Complex Psychiatric Comorbidity of Treatment-Seeking Youth With Autism Spectrum Disorder and Anxiety Symptoms

PubMed Central

HEPBURN, SUSAN L.; STERN, JESSICA A.; BLAKELEY-SMITH, AUDREY; KIMEL, LILA K.; REAVEN, JUDITH A.

2015-01-01

Anxiety disorders and other co-occurring psychiatric disorders significantly impact adaptive functioning for many children with autism spectrum disorder (ASD). This descriptive study examines the complexity of psychiatric comorbidity in treatment-seeking youth with ASD and anxiety symptoms. Forty-two parents of 8- to 14-year-old children with ASD and anxiety symptoms completed a structured psychiatric interview (K-SADS) and provided information about the child’s past and current psychological functioning as part of a screening process to enter an anxiety intervention program. Overall, comorbidity was very complex, with children obtaining an average of 4 psychiatric diagnoses (including anxiety disorders) on a structured clinical interview (range = 0–9). Onset and course differed by psychiatric disorder. Complexity of comorbidity did not differ significantly by age, sex, or autism severity. Despite clinical significance of the symptoms reported, few children were currently (or ever) engaged in mental health treatment or group psychosocial intervention. Although the specificity of the current sample limits the generalizability of these results, findings suggest that treatment-seeking children with ASD and anxiety often present with additional psychiatric symptoms, which supports a transdiagnostic approach to research and intervention in this area. Accurate assessment of comorbidity may provide valuable information for families and clinicians regarding individualized treatment approaches. PMID:25960821

Disease signatures for schizophrenia and bipolar disorder using patient-derived induced pluripotent stem cells.

PubMed

Watmuff, Bradley; Berkovitch, Shaunna S; Huang, Joanne H; Iaconelli, Jonathan; Toffel, Steven; Karmacharya, Rakesh

2016-06-01

Schizophrenia and bipolar disorder are complex psychiatric disorders that present unique challenges in the study of disease biology. There are no objective biological phenotypes for these disorders, which are characterized by complex genetics and prominent roles for gene-environment interactions. The study of the neurobiology underlying these severe psychiatric disorders has been hindered by the lack of access to the tissue of interest - neurons from patients. The advent of reprogramming methods that enable generation of induced pluripotent stem cells (iPSCs) from patient fibroblasts and peripheral blood mononuclear cells has opened possibilities for new approaches to study relevant disease biology using iPSC-derived neurons. While early studies with patient iPSCs have led to promising and intriguing leads, significant hurdles remain in our attempts to capture the complexity of these disorders in vitro. We present here an overview of studies to date of schizophrenia and bipolar disorder using iPSC-derived neuronal cells and discuss potential future directions that can result in the identification of robust and valid cellular phenotypes that in turn can lay the groundwork for meaningful clinical advances. Copyright © 2016 Elsevier Inc. All rights reserved.

Tuberous Sclerosis Associated Neuropsychiatric Disorders (TAND) and the TAND Checklist

PubMed Central

de Vries, Petrus J.; Whittemore, Vicky H.; Leclezio, Loren; Byars, Anna W.; Dunn, David; Ess, Kevin C.; Hook, Dena; King, Bryan H.; Sahin, Mustafa; Jansen, Anna

2015-01-01

BACKGROUND Tuberous sclerosis complex is a multisystem genetic disorder with a range of physical manifestations that require evaluation, surveillance, and management. Individuals with tuberous sclerosis complex also have a range of behavioral, psychiatric, intellectual, academic, neuropsychologic, and psychosocial difficulties. These may represent the greatest burden of the disease. Around 90% of individuals with tuberous sclerosis complex will have some of these difficulties during their lifetime, yet only about 20% ever receive evaluation and treatment. The Neuropsychiatry Panel at the 2012 Tuberous Sclerosis Complex International Consensus Conference expressed concern about the significant “treatment gap” and about confusion regarding terminology relating to the biopsychosocial difficulties associated with tuberous sclerosis complex. METHODS The Tuberous Sclerosis Complex Neuropsychiatry Panel coined the term TAND—tuberous sclerosis complex-associated neuropsychiatric disorders—to bring together these multidimensional manifestations of the disorder, and recommended annual screening for TAND. In addition, the Panel agreed to develop a TAND Checklist as a guide for screening. RESULTS Here, we present an outline of the conceptualization of TAND, rationale for the structure of the TAND Checklist, and include the full US English version of the TAND Checklist. CONCLUSION We hope that the unified term TAND and the TAND Checklist will raise awareness of the importance of tuberous sclerosis complex-associated neuropsychiatric disorders and of the major burden of disease associated with it, provide a shared language and a simple tool to describe and evaluate the different levels of TAND, alert clinical teams and families or individuals of the importance of screening, assessment, and treatment of TAND, and provide a shared framework for future studies of tuberous sclerosis complex-associated neuropsychiatric disorders. PMID:25532776

GLUT1 deficiency syndrome as a cause of encephalopathy that includes cognitive disability, treatment-resistant infantile epilepsy and a complex movement disorder.

PubMed

Graham, John M

2012-05-01

Glucose transporter-1 (GLUT1) deficiency syndrome is caused by heterozygous mutations in the SLC2A1 gene, resulting in impaired glucose transport into the brain. It is characterized by a low glucose concentration in the cerebrospinal fluid (hypoglycorrhachia) in the absence of hypoglycemia, in combination with low to normal lactate in the cerebrospinal fluid (CSF). It often results in treatment-resistant infantile epilepsy with progressive developmental disabilities and a complex movement disorder. Recognizing GLUT1 deficiency syndrome is important, since initiation of a ketogenic diet can reduce the frequency of seizures and the severity of the movement disorder. There can be a considerable delay in diagnosing GLUT1 deficiency syndrome, and this point is illustrated by the natural history of this disorder in a 21-year-old woman with severe, progressive neurological disabilities. Her encephalopathy consisted of treatment-resistant seizures, a complex movement disorder, progressive intellectual disability, and deceleration of her head growth after late infancy. Focused evaluation at age 21 revealed GLUT1 deficiency caused by a novel heterozygous missence mutation in exon 7 (c.938C > A; p.Ser313Try) in SLC2A1 as the cause for her disabilities. Copyright © 2011 Elsevier Masson SAS. All rights reserved.

Spectroscopy of disordered low-field sites in Cr3+: Mullite glass ceramic

NASA Astrophysics Data System (ADS)

Knutson, Robert; Liu, Huimin; Yen, W. M.; Morgan, T. V.

1989-09-01

In this article we present results of optical and ESR studies that have allowed us to study the behavior of Cr3+ at disordered low-field sites within a mullite ceramic host. The results indicate that the existence of these low-field ions, which are likely at sites in regions of disorder, accounts for most of the spectroscopic anomalies previously noted in these materials. Furthermore, energy transfer from ordered high-field to disordered low-field ions is observed. The resulting complex spectra are deconvoluted by means of the recently developed technique of saturation-resolved fluorescence spectroscopy.

Heartbeat Complexity Modulation in Bipolar Disorder during Daytime and Nighttime.

PubMed

Nardelli, Mimma; Lanata, Antonio; Bertschy, Gilles; Scilingo, Enzo Pasquale; Valenza, Gaetano

2017-12-20

This study reports on the complexity modulation of heartbeat dynamics in patients affected by bipolar disorder. In particular, a multiscale entropy analysis was applied to the R-R interval series, that were derived from electrocardiographic (ECG) signals for a group of nineteen subjects comprised of eight patients and eleven healthy control subjects. They were monitored using a textile-based sensorized t-shirt during the day and overnight for a total of 47 diurnal and 27 nocturnal recordings. Patients showed three different mood states: depression, hypomania and euthymia. Results show a clear loss of complexity during depressive and hypomanic states as compared to euthymic and healthy control states. In addition, we observed that a more significant complexity modulation among healthy and pathological mood states occurs during the night. These findings suggest that bipolar disorder is associated with an enhanced sleep-related dysregulation of the Autonomic Nervous System (ANS) activity, and that heartbeat complex dynamics may serve as a viable marker of pathological conditions in mental health.

Temperature-dependent vibrational spectroscopy to study order-disorder transitions in charge transfer complexes

NASA Astrophysics Data System (ADS)

Isaac, Rohan; Goetz, Katelyn P.; Roberts, Drew; Jurchescu, Oana D.; McNeil, L. E.

2018-02-01

Charge-transfer (CT) complexes are a promising class of materials for the semiconductor industry because of their versatile properties. This class of compounds shows a variety of phase transitions, which are of interest because of their potential impact on the electronic characteristics. Here temperature-dependent vibrational spectroscopy is used to study structural phase transitions in a set of organic CT complexes. Splitting and broadening of infrared-active phonons in the complex formed between pyrene and pyromellitic dianhydride (PMDA) confirm the structural transition is of the order-disorder type and complement previous x-ray diffraction (XRD) results. We show that this technique is a powerful tool to characterize transitions, and apply it to a range of binary CT complexes composed of polyaromatic hyrdocarbons (anthracene, perylene, phenanthrene, pyrene, and stilbene) and PMDA. We extend the understanding of transitions in perylene-PMDA and pyrene-PMDA, and show that there are no order-disorder transitions present in anthracene-PMDA, stilbene-PMDA and phenanthrene-PMDA in the temperature range investigated here.

Intrinsic disorder in the partitioning protein KorB persists after co-operative complex formation with operator DNA and KorA.

PubMed

Hyde, Eva I; Callow, Philip; Rajasekar, Karthik V; Timmins, Peter; Patel, Trushar R; Siligardi, Giuliano; Hussain, Rohanah; White, Scott A; Thomas, Christopher M; Scott, David J

2017-08-30

The ParB protein, KorB, from the RK2 plasmid is required for DNA partitioning and transcriptional repression. It acts co-operatively with other proteins, including the repressor KorA. Like many multifunctional proteins, KorB contains regions of intrinsically disordered structure, existing in a large ensemble of interconverting conformations. Using NMR spectroscopy, circular dichroism and small-angle neutron scattering, we studied KorB selectively within its binary complexes with KorA and DNA, and within the ternary KorA/KorB/DNA complex. The bound KorB protein remains disordered with a mobile C-terminal domain and no changes in the secondary structure, but increases in the radius of gyration on complex formation. Comparison of wild-type KorB with an N-terminal deletion mutant allows a model of the ensemble average distances between the domains when bound to DNA. We propose that the positive co-operativity between KorB, KorA and DNA results from conformational restriction of KorB on binding each partner, while maintaining disorder. © 2017 The Author(s).

Mutations in the mitochondrial cysteinyl-tRNA synthase gene, CARS2, lead to a severe epileptic encephalopathy and complex movement disorder.

PubMed

Coughlin, Curtis R; Scharer, Gunter H; Friederich, Marisa W; Yu, Hung-Chun; Geiger, Elizabeth A; Creadon-Swindell, Geralyn; Collins, Abigail E; Vanlander, Arnaud V; Coster, Rudy Van; Powell, Christopher A; Swanson, Michael A; Minczuk, Michal; Van Hove, Johan L K; Shaikh, Tamim H

2015-08-01

Mitochondrial disease is often suspected in cases of severe epileptic encephalopathy especially when a complex movement disorder, liver involvement and progressive developmental regression are present. Although mutations in either mitochondrial DNA or POLG are often present, other nuclear defects in mitochondrial DNA replication and protein translation have been associated with a severe epileptic encephalopathy. We identified a proband with an epileptic encephalopathy, complex movement disorder and a combined mitochondrial respiratory chain enzyme deficiency. The child presented with neurological regression, complex movement disorder and intractable seizures. A combined deficiency of mitochondrial complexes I, III and IV was noted in liver tissue, along with increased mitochondrial DNA content in skeletal muscle. Incomplete assembly of complex V, using blue native polyacrylamide gel electrophoretic analysis and complex I, using western blotting, suggested a disorder of mitochondrial transcription or translation. Exome sequencing identified compound heterozygous mutations in CARS2, a mitochondrial aminoacyl-tRNA synthetase. Both mutations affect highly conserved amino acids located within the functional ligase domain of the cysteinyl-tRNA synthase. A specific decrease in the amount of charged mt-tRNA(Cys) was detected in patient fibroblasts compared with controls. Retroviral transfection of the wild-type CARS2 into patient skin fibroblasts led to the correction of the incomplete assembly of complex V, providing functional evidence for the role of CARS2 mutations in disease aetiology. Our findings indicate that mutations in CARS2 result in a mitochondrial translational defect as seen in individuals with mitochondrial epileptic encephalopathy. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Psychiatric genetic research at the National Institute of Mental Health

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

Berg, K.; Mullican, C.; Maestri, N.

For some time it has been known through the results of family, twin, and adoption studies that hereditary appears to play a significant casual role in many mental disorders, including schizophrenia, bipolar disorder, and other mood disorders, Alzheimer`s Disease, panic disorder, obsessive compulsive disorder, autism, dyslexia, and Tourette`s syndrome. The precise patterns of inheritance of these complex disorders have not been determined, nor have the relevant genes been localized or cloned. Because the genetics are complex and because there is also clearly an environmental contribution to behavior, we expect the analysis of the genetics of mental illness to be arduousmore » and not quickly resolved. There are several compelling reasons to continue to focus our attention on uncovering the genetic factors for severe mental illness. Prominent among these are the implications for better treatment of mental disorders. The National Institute of Mental Health supports a wide range of studies on psychiatric genetic research. 16 refs.« less

[Diagnosis and treatment of anxiety-depressive disorders in patients with myocardial infarction].

PubMed

Semiglazova, M V; Krasnov, V N; Dovzhenko, T V; Lebedev, A V

2012-01-01

The results of the study of psychopathological, somatic and functional characteristics of anxiety-depressive disorders in patients with acute myocardial infarction are presented. The authors confirmed the wide prevalence of these disorders in acute myocardial infarction and described the features of their diagnostics, dynamics and response to complex treatment. The impact of anxiety-depressive disorders on the clinical and functional state of the cardiovascular system and the dynamics of the patient's status due the concomitant anxiety-depressive disorder are considered.

Psychiatric disorders and sleep issues.

PubMed

Sutton, Eliza L

2014-09-01

Sleep issues are common in people with psychiatric disorders, and the interaction is complex. Sleep disorders, particularly insomnia, can precede and predispose to psychiatric disorders, can be comorbid with and exacerbate psychiatric disorders, and can occur as part of psychiatric disorders. Sleep disorders can mimic psychiatric disorders or result from medication given for psychiatric disorders. Impairment of sleep and of mental health may be different manifestations of the same underlying neurobiological processes. For the primary care physician, key tools include recognition of potential sleep effects of psychiatric medications and familiarity with treatment approaches for insomnia in depression and anxiety. Copyright © 2014 Elsevier Inc. All rights reserved.

A Parent-Child Interactional Model of Social Anxiety Disorder in Youth

ERIC Educational Resources Information Center

Ollendick, Thomas H.; Benoit, Kristy E.

2012-01-01

In this paper, one of the most common disorders of childhood and adolescence, social anxiety disorder (SAD), is examined to illustrate the complex and delicate interplay between parent and child factors that can result in normal development gone awry. Our parent-child model of SAD posits a host of variables that converge to occasion the onset and…

Complexity analysis of spontaneous brain activity in mood disorders: A magnetoencephalography study of bipolar disorder and major depression.

PubMed

Fernández, Alberto; Al-Timemy, Ali H; Ferre, Francisco; Rubio, Gabriel; Escudero, Javier

2018-04-26

The lack of a biomarker for Bipolar Disorder (BD) causes problems in the differential diagnosis with other mood disorders such as major depression (MD), and misdiagnosis frequently occurs. Bearing this in mind, we investigated non-linear magnetoencephalography (MEG) patterns in BD and MD. Lempel-Ziv Complexity (LZC) was used to evaluate the resting-state MEG activity in a cross-sectional sample of 60 subjects, including 20 patients with MD, 16 patients with BD type-I, and 24 control (CON) subjects. Particular attention was paid to the role of age. The results were aggregated by scalp region. Overall, MD patients showed significantly higher LZC scores than BD patients and CONs. Linear regression analyses demonstrated distinct tendencies of complexity progression as a function of age, with BD patients showing a divergent tendency as compared with MD and CON groups. Logistic regressions confirmed such distinct relationship with age, which allowed the classification of diagnostic groups. The patterns of neural complexity in BD and MD showed not only quantitative differences in their non-linear MEG characteristics but also divergent trajectories of progression as a function of age. Moreover, neural complexity patterns in BD patients resembled those previously observed in schizophrenia, thus supporting preceding evidence of common neuropathological processes. Copyright © 2018 Elsevier Inc. All rights reserved.

Alteration of complex negative emotions induced by music in euthymic patients with bipolar disorder.

PubMed

Choppin, Sabine; Trost, Wiebke; Dondaine, Thibaut; Millet, Bruno; Drapier, Dominique; Vérin, Marc; Robert, Gabriel; Grandjean, Didier

2016-02-01

Research has shown bipolar disorder to be characterized by dysregulation of emotion processing, including biases in facial expression recognition that is most prevalent during depressive and manic states. Very few studies have examined induced emotions when patients are in a euthymic phase, and there has been no research on complex emotions. We therefore set out to test emotional hyperreactivity in response to musical excerpts inducing complex emotions in bipolar disorder during euthymia. We recruited 21 patients with bipolar disorder (BD) in a euthymic phase and 21 matched healthy controls. Participants first rated their emotional reactivity on two validated self-report scales (ERS and MAThyS). They then rated their music-induced emotions on nine continuous scales. The targeted emotions were wonder, power, melancholy and tension. We used a specific generalized linear mixed model to analyze the behavioral data. We found that participants in the euthymic bipolar group experienced more intense complex negative emotions than controls when the musical excerpts induced wonder. Moreover, patients exhibited greater emotional reactivity in daily life (ERS). Finally, a greater experience of tension while listening to positive music seemed to be mediated by greater emotional reactivity and a deficit in executive functions. The heterogeneity of the BD group in terms of clinical characteristics may have influenced the results. Euthymic patients with bipolar disorder exhibit more complex negative emotions than controls in response to positive music. Copyright © 2015 Elsevier B.V. All rights reserved.

Effects of a dolphin interaction program on children with autism spectrum disorders – an exploratory research

PubMed Central

2012-01-01

Background Interaction programs involving dolphins and patients with various pathologies or developmental disorders (e.g., cerebral palsy, intellectual impairment, autism, atopic dermatitis, post-traumatic stress disorder, depression) have stimulated interest in their beneficial effects and therapeutic potential. However, the true effects observed in different clinical and psycho-educational setups are still controversial. Results An evaluation protocol consisting of the Childhood Autism Rating Scale (CARS), Psychoeducational Profile-Revised (PEP-R), Autism Treatment Evaluation Checklist (ATEC), Theory of Mind Tasks (ToM Tasks) and a custom-made Interaction Evaluation Grid (IEG) to evaluate behavioural complexity during in-pool interactions was applied to 10 children diagnosed with Autism Spectrum Disorders. The ATEC, ToM Tasks and CARS results show no benefits of the dolphin interaction program. Interestingly, the PEP-R suggests some statistically significant effects on ‘Overall development score’, as well as on their ‘Fine motor development’, ‘Cognitive performance’ and ‘Cognitive verbal development’. Also, a significant evolution in behavioural complexity was shown by the IEG. Conclusions This study does not support significant developmental progress resulting from the dolphin interaction program. PMID:22537536

Evidence for phase-based psychotherapy as a treatment for dissociative identity disorder comorbid with major depressive disorder and alcohol dependence.

PubMed

Pollock, Brianna E; Macfie, Jenny; Elledge, L Christian

2017-01-01

We report on the treatment and successful outcome of a 58-year-old Native American male with a history of complex trauma presenting with dissociative identity disorder (DID) and major depressive disorder. The treatment included a trauma-informed phase-based psychotherapy as recommended by the International Society for the Study of Trauma and Dissociation for treating DID. We assessed symptoms at baseline and at three additional time points over the course of 14 months. We utilized the Reliable Change Index to examine statistically significant change in symptoms over the course of treatment. Significant symptom improvements were realized posttreatment across all measured domains of functioning, including dissociative symptoms, alcohol abuse, depression, anxiety, and emotion regulation skills. Moreover, the client no longer met criteria for DID, major depressive disorder, or alcohol abuse. Results are discussed in terms of the effectiveness of trauma-focused, phase-based treatment for DID for cases of complex trauma with comorbid disorders.

Complex biomarker discovery in neuroimaging data: Finding a needle in a haystack☆

PubMed Central

Atluri, Gowtham; Padmanabhan, Kanchana; Fang, Gang; Steinbach, Michael; Petrella, Jeffrey R.; Lim, Kelvin; MacDonald, Angus; Samatova, Nagiza F.; Doraiswamy, P. Murali; Kumar, Vipin

2013-01-01

Neuropsychiatric disorders such as schizophrenia, bipolar disorder and Alzheimer's disease are major public health problems. However, despite decades of research, we currently have no validated prognostic or diagnostic tests that can be applied at an individual patient level. Many neuropsychiatric diseases are due to a combination of alterations that occur in a human brain rather than the result of localized lesions. While there is hope that newer imaging technologies such as functional and anatomic connectivity MRI or molecular imaging may offer breakthroughs, the single biomarkers that are discovered using these datasets are limited by their inability to capture the heterogeneity and complexity of most multifactorial brain disorders. Recently, complex biomarkers have been explored to address this limitation using neuroimaging data. In this manuscript we consider the nature of complex biomarkers being investigated in the recent literature and present techniques to find such biomarkers that have been developed in related areas of data mining, statistics, machine learning and bioinformatics. PMID:24179856

Influence of chemical disorder on energy dissipation and defect evolution in concentrated solid solution alloys

PubMed Central

Zhang, Yanwen; Stocks, G. Malcolm; Jin, Ke; Lu, Chenyang; Bei, Hongbin; Sales, Brian C.; Wang, Lumin; Béland, Laurent K.; Stoller, Roger E.; Samolyuk, German D.; Caro, Magdalena; Caro, Alfredo; Weber, William J.

2015-01-01

A grand challenge in materials research is to understand complex electronic correlation and non-equilibrium atomic interactions, and how such intrinsic properties and dynamic processes affect energy transfer and defect evolution in irradiated materials. Here we report that chemical disorder, with an increasing number of principal elements and/or altered concentrations of specific elements, in single-phase concentrated solid solution alloys can lead to substantial reduction in electron mean free path and orders of magnitude decrease in electrical and thermal conductivity. The subsequently slow energy dissipation affects defect dynamics at the early stages, and consequentially may result in less deleterious defects. Suppressed damage accumulation with increasing chemical disorder from pure nickel to binary and to more complex quaternary solid solutions is observed. Understanding and controlling energy dissipation and defect dynamics by altering alloy complexity may pave the way for new design principles of radiation-tolerant structural alloys for energy applications. PMID:26507943

Mutational Analysis of Cell Types in Tuberous Sclerosis Complex (TSC)

DTIC Science & Technology

2007-01-01

disorder resulting from mutations in the TSC1 or TSC2 genes that is associated with epilepsy, cognitive disability, and autism . TSC1/TSC2 gene mutations...cognitive disability, and autism . TSC1/TSC2 gene mutations lead to developmental alterations in brain structure known as tubers in over 80% of TSC...TSC (Sparagana and Roach, 2000). Comorbid neuropsychological disorders such as autism , mental retardation (MR), pervasive developmental disorder

Mutation of Neuron-Specific Chromatin Remodeling Subunit BAF53b: Rescue of Plasticity and Memory by Manipulating Actin Remodeling

ERIC Educational Resources Information Center

Ciernia, Annie Vogel; Kramár, Enikö A.; Matheos, Dina P.; Havekes, Robbert; Hemstedt, Thekla J.; Magnan, Christophe N.; Sakata, Keith; Tran, Ashley; Azzawi, Soraya; Lopez, Alberto; Dang, Richard; Wang, Weisheng; Trieu, Brian; Tong, Joyce; Barrett, Ruth M.; Post, Rebecca J.; Baldi, Pierre; Abel, Ted; Lynch, Gary; Wood, Marcelo A.

2017-01-01

Recent human exome-sequencing studies have implicated polymorphic Brg1-associated factor (BAF) complexes (mammalian SWI/SNF chromatin remodeling complexes) in several intellectual disabilities and cognitive disorders, including autism. However, it remains unclear how mutations in BAF complexes result in impaired cognitive function. Post-mitotic…

Voltage-Gated Potassium Channel Antibodies in Slow-Progression Motor Neuron Disease.

