering due to symptom severity, functional impairment, and quality of life deficits. The aim of this study was to compare the differences between electroconvulsive therapy and pharmacotherapy in reducing such burdens. Methods This was a pooled analysis study including 2 open-label trials for major depressive disorder inpatients receiving either standard bitemporal and modified electroconvulsive therapy with a maximum of 12 sessions or 20 mg/d of fluoxetine for 6 weeks. Symptom severity, functioning, and quality of life were assessed using the 17-item Hamilton Rating Scale for Depression, the Modified Work and Social Adjustment Scale, and SF-36. Side effects following treatment, including subjective memory impairment, nausea/vomiting, and headache, were recorded. The differences between these 2 groups in 17-item Hamilton Rating Scale for Depression, Modified Work and Social Adjustment Scale, quality of life, side effects, and time to response (at least a 50% reduction of 17-item Hamilton Rating Scale for Depression) and remission (17-item Hamilton Rating Scale for Depression ≤7) following treatment were analyzed. Results Electroconvulsive therapy (n=116) showed a significantly greater reduction in 17-item Hamilton Rating Scale for Depression, Modified Work and Social Adjustment Scale, and quality of life deficits and had significantly shorter time to response/remission than fluoxetine (n=126). However, the electroconvulsive therapy group was more likely to experience subjective memory impairment and headache. Conclusions Compared with fluoxetine, electroconvulsive therapy was more effective in alleviating the burden of major depressive disorder and had a substantially increased speed of response/remission in the acute phase. Increased education and information about electroconvulsive therapy for clinicians, patients, and their families and the general public is warranted. PMID:29228200

Systemic correction of the muscle disorder glycogen storage disease type II after hepatic targeting of a modified adenovirus vector encoding human acid-α-glucosidase

PubMed Central

Amalfitano, A.; McVie-Wylie, A. J.; Hu, H.; Dawson, T. L.; Raben, N.; Plotz, P.; Chen, Y. T.

1999-01-01

This report demonstrates that a single intravenous administration of a gene therapy vector can potentially result in the correction of all affected muscles in a mouse model of a human genetic muscle disease. These results were achieved by capitalizing both on the positive attributes of modified adenovirus-based vectoring systems and receptor-mediated lysosomal targeting of enzymes. The muscle disease treated, glycogen storage disease type II, is a lysosomal storage disorder that manifests as a progressive myopathy, secondary to massive glycogen accumulations in the skeletal and/or cardiac muscles of affected individuals. We demonstrated that a single intravenous administration of a modified Ad vector encoding human acid α-glucosidase (GAA) resulted in efficient hepatic transduction and secretion of high levels of the precursor GAA proenzyme into the plasma of treated animals. Subsequently, systemic distribution and uptake of the proenzyme into the skeletal and cardiac muscles of the GAA-knockout mouse was confirmed. As a result, systemic decreases (and correction) of the glycogen accumulations in a variety of muscle tissues was demonstrated. This model can potentially be expanded to include the treatment of other lysosomal enzyme disorders. Lessons learned from systemic genetic therapy of muscle disorders also should have implications for other muscle diseases, such as the muscular dystrophies. PMID:10430861

Effects of cognitive-behavioral therapy on improving anxiety symptoms, behavioral problems and parenting stress in Taiwanese children with anxiety disorders and their mothers.

PubMed

Yen, Cheng-Fang; Chen, Yu-Min; Cheng, Jen-Wen; Liu, Tai-Ling; Huang, Tzu-Yu; Wang, Peng-Wei; Yang, Pinchen; Chou, Wen-Jiun

2014-06-01

The aims of this intervention study were to examine the effects of individual cognitive-behavioral therapy (CBT) based on the modified Coping Cat Program on improving anxiety symptoms and behavioral problems in Taiwanese children with anxiety disorders and parenting stress perceived by their mothers. A total of 24 children with anxiety disorders in the treatment group completed the 17-session individual CBT based on the modified Coping Cat Program, and 26 children in the control group received the treatment as usual intervention. The Taiwanese version of the MASC (MASC-T), the Child Behavior Checklist for Ages 6-18 (CBCL/6-18) and the Chinese version of the Parenting Stress Index (C-PSI) were applied to assess the severities of anxiety symptoms, behavioral problems and parenting stress, respectively. The effects of CBT on improving anxiety symptoms, behavioral problems and parenting stress were examined by using linear mixed-effect model with maximum likelihood estimation. The results indicated that the CBT significantly improved the severities of MASC-T Physical Symptoms and Social Anxiety subscales, CBCL/6-18 DSM-oriented Anxiety Problem subscale, and C-PSI Child domains Mood and Adaptability subscales. Individual CBT based on the modified Coping Cat Program can potentially improve anxiety symptoms in Taiwanese children with anxiety disorders and some child domains of parenting stress perceived by their mothers.

Self-Management Procedures: A Comparison across the Autism Spectrum

ERIC Educational Resources Information Center

Southall, Candice M.; Gast, David L.

2011-01-01

Individuals with autism spectrum disorders (ASD) have difficulty generalizing learned behavior to varied environments with independence. This review of 24 empirical studies compares self-management as a systematic procedure for modifying one's own behavior, to increase target behaviors in students with either autistic disorder (AD) or…

A modified ketogenic gluten-free diet with MCT improves behavior in children with autism spectrum disorder

PubMed Central

Lee, Ryan W.Y.; Corley, Michael J.; Pang, Alina; Arakaki, Gaye; Abbott, Lisa; Nishimoto, Michael; Miyamoto, Rob; Lee, Erica; Yamamoto, Susan; Maunakea, Alika K.; Lum-Jones, Annette; Wong, Miki

2018-01-01

Purpose The ketogenic diet is a low-carbohydrate, moderate protein, high-fat diet that has emerged as a potential treatment for autism spectrum disorder. Autism spectrum disorder is a neurodevelopmental disorder of social communication, and restricted, repetitive behaviors and interests in need of novel therapies. An open-label clinical trial was done in Honolulu, Hawaii to test a modified ketogenic diet for improvement of core clinical impairments in children with ASD. Intervention A modified ketogenic gluten-free diet regimen with supplemental MCT was completed in 15 children ages 2 to 17 years for 3 months. Clinical (ADOS-2, CARS-2) and biochemical measures were performed at baseline and 3-months on the ketogenic diet. Main outcome Children administered a modified ketogenic gluten-free diet with supplemental MCT significantly improved core autism features assessed from the ADOS-2 after 3 months on diet (P = 0.006). No significant difference was observed in restricted and repetitive behavior score (P = 0.125) after 3 months on the diet protocol. Substantial improvement (> 30% decrease ADOS-2 total score) was observed in six participants, moderate improvement (> 3 units) in two participants, and minor/no improvement in seven participants. Ten participants assessed at a six-month time point sustained improvement in total ADOS-2 and social affect subdomain scores comparing baseline and 6 months (P = 0.019; P = 0.023), but no significant improvement in restricted and repetitive behavior scores were noted (P = 0.197). Significant improvements in CARS-2 items after 3 months of the modified ketogenic protocol were observed in imitation, body use, and fear or nervousness (P = 0.031, P = 0.008, P = 0.039). The percent change on ADOS-2 score from baseline to 3 months was associated with baseline high-density lipoprotein levels (ρ = −0.67, P = 0.007) and albumin levels (ρ = −0.60, P = 0.019). Moreover, the percent change from baseline to 3 months in ADOS-2 scores was significantly associated with percent change in high-density lipoprotein levels (ρ = 0.54, P = 0.049) and albumin levels (ρ = 0.67, P = 0.010). Conclusions A modified gluten-free ketogenic diet with supplemental MCT is a potentially beneficial treatment option to improve the core features of autism spectrum disorder and warrants further investigation. Trial registration Trial Registry: Clinicaltrials.gov Registration Number: NCT02477904URL: https://www.clinicaltrials.gov/ct2/show/NCT02477904?term=ketogenic+diet&cond=Autism&rank=1 PMID:29421589

The Effect of Disorder on the Free-Energy for the Random Walk Pinning Model: Smoothing of the Phase Transition and Low Temperature Asymptotics

NASA Astrophysics Data System (ADS)

Berger, Quentin; Lacoin, Hubert

2011-01-01

We consider the continuous time version of the Random Walk Pinning Model (RWPM), studied in (Berger and Toninelli (Electron. J. Probab., to appear) and Birkner and Sun (Ann. Inst. Henri Poincaré Probab. Stat. 46:414-441, 2010; arXiv:0912.1663). Given a fixed realization of a random walk Y on ℤ d with jump rate ρ (that plays the role of the random medium), we modify the law of a random walk X on ℤ d with jump rate 1 by reweighting the paths, giving an energy reward proportional to the intersection time Lt(X,Y)=int0t {1}_{Xs=Ys} {d}s: the weight of the path under the new measure is exp ( βL t ( X, Y)), β∈ℝ. As β increases, the system exhibits a delocalization/localization transition: there is a critical value β c , such that if β> β c the two walks stick together for almost-all Y realizations. A natural question is that of disorder relevance, that is whether the quenched and annealed systems have the same behavior. In this paper we investigate how the disorder modifies the shape of the free energy curve: (1) We prove that, in dimension d≥3, the presence of disorder makes the phase transition at least of second order. This, in dimension d≥4, contrasts with the fact that the phase transition of the annealed system is of first order. (2) In any dimension, we prove that disorder modifies the low temperature asymptotic of the free energy.

[The modified method registration of kinesthetic evoked potentials and its application for research of proprioceptive sensitivity disorders at spondylogenic cervical myelopathy].

PubMed

Gordeev, S A; Voronin, S G

2016-01-01

To analyze the efficacy of modified (passive radiocarpal articulation flexion/extension) and «standard» (passive radiocarpal articulation flexion) methods of kinesthetic evoked potentials for proprioceptive sensitivity assessment in healthy subjects and patients with spondylotic cervical myelopathy. The study included 14 healthy subjects (4 women and 10 men, mean age 54.1±10.5 years) and 8 patients (2 women and 6 men, mean age 55.8±10.9 years) with spondylotic cervical myelopathy. Muscle-joint sensation was examined during the clinical study. A modified method of kinesthetic evoked potentials was developed. This method differed from the "standard" one by the organization of a cycle including several passive movements,where each new movement differed from the preceding one by the direction. The modified method of kinesthetic evoked potentials ensures more reliable kinesthetic sensitivity assessment due to movement variability. Asignificant increaseof the latent periods of the early components of the response was found in patients compared to healthy subjects. The modified method of kinesthetic evoked potentials can be used for objective diagnosis of proprioceptive sensitivity disorders in patients with spondylotic cervical myelopathy.

How does relaxing the algorithm for autism affect DSM-V prevalence rates?

PubMed

Matson, Johnny L; Hattier, Megan A; Williams, Lindsey W

2012-08-01

Although it is still unclear what causes autism spectrum disorders (ASDs), over time researchers and clinicians have become more precise with detecting and diagnosing ASD. Many diagnoses, however, are based on the criteria established within the Diagnostic and Statistical Manual of Mental Disorders (DSM); thus, any change in these diagnostic criteria can have a great effect upon children with ASD and their families. It is predicted that the prevalence of ASD diagnoses will dramatically decrease with the adoption of the proposed DSM-5 criteria in 2013. The aim of this current study was to inspect the changes in prevalence first using a diagnostic criteria set which was modified slightly from the DSM-5 criteria (Modified-1 criteria) and again using a set of criteria which was relaxed even a bit more (Modified-2 criteria). Modified-1 resulted in 33.77 % fewer toddlers being diagnosed with ASD compared to the DSM-IV, while Modified-2 resulted in only a 17.98 % decrease in ASD diagnoses. Children diagnosed with the DSM-5 criteria exhibited the greatest levels of autism symptomatology, but the Mod-1, Mod-2, and DSM-IV groups still demonstrated significant impairments. Implications of these findings are discussed.

Severe vascular calcification and tumoral calcinosis in a family with hyperphosphatemia: a fibroblast growth factor 23 mutation identified by exome sequencing

PubMed Central

Shah, Anuja; Miller, Clinton J.; Nast, Cynthia C.; Adams, Mark D.; Truitt, Barbara; Tayek, John A.; Tong, Lili; Mehtani, Parag; Monteon, Francisco; Sedor, John R.; Clinkenbeard, Erica L.; White, Kenneth; Mehrotra, Rajnish; LaPage, Janine; Dickson, Patricia; Adler, Sharon G.; Iyengar, Sudha K.

2014-01-01

Background Tumoral calcinosis is an autosomal recessive disorder characterized by ectopic calcification and hyperphosphatemia. Methods We describe a family with tumoral calcinosis requiring amputations. The predominant metabolic anomaly identified in three affected family members was hyperphosphatemia. Biochemical and phenotypic analysis of 13 kindred members, together with exome analysis of 6 members, was performed. Results We identified a novel Q67K mutation in fibroblast growth factor 23 (FGF23), segregating with a null (deletion) allele on the other FGF23 homologue in three affected members. Affected siblings had high circulating plasma C-terminal FGF23 levels, but undetectable intact FGF23 or N-terminal FGF23, leading to loss of FGF23 function. Conclusions This suggests that in human, as in experimental models, severe prolonged hyperphosphatemia may be sufficient to produce bone differentiation proteins in vascular cells, and vascular calcification severe enough to require amputation. Genetic modifiers may contribute to the phenotypic variation within and between families. PMID:25378588

Exome sequencing of extreme phenotypes identifies DCTN4 as a modifier of chronic Pseudomonas aeruginosa infection in cystic fibrosis.

PubMed

Emond, Mary J; Louie, Tin; Emerson, Julia; Zhao, Wei; Mathias, Rasika A; Knowles, Michael R; Wright, Fred A; Rieder, Mark J; Tabor, Holly K; Nickerson, Deborah A; Barnes, Kathleen C; Gibson, Ronald L; Bamshad, Michael J

2012-07-08

Exome sequencing has become a powerful and effective strategy for the discovery of genes underlying Mendelian disorders. However, use of exome sequencing to identify variants associated with complex traits has been more challenging, partly because the sample sizes needed for adequate power may be very large. One strategy to increase efficiency is to sequence individuals who are at both ends of a phenotype distribution (those with extreme phenotypes). Because the frequency of alleles that contribute to the trait are enriched in one or both phenotype extremes, a modest sample size can potentially be used to identify novel candidate genes and/or alleles. As part of the National Heart, Lung, and Blood Institute (NHLBI) Exome Sequencing Project (ESP), we used an extreme phenotype study design to discover that variants in DCTN4, encoding a dynactin protein, are associated with time to first P. aeruginosa airway infection, chronic P. aeruginosa infection and mucoid P. aeruginosa in individuals with cystic fibrosis.

MicroRNAs in CAG trinucleotide repeat expansion disorders: an integrated review of the literature.

PubMed

Dumitrescu, Laura; Popescu, Bogdan O

2015-01-01

MicroRNAs are small RNAs involved in gene silencing. They play important roles in transcriptional regulation and are selectively and abundantly expressed in the central nervous system. A considerable amount of the human genome is comprised of tandem repeating nucleotide streams. Several diseases are caused by above-threshold expansion of certain trinucleotide repeats occurring in a protein-coding or non-coding region. Though monogenic, CAG trinucleotide repeat expansion disorders have a complex pathogenesis, various combinations of multiple coexisting pathways resulting in one common final consequence: selective neurodegeneration. Mutant protein and mutant transcript gain of toxic function are considered to be the core pathogenic mechanisms. The profile of microRNAs in CAG trinucleotide repeat disorders is scarcely described, however microRNA dysregulation has been identified in these diseases and microRNA-related intereference with gene expression is considered to be involved in their pathogenesis. Better understanding of microRNAs functions and means of manipulation promises to offer further insights into the pathogenic pathways of CAG repeat expansion disorders, to point out new potential targets for drug intervention and to provide some of the much needed etiopathogenic therapeutic agents. A number of disease-modifying microRNA silencing strategies are under development, but several implementation impediments still have to be resolved. CAG targeting seems feasible and efficient in animal models and is an appealing approach for clinical practice. Preliminary human trials are just beginning.

The definition of HIV-associated neurocognitive disorders: are we overestimating the real prevalence?

PubMed

Gisslén, Magnus; Price, Richard W; Nilsson, Staffan

2011-12-28

A substantial prevalence of mild neurocognitive disorders has been reported in HIV, also in patients treated with combination antiretroviral therapy (cART). This includes a new disorder that has been termed asymptomatic neurocognitive impairment (ANI). ANI is identified by performance on formal neuropsychological testing that is at least 1 SD below the mean of normative scores in at least two cognitive domains out of at least five examined in patients without associated symptoms or evident functional impairment in daily living. While two tests are recommended to assess each domain, only one is required to fulfill this diagnostic criterion. Unfortunately, this definition necessitates that about 20% of the cognitively normal HIV-infected population is classified as suffering ANI. This liberal definition raises important ethical concerns and has as well diagnostic and therapeutic implications. Since neither its biological substrate, prognostic significance nor therapeutic implications are clearly established, we recommend that this diagnosis be modified or applied cautiously. The diagnoses of less severe forms of neurocognitive disorders in HIV relies on the outcomes of neuropsychological testing, and a high proportion of HIV-infected patients with effective cART may be classified as neurocognitively abnormal using the current criteria. The definition of ANI is not stringent, and results in approximately 20% of the population being classified as abnormal. To us this seems an unacceptable false-positive rate.

EEG entropy measures indicate decrease of cortical information processing in Disorders of Consciousness.

PubMed

Thul, Alexander; Lechinger, Julia; Donis, Johann; Michitsch, Gabriele; Pichler, Gerald; Kochs, Eberhard F; Jordan, Denis; Ilg, Rüdiger; Schabus, Manuel

2016-02-01

Clinical assessments that rely on behavioral responses to differentiate Disorders of Consciousness are at times inapt because of some patients' motor disabilities. To objectify patients' conditions of reduced consciousness the present study evaluated the use of electroencephalography to measure residual brain activity. We analyzed entropy values of 18 scalp EEG channels of 15 severely brain-damaged patients with clinically diagnosed Minimally-Conscious-State (MCS) or Unresponsive-Wakefulness-Syndrome (UWS) and compared the results to a sample of 24 control subjects. Permutation entropy (PeEn) and symbolic transfer entropy (STEn), reflecting information processes in the EEG, were calculated for all subjects. Participants were tested on a modified active own-name paradigm to identify correlates of active instruction following. PeEn showed reduced local information content in the EEG in patients, that was most pronounced in UWS. STEn analysis revealed altered directed information flow in the EEG of patients, indicating impaired feed-backward connectivity. Responses to auditory stimulation yielded differences in entropy measures, indicating reduced information processing in MCS and UWS. Local EEG information content and information flow are affected in Disorders of Consciousness. This suggests local cortical information capacity and feedback information transfer as neural correlates of consciousness. The utilized EEG entropy analyses were able to relate to patient groups with different Disorders of Consciousness. Copyright © 2015 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.

Clinical psychopharmacology of borderline personality disorder: an update on the available evidence in light of the Diagnostic and Statistical Manual of Mental Disorders - 5.

PubMed

Ripoll, Luis H

2012-01-01

Clinical considerations for evidence-based treatment of borderline personality disorder (BPD) are outlined in the context of the best available evidence, discussed with reference to BPD traits currently identified in the upcoming Diagnostic and Statistical Manual of Mental Disorders - 5 (DSM-5) revision. The DSM-5 will highlight refractory affective, interpersonal, and identity symptoms in BPD as potential treatment targets. In addition to providing a framework for clinical decision-making, future research strategies will also focus on neurotransmitter systems of greater relevance to understanding overall personality functioning. Although only a few randomized controlled trials of psychopharmacological treatments for BPD have been published recently, several meta-analyses and systematic reviews converge on the consensus effectiveness of lamotrigine, topiramate, valproate, aripiprazole, olanzapine, and omega-3 fatty acid supplementation. Stronger evidence exists for treating disinhibition and antagonism than negative affectivity, particularly interpersonal facets of such traits. In addition, basic research suggests a future role for modifying glutamatergic, opioid, and oxytocinergic neurotransmitter systems to treat BPD. Clinicians should utilize omega-3, anticonvulsants, and atypical antipsychotic agents in treating specific DSM-5 BPD traits, notably disinhibition, antagonism, and some aspects of negative affectivity. Future research will focus on normalizing opioid and oxytocin dysregulation, as an adjunct to evidence-based psychotherapy, in an effort to improve interpersonal functioning.

Developmental Coordination Disorder and Reported Enjoyment of Physical Education in Children

ERIC Educational Resources Information Center

Cairney, John; Hay, John; Mandigo, James; Wade, Terrance; Faught, Brent E.; Flouris, Andreas

2007-01-01

Children with developmental coordination disorder (DCD) are less likely to enjoy participating in physical education (PE) than children without motor coordination difficulties. However, no studies have attempted to quantify this relationship or examine potentially modifiable mediating variables. Using a large sample (N = 590) of children (aged 9…

Early High School Engagement in Students with Attention/Deficit Hyperactivity Disorder

ERIC Educational Resources Information Center

Zendarski, Nardia; Sciberras, Emma; Mensah, Fiona; Hiscock, Harriet

2017-01-01

Background: Students with attention/deficit hyperactivity disorder (ADHD) continue to languish behind their peers with regard to academic achievement and education attainment. School engagement is potentially modifiable, and targeting engagement may be a means to improve education outcomes. Aims: To investigate school engagement for students with…

Gender and Agreement Processing in Children with Developmental Language Disorder

ERIC Educational Resources Information Center

Rakhlin, Natalia; Kornilov, Sergey A.; Grigorenko, Elena L.

2014-01-01

Two experiments tested whether Russian-speaking children with Developmental Language Disorder (DLD) are sensitive to gender agreement when performing a gender decision task. In Experiment 1, the presence of overt gender agreement between verbs and/or adjectival modifiers and postverbal subject nouns memory was varied. In Experiment 2, agreement…

Neural Basis of Visual Attentional Orienting in Childhood Autism Spectrum Disorders

ERIC Educational Resources Information Center

Murphy, Eric R.; Norr, Megan; Strang, John F.; Kenworthy, Lauren; Gaillard, William D.; Vaidya, Chandan J.

2017-01-01

We examined spontaneous attention orienting to visual salience in stimuli without social significance using a modified Dot-Probe task during functional magnetic resonance imaging in high-functioning preadolescent children with Autism Spectrum Disorder (ASD) and age- and IQ-matched control children. While the magnitude of attentional bias (faster…

Anxiety and Alcohol Use Disorders

PubMed Central

Smith, Joshua P.; Randall, Carrie L.

2012-01-01

The co-occurrence of anxiety disorders and alcohol use disorders (AUDs) is relatively common and is associated with a complex clinical presentation. Sound diagnosis and treatment planning requires that clinicians have an integrated understanding of the developmental pathways and course of this comorbidity. Moreover, standard interventions for anxiety disorders or AUDs may need to be modified and combined in targeted ways to accommodate the unique needs of people who have both disorders. Optimal combination of evidence-based treatments should be based on a comparative balance that considers the advantages and disadvantages of sequential, parallel, and integrated approaches. PMID:23584108

Use of abstracts, orientations, and codas in narration by language-disordered and nondisordered children.

PubMed

Sleight, C C; Prinz, P M

1985-11-01

In this study language-disordered and nondisordered children viewed a nonverbal film, wrote the story, and narrated it to language-disordered and nondisordered peers who were unfamiliar with the film. The narratives were analyzed for the use of abstracts, orientations (background information), and codas. Language-disordered children made fewer references to the orientation clauses of props and activities than nondisordered children. Neither group modified their language in the areas examined to take into account the communicative status of their listeners. Therapeutic implications for the language-disordered children are presented as are suggestions for future research.

Cell therapy for basement membrane-linked diseases.

PubMed

Nyström, Alexander; Bornert, Olivier; Kühl, Tobias

2017-01-01

For most disorders caused by mutations in genes encoding basement membrane (BM) proteins, there are at present only limited treatment options available. Genetic BM-linked disorders can be viewed as especially suited for treatment with cell-based therapy approaches because the proteins that need to be restored are located in the extracellular space. In consequence, complete and permanent engraftment of cells does not necessarily have to occur to achieve substantial causal therapeutic effects. For these disorders cells can be used as transient vehicles for protein replacement. In addition, it is becoming evident that BM-linked genetic disorders are modified by secondary diseases mechanisms. Cell-based therapies have also the ability to target such disease modifying mechanisms. Thus, cell therapies can simultaneously provide causal treatment and symptomatic relief, and accordingly hold great potential for treatment of BM-linked disorders. However, this potential has for most applications and diseases so far not been realized. Here, we will present the state of cell therapies for BM-linked diseases. We will discuss use of both pluripotent and differentiated cells, the limitation of the approaches, their challenges, and the way forward to potential wider implementation of cell therapies in the clinics. Copyright © 2016 Elsevier B.V. All rights reserved.

Depressive disorders: Processes leading to neurogeneration and potential novel treatments.

PubMed

Brown, Gregory M; McIntyre, Roger S; Rosenblat, Joshua; Hardeland, Rüdiger

2018-01-03

Mood disorders are wide spread with estimates that one in seven of the population are affected at some time in their life (Kessler et al., 2012). Many of those affected with severe depressive disorders have cognitive deficits which may progress to frank neurodegeneration. There are several peripheral markers shown by patients who have cognitive deficits that could represent causative factors and could potentially serve as guides to the prevention or even treatment of neurodegeneration. Circadian rhythm misalignment, immune dysfunction and oxidative stress are key pathologic processes implicated in neurodegeneration and cognitive dysfunction in depressive disorders. Novel treatments targeting these pathways may therefore potentially improve patient outcomes whereby the primary mechanism of action is outside of the monoaminergic system. Moreover, targeting immune dysfunction, oxidative stress and circadian rhythm misalignment (rather than primarily the monoaminergic system) may hold promise for truly disease modifying treatments that may prevent neurodegeneration rather than simply alleviating symptoms with no curative intent. Further research is required to more comprehensively understand the contributions of these pathways to the pathophysiology of depressive disorders to allow for disease modifying treatments to be discovered. Copyright © 2017 Elsevier Inc. All rights reserved.

Molecular Basis and Genetic Modifiers of Thalassemia.

PubMed

Mettananda, Sachith; Higgs, Douglas R

2018-04-01

Thalassemia is a disorder of hemoglobin characterized by reduced or absent production of one of the globin chains in human red blood cells with relative excess of the other. Impaired synthesis of β-globin results in β-thalassemia, whereas defective synthesis of α-globin leads to α-thalassemia. Despite being a monogenic disorder, thalassemia exhibits remarkable clinical heterogeneity that is directly related to the intracellular imbalance between α- and β-like globin chains. Novel insights into the genetic modifiers have contributed to the understanding of the correlation between genotype and phenotype and are being explored as therapeutic pathways to cure this life-limiting disease. Copyright © 2017 Elsevier Inc. All rights reserved.

Management of Sleep Disordered Breathing in Patients with Heart Failure.

PubMed

Oates, Connor P; Ananthram, Manjula; Gottlieb, Stephen S

2018-06-01

This paper reviews treatment options for sleep disordered breathing (SDB) in patients with heart failure. We sought to identify therapies for SDB with the best evidence for long-term use in patients with heart failure and to minimize uncertainties in clinical practice by examining frequently discussed questions: what is the role of continuous positive airway pressure (CPAP) in patients with heart failure? Is adaptive servo-ventilation (ASV) safe in patients with heart failure? To what extent is SDB a modifiable risk factor? Consistent evidence has demonstrated that the development of SDB in patients with heart failure is a poor prognostic indicator and a risk factor for cardiovascular mortality. However, despite numerous available interventions for obstructive sleep apnea and central sleep apnea, it remains unclear what effect these therapies have on patients with heart failure. To date, all major randomized clinical trials have failed to demonstrate a survival benefit with SDB therapy and one major study investigating the use of adaptive servo-ventilation demonstrated harm. Significant questions persist regarding the management of SDB in patients with heart failure. Until appropriately powered trials identify a treatment modality that increases cardiovascular survival in patients with SDB and heart failure, a patient's heart failure management should remain the priority of medical care.

Interaction of Physical Exposures and Occupational Factors on Sickness Absence in Automotive Industry Workers.

PubMed

Valirad, Fateme; Ghaffari, Mostafa; Abdi, Alireza; Attarchi, Mirsaeed; Mircheraghi, Seyed Farzin; Mohammadi, Saber

2015-04-23

Increased sickness absence in recent years has been a trouble making issue in industrial society. Identify the causes of sickness absence and its influencing factors, is an important step to control and reduce its associated complications and costs. The aim of this study was to evaluate main factors associated with the incidence of sickness absence. In 2012, a cross-sectional study on 758 employees of a car accessories producing company was applied and relevant information about the number of days and episodes of sickness absence, Disease resulting in absence from work, personal features, occupational factors and physical exposures were collected. To determine risk factors associated with sickness absence, Logistic regression analysis was used. The most common diseases leading to sickness absence in order of frequency were Respiratory diseases, musculoskeletal disorders, gastrointestinal diseases and injuries at work. Musculoskeletal disorders increased the danger of long term absence by 4/33 times. Blue collar and shift works were the most important occupational factors associated with the incidence of sickness absence. The main physical factors that affect incidence of sickness absence were frequent bending-twisting and heavy lifting. Identifying controllable factors of sickness absence and trying to prevent and modify them such as compliance of ergonomic principals to decrease physical can be effective in reducing sickness absence.

The Wundt-Jastrow illusion in the study of spatial hemi-inattention.

PubMed

Massironi, M; Antonucci, G; Pizzamiglio, L; Vitale, M V; Zoccolotti, P

1988-01-01

A new test to detect unilateral neglect was devised using a modified version of the Wundt-Jastrow area illusion. The test was given to three groups of subjects: left brain damaged (LBD), right brain damaged (RBD) patients and controls. Of RBD patients, 40.4% but no LBD patient or control, showed responses inconsistent with the visual illusion when the determinant features of the illusion pointed to the left visual field. These unexpected responses were highly related to a clinical evaluation of the severity of the hemi-inattention disorder. The sensitivity of this test and of other standard measures of hemi-neglect were compared. The possibility of identifying qualitatively different forms of hemi-neglect was also discussed.

Academic Achievement in Children With Oral Clefts Versus Unaffected Siblings

PubMed Central

Wehby, George L.; Barron, Sheila; Romitti, Paul A.; Ansley, Timothy N.; Speltz, Matthew L.

2014-01-01

Objective To compare academic achievement in children with oral-facial clefts (OFC) with their unaffected siblings. Methods 256 children with OFC were identified from the Iowa Registry for Congenital and Inherited Disorders, and 387 unaffected siblings were identified from birth certificates. These data were linked to Iowa Testing Programs achievement data. We compared academic achievement in children with OFC with their unaffected siblings using linear regression models, adjusted for potential confounders. In post hoc analyses, we explored modifiers of siblings’ academic performance. Results Achievement scores were similar between children with OFC and their siblings. Children with cleft palate only were significantly more likely to use special education than their unaffected siblings. Siblings’ academic achievement was inversely related to distance in birth order and age from the affected child. Conclusion Children with OFC and their siblings received similar achievement scores. Younger siblings, in particular, may share a vulnerability to poor academic outcomes. PMID:24993102

In vivo SELEX for Identification of Brain-penetrating Aptamers

PubMed Central

Cheng, Congsheng; Chen, Yong Hong; Lennox, Kim A; Behlke, Mark A; Davidson, Beverly L

2013-01-01

The physiological barriers of the brain impair drug delivery for treatment of many neurological disorders. One delivery approach that has not been investigated for their ability to penetrate the brain is RNA-based aptamers. These molecules can impart delivery to peripheral tissues and circulating immune cells, where they act as ligand mimics or can be modified to carry payloads. We developed a library of aptamers and an in vivo evolution protocol to determine whether specific aptamers could be identified that would home to the brain after injection into the peripheral vasculature. Unlike biopanning with recombinant bacteriophage libraries, we found that the aptamer library employed here required more than 15 rounds of in vivo selection for convergence to specific sequences. The aptamer species identified through this approach bound to brain capillary endothelia and penetrated into the parenchyma. The methods described may find general utility for targeting various payloads to the brain. PMID:23299833

Obsessive-Compulsive Personality Traits in Youth with Obsessive-Compulsive Disorder.

PubMed

Park, Jennifer M; Storch, Eric A; Pinto, Anthony; Lewin, Adam B

2016-04-01

While interest in the relationship between obsessive-compulsive disorder (OCD) and obsessive compulsive personality disorder has increased, there are currently no studies that have examined the presence of obsessive compulsive personality traits (OCPTs) in youth. The current study sought to determine the latent factors and psychometric properties of a modified version of the Childhood Retrospective Perfectionism Questionnaire (CHIRP) and examine the correlates of specific OCPTs (e.g., rigidity, perfectionism) in youth with OCD. Participants included 96 treatment-seeking youth diagnosed with primary OCD (and a parent). Parents and youth completed measures of OCPTs, OCD severity, depression, and disability. A confirmatory factor analysis of the modified CHIRP resulted in a two-factor model: perfectionism and preoccupation with details. The CHIRP and its subscales demonstrated acceptable internal consistency and preliminary evidence for convergent and divergent validity. Obsessive compulsive traits in youth were also found to be associated with the checking, symmetry and contamination symptom dimensions.

Job strain, rank, and mental health in the UK Armed Forces.

PubMed

Fear, Nicola Townsend; Rubin, G James; Hatch, Stephani; Hull, Lisa; Jones, Margaret; Hotopf, Matthew; Wessely, Simon; Rona, Roberto J

2009-01-01

We assessed whether job demand and job control have independent effects on psychological symptoms or whether job control modifies effect of job demand; we also assessed whether rank modified associations between job strain and psychological symptoms. We used the Post Traumatic Stress Disorder (PTSD) Checklist (PCL-C), General Health Questionnaire-12 (GHQ-12), Chalder Fatigue Scale, a checklist of 53 physical symptoms, and the WHO's Alcohol Use Disorders Identification Test (AUDIT). Job control, job demand, and rank were independently associated with PTSD, common mental disorders, multiple physical symptoms, and fatigue, but not with severe alcohol problems. Job control and demand had additive effects on psychological symptoms. Commissioned officers had lower risk of caseness for psychological symptoms than other ranks. Adjustment for rank had negligible effect on level of association between job strain and psychological symptoms. Reported job strain and rank contributed independently to psychological symptoms.

The Modified-Classroom Observation Schedule to Measure Intentional Communication (M-COSMIC): Evaluation of Reliability and Validity

ERIC Educational Resources Information Center

Clifford, Sally; Hudry, Kristelle; Brown, Laura; Pasco, Greg; Charman, Tony

2010-01-01

The Modified-Classroom Observation Schedule to Measure Intentional Communication (M-COSMIC) was developed as an ecologically valid measure of social-communication behaviour, delineating forms, functions, and intended partners of children's spontaneous communication acts. Forty-one children with autism spectrum disorder (ASD) aged 48-73 months were…

Modified Checklist for Autism in Toddlers: Cross-Cultural Adaptation and Validation in Spain

ERIC Educational Resources Information Center

Canal-Bedia, Ricardo; Garcia-Primo, Patricia; Martin-Cilleros, Maria Victoria; Santos-Borbujo, Jose; Guisuraga-Fernandez, Zoila; Herraez-Garcia, Lorena; Herraez-Garcia, Maria del Mar; Boada-Munoz, Leticia; Fuentes-Biggi, Joaquin; Posada-de La Paz, Manuel

2011-01-01

Early detection and treatment have been shown to be effective in reducing disability severity caused by Autistic Spectrum Disorders (ASDs). As Spanish pediatricians have no detection tool, the Modified Checklist for Autism in Toddlers (M-CHAT) was first translated into and culturally adapted to Spanish. Validity and reliability studies were…

Anterior EEG Asymmetry and the Modifier Model of Autism

ERIC Educational Resources Information Center

Burnette, Courtney P.; Henderson, Heather A.; Inge, Anne Pradella; Zahka, Nicole E.; Schwartz, Caley B.; Mundy, Peter C.

2011-01-01

Individual differences in the expression of autism complicate research on the nature and treatment of this disorder. In the Modifier Model of Autism (Mundy et al. 2007), we proposed that individual differences in autism may result not only from syndrome specific causal processes, but also from variability in generic, non-syndrome specific…

Polyethylene imine modified hydrochar adsorption for chromium (VI) and nickel (II) removal from aqueous solution.

PubMed

Shi, Yuanji; Zhang, Tao; Ren, Hongqiang; Kruse, Andrea; Cui, Ruofan

2018-01-01

An adsorbent hydrochar was synthesized from corn cobs and modified with polyethylene imine (PEI). The hydrochars before and after modification were characterized by scanning electron microscopy, Fourier transform infrared spectroscopy (FTIR), X-ray photoelectron spectroscopy (XPS), and thermogravimetric analysis. FTIR and XPS revealed that the PEI was grafted onto the hydrochar via ether and imine bonds formed with glutaraldehyde. The maximum adsorption capacities for Cr(VI) (33.663mg/g) and Ni(II) (29.059mg/g) on the modified hydrochars were 365% and 43.7% higher, respectively, than those on the unmodified hydrochar. A pseudo-second-order model described the adsorption of Ni(II) and Cr(VI) on all the adsorbents. The adsorption of Cr(VI) was endothermic, spontaneous, increased disorder, and obeyed the Langmuir model. By contrast, the adsorption of Ni(II) was exothermic, spontaneous, decreased disorder, and obeyed the Freundlich model. XPS confirmed that the adsorption sites and mechanisms for Ni(II) and Cr(VI) on the modified hydrochars were different. Copyright © 2017 Elsevier Ltd. All rights reserved.

Reconsideration of Harm's Way: Onsets and Comorbidity Patterns of Disorders in Preschool Children and Their Caregivers Following Hurricane Katrina

ERIC Educational Resources Information Center

Scheeringa, Michael S.; Zeanah, Charles H.

2008-01-01

This study examined posttraumatic stress disorder (PTSD) and comorbid disorders in 70 preschool children (ages 3-6) and their caregivers following Hurricane Katrina. Children's rate of PTSD was 50.0% using age-modified criteria. The rate of PTSD was 62.5% for those who stayed in the city and 43.5% in those who evacuated. Of those with PTSD, 88.6%…

Child and Parent Perceived Food-Induced Gastrointestinal Symptoms and Quality of Life in Children with Functional Gastrointestinal Disorders

PubMed Central

Carlson, Michelle J.; Moore, Carolyn E.; Tsai, Cynthia M.; Shulman, Robert J.; Chumpitazi, Bruno P.

2014-01-01

It is unknown whether children with functional gastrointestinal disorders (FGIDs) identify specific foods that exacerbate their gastrointestinal (GI) symptoms. The objectives of this study were to determine the perceived role of food on GI symptoms and to determine the impact of food-induced symptoms on quality of life (QOL) in children with FGIDs. Between August and November 2010, 25 children ages 11–17 years old with FGIDs and a parent completed a food symptom association questionnaire and validated questionnaires assessing FGID symptoms and QOL. In addition, children completed a 24-hour food recall, participated in focus groups to identify problematic foods and any coping strategies, and discussed how their QOL was affected. Statistical analyses were conducted using chi-squared, t-testing, Mann-Whitney U, Wilcoxon signed-rank, and Spearman’s rho. Children identified a median of 11 (range 2–25) foods as exacerbating a GI symptom, with the most commonly identified foods being spicy foods, cow’s milk, and pizza. Several coping strategies were identified including consuming smaller portions, modifying foods, and avoiding a median of 8 (range 1–20) foods. Children reported that food-induced symptoms interfered with school performance, sports, and social activities. Although the parent’s assessment of their child’s QOL negatively correlated with the number of perceived symptom-inducing foods in their child, this relationship was not found in the children. Findings suggest that specific foods are perceived to exacerbate GI symptoms in children with FGIDs. Moreover, despite use of several coping strategies, food-induced symptoms may adversely impact children’s QOL in several important areas. PMID:24360501

High prevalence of body dysmorphic disorder symptoms in patients seeking rhinoplasty.

PubMed

Picavet, Valerie A; Prokopakis, Emmanuel P; Gabriëls, Lutgardis; Jorissen, Mark; Hellings, Peter W

2011-08-01

Nasal aesthetic deformities may be associated with significant body image dissatisfaction. The only diagnostic category in the current list of psychiatric disorders that directly addresses these concerns is body dysmorphic disorder. This large-scale study determined the prevalence of body dysmorphic disorder and its symptoms in patients seeking rhinoplasty and evaluated the clinical profile of these patients. Two hundred twenty-six patients were given questionnaires including demographic characteristics, visual analogue scales for nasal shape, the Yale-Brown Obsessive Compulsive Scale modified for body dysmorphic disorder to assess severity of symptoms, a generic quality-of-life questionnaire, and the Derriford Appearance Scale 59, to assess appearance-related disruption of everyday living. Independent observers scored the nasal shape. Thirty-three percent of patients showed at least moderate symptoms of body dysmorphic disorder. Aesthetic goals (p < 0.001), revision rhinoplasty (p = 0.003), and psychiatric history (p = 0.031) were associated with more severe symptoms. There was no correlation between the objective and subjective scoring of the nasal shape. Yale-Brown scale modified for body dysmorphic disorder scores correlated inversely with the subjective nasal scoring (n = 210, p < 0.001), without relation to the objective deformity of the nose. Body dysmorphic disorder symptoms significantly reduced the generic quality of life (n = 160, p < 0.001) and led to significant appearance-related disruption of everyday living (n = 161, p < 0.001). The prevalence of moderate to severe body dysmorphic disorder symptoms in an aesthetic rhinoplasty population is high. Patients undergoing revision rhinoplasty and with psychiatric history are particularly at risk. Body dysmorphic disorder symptoms significantly reduce the quality of life and cause significant appearance-related disruption of everyday living. Risk, III.

Mutation screening of SEMA3A and SEMA7A in patients with congenital hypogonadotropic hypogonadism.

PubMed

Känsäkoski, Johanna; Fagerholm, Rainer; Laitinen, Eeva-Maria; Vaaralahti, Kirsi; Hackman, Peter; Pitteloud, Nelly; Raivio, Taneli; Tommiska, Johanna

2014-05-01

Congenital hypogonadotropic hypogonadism (HH), a rare disorder characterized by absent, partial, or delayed puberty, can be caused by the lack or deficient number of hypothalamic gonadotropin-releasing hormone (GnRH) neurons. SEMA3A was recently implicated in the etiology of the disorder, and Sema7A-deficient mice have a reduced number of GnRH neurons in their brains. SEMA3A and SEMA7A were screened by Sanger sequencing in altogether 50 Finnish HH patients (34 with Kallmann syndrome (KS; HH with hyposmia/anosmia) and 16 with normosmic HH (nHH)). In 20 patients, mutation(s) had already been found in genes known to be implicated in congenital HH. Three heterozygous variants (c.458A>G (p.Asn153Ser), c.1253A>G (p.Asn418Ser), and c.1303G>A (p.Val435Ile)) were found in SEMA3A in three KS patients, two of which also had a mutation in FGFR1. Two rare heterozygous variants (c.442C>T (p.Arg148Trp) and c.1421G>A (p.Arg474Gln)) in SEMA7A were found in one male nHH patient with a previously identified KISS1R nonsense variant and one male KS patient with a previously identified mutation in KAL1, respectively. Our results suggest that heterozygous missense variants in SEMA3A and SEMA7A may modify the phenotype of KS but most likely are not alone sufficient to cause the disorder.

Worry and cognitive control predict course trajectories of anxiety in older adults with late-life depression.

PubMed

Spinhoven, P; van der Veen, D C; Voshaar, R C Oude; Comijs, H C

2017-07-01

Many older adults with depressive disorder manifest anxious distress. This longitudinal study examines the predictive value of worry as a maladaptive cognitive emotion regulation strategy, and resources necessary for successful emotion regulation (i.e., cognitive control and resting heart rate variability [HRV]) for the course of anxiety symptoms in depressed older adults. Moreover, it examines whether these emotion regulation variables moderate the impact of negative life events on severity of anxiety symptoms. Data of 378 depressed older adults (CIDI) between 60 and 93 years (of whom 144 [41%] had a comorbid anxiety disorder) from the Netherlands Study of Depression in Older Adults (NESDO) were used. Latent Growth Mixture Modeling was used to identify different course trajectories of six-months BAI scores. Univariable and multivariable longitudinal associations of worry, cognitive control and HRV with symptom course trajectories were assessed. We identified a course trajectory with low and improving symptoms (57.9%), a course trajectory with moderate and persistent symptoms (33.5%), and a course trajectory with severe and persistent anxiety symptoms (8.6%). Higher levels of worry and lower levels of cognitive control predicted persistent and severe levels of anxiety symptoms independent of presence of anxiety disorder. However, worry, cognitive control and HRV did not moderate the impact of negative life events on anxiety severity. Worry may be an important and malleable risk factor for persistence of anxiety symptoms in depressed older adults. Given the high prevalence of anxious depression in older adults, modifying worry may constitute a viable venue for alleviating anxiety levels. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Borderline personality disorder and the emerging field of developmental neuroscience.

PubMed

Crowell, Sheila E; Kaufman, Erin A

2016-10-01

Over the past 2 decades there has been a dramatic shift in understanding of personality disorders, such as borderline personality disorder (BPD). What was historically viewed as an entrenched pattern of antagonistic, interpersonally dependent, and uncorrectable conduct is now seen as the outcome of complex-yet modifiable-developmental processes. The borderline label, which once inspired such harsh opprobrium in clinical communities that early diagnosis was considered taboo, is now increasingly applied to adolescents who are receiving effective treatment and desisting from a borderline trajectory. Research examining the developmental origins and early manifestations of BPD is increasing rapidly, making it an appropriate time to take stock of current developmental research and articulate an agenda for the future. We identify 4 challenges that continue to impede innovative research on borderline personality development: (a) inadequate attention to continuity and discontinuity across development, (b) medical and diagnostic systems that localize personality pathology within the individual, (c) the lingering belief that biological research is antithetical to contextual/interpersonal understandings of psychopathology (and vice versa), and (d) reluctance to reach across disciplinary and developmental boundaries to identify creative paradigms and foster innovative discovery. In order to overcome these challenges, we propose an approach to future research on adolescent borderline pathology that integrates developmental psychopathology, social and affective neuroscience, and personality theory perspectives. This intersection-the developmental neuroscience of personality pathology-offers theoretical and methodological advantages over disciplinary isolation and is fertile ground for generating novel hypotheses on the development and prevention of BPD. (PsycINFO Database Record (c) 2016 APA, all rights reserved).