PubMed

Godani, Massimiliano; Zoccarato, Marco; Beronio, Alessandro; Zuliani, Luigi; Benedetti, Luana; Giometto, Bruno; Del Sette, Massimo; Raggio, Elisa; Baldi, Roberta; Vincent, Angela

2017-01-01

The spectrum of autoimmune neurological diseases associated with voltage-gated potassium channel (VGKC)-complex antibodies (Abs) ranges from peripheral nerve disorders to limbic encephalitis. Recently, low titers of VGKC-complex Abs have also been reported in neurodegenerative disorders, but their clinical relevance is unknown. The aim of the study was to explore the prevalence of VGKC-complex Abs in slow-progression motor neuron disease (MND). We compared 11 patients affected by slow-progression MND with 9 patients presenting typical progression illness. Sera were tested for VGKC-complex Abs by radioimmunoassay. The distribution of VGKC-complex Abs was analyzed with the Mann-Whitney U test. The statistical analysis showed a significant difference between the mean values in the study and control groups. A case with long-survival MND harboring VGKC-complex Abs and treated with intravenous immunoglobulins is described. Although VGKC-complex Abs are not likely to be pathogenic, these results could reflect the coexistence of an immunological activation in patients with slow disease progression. © 2016 S. Karger AG, Basel.

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

[Minimal emotional dysfunction and first impression formation in personality disorders].

PubMed

Linden, M; Vilain, M

2011-01-01

"Minimal cerebral dysfunctions" are isolated impairments of basic mental functions, which are elements of complex functions like speech. The best described are cognitive dysfunctions such as reading and writing problems, dyscalculia, attention deficits, but also motor dysfunctions such as problems with articulation, hyperactivity or impulsivity. Personality disorders can be characterized by isolated emotional dysfunctions in relation to emotional adequacy, intensity and responsivity. For example, paranoid personality disorders can be characterized by continuous and inadequate distrust, as a disorder of emotional adequacy. Schizoid personality disorders can be characterized by low expressive emotionality, as a disorder of effect intensity, or dissocial personality disorders can be characterized by emotional non-responsivity. Minimal emotional dysfunctions cause interactional misunderstandings because of the psychology of "first impression formation". Studies have shown that in 100 ms persons build up complex and lasting emotional judgements about other persons. Therefore, minimal emotional dysfunctions result in interactional problems and adjustment disorders and in corresponding cognitive schemata.From the concept of minimal emotional dysfunctions specific psychotherapeutic interventions in respect to the patient-therapist relationship, the diagnostic process, the clarification of emotions and reality testing, and especially an understanding of personality disorders as impairment and "selection, optimization, and compensation" as a way of coping can be derived.

To include or not to include: Evaluations and reasoning about the failure to include peers with autism spectrum disorder in elementary students.

PubMed

Bottema-Beutel, Kristen; Turiel, Elliot; DeWitt, Mila N; Wolfberg, Pamela J

2017-01-01

Given the significant role that typically developing children play in the social lives of children with autism spectrum disorder, it is important to understand how they evaluate and reason about the inclusion/exclusion of children with autism spectrum disorder in social situations. The objective of this study is to determine elementary students' evaluations, reasoning patterns, and reasoning complexity regarding the failure to include children with autism spectrum disorder in social activities. Forty-four elementary-aged students participated in interviews, which included vignettes describing four contexts in which a child with autism spectrum disorder is not invited to a social event. Responses were analyzed according to social domain theory, an approach emphasizing that children identify and coordinate different domains of social knowledge, including the moral, personal, societal, and prudential. Results showed that regardless of grade and context, most children judge that failure to include on the basis of disability status is not acceptable. However, the complexity of children's reasoning (i.e. the extent to which they drew upon and coordinated multiple domains) was higher in older children. Mean complexity scores were also higher in a birthday party context as compared to a playdate context. We offer implications for future research and practice regarding the social inclusion of children with autism spectrum disorder. © The Author(s) 2016.

Attention-deficit hyperactivity disorder (ADHD): an updated review of the essential facts.

PubMed

Tarver, J; Daley, D; Sayal, K

2014-11-01

Attention-deficit hyperactivity disorder (ADHD) is a complex disorder that can affect individuals across the lifespan. It is associated with substantial heterogeneity in terms of aetiology, clinical presentation and treatment outcome and is the subject of extensive research. Because of this, it can be difficult for clinicians to stay up to date with the most relevant findings and know how best to respond to parents' questions and concerns about the disorder and interventions. This is a narrative review that aims to summarize key findings from recent research into ADHD and its treatment that clinicians can share with families in order to increase their knowledge about ADHD and intervention options. ADHD develops as a result of complex interplay between interdependent genetic and non-genetic factors. The disorder is associated with substantial impairments in functioning and poor long-term outcomes. Pharmacological and non-pharmacological treatment options are available for symptom management and to improve function, but functioning outcomes often fail to normalize in children with ADHD. Despite extensive advances in understanding this complex disorder, it is clear that there is still a long way to go. In particular, we address the need for future non-pharmacological interventions to be more specifically targeted for ADHD symptoms and its commonly associated functioning deficits in order to ensure the best long-term outcomes for children with ADHD. © 2014 John Wiley & Sons Ltd.

Opposite correlations between cation disordering and amorphization resistance in spinels versus pyrochlores

PubMed Central

Uberuaga, Blas Pedro; Tang, Ming; Jiang, Chao; Valdez, James A.; Smith, Roger; Wang, Yongqiang; Sickafus, Kurt E.

2015-01-01

Understanding and predicting radiation damage evolution in complex materials is crucial for developing next-generation nuclear energy sources. Here, using a combination of ion beam irradiation, transmission electron microscopy and X-ray diffraction, we show that, contrary to the behaviour observed in pyrochlores, the amorphization resistance of spinel compounds correlates directly with the energy to disorder the structure. Using a combination of atomistic simulation techniques, we ascribe this behaviour to structural defects on the cation sublattice that are present in spinel but not in pyrochlore. Specifically, because of these structural defects, there are kinetic pathways for the relaxation of disorder in spinel that are absent in pyrochlore. This leads to a direct correlation between amorphization resistance and disordering energetics in spinel, the opposite of that observed in pyrochlores. These results provide new insight into the origins of amorphization resistance in complex oxides beyond fluorite derivatives. PMID:26510750

Opposite correlations between cation disordering and amorphization resistance in spinels versus pyrochlores

DOE PAGES

Uberuaga, Blas Pedro; Tang, Ming; Jiang, Chao; ...

2015-10-29

Understanding and predicting radiation damage evolution in complex materials is crucial for developing next-generation nuclear energy sources. Here, using a combination of ion beam irradiation, transmission electron microscopy and X-ray diffraction, we show that, contrary to the behaviour observed in pyrochlores, the amorphization resistance of spinel compounds correlates directly with the energy to disorder the structure. Using a combination of atomistic simulation techniques, we ascribe this behaviour to structural defects on the cation sublattice that are present in spinel but not in pyrochlore. Specifically, because of these structural defects, there are kinetic pathways for the relaxation of disorder in spinelmore » that are absent in pyrochlore. This leads to a direct correlation between amorphization resistance and disordering energetics in spinel, the opposite of that observed in pyrochlores. Furthermore, these results provide new insight into the origins of amorphization resistance in complex oxides beyond fluorite derivatives.« less

Opposite correlations between cation disordering and amorphization resistance in spinels versus pyrochlores.

PubMed

Uberuaga, Blas Pedro; Tang, Ming; Jiang, Chao; Valdez, James A; Smith, Roger; Wang, Yongqiang; Sickafus, Kurt E

2015-10-29

Understanding and predicting radiation damage evolution in complex materials is crucial for developing next-generation nuclear energy sources. Here, using a combination of ion beam irradiation, transmission electron microscopy and X-ray diffraction, we show that, contrary to the behaviour observed in pyrochlores, the amorphization resistance of spinel compounds correlates directly with the energy to disorder the structure. Using a combination of atomistic simulation techniques, we ascribe this behaviour to structural defects on the cation sublattice that are present in spinel but not in pyrochlore. Specifically, because of these structural defects, there are kinetic pathways for the relaxation of disorder in spinel that are absent in pyrochlore. This leads to a direct correlation between amorphization resistance and disordering energetics in spinel, the opposite of that observed in pyrochlores. These results provide new insight into the origins of amorphization resistance in complex oxides beyond fluorite derivatives.

Diminished heart rate complexity in adolescent girls: a sign of vulnerability to anxiety disorders?

PubMed

Fiol-Veny, Aina; De la Torre-Luque, Alejandro; Balle, Maria; Bornas, Xavier

2018-07-01

Diminished heart rate variability has been found to be associated with high anxiety symptomatology. Since adolescence is the period of onset for many anxiety disorders, this study aimed to determine sex- and anxiety-related differences in heart rate variability and complexity in adolescents. We created four groups according to sex and anxiety symptomatology: high-anxiety girls (n = 24) and boys (n = 25), and low-anxiety girls (n = 22) and boys (n = 24) and recorded their cardiac function while they performed regular school activities. A series of two-way (sex and anxiety) MANOVAs were performed on time domain variability, frequency domain variability, and non-linear complexity. We obtained no multivariate interaction effects between sex and anxiety, but highly anxious participants had lower heart rate variability than the low-anxiety group. Regarding sex, girls showed lower heart rate variability and complexity than boys. The results suggest that adolescent girls have a less flexible cardiac system that could be a marker of the girls' vulnerability to developing anxiety disorders.

Developmental Disorders of Language and Literacy: Special Issue

ERIC Educational Resources Information Center

Marshall, Chloe R.; Messaoud-Galusi, Souhila

2010-01-01

Language and literacy are cognitive skills of exceptional complexity. It is therefore not surprising that they are at risk of impairment either during development or as a result of damage (e.g. stroke) later in life. Impaired language and literacy can arise from a general learning impairment. However, two developmental disorders, specific language…

Increased Treatment Complexity for Major Depressive Disorder for Inpatients With Comorbid Personality Disorder.

PubMed

Wiegand, Hauke F; Godemann, Frank

2017-05-01

The study examined inpatient treatment for major depressive disorder (MDD) when it is complicated by comorbid personality disorder. In this descriptive analysis of a large data sample from 2013 (German VIPP data set) of 58,913 cases from 75 hospitals, three groups were compared: patients with MDD, patients with MDD and a comorbid personality disorder, and patients with a main diagnosis of personality disorder. Compared with MDD patients, those with comorbid personality disorder had higher rates of recurrent depression and nearly twice as many readmissions within one year, despite longer mean length of stay. Records of patients with comorbidities more often indicated accounting codes for "complex diagnostic procedures," "crisis intervention," and "constant observation." Patients with comorbid disorders differed from patients with a main diagnosis of personality disorder in treatment indicator characteristics and distribution of personality disorder diagnoses. Personality disorder comorbidity made MDD treatment more complex, and recurrence of MDD episodes and hospital readmission occurred more often than if patients had a sole MDD diagnosis.

Phase-based treatment of a complex severely mentally ill case involving complex posttraumatic stress disorder and psychosis related to Dandy Walker syndrome.

PubMed

Mauritz, Maria W; van de Sande, Roland; Goossens, Peter J J; van Achterberg, Theo; Draijer, Nel

2014-01-01

For patients with comorbid complex posttraumatic stress disorder (PTSD) and psychotic disorder, trauma-focused therapy may be difficult to endure. Phase-based treatment including (a) stabilization, (b) trauma-focused therapy, and (c) integration of personality with recovery of connection appears to be the treatment of choice. The objective of this article is to describe and evaluate the therapeutic process of a single case from a holistic perspective. We present a case report of a 47-year-old woman treated for severe complex PTSD resulting from repeated sexual and physical abuse in early childhood and moderate psychotic symptoms stemming from Dandy Walker Syndrome with hydrocephalus. The patient was treated with quetiapine (600-1,000 mg) and citalopram (40 mg). Stabilization consisted of intensive psychiatric nursing care in the home and stabilizing group treatment for complex PTSD. After stabilization, the following symptom domains showed improvement: self-regulation, self-esteem, assertiveness, avoidance of social activities, and negative cognitions. However, intrusions and arousal persisted and were therefore subsequently treated with prolonged imaginary exposure that also included narrative writing assignments and a final closing ritual. This intensive multidisciplinary, phase-based approach proved effective: All symptoms of complex PTSD were in full remission. Social integration and recovery were promoted with the reduction of polypharmacy and the provision of social skills training and lifestyle training. The present case shows a phase-based treatment approach with multidisciplinary collaborative care to be effective for the treatment of a case of complex PTSD with comorbid psychotic disorder stemming from severe neurological impairment. Replication of this promising approach is therefore called for.

Autism Phenotypes in Tuberous Sclerosis Complex: Diagnostic and Treatment Considerations.

PubMed

Gipson, Tanjala T; Poretti, Andrea; Thomas, Emily A; Jenkins, Kosunique T; Desai, Sonal; Johnston, Michael V

2015-12-01

Tuberous sclerosis complex is a multisystem, chronic genetic condition characterized by systemic growth of benign tumors and often accompanied by epilepsy, autism spectrum disorders, and intellectual disability. Nonetheless, the neurodevelopmental phenotype of these patients is not often detailed. The authors describe 3 individuals with tuberous sclerosis complex who share common characteristics that can help to identify a distinct profile of autism spectrum disorder. These findings include typical cognitive development, expressive and pragmatic language deficits, and anxiety. The authors also describe features specific to tuberous sclerosis complex that require consideration before diagnosing an autism spectrum disorder. Identifying distinct profiles of autism spectrum disorder in tuberous sclerosis complex can help optimize treatment across the life span. © The Author(s) 2015.

Considering Valproate as a Risk Factor for Rapid Exacerbation of Complex Movement Disorder in Progressed Stages of Late-Infantile CLN2 Disease.

PubMed

Johannsen, Jessika; Nickel, Miriam; Schulz, Angela; Denecke, Jonas

2016-06-01

Neuronal ceroid lipofuscinosis type 2 (CLN2 disease, OMIM 204500) is a rare autosomal-recessive lysosomal storage disorder. It is one of the most common neurodegenerative disorders in childhood. Symptoms include epilepsy, rapid motor and language regression, dementia, visual loss, and a complex movement disorder in later stages of the disease. We report on two children with genetically confirmed late-infantile CLN2 disease who developed a severe exacerbation of their complex movement disorder leading to hyperthermia, hyper-CK-emia and decreased level of consciousness over several weeks despite different therapeutic approaches. Both patients were on long-term antiepileptic treatment with valproate and only after the withdrawal of valproate, the movement disorder disappeared and level of consciousness improved. These observations emphasize that valproate has to be considered as a possible risk factor in patients in later stages of late-infantile CLN2 disease who develop a rapidly progressive complex movement disorder. Georg Thieme Verlag KG Stuttgart · New York.

Tourette Syndrome: Overview and Classroom Interventions. A Complex Neurobehavioral Disorder Which May Involve Learning Problems, Attention Deficit Hyperactivity Disorder, Obsessive Compulsive Symptoms, and Stereotypical Behaviors.

ERIC Educational Resources Information Center

Fisher, Ramona A.; Collins, Edward C.

Tourette Syndrome is conceptualized as a neurobehavioral disorder, with behavioral aspects that are sometimes difficult for teachers to understand and deal with. The disorder has five layers of complexity: (1) observable multiple motor, vocal, and cognitive tics and sensory involvement; (2) Attention Deficit Hyperactivity Disorder; (3)…

Mutations in UNC80, Encoding Part of the UNC79-UNC80-NALCN Channel Complex, Cause Autosomal-Recessive Severe Infantile Encephalopathy

PubMed Central

Shamseldin, Hanan E.; Faqeih, Eissa; Alasmari, Ali; Zaki, Maha S.; Gleeson, Joseph G.; Alkuraya, Fowzan S.

2016-01-01

Brain channelopathies represent a growing class of brain disorders that usually result in paroxysmal disorders, although their role in other neurological phenotypes, including the recently described NALCN-related infantile encephalopathy, is increasingly recognized. In three Saudi Arabian families and one Egyptian family all affected by a remarkably similar phenotype (infantile encephalopathy and largely normal brain MRI) to that of NALCN-related infantile encephalopathy, we identified a locus on 2q34 in which whole-exome sequencing revealed three, including two apparently loss-of-function, recessive mutations in UNC80. UNC80 encodes a large protein that is necessary for the stability and function of NALCN and for bridging NALCN to UNC79 to form a functional complex. Our results expand the clinical relevance of the UNC79-UNC80-NALCN channel complex. PMID:26708753

Ethical and social implications of genetic testing for communication disorders.

PubMed

Arnos, Kathleen S

2008-01-01

Advances in genetics and genomics have quickly led to clinical applications to human health which have far-reaching consequences at the individual and societal levels. These new technologies have allowed a better understanding of the genetic factors involved in a wide range of disorders. During the past decade, incredible progress has been made in the identification of genes involved in the normal process of hearing. The resulting clinical applications have presented consumers with new information and choices. Many of the same gene identification techniques are increasingly being applied to the investigation of complex disorders of speech and language. In parallel with gene identification, studies of the legal, ethical and psychosocial impacts of the clinical application of these advances and their influence on specific behaviors of individuals with communication disorders are paramount, but often lag behind. These studies will help to ensure that new technologies are introduced into clinical practice in a responsible manner. As a result of this activity, the participant will be able to (1) explain the differences between Mendelian and complex forms of inheritance and why these differences complicate the ethical impact of genetic testing, (2) explain how publicly funded genome research through the Human Genome Project, the International HapMap Project and others have examined the ethical, legal and social implications of genome research, (3) list some of the ethical complexities of prenatal, newborn and predictive testing for various genetic disorders and (4) discuss the importance of evidence-based practice to the development of public policy for the introduction and clinical use of genetic tests.

Ethical and social implications of genetic testing for communication disorders

PubMed Central

Arnos, Kathleen S.

2013-01-01

Advances in genetics and genomics have quickly led to clinical applications to human health which have far-reaching consequences at the individual and societal levels. These new technologies have allowed a better understanding of the genetic factors involved in a wide range of disorders. During the past decade, incredible progress has been made in the identification of genes involved in the normal process of hearing. The resulting clinical applications have presented consumers with new information and choices. Many of the same gene identification techniques are increasingly being applied to the investigation of complex disorders of speech and language. In parallel with gene identification, studies of the legal, ethical and psychosocial impacts of the clinical application of these advances and their influence on specific behaviors of individuals with communication disorders are paramount, but often lag behind. These studies will help to ensure that new technologies are introduced into clinical practice in a responsible manner. Learning outcomes As a result of this activity, the participant will be able to (1) explain the differences between Mendelian and complex forms of inheritance and why these differences complicate the ethical impact of genetic testing, (2) explain how publicly funded genome research through the Human Genome Project, the International HapMap Project and others have examined the ethical, legal and social implications of genome research, (3) list some of the ethical complexities of prenatal, newborn and predictive testing for various genetic disorders and (4) discuss the importance of evidence-based practice to the development of public policy for the introduction and clinical use of genetic tests. PMID:18452941

The association of posttraumatic stress disorder, complex posttraumatic stress disorder, and borderline personality disorder from a network analytical perspective.

PubMed

Knefel, Matthias; Tran, Ulrich S; Lueger-Schuster, Brigitte

2016-10-01

Posttraumatic Stress Disorder (PTSD), Complex PTSD, and Borderline Personality Disorder (BPD) share etiological risk factors and an overlapping set of associated symptoms. Since the ICD-11 proposal for trauma-related disorders, the relationship of these disorders has to be clarified. A novel approach to psychopathology, network analysis, allows for a detailed analysis of comorbidity on symptom level. Symptoms were assessed in adult survivors of childhood abuse (N=219) using the newly developed ICD-11 Trauma-Questionnaire and the SCID-II. The psychopathological network was analyzed using the network approach. PTSD and Complex PTSD symptoms were strongly connected within disorders and to a lesser degree between disorders. Symptoms of BPD were weakly connected to others. Re-experiencing and dissociation were the most central symptoms. Mental disorders are no discrete entities, clear boundaries are unlikely to be found. The psychopathological network revealed central symptoms that might be important targets for specific first interventions. Copyright © 2016 Elsevier Ltd. All rights reserved.

A YinYang bipolar fuzzy cognitive TOPSIS method to bipolar disorder diagnosis.

PubMed

Han, Ying; Lu, Zhenyu; Du, Zhenguang; Luo, Qi; Chen, Sheng

2018-05-01

Bipolar disorder is often mis-diagnosed as unipolar depression in the clinical diagnosis. The main reason is that, different from other diseases, bipolarity is the norm rather than exception in bipolar disorder diagnosis. YinYang bipolar fuzzy set captures bipolarity and has been successfully used to construct a unified inference mathematical modeling method to bipolar disorder clinical diagnosis. Nevertheless, symptoms and their interrelationships are not considered in the existing method, circumventing its ability to describe complexity of bipolar disorder. Thus, in this paper, a YinYang bipolar fuzzy multi-criteria group decision making method to bipolar disorder clinical diagnosis is developed. Comparing with the existing method, the new one is more comprehensive. The merits of the new method are listed as follows: First of all, multi-criteria group decision making method is introduced into bipolar disorder diagnosis for considering different symptoms and multiple doctors' opinions. Secondly, the discreet diagnosis principle is adopted by the revised TOPSIS method. Last but not the least, YinYang bipolar fuzzy cognitive map is provided for the understanding of interrelations among symptoms. The illustrated case demonstrates the feasibility, validity, and necessity of the theoretical results obtained. Moreover, the comparison analysis demonstrates that the diagnosis result is more accurate, when interrelations about symptoms are considered in the proposed method. In a conclusion, the main contribution of this paper is to provide a comprehensive mathematical approach to improve the accuracy of bipolar disorder clinical diagnosis, in which both bipolarity and complexity are considered. Copyright © 2018 Elsevier B.V. All rights reserved.

Integrative Etiopathogenetic Models of Psychotic Disorders: Methods, Evidence and Concepts

PubMed Central

Gaebel, Wolfgang; Zielasek, Jürgen

2011-01-01

Integrative models of the etiopathogesnesis of psychotic disorders are needed since a wealth of information from such diverse fields as neurobiology, psychology, and the social sciences is currently changing the concepts of mental disorders. Several approaches to integrate these streams of information into coherent concepts of psychosis are feasible and will need to be assessed in future experimental studies. Common to these concepts are the notion of psychotic disorders as brain disorders and a polythetic approach in that it is increasingly realized that a multitude of interindividually partially different pathogenetic factors interact in individual persons in a complex fashion resulting in the clinical symptoms of psychosis. PMID:21860047

Binding of Multiple Features in Memory by High-Functioning Adults with Autism Spectrum Disorder

ERIC Educational Resources Information Center

Bowler, Dermot M.; Gaigg, Sebastian B.; Gardiner, John M.

2014-01-01

Diminished episodic memory and diminished use of semantic information to aid recall by individuals with autism spectrum disorder (ASD) are both thought to result from diminished relational binding of elements of complex stimuli. To test this hypothesis, we asked high-functioning adults with ASD and typical comparison participants to study grids in…

Developing Family Psychoeducational Treatments for Patients with Bipolar and Other Severe Psychiatric Disorders: A Pathway from Basic Research to Clinical Trials.

ERIC Educational Resources Information Center

Miklowitz, David J.; Hooley, Jill M.

1998-01-01

Describes the development pathway of family treatments for patients with severe and persistent psychiatric disorders in a population for whom family attributes have prognostic importance. The methodological complexities of psychosocial treatment studies are many. Moreover, the results of these studies often reflect interactions between treatment,…

The potential of induced pluripotent stem cells in models of neurological disorders: implications on future therapy.

PubMed

Crook, Jeremy Micah; Wallace, Gordon; Tomaskovic-Crook, Eva

2015-03-01

There is an urgent need for new and advanced approaches to modeling the pathological mechanisms of complex human neurological disorders. This is underscored by the decline in pharmaceutical research and development efficiency resulting in a relative decrease in new drug launches in the last several decades. Induced pluripotent stem cells represent a new tool to overcome many of the shortcomings of conventional methods, enabling live human neural cell modeling of complex conditions relating to aberrant neurodevelopment, such as schizophrenia, epilepsy and autism as well as age-associated neurodegeneration. This review considers the current status of induced pluripotent stem cell-based modeling of neurological disorders, canvassing proven and putative advantages, current constraints, and future prospects of next-generation culture systems for biomedical research and translation.

Complexity in language learning and treatment.

PubMed

Thompson, Cynthia K

2007-02-01

To introduce a Clinical Forum focused on the Complexity Account of Treatment Efficacy (C. K. Thompson, L. P. Shapiro, S. Kiran, & J. Sobecks, 2003), a counterintuitive but effective approach for treating language disorders. This approach espouses training complex structures to promote generalized improvement of simpler, linguistically related structures. Three articles are included, addressing complexity in treatment of phonology, lexical-semantics, and syntax. Complexity hierarchies based on models of normal language representation and processing are discussed in each language domain. In addition, each article presents single-subject controlled experimental studies examining the complexity effect. By counterbalancing treatment of complex and simple structures across participants, acquisition and generalization patterns are examined as they emerge. In all language domains, cascading generalization occurs from more to less complex structures; however, the opposite pattern is rarely seen. The results are robust, with replication within and across participants. The construct of complexity appears to be a general principle that is relevant to treating a range of language disorders in both children and adults. While challenging the long-standing clinical notion that treatment should begin with simple structures, mounting evidence points toward the facilitative effects of using more complex structures as a starting point for treatment.