Pathogen-specific risk of chronic gastrointestinal disorders following bacterial causes of foodborne illness

PubMed Central

2013-01-01

Background The US CDC estimates over 2 million foodborne illnesses are annually caused by 4 major enteropathogens: non-typhoid Salmonella spp., Campylobacter spp., Shigella spp. and Yersinia enterocoltica. While data suggest a number of costly and morbid chronic sequelae associated with these infections, pathogen-specific risk estimates are lacking. We utilized a US Department of Defense medical encounter database to evaluate the risk of several gastrointestinal disorders following select foodborne infections. Methods We identified subjects with acute gastroenteritis between 1998 to 2009 attributed to Salmonella (nontyphoidal) spp., Shigella spp., Campylobacter spp. or Yersinia enterocolitica and matched each with up to 4 unexposed subjects. Medical history was analyzed for the duration of military service time (or a minimum of 1 year) to assess for incident chronic gastrointestinal disorders. Relative risks were calculated using modified Poisson regression while controlling for the effect of covariates. Results A total of 1,753 pathogen-specific gastroenteritis cases (Campylobacter: 738, Salmonella: 624, Shigella: 376, Yersinia: 17) were identified and followed for a median of 3.8 years. The incidence (per 100,000 person-years) of PI sequelae among exposed was as follows: irritable bowel syndrome (IBS), 3.0; dyspepsia, 1.8; constipation, 3.9; gastroesophageal reflux disease (GERD), 9.7. In multivariate analyses, we found pathogen-specific increased risk of IBS, dyspepsia, constipation and GERD. Conclusions These data confirm previous studies demonstrating risk of chronic gastrointestinal sequelae following bacterial enteric infections and highlight additional preventable burden of disease which may inform better food security policies and practices, and prompt further research into pathogenic mechanisms. PMID:23510245

Studies on glycoxidatively modified human IgG: Implications in immuno-pathology of type 2 diabetes mellitus.

PubMed

Islam, Sidra; Moinuddin; Mir, Abdul Rouf; Arfat, Mir Yasir; Alam, Khursheed; Ali, Asif

2017-11-01

Structural rearrangements and condensations of proteins under hyperglycemic stress have been implicated in various pathological disorders. This study aims to probe the role of methylglyoxal (MG) modified human immunoglobulin G (MG-IgG) in immuno-pathology of type 2 diabetes mellitus (T2DM). MG was found to perturb the structural integrity of IgG, affect its aromatic micro-environment and cause the generation of advanced glycation end products (AGEs) and aggregate adducts. It liberated the hydrophobic pockets of the protein, reduced its β pleated sheet structure and affected its tertiary conformation. Transition from β sheet to α helix and random coil was also observed in IgG upon modification by MG. It acted with strong oxidative potential and caused oligomerisation and disordered or amorphous type aggregation in the modified protein. Modified IgG had a cytotoxic and genotoxic impact. The MG modified IgG presented novel antigenic determinants that lead to an aggressive immune response. The antibodies had high affinity towards the immunogen. Auto-antibodies derived from T2DM patients exhibited strong affinity towards the modified IgG in comparison to the unmodified protein. Specificity of serum antibodies from T2DM patients was further confirmed by competitive-inhibition ELISA. The potential role of MG-IgG in the immunopathogenesis of T2DM has been discussed. Copyright © 2017 Elsevier B.V. All rights reserved.

Substance use disorders in a sample of Canadian patients with chronic mental illness.

PubMed

Toner, B B; Gillies, L A; Prendergast, P; Cote, F H; Browne, C

1992-03-01

In a study designed to investigate the pattern of substance use disorders among a group of chronic mentally ill patients in Toronto, 102 patients completed the Structured Clinical Interview for DSM-III-R and a modified substance-use-disorder module of the Diagnostic Interview Schedule. Forty percent of the sample met criteria for substance use disorders, and 49 percent for personality disorder. Among patients with personality disorder, all those with a personality disorder in cluster B (that is, with antisocial, borderline, histrionic, or narcissistic personality disorder) had a substance use disorder, while the majority of patients in cluster A and cluster C were not substance abusers. In the overall sample, the group with substance use disorders was significantly younger than the group without. In contrast to findings of previous studies, women met criteria for substance use disorders as often as men did.

Modifying Exposure-Based CBT for Cambodian Refugees with Posttraumatic Stress Disorder

ERIC Educational Resources Information Center

Otto, Michael W.; Hinton, Devon E.

2006-01-01

Cambodian refugees represent a severely traumatized population living in the United States. In this paper, we describe the modification of a cognitive-behavior therapy program to facilitate delivery of an exposure-based treatment for posttraumatic stress disorder while addressing some of the challenges brought by differences in language and…

Post-Traumatic Stress Disorder: A Reaction to State-Supported Child Abuse and Neglect.

ERIC Educational Resources Information Center

Straker, G.; Moosa, F.

1988-01-01

Posttraumatic Stress Disorder developed in many youths who were exposed to multiple trauma in South Africa's black townships. A modified treatment program was developed for 60 youths, with the goals of alleviating symptoms, documenting events for court cases, and helping individuals reevaluate their position in the struggle against apartheid. (JDD)

Treatment Choices in Autism Spectrum Disorder: The Role of Parental Illness Perceptions

ERIC Educational Resources Information Center

Al Anbar, Nebal N.; Dardennes, Roland M.; Prado-Netto, Arthur; Kaye, Kelley; Contejean, Yves

2010-01-01

A cross-sectional design was employed. Parents of a child with Autism Spectrum Disorder (ASD) were asked to complete a modified version of the Revised Illness-Perception Questionnaire (IPQ-RA) and answer questions about information-seeking activities and treatments used. Internal consistency, construct validity, and factor structure were assessed.…

A Test of Motor (Not Executive) Planning in Developmental Coordination Disorder and Autism

ERIC Educational Resources Information Center

van Swieten, Lisa M.; van Bergen, Elsje; Williams, Justin H. G.; Wilson, Andrew D.; Plumb, Mandy S.; Kent, Samuel W.; Mon-Williams, Mark A.

2010-01-01

Grip selection tasks have been used to test "planning" in both autism and developmental coordination disorder (DCD). We differentiate between "motor" and "executive" planning and present a modified motor planning task. Participants grasped a cylinder in 1 of 2 orientations before turning it clockwise or anticlockwise.…

Using a Multicomponent Function-Based Intervention to Support Students with Attention Deficit Hyperactivity Disorder

ERIC Educational Resources Information Center

Cho, Su-Je; Blair, Kwang-Sun Cho

2017-01-01

The current study evaluated the effects of a multicomponent function-based intervention on students with other health impairment (OHI) for attention deficit hyperactivity disorder (ADHD) in a private special education school. The focus of the intervention was to prevent problem behaviors and to increase academic engagement by modifying classroom…

Group Cognitive Behavior Therapy for Children with High-Functioning Autism Spectrum Disorders and Anxiety: A Randomized Trial

ERIC Educational Resources Information Center

Reaven, Judy; Blakeley-Smith, Audrey; Culhane-Shelburne, Kathy; Hepburn, Susan

2012-01-01

Background: Children with high-functioning autism spectrum disorders (ASD) are at high risk for developing significant anxiety. Anxiety can adversely impact functioning across school, home and community environments. Cognitive behavioral therapies (CBT) are frequently used with success for children with anxiety symptoms. Modified CBT interventions…

Does Anxiety Modify the Risk for, or Severity of, Conduct Problems Among Children With Co-Occurring ADHD: Categorical and Dimensional and Analyses.

PubMed

Danforth, Jeffrey S; Doerfler, Leonard A; Connor, Daniel F

2017-08-01

The goal was to examine whether anxiety modifies the risk for, or severity of, conduct problems in children with ADHD. Assessment included both categorical and dimensional measures of ADHD, anxiety, and conduct problems. Analyses compared conduct problems between children with ADHD features alone versus children with co-occurring ADHD and anxiety features. When assessed by dimensional rating scales, results showed that compared with children with ADHD alone, those children with ADHD co-occurring with anxiety are at risk for more intense conduct problems. When assessment included a Diagnostic and Statistical Manual of Mental Disorders (4th ed.; DSM-IV) diagnosis via the Schedule for Affective Disorders and Schizophrenia for School Age Children-Epidemiologic Version (K-SADS), results showed that compared with children with ADHD alone, those children with ADHD co-occurring with anxiety neither had more intense conduct problems nor were they more likely to be diagnosed with oppositional defiant disorder or conduct disorder. Different methodological measures of ADHD, anxiety, and conduct problem features influenced the outcome of the analyses.

Getting by, getting back, and getting on: Matching mental health services to consumers' recovery goals.

PubMed

Yarborough, Bobbi Jo H; Yarborough, Micah T; Janoff, Shannon L; Green, Carla A

2016-06-01

The goal of this study was to better understand mental health recovery from the point of view of mental health consumers to identify opportunities for practice improvements that closely align services with consumer goals and consumer-preferred outcomes. As part of an exploratory study of recovery, semistructured interviews were conducted with 177 integrated health plan members diagnosed with schizophrenia, schizoaffective disorder, bipolar disorder, or affective psychosis. Transcripts of in-depth interviews were coded using Atlas.ti, and definitions of recovery were further subcoded. A qualitative analysis using a modified grounded theory approach and constant comparative method identified common themes and less common but potentially important recovery-related experiences and perspectives. Three primary and 2 cross-cutting themes emerged. "Getting by" meant coping and meeting basic needs. "Getting back" meant learning to live with mental illness. "Getting on" meant living a life where mental illness was no longer prominent. Regaining control and recouping losses were cross-cutting themes. Mental health recovery is complex and dynamic; individuals' recovery goals can be expected to change over time. Person-centered care must accommodate changing consumer priorities, services must be flexible and responsive, and outcomes need to match consumers' objectives. Clinicians can assist in (a) identifying recovery goals, (b) monitoring progress toward and recognizing movement away from goals, (c) tailoring support to different phases/stages, and (d) supporting transitions between phases/stages. (PsycINFO Database Record (c) 2016 APA, all rights reserved).

Evolution of intrinsic disorder in eukaryotic proteins.

PubMed

Ahrens, Joseph B; Nunez-Castilla, Janelle; Siltberg-Liberles, Jessica

2017-09-01

Conformational flexibility conferred though regions of intrinsic structural disorder allows proteins to behave as dynamic molecules. While it is well-known that intrinsically disordered regions can undergo disorder-to-order transitions in real-time as part of their function, we also are beginning to learn more about the dynamics of disorder-to-order transitions along evolutionary time-scales. Intrinsically disordered regions endow proteins with functional promiscuity, which is further enhanced by the ability of some of these regions to undergo real-time disorder-to-order transitions. Disorder content affects gene retention after whole genome duplication, but it is not necessarily conserved. Altered patterns of disorder resulting from evolutionary disorder-to-order transitions indicate that disorder evolves to modify function through refining stability, regulation, and interactions. Here, we review the evolution of intrinsically disordered regions in eukaryotic proteins. We discuss the interplay between secondary structure and disorder on evolutionary time-scales, the importance of disorder for eukaryotic proteome expansion and functional divergence, and the evolutionary dynamics of disorder.

Circuit- and Diagnosis-Specific DNA Methylation Changes at γ-Aminobutyric Acid-Related Genes in Postmortem Human Hippocampus in Schizophrenia and Bipolar Disorder.

PubMed

Ruzicka, W Brad; Subburaju, Sivan; Benes, Francine M

2015-06-01

Dysfunction related to γ-aminobutyric acid (GABA)-ergic neurotransmission in the pathophysiology of major psychosis has been well established by the work of multiple groups across several decades, including the widely replicated downregulation of GAD1. Prior gene expression and network analyses within the human hippocampus implicate a broader network of genes, termed the GAD1 regulatory network, in regulation of GAD1 expression. Several genes within this GAD1 regulatory network show diagnosis- and sector-specific expression changes within the circuitry of the hippocampus, influencing abnormal GAD1 expression in schizophrenia and bipolar disorder. To investigate the hypothesis that aberrant DNA methylation contributes to circuit- and diagnosis-specific abnormal expression of GAD1 regulatory network genes in psychotic illness. This epigenetic association study targeting GAD1 regulatory network genes was conducted between July 1, 2012, and June 30, 2014. Postmortem human hippocampus tissue samples were obtained from 8 patients with schizophrenia, 8 patients with bipolar disorder, and 8 healthy control participants matched for age, sex, postmortem interval, and other potential confounds from the Harvard Brain Tissue Resource Center, McLean Hospital, Belmont, Massachusetts. We extracted DNA from laser-microdissected stratum oriens tissue of cornu ammonis 2/3 (CA2/3) and CA1 postmortem human hippocampus, bisulfite modified it, and assessed it with the Infinium HumanMethylation450 BeadChip (Illumina, Inc). The subset of CpG loci associated with GAD1 regulatory network genes was analyzed in R version 3.1.0 software (R Foundation) using the minfi package. Findings were validated using bisulfite pyrosequencing. Methylation levels at 1308 GAD1 regulatory network-associated CpG loci were assessed both as individual sites to identify differentially methylated positions and by sharing information among colocalized probes to identify differentially methylated regions. A total of 146 differentially methylated positions with a false detection rate lower than 0.05 were identified across all 6 groups (2 circuit locations in each of 3 diagnostic categories), and 54 differentially methylated regions with P < .01 were identified in single-group comparisons. Methylation changes were enriched in MSX1, CCND2, and DAXX at specific loci within the hippocampus of patients with schizophrenia and bipolar disorder. This work demonstrates diagnosis- and circuit-specific DNA methylation changes at a subset of GAD1 regulatory network genes in the human hippocampus in schizophrenia and bipolar disorder. These genes participate in chromatin regulation and cell cycle control, supporting the concept that the established GABAergic dysfunction in these disorders is related to disruption of GABAergic interneuron physiology at specific circuit locations within the human hippocampus.

Circuit- and Diagnosis-Specific DNA Methylation Changes at γ-Aminobutyric Acid–Related Genes in Postmortem Human Hippocampus in Schizophrenia and Bipolar Disorder

PubMed Central

Ruzicka, W. Brad; Subburaju, Sivan; Benes, Francine M.

2017-01-01

IMPORTANCE Dysfunction related to γ-aminobutyric acid (GABA)–ergic neurotransmission in the pathophysiology of major psychosis has been well established by the work of multiple groups across several decades, including the widely replicated downregulation of GAD1. Prior gene expression and network analyses within the human hippocampus implicate a broader network of genes, termed the GAD1 regulatory network, in regulation of GAD1 expression. Several genes within this GAD1 regulatory network show diagnosis- and sector-specific expression changes within the circuitry of the hippocampus, influencing abnormal GAD1 expression in schizophrenia and bipolar disorder. OBJECTIVE To investigate the hypothesis that aberrant DNA methylation contributes to circuit- and diagnosis-specific abnormal expression of GAD1 regulatory network genes in psychotic illness. DESIGN, SETTING, AND PARTICIPANTS This epigenetic association study targeting GAD1 regulatory network genes was conducted between July 1, 2012, and June 30, 2014. Postmortem human hippocampus tissue samples were obtained from 8patients with schizophrenia, 8 patients with bipolar disorder, and 8 healthy control participants matched for age, sex, postmortem interval, and other potential confounds from the Harvard Brain Tissue Resource Center, McLean Hospital, Belmont,Massachusetts. We extracted DNA from laser-microdissected stratum oriens tissue of cornu ammonis 2/3 (CA2/3) and CA1 postmortem human hippocampus, bisulfite modified it, and assessed it with the Infinium HumanMethylation450 BeadChip (Illumina, Inc). The subset of CpG loci associated with GAD1 regulatory network genes was analyzed in R version 3.1.0 software (R Foundation) using the minfi package. Findings were validated using bisulfite pyrosequencing. MAIN OUTCOMES AND MEASURES Methylation levels at 1308 GAD1 regulatory network–associated CpG loci were assessed both as individual sites to identify differentially methylated positions and by sharing information among colocalized probes to identify differentially methylated regions. RESULTS A total of 146 differentially methylated positions with a false detection rate lower than 0.05 were identified across all 6 groups (2 circuit locations in each of 3 diagnostic categories), and 54 differentially methylated regions with P < .01 were identified in single-group comparisons. Methylation changes were enriched in MSX1, CCND2, and DAXX at specific loci within the hippocampus of patients with schizophrenia and bipolar disorder. CONCLUSIONS AND RELEVANCE This work demonstrates diagnosis- and circuit-specific DNA methylation changes at a subset of GAD1 regulatory network genes in the human hippocampus in schizophrenia and bipolar disorder. These genes participate in chromatin regulation and cell cycle control, supporting the concept that the established GABAergic dysfunction in these disorders is related to disruption of GABAergic interneuron physiology at specific circuit locations within the human hippocampus. PMID:25738424

Improving the Care of Individuals with Schizophrenia and Substance Use Disorders: Consensus Recommendations

PubMed Central

ZIEDONIS, DOUGLAS M.; SMELSON, DAVID; ROSENTHAL, RICHARD N.; BATKI, STEVEN L.; GREEN, ALAN I.; HENRY, RENATA J.; MONTOYA, IVAN; PARKS, JOE; D. WEISS, ROGER

2008-01-01

National attention continues to focus on the need to improve care for individuals with co-occurring mental illnesses and substance use disorders, as emphasized in the 2003 President's New Freedom Commission Report on Mental Health and recent publications from the Substance Abuse and Mental Health Services Administration (SAMHSA). These reports document the need for best practice recommendations that can be translated into routine clinical care. Although efforts are underway to synthesize literature in this area, few focused recommendations are available that include expert opinion and evidence-based findings on the management of specific co-occurring disorders, such as schizophrenia and addiction. In response to the need for user-friendly recommendations on the treatment of schizophrenia and addiction, a consensus conference of experts from academic institutions and state mental health systems was organized to 1) frame the problem from clinical and systems-level perspectives; 2) identify effective and problematic psychosocial, pharmacological, and systems practices; and 3) develop a summary publication with recommendations for improving current practice. The results of the consensus meeting served as the foundation for this publication, which presents a broad set of recommendations for clinicians who treat individuals with schizophrenia. “Integrated treatment” is the new standard for evidence-based treatment for this population and recommendations are given to help clinicians implement such integrated treatment. Specific recommendations are provided concerning screening for substance use disorders in patients with schizophrenia, assessing motivation for change, managing medical conditions that commonly occur in patients with dual diagnoses (e.g., cardiovascular disease, liver complications, lung cancer, HIV, and hepatitis B or C infections) and selecting the most appropriate medications for such patients to maximize safety and minimize drug interactions, use of evidence-based psychosocial interventions for patients with dual diagnoses (e.g., Dual Recovery Therapy, modified cognitive-behavioral therapy, modified motivational enhancement therapy, and the Substance Abuse Management Module), and key pharmacotherapy principles for treating schizophrenia, substance use disorders, and comorbid anxiety, depression, and sleep problems in this population. Finally the article reviews programmatic and systemic changes needed to overcome treatment barriers and promote the best outcomes for this patient population. An algorithm summarizing the consensus recommendations is provided in an appendix to the article. PMID:16184072

Phosphodiesterase 7 Inhibition Induces Dopaminergic Neurogenesis in Hemiparkinsonian Rats

PubMed Central

Morales-Garcia, Jose A.; Alonso-Gil, Sandra; Gil, Carmen; Martinez, Ana; Santos, Angel

2015-01-01

Parkinson’s disease is characterized by a loss of dopaminergic neurons in a specific brain region, the ventral midbrain. Parkinson’s disease is diagnosed when approximately 50% of the dopaminergic neurons of the substantia nigra pars compacta (SNpc) have degenerated and the others are already affected by the disease. Thus, it is conceivable that all therapeutic strategies, aimed at neuroprotection, start too late. Therefore, an urgent medical need exists to discover new pharmacological targets and novel drugs with disease-modifying properties. In this regard, modulation of endogenous adult neurogenesis toward a dopaminergic phenotype might provide a new strategy to target Parkinson’s disease by partially ameliorating the dopaminergic cell loss that occurs in this disorder. We have previously shown that a phosphodiesterase 7 (PDE7) inhibitor, S14, exerts potent neuroprotective and anti-inflammatory effects in different rodent models of Parkinson’s disease, indicating that this compound could represent a novel therapeutic agent to stop the dopaminergic cell loss that occurs during the progression of the disease. In this report we show that, in addition to its neuroprotective effect, the PDE7 inhibitor S14 is also able to induce endogenous neuroregenerative processes toward a dopaminergic phenotype. We describe a population of actively dividing cells that give rise to new neurons in the SNpc of hemiparkinsonian rats after treatment with S14. In conclusion, our data identify S14 as a novel regulator of dopaminergic neuron generation. Significance Parkinson’s disease is a neurodegenerative disorder characterized by the loss of dopaminergic neurons in the ventral midbrain. Currently, no cure and no effective disease-modifying therapy are available for Parkinson’s disease; therefore, an urgent medical need exists to discover new pharmacological targets and novel drugs for the treatment of this disorder. The present study reports that an inhibitor of the enzyme phosphodiesterase 7 (S14) induces proliferation in vitro and in vivo of neural stem cells, promoting its differentiation toward a dopaminergic phenotype and therefore enhancing dopaminergic neuron generation. Because this drug is also able to confer neuroprotection of these cells in animal models of Parkinson’s disease, S14 holds great promise as a therapeutic new strategy for this disorder. PMID:25925836

Physical activity and the pelvic floor.

PubMed

Nygaard, Ingrid E; Shaw, Janet M

2016-02-01

Pelvic floor disorders are common, with 1 in 4 US women reporting moderate to severe symptoms of urinary incontinence, pelvic organ prolapse, or fecal incontinence. Given the high societal burden of these disorders, identifying potentially modifiable risk factors is crucial. Physical activity is one such potentially modifiable risk factor; the large number of girls and women participating in sport and strenuous training regimens increases the need to understand associated risks and benefits of these exposures. The aim of this review was to summarize studies reporting the association between physical activity and pelvic floor disorders. Most studies are cross-sectional and most include small numbers of participants. The primary findings of this review include that urinary incontinence during exercise is common and is more prevalent in women during high-impact sports. Mild to moderate physical activity, such as brisk walking, decreases both the odds of having and the risk of developing urinary incontinence. In older women, mild to moderate activity also decreases the odds of having fecal incontinence; however, young women participating in high-intensity activity are more likely to report anal incontinence than less active women. Scant data suggest that in middle-aged women, lifetime physical activity increases the odds of stress urinary incontinence slightly and does not increase the odds of pelvic organ prolapse. Women undergoing surgery for pelvic organ prolapse are more likely to report a history of heavy work than controls; however, women recruited from the community with pelvic organ prolapse on examination report similar lifetime levels of strenuous activity as women without this examination finding. Data are insufficient to determine whether strenuous activity while young predisposes to pelvic floor disorders later in life. The existing literature suggests that most physical activity does not harm the pelvic floor and does provide numerous health benefits for women. However, future research is needed to fill the many gaps in our knowledge. Prospective studies are needed in all populations, including potentially vulnerable women, such as those with high genetic risk, levator ani muscle injury, or asymptomatic pelvic organ prolapse, and on women during potentially vulnerable life periods, such as the early postpartum or postoperative periods. Copyright © 2016 Elsevier Inc. All rights reserved.

Diagnostic cost groups (DCGs) and concurrent utilization among patients with substance abuse disorders.

PubMed

Rosen, Amy K; Loveland, Susan A; Anderson, Jennifer J; Hankin, Cheryl S; Breckenridge, James N; Berlowitz, Dan R

2002-08-01

To assess the performance of Diagnostic Cost Groups (DCGs) in explaining variation in concurrent utilization for a defined subgroup, patients with substance abuse (SA) disorders, within the Department of Veterans Affairs (VA). A 60 percent random sample of veterans who used health care services during Fiscal Year (FY) 1997 was obtained from VA administrative databases. Patients with SA disorders (13.3 percent) were identified from primary and secondary ICD-9-CM diagnosis codes. Concurrent risk adjustment models were fitted and tested using the DCG/HCC model. Three outcome measures were defined: (1) "service days" (the sum of a patient's inpatient and outpatient visit days), (2) mental health/substance abuse (MH/SA) service days, and (3) ambulatory provider encounters. To improve model performance, we ran three DCG/HCC models with additional indicators for patients with SA disorders. To create a single file of veterans who used health care services in FY 1997, we merged records from all VA inpatient and outpatient files. Adding indicators for patients with mild/moderate SA disorders did not appreciably improve the R-squares for any of the outcome measures. When indicators were added for patients with severe SA who were in the most costly category, the explanatory ability of the models was modestly improved for all three outcomes. Modifying the DCG/HCC model with additional markers for SA modestly improved homogeneity and model prediction. Because considerable variation still remained after modeling, we conclude that health care systems should evaluate "off-the-shelf" risk adjustment systems before applying them to their own populations.

ROCK inhibition in models of neurodegeneration and its potential for clinical translation.

PubMed

Koch, Jan Christoph; Tatenhorst, Lars; Roser, Anna-Elisa; Saal, Kim-Ann; Tönges, Lars; Lingor, Paul

2018-04-03

Neurodegenerative disorders like Parkinson's disease, Alzheimer's disease, or amyotrophic lateral sclerosis are affecting a rapidly increasing population worldwide. While common pathomechanisms such as protein aggregation, axonal degeneration, dysfunction of protein clearing and an altered immune response have been characterized, no disease-modifying therapies have been developed so far. Interestingly, a significant involvement of the Rho kinase (ROCK) signaling pathway has been described in all of these mechanisms making it a promising target for new therapeutic approaches. In this article, we first review current knowledge of the involvement of ROCK in neurodegenerative disorders and the utility of its inhibition as a disease-modifying therapy in different neurodegenerative disorders. After a detailed description of the biochemical characteristics of ROCK and its molecular interactors, differences of ROCK-expression under physiological and pathological conditions are compared. Next, different pharmacological and molecular-genetic strategies to inhibit ROCK-function are discussed, focusing on pharmacological ROCK-inhibitors. The role of the ROCK-pathway in cellular processes that are central in neurodegenerative disorders pathology like axonal degeneration, autophagy, synaptic and glial function is explained in detail. Finally, all available data on ROCK-inhibition in different animal models of neurodegenerative disorders is reviewed and first approaches for translation into human patients are discussed. Taken together, there is now extensive evidence from preclinical studies in several neurodegenerative disorders that characterize ROCK as a promising drug target for further translational research in neurodegenerative disorders. Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.

The PHQ-PD as a Screening Tool for Panic Disorder in the Primary Care Setting in Spain

PubMed Central

Wood, Cristina Mae; Ruíz-Rodríguez, Paloma; Tomás-Tomás, Patricia; Gracia-Gracia, Irene; Dongil-Collado, Esperanza; Iruarrizaga, M. Iciar

2016-01-01

Introduction Panic disorder is a common anxiety disorder and is highly prevalent in Spanish primary care centres. The use of validated tools can improve the detection of panic disorder in primary care populations, thus enabling referral for specialized treatment. The aim of this study is to determine the accuracy of the Patient Health Questionnaire-Panic Disorder (PHQ-PD) as a screening and diagnostic tool for panic disorder in Spanish primary care centres. Method We compared the psychometric properties of the PHQ-PD to the reference standard, the Structured Clinical Interview for DSM-IV Axis I Disorders (SCID-I) interview. General practitioners referred 178 patients who completed the entire PHQ test, including the PHQ-PD, to undergo the SCID-I. The sensitivity, specificity, positive and negative predictive values and positive and negative likelihood ratios of the PHQ-PD were assessed. Results The operating characteristics of the PHQ-PD are moderate. The best cut-off score was 5 (sensitivity .77, specificity .72). Modifications to the questionnaire's algorithms improved test characteristics (sensitivity .77, specificity .72) compared to the original algorithm. The screening question alone yielded the highest sensitivity score (.83). Conclusion Although the modified algorithm of the PHQ-PD only yielded moderate results as a diagnostic test for panic disorder, it was better than the original. Using only the first question of the PHQ-PD showed the best psychometric properties (sensitivity). Based on these findings, we suggest the use of the screening questions for screening purposes and the modified algorithm for diagnostic purposes. PMID:27525977

Lifetime psychiatric comorbidity with substance use disorders: does healthcare use modify the strength of associations ?

PubMed

Encrenaz, Gaelle; Messiah, Antoine

2006-05-01

The frequent psychiatric comorbidity among subjects with a substance use disorder (SUD) can be explained by an increased vulnerability to problematic drug use among subjects with a non-substance-related psychiatric disorder (NSRPD). The care of this disorder should then reduce the likelihood of a secondary SUD. To examine how healthcare use for psychological symptoms modifies the lifetime association between SUD and NSRPD. Two hundred and twenty four students were evaluated for mental disorders and healthcare use. Mental disorders were assessed with the Mini-International Neuropsychiatric Interview (MINI). Healthcare use included consultations with a general practitioner (GP), a psychiatrist or a psychologist. The lifetime occurrence of a SUD was analysed by lifetime number of NSRPD and healthcare use for psychological symptoms. Analyses were adjusted on gender, university affiliation, living environment and temperament and character dimensions. Compared to subjects without NSRPD, those with at least two NSRPD who did not use healthcare were more likely to have had a lifetime SUD (OR = 3.9). By contrast, those who had only one NSRPD seemed to be as likely as those with no NSRPD to have had a SUD. These results suggest a decreased probability of SUD among subjects with several NSRPD who used healthcare. Due to the cross-sectional design of this study, causal inferences cannot be drawn. This analysis shows the importance, however, of taking healthcare use into account in comorbidity studies.

Exome sequencing of a large family identifies potential candidate genes contributing risk to bipolar disorder.

PubMed

Zhang, Tianxiao; Hou, Liping; Chen, David T; McMahon, Francis J; Wang, Jen-Chyong; Rice, John P

2018-03-01

Bipolar disorder is a mental illness with lifetime prevalence of about 1%. Previous genetic studies have identified multiple chromosomal linkage regions and candidate genes that might be associated with bipolar disorder. The present study aimed to identify potential susceptibility variants for bipolar disorder using 6 related case samples from a four-generation family. A combination of exome sequencing and linkage analysis was performed to identify potential susceptibility variants for bipolar disorder. Our study identified a list of five potential candidate genes for bipolar disorder. Among these five genes, GRID1(Glutamate Receptor Delta-1 Subunit), which was previously reported to be associated with several psychiatric disorders and brain related traits, is particularly interesting. Variants with functional significance in this gene were identified from two cousins in our bipolar disorder pedigree. Our findings suggest a potential role for these genes and the related rare variants in the onset and development of bipolar disorder in this one family. Additional research is needed to replicate these findings and evaluate their patho-biological significance. Copyright © 2017 Elsevier B.V. All rights reserved.

Using the Teaching Interactions Procedure to Teach Social Skills to Children with Autism and Intellectual Disability

ERIC Educational Resources Information Center

Ng, Aubrey Hui Shyuan; Schulze, Kim; Rudrud, Eric; Leaf, Justin B.

2016-01-01

This study implemented a modified teaching interaction procedure to teach social skills to 4 children diagnosed with autism spectrum disorder with an intellectual disability. A multiple baseline design across social skills and replicated across participants was utilized to evaluate the effects of the modified teaching interaction procedure. The…

Defining Characteristics for Young Children Meeting Cutoff on the Modified Checklist for Autism in Toddlers

ERIC Educational Resources Information Center

Kozlowski, Alison M.; Matson, Johnny L.; Worley, Julie A.; Sipes, Megan; Horovitz, Max

2012-01-01

Early diagnosis of Autism Spectrum Disorders (ASDs) is crucial so that early intervention services, which have been found to best alleviate symptoms of ASD in children, can be implemented. Currently, the "Modified Checklist for Autism in Toddlers" ("M-CHAT") and the "Baby and Infant Screen for Children with aUtIsm…

Aging children of long-lived parents experience slower cognitive decline.

PubMed

Dutta, Ambarish; Henley, William; Robine, Jean-Marie; Llewellyn, David; Langa, Kenneth M; Wallace, Robert B; Melzer, David

2014-10-01

Parental longevity confers lower risks for some age-related diseases in offspring. We tested the association between parental longevity and late-life cognitive decline or dementia. Data were from the Health and Retirement Study (HRS), a US national sample. Biennial cognitive assessment (Telephone Interview of Cognitive Status-Modified [TICS-m]) occurred for ages 64 years or older in 1996 through 2008 (maximum, 79 years), including physician-diagnosed memory disorder. Offspring were categorized into parental longevity groups based on gender-specific distributional cut points. Model covariates included race, respondents' education, and income status during childhood and adulthood. Offspring groups did not differ on TICS-m scores at baseline. During follow-up, offspring of two long-lived parents experienced 40% slower rates of TICS-m decline than those with no long-lived parents (95% confidence interval, 12-72; P=.003; n=4731). Increased parental longevity was also associated with lower risk of physician-diagnosed memory disorder. Estimates did not change after controlling for environmental variables. Parental longevity is associated inversely with cognitive decline and self-reported diagnosed memory disorders in aging offspring. Parental longevity may be a valuable trait for identifying early biomarkers for resistance to cognitive decline in aging. Copyright © 2014 The Alzheimer's Association. Published by Elsevier Inc. All rights reserved.

Treatment of Internet Addiction with Anxiety Disorders: Treatment Protocol and Preliminary Before-After Results Involving Pharmacotherapy and Modified Cognitive Behavioral Therapy.

PubMed

Santos, Veruska Andrea; Freire, Rafael; Zugliani, Morená; Cirillo, Patricia; Santos, Hugo Henrique; Nardi, Antonio Egidio; King, Anna Lucia

2016-03-22

The growth of the Internet has led to significant change and has become an integral part of modern life. It has made life easier and provided innumerous benefits; however, excessive use has brought about the potential for addiction, leading to severe impairments in social, academic, financial, psychological, and work domains. Individuals addicted to the Internet usually have comorbid psychiatric disorders. Panic disorder (PD) and generalized anxiety disorder (GAD) are prevalent mental disorders, involving a great deal of damage in the patient's life. This open trial study describes a treatment protocol among 39 patients with anxiety disorders and Internet addiction (IA) involving pharmacotherapy and modified cognitive behavioral therapy (CBT). Of the 39 patients, 25 were diagnosed with PD and 14 with GAD, in addition to Internet addiction. At screening, patients responded to the MINI 5.0, Hamilton Anxiety Rating Scale, Hamilton Depression Rating Scale, Clinical Global Impressions Scale, and the Young Internet Addiction Scale. At that time, IA was observed taking into consideration the IAT scale (cutoff score above 50), while anxiety disorders were diagnosed by a psychiatrist. Patients were forwarded for pharmacotherapy and a modified CBT protocol. Psychotherapy was conducted individually, once a week, over a period of 10 weeks, and results suggest that the treatment was effective for anxiety and Internet addiction. Before treatment, anxiety levels suggested severe anxiety, with an average score of 34.26 (SD 6.13); however, after treatment the mean score was 15.03 (SD 3.88) (P<.001). A significant improvement in mean Internet addiction scores was observed, from 67.67 (SD 7.69) before treatment, showing problematic internet use, to 37.56 (SD 9.32) after treatment (P<.001), indicating medium Internet use. With respect to the relationship between IA and anxiety, the correlation between scores was .724. This study is the first research into IA treatment of a Brazilian population. The improvement was remarkable due to the complete engagement of patients in therapy, which contributed to the success of the treatment from a behavioral perspective, and gave patients the confidence to continue to manage Internet use in their lives.

State-Level Policies and Psychiatric Morbidity In Lesbian, Gay, and Bisexual Populations

PubMed Central

Keyes, Katherine M.; Hasin, Deborah S.

2009-01-01

Objectives. We investigated the modifying effect of state-level policies on the association between lesbian, gay, or bisexual status and the prevalence of psychiatric disorders. Methods. Data were from wave 2 of the National Epidemiologic Survey on Alcohol and Related Conditions (NESARC), a nationally representative study of noninstitutionalized US adults (N = 34 653). States were coded for policies extending protections against hate crimes and employment discrimination based on sexual orientation. Results. Compared with living in states with policies extending protections, living in states without these policies predicted a significantly stronger association between lesbian, gay, or bisexual status and psychiatric disorders in the past 12 months, including generalized anxiety disorder (F = 3.87; df = 2; P = .02), post-traumatic stress disorder (F = 3.42; df = 2; P = .04), and dysthymia (F = 5.20; df = 2; P = .02). Living in states with policies that did not extend protections also predicted a stronger relation between lesbian, gay, or bisexual status and psychiatric comorbidity (F = 2.47; df = 2; P = .04). Conclusions. State-level protective policies modify the effect of lesbian, gay, or bisexual status on psychiatric disorders. Policies that reduce discrimination against gays and lesbians are urgently needed to protect the health and well-being of this population. PMID:19833997

Relationships between allostatic load, unhealthy behaviors, and depressive disorder in U.S. adults, 2005-2012 NHANES.

PubMed

Rodriquez, Erik J; Livaudais-Toman, Jennifer; Gregorich, Steven E; Jackson, James S; Nápoles, Anna M; Pérez-Stable, Eliseo J

2018-05-01

Unhealthy behaviors may modify relationships between chronic stress and depression among diverse older adults. We analyzed nationally representative cross-sectional data from participants aged 40-79 years of the 2005-2012 National Health and Nutrition Examination Survey. Unhealthy behaviors included current smoking, excessive/binge drinking, insufficient physical activity, and fair/poor diet. Allostatic load was defined by 10 biomarkers indicating the cumulative physiologic burden of stress. Depressive disorder was assessed using the Patient Health Questionnaire. Multivariable logistic regression examined whether current smoking, excessive/binge drinking, insufficient physical activitiy, and fair/poor diet modified relationships between allostatic load and depressive disorder. Mean age of 12,272 participants was 55.6 years (standard error = 0.19), 51.9% were women, and most had at least a high school education (81.8%). Latinos (11.3%) and African Americans (10.4%) were more likely than Whites (7.1%; p < 0.001) to meet depressive disorder criteria. Allostatic load was not associated independently with depressive disorder in any racial/ethnic group and this lack of a relationship did not differ by the extent of unhealthy behaviors. Although Latinos and African Americans report higher levels of depression than Whites, physiological markers of stress do not appear to explain these differences. Published by Elsevier Inc.

Establishing a Pedagogical Framework for the Multicultural Course in Communication Sciences and Disorders

ERIC Educational Resources Information Center

Horton-Ikard, RaMonda; Munoz, Maria L.; Thomas-Tate, Shurita; Keller-Bell, Yolanda

2009-01-01

Purpose: To provide an overview of a model for teaching a foundational course in multicultural (MC) issues and to demonstrate how it can be modified for use in communication sciences and disorders (CSD) by integrating 3 primary dimensions of cultural competence: awareness, knowledge, and skills. Method: This tutorial begins by establishing the…

Effects of a Modified Milieu Therapy Intervention on the Social Communicative Behaviors of Young Children with Autism Spectrum Disorders

ERIC Educational Resources Information Center

Mancil, G. Richmond; Conroy, Maureen A.; Haydon, Todd F.

2009-01-01

The purpose of the current study was to evaluate the effectiveness of combining milieu therapy and functional communication training (FCT) to replace aberrant behavior with functional communicative skills in 3 male preschool or elementary aged children with Autism Spectrum Disorders (ASD). Study activities were conducted in the natural…

The Validity of Virtual Environments for Eliciting Emotional Responses in Patients with Eating Disorders and in Controls

ERIC Educational Resources Information Center

Ferrer-Garcia, Marta; Gutierrez-Maldonado, Jose; Caqueo-Urizar, Alejandra; Moreno, Elena

2009-01-01

This article explores the efficacy of virtual environments representing situations that are emotionally significant to patients with eating disorders (ED) to modify depression and anxiety levels both in these patients and in controls. Eighty-five ED patients and 108 students were randomly exposed to five experimental virtual environments (a…

Establishing a Scale for Assessing the Social Validity of Skill Building Interventions for Young Children with Autism Spectrum Disorder

ERIC Educational Resources Information Center

Berger, Natalie I.; Manston, Lauren; Ingersoll, Brooke

2016-01-01

This study evaluated the psychometric properties of the Scale of Treatment Perceptions (STP), a measure of treatment acceptability targeting skill-building interventions for Autism Spectrum Disorder (ASD). This scale utilizes a strength-based approach to intervention assessment, and was established by modifying the Behavior Intervention Rating…

The Texas Children's Medication Algorithm Project: Revision of the Algorithm for Pharmacotherapy of Attention-Deficit/Hyperactivity Disorder

ERIC Educational Resources Information Center

Pliszka, Steven R.; Crismon, M. Lynn; Hughes, Carroll W.; Corners, C. Keith; Emslie, Graham J.; Jensen, Peter S.; McCracken, James T.; Swanson, James M.; Lopez, Molly

2006-01-01

Objective: In 1998, the Texas Department of Mental Health and Mental Retardation developed algorithms for medication treatment of attention-deficit/hyperactivity disorder (ADHD). Advances in the psychopharmacology of ADHD and results of a feasibility study of algorithm use in community mental health centers caused the algorithm to be modified and…

Do Anxiety-Disordered Children Need to Come into the Clinic for Efficacious Treatment?

ERIC Educational Resources Information Center

Cobham, Vanessa E.

2012-01-01

Objective: This study compared 3 experimental conditions: wait-list, therapist-supported bibliotherapy, and individual therapy, in the treatment of child anxiety. Method: Participants were 55 children (25 girls and 30 boys), aged 7 to 14 years diagnosed with an anxiety disorder, and their parents. Families were assigned using a modified random…

State-Dependent Changes of Connectivity Patterns and Functional Brain Network Topology in Autism Spectrum Disorder

ERIC Educational Resources Information Center

Barttfeld, Pablo; Wicker, Bruno; Cukier, Sebastian; Navarta, Silvana; Lew, Sergio; Leiguarda, Ramon; Sigman, Mariano

2012-01-01

Anatomical and functional brain studies have converged to the hypothesis that autism spectrum disorders (ASD) are associated with atypical connectivity. Using a modified resting-state paradigm to drive subjects' attention, we provide evidence of a very marked interaction between ASD brain functional connectivity and cognitive state. We show that…

The Impact of Labels and Behaviors on the Stigmatization of Adults with Asperger's Disorder

ERIC Educational Resources Information Center

Butler, Robert C.; Gillis, Jennifer M.

2011-01-01

Currently, there is a paucity of literature on stigmatization of adults with Asperger's Disorder (AD). Therefore, this study examined whether young adults hold stigmatizing views towards individuals with AD and if that stigmatization is elicited by behaviors or labels. College students (N = 195) read one of six vignettes. A modified Social…

Influence of schooling on language abilities of adults without linguistic disorders.

PubMed

Soares, Ellen Cristina Siqueira; Ortiz, Karin Zazo

2009-01-01

In order to properly assess language, sociodemographic variables that can influence the linguistic performance of individuals with or without linguistic disorders need to be taken into account. The aim of this study was to evaluate the influence of schooling and age on the results from the Montreal Toulouse (Modified MT Beta-86) language assessment test among individuals without linguistic disorders. Cross-sectional study carried out between March 2006 and August 2007 in the Speech, Language and Hearing Pathology Department of Universidade Federal de São Paulo (Unifesp), São Paulo, Brazil. Eighty volunteers were selected. Schooling was stratified into three bands: A (1-4 years), B (5-8 years) and C (nine years and over). The age range was from 17 to 80 years. All the subjects underwent the Montreal Toulouse (Modified MT Beta-86) language assessment protocol. Statistically significant differences were found in relation to schooling levels, in the tasks of oral comprehension, reading, graphical comprehension, naming, lexical availability, dictation, graphical naming of actions and number reading. Statistically significant age-related differences in dictation and lexical availability tasks were observed. The Montreal Toulouse (Modified MT Beta-86) test seems to be sensitive to variations in schooling and age. These variables should be taken into account when this test is used for assessing patients with brain damage.

Burnout as a risk factor for antidepressant treatment - a repeated measures time-to-event analysis of 2936 Danish human service workers.

PubMed

Madsen, Ida E H; Lange, Theis; Borritz, Marianne; Rugulies, Reiner

2015-06-01

Burnout is a state of emotional exhaustion, feelings of reduced personal accomplishment, and withdrawal from work thought to occur as a consequence of prolonged occupational stress. The condition is not included in the diagnostic classifications, but is considered likely to develop into depressive disorder in some cases. We examined the prospective association between burnout and antidepressant treatment, as an indicator of clinically significant mental disorder. We further investigated potential effect-modifiers of the association, to identify factors that may prevent this progression of burnout. We used questionnaire data from a three-wave study of Danish human service workers conducted during 1999-2005, linked with national register data on purchases of antidepressants (ATC: N06A). We included 4788 observations from 2936 individuals (81% women) and analysed data by Aalens additive hazards modeling, examining the risk of entering antidepressant treatment in relation to the level of work-related burnout measured by the Copenhagen Burnout inventory. As effect-modifiers we examined both sociodemographic factors and a range of psychosocial work environment factors. The level of burnout predicted antidepressant treatment. This association was modified by sex (p < 0.01). In men, high vs. intermediate burnout was associated with a 5% increased risk of antidepressant treatment per year of follow-up. This risk difference was 1% for women. Due to the sex specific patterns, we restricted effect modification analyses to women. We found no effect-modification by the examined work environment factors, though a sensitivity analysis indicated a possible stronger association in women of lower occupational position. In conclusion, burnout predicted antidepressant treatment, with a stronger association in men than women. We found no evidence of effect-modification by any of the examined psychosocial work environment factors. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

Diastolic blood pressure is a potentially modifiable risk factor for preeclampsia in women with pre-existing diabetes.

PubMed

Nørgaard, Sidse Kjærhus; Vestgaard, Marianne Jenlev; Jørgensen, Isabella Lindegaard; Ásbjörnsdóttir, Björg; Ringholm, Lene; McIntyre, Harold David; Damm, Peter; Mathiesen, Elisabeth Reinhardt

2018-04-01

To identify early clinical, modifiable risk factors for preeclampsia present at first antenatal visit and assess the prevalence of pregnancy-related hypertensive disorders in women with pre-existing diabetes treated with tight glycemic and blood pressure (BP) control. A population-based cohort study of 494 women with pre-existing diabetes (307 and 187 women with type 1 and type 2 diabetes, respectively), included at their first antenatal visit from 2012 to 2016. The prevalence of chronic hypertension (without diabetic nephropathy or microalbuminuria), gestational hypertension and preeclampsia was recorded. Diabetic microangiopathy included presence of nephropathy, microalbuminuria and/or retinopathy. Treatment target was BP <135/85 mmHg. HbA1c was 6.9 ± 2.4% (50 ± 12 mmol/mol) at first antenatal visit and 6.0 ± 0.6% (43 ± 6 mmol/mol) before delivery with no differences between women with type 1 and type 2 diabetes. At the first antenatal visit, the prevalence of microalbuminuria was 6% (6% vs. 6%), nephropathy 2% (1% vs. 2%) and chronic hypertension 6% (3% vs. 10%, p = 0.03). Gestational hypertension developed in 8% (9% vs. 6%) and preeclampsia developed in 8% (9% vs. 7%). Presence of diabetic microangiopathy (adjusted odds ratio (OR) 4.35 (confidence interval 2.12-8.93)) and diastolic BP (adjusted OR 1.72 per 10 mmHg (1.05-2.82)) at the first antenatal visit were independent risk factors for preeclampsia. At the first antenatal visit, diastolic BP was the only independent, potentially modifiable risk factor for preeclampsia in women with pre-existing diabetes in the context of tight glycemic and BP control. One out of four women had hypertensive disorders during pregnancy. Copyright © 2018 Elsevier B.V. All rights reserved.

Use of a modified Comprehensive Pain Evaluation Questionnaire: Characteristics and functional status of patients on entry to a tertiary care pain clinic

PubMed Central

Nelli, Jennifer M; Nicholson, Keith; Lakha, S Fatima; Louffat, Ada F; Chapparo, Luis; Furlan, Julio; Mailis-Gagnon, Angela

2012-01-01

BACKGROUND: With increasing knowledge of chronic pain, clinicians have attempted to assess chronic pain patients with lengthy assessment tools. OBJECTIVES: To describe the functional and emotional status of patients presenting to a tertiary care pain clinic; to assess the reliability and validity of a diagnostic classification system for chronic pain patients modelled after the Multidimensional Pain Inventory; to provide psychometric data on a modified Comprehensive Pain Evaluation Questionnaire (CPEQ); and to evaluate the relationship between the modified CPEQ construct scores and clusters with Diagnostic and Statistical Manual, Fourth Edition – Text Revision Pain Disorder diagnoses. METHODS: Data on 300 new patients over the course of nine months were collected using standardized assessment procedures plus a modified CPEQ at the Comprehensive Pain Program, Toronto Western Hospital, Toronto, Ontario. RESULTS: Cluster analysis of the modified CPEQ revealed three patient profiles, labelled Adaptive Copers, Dysfunctional, and Interpersonally Distressed, which closely resembled those previously reported. The distribution of modified CPEQ construct T scores across profile subtypes was similar to that previously reported for the original CPEQ. A novel finding was that of a strong relationship between the modified CPEQ clusters and constructs with Diagnostic and Statistical Manual, Fourth Edition – Text Revision Pain Disorder diagnoses. DISCUSSION AND CONCLUSIONS: The CPEQ, either the original or modified version, yields reproducible results consistent with the results of other studies. This technique may usefully classify chronic pain patients, but more work is needed to determine the meaning of the CPEQ clusters, what psychological or biomedical variables are associated with CPEQ constructs or clusters, and whether this instrument may assist in treatment planning or predict response to treatment. PMID:22518368

Unraveling Biochemical Pathways Affected by Mitochondrial Dysfunctions Using Metabolomic Approaches

PubMed Central

Demine, Stéphane; Reddy, Nagabushana; Renard, Patricia; Raes, Martine; Arnould, Thierry

2014-01-01

Mitochondrial dysfunction(s) (MDs) can be defined as alterations in the mitochondria, including mitochondrial uncoupling, mitochondrial depolarization, inhibition of the mitochondrial respiratory chain, mitochondrial network fragmentation, mitochondrial or nuclear DNA mutations and the mitochondrial accumulation of protein aggregates. All these MDs are known to alter the capacity of ATP production and are observed in several pathological states/diseases, including cancer, obesity, muscle and neurological disorders. The induction of MDs can also alter the secretion of several metabolites, reactive oxygen species production and modify several cell-signalling pathways to resolve the mitochondrial dysfunction or ultimately trigger cell death. Many metabolites, such as fatty acids and derived compounds, could be secreted into the blood stream by cells suffering from mitochondrial alterations. In this review, we summarize how a mitochondrial uncoupling can modify metabolites, the signalling pathways and transcription factors involved in this process. We describe how to identify the causes or consequences of mitochondrial dysfunction using metabolomics (liquid and gas chromatography associated with mass spectrometry analysis, NMR spectroscopy) in the obesity and insulin resistance thematic. PMID:25257998

Intestinal bacteria modify lymphoma incidence and latency by affecting systemic inflammatory state, oxidative stress, and leucocyte genotoxicity

PubMed Central

Yamamoto, Mitsuko L.; Maier, Irene; Dang, Angeline Tilly; Berry, David; Liu, Jared; Ruegger, Paul M.; Yang, Jiue-in; Soto, Phillip A.; Presley, Laura L.; Reliene, Ramune; Westbrook, Aya M.; Wei, Bo; Loy, Alexander; Chang, Christopher; Braun, Jonathan; Borneman, James; Schiestl, Robert H.

2013-01-01

Ataxia-telangiectasia (A-T) is a genetic disorder associated with high incidence of B cell lymphoma. Using an A-T mouse model, we compared lymphoma incidence in several isogenic mouse colonies harboring different bacterial communities, finding that intestinal microbiota are a major contributor to disease penetrance and latency, lifespan, molecular oxidative stress and systemic leucocyte genotoxicity. High throughput sequence analysis of rRNA genes identified mucosa-associated bacterial phylotypes that were colony-specific. Lactobacillus johnsonii, which was deficient in the more cancer-prone mouse colony, was causally tested for its capacity to confer reduced genotoxicity when restored by short-term oral transfer. This intervention decreased systemic genotoxicity, a response associated with reduced basal leucocytes and the cytokine-mediated inflammatory state, and mechanistically linked to the host cell biology of systemic genotoxicity. Our results suggest that intestinal microbiota are a potentially modifiable trait for translational intervention in individuals at risk for B cell lymphoma, or for other diseases that are driven by genotoxicity or the molecular response to oxidative stress. PMID:23860718

Condensation of helium in aerogel and athermal dynamics of the random-field Ising model.

PubMed

Aubry, Geoffroy J; Bonnet, Fabien; Melich, Mathieu; Guyon, Laurent; Spathis, Panayotis; Despetis, Florence; Wolf, Pierre-Etienne

2014-08-22

High resolution measurements reveal that condensation isotherms of (4)He in high porosity silica aerogel become discontinuous below a critical temperature. We show that this behavior does not correspond to an equilibrium phase transition modified by the disorder induced by the aerogel structure, but to the disorder-driven critical point predicted for the athermal out-of-equilibrium dynamics of the random-field Ising model. Our results evidence the key role of nonequilibrium effects in the phase transitions of disordered systems.

ECT Has Greater Efficacy Than Fluoxetine in Alleviating the Burden of Illness for Patients with Major Depressive Disorder: A Taiwanese Pooled Analysis.

PubMed

Lin, Ching-Hua; Huang, Chun-Jen; Chen, Cheng-Chung

2018-01-01

The burden of major depressive disorder includes suffering due to symptom severity, functional impairment, and quality of life deficits. The aim of this study was to compare the differences between electroconvulsive therapy and pharmacotherapy in reducing such burdens. This was a pooled analysis study including 2 open-label trials for major depressive disorder inpatients receiving either standard bitemporal and modified electroconvulsive therapy with a maximum of 12 sessions or 20 mg/d of fluoxetine for 6 weeks. Symptom severity, functioning, and quality of life were assessed using the 17-item Hamilton Rating Scale for Depression, the Modified Work and Social Adjustment Scale, and SF-36. Side effects following treatment, including subjective memory impairment, nausea/vomiting, and headache, were recorded. The differences between these 2 groups in 17-item Hamilton Rating Scale for Depression, Modified Work and Social Adjustment Scale, quality of life, side effects, and time to response (at least a 50% reduction of 17-item Hamilton Rating Scale for Depression) and remission (17-item Hamilton Rating Scale for Depression ≤7) following treatment were analyzed. Electroconvulsive therapy (n=116) showed a significantly greater reduction in 17-item Hamilton Rating Scale for Depression, Modified Work and Social Adjustment Scale, and quality of life deficits and had significantly shorter time to response/remission than fluoxetine (n=126). However, the electroconvulsive therapy group was more likely to experience subjective memory impairment and headache. Compared with fluoxetine, electroconvulsive therapy was more effective in alleviating the burden of major depressive disorder and had a substantially increased speed of response/remission in the acute phase. Increased education and information about electroconvulsive therapy for clinicians, patients, and their families and the general public is warranted. © The Author(s) 2017. Published by Oxford University Press on behalf of CINP.

Bipolar disorder and diabetes mellitus: evidence for disease-modifying effects and treatment implications.

PubMed

Charles, Ellen F; Lambert, Christophe G; Kerner, Berit

2016-12-01

Bipolar disorder refers to a group of chronic psychiatric disorders of mood and energy levels. While dramatic psychiatric symptoms dominate the acute phase of the diseases, the chronic course is often determined by an increasing burden of co-occurring medical conditions. High rates of diabetes mellitus in patients with bipolar disorder are particularly striking, yet unexplained. Treatment and lifestyle factors could play a significant role, and some studies also suggest shared pathophysiology and risk factors. In this systematic literature review, we explored data around the relationship between bipolar disorder and diabetes mellitus in recently published population-based cohort studies with special focus on the elderly. A systematic search in the PubMed database for the combined terms "bipolar disorder" AND "elderly" AND "diabetes" in papers published between January 2009 and December 2015 revealed 117 publications; 7 studies were large cohort studies, and therefore, were included in our review. We found that age- and gender- adjusted risk for diabetes mellitus was increased in patients with bipolar disorder and vice versa (odds ratio range between 1.7 and 3.2). Our results in large population-based cohort studies are consistent with the results of smaller studies and chart reviews. Even though it is likely that heterogeneous risk factors may play a role in diabetes mellitus and in bipolar disorder, growing evidence from cell culture experiments and animal studies suggests shared disease mechanisms. Furthermore, disease-modifying effects of bipolar disorder and diabetes mellitus on each other appear to be substantial, impacting both treatment response and outcomes. The risk of diabetes mellitus in patients with bipolar disorder is increased. Our findings add to the growing literature on this topic. Increasing evidence for shared disease mechanisms suggests new disease models that could explain the results of our study. A better understanding of the complex relationship between bipolar disorder and diabetes mellitus could lead to novel therapeutic approaches and improved outcomes.

Risk factor modifications and depression incidence: a 4-year longitudinal Canadian cohort of the Montreal Catchment Area Study

PubMed Central

Meng, Xiangfei; Brunet, Alain; Turecki, Gustavo; Liu, Aihua; D'Arcy, Carl; Caron, Jean

2017-01-01

Objective Few studies have examined the effect of risk factor modifications on depression incidence. This study was to explore psychosocial risk factors for depression and quantify the effect of risk factor modifications on depression incidence in a large-scale, longitudinal population-based study. Methods Data were from the Montreal Longitudinal Catchment Area study (N=2433). Multivariate modified Poisson regression was used to estimate relative risk (RR). Population attributable fractions were also used to estimate the potential impact of risk factor modifications on depression incidence. Results The cumulative incidence rate of major depressive disorder at the 2-year follow-up was 4.8%, and 6.6% at the 4-year follow-up. Being a younger adult, female, widowed, separated or divorced, Caucasian, poor, occasional drinker, having a family history of mental health problems, having less education and living in areas with higher unemployment rates and higher proportions of visible minorities, more cultural community centres and community organisations, were consistently associated with the increased risk of incident major depressive disorder. Although only 5.1% of the disease incidence was potentially attributable to occasional drinking (vs abstainers) at the 2-year follow-up, the attribution of occasional drinking doubled at the 4-year follow-up. A 10% reduction in the prevalence of occasional drinking in this population could potentially prevent half of incident cases. Conclusions Modifiable risk factors, both individual and societal, could be the targets for public depression prevention programmes. These programmes should also be gender-specific, as different risk factors have been identified for men and women. Public health preventions at individual levels could focus on the better management of occasional drinking, as it explained around 5%~10% of incident major depressive disorders. Neighbourhood characteristics could also be the target for public prevention programmes. However, this could be very challenging. A cost-effectiveness analysis of a variety of prevention efforts is warranted. PMID:28601831

Protocol for development and validation of a context-appropriate tool for assessing organisational readiness for change in primary health clinics in South Africa

PubMed Central

Sorsdahl, Katherine; Lombard, Carl; Petersen-Williams, Petal; Myers, Bronwyn

2018-01-01

Introduction A large treatment gap for common mental disorders (such as depression) exists in South Africa. Comorbidity with other chronic diseases, including HIV and diseases of lifestyle, is an increasing public health concern globally. Currently, primary health facilities as points of care for those with chronic disease provide limited services for common mental disorders. Assessing organisational readiness for change (ORC) towards adopting health innovations (such as mental health services) using contextually appropriate measures is needed to facilitate implementation of these services. This study aims to investigate the validity of the Texas Christian University Organisational Readiness for Change (TCU-ORC) scale in the South African context. Subsequently, we will develop a shortened version of this scale. This study is nested within Project MIND, a multiyear randomised controlled trial that is testing two different approaches for integrating counselling for common mental disorders into chronic disease care. Although the modified, contextually appropriate ORC measure resulting from the proposed study will be developed in the context of integrating mental health into primary healthcare services, the potential for the tool to be generalised to further understanding barriers to any change being implemented in primary care settings is high. Methods and analysis We will establish internal consistency (Cronbach’s alpha coefficients), test-retest reliability (intraclass correlation coefficient) and construct validity of the long-form TCU-ORC questionnaire. Survey data will be collected from 288 clinical, management and operational staff from 24 primary health facilities where the Project MIND trial is implemented. A modified Delphi approach will assess the content validity of the TCU-ORC items and identify areas for potential adaptation and item reduction. Ethics and dissemination Ethical approval has been granted by the South African Medical Research Council (Protocol ID EC004-2-2015, amendment of 20 August 2017). Results will be submitted to peer-reviewed journals relevant to implementation and health systems strengthening. PMID:29632084

Effect of Internet-Based Guided Self-help vs Individual Face-to-Face Treatment on Full or Subsyndromal Binge Eating Disorder in Overweight or Obese Patients: The INTERBED Randomized Clinical Trial.

PubMed

de Zwaan, Martina; Herpertz, Stephan; Zipfel, Stephan; Svaldi, Jennifer; Friederich, Hans-Christoph; Schmidt, Frauke; Mayr, Andreas; Lam, Tony; Schade-Brittinger, Carmen; Hilbert, Anja

2017-10-01

Although cognitive behavioral therapy (CBT) represents the criterion standard for treatment of binge eating disorder (BED), most individuals do not have access to this specialized treatment. To evaluate the efficacy of internet-based guided self-help (GSH-I) compared with traditional, individual face-to-face CBT. The Internet and Binge Eating Disorder (INTERBED) study is a prospective, multicenter, randomized, noninferiority clinical trial (treatment duration, 4 months; follow-ups, 6 months and 1.5 years). A volunteer sample of 178 adult outpatients with full or subsyndromal BED were recruited from 7 university-based outpatient clinics from August 1, 2010, through December 31, 2011; final follow-up assessment was in April 2014. Data analysis was performed from November 30, 2014, to May 27, 2015. Participants received 20 individual face-to-face CBT sessions of 50 minutes each or sequentially completed 11 internet modules and had weekly email contacts. The primary outcome was the difference in the number of days with objective binge eating episodes (OBEs) during the previous 28 days between baseline and end of treatment. Secondary outcomes included OBEs at follow-ups, eating disorder and general psychopathologic findings, body mass index, and quality of life. A total of 586 patients were screened, 178 were randomized, and 169 had at least one postbaseline assessment and constituted the modified intention-to-treat analysis group (mean [SD] age, 43.2 [12.3] years; 148 [87.6%] female); the 1.5-year follow-up was available in 116 patients. The confirmatory analysis using the per-protocol sample (n = 153) failed to show noninferiority of GSH-I (adjusted effect, 1.47; 95% CI, -0.01 to 2.91; P = .05). Using the modified intention-to-treat sample, GSH-I was inferior to CBT in reducing OBE days at the end of treatment (adjusted effect, 1.63; 95% CI, 0.17-3.05; P = .03). Exploratory longitudinal analyses also showed the superiority of CBT over GSH-I by the 6-month (adjusted effect, 0.36; 95% CI, 0.23-0.55; P < .001) but not the 1.5-year follow-up (adjusted effect, 0.91; 95% CI, 0.54-1.50; P = .70). Reductions in eating disorder psychopathologic findings were significantly higher in the CBT group than in the GSH-I group at 6-month follow-up (adjusted effect, -0.4; 95% CI, -0.68 to -0.13; P = .005). No group differences were found for body mass index, general psychopathologic findings, and quality of life. Face-to-face CBT leads to quicker and greater reductions in the number of OBE days, abstinence rates, and eating disorder psychopathologic findings and may be a better initial treatment option than GSH-I. Internet-based guided self-help remains a viable, slower-acting, low-threshold treatment alternative compared with CBT for adults with BED. isrctn.org Identifier: ISRCTN40484777 and germanctr.de Identifier: DRKS00000409.

Characterization of individuals seeking treatment for caffeine dependence.

PubMed

Juliano, Laura M; Evatt, Daniel P; Richards, Brian D; Griffiths, Roland R

2012-12-01

Previous investigations have identified individuals who meet criteria for Diagnostic and Statistical Manual of Mental Disorders (4th ed., text rev.; DSM-IV-TR; American Psychiatric Association, 2000) substance dependence as applied to caffeine, but there is little research on treatments for caffeine dependence. This study aimed to thoroughly characterize individuals who are seeking treatment for problematic caffeine use. Ninety-four individuals who identified as being psychologically or physically dependent on caffeine, or who had tried unsuccessfully to modify caffeine consumption participated in a face-to-face diagnostic clinical interview. They also completed measures concerning caffeine use and quitting history, reasons for seeking treatment, and standardized self-report measures of psychological functioning. Caffeine treatment seekers (mean age 41 years, 55% women) consumed an average of 548 mg caffeine per day. The primary source of caffeine was coffee for 50% of the sample and soft drinks for 37%. Eighty-eight percent reported prior serious attempts to modify caffeine use (mean 2.7 prior attempts), and 43% reported being advised by a medical professional to reduce or eliminate caffeine. Ninety-three percent met criteria for caffeine dependence when generic DSM-IV-TR substance dependence criteria were applied to caffeine use. The most commonly endorsed criteria were withdrawal (96%), persistent desire or unsuccessful efforts to control use (89%), and use despite knowledge of physical or psychological problems caused by caffeine (87%). The most common reasons for wanting to modify caffeine use were health-related (59%) and not wanting to be dependent on caffeine (35%). This investigation reveals that there are individuals with problematic caffeine use who are seeking treatment and suggests that there is a need for effective caffeine dependence treatments. 2013 APA, all rights reserved

Validity of DSM-IV attention deficit/hyperactivity disorder symptom dimensions and subtypes.

PubMed

Willcutt, Erik G; Nigg, Joel T; Pennington, Bruce F; Solanto, Mary V; Rohde, Luis A; Tannock, Rosemary; Loo, Sandra K; Carlson, Caryn L; McBurnett, Keith; Lahey, Benjamin B

2012-11-01

Diagnostic and Statistical Manual of Mental Disorders, 4th Edition (DSM-IV) criteria for attention deficit/hyperactivity disorder (ADHD) specify two dimensions of inattention and hyperactivity-impulsivity symptoms that are used to define three nominal subtypes: predominantly hyperactive-impulsive type (ADHD-H), predominantly inattentive type (ADHD-I), and combined type (ADHD-C). To aid decision making for DSM-5 and other future diagnostic systems, a comprehensive literature review and meta-analysis of 546 studies was completed to evaluate the validity of the DSM-IV model of ADHD. Results indicated that DSM-IV criteria identify individuals with significant and persistent impairment in social, academic, occupational, and adaptive functioning when intelligence, demographic factors, and concurrent psychopathology are controlled. Available data overwhelmingly support the concurrent, predictive, and discriminant validity of the distinction between inattention and hyperactivity-impulsivity symptoms, and indicate that nearly all differences among the nominal subtypes are consistent with the relative levels of inattention and hyperactivity-impulsivity symptoms that define the subtypes. In contrast, the DSM-IV subtype model is compromised by weak evidence for the validity of ADHD-H after first grade, minimal support for the distinction between ADHD-I and ADHD-C in studies of etiological influences, academic and cognitive functioning, and treatment response, and the marked longitudinal instability of all three subtypes. Overall, we conclude that the DSM-IV ADHD subtypes provide a convenient clinical shorthand to describe the functional and behavioral correlates of current levels of inattention and hyperactivity-impulsivity symptoms, but do not identify discrete subgroups with sufficient long-term stability to justify the classification of distinct forms of the disorder. Empirical support is stronger for an alternative model that would replace the subtypes with dimensional modifiers that reflect the number of inattention and hyperactivity-impulsivity symptoms at the time of assessment. (PsycINFO Database Record (c) 2012 APA, all rights reserved).

Sensitivity of the Modified Children's Yale-Brown Obsessive Compulsive Scale to Detect Change: Results from Two Multi-Site Trials

ERIC Educational Resources Information Center

Scahill, Lawrence; Sukhodolsky, Denis G.; Anderberg, Emily; Dimitropoulos, Anastasia; Dziura, James; Aman, Michael G.; McCracken, James; Tierney, Elaine; Hallett, Victoria; Katz, Karol; Vitiello, Benedetto; McDougle, Christopher

2016-01-01

Repetitive behavior is a core feature of autism spectrum disorder. We used 8-week data from two federally funded, multi-site, randomized trials with risperidone conducted by the Research Units on Pediatric Psychopharmacology Autism Network to evaluate the sensitivity of the Children's Yale-Brown Obsessive Compulsive Scale modified for autism…

D-lactic acidosis: an unusual cause of encephalopathy in a patient with short bowel syndrome.

PubMed

Dahlqvist, G; Guillen-Anaya, M A; Vincent, M F; Thissen, J P; Hainaut, P

2013-01-01

A 24-year-old woman with a short bowel syndrome following post-ischemic small bowel resection, developed several episodes of lethargy, echolalia and ataxia. D-lactic acidosis was identified as the cause of neurological disturbances. This infrequent disorder can be precipitated by intake of a large amount of sugars, in patients with short bowel syndrome. It should be suspected in the presence of metabolic acidosis with increased anion gap and a normal level of L-lactic acid. The diagnosis relies on the specific dosage of D-lactic stereoisomer. Proper management involves rehydration, diet adaptation and oral administration of poorly absorbed antibiotics in order to modify the colonic flora responsible for D-lactic production.

Regulating the chromatin landscape: structural and mechanistic perspectives.

PubMed

Bartholomew, Blaine

2014-01-01

A large family of chromatin remodelers that noncovalently modify chromatin is crucial in cell development and differentiation. They are often the targets of cancer, neurological disorders, and other human diseases. These complexes alter nucleosome positioning, higher-order chromatin structure, and nuclear organization. They also assemble chromatin, exchange out histone variants, and disassemble chromatin at defined locations. We review aspects of the structural organization of these complexes, the functional properties of their protein domains, and variation between complexes. We also address the mechanistic details of these complexes in mobilizing nucleosomes and altering chromatin structure. A better understanding of these issues will be vital for further analyses of subunits of these chromatin remodelers, which are being identified as targets in human diseases by NGS (next-generation sequencing).

Crystallographic identification of an unexpected by-product in an Ullman's reaction toward biphenyls: 1-(4-hexyloxy-3-hydroxyphenyl)ethanone.

PubMed

Manzano, Veronica E; Baggio, Ricardo; Cukiernik, Fabio D

2015-11-01

The synthesis of 3,3'-diacetoxy-4,4'-bis(hexyloxy)biphenyl following the nickel-modified Ullmann reaction yielded a by-product which was identified successfully by crystallographic analysis as 1-(4-hexyloxy-3-hydroxyphenyl)ethanone, C14H20O3. This unexpected nonbiphenyl by-product exhibited IR, (1)H NMR, (13)C NMR and COSY (correlation spectroscopy) spectra fully consistent with the proposed structure. The compound crystallized in the orthorombic Pbca space group, with two independent formula units in the asymmetric unit (one of which was slightly disordered), and showed a supramolecular architecture in which molecules linked by hydroxy-ethanone O-H···O interactions are organized in columns separated by the aliphatic tails.

Performance of Polygenic Scores for Predicting Phobic Anxiety

PubMed Central

Walter, Stefan; Glymour, M. Maria; Koenen, Karestan; Liang, Liming; Tchetgen Tchetgen, Eric J.; Cornelis, Marilyn; Chang, Shun-Chiao; Rimm, Eric; Kawachi, Ichiro; Kubzansky, Laura D.

2013-01-01

Context Anxiety disorders are common, with a lifetime prevalence of 20% in the U.S., and are responsible for substantial burdens of disability, missed work days and health care utilization. To date, no causal genetic variants have been identified for anxiety, anxiety disorders, or related traits. Objective To investigate whether a phobic anxiety symptom score was associated with 3 alternative polygenic risk scores, derived from external genome-wide association studies of anxiety, an internally estimated agnostic polygenic score, or previously identified candidate genes. Design Longitudinal follow-up study. Using linear and logistic regression we investigated whether phobic anxiety was associated with polygenic risk scores derived from internal, leave-one out genome-wide association studies, from 31 candidate genes, and from out-of-sample genome-wide association weights previously shown to predict depression and anxiety in another cohort. Setting and Participants Study participants (n = 11,127) were individuals from the Nurses' Health Study and Health Professionals Follow-up Study. Main Outcome Measure Anxiety symptoms were assessed via the 8-item phobic anxiety scale of the Crown Crisp Index at two time points, from which a continuous phenotype score was derived. Results We found no genome-wide significant associations with phobic anxiety. Phobic anxiety was also not associated with a polygenic risk score derived from the genome-wide association study beta weights using liberal p-value thresholds; with a previously published genome-wide polygenic score; or with a candidate gene risk score based on 31 genes previously hypothesized to predict anxiety. Conclusion There is a substantial gap between twin-study heritability estimates of anxiety disorders ranging between 20–40% and heritability explained by genome-wide association results. New approaches such as improved genome imputations, application of gene expression and biological pathways information, and incorporating social or environmental modifiers of genetic risks may be necessary to identify significant genetic predictors of anxiety. PMID:24278274

A case of anorexia nervosa with comorbid Crohn's disease: beneficial effects of anti-TNF-α therapy?

PubMed

Solmi, Marco; Santonastaso, Paolo; Caccaro, Roberta; Favaro, Angela

2013-09-01

This case report describes a 26-year-old woman affected by long-lasting anorexia nervosa (AN) and Crohn's disease. Worsening of the bowel illness led to the prescription of immunosuppressive therapy (biologic infliximab for 4 months, followed by adalimumab for 6 months) and referral to our Eating Disorders Unit. Although she initially demonstrated denial of her eating disorder, in a few months she gradually improved her weight and psychopathology. Crohn's disease can worsen AN by modifying hunger and energy expenditure through the effects of TNF-α and IL-6, pro-inflammatory cytokines which moderate leptin and melanocortin signaling. Previous studies have observed the antidepressant effects of TNF antagonist in patients with treatment-resistant depression with high baseline inflammatory biomarkers. Our case report suggests that future studies are needed to clarify the existence, patterns, and extent of increased inflammatory markers in patients with AN, and whether they determine clinical features or identify subgroups of patients. Potential therapeutic significance of above issues remains to be determined. Copyright © 2013 Wiley Periodicals, Inc.

Examination of the inventory of drug use consequences with individuals with serious and persistent mental illness and co-occurring substance use disorders.

PubMed

Bennett, Melanie E; Nidecker, Melissa; Strong Kinnaman, Joanna E; Li, Lan; Bellack, Alan S

2009-01-01

The Inventory of Drug Use Consequences (InDUC) ( [1] ) is a 50-item measure that evaluates lifetime and recent consequences of substance use. This study examined the psychometric properties of a modified version of the Inventory of Drug Use Consequences (InDUC-M) in individuals with serious and persistent mental illness (SPMI) and co-occurring substance use disorders (SUDs). We examined self-reported consequences in the sample, evaluated internal consistency, identified items for a brief form of the InDUC-M, and explored relationships with indicators of substance use severity. InDUC-M Lifetime and Recent subscales showed good internal consistency and were related to other measures of substance use and problems. A brief version of the InDUC-M Recent (SIP-M) showed excellent internal consistency and was highly correlated with both Lifetime and Recent subscales. The InDUC-M and the SIP-M performed well in individuals with SPMI and SUDs. Overall, these findings are a useful first step in determining the utility of the InDUC-M in people with SPMI and SUDs.

Role of school teachers in identifying attention deficit hyperactivity disorder among primary school children in Mansoura, Egypt.

PubMed

Awadalla, N J; Ali, O F; Elshaer, S; Eissa, M

2016-11-02

There is a knowledge gap in primary school teachers that affects their ability to detect attention deficit hyperactivity disorder (ADHD). This study measured primary school teachers' knowledge about ADHD, and implemented a training programme to improve early detection of ADHD. The prevalence and risk factors of ADHD were also studied. The training programme was implemented through a 2-day workshop for 39 primary school teachers who completed a validated Arabic version of the ADHD Rating Scale for 873 primary school children. The children's parents completed the questionnaire to explore ADHD risk factors. The teachers' pre-training knowledge scores of ADHD ranged from 17.9 to 46.2%. Post-training, their scores improved significantly to 69.2-94.9%. Prevalence rate of ADHD was 12.60%. On logistic regression, independent predictors of ADHD were female gender, unemployed fathers and rural residence. In conclusion, ADHD is a significant health problem among primary school children in Mansoura, Egypt. Efforts should be made to improve teachers' knowledge about ADHD and control modifiable risk factors.

Genome-Wide Identification of CBX2 Targets: Insights in the Human Sex Development Network

PubMed Central

Eid, Wassim; Opitz, Lennart

2015-01-01

Chromobox homolog 2 (CBX2) is a chromatin modifier that plays an important role in sexual development and its disorders (disorders of sex development [DSD]), yet the exact rank and function of human CBX2 in this pathway remains unclear. Here, we performed large-scale mapping and analysis of in vivo target loci of the protein CBX2 in Sertoli-like NT-2D1 cells, using the DNA adenine methyltransferase identification technique. We identified close to 1600 direct targets for CBX2. Intriguingly, validation of selected candidate genes using qRT-PCR in cells overexpressing CBX2 or in which CBX2 has been knocked down indicated that several CBX2-responsive genes encode proteins that are involved in DSD. We further validated these effects on the candidate genes using a mutated CBX2 causing DSD in human patient. Overall, our findings suggest that CBX2 role in the sex development cascade is to stimulate the male pathway and concurrently inhibit the female pathway. These data provide fundamental insights into potential etiology of DSD. PMID:25569159

Awareness of illness and insight into obsessive-compulsive symptoms in schizophrenia patients with obsessive-compulsive disorder.

PubMed

Poyurovsky, Michael; Faragian, Sarit; Kleinman-Balush, Vered; Pashinian, Artashez; Kurs, Rena; Fuchs, Camil

2007-09-01

Obsessive-compulsive symptoms (OCS) have been revealed in a substantial proportion of schizophrenia patients. We sought to evaluate insight into OCS in schizo-obsessive patients. We evaluated insight into OCS and awareness of schizophrenia, using the Brown Assessment of Beliefs Scale (BABS) and the Scale to Assess Unawareness of Mental Disorder (SUMD), respectively. Fifty-seven inpatients that met DSM-IV criteria for both schizophrenia and OCD were recruited. To determine a possible modifying effect of OCS on the awareness of schizophrenia, we included a comparison group of non-OCD schizophrenia patients (N = 80). Nine (15.8%) schizo-obsessive patients revealed lack of insight into OCS, whereas a majority (48 patients, 84.2%) exhibited good or fair insight. In the schizo-obsessive group, insight into OCS positively correlated with awareness of schizophrenia but not with awareness of delusions. Roughly 40% of the schizo-obsessive and non-OCD schizophrenia patients revealed unawareness of schizophrenia. Our findings indicate that OCS in schizophrenia represent an identifiable dimension of psychopathology independent of core schizophrenia symptoms.

Family caregiver distress with children having rare genetic disorders: a qualitative study involving Russell-Silver Syndrome in Taiwan.

PubMed

Weng, Hsin-Ju; Niu, Dau-Ming; Turale, Sue; Tsao, Lee-Ing; Shih, Fu-Jong; Yamamoto-Mitani, Noriko; Chang, Chun-Chi; Shih, Fu-Jin

2012-01-01

To extend nursing knowledge of distress experienced by family caregivers of children with rare genetic disorders, by exploring the perspectives of caregivers of children with Russell-Silver Syndrome in Taiwan. Caring for a child with a rare genetic disorder often has profound effects on families, especially when diagnosis and treatment is complex or not yet well developed, such as that in Russell-Silver Syndrome (or Silver-Russell syndrome). This disorder causes dwarfism and developmental difficulties, requiring long-term care planning. Previous research has focused mostly on medical care, but little is known about families' perspectives of caring difficulties, the help they need and nursing care required. An exploratory qualitative approach was used to inform this study. Family caregivers, whose children were undergoing medical care in a leading Taiwan medical centre, were invited to participate in face-to-face, in-depth interviews. Data were analysed by content analysis. Fifteen caregivers including 11 mothers, two fathers and two grandmothers participated. Five major themes and 13 sub-themes of care-giving distress were identified: endless psychological worries; the lengthy process to confirm a medical diagnosis; adjustment efforts in modifying family roles; dilemmas in deciding between Western or Chinese traditional medicine; and negative responses to society's concerns. Their primary sources of support were spouses, parents and health professionals, accordingly. Complex physio-psycho-social and decision-making distress in caring for children with a rare genetic disorder were systematically revealed from the perspectives of ethnic-Chinese family caregivers. Long-term care plans for children with a rare genetic disorder such as Russell-Silver Syndrome need to focus on positive dynamic family interactions, life-stage development and family caregiver support. Research on care-giving in rare genetic disorders is also warranted across cultures and countries to develop a substantial knowledge basis for nursing practice. © 2011 Blackwell Publishing Ltd.

Anxiety After Stroke

PubMed Central

Whiteley, William N.; Dennis, Martin S.; Mead, Gillian E.; Carson, Alan J.

2018-01-01

Background and Purpose— Anxiety after stroke is common and disabling. Stroke trialists have treated anxiety as a homogenous condition, and intervention studies have followed suit, neglecting the different treatment approaches for phobic and generalized anxiety. Using diagnostic psychiatric interviews, we aimed to report the frequency of phobic and generalized anxiety, phobic avoidance, predictors of anxiety, and patient outcomes at 3 months poststroke/transient ischemic attack. Methods— We followed prospectively a cohort of new diagnosis of stroke/transient ischemic attack at 3 months with a telephone semistructured psychiatric interview, Fear Questionnaire, modified Rankin Scale, EuroQol-5D5L, and Work and Social Adjustment Scale. Results— Anxiety disorder was common (any anxiety disorder, 38 of 175 [22%]). Phobic disorder was the predominant anxiety subtype: phobic disorder only, 18 of 175 (10%); phobic and generalized anxiety disorder, 13 of 175 (7%); and generalized anxiety disorder only, 7 of 175 (4%). Participants with anxiety disorder reported higher level of phobic avoidance across all situations on the Fear Questionnaire. Younger age (per decade increase in odds ratio, 0.64; 95% confidence interval, 0.45–0.91) and having previous anxiety/depression (odds ratio, 4.38; 95% confidence interval, 1.94–9.89) were predictors for anxiety poststroke/transient ischemic attack. Participants with anxiety disorder were more dependent (modified Rankin Scale score 3–5, [anxiety] 55% versus [no anxiety] 29%; P<0.0005), had poorer quality of life on EQ-5D5L, and restricted participation (Work and Social Adjustment Scale: median, interquartile range, [anxiety] 19.5, 10–27 versus [no anxiety] 0, 0–5; P<0.001). Conclusions— Anxiety after stroke/transient ischemic attack is predominantly phobic and is associated with poorer patient outcomes. Trials of anxiety intervention in stroke should consider the different treatment approaches needed for phobic and generalized anxiety. PMID:29437982

Anxiety After Stroke: The Importance of Subtyping.

PubMed

Chun, Ho-Yan Yvonne; Whiteley, William N; Dennis, Martin S; Mead, Gillian E; Carson, Alan J

2018-03-01

Anxiety after stroke is common and disabling. Stroke trialists have treated anxiety as a homogenous condition, and intervention studies have followed suit, neglecting the different treatment approaches for phobic and generalized anxiety. Using diagnostic psychiatric interviews, we aimed to report the frequency of phobic and generalized anxiety, phobic avoidance, predictors of anxiety, and patient outcomes at 3 months poststroke/transient ischemic attack. We followed prospectively a cohort of new diagnosis of stroke/transient ischemic attack at 3 months with a telephone semistructured psychiatric interview, Fear Questionnaire, modified Rankin Scale, EuroQol-5D5L, and Work and Social Adjustment Scale. Anxiety disorder was common (any anxiety disorder, 38 of 175 [22%]). Phobic disorder was the predominant anxiety subtype: phobic disorder only, 18 of 175 (10%); phobic and generalized anxiety disorder, 13 of 175 (7%); and generalized anxiety disorder only, 7 of 175 (4%). Participants with anxiety disorder reported higher level of phobic avoidance across all situations on the Fear Questionnaire. Younger age (per decade increase in odds ratio, 0.64; 95% confidence interval, 0.45-0.91) and having previous anxiety/depression (odds ratio, 4.38; 95% confidence interval, 1.94-9.89) were predictors for anxiety poststroke/transient ischemic attack. Participants with anxiety disorder were more dependent (modified Rankin Scale score 3-5, [anxiety] 55% versus [no anxiety] 29%; P <0.0005), had poorer quality of life on EQ-5D5L, and restricted participation (Work and Social Adjustment Scale: median, interquartile range, [anxiety] 19.5, 10-27 versus [no anxiety] 0, 0-5; P <0.001). Anxiety after stroke/transient ischemic attack is predominantly phobic and is associated with poorer patient outcomes. Trials of anxiety intervention in stroke should consider the different treatment approaches needed for phobic and generalized anxiety. © 2018 The Authors.

Can we reduce eating disorder risk factors in female college athletes? A randomized exploratory investigation of two peer-led interventions

PubMed Central

Becker, Carolyn Black; McDaniel, Leda; Bull, Stephanie; Powell, Marc; McIntyre, Kevin

2011-01-01

Female athletes are at least as at risk as other women for eating disorders (EDs) and at risk for the female athlete triad (i.e., inadequate energy availability, menstrual disorders, and osteoporosis). This study investigated whether two evidence-based programs appear promising for future study if modified to address the unique needs of female athletes. Athletes were randomly assigned to athlete-modified dissonance prevention or healthy weight intervention (AM-HWI). ED risk factors were assessed pre/post-treatment, and 6-week and 1-year follow-up. Results (analyzed sample N = 157) indicated that both interventions reduced thin-ideal internalization, dietary restraint, bulimic pathology, shape and weight concern, and negative affect at 6 weeks, and bulimic pathology, shape concern, and negative affect at 1 year. Unexpectedly we observed an increase in students spontaneously seeking medical consultation for the triad. Qualitative results suggested that AM-HWI may be more preferred by athletes. PMID:22019502

FAMILY STRUCTURE, DYNAMICS AND PSYCHIATRIC DISORDER IN INDIA1

PubMed Central

Chopra, H.D.

1984-01-01

SUMMARY This paper briefly reviews the literature on family structure, dynamics and relationships between family-jointness and different psychiatric disorders in India. Many recent studies indicate that the nuclear families are more vulnerable and plea is made for maintaining the traditional joint family system, even in some modified forms, because of its “built-in-immunity” and supportive networks. PMID:21966010

The National Center on Indigenous Hawaiian Behavioral Health Study of Prevalence of Psychiatric Disorders in Native Hawaiian Adolescents

ERIC Educational Resources Information Center

Andrade, Naleen N.; Hishinuma, Earl S.; McDermott, John F., Jr.; Johnson, Ronald C.; Goebert, Deborah A.; Makini, George K., Jr.; Nahulu, Linda B.; Yuen, Noelle Y. C.; McArdle, John J.; Bell, Cathy K.; Carlton, Barry S.; Miyamoto, Robin H.; Nishimura, Stephanie T.; Else, Iwalani R. N.; Guerrero, Anthony P. S.; Darmal, Arsalan; Yates, Alayne; Waldron, Jane A.

2006-01-01

Objectives: The prevalence rates of disorders among a community-based sample of Hawaiian youths were determined and compared to previously published epidemiological studies. Method: Using a two-phase design, 7,317 adolescents were surveyed (60% participation rate), from which 619 were selected in a modified random sample during the 1992-1993 to…

Non-Drug Interventions for Improving Classroom Behavior and Social Functioning of Young Children with Attention Deficit Hyperactivity Disorder.

ERIC Educational Resources Information Center

Radcliff, David

This paper explores research on use of medication and non-drug interventions to modify the behavior of preschool children with attention deficit hyperactivity disorder (ADHD). It begins by discussing the symptoms of ADHD, neurological differences between children with ADHD and those without ADHD, and expected adolescent and adult outcomes for…

A Modified Obesity Proneness Model Predicts Adolescent Weight Concerns and Inability to Self-Regulate Eating

ERIC Educational Resources Information Center

Nickelson, Jen; Bryant, Carol A.; McDermott, Robert J.; Buhi, Eric R.; DeBate, Rita D.

2012-01-01

Background: The prevalence of obesity among high school students has risen in recent decades. Many high school students report trying to lose weight and some engage in disordered eating to do so. The obesity proneness model suggests that parents may influence their offspring's development of disordered eating. This study examined the viability of…

Validation of the Repetitive Behavior Scale-Revised in Spanish-Speakers Participants with Autism Spectrum Disorder

ERIC Educational Resources Information Center

Martínez-González, A. E.; Piqueras, J. A.

2018-01-01

Restricted and repetitive behavior (RRB) is one of the two key diagnostic features of autism spectrum disorder (ASD). DSM-5 highlights the importance of severity-based diagnostic modifiers assigned on the basis of intensity of needed supports. Therefore, there is a need for available measures that assess the severity of RRB. The repetitive…

Characterization of nutrient disorders of gerbera hybrid 'Festival Light Eye Pink'

USDA-ARS?s Scientific Manuscript database

Gerbera hybrid ‘Festival Yellow with Light Eye’ plants were grown in silica sand culture to induce and photograph nutritional disorder symptoms. Plants were grown with a complete modified Hoagland's all nitrate solution: (macronutrients in mM) 15 NO3-N, 1.0 PO4-P, 6.0 K, 5.0 Ca, 2.0 Mg, and 2.0 SO4...

Characterization of Nutrient Disorders of Primula acaulis ‘Danova Rose'

USDA-ARS?s Scientific Manuscript database

Primula acaulis ‘Danova Rose’ plants were grown in silica sand culture to induce and photograph nutritional disorder symptoms. Plants were grown with a complete modified Hoagland's all nitrate solution: (macronutrients in mM) 15 NO3-N, 1.0 PO4-P, 6.0 K, 5.0 Ca, 2.0 Mg, and 2.0 SO4-S, plus micromola...

Prevalence of Autism Spectrum Disorder in Nurseries in Lebanon: A Cross Sectional Study

ERIC Educational Resources Information Center

Chaaya, Monique; Saab, Dahlia; Maalouf, Fadi T.; Boustany, Rose-Mary

2016-01-01

In Lebanon, no estimate for autism prevalence exists. This cross-sectional study examines the prevalence of Autism spectrum disorder (ASD) in toddlers in nurseries in Beirut and Mount-Lebanon. The final sample included 998 toddlers (16-48 months) from 177 nurseries. We sent parents the Modified Checklist for Autism in Toddlers (M-CHAT) for…

[Therapeutic approaches in autism spectrum disorders].

PubMed

Ruggieri, Víctor L; Arberas, Claudia L

2015-02-25

Autistic spectrum disorders affect one out of every 68 persons, with a 4:1 dominance in males. Since they are dysfunctions rather than irreversible injuries to the central nervous system, which can be attributed to deficits in the neuronal networks and synaptogenesis and are modifiable thanks to the plasticity of the brain, starting therapy as early as possible is essential for more favourable progress. Very few treatments are backed by solid scientific evidence. We will analyse the therapeutic approaches oriented towards improving autism spectrum disorders which showed a clinical improvement that can be related to neurophysiological or functional changes in the central nervous system. We will classify the behavioural educational treatments and those in the research phase into a hierarchy, highlighting the neurogenetic entities with a high prevalence of autism, in which their pathophysiology and molecular base are known, that attempt to modify the consequences of those alterations by means of pharmacological agents. These entities include fragile X syndrome (GABAergic and metabotropic glutamate receptor inhibitors), tuberous sclerosis (mTOR inhibitors), Phelan-McDermid syndrome and Rett syndrome (insulin-like growth factor 1 inhibitors). Oxytocin, which has been shown to improve social cognition in persons with autism spectrum disorders, is analysed separately.

Confirmatory factor analysis for two questionnaires of caregiving in eating disorders

PubMed Central

Hibbs, Rebecca; Rhind, Charlotte; Sallis, Hannah; Goddard, Elizabeth; Raenker, Simone; Ayton, Agnes; Bamford, Bryony; Arcelus, Jon; Boughton, Nicky; Connan, Frances; Goss, Ken; Lazlo, Bert; Morgan, John; Moore, Kim; Robertson, David; Schreiber-Kounine, Christa; Sharma, Sonu; Whitehead, Linette; Lacey, Hubert; Schmidt, Ulrike; Treasure, Janet

2014-01-01

Objective: Caring for someone diagnosed with an eating disorder (ED) is associated with a high level of burden and psychological distress which can inadvertently contribute to the maintenance of the illness. The Eating Disorders Symptom Impact Scale (EDSIS) and Accommodation and Enabling Scale for Eating Disorders (AESED) are self-report scales to assess elements of caregiving theorised to contribute to the maintenance of an ED. Further validation and confirmation of the factor structures for these scales are necessary for rigorous evaluation of complex interventions which target these modifiable elements of caregiving. Method: EDSIS and AESED data from 268 carers of people with anorexia nervosa (AN), recruited from consecutive admissions to 15 UK inpatient or day patient hospital units, were subjected to confirmatory factor analysis to test model fit by applying the existing factor structures: (a) four-factor structure for the EDSIS and (b) five-factor structure for the AESED. Results: Confirmatory factor analytic results support the existing four-factor and five-factor structures for the EDSIS and the AESED, respectively. Discussion: The present findings provide further validation of the EDSIS and the AESED as tools to assess modifiable elements of caregiving for someone with an ED. PMID:25750785

Evidence-based psychological treatments for mental disorders: Modifiable barriers to access and possible solutions

PubMed Central

Harvey, Allison G.; Gumport, Nicole B.