[Systemic lupus erythematosus and pregnancy].

PubMed

Basheva, S; Nikolov, A; Stoilov, R; Stoilov, N

2012-01-01

Connective-tissue disorders, also referred to as collagen-vascular disorders, are characterized by autoantibody-mediated connective-tissue abnormalities. These are also called immune-complex diseases because many involve deposition of immune complexes in specific organ or tissue sites. Some of these disorders are characterized by sterile inflammation, especially of the skin, joints, blood vessels, and kidneys, and are referred to as rheumatic diseases. For inexplicable reasons, many rheumatic diseases primarily affect women. Another major category of connective-tissue diseases includes inherited disorders of bone, skin, cartilage, blood vessels. Examples include Marfan syndrome, osteogenesis imperfecta, and Ehlers-Danlos syndrome. Lupus erythematosus (LE) is the main and most important disease in the group of systemic connective tissue diseases. It is heterogeneous, multiple organs autoimmune inflammatory disease with complex pathogenesis, which is the result of interaction between the susceptible genes and environmental factors that lead to abnormal immune response. In this review will consider: its incidence, pathogenesis, clinical forms and clinical features and diagnosis set based on generally accepted clinical criteria developed by the American College of Rheumatology (ACR), the course of pregnancy in patients suffering from LE, the most common complications of LE during pregnancy and antiphospholipid syndrome as part of LE.

Treatment of borderline personality disorder and co-occurring anxiety disorders

PubMed Central

Valenstein, Helen R.

2013-01-01

Anxiety disorders are highly prevalent among individuals with borderline personality disorder, with comorbidity rates of up to 90%. Anxiety disorders have been found to reduce the likelihood of achieving remission from borderline personality disorder over time and to increase the risk of suicide and self-injury in this population. Evidence-based treatments for borderline personality disorder have not sufficiently focused on targeting anxiety disorders, and their effects on these disorders are either limited or unknown. Conversely, evidence-based treatments for anxiety disorders typically exclude suicidal, self-injuring, and seriously comorbid patients, thereby limiting their generalizability to individuals with borderline personality disorder. To address these limitations, recent research has begun to emerge focused on developing and evaluating treatments for individuals with co-occurring borderline personality disorder and anxiety disorders, specifically posttraumatic stress disorder (PTSD), with promising initial results. However, there is a need for additional research in this area, particularly studies evaluating the treatment of anxiety disorders among high-risk and complex borderline personality disorder patients. PMID:23710329

Altered Astrocyte-Neuron Interactions and Epileptogenesis in Tuberous Sclerosis Complex Disorder

DTIC Science & Technology

2015-06-01

Tsc1-deficient astrocytes on neuronal morphology and neuronal activity associated with seizures . 2. KEY WORDS epilepsy , seizure , tuberous sclerosis...AWARD NUMBER: W81XWH-12-1-0196 TITLE: Altered Astrocyte-Neuron Interactions and Epileptogenesis in Tuberous Sclerosis Complex Disorder PRINCIPAL...TITLE AND SUBTITLE Altered Astrocyte-Neuron Interactions and Epileptogenesis in Tuberous Sclerosis Complex Disorder 5a. CONTRACT NUMBER 5b. GRANT

Complex posttraumatic stress disorder: The need to consolidate a distinct clinical syndrome or to reevaluate features of psychiatric disorders following interpersonal trauma?

PubMed

Giourou, Evangelia; Skokou, Maria; Andrew, Stuart P; Alexopoulou, Konstantina; Gourzis, Philippos; Jelastopulu, Eleni

2018-03-22

Complex posttraumatic stress disorder (Complex PTSD) has been recently proposed as a distinct clinical entity in the WHO International Classification of Diseases, 11 th version, due to be published, two decades after its first initiation. It is described as an enhanced version of the current definition of PTSD, with clinical features of PTSD plus three additional clusters of symptoms namely emotional dysregulation, negative self-cognitions and interpersonal hardship, thus resembling the clinical features commonly encountered in borderline personality disorder (BPD). Complex PTSD is related to complex trauma which is defined by its threatening and entrapping context, generally interpersonal in nature. In this manuscript, we review the current findings related to traumatic events predisposing the above-mentioned disorders as well as the biological correlates surrounding them, along with their clinical features. Furthermore, we suggest that besides the present distinct clinical diagnoses (PTSD; Complex PTSD; BPD), there is a cluster of these comorbid disorders, that follow a continuum of trauma and biological severity on a spectrum of common or similar clinical features and should be treated as such. More studies are needed to confirm or reject this hypothesis, particularly in clinical terms and how they correlate to clinical entities' biological background, endorsing a shift from the phenomenologically only classification of psychiatric disorders towards a more biologically validated classification.

NMDA receptor activation regulates sociability by its effect on mTOR signaling activity.

PubMed

Burket, Jessica A; Benson, Andrew D; Tang, Amy H; Deutsch, Stephen I

2015-07-03

Tuberous Sclerosis Complex is one example of a syndromic form of autism spectrum disorder associated with disinhibited activity of mTORC1 in neurons (e.g., cerebellar Purkinje cells). mTORC1 is a complex protein possessing serine/threonine kinase activity and a key downstream molecule in a signaling cascade beginning at the cell surface with the transduction of neurotransmitters (e.g., glutamate and acetylcholine) and nerve growth factors (e.g., Brain-Derived Neurotrophic Factor). Interestingly, the severity of the intellectual disability in Tuberous Sclerosis Complex may relate more to this metabolic disturbance (i.e., overactivity of mTOR signaling) than the density of cortical tubers. Several recent reports showed that rapamycin, an inhibitor of mTORC1, improved sociability and other symptoms in mouse models of Tuberous Sclerosis Complex and autism spectrum disorder, consistent with mTORC1 overactivity playing an important pathogenic role. NMDA receptor activation may also dampen mTORC1 activity by at least two possible mechanisms: regulating intraneuronal accumulation of arginine and the phosphorylation status of a specific extracellular signal regulating kinase (i.e., ERK1/2), both of which are "drivers" of mTORC1 activity. Conceivably, the prosocial effects of targeting the NMDA receptor with agonists in mouse models of autism spectrum disorders result from their ability to dampen mTORC1 activity in neurons. Strategies for dampening mTORC1 overactivity by NMDA receptor activation may be preferred to its direct inhibition in chronic neurodevelopmental disorders, such as autism spectrum disorders. Copyright © 2015 Elsevier Inc. All rights reserved.

The coeruleus/subcoeruleus complex in idiopathic rapid eye movement sleep behaviour disorder.

PubMed

Ehrminger, Mickael; Latimier, Alice; Pyatigorskaya, Nadya; Garcia-Lorenzo, Daniel; Leu-Semenescu, Smaranda; Vidailhet, Marie; Lehericy, Stéphane; Arnulf, Isabelle

2016-04-01

Idiopathic rapid eye movement sleep behaviour disorder is characterized by nocturnal violence, increased muscle tone during rapid eye movement sleep and the lack of any other neurological disease. However, idiopathic rapid eye movement sleep behaviour disorder can precede parkinsonism and dementia by several years. Using 3 T magnetic resonance imaging and neuromelanin-sensitive sequences, we previously found that the signal intensity was reduced in the locus coeruleus/subcoeruleus area of patients with Parkinson's disease and rapid eye movement sleep behaviour disorder. Here, we studied the integrity of the locus coeruleus/subcoeruleus complex with neuromelanin-sensitive imaging in 21 patients with idiopathic rapid eye movement sleep behaviour disorder and compared the results with those from 21 age- and gender-matched healthy volunteers. All subjects underwent a clinical examination, motor, cognitive, autonomous, psychological, olfactory and colour vision tests, and rapid eye movement sleep characterization using video-polysomnography and 3 T magnetic resonance imaging. The patients more frequently had preclinical markers of alpha-synucleinopathies, including constipation, olfactory deficits, orthostatic hypotension, and subtle motor impairment. Using neuromelanin-sensitive imaging, reduced signal intensity was identified in the locus coeruleus/subcoeruleus complex of the patients with idiopathic rapid eye movement sleep behaviour. The mean sensitivity of the visual analyses of the signal performed by neuroradiologists who were blind to the clinical diagnoses was 82.5%, and the specificity was 81% for the identification of idiopathic rapid eye movement sleep behaviour. The results confirm that this complex is affected in idiopathic rapid eye movement sleep behaviour (to the same degree as it is affected in Parkinson's disease). Neuromelanin-sensitive imaging provides an early marker of non-dopaminergic alpha-synucleinopathy that can be detected on an individual basis. © The Author (2016). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Strategic memory in adults with anorexia nervosa: are there similarities to obsessive compulsive spectrum disorders?

PubMed

Sherman, Bonnie J; Savage, Cary R; Eddy, Kamryn T; Blais, Mark A; Deckersbach, Thilo; Jackson, Safia C; Franko, Debra L; Rauch, Scott L; Herzog, David B

2006-09-01

There is growing interest in the relationship between anorexia nervosa (AN) and obsessive-compulsive (OC) spectrum disorders (e.g., OCD, body dysmorphic disorder [BDD]). Previous neuropsychological investigations of OC spectrum disorders have identified problems with the efficient use of strategy on complex measures of learning and memory. This study evaluated nonverbal strategic memory in AN outpatients using an approach previously applied to OC spectrum disorders. Eighteen patients with AN and 19 healthy control participants completed the Rey-Osterrieth Complex Figure Test (RCFT), a widely used measure of nonverbal strategic planning, learning, and memory. Individuals with AN differed significantly from healthy controls in the organizational strategies used to copy the RCFT figure, and they recalled significantly less information on both immediate and delayed testing. Multiple regression analyses indicated that group differences in learning were mediated by copy organizational strategies. These results are identical to study findings in OCD and BDD, indicating important shared neuropsychological features among AN and these OC spectrum disorders. As in OCD and BDD, the essential cognitive deficit in AN was impaired use of organizational strategies, which may inform our understanding of the pathophysiology of AN and potentially offer treatment implications. Copyright (c) 2006 by Wiley Periodicals, Inc.

Temporal complexity in emission from Anderson localized lasers

NASA Astrophysics Data System (ADS)

Kumar, Randhir; Balasubrahmaniyam, M.; Alee, K. Shadak; Mujumdar, Sushil

2017-12-01

Anderson localization lasers exploit resonant cavities formed due to structural disorder. The inherent randomness in the structure of these cavities realizes a probability distribution in all cavity parameters such as quality factors, mode volumes, mode structures, and so on, implying resultant statistical fluctuations in the temporal behavior. Here we provide direct experimental measurements of temporal width distributions of Anderson localization lasing pulses in intrinsically and extrinsically disordered coupled-microresonator arrays. We first illustrate signature exponential decays in the spatial intensity distributions of the lasing modes that quantify their localized character, and then measure the temporal width distributions of the pulsed emission over several configurations. We observe a dependence of temporal widths on the disorder strength, wherein the widths show a single-peaked, left-skewed distribution in extrinsic disorder and a dual-peaked distribution in intrinsic disorder. We propose a model based on coupled rate equations for an emitter and an Anderson cavity with a random mode structure, which gives excellent quantitative and qualitative agreement with the experimental observations. The experimental and theoretical analyses bring to the fore the temporal complexity in Anderson-localization-based lasing systems.

Weakly-coupled quasi-1D helical modes in disordered 3D topological insulator quantum wires

NASA Astrophysics Data System (ADS)

Dufouleur, J.; Veyrat, L.; Dassonneville, B.; Xypakis, E.; Bardarson, J. H.; Nowka, C.; Hampel, S.; Schumann, J.; Eichler, B.; Schmidt, O. G.; Büchner, B.; Giraud, R.

2017-04-01

Disorder remains a key limitation in the search for robust signatures of topological superconductivity in condensed matter. Whereas clean semiconducting quantum wires gave promising results discussed in terms of Majorana bound states, disorder makes the interpretation more complex. Quantum wires of 3D topological insulators offer a serious alternative due to their perfectly-transmitted mode. An important aspect to consider is the mixing of quasi-1D surface modes due to the strong degree of disorder typical for such materials. Here, we reveal that the energy broadening γ of such modes is much smaller than their energy spacing Δ, an unusual result for highly-disordered mesoscopic nanostructures. This is evidenced by non-universal conductance fluctuations in highly-doped and disordered Bi2Se3 and Bi2Te3 nanowires. Theory shows that such a unique behavior is specific to spin-helical Dirac fermions with strong quantum confinement, which retain ballistic properties over an unusually large energy scale due to their spin texture. Our result confirms their potential to investigate topological superconductivity without ambiguity despite strong disorder.

Weakly-coupled quasi-1D helical modes in disordered 3D topological insulator quantum wires

PubMed Central

Dufouleur, J.; Veyrat, L.; Dassonneville, B.; Xypakis, E.; Bardarson, J. H.; Nowka, C.; Hampel, S.; Schumann, J.; Eichler, B.; Schmidt, O. G.; Büchner, B.; Giraud, R.

2017-01-01

Disorder remains a key limitation in the search for robust signatures of topological superconductivity in condensed matter. Whereas clean semiconducting quantum wires gave promising results discussed in terms of Majorana bound states, disorder makes the interpretation more complex. Quantum wires of 3D topological insulators offer a serious alternative due to their perfectly-transmitted mode. An important aspect to consider is the mixing of quasi-1D surface modes due to the strong degree of disorder typical for such materials. Here, we reveal that the energy broadening γ of such modes is much smaller than their energy spacing Δ, an unusual result for highly-disordered mesoscopic nanostructures. This is evidenced by non-universal conductance fluctuations in highly-doped and disordered Bi2Se3 and Bi2Te3 nanowires. Theory shows that such a unique behavior is specific to spin-helical Dirac fermions with strong quantum confinement, which retain ballistic properties over an unusually large energy scale due to their spin texture. Our result confirms their potential to investigate topological superconductivity without ambiguity despite strong disorder. PMID:28374744

Weakly-coupled quasi-1D helical modes in disordered 3D topological insulator quantum wires.

PubMed

Dufouleur, J; Veyrat, L; Dassonneville, B; Xypakis, E; Bardarson, J H; Nowka, C; Hampel, S; Schumann, J; Eichler, B; Schmidt, O G; Büchner, B; Giraud, R

2017-04-04

Disorder remains a key limitation in the search for robust signatures of topological superconductivity in condensed matter. Whereas clean semiconducting quantum wires gave promising results discussed in terms of Majorana bound states, disorder makes the interpretation more complex. Quantum wires of 3D topological insulators offer a serious alternative due to their perfectly-transmitted mode. An important aspect to consider is the mixing of quasi-1D surface modes due to the strong degree of disorder typical for such materials. Here, we reveal that the energy broadening γ of such modes is much smaller than their energy spacing Δ, an unusual result for highly-disordered mesoscopic nanostructures. This is evidenced by non-universal conductance fluctuations in highly-doped and disordered Bi2Se3 and Bi 2 Te 3 nanowires. Theory shows that such a unique behavior is specific to spin-helical Dirac fermions with strong quantum confinement, which retain ballistic properties over an unusually large energy scale due to their spin texture. Our result confirms their potential to investigate topological superconductivity without ambiguity despite strong disorder.

Isolated Cataplexy and REM Sleep Behavior Disorder After Pontine Stroke

PubMed Central

Reynolds, Thomas Q.; Roy, Asim

2011-01-01

Cataplexy is a complex neurologic phenomenon during wakefulness probably resulting from impairment of pontine and hypothalamic control over muscle tone. REM sleep behavior disorder (RSBD) is characterized by the presence of REM sleep without atonia manifesting clinically as disruptive or injurious behaviors. We present here a patient with both cataplexy and RSBD following pontine encephalomalacia. The clinical presentation provides insight into the possible pathobiology of both waking and sleeping disorders of REM sleep regulation. Citation: Reynolds TQ; Roy A. Isolated cataplexy and REM sleep behavior disorder after pontine stroke. J Clin Sleep Med 2011;7(2):211-213. PMID:21509338

Individual differences in components of impulsivity and effortful control moderate the relation between borderline personality disorder traits and emotion recognition in a sample of university students.

PubMed

Preti, Emanuele; Richetin, Juliette; Suttora, Chiara; Pisani, Alberto

2016-04-30

Dysfunctions in social cognition characterize personality disorders. However, mixed results emerged from literature on emotion processing. Borderline Personality Disorder (BPD) traits are either associated with enhanced emotion recognition, impairments, or equal functioning compared to controls. These apparent contradictions might result from the complexity of emotion recognition tasks used and from individual differences in impulsivity and effortful control. We conducted a study in a sample of undergraduate students (n=80), assessing BPD traits, using an emotion recognition task that requires the processing of only visual information or both visual and acoustic information. We also measured individual differences in impulsivity and effortful control. Results demonstrated the moderating role of some components of impulsivity and effortful control on the capability of BPD traits in predicting anger and happiness recognition. We organized the discussion around the interaction between different components of regulatory functioning and task complexity for a better understanding of emotion recognition in BPD samples. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Mapping multivalency and differential affinities within large intrinsically disordered protein complexes with segmental motion analysis.

PubMed

Milles, Sigrid; Lemke, Edward A

2014-07-07

Intrinsically disordered proteins (IDPs) can bind to multiple interaction partners. Numerous binding regions in the IDP that act in concert through complex cooperative effects facilitate such interactions, but complicate studying IDP complexes. To address this challenge we developed a combined fluorescence correlation and time-resolved polarization spectroscopy approach to study the binding properties of the IDP nucleoporin153 (Nup153) to nuclear transport receptors (NTRs). The detection of segmental backbone mobility of Nup153 within the unperturbed complex provided a readout of local, region-specific binding properties that are usually masked in measurements of the whole IDP. The binding affinities of functionally and structurally diverse NTRs to distinct regions of Nup153 can differ by orders of magnitudes-a result with implications for the diversity of transport routes in nucleocytoplasmic transport. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Lattice-cell orientation disorder in complex spinel oxides

DOE PAGES

Chen, Yan; Cheng, Yongqiang; Li, Juchuan; ...

2016-11-07

Transition metal (TM) substitution has been widely applied to change complex oxides crystal structures to create high energy density electrodes materials in high performance rechargeable lithium-ion batteries. The complex local structure in the oxides imparted by the TM arrangement often impacts their electrochemical behaviors by influencing the diffusion and intercalation of lithium. Here, a major discrepancy is demonstrated between the global and local structures of the promising high energy density and high voltage LiNi 0.5Mn 1.5O 4 spinel cathode material that contradicts the existing structural models. A new single-phase lattice-cell orientation disorder model is proposed as the mechanism for themore » local ordering that explains how the inhomogeneous local distortions and the coherent connection give rise to the global structure in the complex oxide. As a result, the single-phase model is consistent with the electrochemical behavior observation of the materials.« less

Integrated circuits and molecular components for stress and feeding: implications for eating disorders

PubMed Central

Hardaway, J. A.; Crowley, N. A.; Bulik, C. M.; Kash, T. L.

2015-01-01

Eating disorders are complex brain disorders that afflict millions of individuals worldwide. The etiology of these diseases is not fully understood, but a growing body of literature suggests that stress and anxiety may play a critical role in their development. As our understanding of the genetic and environmental factors that contribute to disease in clinical populations like anorexia nervosa, bulimia nervosa and binge eating disorder continue to grow, neuroscientists are using animal models to understand the neurobiology of stress and feeding. We hypothesize that eating disorder clinical phenotypes may result from stress-induced maladaptive alterations in neural circuits that regulate feeding, and that these circuits can be neurochemically isolated using animal model of eating disorders. PMID:25366309

Standards of care for obsessive–compulsive disorder centres

PubMed Central

Menchón, José M.; van Ameringen, Michael; Dell’Osso, Bernardo; Denys, Damiaan; Figee, Martijn; Grant, Jon E.; Hollander, Eric; Marazziti, Donatella; Nicolini, Humberto; Pallanti, Stefano; Ruck, Christian; Shavitt, Roseli; Stein, Dan J.; Andersson, Erik; Bipeta, Rajshekhar; Cath, Danielle C.; Drummond, Lynne; Feusner, Jamie; Geller, Daniel A.; Hranov, Georgi; Lochner, Christine; Matsunaga, Hisato; McCabe, Randy E.; Mpavaenda, Davis; Nakamae, Takashi; O'Kearney, Richard; Pasquini, Massimo; Pérez Rivera, Ricardo; Poyurovsky, Michael; Real, Eva; do Rosário, Maria Conceição; Soreni, Noam; Swinson, Richard P.; Vulink, Nienke; Zohar, Joseph; Fineberg, Naomi

2016-01-01

Abstract In recent years, many assessment and care units for obsessive–compulsive disorder (OCD) have been set up in order to detect, diagnose and to properly manage this complex disorder, but there is no consensus regarding the key functions that these units should perform. The International College of Obsessive-Compulsive Spectrum Disorders (ICOCS) together with the Obsessive Compulsive and Related Disorders Network (OCRN) of the European College of Neuropsychopharmacology (ECNP) and the Anxiety and Obsessive Compulsive Disorders Section of the World Psychiaric Association (WPA) has developed a standards of care programme for OCD centres. The goals of this collaborative initiative are promoting basic standards, improving the quality of clinical care and enhance the validity and reliability of research results provided by different facilities and countries. PMID:27359333

Attention-deficit hyperactivity disorder (ADHD) and tuberous sclerosis complex.

PubMed

D'Agati, Elisa; Moavero, Romina; Cerminara, Caterina; Curatolo, Paolo

2009-10-01

The neurobiological basis of attention-deficit hyperactivity disorder (ADHD) in tuberous sclerosis complex is still largely unknown. Cortical tubers may disrupt several brain networks that control different types of attention. Frontal lobe dysfunction due to seizures or epileptiform electroencephalographic discharges may perturb the development of brain systems that underpin attentional and hyperactive functions during a critical early stage of brain maturation. Comorbidity of attention-deficit hyperactivity disorder (ADHD) with mental retardation and autism spectrum disorders is frequent in children with tuberous sclerosis. Attention-deficit hyperactivity disorder (ADHD) may also reflect a direct effect of the abnormal genetic program. Treatment of children with tuberous sclerosis complex with combined symptoms of attention-deficit hyperactivity disorder (ADHD) and epilepsy may represent a challenge for clinicians, because antiepileptic therapy and drugs used to treat attention-deficit hyperactivity disorder (ADHD) may aggravate the clinical picture of each other.

Sequence Complexity of Amyloidogenic Regions in Intrinsically Disordered Human Proteins

PubMed Central

Das, Swagata; Pal, Uttam; Das, Supriya; Bagga, Khyati; Roy, Anupam; Mrigwani, Arpita; Maiti, Nakul C.

2014-01-01

An amyloidogenic region (AR) in a protein sequence plays a significant role in protein aggregation and amyloid formation. We have investigated the sequence complexity of AR that is present in intrinsically disordered human proteins. More than 80% human proteins in the disordered protein databases (DisProt+IDEAL) contained one or more ARs. With decrease of protein disorder, AR content in the protein sequence was decreased. A probability density distribution analysis and discrete analysis of AR sequences showed that ∼8% residue in a protein sequence was in AR and the region was in average 8 residues long. The residues in the AR were high in sequence complexity and it seldom overlapped with low complexity regions (LCR), which was largely abundant in disorder proteins. The sequences in the AR showed mixed conformational adaptability towards α-helix, β-sheet/strand and coil conformations. PMID:24594841

Complex psychotropic polypharmacy in bipolar disorder across varying mood polarities: A prospective cohort study of 2712 inpatients.

PubMed

Golden, Julia C; Goethe, John W; Woolley, Stephen B

2017-10-15

It is common for patients with bipolar disorder (BP) to receive multiple psychotropics, but few studies have assessed demographic and clinical features associated with risk for receiving complex psychotropic polypharmacy. This longitudinal cohort study examined 2712 inpatients with a DSM-IV clinical diagnosis of BP to assess associations between complex polypharmacy (defined as ≥4 psychotropics) and demographic and clinical features; associations with risk of rehospitalization were also examined. Logistic regressions were performed with the sample as a whole and with each of four DSM-IV BP subtypes individually. Complex polypharmacy was present in 21.0%. BP-I depressed patients were more likely to receive complex regimens than BP-I manic, BP-I mixed or BP-II patients. In the sample as a whole, variables significantly associated with complex polypharmacy included female, white, psychotic features and a co-diagnosis of borderline personality, post-traumatic stress or another anxiety disorder. The only examined medication not significantly associated with complex polypharmacy was lithium, although only in BP-I depressed and BP-I mixed. Complex polypharmacy was associated with rehospitalization in BP-I mania within 15 and 30days post index hospitalization. All data were from one clinical facility; results may not generalize to other settings and patient populations. BP-I depression may pose a greater treatment challenge than the other BP subtypes. Lithium may confer an overall advantage compared to other medications in BP-I depressed and BP-I mixed. Further research is needed to guide pharmacotherapy decisions in BP patients. Copyright © 2017 Elsevier B.V. All rights reserved.