2015-01-01

The prevalence of mental disorders is high and appears to be growing, yet the majority of individuals who meet diagnostic criteria for a mental disorder are not able to access an adequate treatment. While evidence-based psychological treatments (EBPTs) are effective single or adjunctive treatments for mental disorders, there is also evidence that access to these treatments is diminishing. We seek to highlight modifiable barriers to these problems at the patient, therapist, treatment, organization and government-levels of analysis. A range of solutions to each set of contributors is offered and domains for future research are highlighted. In particular, we focus on the need to continue to work toward innovation in treatment development while also solving the difficulties relating to the dissemination of EBPTs. Several relatively new concepts in the field will be discussed (implementation cliff, program drift, voltage drop and deployment treatment development) and we contrast America and England as examples of government-level processes that are in the process of major change with respect to EBPTs. We conclude that there is a need for people in our field to become more knowledgeable about, and get involved in, shaping public policy. PMID:25768982

Identifying proteins that bind to specific RNAs - focus on simple repeat expansion diseases

PubMed Central

Jazurek, Magdalena; Ciesiolka, Adam; Starega-Roslan, Julia; Bilinska, Katarzyna; Krzyzosiak, Wlodzimierz J.

2016-01-01

RNA–protein complexes play a central role in the regulation of fundamental cellular processes, such as mRNA splicing, localization, translation and degradation. The misregulation of these interactions can cause a variety of human diseases, including cancer and neurodegenerative disorders. Recently, many strategies have been developed to comprehensively analyze these complex and highly dynamic RNA–protein networks. Extensive efforts have been made to purify in vivo-assembled RNA–protein complexes. In this review, we focused on commonly used RNA-centric approaches that involve mass spectrometry, which are powerful tools for identifying proteins bound to a given RNA. We present various RNA capture strategies that primarily depend on whether the RNA of interest is modified. Moreover, we briefly discuss the advantages and limitations of in vitro and in vivo approaches. Furthermore, we describe recent advances in quantitative proteomics as well as the methods that are most commonly used to validate robust mass spectrometry data. Finally, we present approaches that have successfully identified expanded repeat-binding proteins, which present abnormal RNA–protein interactions that result in the development of many neurological diseases. PMID:27625393

An innovative strategy for the molecular diagnosis of Usher syndrome identifies causal biallelic mutations in 93% of European patients.

PubMed

Bonnet, Crystel; Riahi, Zied; Chantot-Bastaraud, Sandra; Smagghe, Luce; Letexier, Mélanie; Marcaillou, Charles; Lefèvre, Gaëlle M; Hardelin, Jean-Pierre; El-Amraoui, Aziz; Singh-Estivalet, Amrit; Mohand-Saïd, Saddek; Kohl, Susanne; Kurtenbach, Anne; Sliesoraityte, Ieva; Zobor, Ditta; Gherbi, Souad; Testa, Francesco; Simonelli, Francesca; Banfi, Sandro; Fakin, Ana; Glavač, Damjan; Jarc-Vidmar, Martina; Zupan, Andrej; Battelino, Saba; Martorell Sampol, Loreto; Claveria, Maria Antonia; Catala Mora, Jaume; Dad, Shzeena; Møller, Lisbeth B; Rodriguez Jorge, Jesus; Hawlina, Marko; Auricchio, Alberto; Sahel, José-Alain; Marlin, Sandrine; Zrenner, Eberhart; Audo, Isabelle; Petit, Christine

2016-12-01

Usher syndrome (USH), the most prevalent cause of hereditary deafness-blindness, is an autosomal recessive and genetically heterogeneous disorder. Three clinical subtypes (USH1-3) are distinguishable based on the severity of the sensorineural hearing impairment, the presence or absence of vestibular dysfunction, and the age of onset of the retinitis pigmentosa. A total of 10 causal genes, 6 for USH1, 3 for USH2, and 1 for USH3, and an USH2 modifier gene, have been identified. A robust molecular diagnosis is required not only to improve genetic counseling, but also to advance gene therapy in USH patients. Here, we present an improved diagnostic strategy that is both cost- and time-effective. It relies on the sequential use of three different techniques to analyze selected genomic regions: targeted exome sequencing, comparative genome hybridization, and quantitative exon amplification. We screened a large cohort of 427 patients (139 USH1, 282 USH2, and six of undefined clinical subtype) from various European medical centers for mutations in all USH genes and the modifier gene. We identified a total of 421 different sequence variants predicted to be pathogenic, about half of which had not been previously reported. Remarkably, we detected large genomic rearrangements, most of which were novel and unique, in 9% of the patients. Thus, our strategy led to the identification of biallelic and monoallelic mutations in 92.7% and 5.8% of the USH patients, respectively. With an overall 98.5% mutation characterization rate, the diagnosis efficiency was substantially improved compared with previously reported methods.

An innovative strategy for the molecular diagnosis of Usher syndrome identifies causal biallelic mutations in 93% of European patients

PubMed Central

Bonnet, Crystel; Riahi, Zied; Chantot-Bastaraud, Sandra; Smagghe, Luce; Letexier, Mélanie; Marcaillou, Charles; Lefèvre, Gaëlle M; Hardelin, Jean-Pierre; El-Amraoui, Aziz; Singh-Estivalet, Amrit; Mohand-Saïd, Saddek; Kohl, Susanne; Kurtenbach, Anne; Sliesoraityte, Ieva; Zobor, Ditta; Gherbi, Souad; Testa, Francesco; Simonelli, Francesca; Banfi, Sandro; Fakin, Ana; Glavač, Damjan; Jarc-Vidmar, Martina; Zupan, Andrej; Battelino, Saba; Martorell Sampol, Loreto; Claveria, Maria Antonia; Catala Mora, Jaume; Dad, Shzeena; Møller, Lisbeth B; Rodriguez Jorge, Jesus; Hawlina, Marko; Auricchio, Alberto; Sahel, José-Alain; Marlin, Sandrine; Zrenner, Eberhart; Audo, Isabelle; Petit, Christine

2016-01-01

Usher syndrome (USH), the most prevalent cause of hereditary deafness–blindness, is an autosomal recessive and genetically heterogeneous disorder. Three clinical subtypes (USH1–3) are distinguishable based on the severity of the sensorineural hearing impairment, the presence or absence of vestibular dysfunction, and the age of onset of the retinitis pigmentosa. A total of 10 causal genes, 6 for USH1, 3 for USH2, and 1 for USH3, and an USH2 modifier gene, have been identified. A robust molecular diagnosis is required not only to improve genetic counseling, but also to advance gene therapy in USH patients. Here, we present an improved diagnostic strategy that is both cost- and time-effective. It relies on the sequential use of three different techniques to analyze selected genomic regions: targeted exome sequencing, comparative genome hybridization, and quantitative exon amplification. We screened a large cohort of 427 patients (139 USH1, 282 USH2, and six of undefined clinical subtype) from various European medical centers for mutations in all USH genes and the modifier gene. We identified a total of 421 different sequence variants predicted to be pathogenic, about half of which had not been previously reported. Remarkably, we detected large genomic rearrangements, most of which were novel and unique, in 9% of the patients. Thus, our strategy led to the identification of biallelic and monoallelic mutations in 92.7% and 5.8% of the USH patients, respectively. With an overall 98.5% mutation characterization rate, the diagnosis efficiency was substantially improved compared with previously reported methods. PMID:27460420

Applied behavior analysis: behavior management of children with autism spectrum disorders in dental environments.

PubMed

Hernandez, Purnima; Ikkanda, Zachary

2011-03-01

There are a limited number of studies addressing behavior management techniques and procedural modifications that dentists can use to treat people with an autism spectrum disorder (ASD). The authors conducted a search of the dental and behavioral analytic literature to identify management techniques that address problem behaviors exhibited by children with ASDs in dental and other health-related environments. Applied behavior analysis (ABA) is a science in which procedures are based on the principles of behavior through systematic experimentation. Clinicians have used ABA procedures successfully to modify socially significant behaviors of people with ASD. Basic behavior management techniques currently used in dentistry may not encourage people with cognitive and behavioral disabilities, such as ASD, to tolerate simple in-office dental procedures consistently. Instead, dental care providers often are required to use advanced behavior management techniques to complete simple in-office procedures such as prophylaxis, sealant placement and obtaining radiographs. ABA procedures can be integrated in the dental environment to manage problem behaviors often exhibited by children with an ASD. The authors found no evidence-based procedural modifications that address the behavioral characteristics and problematic behaviors of children with an ASD in a dental environment. Further research in this area should be conducted. Knowledge and in-depth understanding of behavioral principles is essential when a dentist is concerned with modifying behaviors. Using ABA procedures can help dentists manage problem behaviors effectively and systematically when performing routine dental treatment. Being knowledgeable about each patient's behavioral characteristics and the parents' level of involvement is important in the successful integration of the procedures and reduction of in-office time.

Sleep-Disordered Breathing and Caffeine Consumption

PubMed Central

Aurora, R. Nisha; Crainiceanu, Ciprian; Caffo, Brian

2012-01-01

Background: Sleepiness is one of the most burdensome symptoms of sleep-disordered breathing (SDB). While caffeine is frequently used to avert sleepiness, the association between SDB and caffeine use has not been thoroughly explored. The current study examined whether SDB is associated with caffeine consumption and if factors such as sex, age, and daytime sleepiness explain or modify the association. Methods: Data from the Sleep Heart Health Study, a community-based study on the consequences of SDB, were used to characterize the association between SDB and caffeine intake. SDB was assessed with full-montage polysomnography. Caffeine use was quantified as the number of cans of soda or the cups of coffee or tea consumed daily. The Epworth Sleepiness Scale was used to assess daytime sleepiness. Multivariable negative binomial regression models were used to characterize the independent association between SDB and caffeine use. Results: Caffeinated soda, but not tea or coffee, intake was independently associated with SDB severity. Compared with participants without SDB, the relative ratios for caffeinated soda consumption in women with mild, moderate, and severe SDB were 1.20 (CI, 1.03-1.41), 1.46 (CI, 1.14-1.87), and 1.73 (CI, 1.23-2.42), respectively. For men, an association was only noted with severe SDB and caffeinated soda use. Age did not modify the SDB-caffeine association, and sleepiness could not explain the observed associations. Conclusions: SDB is independently associated with caffeinated soda use in the general community. Identifying excessive caffeine used in SDB has potential significance given the cardiovascular effects of caffeine and untreated SDB. PMID:22459776

Placebo and nocebo reactions in randomized trials of pharmacological treatments for persistent depressive disorder. A meta-regression analysis.

PubMed

Meister, Ramona; Jansen, Alessa; Härter, Martin; Nestoriuc, Yvonne; Kriston, Levente

2017-06-01

We aimed to investigate placebo and nocebo reactions in randomized controlled trials (RCT) of pharmacological treatments for persistent depressive disorder (PDD). We conducted a systematic electronic search and included RCTs investigating antidepressants for the treatment of PDD. Outcomes were the number of patients experiencing response and remission in placebo arms (=placebo reaction). Additional outcomes were the incidence of patients experiencing adverse events and related discontinuations in placebo arms (=nocebo reaction). A priori defined effect modifiers were analyzed using a series of meta-regression analyses. Twenty-three trials were included in the analyses. We found a pooled placebo response rate of 31% and a placebo remission rate of 22%. The pooled adverse event rate and related discontinuations were 57% and 4%, respectively. All placebo arm outcomes were positively associated with the corresponding medication arm outcomes. Placebo response rate was associated with a greater proportion of patients with early onset depression, a smaller chance to receive placebo and a larger sample size. The adverse event rate in placebo arms was associated with a greater proportion of patients with early onset depression, a smaller proportion of females and a more recent publication. Pooled placebo and nocebo reaction rates in PDD were comparable to those in episodic depression. The identified effect modifiers should be considered to assess unbiased effects in RCTs, to influence placebo and nocebo reactions in practice. Limitations result from the methodology applied, the fact that we conducted only univariate analyses, and the number and quality of included trials. Copyright © 2017 Elsevier B.V. All rights reserved.

Biomarker-driven phenotyping in Parkinson disease: a translational missing link in disease-modifying clinical trials

PubMed Central

Espay, Alberto J.; Schwarzschild, Michael A.; Tanner, Caroline M.; Fernandez, Hubert H; Simon, David K.; Leverenz, James B.; Merola, Aristide; Chen-Plotkin, Alice; Brundin, Patrik; Kauffman, Marcelo A.; Erro, Roberto; Kieburtz, Karl; Woo, Daniel; Macklin, Eric A.; Standaert, David G.; Lang, Anthony E.

2016-01-01

Past clinical trials of putative neuroprotective therapies have targeted Parkinson disease (PD) as a single pathogenic disease entity. From an Oslerian clinico-pathologic perspective, the wide complexity of PD converges into Lewy bodies and justifies a reductionist approach to PD: a single-mechanism therapy can affect most of those sharing the classic pathologic hallmark. From a systems-biology perspective, PD is a group of disorders that, while related by sharing the feature of nigral dopamine-neuron degeneration, exhibit unique genetic, biological and molecular abnormalities, which probably respond differentially to a given therapeutic approach, particularly for strategies aimed at neuroprotection. Under this model, only biomarker-defined, homogenous subtypes of PD are likely to respond optimally to therapies proven to affect the biological processes within each subtype. Therefore, we suggest that precision medicine applied to PD requires a reevaluation of the biomarker-discovery effort. This effort is currently centered on correlating biological measures to clinical features of PD and on identifying factors that predict whether various prodromal states will convert into the classical movement disorder. We suggest, instead, that subtyping of PD requires the reverse view, where abnormal biological signals (i.e., biomarkers) rather than clinical definitions are used to define disease phenotypes. Successful development of disease-modifying strategies will depend on how relevant the specific biological processes addressed by an intervention are to the pathogenetic mechanisms in the subgroup of targeted patients. This precision-medicine approach will likely yield smaller but well-defined subsets of PD amenable to successful neuroprotection. PMID:28233927

Drug prescription patterns in patients with Addison's disease: a Swedish population-based cohort study.

PubMed

Björnsdottir, Sigridur; Sundström, Anders; Ludvigsson, Jonas F; Blomqvist, Paul; Kämpe, Olle; Bensing, Sophie

2013-05-01

There are no published data on drug prescription in patients with Addison's disease (AD). Our objective was to describe the drug prescription patterns in Swedish AD patients before and after diagnosis compared with population controls. We conducted a population-based cohort study in Sweden. Through the Swedish National Patient Register and the Swedish Prescribed Drug Register, we identified 1305 patients with both a diagnosis of AD and on combination treatment with hydrocortisone/cortisone acetate and fludrocortisone. Direct evidence of the AD diagnosis from patient charts was not available. We identified 11 996 matched controls by the Register of Population. We determined the ratio of observed to expected number of patients treated with prescribed drugs. Overall, Swedish AD patients received more prescribed drugs than controls, and 59.3% of the AD patients had medications indicating concomitant autoimmune disease. Interestingly, both before and after the diagnosis of AD, patients used more gastrointestinal medications, antianemic preparations, lipid-modifying agents, antibiotics for systemic use, hypnotics and sedatives, and drugs for obstructive airway disease (all P values < .05). Notably, an increased prescription of several antihypertensive drugs and high-ceiling diuretics was observed after the diagnosis of AD. Gastrointestinal symptoms and anemia, especially in conjunction with autoimmune disorders, should alert the physician about the possibility of AD. The higher use of drugs for cardiovascular disorders after diagnosis in patients with AD raises concerns about the replacement therapy.

Ergonomic strategies to improve radiographers' posture during mammography activities.

PubMed

Cernean, Nicolai; Serranheira, Florentino; Gonçalves, Pedro; Sá Dos Reis, Cláudia

2017-08-01

To identify alternatives for radiographers' postures while performing mammography that can contribute to reduce the risk of work-related musculoskeletal disorders (WRMSDs). Radiographers' postures to positioning craniocaudal (CC) and mediolateral oblique (MLO) views were simulated without any intervention for three scenarios: radiographer/patient with similar statures, radiographer smaller than patient and radiographer taller than patient. Actions were taken to modify the postures: seated radiographer; patient on a step; seated patient; radiographer on a step. All the postures were analysed using kinovea 0.8.15 software and the angles were measured twice and classified according to European standard EN1005-4: 2005. The non-acceptable angles were measured mainly during MLO positioning when radiographer was taller than the patient: 139° and 120° for arm-flexion and abduction, 72° for trunk and -24° for head/neck-flexion. The introduction of alternative postures (radiographer seated), allowed improvements in posture (60° and 99° for arm flexion and abduction, 14° for trunk and 0° for head/neck flexion), being classified as acceptable. The alternative postures simulated have the potential to reduce the risk of developing WRMSDs when radiographers and patients have different statures. • Radiographers' postures in mammography can contribute to work-related musculoskeletal disorders • Non-acceptable posture was identified for MLO breast positioning (radiographer taller than patient) • Adapting posture to patient biotype reduces the WRMSD risk for radiographers.

Microbiota abnormalities and the therapeutic potential of probiotics in the treatment of mood disorders.

PubMed

Rios, Adiel C; Maurya, Pawan Kumar; Pedrini, Mariana; Zeni-Graiff, Maiara; Asevedo, Elson; Mansur, Rodrigo B; Wieck, Andrea; Grassi-Oliveira, Rodrigo; McIntyre, Roger S; Hayashi, Mirian A F; Brietzke, Elisa

2017-10-26

Major depressive disorder (MDD) and bipolar disorder (BD) are among the leading causes of burden and disability worldwide. Despite intensified research efforts to improve the treatment options and remission rates in mood disorders, no disease modifying treatment exists for these disorders. Accumulating evidence implicates the involvement of the gut microbiota in processes relevant to etiopathology of central nervous system-based disorders. The objective of this article was to critically evaluate the evidence supporting the link between gastrointestinal microbiota and mood disorders and to discuss the potential benefits of using probiotics in the treatment of MDD and BD. The concept of psychobiotics, which is bacterial-based interventions with mental health benefit, is emerging in the field. On the other hand, while probiotics might potentially represent a significant advance, specific roles of microbiota in the pathophysiology of mood disorders still need further investigation along with intervention studies.

Discrimination and common mental disorders of undergraduate students of the Universidade Federal de Santa Catarina.

PubMed

de Souza, Maria Vitória Cordeiro; Lemkuhl, Isabel; Bastos, João Luiz

2015-01-01

The pathogenic and consistent effect of discrimination on mental health has been largely documented in the literature. However, there are few studies measuring multiple types of discrimination, evaluating the existence of a dose-response relationship or investigating possible effect modifiers of such an association. To investigate the association between experiences of discrimination attributed to multiple reasons and common mental disorders, including the adjustment for potential confounders, assessment of dose-response relations, and examination of effect modifiers in undergraduate students from southern Brazil. In the first semester of 2012, 1,023 students from the Universidade Federal de Santa Catarina answered a self-administered questionnaire on socio-demographic characteristics, undergraduate course, experiences of discrimination and common mental disorders. Associations were analyzed through logistic regression models, estimation of Odds Ratios and 95% confidence intervals (95%CI). The study results showed that students reporting discrimination at high frequency and intensity were 4.4 (95%CI 1.6 - 12.4) times more likely to present common mental disorders. However, the relationship between discrimination and common mental disorders was protective among Electrical Engineering students, when compared to Accounting Sciences students who did not report discrimination. The findings suggest that the dose-response relationship between experiences of discrimination and common mental disorders reinforces the hypothetical causal nature of this association. Nevertheless, the modification of effect caused by the undergraduate course should be considered in future studies for a better understanding and measurement of both phenomena.

Measurement instruments to assess posture, gait, and balance in Parkinson's disease: Critique and recommendations.

PubMed

Bloem, Bastiaan R; Marinus, Johan; Almeida, Quincy; Dibble, Lee; Nieuwboer, Alice; Post, Bart; Ruzicka, Evzen; Goetz, Christopher; Stebbins, Glenn; Martinez-Martin, Pablo; Schrag, Anette

2016-09-01

Disorders of posture, gait, and balance in Parkinson's disease (PD) are common and debilitating. This MDS-commissioned task force assessed clinimetric properties of existing rating scales, questionnaires, and timed tests that assess these features in PD. A literature review was conducted. Identified instruments were evaluated systematically and classified as "recommended," "suggested," or "listed." Inclusion of rating scales was restricted to those that could be used readily in clinical research and practice. One rating scale was classified as "recommended" (UPDRS-derived Postural Instability and Gait Difficulty score) and 2 as "suggested" (Tinetti Balance Scale, Rating Scale for Gait Evaluation). Three scales requiring equipment (Berg Balance Scale, Mini-BESTest, Dynamic Gait Index) also fulfilled criteria for "recommended" and 2 for "suggested" (FOG score, Gait and Balance Scale). Four questionnaires were "recommended" (Freezing of Gait Questionnaire, Activities-specific Balance Confidence Scale, Falls Efficacy Scale, Survey of Activities, and Fear of Falling in the Elderly-Modified). Four tests were classified as "recommended" (6-minute and 10-m walk tests, Timed Up-and-Go, Functional Reach). We identified several questionnaires that adequately assess freezing of gait and balance confidence in PD and a number of useful clinical tests. However, most clinical rating scales for gait, balance, and posture perform suboptimally or have been evaluated insufficiently. No instrument comprehensively and separately evaluates all relevant PD-specific gait characteristics with good clinimetric properties, and none provides separate balance and gait scores with adequate content validity for PD. We therefore recommend the development of such a PD-specific, easily administered, comprehensive gait and balance scale that separately assesses all relevant constructs. © 2016 International Parkinson and Movement Disorder Society. © 2016 International Parkinson and Movement Disorder Society.

Technology in Parkinson's disease: Challenges and opportunities.

PubMed

Espay, Alberto J; Bonato, Paolo; Nahab, Fatta B; Maetzler, Walter; Dean, John M; Klucken, Jochen; Eskofier, Bjoern M; Merola, Aristide; Horak, Fay; Lang, Anthony E; Reilmann, Ralf; Giuffrida, Joe; Nieuwboer, Alice; Horne, Malcolm; Little, Max A; Litvan, Irene; Simuni, Tanya; Dorsey, E Ray; Burack, Michelle A; Kubota, Ken; Kamondi, Anita; Godinho, Catarina; Daneault, Jean-Francois; Mitsi, Georgia; Krinke, Lothar; Hausdorff, Jeffery M; Bloem, Bastiaan R; Papapetropoulos, Spyros

2016-09-01

The miniaturization, sophistication, proliferation, and accessibility of technologies are enabling the capture of more and previously inaccessible phenomena in Parkinson's disease (PD). However, more information has not translated into a greater understanding of disease complexity to satisfy diagnostic and therapeutic needs. Challenges include noncompatible technology platforms, the need for wide-scale and long-term deployment of sensor technology (among vulnerable elderly patients in particular), and the gap between the "big data" acquired with sensitive measurement technologies and their limited clinical application. Major opportunities could be realized if new technologies are developed as part of open-source and/or open-hardware platforms that enable multichannel data capture sensitive to the broad range of motor and nonmotor problems that characterize PD and are adaptable into self-adjusting, individualized treatment delivery systems. The International Parkinson and Movement Disorders Society Task Force on Technology is entrusted to convene engineers, clinicians, researchers, and patients to promote the development of integrated measurement and closed-loop therapeutic systems with high patient adherence that also serve to (1) encourage the adoption of clinico-pathophysiologic phenotyping and early detection of critical disease milestones, (2) enhance the tailoring of symptomatic therapy, (3) improve subgroup targeting of patients for future testing of disease-modifying treatments, and (4) identify objective biomarkers to improve the longitudinal tracking of impairments in clinical care and research. This article summarizes the work carried out by the task force toward identifying challenges and opportunities in the development of technologies with potential for improving the clinical management and the quality of life of individuals with PD. © 2016 International Parkinson and Movement Disorder Society. © 2016 International Parkinson and Movement Disorder Society.

Role of olfactory reactions, nociception, and immunoendocrine shifts in addictive disorders.

PubMed

Masterova, Elena; Nevidimova, Tatiana; Savochkina, Dariya; Nikitina, Valentina; Lobacheva, Olga; Vetlugina, Tamara; Bokhan, Nikolay

2017-09-01

Addictive pathology is associated with nervous, immune, and endocrine shifts. Meanwhile, the nature of intersystemic relationship lying beneath addictive disorders remains unclear. The purpose of the study was to identify neuroimmunoendocrine markers of addictive disorders in male subjects defining the nature of their interaction. The study enrolled 69 subjects aged 18-43 years: 59 males and 10 females divided into those with addictive disorders (n = 39) and conditionally healthy subjects (n = 30). EEG testing with olfactory stimulation, olfactometric, and pressure algometric examinations was carried out. Multiplex technique was applied to determine mitogen-induced production of cytokines IL-10, IL-1, IL-1RA, IL-2, IFN-gamma, TNF-alpha. ELISA method was applied to measure serum cortisol and testosterone levels. Olfactory responses to isopropanol with open eyes in addicted patients manifested as increase in alpha-rhythm and beta1-rhythm, with closed eyes presentation of this odorant was accompanied by increase of theta-rhythm in opioid-addicted patients. Male subjects with addictive disorders showed reduced alpha-rhythm in terms of olfactory stimulation with modified emotional evaluation of the odorant, deficient mitogen-induced production of IFN-gamma, and reduced pain sensitivity. Male subjects with opioid addiction had reduced beta1-rhythm in terms of olfactory stimulation, mitogen-induced production of IFN-gamma, and elevated testosterone level. The findings obtained verify potential involvement of nociception, olfaction, and cytokine production in addiction pathogenesis evidencing their various roles depending on the range of psychoactive substances (PAS) and pathology progression. The data obtained may provide background for unification of reward circuit and inhibitory control concepts in regulation of addictive behavior. (Am J Addict 2017;26:640-648). © 2017 American Academy of Addiction Psychiatry.

Stimulant-Responsive and Stimulant-Refractory Aggressive Behavior Among Children with ADHD

PubMed Central

Blader, Joseph C.; Pliszka, Steven R.; Jensen, Peter S.; Schooler, Nina R.; Kafantaris, Vivian

2010-01-01

OBJECTIVES The objective of this study was to examine factors that are associated with aggression that is responsive versus refractory to individualized optimization of stimulant monotherapy among children with attention-deficit/hyperactivity disorder (ADHD). METHODS Children who were aged 6 to 13 years and had ADHD, either oppositional defiant disorder or conduct disorder, significant aggressive behavior, and a history of insufficient response to stimulants completed an open stimulant monotherapy optimization protocol. Stimulant titration with weekly assessments of behavior and tolerability identified an optimal regimen for each child. Families also received behavioral therapy. Parents completed the Retrospective-Modified Overt Aggression Scale (R-MOAS) at each visit. Children were classified as having stimulant-refractory aggression on the basis of R-MOAS ratings and clinician judgment. Differences that pertained to treatment, demographic, and psychopathology between groups with stimulant monotherapy–responsive and –refractory aggression were evaluated. RESULTS Aggression among 32 (49.3%) of 65 children was reduced sufficiently after stimulant dosage adjustment and behavioral therapy to preclude adjunctive medication. Those who responded to stimulant monotherapy were more likely to benefit from the protocol’s methylphenidate preparation (once-daily, triphasic release), showed a trend for lower average dosages, and received fewer behavioral therapy sessions than did children with stimulant-refractory aggression. Boys, especially those with higher ratings of baseline aggression and of depressive and manic symptoms, more often exhibited stimulant-refractory aggression. CONCLUSIONS Among children whose aggressive behavior develops in the context of ADHD and of oppositional defiant disorder or conduct disorder, and who had insufficient response to previous stimulant treatment in routine clinical care, systematic, well-monitored titration of stimulant monotherapy often culminates in reduced aggression that averts the need for additional agents. PMID:20837589

Gastrointestinal symptoms predictors of health-related quality of life in pediatric patients with functional gastrointestinal disorders.

PubMed

Varni, James W; Shulman, Robert J; Self, Mariella M; Nurko, Samuel; Saps, Miguel; Saeed, Shehzad A; Patel, Ashish S; Dark, Chelsea Vaughan; Bendo, Cristiane B; Pohl, John F

2017-04-01

To investigate the patient-reported multidimensional gastrointestinal symptoms predictors of generic health-related quality of life (HRQOL) in pediatric patients with functional gastrointestinal disorders (FGIDs). The Pediatric Quality of Life Inventory™ (PedsQL™) Gastrointestinal Symptoms Scales and PedsQL™ 4.0 Generic Core Scales were completed in a 9-site study by 259 pediatric patients with functional constipation, functional abdominal pain (FAP), or irritable bowel syndrome (IBS). Gastrointestinal Symptoms Scales measuring stomach pain, stomach discomfort when eating, food and drink limits, trouble swallowing, heartburn and reflux, nausea and vomiting, gas and bloating, constipation, blood in poop, and diarrhea were identified as clinically important symptom differentiators from healthy controls based on prior findings, and subsequently tested for bivariate and multivariate linear associations with overall HRQOL. Gastrointestinal symptoms were differentially associated with decreased HRQOL in bivariate analyses for the three FGIDs. In predictive models utilizing hierarchical multiple regression analyses controlling for age, gender, and race/ethnicity, gastrointestinal symptoms differentially accounted for an additional 47, 40, and 60 % of the variance in patient-reported HRQOL for functional constipation, FAP, and IBS, respectively, reflecting large effect sizes. Significant individual gastrointestinal symptoms predictors were identified after controlling for the other gastrointestinal symptoms in the FGID-specific predictive models. Gastrointestinal symptoms represent potentially modifiable predictors of generic HRQOL in pediatric patients with FGIDs. Identifying the condition-specific gastrointestinal symptoms that are the most important predictors from the patient perspective facilitates a patient-centered approach to targeted interventions designed to ameliorate impaired overall HRQOL.

Association analysis for feet and legs disorders with whole-genome sequence variants in 3 dairy cattle breeds.

PubMed

Wu, Xiaoping; Guldbrandtsen, Bernt; Lund, Mogens Sandø; Sahana, Goutam

2016-09-01

Identification of genetic variants associated with feet and legs disorders (FLD) will aid in the genetic improvement of these traits by providing knowledge on genes that influence trait variations. In Denmark, FLD in cattle has been recorded since the 1990s. In this report, we used deregressed breeding values as response variables for a genome-wide association study. Bulls (5,334 Danish Holstein, 4,237 Nordic Red Dairy Cattle, and 1,180 Danish Jersey) with deregressed estimated breeding values were genotyped with the Illumina Bovine 54k single nucleotide polymorphism (SNP) genotyping array. Genotypes were imputed to whole-genome sequence variants, and then 22,751,039 SNP on 29 autosomes were used for an association analysis. A modified linear mixed-model approach (efficient mixed-model association eXpedited, EMMAX) and a linear mixed model were used for association analysis. We identified 5 (3,854 SNP), 3 (13,642 SNP), and 0 quantitative trait locus (QTL) regions associated with the FLD index in Danish Holstein, Nordic Red Dairy Cattle, and Danish Jersey populations, respectively. We did not identify any QTL that were common among the 3 breeds. In a meta-analysis of the 3 breeds, 4 QTL regions were significant, but no additional QTL region was identified compared with within-breed analyses. Comparison between top SNP locations within these QTL regions and known genes suggested that RASGRP1, LCORL, MOS, and MITF may be candidate genes for FLD in dairy cattle. Copyright © 2016 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

A Family History of Psychopathology Modifies the Decrement in Cognitive Control among Patients with HIV/AIDS

ERIC Educational Resources Information Center

Bauer, Lance O.

2008-01-01

The present study was designed to evaluate the effect of HIV/AIDS on cognitive control and to determine if the effect is modified by familial risk for either alcohol or mood disorders. Sixty HIV-1 seropositive and 75 seronegative volunteers were assigned to four subgroups defined by the crossing of a diagnosis of alcohol dependence in the…

The Relationship between Symptom Relief and Psychosocial Functional Improvement during Acute Electroconvulsive Therapy for Patients with Major Depressive Disorder.

PubMed

Lin, Ching-Hua; Yang, Wei-Cheng

2017-07-01

We aimed to compare the degree of symptom relief to psychosocial functional (abbreviated as "functional") improvement and explore the relationships between symptom relief and functional improvement during acute electroconvulsive therapy for patients with major depressive disorder. Major depressive disorder inpatients (n=130) requiring electroconvulsive therapy were recruited. Electroconvulsive therapy was generally performed for a maximum of 12 treatments. Symptom severity, using the 17-item Hamilton Depression Rating Scale, and psychosocial functioning (abbreviated as "functioning"), using the Modified Work and Social Adjustment Scale, were assessed before electroconvulsive therapy, after every 3 electroconvulsive therapy treatments, and after the final electroconvulsive therapy. Both 17-item Hamilton Depression Rating Scale and Modified Work and Social Adjustment Scale scores were converted to T-score units to compare the degrees of changes between depressive symptoms and functioning after electroconvulsive therapy. Structural equation modeling was used to test the relationships between 17-item Hamilton Depression Rating Scale and Modified Work and Social Adjustment Scale during acute electroconvulsive therapy. One hundred sixteen patients who completed at least the first 3 electroconvulsive therapy treatments entered the analysis. Reduction of 17-item Hamilton Depression Rating Scale T-scores was significantly greater than that of Modified Work and Social Adjustment Scale T-scores at assessments 2, 3, 4, and 5. The model analyzed by structural equation modeling satisfied all indices of goodness-of-fit (chi-square = 32.882, P =.107, TLI = 0.92, CFI = 0.984, RMSEA = 0.057). The 17-item Hamilton Depression Rating Scale change did not predict subsequent Modified Work and Social Adjustment Scale change. Functioning improved less than depressive symptoms during acute electroconvulsive therapy. Symptom reduction did not predict subsequent functional improvement. Depressive symptoms and functional impairment are distinct domains and should be assessed independently to accurately reflect the effectiveness of electroconvulsive therapy. © The Author 2017. Published by Oxford University Press on behalf of CINP.

Abundant pyroglutamate-modified ABri and ADan peptides in extracellular and vascular amyloid deposits in familial British and Danish dementias

PubMed Central

Saul, Anika; Lashley, Tammaryn; Revesz, Tamas; Holton, Janice; Ghiso, Jorge A.; Coomaraswamy, Janaky; Wirths, Oliver

2013-01-01

Familial British (FBD) and familial Danish dementia (FDD) are progressive neurodegenerative disorders characterized by cerebral deposition of the amyloidogenic peptides ABri and ADan. These amyloid peptides start with an N-terminal glutamate residue, which can be posttranslationally converted into a pyroglutamate (pGlu-) modified form, a mechanism which has been extensively described to be relevant for Aβ peptides in Alzheimer’s disease (AD). Like pGlu-Aβ peptides, pGlu-ABri peptides have an increased aggregation propensity and show higher toxicity on human neuroblastoma cells as their non-modified counterparts. We have generated novel N-terminal specific antibodies detecting the pGlu-modified forms of ABri and ADan peptides. With these antibodies we were able to identify abundant extracellular amyloid plaques, vascular and parenchymal deposits in human FBD and FDD brain tissue, as well as in a mouse model for FDD. Double-stainings using C-terminal specific antibodies in human samples revealed that highly aggregated pGlu-ABri and pGlu-ADan peptides are mainly present in plaque cores and central vascular deposits, leading to the assumption that these peptides have seeding properties. Furthermore, in an FDD-mouse model ADan peptides were detected in pre-synaptic terminals of the hippocampus where they might contribute to impaired synaptic transmission. These similarities of ABri and ADan to Aβ in AD suggest that the posttranslational pGlu-modification of amyloid peptides might represent a general pathological mechanism leading to increased aggregation and toxicity in these forms of degenerative dementias. PMID:23261769

q Breathers in Finite Lattices: Nonlinearity and Weak Disorder

NASA Astrophysics Data System (ADS)

Ivanchenko, M. V.

2009-05-01

Nonlinearity and disorder are the recognized ingredients of the lattice vibrational dynamics, the factors that could be diminished, but never excluded. We generalize the concept of q breathers—periodic orbits in nonlinear lattices, exponentially localized in the linear mode space—to the case of weak disorder, taking the Fermi-Pasta-Ulan chain as an example. We show that these nonlinear vibrational modes remain exponentially localized near the central mode and stable, provided the disorder is sufficiently small. The instability threshold depends sensitively on a particular realization of disorder and can be modified by specifically designed impurities. Based on this sensitivity, an approach to controlling the energy flow between the modes is proposed. The relevance to other model lattices and experimental miniature arrays is discussed.

Fusion or confusion in obsessive compulsive disorder.

PubMed

O'Connor, Kieron; Aardema, Frederick

2003-08-01

Inferential confusion occurs when a person mistakes an imagined possibility for a real probability and might account for some types of thought-action and other fusions reported in obsessive-compulsive disorder. Inferential confusion could account for the ego-dystonic nature of obsessions and their recurrent nature, since the person acts "as if" an imagined aversive inference is probable and tries unsuccessfully to modify this imaginary probability in reality. The clinical implications of the inferential confusion model focus primarily on the role of the imagination in obsessive-compulsive disorder rather than on cognitive beliefs.

Screening for social anxiety disorder with the self-report version of the Liebowitz Social Anxiety Scale.

PubMed

Rytwinski, Nina K; Fresco, David M; Heimberg, Richard G; Coles, Meredith E; Liebowitz, Michael R; Cissell, Shadha; Stein, Murray B; Hofmann, Stefan G

2009-01-01

This study examined whether the self-report version of the Liebowitz Social Anxiety Scale (LSAS-SR) could accurately identify individuals with social anxiety disorder and individuals with the generalized subtype of social anxiety disorder. Furthermore, the study sought to determine the optimal cutoffs for the LSAS-SR for identifying patients with social anxiety disorder and its generalized subtype. Two hundred and ninety-one patients with clinician-assessed social anxiety disorder (240 with generalized social anxiety disorder) and 53 control participants who were free from current Axis-1 disorders completed the LSAS-SR. Receiver Operating Characteristic analyses revealed that the LSAS-SR performed well in identifying participants with social anxiety disorder and generalized social anxiety disorder. Consistent with Mennin et al.'s [2002: J Anxiety Disord 16:661-673] research on the clinician-administered version of the LSAS, cutoffs of 30 and 60 on the LSAS-SR provided the best balance of sensitivity and specificity for classifying participants with social anxiety and generalized social anxiety disorder, respectively. The LSAS-SR may be an accurate and cost-effective way to identify and subtype patients with social anxiety disorder, which could help increase the percentage of people who receive appropriate treatment for this debilitating disorder. (c) 2008 Wiley-Liss, Inc.

Urban and Education Disparity for Autism Spectrum Disorders in Taiwan Birth Cohort Study

ERIC Educational Resources Information Center

Lung, For-Wey; Chiang, Tung-Liang; Lin, Shio-Jean; Shu, Bih-Ching

2017-01-01

This study aimed to determine the optimal cut-off for autism spectrum disorder (ASD) screening in 66-month-old children, and to explore the distribution of ASD screening and diagnosis in Taiwan. The Taiwan Birth Cohort Study dataset was used (N = 20,095). The Modified Checklist for Autism in Toddlers (M-CHAT) cut-off point of 13/14 was considered…

An Analysis of the Effects of Functional Communication and a Voice Output Communication Aid for a Child with Autism Spectrum Disorder

ERIC Educational Resources Information Center

Olive, Melissa L.; Lang, Russell B.; Davis, Tonya N.

2008-01-01

The purpose of this study was to examine the effects of Functional Communication Training (FCT) and a Voice Output Communication Aid (VOCA) on the challenging behavior and language development of a 4-year-old girl with autism spectrum disorder. The participant's mother implemented modified functional analysis (FA) and intervention procedures in…

Comparison of the Pervasive Developmental Disorders Screening Test and Modified Checklist for Autism in Toddlers: Which Is the Better Predictor of Autism in Toddlers?

ERIC Educational Resources Information Center

Fessenden, Vanessa Marie

2013-01-01

Early intervention for children with autism spectrum disorders (ASD) has significant impact on children and families. Early intervention optimizes long-term diagnosis for children with ASD. Unfortunately, many children with ASD are not diagnosed until after age three and often receive services from a local school district rather than through early…

Characterization of nutrient disorders of Pericallis x hybrida ‘Jester Pure Blue’

USDA-ARS?s Scientific Manuscript database

Cineraria cruentus ‘Jester Purple Blue’ plants were grown in silica sand culture to induce and photograph nutritional disorder symptoms. Plants were grown with a complete modified Hoagland's all nitrate solution: (macronutrients in mM) 15 NO3-N, 1.0 PO4-P, 6.0 K, 5.0 Ca, 2.0 Mg, and 2.0 SO4-S, plus...

Characterization of nutrient disorders of pot rose ‘Karina Parade’

USDA-ARS?s Scientific Manuscript database

Pot rose cultivar ‘Karina Parade’ plants were grown in silica sand culture to induce and photograph nutritional disorder symptoms. Plants were grown with a complete modified Hoagland's all nitrate solution: (macronutrients in mM) 15 NO3-N, 1.0 PO4-P, 6.0 K, 5.0 Ca, 2.0 Mg, and 2.0 SO4-S, plus 'M con...

Limitations of the Patient Health Questionnaire in Identifying Anxiety and Depression: Many Cases Are Undetected

PubMed Central

Eack, Shaun M.; Greeno, Catherine G.; Lee, Bong-Jae

2013-01-01

Objective To determine the concordance between the Structured Clinical Interview for DSM-IV (SCID) and the Patient Health Questionnaire (PHQ) in diagnosing anxiety and depressive disorders. Method Fifty women seeking psychiatric services for their children at two mental health centers in Western Pennsylvania were assessed for anxiety and depressive disorders using the SCID and the PHQ. Results Twenty-five women met SCID criteria for at least one anxiety disorder, 11 (44%) of whom the PHQ failed to identify. The PHQ was particularly limited in identifying individuals with anxiety disorders other than panic disorder. Seventeen women met SCID criteria for at least one major depressive disorder, 6 (35%) of whom the PHQ failed to identify. The PHQ was particularly limited in identifying depressed individuals with dysthymia. Conclusions Caution should be used when screening for anxiety and depression with the PHQ. Implications for improving diagnostic accuracy in social work practice are discussed. PMID:24465121

Identifying the Transgender Population in the Medicare Program

PubMed Central

Proctor, Kimberly; Haffer, Samuel C.; Ewald, Erin; Hodge, Carla; James, Cara V.

2016-01-01

Abstract Purpose: To identify and describe the transgender population in the Medicare program using administrative data. Methods: Using a combination of International Classification of Diseases ninth edition (ICD-9) codes relating to transsexualism and gender identity disorder, we analyzed 100% of the 2013 Centers for Medicare & Medicaid Services (CMS) Medicare Fee-For-Service (FFS) “final action” claims from both institutional and noninstitutional providers (∼1 billion claims) to identify individuals who may be transgender Medicare beneficiaries. To confirm, we developed and applied a multistage validation process. Results: Four thousand ninety-eight transgender beneficiaries were identified, of which ∼90% had confirmatory diagnoses, billing codes, or evidence of a hormone prescription. In general, the racial, ethnic, and geographic distribution of the Medicare transgender population tends to reflect the broader Medicare population. However, age, original entitlement status, and disease burden of the transgender population appear substantially different. Conclusions: Using a variety of claims information, ranging from claims history to additional diagnoses, billing modifiers, and hormone prescriptions, we demonstrate that administrative data provide a valuable resource for identifying a lower bound of the Medicare transgender population. In addition, we provide a baseline description of the diversity and disease burden of the population and a framework for future research. PMID:28861539

Treatment of Internet Addiction with Anxiety Disorders: Treatment Protocol and Preliminary Before-After Results Involving Pharmacotherapy and Modified Cognitive Behavioral Therapy

PubMed Central

Santos, Hugo Henrique

2016-01-01

Background The growth of the Internet has led to significant change and has become an integral part of modern life. It has made life easier and provided innumerous benefits; however, excessive use has brought about the potential for addiction, leading to severe impairments in social, academic, financial, psychological, and work domains. Individuals addicted to the Internet usually have comorbid psychiatric disorders. Panic disorder (PD) and generalized anxiety disorder (GAD) are prevalent mental disorders, involving a great deal of damage in the patient’s life. Objective This open trial study describes a treatment protocol among 39 patients with anxiety disorders and Internet addiction (IA) involving pharmacotherapy and modified cognitive behavioral therapy (CBT). Methods Of the 39 patients, 25 were diagnosed with PD and 14 with GAD, in addition to Internet addiction. At screening, patients responded to the MINI 5.0, Hamilton Anxiety Rating Scale, Hamilton Depression Rating Scale, Clinical Global Impressions Scale, and the Young Internet Addiction Scale. At that time, IA was observed taking into consideration the IAT scale (cutoff score above 50), while anxiety disorders were diagnosed by a psychiatrist. Patients were forwarded for pharmacotherapy and a modified CBT protocol. Psychotherapy was conducted individually, once a week, over a period of 10 weeks, and results suggest that the treatment was effective for anxiety and Internet addiction. Results Before treatment, anxiety levels suggested severe anxiety, with an average score of 34.26 (SD 6.13); however, after treatment the mean score was 15.03 (SD 3.88) (P<.001). A significant improvement in mean Internet addiction scores was observed, from 67.67 (SD 7.69) before treatment, showing problematic internet use, to 37.56 (SD 9.32) after treatment (P<.001), indicating medium Internet use. With respect to the relationship between IA and anxiety, the correlation between scores was .724. Conclusions This study is the first research into IA treatment of a Brazilian population. The improvement was remarkable due to the complete engagement of patients in therapy, which contributed to the success of the treatment from a behavioral perspective, and gave patients the confidence to continue to manage Internet use in their lives. PMID:27005889

Heat Shock Protein Beta-1 Modifies Anterior to Posterior Purkinje Cell Vulnerability in a Mouse Model of Niemann-Pick Type C Disease.

PubMed

Chung, Chan; Elrick, Matthew J; Dell'Orco, James M; Qin, Zhaohui S; Kalyana-Sundaram, Shanker; Chinnaiyan, Arul M; Shakkottai, Vikram G; Lieberman, Andrew P

2016-05-01

Selective neuronal vulnerability is characteristic of most degenerative disorders of the CNS, yet mechanisms underlying this phenomenon remain poorly characterized. Many forms of cerebellar degeneration exhibit an anterior-to-posterior gradient of Purkinje cell loss including Niemann-Pick type C1 (NPC) disease, a lysosomal storage disorder characterized by progressive neurological deficits that often begin in childhood. Here, we sought to identify candidate genes underlying vulnerability of Purkinje cells in anterior cerebellar lobules using data freely available in the Allen Brain Atlas. This approach led to the identification of 16 candidate neuroprotective or susceptibility genes. We demonstrate that one candidate gene, heat shock protein beta-1 (HSPB1), promoted neuronal survival in cellular models of NPC disease through a mechanism that involved inhibition of apoptosis. Additionally, we show that over-expression of wild type HSPB1 or a phosphomimetic mutant in NPC mice slowed the progression of motor impairment and diminished cerebellar Purkinje cell loss. We confirmed the modulatory effect of Hspb1 on Purkinje cell degeneration in vivo, as knockdown by Hspb1 shRNA significantly enhanced neuron loss. These results suggest that strategies to promote HSPB1 activity may slow the rate of cerebellar degeneration in NPC disease and highlight the use of bioinformatics tools to uncover pathways leading to neuronal protection in neurodegenerative disorders.

A neural network method for detection of obstructive sleep apnea and narcolepsy based on pupil size and EEG.

PubMed

Liu, D; Pang, Z; Lloyd, S R

2008-02-01

Electroencephalogram (EEG) is able to indicate states of mental activity ranging from concentrated cognitive efforts to sleepiness. Such mental activity can be reflected by EEG energy. In particular, intrusion of EEG theta wave activity into the beta activity of active wakefulness has been interpreted as ensuing sleepiness. Pupil behavior can also provide information regarding alertness. This paper develops an innovative signal classification method that is capable of differentiating subjects with sleep disorders which cause excessive daytime sleepiness (EDS) from normal control subjects who do not have a sleep disorder based on EEG and pupil size. Subjects with sleep disorders include persons with untreated obstructive sleep apnea (OSA) and narcolepsy. The Yoss pupil staging rule is used to scale levels of wakefulness and at the same time theta energy ratios are calculated from the same 2-s sliding windows by Fourier or wavelet transforms. Then, an artificial neural network (NN) of modified adaptive resonance theory (ART2) is utilized to identify the two groups within a combined group of subjects including those with OSA and healthy controls. This grouping from the NN is then compared with the actual diagnostic classification of subjects as OSA or controls and is found to be 91% accurate in differentiating between the two groups. The same algorithm results in 90% correct differentiation between narcoleptic and control subjects.

Case definition and classification of leukodystrophies and leukoencephalopathies.

PubMed

Vanderver, Adeline; Prust, Morgan; Tonduti, Davide; Mochel, Fanny; Hussey, Heather M; Helman, Guy; Garbern, James; Eichler, Florian; Labauge, Pierre; Aubourg, Patrick; Rodriguez, Diana; Patterson, Marc C; Van Hove, Johan L K; Schmidt, Johanna; Wolf, Nicole I; Boespflug-Tanguy, Odile; Schiffmann, Raphael; van der Knaap, Marjo S

2015-04-01

An approved definition of the term leukodystrophy does not currently exist. The lack of a precise case definition hampers efforts to study the epidemiology and the relevance of genetic white matter disorders to public health. Thirteen experts at multiple institutions participated in iterative consensus building surveys to achieve definition and classification of disorders as leukodystrophies using a modified Delphi approach. A case definition for the leukodystrophies was achieved, and a total of 30 disorders were classified under this definition. In addition, a separate set of disorders with heritable white matter abnormalities but not meeting criteria for leukodystrophy, due to presumed primary neuronal involvement and prominent systemic manifestations, was classified as genetic leukoencephalopathies (gLE). A case definition of leukodystrophies and classification of heritable white matter disorders will permit more detailed epidemiologic studies of these disorders. Copyright © 2015 Elsevier Inc. All rights reserved.

The associations between personality characteristics and absenteeism: a cross-sectional study in workers with and without depressive and anxiety disorders.

PubMed

Vlasveld, Moniek C; van der Feltz-Cornelis, Christina M; Anema, Johannes R; van Mechelen, Willem; Beekman, Aartjan T F; van Marwijk, Harm W J; Penninx, Brenda W J H

2013-09-01

Although numerous studies have identified risk factors for sickness absence, few studies have addressed the role of personality characteristics in absenteeism. The aim of this study was to examine the associations of the Big 5 personality characteristics (neuroticism, extraversion, openness, agreeableness and conscientiousness) and locus of control with absenteeism, taking the presence of depressive and anxiety disorders into account. Cross-sectional data from the baseline measurement of the Netherlands Study of Depression and Anxiety (NESDA) were examined. NESDA includes persons with current or remitted depressive and anxiety disorders and healthy controls, of which 1883 working participants were selected. Personality characteristics were included as predictor variables, short-term (0-2 weeks) and long-term (>2 weeks) absenteeism as outcome measure. The presence of depressive and anxiety disorders was considered as modifying covariate. In healthy workers, high neuroticism, external locus of control, low extraversion, low agreeableness and low conscientiousness were associated with short-term absenteeism. In addition, high neuroticism, low extraversion and low openness were related to long-term absenteeism in healthy workers. In workers with psychopathology, similar associations were found for persons with this profile (high neuroticism, external locus of control, low extraversion and low conscientiousness) with long-term absenteeism, but no associations of these characteristics were found with short-term absenteeism. Personality characteristics were significantly associated with work absenteeism in both workers with and without anxiety or depression. Interventions aimed at preventing sickness absence may focus on reducing neuroticism and strengthening extraversion, conscientiousness and locus of control.

Diagnostics Cost Groups and Concurrent Utilization among Patients

PubMed Central

Rosen, Amy K; Loveland, Susan A; Anderson, Jennifer J; Hankin, Cheryl S; Breckenridge, James N; Berlowitz, Dan R

2002-01-01

Objective To assess the performance of Diagnostic Cost Groups (DCGs) in explaining variation in concurrent utilization for a defined subgroup, patients with substance abuse (SA) disorders, within the Department of Veterans Affairs (VA). Data Sources A 60 percent random sample of veterans who used health care services during Fiscal Year (FY) 1997 was obtained from VA administrative databases. Patients with SA disorders (13.3 percent) were identified from primary and secondary ICD-9-CM diagnosis codes. Study Design Concurrent risk adjustment models were fitted and tested using the DCG/HCC model. Three outcome measures were defined: (1) “service days” (the sum of a patient's inpatient and outpatient visit days), (2) mental health/substance abuse (MH/SA) service days, and (3) ambulatory provider encounters. To improve model performance, we ran three DCG/HCC models with additional indicators for patients with SA disorders. Data Collection To create a single file of veterans who used health care services in FY 1997, we merged records from all VA inpatient and outpatient files. Principal Findings Adding indicators for patients with mild/moderate SA disorders did not appreciably improve the R-squares for any of the outcome measures. When indicators were added for patients with severe SA who were in the most costly category, the explanatory ability of the models was modestly improved for all three outcomes. Conclusions Modifying the DCG/HCC model with additional markers for SA modestly improved homogeneity and model prediction. Because considerable variation still remained after modeling, we conclude that health care systems should evaluate “off-the-shelf” risk adjustment systems before applying them to their own populations. PMID:12236385

Pain Information Brochure

MedlinePlus

... National Institute of Neurological Disorders and Stroke Complex Regional Pain Syndrome Complex Regional Pain Syndrome Information Page ... ACTTION Analgesic, Anesthetic, and Addiction Clinical Trial Translations, Innovations, Opportunities, and Networks. Date last modified: Contact Us ...

Relative variations of gut microbiota in disordered cholesterol metabolism caused by high-cholesterol diet and host genetics.

PubMed

Bo, Tao; Shao, Shanshan; Wu, Dongming; Niu, Shaona; Zhao, Jiajun; Gao, Ling

2017-08-01

Recent studies performed provide mechanistic insight into effects of the microbiota on cholesterol metabolism, but less focus was given to how cholesterol impacts the gut microbiota. In this study, ApoE -/- Sprague Dawley (SD) rats and their wild-type counterparts (n = 12) were, respectively, allocated for two dietary condition groups (normal chow and high-cholesterol diet). Total 16S rDNA of fecal samples were extracted and sequenced by high-throughput sequencing to determine differences in microbiome composition. Data were collected and performed diversity analysis and phylogenetic analysis. The influence of cholesterol on gut microbiota was discussed by using cholesterol dietary treatment as exogenous cholesterol disorder factor and genetic modification as endogenous metabolic disorder factor. Relative microbial variations were compared to illustrate the causality and correlation of cholesterol and gut microbiota. It turned out comparing to genetically modified rats, exogenous cholesterol intake may play more effective role in changing gut microbiota profile, although the serum cholesterol level of genetically modified rats was even higher. Relative abundance of some representative species showed that the discrepancies due to dietary variation were more obvious, whereas some low abundance species changed because of genetic disorders. Our results partially demonstrated that gut microbiota are relatively more sensitive to dietary variation. Nevertheless, considering the important effect of bacteria in cholesterol metabolism, the influence to gut flora by "genetically caused cholesterol disorder" cannot be overlooked. Manipulation of gut microbiota might be an effective target for preventing cholesterol-related metabolic disorders. © 2017 The Authors. MicrobiologyOpen published by John Wiley & Sons Ltd.

Dopamine signaling in reward-related behaviors.

PubMed

Baik, Ja-Hyun

2013-01-01

Dopamine (DA) regulates emotional and motivational behavior through the mesolimbic dopaminergic pathway. Changes in DA mesolimbic neurotransmission have been found to modify behavioral responses to various environmental stimuli associated with reward behaviors. Psychostimulants, drugs of abuse, and natural reward such as food can cause substantial synaptic modifications to the mesolimbic DA system. Recent studies using optogenetics and DREADDs, together with neuron-specific or circuit-specific genetic manipulations have improved our understanding of DA signaling in the reward circuit, and provided a means to identify the neural substrates of complex behaviors such as drug addiction and eating disorders. This review focuses on the role of the DA system in drug addiction and food motivation, with an overview of the role of D1 and D2 receptors in the control of reward-associated behaviors.

The need for a disease-specific prospective pregnancy registry for multiple sclerosis (MS).

PubMed

Alwan, Sura; Chambers, Christina D; Armenti, Vincent T; Sadovnick, A Dessa

2015-01-01

Multiple sclerosis (MS) is the most commonly acquired neurological disorder affecting young adults of reproductive age with an approximately 3:1 female to male ratio. Although pregnancy is not contraindicated in MS, data are limited regarding pregnancy outcome among MS patients, and the safety or risk to the fetus associated with most maternal MS treatments, such as disease modifying therapies (DMTs), during pregnancy is unknown. We review available epidemiological and registry data on MS and pregnancy and discuss the need to initiate a North American Multiple Sclerosis Pregnancy Registry that will prospectively identify pregnancies in women with MS, obtain information on the disease, and its treatment during gestation and lactation and follow the children to determine their health status. Copyright © 2014 Elsevier B.V. All rights reserved.

Ptosis, extraocular motility disorder, and myopia as features of pompe disease.

PubMed

Slingerland, Niki W R; Polling, Jan Roelof; van Gelder, Catharina M; van der Ploeg, Ans T; Bleyen, Isabel

2011-03-01

The assets of this report are a thorough description of new clinical findings, namely the combination of ptosis, extraocular motility disorder and myopia, in consequence of prolonged survival in classic infantile-onset Pompe disease through enzyme therapy. Single case description. This manuscript describes a combination of ptosis, extraocular motility disorder and myopia in a 4.5-year-old patient with classic infantile-onset Pompe disease, who survived through enzyme therapy. This patient was treated with a bilateral frontalis suspension (modified Crawford technique) using prolene 3-0 sutures. The combination of ptosis, extraocular motility disorder and myopia, is a new clinical finding in children with classic infantile-onset Pompe disease.

Recent advances in autism research as reflected in DSM-5 criteria for autism spectrum disorder.

PubMed

Lord, Catherine; Bishop, Somer L

2015-01-01

This article provides a selective review of advances in scientific knowledge about autism spectrum disorder (ASD), using DSM-5 (Diagnostic and Statistical Manual of Mental Disorders, fifth edition) diagnostic criteria as a framework for the discussion. We review literature that prompted changes to the organization of ASD symptoms and diagnostic subtypes in DSM-IV, and we examine the rationale for new DSM-5 specifiers, modifiers, and severity ratings as well as the introduction of the diagnosis of social (pragmatic) communication disorder. Our goal is to summarize and critically consider the contribution of clinical psychology research, along with that of other disciplines, to the current conceptualization of ASD.

The Coping Cat Program for Children with Anxiety and Autism Spectrum Disorder: A Pilot Randomized Controlled Trial

ERIC Educational Resources Information Center

McNally Keehn, Rebecca H.; Lincoln, Alan J.; Brown, Milton Z.; Chavira, Denise A.

2013-01-01

The purpose of this pilot study was to evaluate whether a modified version of the Coping Cat program could be effective in reducing anxiety in children with autism spectrum disorder (ASD). Twenty-two children (ages 8-14; IQ greater than or equal to 70) with ASD and clinically significant anxiety were randomly assigned to 16 sessions of the Coping…

Daily Stress, Hearing-Specific Stress and Coping: Self-Reports from Deaf or Hard of Hearing Children and Children with Auditory Processing Disorder

ERIC Educational Resources Information Center

Eschenbeck, Heike; Gillé, Vera; Heim-Dreger, Uwe; Schock, Alexandra; Schott, Andrea

2017-01-01

This study evaluated stressors and coping strategies in 70 children who are deaf or hard of hearing (D/HH) or with auditory processing disorder (APD) attending Grades 5 and 6 of a school for deaf and hard-of-hearing children. Everyday general stressors and more hearing-specific stressors were examined in a hearing-specific modified stress and…

Effects of an Appearance-Focused Interpretation Training Intervention on Eating Disorder Symptoms.

PubMed

Summers, Berta J; Cougle, Jesse R

2018-03-13

Previous research suggests that computerized interpretation bias modification (IBM) techniques may be useful for modifying thoughts and behaviours relevant to eating pathology; however, little is known about the utility of IBM for decreasing specific eating disorder (ED) symptoms (e.g. bulimia, drive for thinness). The current study sought to further examine the utility of IBM for ED symptoms via secondary analyses of an examination of IBM for individuals with elevated body dysmorphic disorder (BDD) symptoms (see Summers and Cougle, 2016), as these disorders are both characterized by threat interpretation biases of ambiguous appearance-related information. We recruited 41 participants for a randomized trial comparing four sessions of IBM aimed at modifying problematic social and appearance-related threat interpretation biases with a placebo control training (PC). At 1-week post-treatment, and relative to the PC, the IBM group reported greater reductions in negative/threat interpretations of ambiguous information in favour of positive/benign biases. Furthermore, among individuals with high pre-treatment bulimia symptoms, IBM yielded greater reductions in bulimia symptoms compared with PC at post-treatment. No treatment effects were observed on drive for thinness symptoms. The current study suggests that cognitive interventions for individuals with primary BDD symptoms may improve co-occurring ED symptoms such as bulimia.

Assessing Disordered Thoughts in Preschoolers with Dysregulated Mood

ERIC Educational Resources Information Center

Hutchison, Amanda K.; Beresford, Carol; Robinson, JoAnn; Ross, Randal G.

2010-01-01

There is rising interest in identifying precursors to bipolar disorder symptoms, including thought disorder. Thought disorder is identified in adults through self-report and in school-aged children through parent report and child story-telling. This study is an exploration to determine if preschoolers with mood dysregulation have evidence of…

Measuring word complexity in speech screening: single-word sampling to identify phonological delay/disorder in preschool children.

PubMed

Anderson, Carolyn; Cohen, Wendy

2012-01-01

Children's speech sound development is assessed by comparing speech production with the typical development of speech sounds based on a child's age and developmental profile. One widely used method of sampling is to elicit a single-word sample along with connected speech. Words produced spontaneously rather than imitated may give a more accurate indication of a child's speech development. A published word complexity measure can be used to score later-developing speech sounds and more complex word patterns. There is a need for a screening word list that is quick to administer and reliably differentiates children with typically developing speech from children with patterns of delayed/disordered speech. To identify a short word list based on word complexity that could be spontaneously named by most typically developing children aged 3;00-5;05 years. One hundred and five children aged between 3;00 and 5;05 years from three local authority nursery schools took part in the study. Items from a published speech assessment were modified and extended to include a range of phonemic targets in different word positions in 78 monosyllabic and polysyllabic words. The 78 words were ranked both by phonemic/phonetic complexity as measured by word complexity and by ease of spontaneous production. The ten most complex words (hereafter Triage 10) were named spontaneously by more than 90% of the children. There was no significant difference between the complexity measures for five identified age groups when the data were examined in 6-month groups. A qualitative analysis revealed eight children with profiles of phonological delay or disorder. When these children were considered separately, there was a statistically significant difference (p < 0.005) between the mean word complexity measure of the group compared with the mean for the remaining children in all other age groups. The Triage 10 words reliably differentiated children with typically developing speech from those with delayed or disordered speech patterns. The Triage 10 words can be used as a screening tool for triage and general assessment and have the potential to monitor progress during intervention. Further testing is being undertaken to establish reliability with children referred to speech and language therapy services. © 2012 Royal College of Speech and Language Therapists.

Survey of Neurological Disorders in Children Aged 9-15 Years in Northern India.

PubMed

Kumar, Rashmi; Bhave, Anupama; Bhargava, Roli; Agarwal, G G

2016-04-01

The prevalence of neurological disorders in resource-poor settings, although likely to be high, is largely unexplored. The prevalence and risk factors for neurological disorders, including epilepsy and intellectual, motor, vision, and hearing deficits, in children aged 9 to 15 years in the community were investigated. A new instrument was developed, validated, and used in a 2-stage community survey for neurological disorders in Lucknow, India. Screen-positives and random proportion of screen-negatives were validated using predefined criteria. Prevalence of different neurological disorders was calculated by weighted proportions. Of 6431 children screened, 221 were positive. A total of 214 screen-positives and 251 screen-negatives were validated. Prevalence of neurological disorders was 31.3 per 1000 children of this age group (weighted 95% confidence interval = 16.5, 46.4). The final model for risk factors included age, mud house, delayed cry at birth, and previous head injury. The prevalence of neurological disorders is high in this region. Predictors of neurological disorders are largely modifiable. © The Author(s) 2015.

Adolescent eating disorder behaviours and cognitions: gender-specific effects of child, maternal and family risk factors

PubMed Central

Micali, N.; De Stavola, B.; Ploubidis, G.; Simonoff, E.; Treasure, J.; Field, A. E.

2015-01-01

Background Eating disorder behaviours begin in adolescence. Few longitudinal studies have investigated childhood risk and protective factors. Aims To investigate the prevalence of eating disorder behaviours and cognitions and associated childhood psychological, physical and parental risk factors among a cohort of 14-year-old children. Method Data were collected from 6140 boys and girls aged 14 years. Gender-stratified models were used to estimate prospective associations between childhood body dissatisfaction, body mass index (BMI), self-esteem, maternal eating disorder and family economic disadvantage on adolescent eating disorder behaviours and cognitions. Results Childhood body dissatisfaction strongly predicted eating disorder cognitions in girls, but only in interaction with BMI in boys. Higher self-esteem had a protective effect, particularly in boys. Maternal eating disorder predicted body dissatisfaction and weight/shape concern in adolescent girls and dieting in boys. Conclusions Risk factors for eating disorder behaviours and cognitions vary according to gender. Prevention strategies should be gender-specific and target modifiable predictors in childhood and early adolescence. PMID:26206865

Restoring Ureagenesis in Hepatocytes by CRISPR/Cas9-mediated Genomic Addition to Arginase-deficient Induced Pluripotent Stem Cells.

PubMed

Lee, Patrick C; Truong, Brian; Vega-Crespo, Agustin; Gilmore, W Blake; Hermann, Kip; Angarita, Stephanie Ak; Tang, Jonathan K; Chang, Katherine M; Wininger, Austin E; Lam, Alex K; Schoenberg, Benjamen E; Cederbaum, Stephen D; Pyle, April D; Byrne, James A; Lipshutz, Gerald S

2016-11-29

Urea cycle disorders are incurable enzymopathies that affect nitrogen metabolism and typically lead to hyperammonemia. Arginase deficiency results from a mutation in Arg1, the enzyme regulating the final step of ureagenesis and typically results in developmental disabilities, seizures, spastic diplegia, and sometimes death. Current medical treatments for urea cycle disorders are only marginally effective, and for proximal disorders, liver transplantation is effective but limited by graft availability. Advances in human induced pluripotent stem cell research has allowed for the genetic modification of stem cells for potential cellular replacement therapies. In this study, we demonstrate a universally-applicable CRISPR/Cas9-based strategy utilizing exon 1 of the hypoxanthine-guanine phosphoribosyltransferase locus to genetically modify and restore arginase activity, and thus ureagenesis, in genetically distinct patient-specific human induced pluripotent stem cells and hepatocyte-like derivatives. Successful strategies restoring gene function in patient-specific human induced pluripotent stem cells may advance applications of genetically modified cell therapy to treat urea cycle and other inborn errors of metabolism.

Conserved Genes Act as Modifiers of Invertebrate SMN Loss of Function Defects

PubMed Central

Chang, Howard C.; Sen, Anindya; Kalloo, Geetika; Harris, Jevede; Barsby, Tom; Walsh, Melissa B.; Satterlee, John S.; Li, Chris; Van Vactor, David; Artavanis-Tsakonas, Spyros; Hart, Anne C.

2010-01-01

Spinal Muscular Atrophy (SMA) is caused by diminished function of the Survival of Motor Neuron (SMN) protein, but the molecular pathways critical for SMA pathology remain elusive. We have used genetic approaches in invertebrate models to identify conserved SMN loss of function modifier genes. Drosophila melanogaster and Caenorhabditis elegans each have a single gene encoding a protein orthologous to human SMN; diminished function of these invertebrate genes causes lethality and neuromuscular defects. To find genes that modulate SMN function defects across species, two approaches were used. First, a genome-wide RNAi screen for C. elegans SMN modifier genes was undertaken, yielding four genes. Second, we tested the conservation of modifier gene function across species; genes identified in one invertebrate model were tested for function in the other invertebrate model. Drosophila orthologs of two genes, which were identified originally in C. elegans, modified Drosophila SMN loss of function defects. C. elegans orthologs of twelve genes, which were originally identified in a previous Drosophila screen, modified C. elegans SMN loss of function defects. Bioinformatic analysis of the conserved, cross-species, modifier genes suggests that conserved cellular pathways, specifically endocytosis and mRNA regulation, act as critical genetic modifiers of SMN loss of function defects across species. PMID:21124729

I Should but I Can’t: Controlled Motivation and Self-efficacy are Related to Disordered Eating Behaviors in Adolescents with Type 1 Diabetes

PubMed Central

Eisenberg, Miriam H.; Lipsky, Leah M.; Dempster, Katherine; Liu, Aiyi; Nansel, Tonja R.

2016-01-01

Purpose Among adolescents with type 1 diabetes, disordered eating behaviors (DEB) are more prevalent and have more serious health implications than in adolescents without diabetes, necessitating identification of modifiable correlates of DEB in this population. This study hypothesized that 1) autonomous motivation and 2) controlled motivation for healthy eating (i.e., eating healthfully because it’s important to oneself versus important to others respectively) are associated with DEB among adolescents with type 1 diabetes. The third hypothesis was that baseline healthy eating self-efficacy moderates these associations. Methods Adolescents with T1D (n = 90; 13–16 years) participating in a behavioral nutrition intervention efficacy trial reported DEB, controlled and autonomous motivation, and self-efficacy at baseline, 6, 12, and 18 months. Linear mixed models estimated associations of controlled and autonomous motivation with DEB, adjusting for treatment group, BMI, socio-economic status, age, and gender. Separate models investigated the interaction of self-efficacy with each motivation type. Results Controlled motivation was positively associated with DEB (B=2.18±.33, p<.001); the association was stronger for those with lower self-efficacy (B= 3.33±.55, p<.001) than those with higher self-efficacy (B=1.36±.36, p<.001). Autonomous motivation was not associated with DEB (B=−.70± .43, p=.11). Conclusions Findings identify controlled motivation for healthy eating as a novel correlate of DEB among adolescents with type 1 diabetes and show that self-efficacy can modify this association. Motivation and self-efficacy for healthy eating represent potential intervention targets to reduce DEB in adolescents with type 1 diabetes. PMID:27567063

Early high school engagement in students with attention/deficit hyperactivity disorder.

PubMed

Zendarski, Nardia; Sciberras, Emma; Mensah, Fiona; Hiscock, Harriet

2017-06-01

Students with attention/deficit hyperactivity disorder (ADHD) continue to languish behind their peers with regard to academic achievement and education attainment. School engagement is potentially modifiable, and targeting engagement may be a means to improve education outcomes. To investigate school engagement for students with ADHD during the crucial high school transition period and to identify factors associated with low school engagement. Participants are adolescents (12-15 years) in the first and third year of high school with diagnosed ADHD (n = 130). Participants were recruited from 21 paediatric practices. Cross-sectional study assessing school engagement. Data were collected through direct assessment and child, parent, and teacher surveys. School engagement is measured as student attitudes to school (cognitive and emotional) and suspension rates (behavioural). Multivariable regression analyses examined student, family, and school factors affecting engagement. In comparison with state data, students with ADHD in the first year of high school were less motivated (p < .01) and less connected to peers (p < .01). Overall, there was no discordance in third year attitudes. There were high rates of suspension in both years in comparison to state-wide suspensions (21% vs. 6%, p < .01). Explanatory factors for poor attitudes include adolescent depression, poor adolescent supervision, and devaluing education. Conduct problems and increased hyperactivity were related to increased likelihood of being suspended, whilst higher cognitive ability, family socio-economic status, and independent schools reduced risk. Potentially modifiable individual and family factors including adolescent depression, behavioural problems, education values, and family supervision could be targeted to better manage the high school transition for students with ADHD. © 2017 The British Psychological Society.

I Should but I Can't: Controlled Motivation and Self-Efficacy Are Related to Disordered Eating Behaviors in Adolescents With Type 1 Diabetes.

PubMed

Eisenberg, Miriam H; Lipsky, Leah M; Dempster, Katherine W; Liu, Aiyi; Nansel, Tonja R

2016-11-01

Among adolescents with type 1 diabetes, disordered eating behaviors (DEBs) are more prevalent and have more serious health implications than in adolescents without diabetes, necessitating identification of modifiable correlates of DEB in this population. This study hypothesized that (1) autonomous motivation and (2) controlled motivation for healthy eating (i.e., eating healthfully because it is important to oneself vs. important to others, respectively) are associated with DEB among adolescents with type 1 diabetes. The third hypothesis was that baseline healthy eating self-efficacy moderates these associations. Adolescents with type 1 diabetes (n = 90; 13-16 years) participating in a behavioral nutrition intervention efficacy trial reported DEB, controlled and autonomous motivation, and self-efficacy at baseline, 6, 12, and 18 months. Linear-mixed models estimated associations of controlled and autonomous motivation with DEB, adjusting for treatment group, body mass index, socioeconomic status, age, and gender. Separate models investigated the interaction of self-efficacy with each motivation type. Controlled motivation was positively associated with DEB (B = 2.18 ± .33, p < .001); the association was stronger for those with lower self-efficacy (B = 3.33 ± .55, p < .001) than those with higher self-efficacy (B = 1.36 ± .36, p < .001). Autonomous motivation was not associated with DEB (B = -.70 ± .43, p = .11). Findings identify controlled motivation for healthy eating as a novel correlate of DEB among adolescents with type 1 diabetes and show that self-efficacy can modify this association. Motivation and self-efficacy for healthy eating represent potential intervention targets to reduce DEB in adolescents with type 1 diabetes. Published by Elsevier Inc.

Convergent beam electron-diffraction investigation of lattice mismatch and static disorder in GaAs/GaAs1-xNx intercalated GaAs/GaAs1-xNx:H heterostructures

NASA Astrophysics Data System (ADS)

Frabboni, S.; Grillo, V.; Gazzadi, G. C.; Balboni, R.; Trotta, R.; Polimeni, A.; Capizzi, M.; Martelli, F.; Rubini, S.; Guzzinati, G.; Glas, F.

2012-09-01

Hydrogen incorporation in diluted nitride semiconductors dramatically modifies the electronic and structural properties of the crystal through the creation of nitrogen-hydrogen complexes. We report a convergent beam electron-diffraction characterization of diluted nitride semiconductor-heterostructures patterned at a sub-micron scale and selectively exposed to hydrogen. We present a method to determine separately perpendicular mismatch and static disorder in pristine and hydrogenated heterostructures. The roles of chemical composition and strain on static disorder have been separately assessed.

Risk factors for secondary substance use disorders in people with childhood and adolescent-onset bipolar disorder: opportunities for prevention.

PubMed

Kenneson, Aileen; Funderburk, Jennifer S; Maisto, Stephen A

2013-07-01

Compared to other mental illnesses, bipolar disorder is associated with a disproportionately high rate of substance use disorders (SUDs), and the co-occurrence is associated with significant morbidity and mortality. Early diagnosis of primary bipolar disorder may provide opportunities for SUD prevention, but little is known about the risk factors for secondary SUD among individuals with bipolar disorder. The purposes of this study were to describe the population of people with childhood and adolescent-onset primary bipolar disorder, and to identify risk factors for secondary SUD in this population. Using data collected from the National Comorbidity Survey Replication study, we identified 158 individuals with childhood-onset (<13 years) or adolescent-onset (13-18 years) primary bipolar disorder (I, II or subthreshold). Survival analysis was used to identify risk factors for SUD. Compared to adolescent-onset, people with childhood-onset bipolar disorder had increased likelihoods of attention deficit hyperactivity disorder (ADHD) (adjusted odds ratio=2.81) and suicide attempt (aOR=3.61). Males were more likely than females to develop SUD, and did so at a faster rate. Hazard ratios of risk factors for SUD were: lifetime oppositional defiant disorder (2.048), any lifetime anxiety disorder (3.077), adolescent-onset bipolar disorder (1.653), and suicide attempt (15.424). SUD was not predicted by bipolar disorder type, family history of bipolar disorder, hospitalization for a mood episode, ADHD or conduct disorder. As clinicians struggle to help individuals with bipolar disorder, this study provides information that might be useful in identifying individuals at higher risk for SUD. Future research can examine whether targeting these risk factors may help prevent secondary SUD. Published by Elsevier Inc.

The epigenetic lorax: gene–environment interactions in human health

PubMed Central

Latham, Keith E; Sapienza, Carmen; Engel, Nora

2012-01-01

Over the last decade, we have witnessed an explosion of information on genetic factors underlying common human diseases and disorders. This ‘human genomics’ information revolution has occurred as a backdrop to a rapid increase in the rates of many human disorders and diseases. For example, obesity, Type 2 diabetes, asthma, autism spectrum disorder and attention deficit hyperactivity disorder have increased at rates that cannot be due to changes in the genetic structure of the population, and are difficult to ascribe to changes in diagnostic criteria or ascertainment. A likely cause of the increased incidence of these disorders is increased exposure to environmental factors that modify gene function. Many environmental factors that have epidemiological association with common human disorders are likely to exert their effects through epigenetic alterations. This general mechanism of gene–environment interaction poses special challenges for individuals, educators, scientists and public policy makers in defining, monitoring and mitigating exposures. PMID:22920179

Classification and correlates of eating disorders among Blacks: findings from the National Survey of American Life.

PubMed

Taylor, Jacquelyn Y; Caldwell, Cleopatra Howard; Baser, Raymond E; Matusko, Niki; Faison, Nakesha; Jackson, James S

2013-02-01

To assess classification adjustments and examine correlates of eating disorders among Blacks. The National Survey of American Life (NSAL) was conducted from 2001-2003 and consisted of adults (n=5,191) and adolescents (n=1,170). The World Mental Health Composite International Diagnostic Interview (WMH-CIDI-World Health Organization 2004-modified) and DSM-IV-TR eating disorder criteria were used. Sixty-six percent of African American and 59% Caribbean Black adults were overweight or obese, while 30% and 29% of adolescents were overweight or obese. Although lifetime rates of anorexia nervosa and bulimia nervosa were low, binge eating disorder was high for both ethnic groups among adults and adolescents. Eliminating certain classification criteria resulted in higher rates of eating disorders for all groups. Culturally sensitive criteria should be incorporated into future versions of Diagnostic Statistical Manual (DSM) classifications for eating disorders that consider within-group ethnic variations.

Making Creative Drama Accessible to Handicapped Children.

ERIC Educational Resources Information Center

Warger, Cynthia L.

1985-01-01

A case study illustrates ways in which creative drama activities can be modified to foster accessibility for students with hearing impairments, orthopedic disabilities, visual problems, learning disabilities, mental retardation, and behavior disorders. (CL)

Pilot Study on the Effectiveness of Systematic Desensitization with Neurologically Impaired Children with Phobic Disorders

ERIC Educational Resources Information Center

Obler, Martin; Terwilliger, Robert F.

1970-01-01

A modified version of Wolpe's systematic desensitization therapy involving direct confrontation with the fear inducing stimulus was attempted with neurologically impaired children with phobic symptoms. (Author)

Neural correlates of the modified Stroop effect in post-traumatic stress disorder: an event-related potential study.

PubMed

Chen, Xiaoyi; Wei, Dongtao; Dupuis-Roy, Nicolas; Du, Xue; Qiu, Jiang; Zhang, Qinglin

2012-12-19

Previous studies have provided electrophysiological evidence for attentional abnormalities in patients with post-traumatic stress disorder (PTSD). The present study examined the electrophysiological activity of trauma-exposed patients with or without a PTSD during a modified Stroop task. The PTSD group showed a reduced P2 and P3 amplitude relative to the non-PTSD group under both the earthquake-related and earthquake-unrelated words conditions. Importantly, the earthquake-related words elicited a greater P3 amplitude (350-450 ms after stimulus) than did unrelated words in the non-PTSD group, whereas no significant difference was found in the PTSD group. This indicates that PTSD patients had some attention deficits compared with non-PTSD individuals, and that these attention deficits were not just limited to earthquake-related words.

SUMOylation in Neurological Diseases.

PubMed

Liu, F-Y; Liu, Y-F; Yang, Y; Luo, Z-W; Xiang, J-W; Chen, Z-G; Qi, R-L; Yang, T-H; Xiao, Y; Qing, W-J; Li, D W-C

2017-01-01

Since the discovery of SUMOs (small ubiquitin-like modifiers) over 20 years ago, sumoylation has recently emerged as an important posttranslational modification involved in almost all aspects of cellular physiology. In neurons, sumoylation dynamically modulates protein function and consequently plays an important role in neuronal maturation, synapse formation and plasticity. Thus, the dysfunction of sumoylation pathway is associated with many different neurological disorders. Hundreds of different proteins implicated in the pathogenesis of neurological disorders are SUMO-modified, indicating the importance of sumoylation involved in the neurological diseases. In this review, we summarize the growing findings on protein sumoylation in neuronal function and dysfunction. It is essential to have a thorough understanding on the mechanism how sumoylation contributes to neurological diseases in developing efficient therapy for these diseases. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Small-angle x-ray scattering from lipid bilayers is well described by modified Caillé theory but not by paracrystalline theory.

PubMed Central

Zhang, R; Tristram-Nagle, S; Sun, W; Headrick, R L; Irving, T C; Suter, R M; Nagle, J F

1996-01-01

X-ray scattering data at high instrumental resolution are reported for multilamellar vesicles of L alpha phase lipid bilayers of 1,2-dipalmitoyl-sn-glycero-3-phosphatidylcholine at 50 degrees C under varying osmotic pressure. The data are fitted to two theories that account for noncrystalline disorder, paracrystalline theory (PT) and modified Caillé theory (MCT). The MCT provides good fits to the data, much better than the PT fits. The particularly important characteristic of MCT is the long power law tails in the scattering. PT fits (as well as ordinary integration with no attempt to account for the noncrystalline disorder) increasingly underestimate this scattering intensity as the order h increases, thereby underestimating the form factors used to obtain electron density profiles. Images FIGURE 4 PMID:8770211

Behavior therapy and callous-unemotional traits: Effects of a pilot study examining modified behavioral contingencies on child behavior

PubMed Central

Miller, Natalie V.; Haas, Sarah M.; Waschbusch, Daniel A.; Willoughby, Michael T.; Helseth, Sarah A.; Crum, Kathleen I.; Coles, Erika K.; Pelham, William E.

2014-01-01

The conduct problems of children with callous-unemotional traits (i.e., lack of empathy, guilt/lack of caring behaviors) (CU) are particularly resistant to current behavioral interventions, and it is possible that differential sensitivities to punishment and reward may underlie this resistance. Children with conduct problems and CU (CPCU) are less responsive to behavioral punishment techniques (e.g., time-out), however reward techniques (e.g., earning points for prizes or activities) are effective for reducing conduct problems. This study examined the efficacy of modified behavioral interventions, which de-emphasized punishment (condition B) and emphasized reward techniques (condition C), compared to a standard behavioral intervention (condition A). Interventions were delivered through a Summer Treatment Program over seven weeks with an A-B-A-C-A-BC-A design to a group of eleven children (7–11 years; 91% male). All children were diagnosed with either oppositional defiant disorder or conduct disorder, in addition to attention-deficit/hyperactivity disorder. Results revealed the best treatment response occurred during the low punishment condition, with rates of negative behavior (e.g., aggression, teasing, stealing) increasing over the seven weeks. However, there was substantial individual variability in treatment response, and several children demonstrated improvement during the modified intervention conditions. Future research is necessary to disentangle treatment effects from order effects, and implications of group treatment of CPCU children (i.e., deviancy training) are discussed. PMID:25022772

Tryptophan hydroxylase 2 (TPH2) in a neuronal cell line: modulation by cell differentiation and NRSF/rest activity.

PubMed

Gentile, Maria Teresa; Nawa, Yukino; Lunardi, Gianluigi; Florio, Tullio; Matsui, Hiroaki; Colucci-D'Amato, Luca

2012-12-01

Serotonin (5-HT) is a neurotransmitter involved in many aspects of the neuronal function. The synthesis of 5-HT is initiated by the hydroxylation of tryptophan, catalyzed by tryptophan hydroxylase (TPH). Two isoforms of TPH (TPH1 and TPH2) have been identified, with TPH2 almost exclusively expressed in the brain. Following TPH2 discovery, it was reported that polymorphisms of both gene and non-coding regions are associated with a spectrum of psychiatric disorders. Thus, insights into the mechanisms that specifically regulate TPH2 expression and its modulation by exogenous stimuli may represent a new therapeutic approach to modify serotonergic neurotransmission. To this aim, a CNS-originated cell line expressing TPH2 endogenously represents a valid model system. In this study, we report that TPH2 transcript and protein are modulated by neuronal differentiation in the cell line A1 mes-c-myc (A1). Moreover, we show luciferase activity driven by the human TPH2 promoter region and demonstrate that upon mutation of the NRSF/REST responsive element, the promoter activity strongly increases with cell differentiation. Our data suggest that A1 cells could represent a model system, allowing an insight into the mechanisms of regulation of TPH2 and to identify novel therapeutic targets in the development of drugs for the management of psychiatric disorders. © 2012 The Authors Journal of Neurochemistry © 2012 International Society for Neurochemistry.

Congenital heart defects in newborns with apparently isolated single gastrointestinal malformation: A retrospective study.

PubMed

Schierz, Ingrid Anne Mandy; Pinello, Giuseppa; Giuffrè, Mario; La Placa, Simona; Piro, Ettore; Corsello, Giovanni

2016-12-01

Congenital gastrointestinal system malformations/abdominal wall defects (GISM) may appear as isolated defects (single or complex), or in association with multiple malformations. The high incidence of association of GISM and congenital heart defects (CHD) in patients with syndromes and malformative sequences is known, but less expected is the association of apparently isolated single GISM and CHD. The aim of this study was to investigate the frequency of CHD in newborns with isolated GISM, and the possibility to modify the diagnostic-therapeutic approach just before the onset of cardiac symptoms or complications. Anamnestic, clinical, and imaging data of newborns requiring abdominal surgery for GISM, between 2009 and 2014, were compared with a control group of healthy newborns. Distribution of GISM and cardiovascular abnormalities were analyzed, and risk factors for adverse outcomes were identified. Seventy-one newborns with isolated GISM were included in this study. More frequent GISM were intestinal rotation and fixation disorders. CHD were observed in 15.5% of patients, augmenting their risk for morbidity. Risk factors for morbidity related to sepsis were identified in central venous catheter, intestinal stoma, and H2-inhibitor-drugs. Moreover, 28.2% of newborns presented only functional cardiac disorders but an unexpectedly higher mortality. The high incidence of congenital heart disease in infants with apparently isolated GISM confirms the need to perform an echocardiographic study before surgery to improve perioperative management and prevent complications such as sepsis and endocarditis. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Effects of chemoradiotherapy on voice and swallowing

PubMed Central

Lazarus, Cathy L.

2009-01-01

Purpose of review Chemotherapy has been found to result in comparable survival rates to surgery for head and neck cancer. However, toxicity can often be worse after chemoradiotherapy, with impairment in voice, swallowing, nutrition, and quality of life. Investigators are attempting to modify radiotherapy treatment regimens to spare organs that have an impact on swallowing. This review will highlight voice and swallowing impairment seen after chemoradiotherapy, as well as treatment for voice and swallowing disorders in this population. Results of newer radiotherapy regimens will also be highlighted. Recent findings Specific oropharyngeal swallowing motility disorders after chemoradiotherapy have been identified. Damage to specific structures has been correlated with specific pharyngeal phase swallow impairment. Swallowing function and quality of life have been examined over time, with improvement seen in both. Preventive/prophylactic swallow exercise programs have been encouraging. Chemoradiotherapy effects on voice have been identified in terms of acoustic, aerodynamic, and patient and clinician-rated perception of function. Improvement in voice has also been observed over time after chemoradiotherapy. Voice therapy has been found to have a positive impact on voice and perceptual measures in this population. Summary Current studies show some improvement in swallow function after swallow and voice therapy in patients treated with chemoradiotherapy. Further, there is a suggestion of improved swallow function with sparing of organs with specific radiotherapy protocols. Future research needs to focus on specific voice and swallow treatment regimens in the head and neck cancer patient treated with chemoradiotherapy, specifically, timing, frequency, duration, and specific treatment types. PMID:19337126

Homozygous p.V116* mutation in C12orf65 results in Leigh syndrome.

PubMed

Imagawa, Eri; Fattal-Valevski, Aviva; Eyal, Ori; Miyatake, Satoko; Saada, Ann; Nakashima, Mitsuko; Tsurusaki, Yoshinori; Saitsu, Hirotomo; Miyake, Noriko; Matsumoto, Naomichi

2016-02-01

Leigh syndrome (LS) is an early-onset progressive neurodegenerative disorder associated with mitochondrial dysfunction. LS is characterised by elevated lactate and pyruvate and bilateral symmetric hyperintense lesions in the basal ganglia, thalamus, brainstem, cerebral white matter or spinal cord on T2-weighted MRI. LS is a genetically heterogeneous disease, and to date mutations in approximately 40 genes related to mitochondrial function have been linked to the disorder. We investigated a pair of female monozygotic twins diagnosed with LS from consanguineous healthy parents of Indian origin. Their common clinical features included optic atrophy, ophthalmoplegia, spastic paraparesis and mild intellectual disability. High-blood lactate and high-intensity signal in the brainstem on T2-weighted MRI were consistent with a clinical diagnosis of LS. To identify the genetic cause of their condition, we performed whole exome sequencing. We identified a homozygous nonsense mutation in C12orf65 (NM_001143905; c.346delG, p.V116*) in the affected twins. Interestingly, the identical mutation was previously reported in an Indian family with Charcot-Marie Tooth disease type 6, which displayed some overlapping clinical features with the twins. We demonstrate that the identical nonsense mutation in C12orf65 can result in different clinical features, suggesting the involvement of unknown modifiers. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

Social stressors and air pollution across New York City communities: a spatial approach for assessing correlations among multiple exposures.

PubMed

Shmool, Jessie L C; Kubzansky, Laura D; Newman, Ogonnaya Dotson; Spengler, John; Shepard, Peggy; Clougherty, Jane E

2014-11-06

Recent toxicological and epidemiological evidence suggests that chronic psychosocial stress may modify pollution effects on health. Thus, there is increasing interest in refined methods for assessing and incorporating non-chemical exposures, including social stressors, into environmental health research, towards identifying whether and how psychosocial stress interacts with chemical exposures to influence health and health disparities. We present a flexible, GIS-based approach for examining spatial patterns within and among a range of social stressors, and their spatial relationships with air pollution, across New York City, towards understanding their combined effects on health. We identified a wide suite of administrative indicators of community-level social stressors (2008-2010), and applied simultaneous autoregressive models and factor analysis to characterize spatial correlations among social stressors, and between social stressors and air pollutants, using New York City Community Air Survey (NYCCAS) data (2008-2009). Finally, we provide an exploratory ecologic analysis evaluating possible modification of the relationship between nitrogen dioxide (NO2) and childhood asthma Emergency Department (ED) visit rates by social stressors, to demonstrate how the methods used to assess stressor exposure (and/or consequent psychosocial stress) may alter model results. Administrative indicators of a range of social stressors (e.g., high crime rate, residential crowding rate) were not consistently correlated (rho = - 0.44 to 0.89), nor were they consistently correlated with indicators of socioeconomic position (rho = - 0.54 to 0.89). Factor analysis using 26 stressor indicators suggested geographically distinct patterns of social stressors, characterized by three factors: violent crime and physical disorder, crowding and poor access to resources, and noise disruption and property crimes. In an exploratory ecologic analysis, these factors were differentially associated with area-average NO2 and childhood asthma ED visits. For example, only the 'violent crime and disorder' factor was significantly associated with asthma ED visits, and only the 'crowding and resource access' factor modified the association between area-level NO2 and asthma ED visits. This spatial approach enabled quantification of complex spatial patterning and confounding between chemical and non-chemical exposures, and can inform study design for epidemiological studies of separate and combined effects of multiple urban exposures.

Ethnicity, Socioeconomic Status, and Health Disparities in a Mixed Rural-Urban US Community-Olmsted County, Minnesota.