The Role of the New mTOR Complex, mTORC2, in Autism Spectrum Disorders

DTIC Science & Technology

2015-10-01

1 AWARD NUMBER: W81XWH-13-1-0380 TITLE: "The Role of the New mTOR Complex, mTORC2, in Autism Spectrum Disorders " PRINCIPAL INVESTIGATOR: Mauro...34The Role of the New mTOR Complex, mTORC2, in Autism Spectrum Disorders " 5a. CONTRACT NUMBER W81XWH-13-1-0380 5b. GRANT NUMBER 5c. PROGRAM...Pten. These insights hold the promise for new mTORC2-based treatment of ASD. 15. SUBJECT TERMS Autism Spectrum Disorder (ASD), mTORC2, mTORC1

Emotional and Cognitive Self-regulation, an EEG Study

ClinicalTrials.gov

2016-08-08

Posttraumatic Stress Disorder PTSD); Complex Posttraumatic Stress Disorder (cPTSD); Dissociative Disorder Not Otherwise Specified (DDNOS); Dissociative Identity Disorder (DID); Borderline Personality Disorder (BPD)

Depression as a systemic syndrome: mapping the feedback loops of major depressive disorder

PubMed Central

Wittenborn, A. K.; Rahmandad, H.; Rick, J.; Hosseinichimeh, N.

2016-01-01

Background Depression is a complex public health problem with considerable variation in treatment response. The systemic complexity of depression, or the feedback processes among diverse drivers of the disorder, contribute to the persistence of depression. This paper extends prior attempts to understand the complex causal feedback mechanisms that underlie depression by presenting the first broad boundary causal loop diagram of depression dynamics. Method We applied qualitative system dynamics methods to map the broad feedback mechanisms of depression. We used a structured approach to identify candidate causal mechanisms of depression in the literature. We assessed the strength of empirical support for each mechanism and prioritized those with support from validation studies. Through an iterative process, we synthesized the empirical literature and created a conceptual model of major depressive disorder. Results The literature review and synthesis resulted in the development of the first causal loop diagram of reinforcing feedback processes of depression. It proposes candidate drivers of illness, or inertial factors, and their temporal functioning, as well as the interactions among drivers of depression. The final causal loop diagram defines 13 key reinforcing feedback loops that involve nine candidate drivers of depression. Conclusions Future research is needed to expand upon this initial model of depression dynamics. Quantitative extensions may result in a better understanding of the systemic syndrome of depression and contribute to personalized methods of evaluation, prevention and intervention. PMID:26621339

Tuberous sclerosis associated neuropsychiatric disorders (TAND) and the TAND Checklist.

PubMed

de Vries, Petrus J; Whittemore, Vicky H; Leclezio, Loren; Byars, Anna W; Dunn, David; Ess, Kevin C; Hook, Dena; King, Bryan H; Sahin, Mustafa; Jansen, Anna

2015-01-01

Tuberous sclerosis complex is a multisystem genetic disorder with a range of physical manifestations that require evaluation, surveillance, and management. Individuals with tuberous sclerosis complex also have a range of behavioral, psychiatric, intellectual, academic, neuropsychologic, and psychosocial difficulties. These may represent the greatest burden of the disease. Around 90% of individuals with tuberous sclerosis complex will have some of these difficulties during their lifetime, yet only about 20% ever receive evaluation and treatment. The Neuropsychiatry Panel at the 2012 Tuberous Sclerosis Complex International Consensus Conference expressed concern about the significant "treatment gap" and about confusion regarding terminology relating to the biopsychosocial difficulties associated with tuberous sclerosis complex. The Tuberous Sclerosis Complex Neuropsychiatry Panel coined the term TAND-tuberous sclerosis complex-associated neuropsychiatric disorders-to bring together these multidimensional manifestations of the disorder, and recommended annual screening for TAND. In addition, the Panel agreed to develop a TAND Checklist as a guide for screening. Here, we present an outline of the conceptualization of TAND, rationale for the structure of the TAND Checklist, and include the full US English version of the TAND Checklist. We hope that the unified term TAND and the TAND Checklist will raise awareness of the importance of tuberous sclerosis complex-associated neuropsychiatric disorders and of the major burden of disease associated with it, provide a shared language and a simple tool to describe and evaluate the different levels of TAND, alert clinical teams and families or individuals of the importance of screening, assessment, and treatment of TAND, and provide a shared framework for future studies of tuberous sclerosis complex-associated neuropsychiatric disorders. Copyright © 2015 Elsevier Inc. All rights reserved.

Affect dysregulation, psychoform dissociation, and adult relational fears mediate the relationship between childhood trauma and complex posttraumatic stress disorder independent of the symptoms of borderline personality disorder.

PubMed

van Dijke, Annemiek; Hopman, Juliette A B; Ford, Julian D

2018-01-01

Objective : Complex posttraumatic stress disorder (CPTSD) as defined by the Disorders of Extreme Stress Not Otherwise Specified (DESNOS) formulation is associated with childhood relational trauma and involves relational impairment, affect dysregulation, and identity alterations. However, the distinct contributions of relational impairment (operationalized in the form fears of closeness or abandonment), affect dysregulation (operationalized in the form of overregulation and under-regulation of affect), and identity alterations (operationalized in the form of positive or negative psychoform or somatoform dissociation) to the relationship between childhood trauma and CPTSD/DESNOS have not been systematically tested. Method and Results : In a clinical sample of adults diagnosed with severe and chronic psychiatric and personality disorders ( n  = 472; M  = 34.7 years, SD  = 10.1), structural equation modelling with bootstrap 95% confidence intervals demonstrated that the association between childhood trauma and CPTSD/DESNOS symptoms in adulthood was partially mediated by under-regulation of affect, negative psychoform dissociation, and adult relational fears of closeness and of abandonment. These results also were independent of the effects of borderline personality disorder (BPD) symptoms. Conclusions : Some, but not all, hypothesized components of the DESNOS formulation of CPTSD statistically mediate the relationship between childhood trauma and adult CPTSD/DESNOS. These relationships appear specific to CPTSD/DESNOS and not to the effects of another potential sequelae of childhood trauma BPD. Replication with prospective longitudinal studies is needed.

Evolution of disorder in Mediator complex and its functional relevance

PubMed Central

Nagulapalli, Malini; Maji, Sourobh; Dwivedi, Nidhi; Dahiya, Pradeep; Thakur, Jitendra K.

2016-01-01

Mediator, an important component of eukaryotic transcriptional machinery, is a huge multisubunit complex. Though the complex is known to be conserved across all the eukaryotic kingdoms, the evolutionary topology of its subunits has never been studied. In this study, we profiled disorder in the Mediator subunits of 146 eukaryotes belonging to three kingdoms viz., metazoans, plants and fungi, and attempted to find correlation between the evolution of Mediator complex and its disorder. Our analysis suggests that disorder in Mediator complex have played a crucial role in the evolutionary diversification of complexity of eukaryotic organisms. Conserved intrinsic disordered regions (IDRs) were identified in only six subunits in the three kingdoms whereas unique patterns of IDRs were identified in other Mediator subunits. Acquisition of novel molecular recognition features (MoRFs) through evolution of new subunits or through elongation of the existing subunits was evident in metazoans and plants. A new concept of ‘junction-MoRF’ has been introduced. Evolutionary link between CBP and Med15 has been provided which explain the evolution of extended-IDR in CBP from Med15 KIX-IDR junction-MoRF suggesting role of junction-MoRF in evolution and modulation of protein–protein interaction repertoire. This study can be informative and helpful in understanding the conserved and flexible nature of Mediator complex across eukaryotic kingdoms. PMID:26590257

Influence of religious aspects and personal beliefs on psychological behavior: focus on anxiety disorders

PubMed Central

Agorastos, Agorastos; Demiralay, Cüneyt; Huber, Christian G

2014-01-01

The current paper presents literature relevant to the relationship of religiosity, spirituality, and personal beliefs with mental health and, in particular, anxiety disorders as an empirical narrative review, providing an overview on the most important and clinically relevant research results on the topic. The relationship between religiosity/spirituality, personal beliefs (ie, magical ideation and paranormal beliefs), and mental health has lately been studied extensively, and results have indicated significant associations among these variables. However, scientific approaches to this field are complex and multidimensional, partly leading to poor operationalization, incomparable data, and contradictory results. Literature demonstrates that higher religiosity/spirituality and magical ideation scores have often been associated with increased obsessive–compulsive traits. Similar results could not be confidently replicated for other anxiety disorders. However, it is still unclear if these differences suggest a specific association with obsessive–compulsive traits and reflect deviating etiopathogenetic and cognitive aspects between obsessive–compulsive disorder and other anxiety disorders, or if these results are biased through other factors. Religiosity/spirituality and personal beliefs constitute important parameters of human experience and deserve greater consideration in the psychotherapeutic treatment of psychiatric disorders. PMID:24648780

Tuberous sclerosis complex: Recent advances in manifestations and therapy.

PubMed

Wataya-Kaneda, Mari; Uemura, Motohide; Fujita, Kazutoshi; Hirata, Haruhiko; Osuga, Keigo; Kagitani-Shimono, Kuriko; Nonomura, Norio

2017-09-01

Tuberous sclerosis complex is an autosomal dominant inherited disorder characterized by generalized involvement and variable manifestations with a birth incidence of 1:6000. In a quarter of a century, significant progress in tuberous sclerosis complex has been made. Two responsible genes, TSC1 and TSC2, which encode hamartin and tuberin, respectively, were discovered in the 1990s, and their functions were elucidated in the 2000s. Hamartin-Tuberin complex is involved in the phosphoinositide 3-kinase-protein kinase B-mammalian target of rapamycin signal transduction pathway, and suppresses mammalian target of rapamycin complex 1 activity, which is a center for various functions. Constitutive activation of mammalian target of rapamycin complex 1 causes variable manifestations in tuberous sclerosis complex. Recently, genetic tests were launched to diagnose tuberous sclerosis complex, and mammalian target of rapamycin complex 1 inhibitors are being used to treat tuberous sclerosis complex patients. As a result of these advances, new diagnostic criteria have been established and an indispensable new treatment method; that is, "a cross-sectional medical examination system," a system to involve many experts for tuberous sclerosis complex diagnosis and treatments, was also created. Simultaneously, the frequency of genetic tests and advances in diagnostic technology have resulted in new views on symptoms. The numbers of tuberous sclerosis complex patients without neural symptoms are increasing, and for these patients, renal manifestations and pulmonary lymphangioleiomyomatosis have become important manifestations. New concepts of tuberous sclerosis complex-associated neuropsychiatric disorders or perivascular epithelioid cell tumors are being created. The present review contains a summary of recent advances, significant manifestations and therapy in tuberous sclerosis complex. © 2017 The Japanese Urological Association.

Chromatin Remodeling BAF (SWI/SNF) Complexes in Neural Development and Disorders

PubMed Central

Sokpor, Godwin; Xie, Yuanbin; Rosenbusch, Joachim; Tuoc, Tran

2017-01-01

The ATP-dependent BRG1/BRM associated factor (BAF) chromatin remodeling complexes are crucial in regulating gene expression by controlling chromatin dynamics. Over the last decade, it has become increasingly clear that during neural development in mammals, distinct ontogenetic stage-specific BAF complexes derived from combinatorial assembly of their subunits are formed in neural progenitors and post-mitotic neural cells. Proper functioning of the BAF complexes plays critical roles in neural development, including the establishment and maintenance of neural fates and functionality. Indeed, recent human exome sequencing and genome-wide association studies have revealed that mutations in BAF complex subunits are linked to neurodevelopmental disorders such as Coffin-Siris syndrome, Nicolaides-Baraitser syndrome, Kleefstra's syndrome spectrum, Hirschsprung's disease, autism spectrum disorder, and schizophrenia. In this review, we focus on the latest insights into the functions of BAF complexes during neural development and the plausible mechanistic basis of how mutations in known BAF subunits are associated with certain neurodevelopmental disorders. PMID:28824374

Chromatin Remodeling BAF (SWI/SNF) Complexes in Neural Development and Disorders.

PubMed

Sokpor, Godwin; Xie, Yuanbin; Rosenbusch, Joachim; Tuoc, Tran

2017-01-01

The ATP-dependent BRG1/BRM associated factor (BAF) chromatin remodeling complexes are crucial in regulating gene expression by controlling chromatin dynamics. Over the last decade, it has become increasingly clear that during neural development in mammals, distinct ontogenetic stage-specific BAF complexes derived from combinatorial assembly of their subunits are formed in neural progenitors and post-mitotic neural cells. Proper functioning of the BAF complexes plays critical roles in neural development, including the establishment and maintenance of neural fates and functionality. Indeed, recent human exome sequencing and genome-wide association studies have revealed that mutations in BAF complex subunits are linked to neurodevelopmental disorders such as Coffin-Siris syndrome, Nicolaides-Baraitser syndrome, Kleefstra's syndrome spectrum, Hirschsprung's disease, autism spectrum disorder, and schizophrenia. In this review, we focus on the latest insights into the functions of BAF complexes during neural development and the plausible mechanistic basis of how mutations in known BAF subunits are associated with certain neurodevelopmental disorders.

Clinical utility of seropositive voltage-gated potassium channel–complex antibody

PubMed Central

Jammoul, Adham; Shayya, Luay; Mente, Karin; Li, Jianbo; Rae-Grant, Alexander

2016-01-01

Abstract Background: Antibodies against voltage-gated potassium channel (VGKC)–complex are implicated in the pathogenesis of acquired neuromyotonia, limbic encephalitis, faciobrachial dystonic seizure, and Morvan syndrome. Outside these entities, the clinical value of VGKC-complex antibodies remains unclear. Methods: We conducted a single-center review of patients positive for VGKC-complex antibodies over an 8-year period. Results: Among 114 patients positive for VGKC-complex antibody, 11 (9.6%) carrying the diagnosis of limbic encephalitis (n = 9) or neuromyotonia (n = 2) constituted the classic group, and the remaining 103 cases of various neurologic and non-neurologic disorders comprised the nonclassic group. The median titer for the classic group was higher than the nonclassic group (p < 0.0001). A total of 90.9% of the patients in the classic and 21.4% in the nonclassic group possessed high (>0.25 nM) VGKC-complex antibody levels (p < 0.0001). A total of 75.0% of the patients in the high-level group had definite or probable autoimmune basis, while nonautoimmune disorders were seen in 75.6% of patients from the low-level group (p < 0.0001). A total of 26.3% of patients were found with active or remote solid organ or hematologic malignancy, but no antibody titer difference was observed among subgroups of absent, active, or remote malignancy. Compared to age-matched US national census, rates of active cancer in our cohort were higher in patients older than 45 years. Conclusions: High VGKC-complex antibody titers are more likely found in patients with classically associated syndromes and other autoimmune conditions. Low-level VGKC-complex antibodies can be detected in nonspecific and mostly nonautoimmune disorders. The presence of VGKC-complex antibody, rather than its level, may serve as a marker of malignancy. PMID:27847683

Mutations in UNC80, Encoding Part of the UNC79-UNC80-NALCN Channel Complex, Cause Autosomal-Recessive Severe Infantile Encephalopathy.

PubMed

Shamseldin, Hanan E; Faqeih, Eissa; Alasmari, Ali; Zaki, Maha S; Gleeson, Joseph G; Alkuraya, Fowzan S

2016-01-07

Brain channelopathies represent a growing class of brain disorders that usually result in paroxysmal disorders, although their role in other neurological phenotypes, including the recently described NALCN-related infantile encephalopathy, is increasingly recognized. In three Saudi Arabian families and one Egyptian family all affected by a remarkably similar phenotype (infantile encephalopathy and largely normal brain MRI) to that of NALCN-related infantile encephalopathy, we identified a locus on 2q34 in which whole-exome sequencing revealed three, including two apparently loss-of-function, recessive mutations in UNC80. UNC80 encodes a large protein that is necessary for the stability and function of NALCN and for bridging NALCN to UNC79 to form a functional complex. Our results expand the clinical relevance of the UNC79-UNC80-NALCN channel complex. Copyright © 2016 The American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.

Optimizing the chances of success in the search for epigenetic biomarkers: Embracing genetic variation.

PubMed

Philibert, Robert; Glatt, Stephen J

2017-09-01

The emphasis on clinical translation in biomedical research continues to grow. This focus has been particularly notable in those investigators using epigenetic approaches to decipher the biology of complex behavioral disorders. As a result of these efforts, reproducible findings for several disorders, such as smoking, have been generated, giving rise to hopes that biomarkers for other behavioral illnesses would be forthcoming. Unfortunately, that biomedical cornucopia has not yet materialized. In this editorial, we review progress to date and discuss barriers to generating epigenetic biomarkers for complex behavioral disorders. We highlight the need to incorporate information on genetic variation and develop more powerful bioinformatics tools in order to optimize the likelihood of success. We emphasize that searches should focus on clearly defined, readily distinguishable behavioral constructs and suggest that some well-intentioned methods, such as correction for cellular heterogeneity, may actually impede the identification of clinically relevant biomarkers in peripheral blood. Finally, we describe how the understanding created by the development of these biomarkers may lead to more valid animal models of neuropsychiatric illness. We conclude that the prospects for epigenetic biomarkers for complex disorders are bright, but emphasize that the journey to the clinical implementation of these findings will be a slow, iterative process. © 2017 Wiley Periodicals, Inc.

The Promise of Multi-Omics and Clinical Data Integration to Identify and Target Personalized Healthcare Approaches in Autism Spectrum Disorders

PubMed Central

Higdon, Roger; Earl, Rachel K.; Stanberry, Larissa; Hudac, Caitlin M.; Montague, Elizabeth; Stewart, Elizabeth; Janko, Imre; Choiniere, John; Broomall, William; Kolker, Natali

2015-01-01

Abstract Complex diseases are caused by a combination of genetic and environmental factors, creating a difficult challenge for diagnosis and defining subtypes. This review article describes how distinct disease subtypes can be identified through integration and analysis of clinical and multi-omics data. A broad shift toward molecular subtyping of disease using genetic and omics data has yielded successful results in cancer and other complex diseases. To determine molecular subtypes, patients are first classified by applying clustering methods to different types of omics data, then these results are integrated with clinical data to characterize distinct disease subtypes. An example of this molecular-data-first approach is in research on Autism Spectrum Disorder (ASD), a spectrum of social communication disorders marked by tremendous etiological and phenotypic heterogeneity. In the case of ASD, omics data such as exome sequences and gene and protein expression data are combined with clinical data such as psychometric testing and imaging to enable subtype identification. Novel ASD subtypes have been proposed, such as CHD8, using this molecular subtyping approach. Broader use of molecular subtyping in complex disease research is impeded by data heterogeneity, diversity of standards, and ineffective analysis tools. The future of molecular subtyping for ASD and other complex diseases calls for an integrated resource to identify disease mechanisms, classify new patients, and inform effective treatment options. This in turn will empower and accelerate precision medicine and personalized healthcare. PMID:25831060

Symptom management in complex post-traumatic stress disorder (ICD-11), view and experience of patients and their relatives: a mixed methods approach (Research Proposal).

PubMed

Stadtmann, Manuel P; Maercker, Andreas; Binder, Jochen; Schnepp, Wilfried

2017-09-07

Using the framework of IDC-11, complex post-traumatic stress disorder will be diagnosed using the core criteria of a post-traumatic stress disorder and the presence of at least one symptom from the following three domains: symptoms of emotional dysregulation, negative self-concept, and problems in interpersonal relationships. In the literature, these symptoms are discussed as a common reason for seeking treatment. The symptoms can influence and impair the quality of life. This article describes a mixed methods study with a sequential exploratory design. The aim is to describe specific patient characteristics, levels of symptom burden and perspectives of adult inpatients and to describe the experiences, views and needs of patients' relatives. The study will also investigate facilitators of and barriers to symptom management. The research will be conducted in four phases. The first phase will assess patients' symptom burdens. The second phase will use semi-structured interviews to explore attitudes to symptom management and perceptions of patients and their relatives. The third phase will statistically explore hypotheses generated after the qualitative interviews. The fourth phase will mix the quantitative and qualitative results and interpret critically. The present study will add new results to the growing literature on complex post-traumatic stress disorder. These results could serve as the basis for further research into the development of interventions to improve symptom management. Trial registration Ethical approval has been obtained from the Swiss cantonal ethic commission (Nr. 201500096). This research was also registered to the World Health Organization Clinical Trials Search Portal through the German Clinical Trial Register, Trial DRKS00012268 (21/04/2017).

«Surgery first» or two stage complex rehabilitation plan for patients with malocclusions.

PubMed

Andreishchev, A R; Kavrayskaya, A Yu; Nikolaev, A V

2016-01-01

The article considers stages of complex rehabilitation treatment plans of patients with bite anomalies. The study included 515 patients with various complex malocclusions. Two and conventional three stage treatment plans are described. The article suggests indications for the two stage treatment protocol. The evaluation of efficiency and stability of achieved treatment results obtained with a help of the system of quantitative analysis of dentooralfacial disorders is presented.

[Diabetes and prediabetes in endocrine disorders].

PubMed

Krysiak, Robert; Rudzki, Henryk; Okopień, Bogusław

2012-01-01

Complex hormonal regulation of carbohydrate metabolism causes that presence of many endocrine disorders may disturb glucose homeostasis. Impaired fasting glucose, impaired glucose tolerance and frank diabetes are observed in patients with both common and rare endocrine disorders, particularly in patients with polycystic ovary syndrome, hyperthyroidism, Cushing's syndrome, pheochromocytoma, primary aldosteronism, acromegaly, growth hormone deficiency and endocrine tumors of the digestive system. Because most of these disorders may be effectively treated and the treatment often results in a restoration of normal insulin secretion and receptor action as well as glucose absorption, production and metabolism, it is important to differentiate these disorders from other more common types of diabetes. This article reviews the etiology, clinical manifestation, diagnosis and management of endocrine disorders leading to diabetes and prediabetic states with special emphasis on the pathogenesis and clinical consequences of these disorders.

Thermodynamic characterization of the multivalent interactions underlying rapid and selective translocation through the nuclear pore complex

PubMed Central

Hayama, Ryo; Sparks, Samuel; Hecht, Lee M.; Dutta, Kaushik; Karp, Jerome M.; Cabana, Christina M.; Rout, Michael P.; Cowburn, David

2018-01-01

Intrinsically disordered proteins (IDPs) play important roles in many biological systems. Given the vast conformational space that IDPs can explore, the thermodynamics of the interactions with their partners is closely linked to their biological functions. Intrinsically disordered regions of Phe–Gly nucleoporins (FG Nups) that contain multiple phenylalanine–glycine repeats are of particular interest, as their interactions with transport factors (TFs) underlie the paradoxically rapid yet also highly selective transport of macromolecules mediated by the nuclear pore complex. Here, we used NMR and isothermal titration calorimetry to thermodynamically characterize these multivalent interactions. These analyses revealed that a combination of low per-FG motif affinity and the enthalpy–entropy balance prevents high-avidity interaction between FG Nups and TFs, whereas the large number of FG motifs promotes frequent FG–TF contacts, resulting in enhanced selectivity. Our thermodynamic model underlines the importance of functional disorder of FG Nups. It helps explain the rapid and selective translocation of TFs through the nuclear pore complex and further expands our understanding of the mechanisms of “fuzzy” interactions involving IDPs. PMID:29374059

[Locomotive syndrome and frailty. Musculoskeletal ambulation disorder symptom complex and locomotive syndrome].

PubMed

Yamamoto, Noriaki

2012-04-01

Musculoskeletal ambulation disorder symptom complex is the new concept of musculoskeletal disorders with disability in walking and balance, which lead to the high risk of fall and lower activity in elderly. Locomotive syndrome is another concept to aware of healthy locomotive organ for early prevention of orthopedic disease.

Integrated circuits and molecular components for stress and feeding: implications for eating disorders.

PubMed

Hardaway, J A; Crowley, N A; Bulik, C M; Kash, T L

2015-01-01

Eating disorders are complex brain disorders that afflict millions of individuals worldwide. The etiology of these diseases is not fully understood, but a growing body of literature suggests that stress and anxiety may play a critical role in their development. As our understanding of the genetic and environmental factors that contribute to disease in clinical populations like anorexia nervosa, bulimia nervosa and binge eating disorder continue to grow, neuroscientists are using animal models to understand the neurobiology of stress and feeding. We hypothesize that eating disorder clinical phenotypes may result from stress-induced maladaptive alterations in neural circuits that regulate feeding, and that these circuits can be neurochemically isolated using animal model of eating disorders. © 2014 John Wiley & Sons Ltd and International Behavioural and Neural Genetics Society.