PubMed

Wi, Chung-Il; St Sauver, Jennifer L; Jacobson, Debra J; Pendegraft, Richard S; Lahr, Brian D; Ryu, Euijung; Beebe, Timothy J; Sloan, Jeff A; Rand-Weaver, Jennifer L; Krusemark, Elizabeth A; Choi, YuBin; Juhn, Young J

2016-05-01

To characterize health disparities in common chronic diseases among adults by socioeconomic status (SES) and ethnicity in a mixed rural-urban community of the United States. We conducted a cross-sectional study to assess the association of the prevalence of the 5 most burdensome chronic diseases in adults with SES and ethnicity and their interaction. The Rochester Epidemiology Project medical records linkage system was used to identify the prevalence of coronary heart disease, asthma, diabetes, hypertension, and mood disorder using International Classification of Diseases, Ninth Revision codes recorded from January 1, 2005, through December 31, 2009, among all adult residents of Olmsted County, Minnesota, on April 1, 2009. For SES measurements, an individual HOUsing-based index of SocioEconomic Status (HOUSES) derived from real property data was used. Logistic regression models were used to examine the association of the prevalence of chronic diseases with ethnicity and HOUSES score and their interaction. We identified 88,010 eligible adults with HOUSES scores available, of whom 48,086 (54.6%) were female and 80,699 (91.7%) were non-Hispanic white; the median (interquartile range) age was 45 years (30-58 years). Overall and in the subgroup of non-Hispanic whites, SES measured by HOUSES was inversely associated with the prevalence of all 5 chronic diseases independent of age, sex, and ethnicity (P<.001). While an association of ethnicity with disease prevalence was observed for all the chronic diseases, SES modified the effect of ethnicity for clinically less overt conditions (interaction P<.05 for each condition [diabetes, hypertension, and mood disorder]) but not for coronary heart disease, a clinically more overt condition. In a mixed rural-urban setting with a predominantly non-Hispanic white population, health disparities in chronic diseases still exist across SES. The extent to which SES modifies the effect of ethnicity on the risk of chronic diseases may depend on the nature of the disease. Copyright © 2016 Mayo Foundation for Medical Education and Research. Published by Elsevier Inc. All rights reserved.

Can personality traits predict increases in manic and depressive symptoms?

PubMed

Lozano, B E; Johnson, S L

2001-03-01

There has been limited research investigating personality traits as predictors of manic and depressive symptoms in bipolar individuals. The present study investigated the relation between personality traits and the course of bipolar disorder. The purpose of this study was to identify specific personality traits that predict the course of manic and depressive symptoms experienced by bipolar individuals. The sample consisted of 39 participants with bipolar I disorder assessed by the Structured Clinical Interview for DSM-IV. Personality was assessed using the NEO Five-Factor Inventory. The Modified Hamilton Rating Scale for Depression and the Bech-Rafaelsen Mania Rating Scale were used to assess symptom severity on a monthly basis. Consistent with previous research on unipolar depression, high Neuroticism predicted increases in depressive symptoms across time while controlling for baseline symptoms. Additionally, high Conscientiousness, particularly the Achievement Striving facet, predicted increases in manic symptoms across time. The current study was limited by the small number of participants, the reliance on a shortened version of a self-report personality measure, and the potential state-dependency of the personality measures. Specific personality traits may assist in predicting bipolar symptoms across time. Further studies are needed to tease apart the state-dependency of personality.

An update on anxiety in youth with autism spectrum disorders

PubMed Central

Vasa, Roma A.; Mazurek, Micah O.

2017-01-01

Purpose of review Anxiety is one of the most common co-occurring psychiatric conditions in youth with autism spectrum disorders (ASDs). This article reviews recent evidence as well as earlier relevant studies regarding the characteristics, assessment, and treatment of anxiety in youth with ASD. Recent findings It is well established that the prevalence of anxiety in youth with an ASD is significantly greater than the prevalence of anxiety in the general population. Recent studies have highlighted the importance of informant, method, and instrument when measuring anxiety in this population. Despite the high prevalence, findings to date have been unable to identify any consistent risk factors for anxiety. New psychological treatments, including modified cognitive behavioral therapy for youth with high functioning ASD and co-occurring anxiety, are emerging. Pharmacological data, however, are scant. Existing studies show that youth with ASD are at increased risk for behavioral activation when taking SSRIs. Summary Clinicians working with youth with ASD are encouraged to routinely screen for anxiety. Until further data are available, clinical judgment is needed when prescribing treatments, particularly selective serotonin reuptake inhibitors, which require close monitoring of side-effects. Research on risk factors, pathophysiology, and treatment of this condition is needed. PMID:25602249

Vitamin D and Autism Spectrum Disorder: A Literature Review

PubMed Central

Mazahery, Hajar; Camargo, Carlos A.; Conlon, Cathryn; Beck, Kathryn L.; Kruger, Marlena C.; von Hurst, Pamela R.

2016-01-01

Low vitamin D status in early development has been hypothesised as an environmental risk factor for Autism Spectrum Disorder (ASD), given the concurrent increase in the prevalence of these two conditions, and the association of vitamin D with many ASD-associated medical conditions. Identification of vitamin D-ASD factors may provide indications for primary and secondary prevention interventions. We systematically reviewed the literature for studies on vitamin D-ASD relationship, including potential mechanistic pathways. We identified seven specific areas, including: latitude, season of conception/birth, maternal migration/ethnicity, vitamin D status of mothers and ASD patients, and vitamin D intervention to prevent and treat ASD. Due to differences in the methodological procedures and inconsistent results, drawing conclusions from the first three areas is difficult. Using a more direct measure of vitamin D status—that is, serum 25(OH)D level during pregnancy or childhood—we found growing evidence for a relationship between vitamin D and ASD. These findings are supported by convincing evidence from experimental studies investigating the mechanistic pathways. However, with few primary and secondary prevention intervention trials, this relationship cannot be determined, unless randomised placebo-controlled trials of vitamin D as a preventive or disease-modifying measure in ASD patients are available. PMID:27110819

Examination of the Inventory of Drug Use Consequences with Individuals with Serious and Persistent Mental Illness and Co-occurring Substance Use Disorders

PubMed Central

Bennett, Melanie E.; Nidecker, Melissa; Kinnaman, Joanna E. Strong; Li, Lan; Bellack, Alan S.

2015-01-01

Background The Inventory of Drug Use Consequences (InDUC) (1) is a 50-item measure that evaluates lifetime and recent consequences of substance use. Objectives This study examined the psychometric properties of a modified version of the Inventory of Drug Use Consequences (InDUC-M) in individuals with serious and persistent mental illness and cooccurring substance use disorders. Methods We examined self-reported consequences in the sample, evaluated internal consistency, identified items for a brief form of the InDUC-M, and explored relationships with indicators of substance use severity. Results InDUC-M Lifetime and Recent subscales showed good internal consistency and were related to other measures of substance use and problems. A brief version of the InDUC-M Recent showed excellent internal consistency and was highly correlated with both Lifetime and Recent subscales. Conclusion The InDUC-M and the SIP-M performed well in individuals with SPMI and SUDs. Scientific Significance Overall, these findings are a useful first step in determining the utility of the InDUC-M in people with SPMI and SUDs. PMID:20180669

Empirical testing of criteria for dissociative schizophrenia.

PubMed

Laferrière-Simard, Marie-Christine; Lecomte, Tania; Ahoundova, Lola

2014-01-01

This study examined the validity of dissociative schizophrenia diagnostic criteria. In the first phase, 50 participants with a psychotic disorder were administered the Dissociative Experiences Scale and the Childhood Trauma Questionnaire to identify those with dissociative characteristics. In the second phase, we selected those who had a score of 15 or above on the Dissociative Experiences Scale. Fifteen of these participants were evaluated thoroughly with the Structured Clinical Interview for DSM-IV Axis I, Structured Clinical Interview for DSM-IV Axis II, and Structured Clinical Interview for DSM-IV Dissociative Disorders to determine whether they met the criteria for dissociative schizophrenia and to generate a clinical description. Our results indicated that 24% of the individuals we tested met these criteria. We propose making mandatory 1 of the 3 dissociative symptoms of the criteria to eliminate people with only nonspecific symptoms (e.g., extensive comorbidity). According to this modified criterion, 14% of our sample would receive a diagnosis of dissociative schizophrenia. However, a more comprehensive look at the clinical picture begs the question of whether dissociative schizophrenia is truly present in every person meeting the criteria. We discuss the relevance of creating a new schizophrenia subtype and offer recommendations for clinicians.

Novel therapy in Parkinson's disease: adenosine A(2A) receptor antagonists.

PubMed

Szabó, Nikoletta; Kincses, Zsigmond Tamás; Vécsei, László

2011-04-01

Parkinson's disease (PD) is a progressive neurodegenerative disorder. To date, most of the currently available therapies in PD target the dopaminergic system and none of these therapeutic approaches have been proven to modify the course of the disease. To various extents, these drugs can also cause motor and non-motor complications. A novel target, the adenosine A(2A) receptor (AA2AR), was recently identified, blockade of which may alleviate Parkinsonian symptoms, reduce motor fluctuations and potentially afford neuroprotection. This review is based on a PubMed search covering the relationship of the adenosine receptors and PD. The role of the AA2AR is reviewed and the results of preclinical investigations of antagonists are assessed. A synopsis of current drug development is provided, with a special focus on the pharmacokinetics and relevant clinical trials. The localization of the AA2AR in the central nervous system, the ultra structural localization and the molecular mechanism of its action reveal the potential importance of the AA2AR in movement disorders. The theoretical background and experimental data indicate that AA2AR antagonists may have a potential therapeutic effect in Parkinson's disease. More importantly, the putative neuroprotective effect needs further investigation.

Major depressive disorder is characterized by greater reward network activation to monetary than pleasant image rewards

PubMed Central

Smoski, Moria J.; Rittenberg, Alison; Dichter, Gabriel S.

2011-01-01

Anhedonia, the loss of interest or pleasure in normally rewarding activities, is a hallmark feature of unipolar Major Depressive Disorder (MDD). A growing body of literature has identified frontostriatal dysfunction during reward anticipation and outcomes in MDD. However, no study to date has directly compared responses to different types of rewards such as pleasant images and monetary rewards in MDD. To investigate the neural responses to monetary and pleasant image rewards in MDD, a modified Monetary Incentive Delay task was used during fMRI scanning to assess neural responses during anticipation and receipt of monetary and pleasant image rewards. Participants included nine adults with MDD and thirteen affectively healthy controls. The MDD group showed lower activation than controls when anticipating monetary rewards in right orbitofrontal cortex and subcallosal cortex, and when anticipating pleasant image rewards in paracingulate and supplementary motor cortex. The MDD group had relatively greater activation in right putamen when anticipating monetary versus pleasant image rewards, relative to the control group. Results suggest reduced reward network activation in MDD when anticipating rewards, as well as relatively greater hypoactivation to pleasant image than monetary rewards. PMID:22079658

Major depressive disorder is characterized by greater reward network activation to monetary than pleasant image rewards.

PubMed

Smoski, Moria J; Rittenberg, Alison; Dichter, Gabriel S

2011-12-30

Anhedonia, the loss of interest or pleasure in normally rewarding activities, is a hallmark feature of unipolar Major Depressive Disorder (MDD). A growing body of literature has identified frontostriatal dysfunction during reward anticipation and outcomes in MDD. However, no study to date has directly compared responses to different types of rewards such as pleasant images and monetary rewards in MDD. To investigate the neural responses to monetary and pleasant image rewards in MDD, a modified Monetary Incentive Delay task was used during functional magnetic resonance imaging to assess neural responses during anticipation and receipt of monetary and pleasant image rewards. Participants included nine adults with MDD and 13 affectively healthy controls. The MDD group showed lower activation than controls when anticipating monetary rewards in right orbitofrontal cortex and subcallosal cortex, and when anticipating pleasant image rewards in paracingulate and supplementary motor cortex. The MDD group had relatively greater activation in right putamen when anticipating monetary versus pleasant image rewards, relative to the control group. Results suggest reduced reward network activation in MDD when anticipating rewards, as well as relatively greater hypoactivation to pleasant image than monetary rewards. 2011 Elsevier Ireland Ltd. All rights reserved.

Enigmatic insight into collagen

PubMed Central

Deshmukh, Shrutal Narendra; Dive, Alka M; Moharil, Rohit; Munde, Prashant

2016-01-01

Collagen is a unique, triple helical molecule which forms the major part of extracellular matrix. It is the most abundant protein in the human body, representing 30% of its dry weight. It is the fibrous structural protein that makes up the white fibers (collagen fibers) of skin, tendons, bones, cartilage and all other connective tissues. Collagens are not only essential for the mechanical resistance and resilience of multicellular organisms, but are also signaling molecules defining cellular shape and behavior. The human body has at least 16 types of collagen, but the most prominent types are I, II and III. Collagens are produced by several cell types and are distinguishable by their molecular compositions, morphologic characteristics, distribution, functions and pathogenesis. This is the major fibrous glycoprotein present in the extracellular matrix and in connective tissue and helps in maintaining the structural integrity of these tissues. It has a triple helical structure. Various studies have proved that mutations that modify folding of the triple helix result in identifiable genetic disorders. Collagen diseases share certain similarities with autoimmune diseases, because autoantibodies specific to each collagen disease are produced. Therefore, this review highlights the role of collagen in normal health and also the disorders associated with structural and functional defects in collagen. PMID:27601823

Noise and autism spectrum disorder in children: An exploratory survey.

PubMed

Kanakri, Shireen M; Shepley, Mardelle; Varni, James W; Tassinary, Louis G

2017-04-01

With more students being educated in schools for Autism Spectrum Disorder (ASD) than ever before, architects and interior designers need to consider the environmental features that may be modified to enhance the academic and social success of autistic students in school. This study explored existing empirical research on the impact of noise on children with ASD and provides recommendations regarding design features that can contribute to noise reduction. A survey, which addressed the impact of architectural design elements on autism-related behavior, was developed for teachers of children with ASD and distributed to three schools. Most teachers found noise control to be an important issue for students with autism and many observed children using ear defenders. In terms of managing issues related to noise, most teachers agreed that thick or soundproof walls and carpet in the classroom were the most important issues for children with ASD. Suggested future research should address architectural considerations for building an acoustically friendly environment for children with autism, identifying patterns of problematic behaviors in response to acoustical features of the built environment of the classroom setting, and ways to manage maladaptive behaviors in acoustically unfriendly environments. Copyright © 2017 Elsevier Ltd. All rights reserved.

On the qi deficiency in traditional Chinese medicine.

PubMed

Chiang, Hui-Chu; Chang, Hen-Hong; Huang, Po-Yu; Hsu, Mutsu

2014-09-01

Qi deficiency (QD), one of the most common disorders in Traditional Chinese medicine (TCM), is relevant to many disorders in obstetrics and gynecology. This study aimed to identify the common processes and criteria for diagnosing QD among contemporary proficient TCM practitioners. Steps of decision tree analysis and modified Delphi method were merged together into four-round postal questionnaires to collect qualitative and quantitative data. Open-ended questions and content analysis were used to explore the proficient TCM practitioners' cognitive activities used for diagnosis. The statements obtained from the qualitative responses were used to develop the items for subsequent questionnaires. Based on the TCM practitioners' responses, the diagnostic processes and criteria for making diagnosis were generated. Twenty-eight out of the 30 participants completed all four questionnaires from June 2007 to January 2010. The 11 diagnostic procedures identified in the returned first round of questionnaires were used as the alternatives to select and rank for all the steps to diagnose QD. After three more rounds of postal surveys, an algorithm with a five-stage diagnostic process as well as sets of decision criteria were identified. Although the priorities of procedures and descriptions of reasoning were varied, the content revealed the major themes in the model. The criteria to differentiate signs and symptoms (S/S) included five principles for correlating S/S with QD, and 17 S/S should be differentiated carefully. The results demonstrate that the TCM practitioners precisely diagnosed QD using a number of specific procedures and criteria that could be used as a reference to understand women complaining of S/S that could be similar to QD. Copyright © 2014. Published by Elsevier B.V.

The Effect of the Hemochromatosis (HFE) Genotype on Lead Load and Iron Metabolism among Lead Smelter Workers

PubMed Central

Fan, Guangqin; Du, Guihua; Li, Huijun; Lin, Fen; Sun, Ziyong; Yang, Wei; Feng, Chang; Zhu, Gaochun; Li, Yanshu; Chen, Ying; Jiao, Huan; Zhou, Fankun

2014-01-01

Background Both an excess of toxic lead (Pb) and an essential iron disorder have been implicated in many diseases and public health problems. Iron metabolism genes, such as the hemochromatosis (HFE) gene, have been reported to be modifiers for lead absorption and storage. However, the HFE gene studies among the Asian population with occupationally high lead exposure are lacking. Objectives To explore the modifying effects of the HFE genotype (wild-type, H63D variant and C282Y variant) on the Pb load and iron metabolism among Asian Pb-workers with high occupational exposure. Methods Seven hundred and seventy-one employees from a lead smelter manufacturing company were tested to determine their Pb intoxication parameters, iron metabolic indexes and identify the HFE genotype. Descriptive and multivariate analyses were conducted. Results Forty-five H63D variant carriers and no C282Y variant carrier were found among the 771 subjects. Compared with subjects with the wild-type genotype, H63D variant carriers had higher blood lead levels, even after controlling for factors such as age, sex, marriage, education, smoking and lead exposure levels. Multivariate analyses also showed that the H63D genotype modifies the associations between the blood lead levels and the body iron burden/transferrin. Conclusions No C282Y variant was found in this Asian population. The H63D genotype modified the association between the lead and iron metabolism such that increased blood lead is associated with a higher body iron content or a lower transferrin in the H63D variant. It is indicated that H63D variant carriers may be a potentially highly vulnerable sub-population if they are exposed to high lead levels occupationally. PMID:24988074

The effect of the hemochromatosis (HFE) genotype on lead load and iron metabolism among lead smelter workers.

PubMed

Fan, Guangqin; Du, Guihua; Li, Huijun; Lin, Fen; Sun, Ziyong; Yang, Wei; Feng, Chang; Zhu, Gaochun; Li, Yanshu; Chen, Ying; Jiao, Huan; Zhou, Fankun

2014-01-01

Both an excess of toxic lead (Pb) and an essential iron disorder have been implicated in many diseases and public health problems. Iron metabolism genes, such as the hemochromatosis (HFE) gene, have been reported to be modifiers for lead absorption and storage. However, the HFE gene studies among the Asian population with occupationally high lead exposure are lacking. To explore the modifying effects of the HFE genotype (wild-type, H63D variant and C282Y variant) on the Pb load and iron metabolism among Asian Pb-workers with high occupational exposure. Seven hundred and seventy-one employees from a lead smelter manufacturing company were tested to determine their Pb intoxication parameters, iron metabolic indexes and identify the HFE genotype. Descriptive and multivariate analyses were conducted. Forty-five H63D variant carriers and no C282Y variant carrier were found among the 771 subjects. Compared with subjects with the wild-type genotype, H63D variant carriers had higher blood lead levels, even after controlling for factors such as age, sex, marriage, education, smoking and lead exposure levels. Multivariate analyses also showed that the H63D genotype modifies the associations between the blood lead levels and the body iron burden/transferrin. No C282Y variant was found in this Asian population. The H63D genotype modified the association between the lead and iron metabolism such that increased blood lead is associated with a higher body iron content or a lower transferrin in the H63D variant. It is indicated that H63D variant carriers may be a potentially highly vulnerable sub-population if they are exposed to high lead levels occupationally.

Prevalence of Autism Spectrum Disorders in Siblings of Indian Children With Autism Spectrum Disorders.

PubMed

Kumar, Ankur; Juneja, Monica; Mishra, Devendra

2016-06-01

This study determined the prevalence of autism spectrum disorders in 201 siblings of children with autism spectrum disorders. Siblings were screened using Modified Checklist for Autism in Toddlers and Social Responsiveness Scale, parent version. Screen-positive siblings were assessed using Diagnostic and Statistical Manual of Mental Disorders (Fourth Edition) criteria. The risk of autism spectrum disorder in siblings was correlated with various familial and disease characteristics of the index case. Prevalence of autism spectrum disorder in siblings was 4.97%. There was a significant effect of the presence of aggressive behavior, externalizing problems and total problems in the proband, assessed using Childhood Behavior Checklist, and the young age of the father at conception on sibling risk of autism spectrum disorder. Results of our study are in line with previous studies reporting similar prevalence but have also brought up the association with behavioral problems as a possible risk factor. Siblings of children with autism spectrum disorder should be routinely screened, and genetic counseling for this increased risk should be explained to the family. © The Author(s) 2016.

Rare variants and cardiovascular disease.

PubMed

Wain, Louise V

2014-09-01

Cardiovascular disease (CVD) is a leading cause of mortality and morbidity in the Western world. Large genome-wide association studies (GWASs) of coronary artery disease, myocardial infarction, stroke and dilated cardiomyopathy have identified a number of common genetic variants with modest effects on disease risk. Similarly, studies of important modifiable risk factors of CVD have identified a large number of predominantly common variant associations, for example, with blood pressure and blood lipid levels. In each case, despite the often large numbers of loci identified, only a small proportion of the phenotypic variance is explained. It has been hypothesised that rare variants with large effects may account for some of the missing variance but large-scale studies of rare variation are in their infancy for cardiovascular traits and have yet to produce fruitful results. Studies of monogenic CVDs, inherited disorders believed to be entirely driven by individual rare mutations, have highlighted genes that play a key role in disease aetiology. In this review, we discuss how findings from studies of rare variants in monogenic disease and GWAS of predominantly common variants are converging to provide further insight into biological disease mechanisms. © The Author 2014. Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.

Exome sequencing identifies CTSK mutations in patients originally diagnosed as intermediate osteopetrosis☆

PubMed Central

Pangrazio, Alessandra; Puddu, Alessandro; Oppo, Manuela; Valentini, Maria; Zammataro, Luca; Vellodi, Ashok; Gener, Blanca; Llano-Rivas, Isabel; Raza, Jamal; Atta, Irum; Vezzoni, Paolo; Superti-Furga, Andrea; Villa, Anna; Sobacchi, Cristina

2014-01-01

Autosomal Recessive Osteopetrosis is a genetic disorder characterized by increased bone density due to lack of resorption by the osteoclasts. Genetic studies have widely unraveled the molecular basis of the most severe forms, while cases of intermediate severity are more difficult to characterize, probably because of a large heterogeneity. Here, we describe the use of exome sequencing in the molecular diagnosis of 2 siblings initially thought to be affected by “intermediate osteopetrosis”, which identified a homozygous mutation in the CTSK gene. Prompted by this finding, we tested by Sanger sequencing 25 additional patients addressed to us for recessive osteopetrosis and found CTSK mutations in 4 of them. In retrospect, their clinical and radiographic features were found to be compatible with, but not typical for, Pycnodysostosis. We sought to identify modifier genes that might have played a role in the clinical manifestation of the disease in these patients, but our results were not informative. In conclusion, we underline the difficulties of differential diagnosis in some patients whose clinical appearance does not fit the classical malignant or benign picture and recommend that CTSK gene be included in the molecular diagnosis of high bone density conditions. PMID:24269275

JointMMCC: Joint Maximum-Margin Classification and Clustering of Imaging Data

PubMed Central

Filipovych, Roman; Resnick, Susan M.; Davatzikos, Christos

2012-01-01

A number of conditions are characterized by pathologies that form continuous or nearly-continuous spectra spanning from the absence of pathology to very pronounced pathological changes (e.g., normal aging, Mild Cognitive Impairment, Alzheimer's). Moreover, diseases are often highly heterogeneous with a number of diagnostic subcategories or subconditions lying within the spectra (e.g., Autism Spectrum Disorder, schizophrenia). Discovering coherent subpopulations of subjects within the spectrum of pathological changes may further our understanding of diseases, and potentially identify subconditions that require alternative or modified treatment options. In this paper, we propose an approach that aims at identifying coherent subpopulations with respect to the underlying MRI in the scenario where the condition is heterogeneous and pathological changes form a continuous spectrum. We describe a Joint Maximum-Margin Classification and Clustering (JointMMCC) approach that jointly detects the pathologic population via semi-supervised classification, as well as disentangles heterogeneity of the pathological cohort by solving a clustering subproblem. We propose an efficient solution to the non-convex optimization problem associated with JointMMCC. We apply our proposed approach to an MRI study of aging, and identify coherent subpopulations (i.e., clusters) of cognitively less stable adults. PMID:22328179

A model for diagnosing and explaining multiple disorders.

PubMed

Jamieson, P W

1991-08-01

The ability to diagnose multiple interacting disorders and explain them in a coherent causal framework has only partially been achieved in medical expert systems. This paper proposes a causal model for diagnosing and explaining multiple disorders whose key elements are: physician-directed hypotheses generation, object-oriented knowledge representation, and novel explanation heuristics. The heuristics modify and link the explanations to make the physician aware of diagnostic complexities. A computer program incorporating the model currently is in use for diagnosing peripheral nerve and muscle disorders. The program successfully diagnoses and explains interactions between diseases in terms of underlying pathophysiologic concepts. The model offers a new architecture for medical domains where reasoning from first principles is difficult but explanation of disease interactions is crucial for the system's operation.

Nucleation versus percolation: Scaling criterion for failure in disordered solids

NASA Astrophysics Data System (ADS)

Biswas, Soumyajyoti; Roy, Subhadeep; Ray, Purusattam

2015-05-01

One of the major factors governing the mode of failure in disordered solids is the effective range R over which the stress field is modified following a local rupture event. In a random fiber bundle model, considered as a prototype of disordered solids, we show that the failure mode is nucleation dominated in the large system size limit, as long as R scales slower than Lζ, with ζ =2 /3 . For a faster increase in R , the failure properties are dominated by the mean-field critical point, where the damages are uncorrelated in space. In that limit, the precursory avalanches of all sizes are obtained even in the large system size limit. We expect these results to be valid for systems with finite (normalizable) disorder.

Disturbed sleep: linking allergic rhinitis, mood and suicidal behavior.

PubMed

Fang, Beverly J; Tonelli, Leonardo H; Soriano, Joseph J; Postolache, Teodor T

2010-01-01

Allergic inflammation is associated with mood disorders, exacerbation of depression, and suicidal behavior. Mediators of inflammation modulate sleep , with Th1 cytokines promoting NREM sleep and increasing sleepiness and Th2 cytokines (produced during allergic inflammation) impairing sleep. As sleep impairment is a rapidly modifiable suicide risk factor strongly associated with mood disorders, we review the literature leading to the hypothesis that allergic rhinitis leads to mood and anxiety disorders and an increased risk of suicide via sleep impairment. Specifically, allergic rhinitis can impair sleep through mechanical (obstructive) and molecular (cytokine production) processes. The high prevalence of mood and anxiety disorders and allergy, the nonabating suicide incidence, the currently available treatment modalities to treat sleep impairment and the need for novel therapeutic targets for mood and anxiety disorders, justify multilevel efforts to explore disturbance of sleep as a pathophysiological link.

Self-reported utilization of mental health services in the adult German population--evidence for unmet needs? Results of the DEGS1-Mental Health Module (DEGS1-MH).

PubMed

Mack, Simon; Jacobi, Frank; Gerschler, Anja; Strehle, Jens; Höfler, Michael; Busch, Markus A; Maske, Ulrike E; Hapke, Ulfert; Seiffert, Ingeburg; Gaebel, Wolfgang; Zielasek, Jürgen; Maier, Wolfgang; Wittchen, Hans-Ulrich

2014-09-01

This paper provides up-to-date data on service use for mental health problems and disorders among adults aged 18-79 years in Germany derived from the Mental Health Module of the German Health Interview and Examination Survey for Adults (DEGS1-MH; N=4483). Data are based exclusively on self-report. Respondents were examined by clinically trained interviewers with a modified version of the Composite International Diagnostic Interview DIA-X/M-CIDI to assess diagnoses according to the criteria of DSM-IV-TR. Service use, i.e. contact to mental health care services, due to mental health problems was assessed for the past 12 months and lifetime, by type of sector and type of institution. Among respondents with a 12-month diagnosis of a mental disorder, 23.5% of the women and 11.6% of the men reported any service use in the past 12 months. Service use depends on type of diagnosis, comorbidity and socio-demographic characteristics. Lowest 12-month utilization rates were found for substance use disorders (15.6%; lifetime use 37.3%), highest for psychotic disorders (40.5%; lifetime 72.1%). Further, a considerable time lap was found between disorder onset and subsequent service use among the majority of cases with anxiety and mood disorders. This paper provides self-reported epidemiological data on mental health service use in Germany, complementing administrative statistics and the predecessor mental health module of the German Health Interview and Examination Survey (GHS-MHS) from 1998. Despite considerable changes in the mental health field in Germany and the existence of a comprehensive mental health care system without major financial barriers, we find no indications of substantially higher utilization rates for mental disorders as compared to other comparable European countries. Further, no indications of major overall changes in utilization rates are apparent. To pinpoint areas with unmet needs, more detailed analyses of the data are needed taking into account type, frequency, and adequacy of service use and treatment of mental disorders. Appropriately matched comparisons with the GHS-MHS are needed to identify changes in patterns of utilization and interventions by type of disorder. Copyright © 2014 John Wiley & Sons, Ltd.

Chemically and compositionally modified solid solution disordered multiphase nickel hydroxide positive electrode for alkaline rechargeable electrochemical cells

DOEpatents

Ovshinsky, Stanford R.; Corrigan, Dennis; Venkatesan, Srini; Young, Rosa; Fierro, Christian; Fetcenko, Michael A.

1994-01-01

A high capacity, long cycle life positive electrode for use in an alkaline rechargeable electrochemical cell comprising: a solid solution nickel hydroxide material having a multiphase structure that comprises at least one polycrystalline .gamma.-phase including a polycrystalline .gamma.-phase unit cell comprising spacedly disposed plates with at least one chemical modifier incorporated around the plates, the plates having a range of stable intersheet distances corresponding to a 2.sup.+ oxidation state and a 3.5.sup.+, or greater, oxidation state; and at least one compositional modifier incorporated into the solid solution nickel hydroxide material to promote the multiphase structure.

PHYSICAL ACTIVITY AND THE PELVIC FLOOR

PubMed Central

Nygaard, Ingrid E.; Shaw, Janet M.

2015-01-01

Pelvic floor disorders (PFDs) are common, with one in four U.S. women reporting moderate to severe symptoms of urinary incontinence, pelvic organ prolapse or fecal incontinence. Given the high societal burden of these disorders, identifying potentially modifiable risk factors is crucial. Physical activity is one such potentially modifiable risk factor; the large number of girls and women participating in sport and strenuous training regimens increases the need to understand associated risks and benefits of these exposures. The aim of this review is to summarize studies reporting the association between physical activity and PFDs. Most studies are cross-sectional and most include small numbers of participants. The primary findings of this review include: Urinary incontinence during exercise is common and is more prevalent in women during high-impact sports. Mild to moderate physical activity, such as brisk walking, decreases both the odds of having and the risk of developing urinary incontinence. In older women, mild to moderate activity also decreases the odds of having fecal incontinence; however, young women participating in high intensity activity are more likely to report anal incontinence than less active women. Scant data suggest that in middle-aged women, lifetime physical activity increases the odds of stress urinary incontinence slightly and does not increase the odds of pelvic organ prolapse. Women undergoing surgery for pelvic organ prolapse are more likely to report a history of heavy work than controls; however, women recruited from the community with pelvic organ prolapse on examination report similar lifetime levels of strenuous activity as women without this exam finding. Data are insufficient to determine whether strenuous activity while young predisposes to pelvic floor disorders later in life. The existing literature suggests that most physical activity does not harm the pelvic floor and does provide numerous health benefits for women. However, future research is needed to fill the many gaps in our knowledge. Prospective studies are needed in all populations, including potentially vulnerable women, such as those with high genetic risk, levator ani muscle injury, or asymptomatic pelvic organ prolapse, and on women during potentially vulnerable life periods, such as the early postpartum or postoperative periods. PMID:26348380

Risk factor modifications and depression incidence: a 4-year longitudinal Canadian cohort of the Montreal Catchment Area Study.

PubMed

Meng, Xiangfei; Brunet, Alain; Turecki, Gustavo; Liu, Aihua; D'Arcy, Carl; Caron, Jean

2017-06-10

Few studies have examined the effect of risk factor modifications on depression incidence. This study was to explore psychosocial risk factors for depression and quantify the effect of risk factor modifications on depression incidence in a large-scale, longitudinal population-based study. Data were from the Montreal Longitudinal Catchment Area study (N=2433). Multivariate modified Poisson regression was used to estimate relative risk (RR). Population attributable fractions were also used to estimate the potential impact of risk factor modifications on depression incidence. The cumulative incidence rate of major depressive disorder at the 2-year follow-up was 4.8%, and 6.6% at the 4-year follow-up. Being a younger adult, female, widowed, separated or divorced, Caucasian, poor, occasional drinker, having a family history of mental health problems, having less education and living in areas with higher unemployment rates and higher proportions of visible minorities, more cultural community centres and community organisations, were consistently associated with the increased risk of incident major depressive disorder. Although only 5.1% of the disease incidence was potentially attributable to occasional drinking (vs abstainers) at the 2-year follow-up, the attribution of occasional drinking doubled at the 4-year follow-up. A 10% reduction in the prevalence of occasional drinking in this population could potentially prevent half of incident cases. Modifiable risk factors, both individual and societal, could be the targets for public depression prevention programmes. These programmes should also be gender-specific, as different risk factors have been identified for men and women. Public health preventions at individual levels could focus on the better management of occasional drinking, as it explained around 5%~10% of incident major depressive disorders. Neighbourhood characteristics could also be the target for public prevention programmes. However, this could be very challenging. A cost-effectiveness analysis of a variety of prevention efforts is warranted. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Protocol for development and validation of a context-appropriate tool for assessing organisational readiness for change in primary health clinics in South Africa.

PubMed

Brooke-Sumner, Carrie; Sorsdahl, Katherine; Lombard, Carl; Petersen-Williams, Petal; Myers, Bronwyn

2018-04-09

A large treatment gap for common mental disorders (such as depression) exists in South Africa. Comorbidity with other chronic diseases, including HIV and diseases of lifestyle, is an increasing public health concern globally. Currently, primary health facilities as points of care for those with chronic disease provide limited services for common mental disorders. Assessing organisational readiness for change (ORC) towards adopting health innovations (such as mental health services) using contextually appropriate measures is needed to facilitate implementation of these services. This study aims to investigate the validity of the Texas Christian University Organisational Readiness for Change (TCU-ORC) scale in the South African context. Subsequently, we will develop a shortened version of this scale. This study is nested within Project MIND, a multiyear randomised controlled trial that is testing two different approaches for integrating counselling for common mental disorders into chronic disease care. Although the modified, contextually appropriate ORC measure resulting from the proposed study will be developed in the context of integrating mental health into primary healthcare services, the potential for the tool to be generalised to further understanding barriers to any change being implemented in primary care settings is high. We will establish internal consistency (Cronbach's alpha coefficients), test-retest reliability (intraclass correlation coefficient) and construct validity of the long-form TCU-ORC questionnaire. Survey data will be collected from 288 clinical, management and operational staff from 24 primary health facilities where the Project MIND trial is implemented. A modified Delphi approach will assess the content validity of the TCU-ORC items and identify areas for potential adaptation and item reduction. Ethical approval has been granted by the South African Medical Research Council (Protocol ID EC004-2-2015, amendment of 20 August 2017). Results will be submitted to peer-reviewed journals relevant to implementation and health systems strengthening. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Can a Canine Companion Modify Cardiac Autonomic Reactivity and Tone in PTSD

DTIC Science & Technology

2016-01-01

aim is to explore the likely generalizability of these effects under conditions of greater service dog availability. Posttraumatic stress disorder...13 Dog participants 29 Non- dog participants  3 currently active (all 3 are dog participants)  5 withdrawn (due to d/c from inpatient treatment... dog no dog Sleep Heart Rate 6 In contrast to the absence of a trend in sleep heart rate, service animal companionship appears to modify reactivity

A Phenotyping Regimen for Genetically Modified Mice Used to Study Genes Implicated in Human Diseases of Aging.

PubMed

Patterson, Victoria L; Thompson, Brian S; Cherry, Catherine; Wang, Shao-Bin; Chen, Bo; Hoh, Josephine

2016-07-14

Age-related diseases are becoming increasingly prevalent and the burden continues to grow as our population ages. Effective treatments are necessary to lessen the impact of debilitating conditions but remain elusive in many cases. Only by understanding the causes and pathology of diseases associated with aging, can scientists begin to identify potential therapeutic targets and develop strategies for intervention. The most common age-related conditions are neurodegenerative disorders such as Parkinson's disease and blindness. Age-related macular degeneration (AMD) is the leading cause of blindness in the elderly. Genome wide association studies have previously identified loci that are associated with increased susceptibility to this disease and identified two regions of interest: complement factor H (CFH) and the 10q26 locus, where the age-related maculopathy susceptibility 2 (ARMS2) and high-temperature requirement factor A1 (HtrA1) genes are located. CFH acts as a negative regulator of the alternative pathway (AP) of the complement system while HtrA1 is an extracellular serine protease. ARMS2 is located upstream of HtrA1 in the primate genome, although the gene is absent in mice. To study the effects of these genes, humanized knock-in mouse lines of Cfh and ARMS2, knockouts of Cfh, HtrA1, HtrA2, HtrA3 and HtrA4 as well as a conditional neural deletion of HtrA2 were generated. Of all the genetically engineered mice produced only mice lacking HtrA2, either systemically or in neural tissues, displayed clear phenotypes. In order to examine these mice thoroughly and systematically, an initial phenotyping schedule was established, consisting of a series of tests related to two main diseases of interest: AMD and Parkinson's. Genetically modified mice can be subjected to appropriate experiments to identify phenotypes that may be related to the associated diseases in humans. A phenotyping regimen with a mitochondrial focus is presented here alongside representative results from the tests of interest.

Preschool Anxiety Disorders in Pediatric Primary Care: Prevalence and Comorbidity

PubMed Central

Franz, Lauren; Angold, Adrian; Copeland, William; Costello, E. Jane; Towe-Goodman, Nissa; Egger, Helen

2013-01-01

Objective We sought to establish prevalence rates and detail patterns of comorbidity for generalized anxiety disorder, separation anxiety disorder, and social phobia, in preschool aged children. Method The Duke Preschool Anxiety Study, a screen-stratified, cross-sectional study, drew from pediatric primary-care and oversampled for children at risk for anxiety. 917 parents of preschoolers (aged 2 to 5 years) completed the Preschool Age Psychiatric Assessment. Results Generalized anxiety disorder, separation anxiety disorder, and social phobia are common in preschool-aged children attending pediatric primary care. Three quarters of preschoolers with an anxiety disorder only had a single anxiety disorder. Generalized anxiety disorder displayed the greatest degree of comorbidity: with separation anxiety disorder (odds ratio [OR] = 4.1, 95% CI, 2.0–8.5), social phobia (OR = 6.4, 95% CI, 3.1–13.4), disruptive behavior disorders (OR = 5.1, 95% CI, 1.6–15.8), and depression (OR = 3.7, 95% CI, 1.1–12.4). Conclusions The weakness of association between generalized anxiety disorder and depression stands in contrast to substantial associations between these 2 disorders reported in older individuals. Attenuated associations in preschool aged children could translate into clinical opportunities for targeted early interventions, aimed at modifying the developmental trajectory of anxiety disorders. PMID:24290462

Neurocognitive Allied Phenotypes for Schizophrenia and Bipolar Disorder

PubMed Central

Hill, S. Kristian; Harris, Margret S. H.; Herbener, Ellen S.; Pavuluri, Mani; Sweeney, John A.

2008-01-01

Psychiatric disorders are genetically complex and represent the end product of multiple biological and social factors. Links between genes and disorder-related abnormalities can be effectively captured via assessment of phenotypes that are both associated with genetic effects and potentially contributory to behavioral abnormalities. Identifying intermediate or allied phenotypes as a strategy for clarifying genetic contributions to disorders has been successful in other areas of medicine and is a promising strategy for identifying susceptibility genes in complex psychiatric disorders. There is growing evidence that schizophrenia and bipolar disorder, rather than being wholly distinct disorders, share genetic risk at several loci. Further, there is growing evidence of similarity in the pattern of cognitive and neurobiological deficits in these groups, which may be the result of the effects of these common genetic factors. This review was undertaken to identify patterns of performance on neurocognitive and affective tasks across probands with schizophrenia and bipolar disorder as well as unaffected family members, which warrant further investigation as potential intermediate trait markers. Available evidence indicates that measures of attention regulation, working memory, episodic memory, and emotion processing offer potential for identifying shared and illness-specific allied neurocognitive phenotypes for schizophrenia and bipolar disorder. However, very few studies have evaluated neurocognitive dimensions in bipolar probands or their unaffected relatives, and much work in this area is needed. PMID:18448479

Effect on return to work or education of Individual Placement and Support modified for people with mood and anxiety disorders: results of a randomised clinical trial.

PubMed

Hellström, Lone; Bech, Per; Hjorthøj, Carsten; Nordentoft, Merete; Lindschou, Jane; Eplov, Lene Falgaard

2017-10-01

The effect of Individual Placement and Support (IPS) on return to work or education among people with mood or anxiety disorders is unclear, while IPS increases return to work for people with severe mental illness. We examined the effect of IPS modified for people with mood and anxiety disorders (IPS-MA) on return to work and education compared with services as usual (SAU). In a randomised clinical superiority trial, 326 participants with mood and anxiety disorders were centrally randomised to IPS-MA, consisting of individual mentor support and career counselling (n=162) or SAU (n=164). The primary outcome was competitive employment or education at 24 months, while weeks of competitive employment or education, illness symptoms and level of functioning, and well-being were secondary outcomes. After 24 months, 44.4% (72/162) of the participants receiving IPS-MA had returned to work or education compared with 37.8% (62/164) following SAU (OR=1.34, 95% CI: 0.86 to 2.10, p=0.20). We found no difference in mean number of weeks in employment or education (IPS-MA 32.4 weeks vs SAU 26.7 weeks, p=0.14), level of depression (Hamilton Depression 6-Item Scale score IPS-MA 5.7 points vs SAU 5.0 points, p=0.12), level of anxiety (Hamilton Anxiety 6-Item Scale score IPS-MA 5.8 points vs SAU 5.1 points, p=0.17), level of functioning (Global Assessment of Functioning IPS-MA 59.1 points vs SAU 59.5 points, p=0.81) or well-being measured by WHO-Five Well-being Index (IPS-MA 49.6 points vs SAU 48.5 points, p=0.83) at 24 months. The modified version of IPS, IPS-MA, was not superior to SAU in supporting people with mood or anxiety disorders in return to work at 24 months. NCT01721824. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Lentiviral vectors in cancer immunotherapy.

PubMed

Oldham, Robyn Aa; Berinstein, Elliot M; Medin, Jeffrey A

2015-01-01

Basic science advances in cancer immunotherapy have resulted in various treatments that have recently shown success in the clinic. Many of these therapies require the insertion of genes into cells to directly kill them or to redirect the host's cells to induce potent immune responses. Other analogous therapies work by modifying effector cells for improved targeting and enhanced killing of tumor cells. Initial studies done using γ-retroviruses were promising, but safety concerns centered on the potential for insertional mutagenesis have highlighted the desire to develop other options for gene delivery. Lentiviral vectors (LVs) have been identified as potentially more effective and safer alternative delivery vehicles. LVs are now in use in clinical trials for many different types of inherited and acquired disorders, including cancer. This review will discuss current knowledge of LVs and the applications of this viral vector-based delivery vehicle to cancer immunotherapy.

"Teach-to-Goal" to Better Assess Informed Consent Comprehension among Incarcerated Clinical Research Participants.

PubMed

Ahalt, Cyrus; Sudore, Rebecca; Bolano, Marielle; Metzger, Lia; Darby, Anna M; Williams, Brie

2017-09-01

Correctional health research requires important safeguards to ensure that research participation is ethically conducted. In addition to having disproportionately low educational attainment and low literacy, incarcerated people suffer from health-related conditions that can affect cognition (e.g., traumatic brain injury, substance use disorders, mental illness). Yet modified informed consent processes that assess participants' comprehension of the risks and benefits of participation are not required by relevant federal guidelines. A push to assess comprehension of informed consent documents is particularly timely given an increase in demand for correctional health research in the context of criminal justice reform. We argue that comprehension assessments can identify persons who should be excluded from research and help those who will ultimately participate in studies better understand the risks and benefits of their participation. © 2017 American Medical Association. All Rights Reserved.

Risk factors associated with work-related musculoskeletal disorders in dentistry.

PubMed

Bozkurt, Sinem; Demirsoy, Nesrin; Günendi, Zafer

2016-12-01

To evaluate musculoskeletal system-related complaints; identify regions at risk in dentists by observing and inquiring the dentists at work; and find out the associations with age, sex, working years, academic position and departments, positions during work and daily working hours. Modified Nordic Questionnaire (m-nMQ) was used to evaluate pain, hospital admissions and absenteeism. Quick Exposure Check (QEC) form was utilized to assess risk exposure levels related with low-back, neck, hand-wrist and shoulder-arm. 163 dentists were included the most painful regions were found to be back (66.9%), neck (65%) and low back (64.4%). Musculoskeletal symptoms were more prevalent in women and research assistants. QEC scores were found to be lower in those who performed regular exercises. Dentists should be educated about ergonomics at the beginning of their professional life.

Detection of Genetically Modified Sugarcane by Using Terahertz Spectroscopy and Chemometrics

NASA Astrophysics Data System (ADS)

Liu, J.; Xie, H.; Zha, B.; Ding, W.; Luo, J.; Hu, C.

2018-03-01

A methodology is proposed to identify genetically modified sugarcane from non-genetically modified sugarcane by using terahertz spectroscopy and chemometrics techniques, including linear discriminant analysis (LDA), support vector machine-discriminant analysis (SVM-DA), and partial least squares-discriminant analysis (PLS-DA). The classification rate of the above mentioned methods is compared, and different types of preprocessing are considered. According to the experimental results, the best option is PLS-DA, with an identification rate of 98%. The results indicated that THz spectroscopy and chemometrics techniques are a powerful tool to identify genetically modified and non-genetically modified sugarcane.

CoQ(10) deficiencies and MNGIE: two treatable mitochondrial disorders.

PubMed

Hirano, Michio; Garone, Caterina; Quinzii, Catarina M

2012-05-01

Although causative mutations have been identified for numerous mitochondrial disorders, few disease-modifying treatments are available. Two examples of treatable mitochondrial disorders are coenzyme Q(10) (CoQ(10) or ubiquinone) deficiency and mitochondrial neurogastrointestinal encephalomyopathy (MNGIE). Here, we describe clinical and molecular features of CoQ(10) deficiencies and MNGIE and explain how understanding their pathomechanisms have led to rationale therapies. Primary CoQ(10) deficiencies, due to mutations in genes required for ubiquinone biosynthesis, and secondary deficiencies, caused by genetic defects not directly related to CoQ(10) biosynthesis, often improve with CoQ(10) supplementation. In vitro and in vivo studies of CoQ(10) deficiencies have revealed biochemical alterations that may account for phenotypic differences among patients and variable responses to therapy. In contrast to the heterogeneous CoQ(10) deficiencies, MNGIE is a single autosomal recessive disease due to mutations in the TYMP gene encoding thymidine phosphorylase (TP). In MNGIE, loss of TP activity causes toxic accumulations of the nucleosides thymidine and deoxyuridine that are incorporated by the mitochondrial pyrimidine salvage pathway and cause deoxynucleoside triphosphate pool imbalances, which, in turn cause mtDNA instability. Allogeneic hematopoetic stem cell transplantation to restore TP activity and eliminate toxic metabolites is a promising therapy for MNGIE. CoQ(10) deficiencies and MNGIE demonstrate the feasibility of treating specific mitochondrial disorders through replacement of deficient metabolites or via elimination of excessive toxic molecules. Studies of CoQ(10) deficiencies and MNGIE illustrate how understanding the pathogenic mechanisms of mitochondrial diseases can lead to meaningful therapies. This article is part of a Special Issue entitled: Biochemistry of Mitochondria, Life and Intervention 2010. Copyright © 2012 Elsevier B.V. All rights reserved.