Social cognition in borderline personality disorder: evidence for dichotomous thinking but no evidence for less complex attributions.

PubMed

Arntz, Arnoud; ten Haaf, José

2012-11-01

This experiment investigated social cognition in borderline personality disorder (BPD). We tested whether BPD-patients' evaluations of others were characterized by splitting, dichotomous thinking, or negativity; and whether they showed less complex understanding of others. Participants discussed a problem with three alleged mental health worker trainees, performing three interpersonal roles (rejecting, accepting and neutral). Participants evaluated trainees in a structured response format and in a semi-structured interview. BPD-patients (n = 18) were compared to Cluster-C personality disorder patients (n = 18) and nonpatients (n = 18). From visual analog scales with opposite trait descriptions (structured response format) negativity, dichotomous thinking, and splitting scores were derived. The interviews were scored by an independent rater on affect tone, differentiation, and complexity of attributions. BPD-patients showed, in all conditions, and in both response formats, more dichotomous thinking than control groups. Evidence for splitting as specific BPD-characteristic was not convincing, and more negativity in BPD was only found with the rejecting role and structured responses. The interview-based evaluations by BPD-patients could not be discriminated from nonpatients in cognitive complexity. Results indicate that dichotomous thinking, and not so much splitting, negativity, or less complexity, is central in the interpretation of others by BPD-patients. Treatment might address dichotomous thinking to reduce BPD-patients' interpersonal problems. Copyright © 2012 Elsevier Ltd. All rights reserved.

Inhibition of Calpains Protects Mn-Induced Neurotransmitter release disorders in Synaptosomes from Mice: Involvement of SNARE Complex and Synaptic Vesicle Fusion.

PubMed

Wang, Can; Xu, Bin; Ma, Zhuo; Liu, Chang; Deng, Yu; Liu, Wei; Xu, Zhao-Fa

2017-06-16

Overexposure to manganese (Mn) could disrupt neurotransmitter release via influencing the formation of SNARE complex, but the underlying mechanisms are still unclear. A previous study demonstrated that SNAP-25 is one of substrate of calpains. The current study investigated whether calpains were involved in Mn-induced disorder of SNARE complex. After mice were treated with Mn for 24 days, Mn deposition increased significantly in basal nuclei in Mn-treated and calpeptin pre-treated groups. Behaviorally, less time spent in the center of the area and decreased average velocity significantly in an open field test after 24 days of Mn exposure. With the increase in MnCl 2 dosage, intracellular Ca 2+ increased significantly, but pretreatment with calpeptin caused a dose-dependent decrease in calpains activity. There were fragments of N-terminal of SNAP-25 protein appearance in Mn-treated groups, but it is decreased with pretreatment of calpeptin. FM1-43-labeled synaptic vesicles also provided evidence that the treatment with Mn resulted in increasing first and then decreasing, which was consistent with Glu release and the 80 kDa protein levels of SNARE complexes. In summary, Mn induced the disorder of neurotransmitter release through influencing the formation of SNARE complex via cleaving SNAP-25 by overactivation of calpains in vivo.

The Challenge and Potential of Metagenomics in the Clinic

PubMed Central

Mulcahy-O’Grady, Heidi; Workentine, Matthew L.

2016-01-01

The bacteria, fungi, and viruses that live on and in us have a tremendous impact on our day-to-day health and are often linked to many diseases, including autoimmune disorders and infections. Diagnosing and treating these disorders relies on accurate identification and characterization of the microbial community. Current sequencing technologies allow the sequencing of the entire nucleic acid complement of a sample providing an accurate snapshot of the community members present in addition to the full genetic potential of that microbial community. There are a number of clinical applications that stand to benefit from these data sets, such as the rapid identification of pathogens present in a sample. Other applications include the identification of antibiotic-resistance genes, diagnosis and treatment of gastrointestinal disorders, and many other diseases associated with bacterial, viral, and fungal microbiomes. Metagenomics also allows the physician to probe more complex phenotypes such as microbial dysbiosis with intestinal disorders and disruptions of the skin microbiome that may be associated with skin disorders. Many of these disorders are not associated with a single pathogen but emerge as a result of complex ecological interactions within microbiota. Currently, we understand very little about these complex phenotypes, yet clearly they are important and in some cases, as with fecal microbiota transplants in Clostridium difficile infections, treating the microbiome of the patient is effective. Here, we give an overview of metagenomics and discuss a number of areas where metagenomics is applicable in the clinic, and progress being made in these areas. This includes (1) the identification of unknown pathogens, and those pathogens particularly hard to culture, (2) utilizing functional information and gene content to understand complex infections such as Clostridium difficile, and (3) predicting antimicrobial resistance of the community using genetic determinants of resistance identified from the sequencing data. All of these applications rely on sophisticated computational tools, and we also discuss the importance of skilled bioinformatic support for the implementation and use of metagenomics in the clinic. PMID:26870044

From degeneration to genetic susceptibility, from eugenics to genethics, from Bezugsziffer to LOD score: the history of psychiatric genetics.

PubMed

Schulze, Thomas G; Fangerau, Heiner; Propping, Peter

2004-11-01

Reviewing the history of psychiatric genetics is a difficult task, since--in contrast to genetic research into most other disorders--it cannot simply be done by chronologically listing methodological achievements and major findings. Instead, it necessitates a comprehensive assessment of how the aetiological concept of mental disorders has developed since as early as the world of ancient Greece. Furthermore, it has to touch upon the sensitive issue of the eugenic movement that was closely linked to the study of heredity in mental disorders in the first half of the 20th century and, in Nazi Germany, led to the systematic mass murder of psychiatric patients. Finally, reviewing the scientific dimensions, history of psychiatric genetics is at the same time a walk through the history of complex genetics in general. In our review, we try to pay tribute to this complexity. We argue that psychiatric genetics has not only propelled our understanding of mental disorders but has significantly benefited genetic research into other complex disorders through the development of methodologically robust approaches (e.g., systematic phenotype characterisation, methods to control for ascertainment biases, age-correction). Given the recent reasons for new optimism, i.e., the identification of susceptibility genes for psychiatric phenotypes, a continued methodologically sound approach is needed more than ever to guarantee robust results. Finally, psychiatric genetic research should never again be performed in an environment void of ethical standards.

Evolution of disorder in Mediator complex and its functional relevance.

PubMed

Nagulapalli, Malini; Maji, Sourobh; Dwivedi, Nidhi; Dahiya, Pradeep; Thakur, Jitendra K

2016-02-29

Mediator, an important component of eukaryotic transcriptional machinery, is a huge multisubunit complex. Though the complex is known to be conserved across all the eukaryotic kingdoms, the evolutionary topology of its subunits has never been studied. In this study, we profiled disorder in the Mediator subunits of 146 eukaryotes belonging to three kingdoms viz., metazoans, plants and fungi, and attempted to find correlation between the evolution of Mediator complex and its disorder. Our analysis suggests that disorder in Mediator complex have played a crucial role in the evolutionary diversification of complexity of eukaryotic organisms. Conserved intrinsic disordered regions (IDRs) were identified in only six subunits in the three kingdoms whereas unique patterns of IDRs were identified in other Mediator subunits. Acquisition of novel molecular recognition features (MoRFs) through evolution of new subunits or through elongation of the existing subunits was evident in metazoans and plants. A new concept of 'junction-MoRF' has been introduced. Evolutionary link between CBP and Med15 has been provided which explain the evolution of extended-IDR in CBP from Med15 KIX-IDR junction-MoRF suggesting role of junction-MoRF in evolution and modulation of protein-protein interaction repertoire. This study can be informative and helpful in understanding the conserved and flexible nature of Mediator complex across eukaryotic kingdoms. © The Author(s) 2015. Published by Oxford University Press on behalf of Nucleic Acids Research.

Enhancing work outcomes of employees with autism spectrum disorder through leadership: leadership for employees with autism spectrum disorder.

PubMed

Parr, Alissa D; Hunter, Samuel T

2014-07-01

The focus of this study was to identify leader behaviors that elicit successful engagement of employees with autism spectrum disorder, a population that is powerfully emerging into the workplace. The ultimate goal was to improve the quality of life of employees with autism spectrum disorder by facilitating an environment leading to their success. Through a series of interviews with 54 employees with autism spectrum disorder, results indicated that leadership has a great effect on employee attitudes and performance, and that the notion of leadership preferences is quite complex culminating in several important behaviors rather than one superior leadership theory. Implications and future research directions are discussed. © The Author(s) 2013.

[Complex Trauma-related Disorders in Research and Practice].

PubMed

Metzner, Franka; Pahlke, Stephanie; Diesing, Alice; Marin, Nina; Klasen, Fionna; Pawils, Silke; Schulte-Markwort, Michael; Richter-Appelt, Hertha

2018-03-01

Complex Trauma-related Disorders in Research and Practice Frequent traumata in childhood and adolescence are long-term or repeated interpersonal traumata caused by perpetrators in the close environment of the minors. For the description of the extensive symptoms after interpersonal Type II traumata, the complex trauma-related disorders Complex Posttraumatic Stress Disorder (CPTSD) or Disorder of Extreme Stress Not Otherwise Specified (DESNOS) and the Developmental Trauma Disorder (DTD) are being discussed for inclusion in the classification systems for mental disorders. Scientific knowledge and practical experiences regarding CPTSD, DESNOS and DTD in children and adolescents up to 18 years were examined by 1) a Systematic Review of 1,070 publications identified by database research and additional search strategies, and 2) a nationwide online survey of 374 psychotherapists and psychiatrists for children and adolescents in Germany. Of 13 included empirical studies (8 CPTSD or DESNOS, 5 DTD), 9 were conducted in the USA, 4 based on file coding and 3 on secondary data analysis and only 7 reported diagnosis rates (range: 0-78 %). Of the interviewed therapists, 100 % considered the CPTSD as being met with at least one patient with interpersonal traumata up to 18 years of age in 2014 and 99 % gave this estimate for the DTD. Two thirds of therapists rated the diagnostic option CPTSD and DTD as "very often" or "often" helpful for their therapeutic work with children and adolescents. While empirical data available is to be considered insufficient and characterized by methodological limitations, the relevance of complex trauma-related disorders is perceived as high by practitioners.

[Double diagnosis and forensic psychiatric opinion].

PubMed

Kocur, Józef; Trendak, Wiesława

2009-01-01

Addiction to alcohol or any other psychoactive substance can run parallel with other diseases or mental disorders. One can then observe co-occurrence and mutual interaction of dysfunctions typical of addiction and of other mental disorders that accompany addiction. That is why, clinical pictures of such states (double diagnosis) are usually less unique, have an unusual course and cause diagnostic and therapeutic difficulty. The problem of forensic psychiatric opinion and treatment of people with a double diagnosis is another aspect of these difficulties. It is caused by the fact that forensic psychiatric assessment of the mental state of such people requires taking into consideration a very complex clinical and legal situation triggered by the interference of various ethiopathogenetic and clinical disorders. It leads to the need for complex evaluation and reference to sanity or other signs of functioning within the current law should result, first of all, from the analyses directly pertaining to the influence of the diagnosed disorders on the state of patients with double diagnosis. The forensic psychiatric aspect of disorders connected with double diagnosis is particularly significant as there is a relatively high risk of behaviours posing a threat to public order in this group of patients.

Thoracic Outlet Syndrome

MedlinePlus

... including rotator cuff injuries, cervical disc disorders, fibromyalgia, multiple sclerosis, complex regional pain syndrome, and tumors of the ... including rotator cuff injuries, cervical disc disorders, fibromyalgia, multiple sclerosis, complex regional pain syndrome, and tumors of the ...

Case Study: Skinny Genes? An Interdisciplinary Look at a Complex Behavioral Disorder

ERIC Educational Resources Information Center

Gow, Joan-Beth; Carpino, Lisa A.

2018-01-01

Anorexia nervosa is a complex behavioral disorder with the highest risk of death of any psychological disorder. Between 15% and 20% of those suffering from anorexia die from complications that are attributed either directly or indirectly to self-starvation. Heritability for anorexia is around 0.5, meaning about 50% of the risk for anorexia is…

Commentary on the Inclusion of Persistent Complex Bereavement-Related Disorder in DSM-5

ERIC Educational Resources Information Center

Boelen, Paul A.; Prigerson, Holly G.

2012-01-01

The DSM-5 Anxiety, Obsessive-Compulsive Spectrum, Posttraumatic, and Dissociative Disorders Work Group has proposed criteria for Persistent Complex Bereavement-Related Disorder (PCBRD) for inclusion in the appendix of DSM-5. The authors feel that it is important that dysfunctional grief will become a formal condition in DSM-5 because that would…

Stabilizing Group Treatment for Complex Posttraumatic Stress Disorder Related to Childhood Abuse Based on Psycho-Education and Cognitive Behavioral Therapy: A Pilot Study

ERIC Educational Resources Information Center

Dorrepaal, Ethy; Thomaes, Kathleen; Smit, Johannes H.; van Balkom, Anton J. L. M.; van Dyck, Richard; Veltman, Dick J.; Draijer, Nel

2010-01-01

Objective: This study tests a Stabilizing Group Treatment protocol, designed for the management of the long-term sequelae of child abuse, that is, Complex Posttraumatic Stress Disorder (Complex PTSD). Evidence-based treatment for this subgroup of PTSD patients is largely lacking. This stabilizing treatment aims at improving Complex PTSD using…

Facial emotion recognition in paranoid schizophrenia and autism spectrum disorder.

PubMed

Sachse, Michael; Schlitt, Sabine; Hainz, Daniela; Ciaramidaro, Angela; Walter, Henrik; Poustka, Fritz; Bölte, Sven; Freitag, Christine M

2014-11-01

Schizophrenia (SZ) and autism spectrum disorder (ASD) share deficits in emotion processing. In order to identify convergent and divergent mechanisms, we investigated facial emotion recognition in SZ, high-functioning ASD (HFASD), and typically developed controls (TD). Different degrees of task difficulty and emotion complexity (face, eyes; basic emotions, complex emotions) were used. Two Benton tests were implemented in order to elicit potentially confounding visuo-perceptual functioning and facial processing. Nineteen participants with paranoid SZ, 22 with HFASD and 20 TD were included, aged between 14 and 33 years. Individuals with SZ were comparable to TD in all obtained emotion recognition measures, but showed reduced basic visuo-perceptual abilities. The HFASD group was impaired in the recognition of basic and complex emotions compared to both, SZ and TD. When facial identity recognition was adjusted for, group differences remained for the recognition of complex emotions only. Our results suggest that there is a SZ subgroup with predominantly paranoid symptoms that does not show problems in face processing and emotion recognition, but visuo-perceptual impairments. They also confirm the notion of a general facial and emotion recognition deficit in HFASD. No shared emotion recognition deficit was found for paranoid SZ and HFASD, emphasizing the differential cognitive underpinnings of both disorders. Copyright © 2014 Elsevier B.V. All rights reserved.

Cognitive Abilities on Transitive Inference Using a Novel Touchscreen Technology for Mice

PubMed Central

Silverman, J.L.; Gastrell, P.T.; Karras, M.N.; Solomon, M.; Crawley, J.N.

2015-01-01

Cognitive abilities are impaired in neurodevelopmental disorders, including autism spectrum disorder (ASD) and schizophrenia. Preclinical models with strong endophenotypes relevant to cognitive dysfunctions offer a valuable resource for therapeutic development. However, improved assays to test higher order cognition are needed. We employed touchscreen technology to design a complex transitive inference (TI) assay that requires cognitive flexibility and relational learning. C57BL/6J (B6) mice with good cognitive skills and BTBR T+tf/J (BTBR), a model of ASD with cognitive deficits, were evaluated in simple and complex touchscreen assays. Both B6 and BTBR acquired visual discrimination and reversal. BTBR displayed deficits on components of TI, when 4 stimuli pairs were interspersed, which required flexible integrated knowledge. BTBR displayed impairment on the A > E inference, analogous to the A > E deficit in ASD. B6 and BTBR mice both reached criterion on the B > D comparison, unlike the B > D impairment in schizophrenia. These results demonstrate that mice are capable of complex discriminations and higher order tasks using methods and equipment paralleling those used in humans. Our discovery that a mouse model of ASD displays a TI deficit similar to humans with ASD supports the use of the touchscreen technology for complex cognitive tasks in mouse models of neurodevelopmental disorders. PMID:24293564

The measles virus N(TAIL)-XD complex: an illustrative example of fuzziness.

PubMed

Longhi, Sonia

2012-01-01

In this chapter, I focus on the biochemical and structural characterization of the complex between the intrinsically disordered C-terminal domain of the measles virus nucleoprotein (N(TAIL)) and the C-terminal X domain (XD) of the viral phosphoprotein (P). I summarize the main experimental data available so far pointing out the prevalently disordered nature of N(TAIL) even after complex formation and the role of the flexible C-terminal appendage in the binding reaction. I finally discuss the possible functional role of these residual disordered regions within the complex in terms of their ability to capture other regulatory, binding partners.

Risk-prone individuals prefer the wrong options on a rat version of the Iowa Gambling Task.

PubMed

Rivalan, Marion; Ahmed, Serge H; Dellu-Hagedorn, Françoise

2009-10-15

Decision making in complex and conflicting situations, as measured in the widely used Iowa Gambling Task (IGT), can be profoundly impaired in psychiatric disorders, such as attention-deficit/hyperactivity disorder, drug addiction, and also in healthy individuals for whom immediate gratification prevails over long-term gain. The cognitive processes underlying these deficits are poorly understood, in part due to a lack of suitable animal models assessing complex decision making with good construct validity. We developed a rat gambling task analogous to the IGT that tracks, for the first time, the ongoing decision process within a single session in an operant cage. Rats could choose between various options. Disadvantageous options, as opposed to advantageous ones, offered bigger immediate food reward but were followed by longer, unpredictable penalties (time-out). The majority of rats can evaluate and deduce favorable options more or less rapidly according to task complexity, whereas others systematically choose disadvantageously. These interindividual differences are stable over time and do not depend on task difficulty or on the level of food restriction. We find that poor decision making does not result from a failure to acquire relevant information but from hypersensitivity to reward and higher risk taking in anxiogenic situations. These results suggest that rats, as well as human poor performers, share similar traits to those observed in decision-making related psychiatric disorders. These traits could constitute risk factors of developing such disorders. The rapid identification of poor decision makers using the rat gambling task should promote the discovery of the specific brain dysfunctions that cause maladapted decision making.

Increased oxidative stress in the mitochondria isolated from lymphocytes of bipolar disorder patients during depressive episodes.

PubMed

Valvassori, Samira S; Bavaresco, Daniela V; Feier, Gustavo; Cechinel-Recco, Kelen; Steckert, Amanda V; Varela, Roger B; Borges, Cenita; Carvalho-Silva, Milena; Gomes, Lara M; Streck, Emílio L; Quevedo, João

2018-06-01

The present study aims to investigate the oxidative stress parameters in isolated mitochondria, as well as looking at mitochondrial complex activity in patients with Bipolar Disorder (BD) during depressive or euthymic episodes. This study evaluated the levels of mitochondrial complex (I, II, II-III and IV) activity in lymphocytes from BD patients. We evaluated the following oxidative stress parameters: superoxide, thiobarbituric acid reactive species (TBARS) and carbonyl levels in submitochondrial particles of lymphocytes from bipolar patients. 51 bipolar patients were recruited into this study: 34 in the euthymic phase, and 17 in the depressive phase. Our results indicated that the depressive phase could increase the levels of mitochondrial superoxide, carbonyl and TBARS, and superoxide dismutase, and could decrease the levels of mitochondrial complex II activity in the lymphocytes of bipolar patients. It was also observed that there was a negative correlation between the Hamilton Depression Rating Scale (HDRS) and complex II activity in the lymphocytes of depressive bipolar patients. In addition, there was a positive correlation between HDRS and superoxide, superoxide dismutase, TBARS and carbonyl. Additionally, there was a negative correlation between complex II activity and oxidative stress parameters. In conclusion, our results suggest that mitochondrial oxidative stress and mitochondrial complex II dysfunction play important roles in the depressive phase of BD. Copyright © 2018. Published by Elsevier B.V.

What Difference Does It Make? Implicit, Explicit and Complex Social Cognition in Autism Spectrum Disorders

ERIC Educational Resources Information Center

Schaller, Ulrich M.; Rauh, Reinhold

2017-01-01

We tested social cognition abilities of adolescents with autism spectrum disorders (ASD) and neurotypically developed peers (NTD). A multi-faceted test-battery including facial emotion categorization (FEC), classical false belief tasks (FBT), and complex social cognition (SC), yielded significantly lower accuracy rates for FEC and complex SC tasks…

A developmental approach to complex PTSD: childhood and adult cumulative trauma as predictors of symptom complexity.

PubMed

Cloitre, Marylene; Stolbach, Bradley C; Herman, Judith L; van der Kolk, Bessel; Pynoos, Robert; Wang, Jing; Petkova, Eva

2009-10-01

Exposure to multiple traumas, particularly in childhood, has been proposed to result in a complex of symptoms that includes posttraumatic stress disorder (PTSD) as well as a constrained, but variable group of symptoms that highlight self-regulatory disturbances. The relationship between accumulated exposure to different types of traumatic events and total number of different types of symptoms (symptom complexity) was assessed in an adult clinical sample (N = 582) and a child clinical sample (N = 152). Childhood cumulative trauma but not adulthood trauma predicted increasing symptom complexity in adults. Cumulative trauma predicted increasing symptom complexity in the child sample. Results suggest that Complex PTSD symptoms occur in both adult and child samples in a principled, rule-governed way and that childhood experiences significantly influenced adult symptoms. Copyright © 2009 International Society for Traumatic Stress Studies.

Using deep learning to investigate the neuroimaging correlates of psychiatric and neurological disorders: Methods and applications.

PubMed

Vieira, Sandra; Pinaya, Walter H L; Mechelli, Andrea

2017-03-01

Deep learning (DL) is a family of machine learning methods that has gained considerable attention in the scientific community, breaking benchmark records in areas such as speech and visual recognition. DL differs from conventional machine learning methods by virtue of its ability to learn the optimal representation from the raw data through consecutive nonlinear transformations, achieving increasingly higher levels of abstraction and complexity. Given its ability to detect abstract and complex patterns, DL has been applied in neuroimaging studies of psychiatric and neurological disorders, which are characterised by subtle and diffuse alterations. Here we introduce the underlying concepts of DL and review studies that have used this approach to classify brain-based disorders. The results of these studies indicate that DL could be a powerful tool in the current search for biomarkers of psychiatric and neurologic disease. We conclude our review by discussing the main promises and challenges of using DL to elucidate brain-based disorders, as well as possible directions for future research. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

Dependent personality features in a complex case of borderline personality disorder.

PubMed

Nirestean, Tudor; Lukacs, Emese; Nirestean, Aurel; Gabos Grecu, Iosif

2016-11-01

Borderline personality disorder is a complex disease model as it encompasses a diversity of pathological personality traits and psychopathological symptoms. It is not surprising, therefore, that it is often manifested by personality disorders across all three clusters and accompanied by other mental (Axis I) disorders. This melange makes both psychological treatment and pharmacotherapy especially challenging, and this paper describes the case of a particularly complex case of a 33-year-old Romanian patient, who has a history of severe deprivation in childhood, mood and substance use disorder in association with borderline pathology. In the course of treatment from many sources and interventions, it has become clear that dependence is a key component of the pathology and has been rewarded with a degree of success in management. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

[Autism in children. Speech, behavior and motor activity point to diagnosis].

PubMed

Neumärker, K J

2001-02-01

Austistic disorders characteristically involve specific impairments of social skills, of the language and of stereotyped body movements. L Kanner and H. Asperger were the first to describe these psychopathologic features, which still form the core of the diagnostic criteria of contemporary psychiatric classification systems, ICD-10 and DSM-IV, in the category pervasive developmental disorders. Useful diagnostic tools have been developed to establish the clinical diagnosis. The results of research point to a predominantly genetic pathogenesis involving a complex interaction of multiple genes. While no causal treatments are available for these heterogenic disorders, there are many therapeutic concepts. Although some treatments may achieve significant improvements, autistic disorders usually mean a lifelong individual impairment.

Is it a tic or Tourette's? Clues for differentiating simple from more complex tic disorders.

PubMed

Evidente, V G

2000-10-01

Tics are characterized by sterotyped, purposeless, and irregularly repetitive movements and usually can be classified as chronic motor or vocal tic disorders, transient tic disorders, or Tourette's syndrome. The latter is a complex disorder associated with multiple tics and often accompanied by other conditions, such as ADHD and obsessive-compulsive disorder. Treatment can be difficult, and drug therapy should begin with agents least likely to cause problems for the patient. Education of the patient and family and support from the physician and other care providers are essential elements of effective management.