Impulse control disorder related behaviours during long-term rotigotine treatment: a post hoc analysis.

PubMed

Antonini, A; Chaudhuri, K R; Boroojerdi, B; Asgharnejad, M; Bauer, L; Grieger, F; Weintraub, D

2016-10-01

Dopamine agonists in Parkinson's disease (PD) are associated with impulse control disorders (ICDs) and other compulsive behaviours (together called ICD behaviours). The frequency of ICD behaviours reported as adverse events (AEs) in long-term studies of rotigotine transdermal patch in PD was evaluated. This was a post hoc analysis of six open-label extension studies up to 6 years in duration. Analyses included patients treated with rotigotine for at least 6 months and administered the modified Minnesota Impulse Disorders Interview. ICD behaviours reported as AEs were identified and categorized. For 786 patients, the mean (±SD) exposure to rotigotine was 49.4 ± 17.6 months. 71 (9.0%) patients reported 106 ICD AEs cumulatively. Occurrence was similar across categories: 2.5% patients reported 'compulsive sexual behaviour', 2.3% 'buying disorder', 2.0% 'compulsive gambling', 1.7% 'compulsive eating' and 1.7% 'punding behaviour'. Examining at 6-month intervals, the incidence was relatively low during the first 30 months; it was higher over the next 30 months, peaking in the 54-60-month period. No ICD AEs were serious, and 97% were mild or moderate in intensity. Study discontinuation occurred in seven (9.9%) patients with ICD AEs; these then resolved in five patients. Dose reduction occurred for 23 AEs, with the majority (73.9%) resolving. In this analysis of >750 patients with PD treated with rotigotine, the frequency of ICD behaviour AEs was 9.0%, with a specific incidence timeline observed. Active surveillance as duration of treatment increases may help early identification and management; once ICD behaviours are present rotigotine dose reduction may be considered. © 2016 The Authors. European Journal of Neurology published by John Wiley & Sons Ltd on behalf of European Academy of Neurology.

Redox Proteomics in Selected Neurodegenerative Disorders: From Its Infancy to Future Applications

PubMed Central

Perluigi, Marzia; Reed, Tanea; Muharib, Tasneem; Hughes, Christopher P.; Robinson, Renã A.S.; Sultana, Rukhsana

2012-01-01

Abstract Several studies demonstrated that oxidative damage is a characteristic feature of many neurodegenerative diseases. The accumulation of oxidatively modified proteins may disrupt cellular functions by affecting protein expression, protein turnover, cell signaling, and induction of apoptosis and necrosis, suggesting that protein oxidation could have both physiological and pathological significance. For nearly two decades, our laboratory focused particular attention on studying oxidative damage of proteins and how their chemical modifications induced by reactive oxygen species/reactive nitrogen species correlate with pathology, biochemical alterations, and clinical presentations of Alzheimer's disease. This comprehensive article outlines basic knowledge of oxidative modification of proteins and lipids, followed by the principles of redox proteomics analysis, which also involve recent advances of mass spectrometry technology, and its application to selected age-related neurodegenerative diseases. Redox proteomics results obtained in different diseases and animal models thereof may provide new insights into the main mechanisms involved in the pathogenesis and progression of oxidative-stress-related neurodegenerative disorders. Redox proteomics can be considered a multifaceted approach that has the potential to provide insights into the molecular mechanisms of a disease, to find disease markers, as well as to identify potential targets for drug therapy. Considering the importance of a better understanding of the cause/effect of protein dysfunction in the pathogenesis and progression of neurodegenerative disorders, this article provides an overview of the intrinsic power of the redox proteomics approach together with the most significant results obtained by our laboratory and others during almost 10 years of research on neurodegenerative disorders since we initiated the field of redox proteomics. Antioxid. Redox Signal. 17, 1610–1655. PMID:22115501

Loss-of-function of neuroplasticity-related genes confers risk for human neurodevelopmental disorders.

PubMed

Smith, Milo R; Glicksberg, Benjamin S; Li, Li; Chen, Rong; Morishita, Hirofumi; Dudley, Joel T

2018-01-01

High and increasing prevalence of neurodevelopmental disorders place enormous personal and economic burdens on society. Given the growing realization that the roots of neurodevelopmental disorders often lie in early childhood, there is an urgent need to identify childhood risk factors. Neurodevelopment is marked by periods of heightened experience-dependent neuroplasticity wherein neural circuitry is optimized by the environment. If these critical periods are disrupted, development of normal brain function can be permanently altered, leading to neurodevelopmental disorders. Here, we aim to systematically identify human variants in neuroplasticity-related genes that confer risk for neurodevelopmental disorders. Historically, this knowledge has been limited by a lack of techniques to identify genes related to neurodevelopmental plasticity in a high-throughput manner and a lack of methods to systematically identify mutations in these genes that confer risk for neurodevelopmental disorders. Using an integrative genomics approach, we determined loss-of-function (LOF) variants in putative plasticity genes, identified from transcriptional profiles of brain from mice with elevated plasticity, that were associated with neurodevelopmental disorders. From five shared differentially expressed genes found in two mouse models of juvenile-like elevated plasticity (juvenile wild-type or adult Lynx1-/- relative to adult wild-type) that were also genotyped in the Mount Sinai BioMe Biobank we identified multiple associations between LOF genes and increased risk for neurodevelopmental disorders across 10,510 patients linked to the Mount Sinai Electronic Medical Records (EMR), including epilepsy and schizophrenia. This work demonstrates a novel approach to identify neurodevelopmental risk genes and points toward a promising avenue to discover new drug targets to address the unmet therapeutic needs of neurodevelopmental disease.

School district resources and identification of children with autistic disorder.

PubMed

Palmer, Raymond F; Blanchard, Stephen; Jean, Carlos R; Mandell, David S

2005-01-01

We estimated the effect of community and school district resources on the identification of children with autistic disorder. Latent growth curve regression models were applied to school district-level data from one large state. The rate of identification of autistic disorder increased on average by 1.0 child per 10000 per year (P<.001), with statistically significant district variation. After adjustment for district and community characteristics, each increase in decile of school revenue was associated with an increase of 0.16 per 10000 children identified with autistic disorder. The proportion of economically disadvantaged children per district was inversely associated with autistic disorder cases. District revenue was associated with higher proportions of children identified with autistic disorder at baseline and increasing rates of identification when measured longitudinally. Economically disadvantaged communities may need assistance to identify children with autistic spectrum disorders and other developmental delays that require attention.

School District Resources and Identification of Children With Autistic Disorder

PubMed Central

Palmer, Raymond F.; Blanchard, Stephen; Jean, Carlos R.; Mandell, David S.

2005-01-01

Objectives. We estimated the effect of community and school district resources on the identification of children with autistic disorder. Methods. Latent growth curve regression models were applied to school district–level data from one large state. Results. The rate of identification of autistic disorder increased on average by 1.0 child per 10000 per year (P<.001), with statistically significant district variation. After adjustment for district and community characteristics, each increase in decile of school revenue was associated with an increase of 0.16 per 10000 children identified with autistic disorder. The proportion of economically disadvantaged children per district was inversely associated with autistic disorder cases. Conclusions. District revenue was associated with higher proportions of children identified with autistic disorder at baseline and increasing rates of identification when measured longitudinally. Economically disadvantaged communities may need assistance to identify children with autistic spectrum disorders and other developmental delays that require attention. PMID:15623872

Post-Thalamic Stroke Movement Disorders: A Systematic Review.

PubMed

Gupta, Navnika; Pandey, Sanjay

2018-06-05

After a stroke, movement disorders are rare manifestations mainly affecting the deep structures of the brain like the basal ganglia (44%) and thalamus (37%), although there have been case studies of movement disorders in strokes affecting the cerebral cortex also. This review aims to delineate the various movement disorders seen in association with thalamic strokes and tries to identify the location of the nuclei affected in each of the described movement disorders. Cases were identified through a search of PubMed database using different search terms related to post-thalamic stroke movement disorders and a secondary search of references of identified articles. We reviewed 2,520 research articles and only 86 papers met the inclusion criteria. Cases were included if they met criteria for post-thalamic stroke movement disorders. Case-cohort studies were also reviewed and will be discussed further. Key Messages: The most common post-stroke abnormal movement disorder reported in our review was dystonia followed by hemiataxia. There was a higher association between ischaemic stroke and movement disorder. Acute onset movement disorders were more common than delayed. The posterolateral thalamus was most commonly involved in post-thalamic stroke movement disorders. © 2018 S. Karger AG, Basel.

Shyness versus social phobia in US youth.

PubMed

Burstein, Marcy; Ameli-Grillon, Leila; Merikangas, Kathleen R

2011-11-01

Scholars and the popular press have suggested that the diagnostic entity of social phobia "medicalizes" normal human shyness. In this study we examined the plausibility of this hypothesis by (1) determining the frequency of shyness and its overlap with social phobia in a nationally representative adolescent sample, (2) investigating the degree to which shyness and social phobia differ with regard to sociodemographic characteristics, functional impairment, and psychiatric comorbidity, and (3) examining differences in rates of prescribed medication use among youth with shyness and/or social phobia. The National Comorbidity Survey-Adolescent Supplement is a nationally representative, face-to-face survey of 10,123 adolescents, aged 13 to 18 years, in the continental United States. Lifetime social phobia was assessed by using a modified version of the fully structured World Health Organization Composite International Diagnostic Interview. Adolescents and parents also provided information on youth shyness and prescribed medication use. Only 12% of the youth who identified themselves as shy also met the criteria for lifetime social phobia. Relative to adolescents who were characterized as shy, adolescents affected with social phobia displayed significantly greater role impairment and were more likely to experience a multitude of psychiatric disorders, including disorders of anxiety, mood, behavior, and substance use. However, those adolescents were no more likely than their same-age counterparts to be taking prescribed medications. The results of this study provide evidence that social phobia is an impairing psychiatric disorder, beyond normal human shyness. Such findings raise questions concerning the "medicalization" hypothesis of social phobia.

Which Kindergarten Children are at Greatest Risk for Attention-deficit/Hyperactivity and Conduct Disorder Symptomatology as Adolescents?

PubMed Central

Morgan, Paul L.; Li, Hui; Cook, Michael; Farkas, George; Hillemeier, Marianne M.; Lin, Yu-chu

2015-01-01

Objective We sought to identify which kindergarten children are simultaneously at risk of moderate or severe symptomatology in both attention-deficit/hyperactivity disorder (ADHD) and conduct disorder (CD) as adolescents. These risk factor estimates have not been previously available. Method Multinomial logistic regression analyses of multi-informant ratings by the end of middle school of a population-based, longitudinal sample of children followed from kindergarten to eighth grade (N = 7,456). Results Kindergarten children from low SES households, those raised by mothers with depressive symptoms or experiencing emotional problems or substance abuse, or those who were punished by spanking were significantly more likely to later display severe levels of ADHD-CD symptomatology in eighth grade. Kindergarten children frequently engaging in ADHD-CD-type behaviors were more likely to later experience both moderate (covariate adjusted OR = 2.37) and severe (covariate adjusted OR = 3.63) ADHD-CD symptomatology. Low academic achievement uniquely increased the risk of both moderate and severe symptomatology (adjusted OR range = 1.7 to 2.24). Conclusions The results should guide early screening and school-based intervention efforts for ADHD-CD. Reducing children’s risk for adolescent ADHD-CD symptomatology may require remediating low behavioral and academic functioning by the end of kindergarten. When these two modifiable factors occur together they increase kindergarten children’s odds of experiencing severe ADHD-CD symptomatology in eighth grade by a multiplicative factor of 8.1. PMID:26192391

The Batten disease gene CLN3 is required for the response to oxidative stress

PubMed Central

Tuxworth, Richard I.; Chen, Haiyang; Vivancos, Valerie; Carvajal, Nancy; Huang, Xun; Tear, Guy

2011-01-01

Mutations in the CLN3 gene cause juvenile neuronal ceroid lipofuscinosis (JNCL or Batten disease), an early onset neurodegenerative disorder. JNCL is the most common of the NCLs, a group of disorders with infant or childhood onset that are caused by single gene mutations. The NCLs, although relatively rare, share many pathological and clinical similarities with the more common late-onset neurodegenerative disorders, while their simple genetic basis makes them an excellent paradigm. The early onset and rapid disease progression in the NCLs suggests that one or more key cellular processes are severely compromised. To identify the functional pathways compromised in JNCL, we have performed a gain-of-function modifier screen in Drosophila. We find that CLN3 interacts genetically with the core stress signalling pathways and components of stress granules, suggesting a function in stress responses. In support of this, we find that Drosophila lacking CLN3 function are hypersensitive to oxidative stress yet they respond normally to other physiological stresses. Overexpression of CLN3 is sufficient to confer increased resistance to oxidative stress. We find that CLN3 mutant flies perceive conditions of increased oxidative stress correctly but are unable to detoxify reactive oxygen species, suggesting that their ability to respond is compromised. Together, our data suggest that the lack of CLN3 function leads to a failure to manage the response to oxidative stress and this may be the key deficit in JNCL that leads to neuronal degeneration. PMID:21372148

Workplace management of upper limb disorders: a systematic review.

PubMed

Dick, F D; Graveling, R A; Munro, W; Walker-Bone, K

2011-01-01

Upper limb pain is common among working-aged adults and a frequent cause of absenteeism. To systematically review the evidence for workplace interventions in four common upper limb disorders. Systematic review of English articles using Medline, Embase, Cinahl, AMED, Physiotherapy Evidence Database PEDro (carpal tunnel syndrome and non-specific arm pain only) and Cochrane Library. Study inclusion criteria were randomized controlled trials, cohort studies or systematic reviews employing any workplace intervention for workers with carpal tunnel syndrome, non-specific arm pain, extensor tenosynovitis or lateral epicondylitis. Papers were selected by a single reviewer and appraised by two reviewers independently using methods based on Scottish Intercollegiate Guidelines Network (SIGN) methodology. 1532 abstracts were identified, 28 papers critically appraised and four papers met the minimum quality standard (SIGN grading + or ++) for inclusion. There was limited evidence that computer keyboards with altered force displacement characteristics or altered geometry were effective in reducing carpal tunnel syndrome symptoms. There was limited, but high quality, evidence that multi-disciplinary rehabilitation for non-specific musculoskeletal arm pain was beneficial for those workers absent from work for at least four weeks. In adults with tenosynovitis there was limited evidence that modified computer keyboards were effective in reducing symptoms. There was a lack of high quality evidence to inform workplace management of lateral epicondylitis. Further research is needed focusing on occupational management of upper limb disorders. Where evidence exists, workplace outcomes (e.g. successful return to pre-morbid employment; lost working days) are rarely addressed.

A specific RAGE-binding peptide biopanning from phage display random peptide library that ameliorates symptoms in amyloid β peptide-mediated neuronal disorder.

PubMed

Cai, Cuizan; Dai, Xiaoyong; Zhu, Yujie; Lian, Mengyang; Xiao, Fei; Dong, Fangyuan; Zhang, Qihao; Huang, Yadong; Zheng, Qing

2016-01-01

Alzheimer's disease (AD) is an age-related neurodegenerative disorder in which amyloid β (Aβ) peptide accumulates in the brain. The receptor for advanced glycation end product (RAGE) is a cellular binding site for Aβ peptide and mediates amyloid β-induced perturbations in cerebral vessels, neurons, and microglia in AD. Here, we identified a specific high-affinity RAGE inhibitor (APDTKTQ named RP-1) from a phage display library. RP-1 bound to RAGE and inhibited Aβ peptide-induced cellular stress in human neuroblastoma SH-SYSY cells in vitro. Three amino acids in RP-1 are identical to those in the Aβ peptide. RP-1 shows high homology to the 16-23 (KLVFFAED) regions in Aβ peptide and high-affinity RAGE. Functional analyses indicated that RP-1 significantly reduced the level of reactive oxygen species (ROS) and ROS products and that it enhanced catalase and glutathione peroxidase (GPx) activity. Furthermore, it inactivated caspase3 and caspase9 and inhibited the upregulation of RAGE, nuclear factor-κB (NF-κB), and beta-site amyloid precursor protein-cleaving enzyme 1 (BACE1) protein expression. In addition, RP-1 activated the PI3K/AKT signaling pathway, inhibiting the interaction between Bax and Bcl-2. Our data suggest that RP-1 is a potent RAGE blocker that effectively controls the progression of Aβ peptide-mediated brain disorders and that it may have potential as a disease-modifying agent for AD.

Causal Evaluation of Acute Recurrent and Chronic Pancreatitis in Children: Consensus From the INSPPIRE Group.

PubMed

Gariepy, Cheryl E; Heyman, Melvin B; Lowe, Mark E; Pohl, John F; Werlin, Steven L; Wilschanski, Michael; Barth, Bradley; Fishman, Douglas S; Freedman, Steven D; Giefer, Matthew J; Gonska, Tanja; Himes, Ryan; Husain, Sohail Z; Morinville, Veronique D; Ooi, Chee Y; Schwarzenberg, Sarah J; Troendle, David M; Yen, Elizabeth; Uc, Aliye

2017-01-01

Acute recurrent pancreatitis (ARP) and chronic pancreatitis (CP) have been diagnosed in children at increasing rates during the past decade. As pediatric ARP and CP are still relatively rare conditions, little quality evidence is available on which to base the diagnosis and determination of etiology. The aim of the study was to review the current state of the literature regarding the etiology of these disorders and to developed a consensus among a panel of clinically active specialists caring for children with these disorders to help guide the diagnostic evaluation and identify areas most in need of future research. A systematic review of the literature was performed and scored for quality, followed by consensus statements developed and scored by each individual in the group for level of agreement and strength of the supporting data using a modified Delphi method. Scores were analyzed for the level of consensus achieved by the group. The panel reached consensus on 27 statements covering the definitions of pediatric ARP and CP, evaluation for potential etiologies of these disorders, and long-term monitoring. Statements for which the group reached consensus to make no recommendation or could not reach consensus are discussed. This consensus helps define the minimal diagnostic evaluation and monitoring of children with ARP and CP. Even in areas in which we reached consensus, the quality of the evidence is weak, highlighting the need for further research. Improved understanding of the underlying cause will facilitate treatment development and targeting.

Replication and meta-analysis of TMEM132D gene variants in panic disorder

PubMed Central

Erhardt, A; Akula, N; Schumacher, J; Czamara, D; Karbalai, N; Müller-Myhsok, B; Mors, O; Borglum, A; Kristensen, A S; Woldbye, D P D; Koefoed, P; Eriksson, E; Maron, E; Metspalu, A; Nurnberger, J; Philibert, R A; Kennedy, J; Domschke, K; Reif, A; Deckert, J; Otowa, T; Kawamura, Y; Kaiya, H; Okazaki, Y; Tanii, H; Tokunaga, K; Sasaki, T; Ioannidis, J P A; McMahon, F J; Binder, E B

2012-01-01

A recent genome-wide association study in patients with panic disorder (PD) identified a risk haplotype consisting of two single-nucleotide polymorphisms (SNPs) (rs7309727 and rs11060369) located in intron 3 of TMEM132D to be associated with PD in three independent samples. Now we report a subsequent confirmation study using five additional PD case–control samples (n=1670 cases and n=2266 controls) assembled as part of the Panic Disorder International Consortium (PanIC) study for a total of 2678 cases and 3262 controls in the analysis. In the new independent samples of European ancestry (EA), the association of rs7309727 and the risk haplotype rs7309727–rs11060369 was, indeed, replicated, with the strongest signal coming from patients with primary PD, that is, patients without major psychiatric comorbidities (n=1038 cases and n=2411 controls). This finding was paralleled by the results of the meta-analysis across all samples, in which the risk haplotype and rs7309727 reached P-levels of P=1.4e−8 and P=1.1e−8, respectively, when restricting the samples to individuals of EA with primary PD. In the Japanese sample no associations with PD could be found. The present results support the initial finding that TMEM132D gene contributes to genetic susceptibility for PD in individuals of EA. Our results also indicate that patient ascertainment and genetic background could be important sources of heterogeneity modifying this association signal in different populations. PMID:22948381

The Causal Evaluation of Acute Recurrent and Chronic Pancreatitis in Children: Consensus From the INSPPIRE Group

PubMed Central

Gariepy, Cheryl E.; Heyman, Melvin B.; Lowe, Mark E.; Pohl, John F.; Werlin, Steven L.; Wilschanski, Michael; Barth, Bradley; Fishman, Douglas S.; Freedman, Steven D.; Giefer, Matthew J.; Gonska, Tanja; Himes, Ryan; Husain, Sohail Z.; Morinville, Veronique D.; Ooi, Chee Y.; Schwarzenberg, Sarah Jane; Troendle, David M.; Yen, Elizabeth; Uc, Aliye

2016-01-01

Acute recurrent pancreatitis (ARP) and chronic pancreatitis (CP) have been diagnosed in children at increasing rates over the past decade. However, as pediatric ARP and CP are still relatively rare conditions, little quality evidence is available on which to base the diagnosis and determination of etiology. Objectives: To review the current state of the literature regarding the etiology of these disorders and to developed a consensus among a panel of clinically active specialists caring for children with these disorders to help guide the diagnostic evaluation and identify areas most in need of future research. Methods: A systematic review of the literature was performed and scored for quality, then consensus statements developed and scored by each individual in the group for level of agreement and strength of the supporting data using a modified Delphi method. Scores were analyzed for the level of consensus achieved by the group. Results: The panel reached consensus on 27 statements covering the definitions of pediatric ARP and CP, evaluation for potential etiologies of these disorders, and long-term monitoring. Statements for which the group reached consensus to make no recommendation or could not reach consensus are discussed. Conclusion: This consensus helps define the minimal diagnostic evaluation and monitoring of children with ARP and CP. Even in areas in which we reached consensus, the quality of the evidence is weak, highlighting the need for further research. Improved understanding of the underlying cause will facilitate treatment development and targeting. PMID:27782962

Impulse-control disorders in a college sample: results from the self-administered Minnesota Impulse Disorders Interview (MIDI).

PubMed

Odlaug, Brian L; Grant, Jon E

2010-01-01

This study sought to examine the prevalence rates of and gender differences among impulse-control disorders in a college sample. During the fall semester of 2006, 791 college students from 2 private colleges in the Midwest completed a self-administered, modified version of the Minnesota Impulse Disorders Interview to assess lifetime rates of DSM-IV-TR-diagnosed impulse-control disorders. Participation was voluntary and anonymous. The mean age of the sample was 20.0 +/- 1.25 years, with females comprising 67.9% of the respondents. Of the individuals, 10.4% (n = 82) met criteria for at least 1 lifetime impulse-control disorder. The most common disorders were trichotillomania (3.91%) and compulsive sexual behavior (3.66%). Kleptomania was the least common (0.38%). Males were significantly more likely to screen positive for pathological gambling (P = .003) and compulsive sexual behavior (P = .002). Females were more likely to have compulsive buying (P = .033). Impulse-control disorders appear to be common among college students. The high rates indicate that these disorders may be incipient during late adolescence and early adulthood and should be addressed prior to onset of clinical versions of the impulse-control disorder.

Trihexyphenidyl for acute life-threatening episodes due to a dystonic movement disorder in Rett syndrome.

PubMed

Gika, Artemis D; Hughes, Elaine; Goyal, Sushma; Sparkes, Matthew; Lin, Jean-Pierre

2010-02-15

In Rett syndrome (RS), acute life-threatening episodes (ALTEs) are usually attributed to epilepsy or autonomic dysfunction but they can represent a movement disorder (MD). We describe three girls with RS who experienced ALTEs from an early age. These were long considered epileptic until video-EEG in Patients 1 and 3 revealed their non-epileptic nature. A primary dystonic mechanism was suspected and Patients 1 and 2 were treated with Trihexyphenidyl with significantly reduced frequency of the ALTEs. Patient 3 died before Trihexyphenidyl was tried. Trihexyphenidyl in RS patients with similar presentations can modify the dystonia and prevent ALTEs. (c) 2009 Movement Disorder Society.

Cognitive-behavioral treatment of food neophobia in adults.

PubMed

Marcontell, Deborah K; Laster, Alison E; Johnson, Jan

2003-01-01

Food neophobia is an eating disturbance defined as the fear of trying new foods. In its extreme, the disorder can lead to malnutrition, limited social functioning, and psychological difficulties. Successful treatment of food neophobia in children has been reported, but if those children are not provided with treatment, it stands to reason that the disorder may follow them into adulthood. To date, adult cases have not been described in the literature and the prevalence in adults is unknown. Our paper will review the methods used to treat children with the disorder then delineate how the procedures were modified for an adult population, giving two case examples.

Cognitive-behavioral treatment of food neophobia in adults.

PubMed

Marcontel, Deborah K; Laster, Alison E; Johnson, Jan

2002-01-01

Food neophobia is an eating disturbance defined as the fear of trying new foods. In its extreme, the disorder can lead to malnutrition, limited social functioning, and psycholo gical difficulties. Successful treatment of food neophobia in children has been reported, but if those children are not provided with treatment, it stands to reason that the disorder may follow them into adulthood. To date, adult cases have not been described in the literature and the prevalence in adults is unknown. Our paper will review the methods used to treat children with the disorder, then delineate how the procedures were modified for an adult population, giving two case examples.

Epigenetics and cardiovascular disease

USDA-ARS?s Scientific Manuscript database

Despite advances in the prevention and management of cardiovascular disease (CVD), this group of multifactorial disorders remains a leading cause of mortality worldwide. CVD is associated with multiple genetic and modifiable risk factors; however, known environmental and genetic influences can only...

Pilot Testing Behavior Therapy for Chronic Tic Disorders in Neurology and Developmental Pediatrics Clinics.

PubMed

Ricketts, Emily J; Gilbert, Donald L; Zinner, Samuel H; Mink, Jonathan W; Lipps, Tara D; Wiegand, Geoffrey A; Vierhile, Amy E; Ely, Laura J; Piacentini, John; Walkup, John T; Woods, Douglas W

2016-03-01

Comprehensive Behavioral Intervention for Tics (CBIT) is an efficacious treatment with limited regional availability. As neurology and pediatric clinics are often the first point of therapeutic contact for individuals with tics, the present study assessed preliminary treatment response, acceptability, and feasibility of an abbreviated version, modified for child neurology and developmental pediatrics clinics. Fourteen youth (9-17) with Tourette disorder across 2 child neurology clinics and one developmental pediatrics clinic participated in a small case series. Clinician-rated tic severity (Yale Global Tic Severity Scale) decreased from pre- to posttreatment, z = -2.0, P < .05, r = -.48, as did tic-related impairment, z = -2.4, P < .05, r = -.57. Five of the 9 completers (56%) were classified as treatment responders. Satisfaction ratings were high, and therapeutic alliance ratings were moderately high. Results provide guidance for refinement of this modified CBIT protocol. © The Author(s) 2015.

CFHR1-Modified Neural Stem Cells Ameliorated Brain Injury in a Mouse Model of Neuromyelitis Optica Spectrum Disorders.

PubMed

Shi, Kaibin; Wang, Zhen; Liu, Yuanchu; Gong, Ye; Fu, Ying; Li, Shaowu; Wood, Kristofer; Hao, Junwei; Zhang, Guang-Xian; Shi, Fu-Dong; Yan, Yaping

2016-11-01

A major hurdle for effective stem cell therapy is ongoing inflammation in the target organ. Reconditioning the lesion microenvironment may be an effective way to promote stem cell therapy. In this study, we showed that engineered neural stem cells (NSCs) with complement factor H-related protein 1, a complement inhibitor protein, can attenuate inflammatory infiltration and immune-mediated damage of astrocytes, an important pathogenic progress in patients with neuromyelitis optica spectrum disorders. Furthermore, we demonstrated that transplantation of the complement factor H-related protein 1-modified NSCs effectively blocked the complement activation cascade and inhibited formation of the membrane attack complex, thus contributing to the protection of endogenous and transplanted NSC-differentiated astrocytes. Therefore, manipulation of the lesion microenvironment contributes to a more effective cell replacement therapeutic strategy for autoimmune diseases of the CNS. Copyright © 2016 by The American Association of Immunologists, Inc.

Dissociative sensibility disorders - A retrospective case series and systematic literature review.

PubMed

Weber, Peter; Erlacher, Rahel

2018-01-01

Dissociative disorders present a huge challenge in clinical settings. In contrast to other dissociative symptoms, dissociative sensibility disorders are rarely focused on. To identify the clinical characteristics and outcomes of dissociative sensibility disorders in children and adolescents, and to review the use of diagnostic procedures. For the review, a literature search used Pubmed, Embase, Web of Science, and PubPsych (to 02/2015) and the reference lists of the studies identified. Screening of titles and abstracts; full-text assessment by two reviewers. The original case series was identified by using the local data register. Two reviewers independently reviewed the data and, if they agreed on the relevance, extracted the data. In the original case series, data were extracted retrospectively from the records. Sixteen studies and seven case reports were identified, including 931 cases with dissociative disorders. In 210 cases the patient suffered either from a single sensibility disorder or predominantly from sensibility disorders. We identified thirteen further cases in our cohort. In both groups there was female predominance; the mean age of manifestation was early adolescence. The timing of admissions was variable. In approximately 50% of cases a premorbid stressful life event could be identified. Over 75% of cases had a good prognosis with complete resolution. Retrospective character of our own data collection, partially missing differentiation between the subgroups of dissociative disorders in the reviewed studies. There is no uniform procedure for diagnostic work-up. The overall short-term prognosis is good. Copyright © 2017 European Paediatric Neurology Society. Published by Elsevier Ltd. All rights reserved.

Canadian clinical practice guidelines for the management of anxiety, posttraumatic stress and obsessive-compulsive disorders

PubMed Central

2014-01-01

Background Anxiety and related disorders are among the most common mental disorders, with lifetime prevalence reportedly as high as 31%. Unfortunately, anxiety disorders are under-diagnosed and under-treated. Methods These guidelines were developed by Canadian experts in anxiety and related disorders through a consensus process. Data on the epidemiology, diagnosis, and treatment (psychological and pharmacological) were obtained through MEDLINE, PsycINFO, and manual searches (1980–2012). Treatment strategies were rated on strength of evidence, and a clinical recommendation for each intervention was made, based on global impression of efficacy, effectiveness, and side effects, using a modified version of the periodic health examination guidelines. Results These guidelines are presented in 10 sections, including an introduction, principles of diagnosis and management, six sections (Sections 3 through 8) on the specific anxiety-related disorders (panic disorder, agoraphobia, specific phobia, social anxiety disorder, generalized anxiety disorder, obsessive-compulsive disorder, and posttraumatic stress disorder), and two additional sections on special populations (children/adolescents, pregnant/lactating women, and the elderly) and clinical issues in patients with comorbid conditions. Conclusions Anxiety and related disorders are very common in clinical practice, and frequently comorbid with other psychiatric and medical conditions. Optimal management requires a good understanding of the efficacy and side effect profiles of pharmacological and psychological treatments. PMID:25081580

Validity of a modified Parkinson's disease screening questionnaire in India: effects of literacy of participants and medical training of screeners and implications for screening efforts in developing countries.

PubMed

Sarangmath, Nagaraja; Rattihalli, Rohini; Ragothaman, Mona; Gopalkrishna, Gururaj; Doddaballapur, Subbakrishna; Louis, Elan D; Muthane, Uday B

2005-12-01

The prevalence of Parkinson's disease (PD) is low among Indians, except in the Parsis. Data for Indians come from studies using different screening tools and criteria to detect PD. An epidemiological study in India, which has nearly a billion people, more than 18 spoken languages, and varying levels of literacy, requires development and validation of a screening tool for PD. The objectives of this study are to (1) validate a modified version of a widely used screening questionnaire for PD to suit the needs of the Indian population; (2) compare the use of a nonmedical assistant (NMA) with the use of a medical person during screening; and (3) compare the effect of literacy of participants on the validity of the screening tool. The validity of the questionnaire was tested on 125 participants from a home for the elderly. NMAs of similar background and medical personnel administered the modified screening questionnaire. A movement disorder neurologist blind to the responses on the questionnaire, examined participants independently and diagnosed if participants had PD. The questionnaire was validated in the movement disorders clinic, on known PD patients and their family members without PD. In the movement disorders clinic, sensitivity and specificity of the questionnaire were 100% and 89%, respectively. Fifty-seven participants were included for analysis. The questionnaire had a higher sensitivity when NMAs (75%) rather than the medical personnel (61%) administered it, and its specificity was higher with the medical personnel (61%) than with NMAs (55% and 25%). The questionnaire had a higher specificity in literates than illiterates, whereas sensitivity varied considerably. The modified questionnaire translated in a local Indian language had reasonable sensitivity and can be used to screen individuals for PD in epidemiological studies in India. This questionnaire can be administered by NMAs to screen PD and this strategy would reduce manpower costs. Literacy may influence epidemiological estimates when screening PD.

The Influence of Emotional Stimuli on Attention Orienting and Inhibitory Control in Pediatric Anxiety

PubMed Central

Mueller, Sven C.; Hardin, Michael G.; Mogg, Karin; Benson, Valerie; Bradley, Brendan P.; Reinholdt-Dunne, Marie Louise; Liversedge, Simon P.; Pine, Daniel S.; Ernst, Monique

2012-01-01

Background Anxiety disorders are highly prevalent in children and adolescents, and are associated with aberrant emotion-related attention orienting and inhibitory control. While recent studies conducted with high-trait anxious adults have employed novel emotion-modified antisaccade tasks to examine the influence of emotional information on orienting and inhibition, similar studies have yet to be conducted in youths. Methods Participants were 22 children/adolescents diagnosed with an anxiety disorder, and 22 age-matched healthy comparison youths. Participants completed an emotion-modified antisaccade task that was similar to those used in studies of high-trait anxious adults. This task probed the influence of abruptly appearing neutral, happy, angry, or fear stimuli on orienting (prosaccade) or inhibitory (antisaccade) responses. Results Anxious compared to healthy children showed facilitated orienting towards angry stimuli. With respect to inhibitory processes, threat-related information improved antisaccade accuracy in healthy but not anxious youth. These findings were not linked to individual levels of reported anxiety or specific anxiety disorders. Conclusions Findings suggest that anxious relative to healthy children manifest enhanced orienting towards threat-related stimuli. Additionally, the current findings suggest that threat may modulate inhibitory control during adolescent development. PMID:22409260

Proteins used as sweeteners: a review.

PubMed

Li, Xiaojian; Alexander, Kenneth S

2007-01-01

For the prevention of obesity, diabetes, dental caries, and some metabolic disorders, ingestion of sugar should be restricted. Although they have high-potency sweetness, artificial low-calorie sweeteners can have severe adverse effects. Public demand for natural and healthy flavors, as well as perceived problems with the toxicity and taste quality of existing synthetic sweeteners, have led to efforts to find natural proteins with high sweetness and tast-modifying properties. Some important properties of natural protein sweeteners and taste-modifying protein sweeteners are discussed in this review.

Using the Teaching Interactions Procedure to Teach Social Skills to Children With Autism and Intellectual Disability.

PubMed

Hui Shyuan Ng, Aubrey; Schulze, Kim; Rudrud, Eric; Leaf, Justin B

2016-11-01

This study implemented a modified teaching interaction procedure to teach social skills to 4 children diagnosed with autism spectrum disorder with an intellectual disability. A multiple baseline design across social skills and replicated across participants was utilized to evaluate the effects of the modified teaching interaction procedure. The results demonstrated that the teaching interaction procedure resulted in all participants acquiring targeted social skills, maintaining the targeted social skills, and generalizing the targeted social skills.

Modified surgical treatment of intermittent open-mouth mandibular locking in a cat.

PubMed

Lobprise, H B; Wiggs, R B

1992-03-01

Intermittent open-mouth locking related to disorders of the temporomandibular joint are not uncommon. As a result of joint laxity, the mandible shifts to one side. The coronoid process then becomes locked lateral to the zygomatic arch. These patients present with the mouth opened and an inability to close the mouth. This article describes a case of intermittent open-mouth mandibular locking in a cat and a modified surgical treatment combining zygomatic arch and coronoid process reduction.

Role of Thyroid Hormones in Skeletal Development and Bone Maintenance

PubMed Central

Bassett, J. H. Duncan

2016-01-01

The skeleton is an exquisitely sensitive and archetypal T3-target tissue that demonstrates the critical role for thyroid hormones during development, linear growth, and adult bone turnover and maintenance. Thyrotoxicosis is an established cause of secondary osteoporosis, and abnormal thyroid hormone signaling has recently been identified as a novel risk factor for osteoarthritis. Skeletal phenotypes in genetically modified mice have faithfully reproduced genetic disorders in humans, revealing the complex physiological relationship between centrally regulated thyroid status and the peripheral actions of thyroid hormones. Studies in mutant mice also established the paradigm that T3 exerts anabolic actions during growth and catabolic effects on adult bone. Thus, the skeleton represents an ideal physiological system in which to characterize thyroid hormone transport, metabolism, and action during development and adulthood and in response to injury. Future analysis of T3 action in individual skeletal cell lineages will provide new insights into cell-specific molecular mechanisms and may ultimately identify novel therapeutic targets for chronic degenerative diseases such as osteoporosis and osteoarthritis. This review provides a comprehensive analysis of the current state of the art. PMID:26862888

Disease-associated missense mutations in GluN2B subunit alter NMDA receptor ligand binding and ion channel properties.

PubMed

Fedele, Laura; Newcombe, Joseph; Topf, Maya; Gibb, Alasdair; Harvey, Robert J; Smart, Trevor G

2018-03-06

Genetic and bioinformatic analyses have identified missense mutations in GRIN2B encoding the NMDA receptor GluN2B subunit in autism, intellectual disability, Lennox Gastaut and West Syndromes. Here, we investigated several such mutations using a near-complete, hybrid 3D model of the human NMDAR and studied their consequences with kinetic modelling and electrophysiology. The mutants revealed reductions in glutamate potency; increased receptor desensitisation; and ablation of voltage-dependent Mg 2+ block. In addition, we provide new views on Mg 2+ and NMDA channel blocker binding sites. We demonstrate that these mutants have significant impact on excitatory transmission in developing neurons, revealing profound changes that could underlie their associated neurological disorders. Of note, the NMDAR channel mutant GluN2B V618G unusually allowed Mg 2+ permeation, whereas nearby N615I reduced Ca 2+ permeability. By identifying the binding site for an NMDAR antagonist that is used in the clinic to rescue gain-of-function phenotypes, we show that drug binding may be modified by some GluN2B disease-causing mutations.

Methods for identifying SNP interactions: a review on variations of Logic Regression, Random Forest and Bayesian logistic regression.

PubMed

Chen, Carla Chia-Ming; Schwender, Holger; Keith, Jonathan; Nunkesser, Robin; Mengersen, Kerrie; Macrossan, Paula

2011-01-01

Due to advancements in computational ability, enhanced technology and a reduction in the price of genotyping, more data are being generated for understanding genetic associations with diseases and disorders. However, with the availability of large data sets comes the inherent challenges of new methods of statistical analysis and modeling. Considering a complex phenotype may be the effect of a combination of multiple loci, various statistical methods have been developed for identifying genetic epistasis effects. Among these methods, logic regression (LR) is an intriguing approach incorporating tree-like structures. Various methods have built on the original LR to improve different aspects of the model. In this study, we review four variations of LR, namely Logic Feature Selection, Monte Carlo Logic Regression, Genetic Programming for Association Studies, and Modified Logic Regression-Gene Expression Programming, and investigate the performance of each method using simulated and real genotype data. We contrast these with another tree-like approach, namely Random Forests, and a Bayesian logistic regression with stochastic search variable selection.

Microbiota-driven transcriptional changes in prefrontal cortex override genetic differences in social behavior

PubMed Central

Gacias, Mar; Gaspari, Sevasti; Santos, Patricia-Mae G; Tamburini, Sabrina; Andrade, Monica; Zhang, Fan; Shen, Nan; Tolstikov, Vladimir; Kiebish, Michael A; Dupree, Jeffrey L; Zachariou, Venetia; Clemente, Jose C; Casaccia, Patrizia

2016-01-01

Gene-environment interactions impact the development of neuropsychiatric disorders, but the relative contributions are unclear. Here, we identify gut microbiota as sufficient to induce depressive-like behaviors in genetically distinct mouse strains. Daily gavage of vehicle (dH2O) in nonobese diabetic (NOD) mice induced a social avoidance behavior that was not observed in C57BL/6 mice. This was not observed in NOD animals with depleted microbiota via oral administration of antibiotics. Transfer of intestinal microbiota, including members of the Clostridiales, Lachnospiraceae and Ruminococcaceae, from vehicle-gavaged NOD donors to microbiota-depleted C57BL/6 recipients was sufficient to induce social avoidance and change gene expression and myelination in the prefrontal cortex. Metabolomic analysis identified increased cresol levels in these mice, and exposure of cultured oligodendrocytes to this metabolite prevented myelin gene expression and differentiation. Our results thus demonstrate that the gut microbiota modifies the synthesis of key metabolites affecting gene expression in the prefrontal cortex, thereby modulating social behavior. DOI: http://dx.doi.org/10.7554/eLife.13442.001 PMID:27097105

Explorations of Substituted Urea Functionality for Discovery of New Activators of the Heme Regulated Inhibitor Kinase

PubMed Central

Chen, Ting; Takrouri, Khuloud; Hee-Hwang, Sung; Rana, Sandeep; Yefidoff-Freedman, Revital; Halperin, Jose; Natarajan, Amarnath; Morisseau, Christophe; Hammock, Bruce; Chorev, Michael; Aktas, Bertal H.

2014-01-01

Heme-regulated inhibitor kinase (HRI), an eukaryotic translation initiation factor 2 alpha (eIF2α) kinase, plays critical roles in cell proliferation, differentiation, and adaptation to cytoplasmic stress. HRI is also a critical modifier of hemoglobin disorders such as β-thalassemia. We previously identified N,N′-diarylureas as potent activators of HRI suitable for studying biology of this important kinase. To expand the repertoire of chemotypes that activate HRI we screened a ~1,900 member N,N′-disubstituted urea library in the surrogate eIF2α phosphorylation assay identifying N-aryl,N′-cyclohexylphenoxyurea as a promising scaffold. We validated hit compounds as a bona-fide HRI activators in secondary assays and explored contributions of substitutions on the N-aryl and N′-cyclohexylphenoxy groups to their activity by studying focused libraries of complementing analogs. We tested these N-aryl,N′-cyclohexylphenoxyureas in the surrogate eIF2α phosphorylation and cell proliferation assays, demonstrating significantly improved bioactivities and specificities. We consider these compounds to represent lead candidates for the development of potent and specific HRI activators. PMID:24261904

Pediatric Multiple Sclerosis: Genes, Environment, and a Comprehensive Therapeutic Approach.

PubMed

Cappa, Ryan; Theroux, Liana; Brenton, J Nicholas

2017-10-01

Pediatric multiple sclerosis is an increasingly recognized and studied disorder that accounts for 3% to 10% of all patients with multiple sclerosis. The risk for pediatric multiple sclerosis is thought to reflect a complex interplay between environmental and genetic risk factors. Environmental exposures, including sunlight (ultraviolet radiation, vitamin D levels), infections (Epstein-Barr virus), passive smoking, and obesity, have been identified as potential risk factors in youth. Genetic predisposition contributes to the risk of multiple sclerosis, and the major histocompatibility complex on chromosome 6 makes the single largest contribution to susceptibility to multiple sclerosis. With the use of large-scale genome-wide association studies, other non-major histocompatibility complex alleles have been identified as independent risk factors for the disease. The bridge between environment and genes likely lies in the study of epigenetic processes, which are environmentally-influenced mechanisms through which gene expression may be modified. This article will review these topics to provide a framework for discussion of a comprehensive approach to counseling and ultimately treating the pediatric patient with multiple sclerosis. Copyright © 2017 Elsevier Inc. All rights reserved.

Genetic dissection of Alzheimer disease, a heterogeneous disorder.

PubMed

Schellenberg, G D

1995-09-12

The genetics of Alzheimer disease (AD) are complex and not completely understood. Mutations in the amyloid precursor protein gene (APP) can cause early-onset autosomal dominant AD. In vitro studies indicate that cells expressing mutant APPs overproduce pathogenic forms of the A beta peptide, the major component of AD amyloid. However, mutations in the APP gene are responsible for 5% or less of all early-onset familial AD. A locus on chromosome 14 is responsible for AD in other early-onset AD families and represents the most severe form of the disease in terms of age of onset and rate of decline. Attempts to identify the AD3 gene by positional cloning methods are underway. At least one additional early-onset AD locus remains to be located. In late-onset AD, the apolipoprotein E gene allele epsilon 4 is a risk factor for AD. This allele appears to act as a dose-dependent age-of-onset modifier. The epsilon 2 allele of this gene may be protective. Other late-onset susceptibility factors remain to be identified.

A review on cardiovascular diseases originated from subclinical hypothyroidism.

PubMed

Mansourian, Azad Reza

2012-01-15

Thyroid hormones play an important role on the cardiovascular systems and thyroid disorder ultimately have a profound adverse effects on myocardium and vascular functions. There are extensive reports on the role of overt thyroid dysfunction which adversely can modify the cardiovascular metabolism but even at the present of some controversial reports, the subclinical thyroid disorders are able also to manipulate cardiovascular system to some extent. The aim of this study is to review the cardiovascular disorders accompanied with subclinical hypothyroidism. It is concluded that adverse effect of thyroid malfunction on myocardium and vascular organs are through the direct role of thyroid hormone and dyslipidemia on heart muscle cells at nuclear level and vascular system, respectively. It seems many cardiovascular disorders initially would not have been occurred in the first place if the thyroid of affected person had functioned properly, therefore thyroid function tests should be one of a prior laboratory examinations in cardiovascular disorders.