Depression as a systemic syndrome: mapping the feedback loops of major depressive disorder.

PubMed

Wittenborn, A K; Rahmandad, H; Rick, J; Hosseinichimeh, N

2016-02-01

Depression is a complex public health problem with considerable variation in treatment response. The systemic complexity of depression, or the feedback processes among diverse drivers of the disorder, contribute to the persistence of depression. This paper extends prior attempts to understand the complex causal feedback mechanisms that underlie depression by presenting the first broad boundary causal loop diagram of depression dynamics. We applied qualitative system dynamics methods to map the broad feedback mechanisms of depression. We used a structured approach to identify candidate causal mechanisms of depression in the literature. We assessed the strength of empirical support for each mechanism and prioritized those with support from validation studies. Through an iterative process, we synthesized the empirical literature and created a conceptual model of major depressive disorder. The literature review and synthesis resulted in the development of the first causal loop diagram of reinforcing feedback processes of depression. It proposes candidate drivers of illness, or inertial factors, and their temporal functioning, as well as the interactions among drivers of depression. The final causal loop diagram defines 13 key reinforcing feedback loops that involve nine candidate drivers of depression. Future research is needed to expand upon this initial model of depression dynamics. Quantitative extensions may result in a better understanding of the systemic syndrome of depression and contribute to personalized methods of evaluation, prevention and intervention.

Etiology of a genetically complex seizure disorder in Celf4 mutant mice

PubMed Central

Wagnon, Jacy L.; Mahaffey, Connie L.; Sun, Wenzhi; Yang, Yan; Chao, Hsiao-Tuan; Frankel, Wayne N.

2011-01-01

Mice deficient for the gene encoding the RNA-binding protein CELF4 (CUGBP, ELAV-like family member 4) have a complex seizure phenotype that includes both convulsive and non-convulsive seizures, depending upon gene dosage and strain background, modeling genetically complex epilepsy. Invertebrate CELF is associated with translational control in fruit fly ovary epithelium and with neurogenesis and neuronal function in the nematode. Mammalian CELF4 is expressed widely during early development, but is restricted to the central nervous system in adult. To better understand the etiology of the seizure disorder of Celf4 deficient mice, we studied seizure incidence with spatial and temporal conditional knockout Celf4 alleles. For convulsive seizure phenotypes, it is sufficient to delete Celf4 in adulthood at seven weeks of age. This timing is in contrast to absence-like non-convulsive seizures, which require deletion before the end of the first postnatal week. Interestingly, selective deletion of Celf4 from cerebral cortex and hippocampus excitatory neurons, but not from inhibitory neurons, is sufficient to lower seizure threshold and to promote spontaneous convulsions. Correspondingly, Celf4 deficient mice have altered excitatory, but not inhibitory, neurotransmission as measured by patch-clamp recordings of cortical layer V pyramidal neurons. Finally, immunostaining in conjunction with an inhibitory neuron-specific reporter shows that CELF4 is expressed predominantly in excitatory neurons. Our results suggest that CELF4 plays a specific role in regulating excitatory neurotransmission. We posit that altered excitatory neurotransmission resulting from Celf4 deficiency underlies the complex seizure disorder in Celf4 mutant mice. PMID:21745337

Childhood trauma and complex posttraumatic stress disorder symptoms in older adults: A study of direct effects and social-interpersonal factors as potential mediators.

PubMed

Krammer, Sandy; Kleim, Birgit; Simmen-Janevska, Keti; Maercker, Andreas

2016-01-01

Childhood traumatic events may lead to long-lasting psychological effects and contribute to the development of complex posttraumatic sequelae. These might be captured by the diagnostic concept of complex posttraumatic stress disorder (CPTSD) as an alternative to classic posttraumatic stress disorder (PTSD). CPTSD comprises a further set of symptoms in addition to those of PTSD, namely, changes in affect, self, and interpersonal relationships. Previous empirical research on CPTSD has focused on middle-aged adults but not on older adults. Moreover, predictor models of CPTSD are still rare. The current study investigated the association between traumatic events in childhood and complex posttraumatic stress symptoms in older adults. The mediation of this association by 2 social-interpersonal factors (social acknowledgment as a survivor and dysfunctional disclosure) was investigated. These 2 factors focus on the perception of acknowledgment by others and either the inability to disclose traumatic experiences or the ability to do so only with negative emotional reactions. A total of 116 older individuals (age range = 59-98 years) who had experienced childhood traumatic events completed standardized self-report questionnaires indexing childhood trauma, complex trauma sequelae, social acknowledgment, and dysfunctional disclosure of trauma. The results showed that traumatic events during childhood were associated with later posttraumatic stress symptoms but with classic rather than complex symptoms. Social acknowledgment and dysfunctional disclosure partially mediated this relationship. These findings suggest that childhood traumatic stress impacts individuals across the life span and may be associated with particular adverse psychopathological consequences.

Immune System and Disorders

MedlinePlus

Your immune system is a complex network of cells, tissues, and organs that work together to defend against germs. It helps ... to find and destroy them. If your immune system cannot do its job, the results can be ...

Ernest Hemingway: a psychological autopsy of a suicide.

PubMed

Martin, Christopher D

2006-01-01

Much has been written about Ernest Hemingway, including discussion of his well-documented mood disorder, alcoholism, and suicide. However, a thorough biopsychosocial approach capable of integrating the various threads of the author's complex psychiatric picture has yet to be applied. Application of such a psychiatric view to the case of Ernest Hemingway in an effort toward better understanding of the author's experience with illness and the tragic outcome is the aim of this investigation. Thus, Hemingway's life is examined through a review and discussion of biographies, psychiatric literature, personal correspondence, photography, and medical records. Significant evidence exists to support the diagnoses of bipolar disorder, alcohol dependence, traumatic brain injury, and probable borderline and narcissistic personality traits. Late in life, Hemingway also developed symptoms of psychosis likely related to his underlying affective illness and superimposed alcoholism and traumatic brain injury. Hemingway utilized a variety of defense mechanisms, including self-medication with alcohol, a lifestyle of aggressive, risk-taking sportsmanship, and writing, in order to cope with the suffering caused by the complex comorbidity of his interrelated psychiatric disorders. Ultimately, Hemingway's defense mechanisms failed, overwhelmed by the burden of his complex comorbid illness, resulting in his suicide. However, despite suffering from multiple psychiatric disorders, Hemingway was able to live a vibrant life until the age of 61 and within that time contribute immortal works of fiction to the literary canon.

Current limitations of SNP data from the public domain for studies of complex disorders: a test for ten candidate genes for obesity and osteoporosis

PubMed Central

Dvornyk, Volodymyr; Long, Ji-Rong; Xiong, Dong-Hai; Liu, Peng-Yuan; Zhao, Lan-Juan; Shen, Hui; Zhang, Yuan-Yuan; Liu, Yong-Jun; Rocha-Sanchez, Sonia; Xiao, Peng; Recker, Robert R; Deng, Hong-Wen

2004-01-01

Background Public SNP databases are frequently used to choose SNPs for candidate genes in the association and linkage studies of complex disorders. However, their utility for such studies of diseases with ethnic-dependent background has never been evaluated. Results To estimate the accuracy and completeness of SNP public databases, we analyzed the allele frequencies of 41 SNPs in 10 candidate genes for obesity and/or osteoporosis in a large American-Caucasian sample (1,873 individuals from 405 nuclear families) by PCR-invader assay. We compared our results with those from the databases and other published studies. Of the 41 SNPs, 8 were monomorphic in our sample. Twelve were reported for the first time for Caucasians and the other 29 SNPs in our sample essentially confirmed the respective allele frequencies for Caucasians in the databases and previous studies. The comparison of our data with other ethnic groups showed significant differentiation between the three major world ethnic groups at some SNPs (Caucasians and Africans differed at 3 of the 18 shared SNPs, and Caucasians and Asians differed at 13 of the 22 shared SNPs). This genetic differentiation may have an important implication for studying the well-known ethnic differences in the prevalence of obesity and osteoporosis, and complex disorders in general. Conclusion A comparative analysis of the SNP data of the candidate genes obtained in the present study, as well as those retrieved from the public domain, suggests that the databases may currently have serious limitations for studying complex disorders with an ethnic-dependent background due to the incomplete and uneven representation of the candidate SNPs in the databases for the major ethnic groups. This conclusion attests to the imperative necessity of large-scale and accurate characterization of these SNPs in different ethnic groups. PMID:15113403

Cross-sectional Imaging Review of Tuberous Sclerosis.

PubMed

Krishnan, Anant; Kaza, Ravi K; Vummidi, Dharshan R

2016-05-01

Tuberous sclerosis complex (TSC) is a multisystem, genetic disorder characterized by development of hamartomas in the brain, abdomen, and thorax. It results from a mutation in one of 2 tumor suppressor genes that activates the mammalian target of rapamycin pathway. This article discusses the origins of the disorder, the recently updated criteria for the diagnosis of TSC, and the cross-sectional imaging findings and recommendations for surveillance. Familiarity with the diverse radiological features facilitates diagnosis and helps in treatment planning and monitoring response to treatment of this multisystem disorder. Copyright © 2016 Elsevier Inc. All rights reserved.

[The use of enerion in the treatment of asthenic disorders in patients after mild cranio-cerebral trauma].

PubMed

Levin, O S; Slizkova, Iu B

2007-01-01

Asthenia is a key symptom of posttraumatic disorders (postcommotion syndrom). The dynamics of the symptom developing after mild cranio-cerebral trauma was studied during the treatment of 36 patients with enerion (20 patients) and piracetam (16 patients - control group). The authors present the results of the complex study, which includes neuropsychological tests and scales. It was shown that enerion was more effective as compared with paracetam.

Joint attention responses of children with autism spectrum disorder to simple versus complex music.

PubMed

Kalas, Amy

2012-01-01

Joint attention deficits are viewed as one of the earliest manifestations and most characteristic features of the social deficits in Autism Spectrum Disorder (ASD). The purpose of this study was to examine the effect of simple versus complex music on joint attention of children with ASD. Thirty children with a diagnosis of ASD participated in this study. Fifteen of the participants were diagnosed with severe ASD and 15 were diagnosed with mild/moderate ASD. Each participant took part in six, 10-minute individual music conditions (3 simple & 3 complex) over a 3-week period. Each condition was designed to elicit responses to joint attention. RESULTS indicated a statistically significant interaction between music modality and functioning level. Therefore, the effect of simple versus complex music was dependent on functioning level. Specifically, the Simple Music Condition was more effective in eliciting Responses to Joint Attention (RJA) for children diagnosed with severe ASD, whereas the Complex Music Condition was more effective in eliciting RJA for children diagnosed with mild/moderate ASD. The results of the present study indicate that for children in the severe range of functioning, music that is simple, with clear and predictable pattems, may be most effective in eliciting responses to bids for joint attention. On the contrary, for children in the mild/moderate range of functioning, music that is more complex and variable may be most effective in eliciting responses to bids for joint attention. These results demonstrate that careful manipulation of specific musical elements can help provide the optimal conditions for facilitating joint attention with children with ASD.

Testing Brain Overgrowth and Synaptic Models of Autism Using NPC’s and Neurons from Patient-Derived IPS Cells

DTIC Science & Technology

2014-10-01

Release; Distribution Unlimited 13. SUPPLEMENTARY NOTES 14. ABSTRACT Autism and autism spectrum disorders (ASD) are complex neurodevelopmental ...1. INTRODUCTION: Autism and autism spectrum disorders (ASD) are complex neurodevelopmental diseases that affect about 1% of children in the...and neurons. 2. KEYWORDS: Autism spectrum disorder, ASD, neurodevelopmental disease, disease modeling, induced pluripotent stem cell, iPS

Influence of specific obsessive-compulsive symptom dimensions on strategic planning in patients with obsessive-compulsive disorder.

PubMed

Pinto, Paula Sanders Pereira; Iego, Sandro; Nunes, Samantha; Menezes, Hemanny; Mastrorosa, Rosana Sávio; Oliveira, Irismar Reis de; Rosário, Maria Conceição do

2011-03-01

This study investigates obsessive-compulsive disorder patients in terms of strategic planning and its association with specific obsessive-compulsive symptom dimensions. We evaluated 32 obsessive-compulsive disorder patients. Strategic planning was assessed by the Rey-Osterrieth Complex Figure Test, and the obsessive-compulsive dimensions were assessed by the Dimensional Yale-Brown Obsessive-Compulsive Scale. In the statistical analyses, the level of significance was set at 5%. We employed linear regression, including age, intelligence quotient, number of comorbidities, the Yale-Brown Obsessive-Compulsive Scale score, and the Dimensional Yale-Brown Obsessive-Compulsive Scale. The Dimensional Yale-Brown Obsessive-Compulsive Scale "worst-ever" score correlated significantly with the planning score on the copy portion of the Rey-Osterrieth Complex Figure Test (r = 0.4, p = 0.04) and was the only variable to show a significant association after linear regression (β = 0.55, t = 2.1, p = 0.04). Compulsive hoarding correlated positively with strategic planning (r = 0.44, p = 0.03). None of the remaining symptom dimensions presented any significant correlations with strategic planning. We found the severity of obsessive-compulsive symptoms to be associated with strategic planning. In addition, there was a significant positive association between the planning score on the copy portion of the Rey-Osterrieth Complex Figure Test copy score and the hoarding dimension score on the Dimensional Yale-Brown Obsessive-Compulsive Scale. Our results underscore the idea that obsessive-compulsive disorder is a heterogeneous disorder and suggest that the hoarding dimension has a specific neuropsychological profile. Therefore, it is important to assess the peculiarities of each obsessive-compulsive symptom dimension.

Birth order rank as a moderator of the relation between behavior problems among children with an autism spectrum disorder and their siblings.

PubMed

Tomeny, Theodore S; Barry, Tammy D; Bader, Stephanie H

2014-02-01

Variability within the literature investigating typically-developing siblings of children with an autism spectrum disorder suggests that the quality of sibling outcomes may depend on specific factors. For this study, 42 parents of a child with an autism spectrum disorder and a typically- developing sibling provided data via online questionnaires. Birth order rank of the child with an autism spectrum disorder significantly moderated the relation between externalizing behaviors in children with an autism spectrum disorder and externalizing behaviors in their typically-developing siblings. Children with an autism spectrum disorder and higher levels of behavior problems had typically-developing siblings with higher levels of behavior problems only when the child with an autism spectrum disorder was older. These results provide a hint of clarification about the complex nature of sibling relations, but a great deal more research is needed to further examine outcomes of typically-developing siblings of children with an autism spectrum disorder.

Genetics Home Reference: seasonal affective disorder

MedlinePlus

... seasonal affective disorder are complex. A shortage of sunlight contributes to the development of the disorder in the fall and winter months, and too much sunlight is associated with seasonal affective disorder in the ...

Shared and differentiated motor skill impairments in children with dyslexia and/or attention deficit disorder: From simple to complex sequential coordination

PubMed Central

Morin-Moncet, Olivier; Bélanger, Anne-Marie; Beauchamp, Miriam H.; Leonard, Gabriel

2017-01-01

Dyslexia and Attention deficit disorder (AD) are prevalent neurodevelopmental conditions in children and adolescents. They have high comorbidity rates and have both been associated with motor difficulties. Little is known, however, about what is shared or differentiated in dyslexia and AD in terms of motor abilities. Even when motor skill problems are identified, few studies have used the same measurement tools, resulting in inconstant findings. The present study assessed increasingly complex gross motor skills in children and adolescents with dyslexia, AD, and with both Dyslexia and AD. Our results suggest normal performance on simple motor-speed tests, whereas all three groups share a common impairment on unimanual and bimanual sequential motor tasks. Children in these groups generally improve with practice to the same level as normal subjects, though they make more errors. In addition, children with AD are the most impaired on complex bimanual out-of-phase movements and with manual dexterity. These latter findings are examined in light of the Multiple Deficit Model. PMID:28542319

Urogenital consequences in ageing women.

PubMed

Doumouchtsis, Stergios K; Chrysanthopoulou, Eleftheria L

2013-10-01

Various anatomical, physiological, genetic, lifestyle and reproductive factors interact throughout a woman's life span and contribute to pelvic floor disorders. Ageing affects pelvic floor anatomy and function, which can result in a variety of disorders, such as pelvic organ prolapse, lower urinary tract symptoms, dysfunctional bowel and bladder evacuation, and sexual dysfunction. The exact mechanisms and pathophysiological processes by which ageing affects pelvic floor and lower urinary and gastrointestinal tract anatomy and function are not always clear. In most cases, it is difficult to ascertain the exact role of ageing per se as an aetiological, predisposing or contributing factor. Other conditions associated with ageing that may co-exist, such as changes in mental status, can result in different types of pelvic floor dysfunction (e.g. functional incontinence). Pelvic organ dysfunction may be associated with significant morbidity and affect quality of life. These groups of patients often pose difficult diagnostic and therapeutic dilemmas owing to complex medical conditions and concurrent morbidities. In this chapter, we summarise the current evidence on the management of pelvic floor disorders, with emphasis on elderly women and the associations between the ageing process and these disorders. Clinicians with an understanding of the affect of ageing on the pelvic floor and lower urinary and gastrointestinal tract anatomy and function, and the complex interplay of other comorbidities, will be able to investigate, diagnose and treat appropriately there women. A holistic approach may result in substantial improvements in their quality of life. Copyright © 2013. Published by Elsevier Ltd.

An Investigation into the Roles of Theory of Mind, Emotion Regulation, and Attachment Styles in Predicting the Traits of Borderline Personality Disorder

PubMed Central

Ghiasi, Hamed; Mohammadi, Abolalfazl; Zarrinfar, Pouria

2016-01-01

Objective: Borderline personality disorder is one of the most complex and prevalent personality disorders. Many variables have so far been studied in relation to this disorder. This study aimed to investigate the role of emotion regulation, attachment styles, and theory of mind in predicting the traits of borderline personality disorder. Method: In this study, 85 patients with borderline personality disorder were selected using convenience sampling method. To measure the desired variables, the questionnaires of Gross emotion regulation, Collins and Read attachment styles, and Baron Cohen's Reading Mind from Eyes Test were applied. The data were analyzed using multivariate stepwise regression technique. Results: Emotion regulation, attachment styles, and theory of mind predicted 41.2% of the variance criterion altogether; among which, the shares of emotion regulation, attachment styles and theory of mind to the distribution of the traits of borderline personality disorder were 27.5%, 9.8%, and 3.9%, respectively.‎‎ Conclusion: The results of the study revealed that emotion regulation, attachment styles, and theory of mind are important variables in predicting the traits of borderline personality disorder and that these variables can be well applied for both the treatment and identification of this disorder. PMID:28050180

An Investigation into the Roles of Theory of Mind, Emotion Regulation, and Attachment Styles in Predicting the Traits of Borderline Personality Disorder.

PubMed

Ghiasi, Hamed; Mohammadi, Abolalfazl; Zarrinfar, Pouria

2016-10-01

Objective: Borderline personality disorder is one of the most complex and prevalent personality disorders. Many variables have so far been studied in relation to this disorder. This study aimed to investigate the role of emotion regulation, attachment styles, and theory of mind in predicting the traits of borderline personality disorder. Method: In this study, 85 patients with borderline personality disorder were selected using convenience sampling method. To measure the desired variables, the questionnaires of Gross emotion regulation, Collins and Read attachment styles, and Baron Cohen's Reading Mind from Eyes Test were applied. The data were analyzed using multivariate stepwise regression technique. Results: Emotion regulation, attachment styles, and theory of mind predicted 41.2% of the variance criterion altogether; among which, the shares of emotion regulation, attachment styles and theory of mind to the distribution of the traits of borderline personality disorder were 27.5%, 9.8%, and 3.9%, respectively.‎‎ Conclusion : The results of the study revealed that emotion regulation, attachment styles, and theory of mind are important variables in predicting the traits of borderline personality disorder and that these variables can be well applied for both the treatment and identification of this disorder.

Work and common psychiatric disorders

PubMed Central

Henderson, M; Harvey, SB; Øverland, S; Mykletun, A; Hotopf, M

2011-01-01

Psychiatric disorders are now the most common reason for long-term sickness absence. The associated loss in productivity and the payment of disability benefits places a substantial burden on the economies of many developed countries. The occupational dysfunction associated with psychiatric disorders can also lead to poverty and social isolation. As a result the area of work and psychiatric disorders is a high priority for policymakers. There are two main agendas: for many researchers and clinicians the focus is on the need to overcome stigma and ensure people with severe psychiatric disorders have meaningful work; however the public health agenda predominantly relates to the more common disorders such as depression and anxiety, which contribute a greater burden of disability benefits and pensions. In this review we attempt to address this second agenda. The relatively sparse evidence available reveals a complex field with significant interplay between medical, psychological social and cultural factors. Sick leave can be a ‘process’ as well as an ‘event’. In this review we propose a staged model where different risk and protective factors contribute to the onset of psychiatric disorders in the working population, the onset of short-term sickness absence, and the transition from short- to long-term absence. We also examine strategies to manage psychiatric disorder in the workforce with a view towards returning the employee to work. Our aim in this review is to highlight the complexity of the area, to stimulate debate and to identify important gaps in knowledge where further research might benefit both patients and wider society. PMID:21558098

Complex oxides: Intricate disorder

DOE PAGES

Uberuaga, Blas Pedro

2016-02-29

In this study, complex oxides such as pyrochlores have a myriad of potential technological applications, including as fast ion conductors and radiation-tolerant nuclear waste forms. They are also of interest for their catalytic and spin ice properties. Many of these functional properties are enabled by the atomic structure of the cation sublattices. Pyrochlores (A2B2O7) contain two different cations (A and B), typically a 3+ rare earth and a 4+ transition metal such as Hf, Zr, or Ti. The large variety of chemistries that can form pyrochlores leads to a rich space in which to search for exotic new materials. Furthermore,more » how cations order or disorder on their respective sublattices for a given chemical composition influences the functional properties of the oxide. For example, oxygen ionic conductivity is directly correlated with the level of cation disorder — the swapping of A and B cations 1. Further, the resistance of these materials against amorphization has also been connected with the ability of the cations to disorder 2, 3. These correlations between cation structure and functionality have spurred great interest in the structure of the cation sublattice under irradiation, with significant focus on the disordering mechanisms and disordered structure. Previous studies have found that, upon irradiation, pyrochlores often undergo an order-to-disorder transformation, in which the resulting structure is, from a diffraction point of view, indistinguishable from fluorite (AO2) (ref. 3). Shamblin et al. now reveal that the structure of disordered pyrochlore is more complicated than previously thought 4.« less

[Attention deficit hyperactivity disorder: its aetiological factors and endophenotypes].

PubMed

Ferrando-Lucas, M T

2006-02-13

Attention deficit hyperactivity disorder (ADHD) is one of the most frequent reasons for patients' visits in everyday practice. The academic and social distortion it produces in those affected by this condition have turned it into a subject that is receiving growing attention from researchers and the progress being made in the neurosciences means that it is being investigated from a wide range of approaches. Genetic aspects, as well as anatomical and neurobiological markers, are some of the new lines of research that are being used together with a more precise neuropsychological approach to obtain a more comprehensive understanding of ADHD. Such knowledge now involves genetic factors, centres of cognitive disorder and the search for endophenotypes that account for the complexity of its semiology. The primary cognitive deficits in ADHD appear to be the underlying problem in the disorder, special attention also being given to both the executive functions and the distortion of the capacity to inhibit responses. Furthermore, anatomical factors have been related to the type and severity of the symptomatology of the disorder, although the dispersion of the results and the genetic findings that focus their attention on anomalous alleles for dopamine transporting and receptor genes suggest that the disorder is more complex. The different aetiological factors that have been associated to the disorder and the variability in the semiology of ADHD place us before a situation in disarray; the determination of endophenotypes, however, could enable us carry out a better systematisation of a disorder that is currently still a long way from being fully understood.

Object-directed imitation in autism spectrum disorder is differentially influenced by motoric task complexity, but not social contextual cues.

PubMed

Chetcuti, Lacey; Hudry, Kristelle; Grant, Megan; Vivanti, Giacomo

2017-11-01

We examined the role of social motivation and motor execution factors in object-directed imitation difficulties in autism spectrum disorder. A series of to-be-imitated actions was presented to 35 children with autism spectrum disorder and 20 typically developing children on an Apple ® iPad ® by a socially responsive or aloof model, under conditions of low and high motor demand. There were no differences in imitation performance (i.e. the number of actions reproduced within a fixed sequence), for either group, in response to a model who acted socially responsive or aloof. Children with autism spectrum disorder imitated the high motor demand task more poorly than the low motor demand task, while imitation performance for typically developing children was equivalent across the low and high motor demand conditions. Furthermore, imitative performance in the autism spectrum disorder group was unrelated to social reciprocity, though positively associated with fine motor coordination. These results suggest that difficulties in object-directed imitation in autism spectrum disorder are the result of motor execution difficulties, not reduced social motivation.

[One of the approaches to psychological-pedagogical help to children with severe movement disorders].

PubMed

Levchenko, I Iu; Simonova, T N

2012-01-01

The objective of the study was to work out an effective model of complex help to children with severe movement disorders. We examined 440 preschoolers with children cerebral palsy with severe movement disorders and 70 children with mild movement disorders. Functions of motor, emotional-personal and cognitive spheres and independence status with determination of 5 levels were studied in 47 patients. Three groups (from the group without concomitant (sensor, intellectual etc) disorders to the group with most severe disorders) were singled out. The authors characterize the model as an open integral system of methods, tools and ways providing the adaptation of children in response to external circumstances and changes in the state of patients. The creation of a correction-developing environment, consisting of 3 components: spatial-objective, technological (methodological) and social, is discussed. We present results of the development of children, evaluated by the following indices: general technique, sensory perceptive development, social adaptation, anxiety, cognitive activity, from 1997 to 2008. The 15 year follow-up demonstrated the stability of achieved positive results.

Understanding psychiatric disorder by capturing ecologically relevant features of learning and decision-making.

PubMed

Scholl, Jacqueline; Klein-Flügge, Miriam

2017-09-28

Recent research in cognitive neuroscience has begun to uncover the processes underlying increasingly complex voluntary behaviours, including learning and decision-making. Partly this success has been possible by progressing from simple experimental tasks to paradigms that incorporate more ecological features. More specifically, the premise is that to understand cognitions and brain functions relevant for real life, we need to introduce some of the ecological challenges that we have evolved to solve. This often entails an increase in task complexity, which can be managed by using computational models to help parse complex behaviours into specific component mechanisms. Here we propose that using computational models with tasks that capture ecologically relevant learning and decision-making processes may provide a critical advantage for capturing the mechanisms underlying symptoms of disorders in psychiatry. As a result, it may help develop mechanistic approaches towards diagnosis and treatment. We begin this review by mapping out the basic concepts and models of learning and decision-making. We then move on to consider specific challenges that emerge in realistic environments and describe how they can be captured by tasks. These include changes of context, uncertainty, reflexive/emotional biases, cost-benefit decision-making, and balancing exploration and exploitation. Where appropriate we highlight future or current links to psychiatry. We particularly draw examples from research on clinical depression, a disorder that greatly compromises motivated behaviours in real-life, but where simpler paradigms have yielded mixed results. Finally, we highlight several paradigms that could be used to help provide new insights into the mechanisms of psychiatric disorders. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

Different patterns of morphological changes in the hippocampus and dentate gyrus accompany the differential expression of disability following nerve injury.

PubMed

Kalman, Eszter; Keay, Kevin A

2014-12-01

Physical and psychological trauma which results in mood disorders and the disruption of complex behaviours is associated with reductions in hippocampal volume. Clinical evaluation of neuropathic pain reveals mood and behavioural change in a significant number of patients. A rat model of neuropathic injury results in complex behavioural changes in a subpopulation (~30%) of injured rats; these changes are co-morbid with a range of other 'disabilities'. The specific objective of this study was to determine in rats the morphology of the hippocampus and dentate gyrus in individuals with and without complex behavioural disruptions following a constriction injury of the sciatic nerve, and to determine whether rats that develop disabilities following nerve injury have a reduced hippocampal volume compared with injured rats with no disabilities. The social behaviours of nerve-injured rats were evaluated before and after nerve injury. The morphology of the hippocampus of rats with and without behavioural disruptions was compared in serial histological sections. Single-housing and repeated social-interaction testing had no effect on the morphology of either the hippocampus or the dentate gyrus. Rats with transient or ongoing disability identified by behavioural disruption following sciatic nerve injury, show bilateral reductions in hippocampal volume, and lateralised reduction in the dentate gyrus (left side). Disabled rats display a combination of behavioural and physiological changes, which resemble many of the criteria used clinically to diagnose mood disorders. They also show reductions in the volume of the hippocampus similar to people with clinically diagnosed mood disorders. The sciatic nerve injury model reveals a similarity to the human neuropathic pain presentation presenting an anatomically specific focus for the investigation of the neural mechanisms underpinning the co-morbidity of chronic pain and mood disorder. © 2014 Anatomical Society.

Towards a functional model of mental disorders incorporating the laws of thermodynamics.

PubMed

Murray, George C; McKenzie, Karen

2013-05-01

The current paper presents the hypothesis that the understanding of mental disorders can be advanced by incorporating the laws of thermodynamics, specifically relating to energy conservation and energy transfer. These ideas, along with the introduction of the notion that entropic activities are symptomatic of inefficient energy transfer or disorder, were used to propose a model of understanding mental ill health as resulting from the interaction of entropy, capacity and work (environmental demands). The model was applied to Attention Deficit Hyperactivity Disorder, and was shown to be compatible with current thinking about this condition, as well as emerging models of mental disorders as complex networks. A key implication of the proposed model is that it argues that all mental disorders require a systemic functional approach, with the advantage that it offers a number of routes into the assessment, formulation and treatment for mental health problems. Copyright © 2013 Elsevier Ltd. All rights reserved.

Malingering dissociative identity disorder: objective and projective assessment.

PubMed

Labott, Susan M; Wallach, Heather R

2002-04-01

Verification of dissociative identity disorder presents challenges given the complex nature of the illness. This study addressed the concern that this disorder can be successfully malingered on objective and projective psychological tests. 50 undergraduate women were assigned to a Malingering or a Control condition, then completed the Rorschach Inkblot Test and the Dissociative Experiences Scale II. The Malingering group were asked to simulate dissociative identity disorder; controls received instructions to answer all materials honestly. Analysis indicated that malingerers were significantly more likely to endorse dissociative experiences on the Dissociative Experiences Scale II in the range common to patients with diagnosed dissociative identity disorder. However, on the Rorschach there were no significant differences between the two groups. Results suggest that the assessment of dissociative identity disorder requires a multifaceted approach with both objective and projective assessment tools. Research is needed to assess these issues in clinical populations.

Comorbidity of Asperger's syndrome and Bipolar disorder

PubMed Central

2008-01-01

Background and objective Asperger's Syndrome (AS) is a pervasive developmental disorder that is sometimes unrecognized, especially in the adult psychiatric setting. On the other hand, in patients with an AS diagnosis, comorbid psychiatric disorders may be unrecognized in the juvenile setting. The aim of the paper is to show and discuss some troublesome and complex problems of the management of patients with AS and comorbid Bipolar Disorder (BD). Methods The paper describes three patients affected by AS and bipolar spectrum disorders. Results and conclusion Mood stabilizers and 2nd generation antipsychotics were effective in the treatment of these AS patients with comorbid BD, while the use of antidepressants was associated with worsening of the mood disorder. It is of importance to recognize both the psychiatric diagnoses in order to arrange an exhaustive therapeutic program and to define specific and realistic goals of treatment. PMID:19014623

Diagnosis of complex acid-base disorders: physician performance versus the microcomputer.

PubMed

Schreck, D M; Zacharias, D; Grunau, C F

1986-02-01

Patients with acid-base disturbances that are often complex frequently present to the emergency department. The sometimes hectic nature of the ED can preclude the appropriate quantitative analysis required by these disorders, especially when mixed disturbances are present. A computer program using generally accepted acid-base and electrolyte formulae was developed for use on the Apple II+ or IBM-PC microcomputer. Each of a series of 35 acid-base disturbances incorporating single, double, and triple disorders was correctly identified by the computer in less than 45 seconds. Problem sets based on the same 35 disturbances were presented to 21 physician-subjects at various levels of training from the emergency medicine, internal medicine, pediatrics, surgery, and family practice specialties. Although the physicians were given unlimited time and the necessary formulae to reach a diagnosis, they were requested to perform their analyses in the same fashion used in the ED. Although times varied widely, no physician spent more than five minutes on any problem. The physician correct response rates were 86%, 49%, and 17% for single, double, and triple disorders, respectively. The primary disorder correct response rate was 89% for double disorders and 94% for triple disorders. The primary and secondary disorder correct response rate was 58% for triple disorders. The data suggest that the microcomputer may be beneficial in the rapid assessment of complex disorders.

[Neuroanatomical, genetic and neurochemical aspects of infantile autism].

PubMed

Gerhant, Aneta; Olajossy, Marcin; Olajossy-Hilkesberger, Luiza

2013-01-01

Infantile autism is a neurodevelopmental disorder characterized by impairments in communication, reciprocal social interaction and restricted repetitive behaviors or interests. Although the cause of these disorders is not yet known, studies strongly suggest a genetic basis with a complex mode of inheritance. The etiopathogenetic processes of autism are extremely complex, which is reflected in the varying course and its symptomatology. Trajectories of brain development and volumes of its structures are aberrant in autistic patients. It is suggested that disturbances in sertotoninergic, gabaergic, glutaminergic, cholinergic and dopaminergic neurotransmission can be responsible for symptoms of autism as well as can disturb the development of the young brain. The objective of this article is to present the results of reasearch on neuroanatomical, neurochemical and genetic aspects of autism.

No evidence for differential dose effects of hydrocortisone on intrusive memories in female patients with complex post-traumatic stress disorder--a randomized, double-blind, placebo-controlled, crossover study.

PubMed

Ludäscher, Petra; Schmahl, Christian; Feldmann, Robert E; Kleindienst, Nikolaus; Schneider, Miriam; Bohus, Martin

2015-10-01

Post-traumatic stress disorder is characterized by intrusive traumatic memories. Presently, a controversial debate is ongoing regarding whether reduced cortisol secretion in post-traumatic stress disorder promotes an automatic retrieval of trauma-associated memories. Hence, a pharmacological elevation of cortisol was proposed to decrease post-traumatic stress disorder symptoms, particularly intrusions. The present study investigated the impact of two different doses of hydrocortisone on automatic memory retrieval using a randomized, double-blind, placebo-controlled, crossover study in 30 inpatients with post-traumatic stress disorder. All participants were female and received various psychotropic medications. They were randomly assigned to one of two groups within a crossover design: they received either 1 week placebo followed by 1 week hydrocortisone 10/d, followed by 1 week placebo, followed by hydrocortisone 30 mg/d (15 participants) or 1 week hydrocortisone 30 mg/d, followed by 1 week placebo, followed by 1 week hydrocortisone 10 mg/d, followed by 1 week placebo (15 participants). The outcome measures were the frequency and the intensity of intrusions, the overall symptomatology of post-traumatic stress disorder and the general psychopathology. We did not find any differences in the frequency and the intensity of post-traumatic stress disorder-related intrusions between the 10 mg hydrocortisone, the 30 mg hydrocortisone and the placebo condition. All effect sizes for the hydrocortisone condition vs. placebo were very small. Additionally, the overall symptomatology of post-traumatic stress disorder and the general psychopathology did not differ between the hydrocortisone therapies and placebo. Our results do not show any effect of the hydrocortisone administration on intrusions in complex post-traumatic stress disorder. © The Author(s) 2015.

Genes for normal sleep and sleep disorders.

PubMed

Tafti, Mehdi; Maret, Stéphanie; Dauvilliers, Yves

2005-01-01

Sleep and wakefulness are complex behaviors that are influenced by many genetic and environmental factors, which are beginning to be discovered. The contribution of genetic components to sleep disorders is also increasingly recognized as important. Point mutations in the prion protein, period 2, and the prepro-hypocretin/orexin gene have been found as the cause of a few sleep disorders but the possibility that other gene defects may contribute to the pathophysiology of major sleep disorders is worth in-depth investigations. However, single gene disorders are rare and most common disorders are complex in terms of their genetic susceptibility, environmental effects, gene-gene, and gene-environment interactions. We review here the current progress in the genetics of normal and pathological sleep.

[Variable magnetic fields in the treatment of tics disorders - preliminary results].

PubMed

Pasek, Jarosław; Jędrzejewska, Anna; Jagodziński, Leszek; Obuchowicz, Anna; Flak, Maria; Sieroń, Aleksander

Tics disorders is frequent pathological syndrome, particularly typical for children's age. The symptoms of this disease are differential, and their intensification individualized, which makes difficult unique recognition. Tics disorders concern the most often the muscles of face, head, upper limbs and trunk. The study group consisted of 16 patients (11 boys and 5 girls) with tics complex disorders about unknown etiology particularly relating of face and upper limbs muscles. In the treatment were the interventions with use a magnetotherapy and magnetostimulation applied. The procedures were ones daily by 3 weeks in two series executed. It author's pool was the frequency of occurrence tics disorders as well as the proportional opinion of effectiveness conducted treatment estimated. After 10 weeks in 14 patients was the decrease of occurrence frequency involuntary movements observed, in proportional scale about 75%. The results of subjective opinion of mood showed, that decrease the frequency tics disorders had in all children the direct shift on improvement their mood, and also satisfaction in their parents. The use of variable magnetic fields influenced on decrease the occurrence frequency tics disorders, and also on improvement quality of life the treated patients.

[Variable magnetic fields in the treatment of tics disorders - preliminary results].

PubMed

Pasek, Jarosław; Jędrzejewska, Anna; Jagodziński, Leszek; Obuchowicz, Anna; Flak, Maria; Sieroń, Aleksander

2016-01-01

Tics disorders is frequent pathological syndrome, particularly typical for children's age. The symptoms of this disease are differential, and their intensification individualized, which makes difficult unique recognition. Tics disorders concern the most often the muscles of face, head, upper limbs and trunk. The study group consisted of 16 patients (11 boys and 5 girls) with tics complex disorders about unknown etiology particularly relating of face and upper limbs muscles. In the treatment were the interventions with use a magnetotherapy and magnetostimulation applied. The procedures were ones daily by 3 weeks in two series executed. It author's pool was the frequency of occurrence tics disorders as well as the proportional opinion of effectiveness conducted treatment estimated. After 10 weeks in 14 patients was the decrease of occurrence frequency involuntary movements observed, in proportional scale about 75%. The results of subjective opinion of mood showed, that decrease the frequency tics disorders had in all children the direct shift on improvement their mood, and also satisfaction in their parents. The use of variable magnetic fields influenced on decrease the occurrence frequency tics disorders, and also on improvement quality of life the treated patients.

Personality disorders at the interface of psychiatry and the law: legal use and clinical classification

PubMed Central

Johnson, Sally C.; Elbogen, Eric B.

2013-01-01

Personality disorders have a complex relationship with the law that in many ways reflects their complexity within the clinical and research communities. This paper addresses expert testimony about personality disorders, outlines how personality disorders are assessed in forensic cases, and describes how personality disorders are viewed in different legal contexts. Reasons are identified why personality disorders are not generally accepted as significant mental illness within the legal system, including high incidence of personality dysfunction in criminal populations, frequent comorbidity of personality disorders making it difficult to determine direct causation, and difficulty determining where on a continuum personality traits should be defined as illness (or not). In summary, the legal system, to a significant degree, mirrors the clinical conception of personality disorders as not severe mental diseases or defects, not likely to change, and most often, under volitional control. PMID:24174894

Personality disorders at the interface of psychiatry and the law: legal use and clinical classification.

PubMed

Johnson, Sally C; Elbogen, Eric B

2013-06-01

Personality disorders have a complex relationship with the law that in many ways reflects their complexity within the clinical and research communities. This paper addresses expert testimony about personality disorders, outlines how personality disorders are assessed in forensic cases, and describes how personality disorders are viewed in different legal contexts. Reasons are identified why personality disorders are not generally accepted as significant mental illness within the legal system, including high incidence of personality dysfunction in criminal populations, frequent comorbidity of personality disorders making it difficult to determine direct causation, and difficulty determining where on a continuum personality traits should be defined as illness (or not). In summary, the legal system, to a significant degree, mirrors the clinical conception of personality disorders as not severe mental diseases or defects, not likely to change, and most often, under volitional control.

Clinical and autoimmune features of a patient with autism spectrum disorder seropositive for anti-NMDA-receptor autoantibody.

PubMed

Gréa, Hélène; Scheid, Isabelle; Gaman, Alexandru; Rogemond, Véronique; Gillet, Sandy; Honnorat, Jérôme; Bolognani, Federico; Czech, Christian; Bouquet, Céline; Toledano, Elie; Bouvard, Manuel; Delorme, Richard; Groc, Laurent; Leboyer, Marion

2017-03-01

Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by dysfunctions in social interactions resulting from a complex interplay between immunogenetic and environmental risk factors. Autoimmunity has been proposed as a major etiological component of ASD. Whether specific autoantibodies directed against brain targets are involved in ASD remains an open question. Here, we identified within a cohort an ASD patient with multiple circulating autoantibodies, including the well-characterized one against glutamate NMDA receptor (NMDAR-Ab). The patient exhibited alexithymia and previously suffered from two major depressive episodes without psychotic symptoms. Using a single molecule-based imaging approach, we demonstrate that neither NMDAR-Ab type G immunoglobulin purified from the ASD patient serum, nor that from a seropositive healthy subject, disorganize membrane NMDAR complexes at synapses. These findings suggest that the autistic patient NMDAR-Abs do not play a direct role in the etiology of ASD and that other autoantibodies directed against neuronal targets should be investigated.

Bone Disease after Kidney Transplantation

PubMed Central

Bouquegneau, Antoine; Salam, Syrazah; Delanaye, Pierre; Eastell, Richard

2016-01-01

Bone and mineral disorders occur frequently in kidney transplant recipients and are associated with a high risk of fracture, morbidity, and mortality. There is a broad spectrum of often overlapping bone diseases seen after transplantation, including osteoporosis as well as persisting high– or low–turnover bone disease. The pathophysiology underlying bone disorders after transplantation results from a complex interplay of factors, including preexisting renal osteodystrophy and bone loss related to a variety of causes, such as immunosuppression and alterations in the parathyroid hormone-vitamin D-fibroblast growth factor 23 axis as well as changes in mineral metabolism. Management is complex, because noninvasive tools, such as imaging and bone biomarkers, do not have sufficient sensitivity and specificity to detect these abnormalities in bone structure and function, whereas bone biopsy is not a widely available diagnostic tool. In this review, we focus on recent data that highlight improvements in our understanding of the prevalence, pathophysiology, and diagnostic and therapeutic strategies of mineral and bone disorders in kidney transplant recipients. PMID:26912549

Challenges in management of complex panic disorder in a palliative care setting

PubMed Central

Udo, Itoro; Gash, Amanda

2012-01-01

This is a complex case of post-traumatic stress disorder (PTSD) with comorbid panic disorder occurring in a woman in her mid-60s, with a family history of neurotic illness. PTSD arose in the context of treatment for terminal lung cancer. This patient who had been close to her father watched him die of cancer, when he was about her age. Her diagnosis and treatment prompted traumatic recollections of her father's illness and death that resulted in her voluntary withdrawal from cancer treatment. The goals of treatment were to promptly reduce anxiety, minimise use of sedating pharmacotherapy, promote lucidity and prolong anxiety-free state thereby allowing time for important family interactions. Prompt, sustained relief of severe anxiety was necessary to achieve comfort at the end of life. Skilled additions of psychological therapies (eye movement desensitisation reprocessing, clinical hypnosis and breathing exercises) with combined pharmacotherapy (mirtazepine and quetiapine) led to control of anxiety and reduction of post-traumatic stress. PMID:23047995

Challenges in management of complex panic disorder in a palliative care setting.

PubMed

Udo, Itoro; Gash, Amanda

2012-10-09

This is a complex case of post-traumatic stress disorder (PTSD) with comorbid panic disorder occurring in a woman in her mid-60s, with a family history of neurotic illness. PTSD arose in the context of treatment for terminal lung cancer. This patient who had been close to her father watched him die of cancer, when he was about her age. Her diagnosis and treatment prompted traumatic recollections of her father's illness and death that resulted in her voluntary withdrawal from cancer treatment. The goals of treatment were to promptly reduce anxiety, minimise use of sedating pharmacotherapy, promote lucidity and prolong anxiety-free state thereby allowing time for important family interactions. Prompt, sustained relief of severe anxiety was necessary to achieve comfort at the end of life. Skilled additions of psychological therapies (eye movement desensitisation reprocessing, clinical hypnosis and breathing exercises) with combined pharmacotherapy (mirtazepine and quetiapine) led to control of anxiety and reduction of post-traumatic stress.

Primary complex motor stereotypies in older children and adolescents: clinical features and longitudinal follow-up.

PubMed

Oakley, Christopher; Mahone, E Mark; Morris-Berry, Christina; Kline, Tina; Singer, Harvey S

2015-04-01

Complex motor stereotypies are rhythmic, repetitive, fixed, and purposeless movements that stop with distraction. Once believed to occur only in children with autism spectrum or other developmental disorders, their presence in otherwise typically developing children (primary) has been well-established. In primary complex motor stereotypies, little information is available about the long-term outcome of these movements or existing comorbidities. Forty-nine healthy participants (31 boys), ages 9 to 20 years with primary complex motor stereotypies who were previously diagnosed at a pediatric movements disorder clinic, were identified from medical records. Parents or the young adult (if older than age 18), completed a telephone interview evaluating family history, outcome, and comorbidities including attention-deficit hyperactivity disorder, obsessive compulsive disorder, anxiety, and tics/Tourette syndrome. Standardized questionnaires assessing attention-deficit hyperactivity, obsessive compulsive disorder, and anxiety were used to validate parent report of comorbidities. Stereotypy onset occurred before age 3 years in 98%. In all but one individual, stereotypies persisted at the time of phone follow-up (follow-up range: 6.8-20.3 years). Positive family history of complex motor stereotypies was identified in 39%. Most participants (92%) had concern for at least one comorbid disorder, including parent-/patient-reported clinically elevated levels of anxiety (73%), attention-deficit hyperactivity (63%), obsessive compulsive disorder (35%), and tics/Tourette syndrome (22%). Primary motor stereotypies typically begin in early childhood and, although reduced in frequency and duration, persist at least through the teenage years. Repetitive movements are associated with a variety of comorbidities that often have a greater functional impact than the stereotypic behavior. Copyright © 2015 Elsevier Inc. All rights reserved.

[Prevalence of sleep-related breathing disorders of inpatients with psychiatric disorders].

PubMed

Behr, M; Acker, J; Cohrs, S; Deuschle, M; Danker-Hopfe, H; Göder, R; Norra, C; Richter, K; Riemann, D; Schilling, C; Weeß, H-G; Wetter, T C; Wollenburg, L M; Pollmächer, T

2018-06-06

Sleep-related breathing disorders seriously impair well-being and increase the risk for relevant somatic and psychiatric disorders. Moreover, risk factors for sleep-related breathing disorders are highly prevalent in psychiatric patients. The aim of this study was for the first time in Germany to study the prevalence of obstructive sleep apnea syndrome (OSAS) as the most common form of sleep-related breathing disorder in patients with psychiatric disorders. In 10 psychiatric hospitals in Germany and 1 hospital in Switzerland, a total of 249 inpatients underwent an 8‑channel sleep polygraphy to investigate the prevalence of sleep apnea in this group of patients. With a conspicuous screening result of 23.7% of the subjects, a high prevalence of sleep-related breathing disorders was found to occur among this group of patients. Male gender, higher age and high body mass index (BMI) were identified as positive risk factors for the detection of OSAS. The high prevalence indicates that sleep apnea is a common sleep disorder among psychiatric patients. Although OSAS can lead to substantial disorders of the mental state and when untreated is accompanied by serious somatic health problems, screening procedures are not part of the routine work-up in psychiatric hospitals; therefore, sleep apnea is presumably underdiagnosed in psychiatric patients. In view of the results of this and previous studies, this topic complex should be the subject of further research studies.

Peroxisome biogenesis disorders in the Zellweger spectrum: An overview of current diagnosis, clinical manifestations, and treatment guidelines.

PubMed

Braverman, Nancy E; Raymond, Gerald V; Rizzo, William B; Moser, Ann B; Wilkinson, Mark E; Stone, Edwin M; Steinberg, Steven J; Wangler, Michael F; Rush, Eric T; Hacia, Joseph G; Bose, Mousumi

2016-03-01

Peroxisome biogenesis disorders in the Zellweger spectrum (PBD-ZSD) are a heterogeneous group of genetic disorders caused by mutations in PEX genes responsible for normal peroxisome assembly and functions. As a result of impaired peroxisomal activities, individuals with PBD-ZSD can manifest a complex spectrum of clinical phenotypes that typically result in shortened life spans. The extreme variability in disease manifestation ranging from onset of profound neurologic symptoms in newborns to progressive degenerative disease in adults presents practical challenges in disease diagnosis and medical management. Recent advances in biochemical methods for newborn screening and genetic testing have provided unprecedented opportunities for identifying patients at the earliest possible time and defining the molecular bases for their diseases. Here, we provide an overview of current clinical approaches for the diagnosis of PBD-ZSD and provide broad guidelines for the treatment of disease in its wide variety of forms. Although we anticipate future progress in the development of more effective targeted interventions, the current guidelines are meant to provide a starting point for the management of these complex conditions in the context of personalized health care. Copyright © 2015 Elsevier Inc. All rights reserved.