“Feeling Disorder” as a Comparative and Contingent Process: Gender, Neighborhood Conditions, and Adolescent Mental Health*

PubMed Central

Browning, Christopher R.; Soller, Brian; Gardner, Margo; Brooks-Gunn, Jeanne

2017-01-01

We explore the effects of neighborhood social disorder on internalizing symptoms among urban youth, focusing on three questions: First, we ask whether the impact of social disorder on internalizing symptoms results from comparisons to conditions measured locally or across the entire city. Second, we consider whether neighborhood collective efficacy modifies disorder’s effect on internalizing symptoms. Finally, we assess whether these effects vary by gender. Analyses of survey data of 2,367 youth from the Project on Human Development in Chicago Neighborhoods indicate social disorder is positively associated with girls’ internalizing symptoms when measured as a deviation from a “neighborhood cluster” (2–3 census tracts) mean. High collective efficacy within girls’ neighborhood cluster attenuates disorder effects on their internalizing symptoms. We find no evidence of disorder or collective efficacy effects on boys’ internalizing symptoms. PMID:24026534

Relationship between neural rhythm generation disorders and physical disabilities in Parkinson's disease patients' walking.

PubMed

Ota, Leo; Uchitomi, Hirotaka; Ogawa, Ken-ichiro; Orimo, Satoshi; Miyake, Yoshihiro

2014-01-01

Walking is generated by the interaction between neural rhythmic and physical activities. In fact, Parkinson's disease (PD), which is an example of disease, causes not only neural rhythm generation disorders but also physical disabilities. However, the relationship between neural rhythm generation disorders and physical disabilities has not been determined. The aim of this study was to identify the mechanism of gait rhythm generation. In former research, neural rhythm generation disorders in PD patients' walking were characterized by stride intervals, which are more variable and fluctuate randomly. The variability and fluctuation property were quantified using the coefficient of variation (CV) and scaling exponent α. Conversely, because walking is a dynamic process, postural reflex disorder (PRD) is considered the best way to estimate physical disabilities in walking. Therefore, we classified the severity of PRD using CV and α. Specifically, PD patients and healthy elderly were classified into three groups: no-PRD, mild-PRD, and obvious-PRD. We compared the contributions of CV and α to the accuracy of this classification. In this study, 45 PD patients and 17 healthy elderly people walked 200 m. The severity of PRD was determined using the modified Hoehn-Yahr scale (mH-Y). People with mH-Y scores of 2.5 and 3 had mild-PRD and obvious-PRD, respectively. As a result, CV differentiated no-PRD from PRD, indicating the correlation between CV and PRD. Considering that PRD is independent of neural rhythm generation, this result suggests the existence of feedback process from physical activities to neural rhythmic activities. Moreover, α differentiated obvious-PRD from mild-PRD. Considering α reflects the intensity of interaction between factors, this result suggests the change of the interaction. Therefore, the interaction between neural rhythmic and physical activities is thought to plays an important role for gait rhythm generation. These characteristics have potential to evaluate the symptoms of PD.

A Longitudinal Investigation of Alcohol Use over the Course of the Year Following Medical-Surgical Intensive Care Unit Admission

PubMed Central

Davydow, Dimitry S.; Zatzick, Douglas; Hough, Catherine L.; Katon, Wayne J.

2013-01-01

Background There have been no studies describing post-intensive care unit (ICU) alcohol use among medical-surgical ICU survivors. Objective To examine alcohol use and identify potentially modifiable risk factors, such as in-hospital probable acute stress disorder, for increased alcohol use following medical-surgical ICU admission. Method This longitudinal investigation included 150 medical-surgical ICU survivors. In-hospital interviews obtained baseline characteristics including pre-ICU alcohol use with the Alcohol Use Disorders Identification Test (AUDIT) and in-hospital probable acute stress disorder with the Posttraumatic Stress Disorder Checklist-civilian version. Clinical factors were obtained from medical records. Post-ICU alcohol use was ascertained via telephone interviews at 3 and 12 months post-discharge using the AUDIT. Mixed-model linear regression was used to examine potential risk factors for increased post-ICU alcohol use. Results There was a significant decline in the mean AUDIT score from baseline (3.9, 95%Confidence Interval [95%CI]: 2.9, 5.0) to 3 months post-ICU (1.5, 95%CI: 1.0, 2.1) (P < 0.001 by one-way analysis of variance [ANOVA]), with a significant increase between 3 and 12 months post-ICU (2.7, 95%CI: 1.8, 3.5) (P < 0.001 by one-way ANOVA). After adjusting for patient and clinical factors, in-hospital probable acute stress disorder (beta: 3.0, 95%CI: 0.9, 5.0) and pre-ICU unhealthy alcohol use (beta: 5.4, 95%CI: 3.4, 7.4) were independently associated with increased post-ICU alcohol use. Conclusions Alcohol use decreases in the early aftermath of medical-surgical ICU admission and then increases significantly by one year post-ICU. Interventions for unhealthy alcohol use among medical-surgical ICU survivors that take into account comorbid psychiatric symptoms are needed. PMID:23414847

Monoamine oxidase-A polymorphisms might modify the association between the dopamine D2 receptor gene and alcohol dependence.

PubMed

Huang, San-Yuan; Lin, Wei-Wen; Wan, Fang-Jung; Chang, Ai-Ju; Ko, Huei-Chen; Wang, Tso-Jen; Wu, Pei-Lin; Lu, Ru-Band

2007-05-01

Low monoamine oxidase (MAO) activity and the neurotransmitter dopamine are 2 important factors in the development of alcohol dependence. MAO is an important enzyme associated with the metabolism of biogenic amines. Therefore, the present study investigates whether the association between the dopamine D2 receptor (DRD2) gene and alcoholism is affected by different polymorphisms of the MAO type A (MAOA) gene. A total of 427 Han Chinese men in Taiwan (201 control subjects and 226 with alcoholism) were recruited for the study. Of the subjects with alcoholism, 108 had pure alcohol dependence (ALC) and 118 had both alcohol dependence and anxiety, depression or both (ANX/DEP ALC). All subjects were assessed with the Chinese Version of the Modified Schedule of Affective Disorders and Schizophrenia-Lifetime. Alcohol dependence, anxiety and major depressive disorders were diagnosed according to Diagnostic and Statistical Manual of Mental Disorders, fourth edition criteria. The genetic variant of the DRD2 gene was only associated with the ANX/DEP ALC phenotype, and the genetic variant of the MAOA gene was associated with pure ALC. Subjects carrying the MAOA 3-repeat allele and genotype A1/A1 of the DRD2 were 3.48 times (95% confidence interval = 1.47-8.25) more likely to be ANX/DEP ALC than the subjects carrying the MAOA 3-repeat allele and DRD2 A2/A2 genotype. The MAOA gene may modify the association between the DRD2 gene and ANX/DEP ALC phenotype.

Effects on readiness to change of an educational intervention on depressive disorders for general physicians in primary care based on a modified Prochaska model--a randomized controlled study.

PubMed

Shirazi, M; Zeinaloo, A A; Parikh, S V; Sadeghi, M; Taghva, A; Arbabi, M; Kashani, A Sabouri; Alaeddini, F; Lonka, K; Wahlström, R

2008-04-01

The Prochaska model of readiness to change has been proposed to be used in educational interventions to improve medical care. To evaluate the impact on readiness to change of an educational intervention on management of depressive disorders based on a modified version of the Prochaska model in comparison with a standard programme of continuing medical education (CME). This is a randomized controlled trial within primary care practices in southern Tehran, Iran. The participants included 192 general physicians working in primary care (GPs) were recruited after random selection and randomized to intervention (96) and control (96). Intervention consisted of interactive, learner-centred educational methods in large and small group settings depending on the GPs' stages of readiness to change. Change in stage of readiness to change measured by the modified version of the Prochaska questionnaire was the The final number of participants was 78 (81%) in the intervention arm and 81 (84%) in the control arm. Significantly (P < 0.01), more GPs (57/96 = 59% versus 12/96 = 12%) in the intervention group changed to higher stages of readiness to change. The intervention effect was 46% points (P < 0.001) and 50% points (P < 0.001) in the large and small group setting, respectively. Educational formats that suit different stages of learning can support primary care doctors to reach higher stages of behavioural change in the topic of depressive disorders. Our findings have practical implications for conducting CME programmes in Iran and are possibly also applicable in other parts of the world.

Genome-wide association study to identify potential genetic modifiers in a canine model for Duchenne muscular dystrophy.

PubMed

Brinkmeyer-Langford, Candice; Balog-Alvarez, Cynthia; Cai, James J; Davis, Brian W; Kornegay, Joe N

2016-08-22

Duchenne muscular dystrophy (DMD) causes progressive muscle degeneration, cardiomyopathy and respiratory failure in approximately 1/5,000 boys. Golden Retriever muscular dystrophy (GRMD) resembles DMD both clinically and pathologically. Like DMD, GRMD exhibits remarkable phenotypic variation among affected dogs, suggesting the influence of modifiers. Understanding the role(s) of genetic modifiers of GRMD may identify genes and pathways that also modify phenotypes in DMD and reveal novel therapies. Therefore, our objective in this study was to identify genetic modifiers that affect discrete GRMD phenotypes. We performed a linear mixed-model (LMM) analysis using 16 variably-affected dogs from our GRMD colony (8 dystrophic, 8 non-dystrophic). All of these dogs were either full or half-siblings, and phenotyped for 19 objective, quantitative biomarkers at ages 6 and 12 months. Each biomarker was individually assessed. Gene expression profiles of 59 possible candidate genes were generated for two muscle types: the cranial tibialis and medial head of the gastrocnemius. SNPs significantly associated with GRMD biomarkers were identified on multiple chromosomes (including the X chromosome). Gene expression levels for candidate genes located near these SNPs correlated with biomarker values, suggesting possible roles as GRMD modifiers. The results of this study enhance our understanding of GRMD pathology and represent a first step toward the characterization of GRMD modifiers that may be relevant to DMD pathology. Such modifiers are likely to be useful for DMD treatment development based on their relationships to GRMD phenotypes.

The 2013 Discovery Award from the Society for Free Radical Biology and Medicine: Selected Discoveries from the Butterfield Laboratory of Oxidative Stress and Its Sequelae in Brain in Cognitive Disorders Exemplified by Alzheimer Disease and Chemotherapy Induced Cognitive Impairment

PubMed Central

Butterfield, D. Allan

2014-01-01

This retrospective review on discoveries of the roles of oxidative stress in brain of subjects with Alzheimer disease (AD) and animal models thereof as well as brain from animal models of chemotherapy induced cognitive impairment (CICI) results from the author receiving the 2013 Discovery Award from the Society for Free Radical Biology and Medicine. The paper reviews our laboratory's discovery of: protein oxidation and lipid peroxidation in AD brain regions rich in amyloid β-peptide (Aβ) but not in Aβ-poor cerebellum; redox proteomics as a means to identify oxidatively modified brain proteins in AD and its earlier forms that are consistent with the pathology, biochemistry, and clinical presentation of these disorders; how Aβ in in vivo, ex vivo, and in vitro studies can lead to oxidative modification of key proteins that also are oxidatively modified in AD brain; the role of the single methionine residue of Aβ(1-42) in these processes; and some of the potential mechanisms in the pathogenesis and progression of AD. CICI affects a significant fraction of the 14 million American cancer survivors, and due to diminished cognitive function, reduced quality of life of the persons with CICI (called “chemobrain” by patients) often results. A proposed mechanism for CICI employed the prototypical ROS-generating and non-blood brain barrier (BBB)-penetrating chemotherapeutic agent doxorubicin (Dox, also called adriamycin, ADR). Because of the quinone moiety within the structure of Dox, this agent undergoes redox cycling to produce superoxide free radical peripherally. This, in turn, leads to oxidative modification of the key plasma protein, Apolipoprotein A1 (ApoA1). Oxidized ApoA1 leads to elevated peripheral TNFα, a pro-inflammatory cytokine that crosses the BBB to induce oxidative stress in brain parenchyma that affects negatively brain mitochondria. This subsequently leads to apoptotic cell death resulting in CICI. This review outlines aspects of CICI consistent with the clinical presentation, biochemistry, and pathology of this disorder. To the author's knowledge this is the only plausible and self-consistent mechanism to explain CICI. These two different disorders of the CNS affect millions of persons worldwide. Both AD and CICI share free radical-mediated oxidative stress in brain, but the source of oxidative stress is not the same. Continued research is necessary to better understand both AD and CICI. The discoveries about these disorders from the Butterfield laboratory that led to the 2013 Discovery Award from the Society of Free Radical and Medicine provides a significant foundation from which this future research can be launched. PMID:24996204

On the association between diabetes and mental disorders in a community sample: results from the German National Health Interview and Examination Survey.

PubMed

Kruse, Johannes; Schmitz, Norbert; Thefeld, Wolfgang

2003-06-01

To determine the relationship between mental disorders and diabetes in a representative community sample. This was a cross-sectional study. Data on diabetes and HbA(1c) values were obtained by structured questionnaires and by laboratory assessments. Current psychiatric disorders were diagnosed by a modified version of the Composite International Diagnostic Interview (CIDI). People with diabetes (PWD) were not more likely to meet Diagnostic and Statistical Manual of Psychiatric Disorders, 4th edition (DSM-IV) criteria for at least one mental disorder than were individuals without diabetes. However, a different diagnostic pattern occurred compared with the general population: odds ratios (ORs) for anxiety disorders in PWD were higher (OR 1.93, 95% CI 1.19-3.14). Although PWD had higher prevalence rates of affective disorders, the relationship between diabetes and affective disorders was not statistically significant after controlling for age, sex, marital status, and socioeconomic status. In contrast, the relationship between diabetes and anxiety disorders remained significant after controlling for these variables. In contrast to individuals without mental disorders, PWD with affective or anxiety disorders more frequently had adequate glycemic control. Diabetes was associated with an increased likelihood of anxiety disorders. The association between mental disorders, diabetes, and glycemic control should be evaluated carefully in terms of potentially confounding sociodemographic variables, sample characteristics, and definitions of the disorders.

ADHD: A Travel Guide to Success.

ERIC Educational Resources Information Center

Hogan, Dawn

1997-01-01

Uses "travel itinerary" structure to provide advice on teaching children with attention deficit hyperactivity disorder (ADHD). Covers such areas as consulting the experts, "landing without frustration" (modifying assignments and materials to match learning styles and abilities), "mapping and orientation" (providing…

ALLIGATORS AND ENDOCRINE DISRUPTING CONTAMINANTS: A CURRENT PERSPECTIVE.AMERICAN ZOOLOGIST

EPA Science Inventory

Many xenobiotic compounds introduced into the environment by human activity have been shown to adversely affect wildlife. Reproductive disorders in wildlife include altered fertility, reduced viability of offspring, impaired hormone secretion or activity and modified reproductive...

Epigenetics lights up the obesity field

USDA-ARS?s Scientific Manuscript database

Despite advances in the prevention and management of cardiovascular disease (CVD), this group of multifactorial disorders remains a leading cause of mortality worldwide. CVD is associated with multiple genetic and modifiable risk factors; however, known environmental and genetic influences can only ...

Predicting Eating Disorders in Women: A Preliminary Measurement Study.

ERIC Educational Resources Information Center

Lundholm, Jean K; And Others

1989-01-01

Identified items from Millon Clinical Multiaxial Inventory (MCMI) that differentiated eating-disordered women (n=173) currently receiving treatment for bulimia from non-eating-disordered university women (n=265). Results identified a list of statements related to social withdrawal and depression that may be appropriate for use in assessing a…

The Temporal Sequencing of Problem Gambling and Comorbid Disorders

ERIC Educational Resources Information Center

Holdsworth, Louise; Haw, John; Hing, Nerilee

2012-01-01

Two qualitative studies were undertaken to identify the prevalent comorbid mental disorders in treatment seeking problem gamblers and to also identify the temporal sequencing of the disorders. A forum with problem gambling counsellors and interviews with 24 mental health experts were undertaken. There was general agreement that the most commonly…

Everyday Discrimination and Mood and Substance Use Disorders: A Latent Profile Analysis with African Americans and Caribbean Blacks

PubMed Central

Clark, Trenette T.; Salas-Wright, Christopher P.; Vaughn, Michael G.; Whitfield, Keith E.

2016-01-01

Perceived discrimination is a major source of health-related stress. The purpose of this study was to model the heterogeneity of everyday-discrimination experiences among African American and Caribbean Blacks and to identify differences in the prevalence of mood and substance use outcomes, including generalized anxiety disorder, major depressive disorder, alcohol-use disorder, and illicit drug-use disorder among the identified subgroups. The study uses data from the National Survey of American Life obtained from a sample of African American and Caribbean Black respondents (N = 4,462) between 18 and 65 years. We used latent profile analysis and multinomial regression analyses to identify and validate latent subgroups and test hypotheses, yielding 4 classes of perceived everyday discrimination: Low Discrimination, Disrespect and Condescension, General Discrimination, and Chronic Discrimination. Findings show significant differences exist between the Low Discrimination and General Discrimination classes for major depressive disorder, alcohol-use disorder, and illicit drug-use disorder. Moreover, we find significant differences exist between the Low Discrimination and Chronic Discrimination classes for the four disorders examined. Compared with the Chronic Discrimination class, members of the other classes were significantly less likely to meet criteria for generalized anxiety disorder, major depressive disorder, alcohol-use disorder, and illicit drug-use disorder. Findings suggest elevated levels of discrimination increase risk for mood and substance-use disorders. Importantly, results suggest the prevalence of mood and substance-use disorders is a function of the type and frequency of discrimination that individuals experience. PMID:25254321

The prevalence of stuttering, voice, and speech-sound disorders in primary school students in Australia.

PubMed

McKinnon, David H; McLeod, Sharynne; Reilly, Sheena

2007-01-01

The aims of this study were threefold: to report teachers' estimates of the prevalence of speech disorders (specifically, stuttering, voice, and speech-sound disorders); to consider correspondence between the prevalence of speech disorders and gender, grade level, and socioeconomic status; and to describe the level of support provided to schoolchildren with speech disorders. Students with speech disorders were identified from 10,425 students in Australia using a 4-stage process: training in the data collection process, teacher identification, confirmation by a speech-language pathologist, and consultation with district special needs advisors. The prevalence of students with speech disorders was estimated; specifically, 0.33% of students were identified as stuttering, 0.12% as having a voice disorder, and 1.06% as having a speech-sound disorder. There was a higher prevalence of speech disorders in males than in females. As grade level increased, the prevalence of speech disorders decreased. There was no significant difference in the pattern of prevalence across the three speech disorders and four socioeconomic groups; however, students who were identified with a speech disorder were more likely to be in the higher socioeconomic groups. Finally, there was a difference between the perceived and actual level of support that was provided to these students. These prevalence figures are lower than those using initial identification by speech-language pathologists and similar to those using parent report.

Longitudinal course of disaster-related PTSD among a prospective sample of adult Chilean natural disaster survivors

PubMed Central

Vicente, Benjamin; Marshall, Brandon DL; Koenen, Karestan C; Arheart, Kristopher L; Kohn, Robert; Saldivia, Sandra; Buka, Stephen L

2017-01-01

Abstract Background: With an increasing number of individuals surviving natural disasters, it is crucial to understand who is most at risk for developing post-traumatic stress disorder (PTSD). The objective of this study was to prospectively examine the role that pre-existing psychopathology plays in developing PTSD after a disaster. Methods: This study uses data from a prospective 5-wave longitudinal cohort (years 2003-11) of Chilean adults from 10 health centres (N = 1708). At baseline, participants completed the Composite International Diagnostic Interview (CIDI), a comprehensive psychiatric diagnostic instrument. In 2010, the sixth most powerful earthquake on record struck Chile. One year later, a modified version of the PTSD module of the CIDI was administered. Marginal structural logistic regressions with inverse probability censoring weights were constructed to identify pre-disaster psychiatric predictors of post-disaster PTSD. Results: The majority of participants were female (75.9%) and had a high-school/college education (66.9%). After controlling for pre-disaster PTSD, pre-existing dysthymia [odds ratio (OR) = 2.21; 95% confidence interval (CI) = 1.39-3.52], brief psychotic disorder (OR = 2.67; 95% CI = 1.21-5.90), anxiety disorders (not including PTSD; OR = 1.49; 95% CI = 1.27-1.76), panic disorder (OR = 2.46; 95% CI = 1.37-4.42), agoraphobia (OR = 2.23; 95% CI = 1.22-4.10), social phobia (OR = 1.86; 95% CI = 1.06-3.29), specific phobia (OR = 2.07; 95% CI = 1.50-2.86) and hypochondriasis (OR = 2.10; 95% CI = 1.05-4.18) were predictors of post-disaster PTSD. After controlling for pre-disaster anxiety disorders, dysthymia, and non-affective psychotic disorders, individuals with pre-disaster PTSD (vs those without pre-disaster PTSD) had higher odds of developing post-disaster PTSD (OR = 2.53; 95% CI = 1.37-4.65). Conclusions: This is the first Chilean study to demonstrate prospectively that pre-disaster psychiatric disorders, independent of a prior history of other psychiatric disorders, increase the vulnerability to develop PTSD following a major natural disaster. PMID:27283159

Longitudinal course of disaster-related PTSD among a prospective sample of adult Chilean natural disaster survivors.

PubMed

Fernandez, Cristina A; Vicente, Benjamin; Marshall, Brandon Dl; Koenen, Karestan C; Arheart, Kristopher L; Kohn, Robert; Saldivia, Sandra; Buka, Stephen L

2017-04-01

With an increasing number of individuals surviving natural disasters, it is crucial to understand who is most at risk for developing post-traumatic stress disorder (PTSD). The objective of this study was to prospectively examine the role that pre-existing psychopathology plays in developing PTSD after a disaster. This study uses data from a prospective 5-wave longitudinal cohort (years 2003-11) of Chilean adults from 10 health centres ( N  = 1708). At baseline, participants completed the Composite International Diagnostic Interview (CIDI), a comprehensive psychiatric diagnostic instrument. In 2010, the sixth most powerful earthquake on record struck Chile. One year later, a modified version of the PTSD module of the CIDI was administered. Marginal structural logistic regressions with inverse probability censoring weights were constructed to identify pre-disaster psychiatric predictors of post-disaster PTSD. The majority of participants were female (75.9%) and had a high-school/college education (66.9%). After controlling for pre-disaster PTSD, pre-existing dysthymia [odds ratio (OR) = 2.21; 95% confidence interval (CI) = 1.39-3.52], brief psychotic disorder (OR = 2.67; 95% CI = 1.21-5.90), anxiety disorders (not including PTSD; OR = 1.49; 95% CI = 1.27-1.76), panic disorder (OR = 2.46; 95% CI = 1.37-4.42), agoraphobia (OR = 2.23; 95% CI = 1.22-4.10), social phobia (OR = 1.86; 95% CI = 1.06-3.29), specific phobia (OR = 2.07; 95% CI = 1.50-2.86) and hypochondriasis (OR = 2.10; 95% CI = 1.05-4.18) were predictors of post-disaster PTSD. After controlling for pre-disaster anxiety disorders, dysthymia, and non-affective psychotic disorders, individuals with pre-disaster PTSD (vs those without pre-disaster PTSD) had higher odds of developing post-disaster PTSD (OR = 2.53; 95% CI = 1.37-4.65). This is the first Chilean study to demonstrate prospectively that pre-disaster psychiatric disorders, independent of a prior history of other psychiatric disorders, increase the vulnerability to develop PTSD following a major natural disaster. © The Author 2016; all rights reserved. Published by Oxford University Press on behalf of the International Epidemiological Association

Brief Report: The Prevalence of Neurofibromatosis Type 1 among Children with Autism Spectrum Disorder Identified by the Autism and Developmental Disabilities Monitoring Network

ERIC Educational Resources Information Center

Bilder, Deborah A.; Bakian, Amanda V.; Stevenson, David A.; Carbone, Paul S.; Cunniff, Christopher; Goodman, Alyson B.; McMahon, William M.; Fisher, Nicole P.; Viskochil, David

2016-01-01

Neurofibromatosis type 1 (NF1) is an inherited neurocutaneous disorder associated with neurodevelopmental disorders including autism spectrum disorder (ASD). The frequency of ASD/NF1 co-occurrence has been subject to debate since the 1980s. This relationship was investigated in a large population-based sample of 8-year-old children identified with…

Effect of transmeridian travel and jetlag on mood disorders: evidence and implications.

PubMed

Inder, Maree L; Crowe, Marie T; Porter, Richard

2016-03-01

Given the sensitivity of individuals with mood disorders to circadian disruption, transmeridian travel would likely be a high-risk endeavour leading to onset or relapses in mood. A systematic review was undertaken to identify the evidence of the impact of transmeridian travel on people with mood disorders. Databases search included the following: CINAHL, MEDLINE, PsycINFO and manual searching using the keywords jetlag, transmeridian travel, circadian rhythm disruption, mood disorder, bipolar, major depression, seasonal affective disorder, depression, mania and hypomania. Only three studies were identified that related to transmeridian travel and jetlag in people with mood disorders. There is some suggestion that transmeridian travel does appear to precipitate mood episodes with an increased rate of episodes of depression with westward compared with an increased rate of manic/hypomanic episodes with eastward travel. Individuals with a previous history of mood disorder appear to be more vulnerable if adherence to medication is compromised. Given the limited evidence that transmeridian travel precipitates mood episodes, this poses difficulties in identifying suitable ways to mitigate the effects of transmeridian travel in mood disorders. However, in the absence of mood-specific guidelines, some guidance can be given based on our current understanding of the relevance of circadian disruption to both jetlag and mood disorders. Further research is required to identify more focused strategies to mitigate the impact of transmeridian travel for individuals with mood disorders. © The Royal Australian and New Zealand College of Psychiatrists 2015.

A world without pain or tears.

PubMed

Axelrod, Felicia B

2006-04-01

The world of the child with familial dysautonomia (FD), a genetic disorder affecting development of the sensory and autonomic nervous system, is not idyllic. However, over the last 35 years advances in supportive treatments have improved morbidity and mortality. Recent genetic breakthroughs have further expanded thinking about this disorder and suggested innovative approaches to modifying genetic expression. This article reviews the current supportive treatment modalities and their rationale, as well as the suggested new treatments that may alter the function and prognosis of an individual affected with FD.

Thrombocytopenia associated with vaccination of a dog with a modified-live paramyxovirus vaccine.

PubMed

McAnulty, J F; Rudd, R G

1985-06-01

Thrombocytopenia (10,000/mm3), with hematochezia and melena, appeared in a dog 8 days after it was given modified-live canine distemper, virus vaccine and persisted for approximately 5 days. Clinical investigation discounted other possible causes of thrombocytopenia; the condition was considered to be associated with vaccination. The problem spontaneously resolved. The appearance of thrombocytopenia after modified-live canine distemper virus vaccination is not unknown and may assume a severe form. This condition may be mistaken for idiopathic thrombocytopenia of immune origin, and in other instances, it may contribute significantly to surgical risk if concurrent coagulation disorders are present. Administration of levamisole HCl may alleviate the decrease in platelet count in affected animals.

A Modified Delphi to Identify the Significant Works Pertaining to the Understanding of Reading Comprehension and Content Analysis of the Identified Works

ERIC Educational Resources Information Center

Zunker, Norma D.; Pearce, Daniel L.

2012-01-01

The first part of this study explored the significant works pertaining to the understanding of reading comprehension using a Modified Delphi Method. A panel of reading comprehension experts identified 19 works they considered to be significant to the understanding of reading comprehension. The panel of experts identified the reasons they…

Functional Analysis of Problem Behavior: A Systematic Approach for Identifying Idiosyncratic Variables

PubMed Central

Roscoe, Eileen M.; Schlichenmeyer, Kevin J.; Dube, William V.

2015-01-01

When inconclusive functional analysis (FA) outcomes occur, a number of modifications have been made to enhance the putative establishing operation or consequence associated with behavioral maintenance. However, a systematic method for identifying relevant events to test during modified FAs has not been evaluated. The purpose of this study was to develop and evaluate a technology for systematically identifying events to test in a modified FA after an initial FA led to inconclusive outcomes. Six individuals whose initial FA showed little or no responding or high levels only in the control condition participated. An indirect assessment (IA) questionnaire developed for identifying idiosyncratic variables was administered, and a descriptive analysis (DA) was conducted. Results from the IA only or a combination of the IA and DA were used to inform modified FA test and control conditions. Conclusive FA outcomes were obtained with five of the six participants during the modified FA phase. PMID:25930176

Preschool anxiety disorders in pediatric primary care: prevalence and comorbidity.

PubMed

Franz, Lauren; Angold, Adrian; Copeland, William; Costello, E Jane; Towe-Goodman, Nissa; Egger, Helen

2013-12-01

We sought to establish prevalence rates and detail patterns of comorbidity for generalized anxiety disorder, separation anxiety disorder, and social phobia in preschool-aged children. The Duke Preschool Anxiety Study, a screen-stratified, cross-sectional study, drew from pediatric primary care and oversampled for children at risk for anxiety. A total of 917 parents of preschool children (aged 2-5 years) completed the Preschool Age Psychiatric Assessment. Generalized anxiety disorder, separation anxiety disorder, and social phobia are common in preschool-aged children attending pediatric primary care. Three-fourths of preschoolers with an anxiety disorder only had a single anxiety disorder. Generalized anxiety disorder displayed the greatest degree of comorbidity: with separation anxiety disorder (odds ratio [OR] = 4.1, 95% CI = 2.0-8.5), social phobia (OR = 6.4, 95% CI = 3.1-13.4), disruptive behavior disorders (OR = 5.1, 95% CI = 1.6-15.8), and depression (OR = 3.7, 95% CI = 1.1-12.4). The weakness of association between generalized anxiety disorder and depression stands in contrast to substantial associations between these 2 disorders reported in older individuals. Attenuated associations in preschool-aged children could translate into clinical opportunities for targeted early interventions, aimed at modifying the developmental trajectory of anxiety disorders. Copyright © 2013 American Academy of Child and Adolescent Psychiatry. Published by Elsevier Inc. All rights reserved.

Initial accuracy assessment of the modified S-LANSS for the detection of neuropathic orofacial pain conditions.

PubMed

Herrero Babiloni, Alberto; Nixdorf, Donald R; Law, Alan S; Moana-Filho, Estephan J; Shueb, Sarah S; Nguyen, Ruby H; Durham, Justin

2017-01-01

To evaluate the accuracy of a questionnaire modified for the identification of intraoral pain with neuropathic characteristics in a clinical orofacial pain sample population. 136 participants with at least one of four orofacial pain diagnoses (temporomandibular disorders [TMD, n = 41], acute dental pain [ADP, n = 41], trigeminal neuralgia [TN, n = 19], persistent dentoalveolar pain disorder [PDAP, n = 14]) and a group of pain-free controls (n = 21) completed the modified S-LANSS, a previously adapted version of the original questionnaire devised to detected patients suffering from intraoral pain with neuropathic characteristics. Psychometric properties (sensitivity, specificity, positive predictive value [PPV], negative predictive value [NPV]) were calculated in two analyses with two different thresholds: (1) Detection of pain with neuropathic characteristics: PDAP + TN were considered positive, and TMD + ADP + controls were considered negative per gold standard (expert opinion). (2) Detection of PDAP: PDAP was considered positive and TMD + ADP were considered negative per gold standard. For both analyses, target values for adequate sensitivity and specificity were defined as ≥ 80%. For detection of orofacial pain with neuropathic characteristics (PDAP + TN), the modified S-LANSS presented with the most optimistic threshold sensitivity of 52% (95% confidence interval [CI], 34-69), specificity of 70% (95% CI, 60-79), PPV of 35% (95% CI, 22-51), and NPV of 82% (95% CI, 72-89). For detection of PDAP only, with the most optimistic threshold sensitivity was 64% (95% CI, 35-87), specificity 63% (95% CI, 52-74), PPV 23% (95% CI, 11-39) and NPV 91% (95% CI, 81-97). Based on a priori defined criteria, the modified S-LANSS did not show adequate accuracy to detect intraoral pain with neuropathic characteristics in a clinical orofacial pain sample.

Directed polymers on a disordered tree with a defect subtree

NASA Astrophysics Data System (ADS)

Madras, Neal; Yıldırım, Gökhan

2018-04-01

We study the question of how the competition between bulk disorder and a localized microscopic defect affects the macroscopic behavior of a system in the directed polymer context at the free energy level. We consider the directed polymer model on a disordered d-ary tree and represent the localized microscopic defect by modifying the disorder distribution at each vertex in a single path (branch), or in a subtree, of the tree. The polymer must choose between following the microscopic defect and finding the best branches through the bulk disorder. We describe three possible phases, called the fully pinned, partially pinned and depinned phases. When the microscopic defect is associated only with a single branch, we compute the free energy and the critical curve of the model, and show that the partially pinned phase does not occur. When the localized microscopic defect is associated with a non-disordered regular subtree of the disordered tree, the picture is more complicated. We prove that all three phases are non-empty below a critical temperature, and that the partially pinned phase disappears above the critical temperature.

Psychiatric disorders and other health dimensions among Holocaust survivors 6 decades later.

PubMed

Sharon, Asaf; Levav, Itzhak; Brodsky, Jenny; Shemesh, Annarosa Anat; Kohn, Robert

2009-10-01

No previous community-based epidemiological study has explored psychiatric disorders among those who survived the Holocaust. To examine anxiety and depressive disorders, sleep disturbances, other health problems and use of services among individuals exposed and unexposed to the Holocaust. The relevant population samples were part of the Israel World Mental Health Survey. The interview schedule included the Composite International Diagnostic Interview and other health-related items. The Holocaust survivor group had higher lifetime (16.1%; OR = 6.8, 95% CI 1.9-24.2) and 12-month (6.9%; OR = 22.5, 95% CI 2.5-204.8) prevalence rates of anxiety disorders, and more current sleep disturbances (62.4%; OR = 2.5, 95% CI 1.4-4.4) and emotional distress (P<0.001) than their counterparts, but did not have higher rates of depressive disorders or post-traumatic stress disorder. Early severe adversity was associated with psychopathological disorder long after the end of the Second World War, but not in all survivors. Age during the Holocaust did not modify the results.

Cannabis regulatory science: risk-benefit considerations for mental disorders.

PubMed

Borodovsky, Jacob T; Budney, Alan J

2018-05-29

The evolving legal cannabis landscape in the US continues to present novel regulatory challenges that necessitate the development of a Cannabis Regulatory Science. Two specific issues of concern within Cannabis Regulatory Science are (1) the impact that cannabis use has on the incidence, prevalence, and severity of mental disorders, and (2) how cannabis laws and regulations modify this impact. This paper first provides several conceptual points that are useful for evaluating the relationship between cannabis use and mental disorders. Second, it selectively reviews and comments on data relevant to the relationship between cannabis use and depression, several forms of anxiety, post-traumatic stress disorder, schizophrenia, and bipolar disorder. Next, regulatory and public health parallels between the nascent cannabis industry and the pharmaceutical, tobacco, and alcohol industries are discussed. The focus is on specific types of industry practices that may harm those with or at risk for mental disorders. Recommendations are then offered for legal cannabis regulations that could mitigate this harm. Last, future research goals are discussed for building the field of Cannabis Regulatory Science and addressing the potential negative impact of cannabis on those with mental disorders.

Presentation and Diagnosis of Tuberous Sclerosis Complex in Infants.

PubMed

Davis, Peter E; Filip-Dhima, Rajna; Sideridis, Georgios; Peters, Jurriaan M; Au, Kit Sing; Northrup, Hope; Bebin, E Martina; Wu, Joyce Y; Krueger, Darcy; Sahin, Mustafa

2017-12-01

Tuberous sclerosis complex (TSC) is a neurocutaneous genetic disorder with a high prevalence of epilepsy and neurodevelopmental disorders. TSC can be challenging to diagnose in infants because they often do not show many clinical signs early in life. In this study, we describe the timing and pattern of presenting and diagnostic features in a prospective longitudinal study of infants with TSC. Two multicenter, prospective studies enrolled 130 infants with definite TSC by clinical or genetic criteria and followed them longitudinally up to 36 months of age. Periodic study visits included medical and seizure histories, physical and neurologic examinations, and developmental assessments. Ages at which major and minor features of TSC and seizures were first identified were analyzed. The most common initial presenting features of TSC were cardiac rhabdomyomas (59%) and hypomelanotic macules or other skin findings (39%), and 85% of infants presented with either or both. Ultimately, the most prevalent diagnostic TSC features were hypomelanotic macules (94%), tubers or other cortical dysplasias (94%), subependymal nodules (90%), and cardiac rhabdomyomas (82%). Thirty-five percent of infants presented prenatally, 41% presented at birth or within the first month of life, and 74% met criteria for TSC diagnosis at or within 30 days of presentation. Seizure onset occurred before or at initial presentation in only 15% of infants, but 73% developed epilepsy within the first year of life. Infants with TSC can often be identified early, before the onset of neurologic sequelae, enabling earlier diagnosis, surveillance, and possibly disease-modifying treatment. Copyright © 2017 by the American Academy of Pediatrics.

The plausibility of maternal toxicant exposure and nutritional status as contributing factors to the risk of autism spectrum disorders.

PubMed

Nuttall, Johnathan R

2017-05-01

Recent research suggests the maternal environment may be especially important for the risk of developing autism spectrum disorders (ASD). In particular maternal infections, micronutrient deficiencies, obesity, and toxicant exposures are likely to interact with genetic risk factors to disrupt fetal brain development. The goal of this paper is to investigate the plausibility of maternal toxicant exposure and nutritional status as causal factors in the development of ASD. This paper reviews current research investigating the hypothesis that maternal toxicant exposure and prenatal micronutrient intake are important modifiable risk factors for ASD. Zinc, copper, iron, and vitamin B9 are identified as specific micronutrients with relevance to the etiology of ASD. Specific toxicants induce a maternal inflammatory response leading to fetal micronutrient deficiencies that disrupt early brain development. Importantly, maternal micronutrient supplementation is associated with reduced risk of ASD. Furthermore, animal studies show that micronutrient supplementation can prevent the teratogenicity and developmental neurotoxicity of specific toxicants. These findings lead to the hypothesis that maternal infection, obesity, and toxicant exposures (e.g. valproic acid, endocrine disrupting plasticizers, ethanol, and heavy metals) are all environmental risk factors for ASD that lead to fetal micronutrient deficiencies resulting from a maternal inflammatory response. It could be possible to use markers of inflammation and micronutrient status to identify women that would benefit from micronutrient supplementation or dietary interventions to reduce the risk of ASD. However, more research is needed to demonstrate a causal role of fetal micronutrient deficiencies and clarify the underlying mechanisms that contribute to ASD.

Association between bovine casein antibody and new onset schizophrenia among US military personnel.

PubMed

Niebuhr, David W; Li, Yuanzhang; Cowan, David N; Weber, Natalya S; Fisher, Jared A; Ford, Glen M; Yolken, Robert

2011-05-01

Schizophrenia is a pervasive neuropsychiatric disorder of uncertain etiology. Multiple studies have documented immune activation in individuals with schizophrenia. One antigen capable of inducing a prolonged immune response is bovine casein derived from ingested milk products. Increased levels of casein antibodies have been found in individuals with schizophrenia after diagnosis. This study was directed at determining the potential association between schizophrenia and pre-illness onset levels of immunoglobulin G (IgG) antibodies to bovine casein. Parallel analyses for casein antibody levels with bipolar disorder were included as comparison. Cases were service members who received medical discharges from the military with a schizophrenia diagnosis from 1992 to 2005. Serum specimens were selected for 855 cases and 1165 matched healthy controls. IgG antibodies to bovine whole-casein were measured by solid phase enzyme-linked immunosorbent assays (ELISAs). Hazard ratios (HR) were calculated to examine the associations of casein IgG level with risk of schizophrenia by time to diagnosis and by subjects' initial level. Increasing casein IgG antibody levels among those with a high initial level, drawn before diagnosis, was associated with an 18% increase in the hazard risk of schizophrenia per unit increase (value of low-positive standard) in IgG antibody levels (HR=1.18; 95% CI 1.04, 1.34). This is the first report to identify an association between the risk of schizophrenia and elevated antibodies to bovine casein prior to disease onset. Additional research is required to elucidate the complex genetic environmental interactions involved in the pathogenesis of schizophrenia and to identify potentially modifiable risk factors. Published by Elsevier B.V.

De novo mutations in regulatory elements in neurodevelopmental disorders

PubMed Central

Short, Patrick J.; McRae, Jeremy F.; Gallone, Giuseppe; Sifrim, Alejandro; Won, Hyejung; Geschwind, Daniel H.; Wright, Caroline F.; Firth, Helen V; FitzPatrick, David R.; Barrett, Jeffrey C.; Hurles, Matthew E.

2018-01-01

We previously estimated that 42% of patients with severe developmental disorders carry pathogenic de novo mutations in coding sequences. The role of de novo mutations in regulatory elements affecting genes associated with developmental disorders, or other genes, has been essentially unexplored. We identified de novo mutations in three classes of putative regulatory elements in almost 8,000 patients with developmental disorders. Here we show that de novo mutations in highly evolutionarily conserved fetal brain-active elements are significantly and specifically enriched in neurodevelopmental disorders. We identified a significant twofold enrichment of recurrently mutated elements. We estimate that, genome-wide, 1-3% of patients without a diagnostic coding variant carry pathogenic de novo mutations in fetal brain-active regulatory elements and that only 0.15% of all possible mutations within highly conserved fetal brain-active elements cause neurodevelopmental disorders with a dominant mechanism. Our findings represent a robust estimate of the contribution of de novo mutations in regulatory elements to this genetically heterogeneous set of disorders, and emphasize the importance of combining functional and evolutionary evidence to identify regulatory causes of genetic disorders. PMID:29562236

Does the disorder matter? Investigating a moderating effect on coached noncredible overreporting using the MMPI-2 and PAI.

PubMed

Veltri, Carlo O C; Williams, John E

2013-04-01

The use of psychological tests to help identify the noncredible overreporting of psychiatric disorders is a long-standing practice that has received considerable attention from researchers. The purpose of this study was to experimentally determine whether feigning specific psychiatric disorders moderated the influence of coaching on the detection of noncredible overreporting using the Minnesota Multiphasic Personality Inventory-2 (MMPI-2) and the Personality Assessment Inventory (PAI). Using a 2 × 3 experimental analogue design, 265 undergraduates were asked to feign schizophrenia, posttraumatic stress disorder, or generalized anxiety disorder and were either coached about validity scales and disorders or not. The results of this study indicated that the specific psychiatric disorder being feigned did moderate the impact coaching had on the detection of overreported psychopathology using several scales on the MMPI-2 and PAI. Future research examining noncredible overreporting should take into account the impact caused by the interaction of psychiatric disorder with coaching on the detection of symptom overreporting and also identify other important moderating/mediating variables in order to develop more effective means of identifying response bias.

Asperger's Disorder Will Be Back

ERIC Educational Resources Information Center

Tsai, Luke Y.

2013-01-01

This review focuses on identifying up-to-date number of publications that compared DSM-IV/ICD-10 Asperger's disorder (AspD) to Autistic Disorder/High-functioning Autism (AD/HFA). One hundred and twenty-eight publications were identified through an extensive search of major electronic databases and journals. Based on more than 90 clinical…

Multicultural Issues in the Education of Students with Behavioral Disorders.

ERIC Educational Resources Information Center

Peterson, Reece L., Ed.; Ishii-Jordan, Sharon, Ed.

This book examines the effect of racial, ethnic, and cultural factors on the process of identifying and serving students with emotional or behavioral disorders. The book acknowledges the importance of diversity among students with behavioral disorders, and the need to consider their diversity in identifying their behaviors and intervening to…

Brief Report: "SETD2" Mutation in a Child with Autism, Intellectual Disabilities and Epilepsy

ERIC Educational Resources Information Center

Lumish, Heidi S.; Wynn, Julia; Devinsky, Orrin; Chung, Wendy K.

2015-01-01

Whole exome sequencing (WES) has been utilized with increasing frequency to identify mutations underlying rare diseases. Autism spectrum disorders (ASD) and intellectual disability (ID) are genetically heterogeneous, and novel genes for these disorders are rapidly being identified, making these disorders ideal candidates for WES. Here we report a…

Predicting Future Suicide Attempts among Depressed Suicide Ideators: A 10-year Longitudinal Study

PubMed Central

May, Alexis M.; Klonsky, E. David; Klein, Daniel N.

2012-01-01

Suicidal ideation and attempts are a major public health problem. Research has identified many risk factors for suicidality; however, most fail to identify which suicide ideators are at greatest risk of progressing to a suicide attempt. Thus, the present study identified predictors of future suicide attempts in a sample of psychiatric patients reporting suicidal ideation. The sample comprised 49 individuals who met full DSM-IV criteria for major depressive disorder and/or dysthymic disorder and reported suicidal ideation at baseline. Participants were followed for 10 years. Demographic, psychological, personality, and psychosocial risk factors were assessed using validated questionnaires and structured interviews. Phi coefficients and point-biserial correlations were used to identify prospective predictors of attempts, and logistic regressions were used to identify which variables predicted future attempts over and above past suicide attempts. Six significant predictors of future suicide attempts were identified – cluster A personality disorder, cluster B personality disorder, lifetime substance abuse, baseline anxiety disorder, poor maternal relationship, and poor social adjustment. Finally, exploratory logistic regressions were used to examine the unique contribution of each significant predictor controlling for the others. Co-morbid cluster B personality disorder emerged as the only robust, unique predictor of future suicide attempts among depressed suicide ideators. Future research should continue to identify variables that predict transition from suicidal thoughts to suicide attempts, as such work will enhance clinical assessment of suicide risk as well as theoretical models of suicide. PMID:22575331

Making a structured psychiatric diagnostic interview faithful to the nomenclature.

PubMed

Robins, Lee N; Cottler, Linda B

2004-10-15

Psychiatric diagnostic interviews to be used in epidemiologic studies by lay interviewers have, since the 1970s, attempted to operationalize existing psychiatric nomenclatures. How to maximize the chances that they do so successfully has not previously been spelled out. In this article, the authors discuss strategies for each of the seven steps involved in writing, updating, or modifying a diagnostic interview and its supporting materials: 1) writing questions that match the nomenclature's criteria, 2) checking that respondents will be willing and able to answer the questions, 3) choosing a format acceptable to interviewers that maximizes accurate answering and recording of answers, 4) constructing a data entry and cleaning program that highlights errors to be corrected, 5) creating a diagnostic scoring program that matches the nomenclature's algorithms, 6) developing an interviewer training program that maximizes reliability, and 7) computerizing the interview. For each step, the authors discuss how to identify errors, correct them, and validate the revisions. Although operationalization will never be perfect because of ambiguities in the nomenclature, specifying methods for minimizing divergence from the nomenclature is timely as users modify existing interviews and look forward to updating interviews based on the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, and the International Classification of Diseases, Eleventh Revision.