Prevalence of interpersonal trauma exposure and trauma-related disorders in severe mental illness

PubMed Central

Mauritz, Maria W.; Goossens, Peter J. J.; Draijer, Nel; van Achterberg, Theo

2013-01-01

Background Interpersonal trauma exposure and trauma-related disorders in people with severe mental illness (SMI) are often not recognized in clinical practice. Objective To substantiate the prevalence of interpersonal trauma exposure and trauma-related disorders in people with SMI. Methods We conducted a systematic review of four databases (1980–2010) and then described and analysed 33 studies in terms of primary diagnosis and instruments used to measure trauma exposure and trauma-related disorders. Results Population-weighted mean prevalence rates in SMI were physical abuse 47% (range 25–72%), sexual abuse 37% (range 24–49%), and posttraumatic stress disorder (PTSD) 30% (range 20–47%). Compared to men, women showed a higher prevalence of sexual abuse in schizophrenia spectrum disorder, bipolar disorder, and mixed diagnosis groups labelled as having SMI. Conclusions Prevalence rates of interpersonal trauma and trauma-related disorders were significantly higher in SMI than in the general population. Emotional abuse and neglect, physical neglect, complex PTSD, and dissociative disorders have been scarcely examined in SMI. PMID:23577228

The social-cognitive basis of personality disorders.

PubMed

Herpertz, Sabine C; Bertsch, Katja

2014-01-01

The review summarizes recent results on abnormalities in social cognition in patients with personality disorders that predispose them to develop dysfunctional interaction with others. The review starts with more basic social cognition processes, such as emotion recognition and reactions to social exclusion that are followed by more complex processes such as cognitive and affective empathy. The deficits in social cognition depend on the particular function that is investigated and is strongly associated with characteristic symptoms of particular personality disorders. Thus, patients with borderline personality disorder are hypersensitive for social threat, they show deficits in cognitive empathy and high emotion contagion, that is, they share emotions of others without properly discriminating between one's own feelings and those of others. Psychopaths are characterized by deficiency in facial fear recognition and emotional empathy similar to patients with narcissistic personality disorder. Studies on social cognition in cluster A and C personality disorders are sparse. Research indicates deficits in social cognition in patients with personality disorders, but more research is needed to investigate social cognition in cluster A and C personality disorders and to compare deficits in social cognitive functions across personality disorders.

Neural correlates of eating disorders: translational potential

PubMed Central

McAdams, Carrie J; Smith, Whitney

2015-01-01

Eating disorders are complex and serious psychiatric illnesses whose etiology includes psychological, biological, and social factors. Treatment of eating disorders is challenging as there are few evidence-based treatments and limited understanding of the mechanisms that result in sustained recovery. In the last 20 years, we have begun to identify neural pathways that are altered in eating disorders. Consideration of how these pathways may contribute to an eating disorder can provide an understanding of expected responses to treatments. Eating disorder behaviors include restrictive eating, compulsive overeating, and purging behaviors after eating. Eating disorders are associated with changes in many neural systems. In this targeted review, we focus on three cognitive processes associated with neurocircuitry differences in subjects with eating disorders such as reward, decision-making, and social behavior. We briefly examine how each of these systems function in healthy people, using Neurosynth meta-analysis to identify key regions commonly implicated in these circuits. We review the evidence for disruptions of these regions and systems in eating disorders. Finally, we describe psychiatric and psychological treatments that are likely to function by impacting these regions. PMID:26767185

[Body dysmorphic disorder: clinical aspects, nosological dimensions and controversies with anorexia nervosa].

PubMed

Behar, Rosa; Arancibia, Marcelo; Heitzer, Cristóbal; Meza, Nicolás

2016-05-01

There is strong evidence about the co-existence of body dysmorphic disorder (BDD) and eating disorders (ED), particularly with anorexia nervosa (AN). An exhaustive review of the specialised literature regarding these disorders was carried out. The results show that their co-occurrence implies a more complex diagnosis and treatment, a more severe clinical symptomatology and a worse prognosis and outcome. Both disorders display common similarities, differences and comorbidities, which allow authors to classify them in different nosological spectra (somatomorphic, anxious, obsessive-compulsive, affective and psychotic). Their crossover involves higher levels of body dissatisfaction and body image distortion, depression, suicidal tendency, personality disorders, substance use/abuse, obsessive-compulsive disorder, social phobia, alexithymia and childhood abuse or neglect background. Treatment including cognitive-behavioral psychotherapy and selective reuptake serotonin inhibitors are effective for both, BDD and ED; nevertheless, plastic surgery could exacerbate BDD. Clinical traits of BDD must be systematically detected in patients suffering from ED and vice versa.

Is Glycogen Synthase Kinase-3 a Central Modulator in Mood Regulation?

PubMed Central

Li, Xiaohua; Jope, Richard S

2010-01-01

Little is known regarding the mechanisms underlying the complex etiology of mood disorders, represented mainly by major depressive disorder and bipolar disorder. The 1996 discovery that lithium inhibits glycogen synthase kinase-3 (GSK3) raised the possibility that impaired inhibition of GSK3 is associated with mood disorders. This is now supported by evidence from animal biochemical, pharmacological, molecular, and behavioral studies and from human post-mortem brain, peripheral tissue, and genetic studies that are reviewed here. Mood disorders may result in part from impairments in mechanisms controlling the activity of GSK3 or GSK3-regulated functions, and disruptions of these regulating systems at different signaling sites may contribute to the heterogeneity of mood disorders. This substantial evidence supports the conclusion that bolstering the inhibitory control of GSK3 is an important component of the therapeutic actions of drugs used to treat mood disorders and that GSK3 is a valid target for developing new therapeutic interventions. PMID:20668436

Severe avoidant/restrictive food intake disorder and coexisting stimulant treated attention deficit hyperactivity disorder.

PubMed

Pennell, Alexandra; Couturier, Jennifer; Grant, Christina; Johnson, Natasha

2016-11-01

There is a growing body of literature describing the development, clinical course, and treatment of avoidant/restrictive food intake disorder (ARFID), a diagnostic category introduced in the DSM-5. However, information surrounding complex cases of ARFID involving coexisting medical and/or psychiatric disorders remains scarce. Here we report on two cases of young patients diagnosed concurrently with ARFID and attention deficit hyperactivity disorder (ADHD) who both experienced significant growth restriction following initiation of stimulant medication. The appetite suppressant effect of stimulants exacerbated longstanding avoidant and restrictive eating behaviors resulting in growth restriction and admission to an inpatient eating disorders unit. The implications of ARFID exacerbated by stimulant-treated ADHD are explored, as well as the treatment delivered. These cases suggest that further research is needed to explore management options to counteract the appetite suppression effects of stimulants, while simultaneously addressing attention deficit symptoms and oppositional behavior. © 2016 Wiley Periodicals, Inc. (Int J Eat Disord 2016; 49:1036-1039). © 2016 Wiley Periodicals, Inc.

Play complexity and toy engagement in preschoolers with autism spectrum disorder: Do girls and boys differ?

PubMed

Harrop, Clare; Green, Jonathan; Hudry, Kristelle

2017-01-01

While sex differences in play have been extensively observed in typical development, only a handful of studies have explored this phenomenon in depth with children with autism spectrum disorders. This study explored sex differences in play complexity and toy engagement within caregiver-child interaction samples for preschool-aged children (2-5 years 11 months) with an autism spectrum disorder who were matched to typically developing children on sex and non-verbal development. Overall we found that girls and boys with autism spectrum disorder were largely equivalent in their play complexity. Despite similar play, girls and boys with autism spectrum disorder differed in a number of ways in their toy engagement, replicating traditional gender differences-girls played more with dolls and domestic items (though at lower rates than typically developing girls) and boys played more with the garage and cars (though at lower rates than typically developing boys). Our findings support the importance and utility of examining sex differences in autism spectrum disorder in light of those observed within typical development. © The Author(s) 2016.

Review of somatic symptoms in post-traumatic stress disorder.

PubMed

Gupta, Madhulika A

2013-02-01

Post-traumatic stress disorder (PTSD) is associated with both (1) 'ill-defined' or 'medically unexplained' somatic syndromes, e.g. unexplained dizziness, tinnitus and blurry vision, and syndromes that can be classified as somatoform disorders (DSM-IV-TR); and (2) a range of medical conditions, with a preponderance of cardiovascular, respiratory, musculoskeletal, neurological, and gastrointestinal disorders, diabetes, chronic pain, sleep disorders and other immune-mediated disorders in various studies. Frequently reported medical co-morbidities with PTSD across various studies include cardiovascular disease, especially hypertension, and immune-mediated disorders. PTSD is associated with limbic instability and alterations in both the hypothalamic- pituitary-adrenal and sympatho-adrenal medullary axes, which affect neuroendocrine and immune functions, have central nervous system effects resulting in pseudo-neurological symptoms and disorders of sleep-wake regulation, and result in autonomic nervous system dysregulation. Hypervigilance, a central feature of PTSD, can lead to 'local sleep' or regional arousal states, when the patient is partially asleep and partially awake, and manifests as complex motor and/or verbal behaviours in a partially conscious state. The few studies of the effects of standard PTSD treatments (medications, CBT) on PTSD-associated somatic syndromes report a reduction in the severity of ill-defined and autonomically mediated somatic symptoms, self-reported physical health problems, and some chronic pain syndromes.

The Neuron-specific Chromatin Regulatory Subunit BAF53b is Necessary for Synaptic Plasticity and Memory

PubMed Central

Vogel-Ciernia, Annie; Matheos, Dina P.; Barrett, Ruth M.; Kramár, Enikö; Azzawi, Soraya; Chen, Yuncai; Magnan, Christophe N.; Zeller, Michael; Sylvain, Angelina; Haettig, Jakob; Jia, Yousheng; Tran, Anthony; Dang, Richard; Post, Rebecca J.; Chabrier, Meredith; Babayan, Alex; Wu, Jiang I.; Crabtree, Gerald R.; Baldi, Pierre; Baram, Tallie Z.; Lynch, Gary; Wood, Marcelo A.

2013-01-01

Recent exome sequencing studies have implicated polymorphic BAF complexes (mammalian SWI/SNF chromatin remodeling complexes) in several human intellectual disabilities and cognitive disorders. However, it is currently unknown how mutations in BAF complexes result in impaired cognitive function. Post mitotic neurons express a neuron specific assembly, nBAF, characterized by the neuron-specific subunit BAF53b. Mice harboring selective genetic manipulations of BAF53b have severe defects in longterm memory and long-lasting forms of hippocampal synaptic plasticity. We rescued memory impairments in BAF53b mutant mice by reintroducing BAF53b in the adult hippocampus, indicating a role for BAF53b beyond neuronal development. The defects in BAF53b mutant mice appear to derive from alterations in gene expression that produce abnormal postsynaptic components, such as spine structure and function, and ultimately lead to deficits in synaptic plasticity. Our studies provide new insight into the role of dominant mutations in subunits of BAF complexes in human intellectual and cognitive disorders. PMID:23525042

Molecular mechanism of Spinocerebellar Ataxia type 6: glutamine repeat disorder, channelopathy and transcriptional dysregulation. The multifaceted aspects of a single mutation

PubMed Central

Giunti, Paola; Mantuano, Elide; Frontali, Marina; Veneziano, Liana

2015-01-01

Spinocerebellar Ataxia type 6 (SCA6) is an autosomal dominant neurodegenerative disease characterized by late onset, slowly progressive, mostly pure cerebellar ataxia. It is one of three allelic disorders associated to CACNA1A gene, coding for the Alpha1 A subunit of P/Q type calcium channel Cav2.1 expressed in the brain, particularly in the cerebellum. The other two disorders are Episodic Ataxia type 2 (EA2), and Familial Hemiplegic Migraine type 1 (FHM1). These disorders show distinct phenotypes that often overlap but have different pathogenic mechanisms. EA2 and FHM1 are due to mutations causing, respectively, a loss and a gain of channel function. SCA6, instead, is associated with short expansions of a polyglutamine stretch located in the cytoplasmic C-terminal tail of the protein. This domain has a relevant role in channel regulation, as well as in transcription regulation of other neuronal genes; thus the SCA6 CAG repeat expansion results in complex pathogenic molecular mechanisms reflecting the complex Cav2.1 C-terminus activity. We will provide a short review for an update on the SCA6 molecular mechanism. PMID:25762895

Evaluation of Oxidative Stress in Bipolar Disorder in terms of Total Oxidant Status, Total Antioxidant Status, and Oxidative Stress Index

PubMed Central

CİNGİ YİRÜN, Merve; ÜNAL, Kübranur; ALTUNSOY ŞEN, Neslihan; YİRÜN, Onur; AYDEMİR, Çiğdem; GÖKA, Erol

2016-01-01

Introduction Bipolar disorder is one of the most debilitating psychiatric disorders characterized by disruptive episodes of mania/hypomania and depression. Considering the complex role of biological and environmental factors in the etiology of affective disorders, recent studies have focused on oxidative stress, which may damage nerve cell components and take part in pathophysiology. The aim of the present study was to contribute to the data about oxidative stress in bipolar disorder by detecting the total antioxidant status (TAS), total oxidant status (TOS), and oxidative stress index (OSI) levels of manic episode (ME) and euthymic (EU) patients and by comparing these results with those of healthy controls (HCs). Methods The study population consisted of 28 EU outpatients meeting the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) criteria for bipolar disorder I and 23 inpatients who were currently hospitalized in a psychiatry ward with the diagnosis of the bipolar disorder ME according to the DSM-5 criteria. Forty-three healthy subjects were included in the study as the control group (HC). Serum TAS, TOS, and OSI levels of all the participants were determined. Results Statistical analysis of serum TAS, TOS, and OSI levels did not show any significant differences between the ME patients, EU patients, and HCs. Comparison between the bipolar disorder patients (ME+EU) and HC also did not reveal any statistically significant difference between these two groups in terms of serum TAS, TOS, and OSI levels. Conclusion To date, studies on oxidative stress in bipolar disorder have led to controversial results. In the present study, no statistically significant difference was detected between the oxidative parameters of bipolar disorder patients and HCs. In order to comprehensively evaluate oxidative stress in bipolar disorder, further studies are needed. PMID:28373794

Nonequilibrium transitions in complex networks: A model of social interaction

NASA Astrophysics Data System (ADS)

Klemm, Konstantin; Eguíluz, Víctor M.; Toral, Raúl; San Miguel, Maxi

2003-02-01

We analyze the nonequilibrium order-disorder transition of Axelrod’s model of social interaction in several complex networks. In a small-world network, we find a transition between an ordered homogeneous state and a disordered state. The transition point is shifted by the degree of spatial disorder of the underlying network, the network disorder favoring ordered configurations. In random scale-free networks the transition is only observed for finite size systems, showing system size scaling, while in the thermodynamic limit only ordered configurations are always obtained. Thus, in the thermodynamic limit the transition disappears. However, in structured scale-free networks, the phase transition between an ordered and a disordered phase is restored.

Intrinsically Disordered Proteins and the Origins of Multicellular Organisms

NASA Astrophysics Data System (ADS)

Dunker, A. Keith

In simple multicellular organisms all of the cells are in direct contact with the surrounding milieu, whereas in complex multicellular organisms some cells are completely surrounded by other cells. Current phylogenetic trees indicate that complex multicellular organisms evolved independently from unicellular ancestors about 10 times, and only among the eukaryotes, including once for animals, twice each for green, red, and brown algae, and thrice for fungi. Given these multiple independent evolutionary lineages, we asked two questions: 1. Which molecular functions underpinned the evolution of multicellular organisms?; and, 2. Which of these molecular functions depend on intrinsically disordered proteins (IDPs)? Compared to unicellularity, multicellularity requires the advent of molecules for cellular adhesion, for cell-cell communication and for developmental programs. In addition, the developmental programs need to be regulated over space and time. Finally, each multicellular organism has cell-specific biochemistry and physiology. Thus, the evolution of complex multicellular organisms from unicellular ancestors required five new classes of functions. To answer the second question we used Key-words in Swiss Protein ranked for associations with predictions of protein structure or disorder. With a Z-score of 18.8 compared to random-function proteins, à differentiation was the biological process most strongly associated with IDPs. As expected from this result, large numbers of individual proteins associated with differentiation exhibit substantial regions of predicted disorder. For the animals for which there is the most readily available data all five of the underpinning molecular functions for multicellularity were found to depend critically on IDP-based mechanisms and other evidence supports these ideas. While the data are more sparse, IDPs seem to similarly underlie the five new classes of functions for plants and fungi as well, suggesting that IDPs were indeed crucial for the evolution of complex multicellular organisms. These new findings necessitate a rethinking of the gene regulatory network models currently used to explain cellular differentiation and the evolution of complex multicellular organisms.

Crystallographic and theoretical studies of an inclusion complex of β-cyclodextrin with fentanyl.

PubMed

Ogawa, Noriko; Nagase, Hiromasa; Loftsson, Thorsteinn; Endo, Tomohiro; Takahashi, Chisato; Kawashima, Yoshiaki; Ueda, Haruhisa; Yamamoto, Hiromitsu

2017-10-15

The crystal structure of an inclusion complex of β-cyclodextrin (β-CD) with fentanyl was determined by single crystal X-ray diffraction analysis. The crystal belongs to the triclinic space group P1 and the complex comprises one fentanyl, two β-CD, and several water molecules. β-CD and fentanyl form a host-guest inclusion complex at a ratio of 2:1 and the asymmetric unit of the complex contains two host molecules (β-CDs) in a head-to-head arrangement that form dimers through hydrogen bonds between the secondary hydroxyl groups of β-CD and one guest molecule. Fentanyl is totally contained within the β-CD cavity and the structure of the phenylethyl part of fentanyl inside the dimeric cavity of the complex is disordered. Furthermore, theoretical molecular conformational calculations were conducted to clarify the mobility of the guest molecule in the β-CD cavity using CONFLEX software. Crystal optimization and crystal energy calculations were also conducted. The results of the theoretical calculations confirmed that the conformation of disorder part 1, which was high in occupancy by crystal structure analysis, was more stable. The phenylethyl part of fentanyl existed in several stable conformations. Copyright © 2017 Elsevier B.V. All rights reserved.

Genomewide Linkage Disequilibrium Mapping of Severe Bipolar Disorder in a Population Isolate

PubMed Central

Ophoff, Roel A.; Escamilla, Michael A.; Service, Susan K.; Spesny, Mitzi; Meshi, Dar B.; Poon, Wingman; Molina, Julio; Fournier, Eduardo; Gallegos, Alvaro; Mathews, Carol; Neylan, Thomas; Batki, Steven L.; Roche, Erin; Ramirez, Margarita; Silva, Sandra; De Mille, Melissa C.; Dong, Penny; Leon, Pedro E.; Reus, Victor I.; Sandkuijl, Lodewijk A.; Freimer, Nelson B.

2002-01-01

Genomewide association studies may offer the best promise for genetic mapping of complex traits. Such studies in outbred populations require very densely spaced single-nucleotide polymorphisms. In recently founded population isolates, however, extensive linkage disequilibrium (LD) may make these studies feasible with currently available sets of short tandem repeat markers, spaced at intervals as large as a few centimorgans. We report the results of a genomewide association study of severe bipolar disorder (BP-I), using patients from the isolated population of the central valley of Costa Rica. We observed LD with BP-I on several chromosomes; the most striking results were in proximal 8p, a region that has previously shown linkage to schizophrenia. This region could be important for severe psychiatric disorders, rather than for a specific phenotype. PMID:12119601

Understanding the Comorbidity between Dyslexia and Attention-Deficit/Hyperactivity Disorder

ERIC Educational Resources Information Center

Boada, Richard; Willcutt, Erik G.; Pennington, Bruce F.

2012-01-01

Dyslexia and attention-deficit/hyperactivity disorder (ADHD) are 2 of the most prevalent complex neurodevelopmental disorders of childhood, each affecting approximately 5% of the population in the United States. These disorders are also each comorbid with speech sound disorder and language impairment. Understanding the nature of the comorbidity…

Time-Resolved and Spatio-Temporal Analysis of Complex Cognitive Processes and their Role in Disorders like Developmental Dyscalculia

PubMed Central

Mórocz, István Akos; Janoos, Firdaus; van Gelderen, Peter; Manor, David; Karni, Avi; Breznitz, Zvia; von Aster, Michael; Kushnir, Tammar; Shalev, Ruth

2012-01-01

The aim of this article is to report on the importance and challenges of a time-resolved and spatio-temporal analysis of fMRI data from complex cognitive processes and associated disorders using a study on developmental dyscalculia (DD). Participants underwent fMRI while judging the incorrectness of multiplication results, and the data were analyzed using a sequence of methods, each of which progressively provided more a detailed picture of the spatio-temporal aspect of this disease. Healthy subjects and subjects with DD performed alike behaviorally though they exhibited parietal disparities using traditional voxel-based group analyses. Further and more detailed differences, however, surfaced with a time-resolved examination of the neural responses during the experiment. While performing inter-group comparisons, a third group of subjects with dyslexia (DL) but with no arithmetic difficulties was included to test the specificity of the analysis and strengthen the statistical base with overall fifty-eight subjects. Surprisingly, the analysis showed a functional dissimilarity during an initial reading phase for the group of dyslexic but otherwise normal subjects, with respect to controls, even though only numerical digits and no alphabetic characters were presented. Thus our results suggest that time-resolved multi-variate analysis of complex experimental paradigms has the ability to yield powerful new clinical insights about abnormal brain function. Similarly, a detailed compilation of aberrations in the functional cascade may have much greater potential to delineate the core processing problems in mental disorders. PMID:22368322

[Genotype/phenotype correlation in autism: genetic models and phenotypic characterization].

PubMed

Bonnet-Brilhault, F

2011-02-01

Autism spectrum disorders are a class of conditions categorized by communication problems, ritualistic behaviors, and deficits in social behaviors. This class of disorders merges a heterogeneous group of neurodevelopmental disorders regarding some phenotypic and probably physiopathological aspects. Genetic basis is well admitted, however, considering phenotypic and genotypic heterogeneity, correspondences between genotype and phenotype have yet to be established. To better identify such correspondences, genetic models have to be identified and phenotypic markers have to be characterized. Recent insights show that a variety of genetic mechanisms may be involved in autism spectrum disorders, i.e. single gene disorders, copy number variations and polygenic mechanisms. These current genetic models are described. Regarding clinical aspects, several approaches can be used in genetic studies. Nosographical approach, especially with the concept of autism spectrum disorders, merges a large group of disorders with clinical heterogeneity and may fail to identify clear genotype/phenotype correlations. Dimensional approach referred in genetic studies to the notion of "Broad Autism Phenotype" related to a constellation of language, personality, and social-behavioral features present in relatives that mirror the symptom domains of autism, but are much milder in expression. Studies of this broad autism phenotype may provide a potentially important complementary approach for detecting the genes involved in these domains. However, control population used in those studies need to be well characterized too. Identification of endophenotypes seems to offer more promising results. Endophenotypes, which are supposed to be more proximal markers of gene action in the same biological pathway, linking genes and complex clinical symptoms, are thought to be less genetically complex than the broader disease phenotype, indexing a limited aspect of genetic risk for the disorder as a whole. However, strategies useful to characterize such phenotypic markers (for example, electrophysiological markers) have to take into account that autism is an early neurodevelopmental disorder occurring during childhood when brain development and maturation are in process. Recent genetic results have improved our knowledge in genetic basis in autism. Nevertheless, correspondences with phenotypic markers remain challenging according to phenotypic and genotypic heterogeneity. Copyright © 2010 L'Encéphale, Paris. Published by Elsevier Masson SAS. All rights reserved.

Left hemisphere dysfunction during verbal dichotic listening tests in patients who have social phobia with or without comorbid depressive disorder.

PubMed

Bruder, Gerard E; Schneier, Franklin R; Stewart, Jonathan W; McGrath, Patrick J; Quitkin, Frederic

2004-01-01

Behavioral, electrophysiological, and imaging studies have found evidence that anxiety disorders are associated with left hemisphere dysfunction or higher than normal activation of right hemisphere regions. Few studies, however, have examined hemispheric asymmetries of function in social phobia, and the influence of comorbidity with depressive disorders is unknown. The present study used dichotic listening tests to assess lateralized cognitive processing in patients with social phobia, depression, or comorbid social phobia and depression. The study used a two-by-two factorial design in which one factor was social phobia (present versus absent) and the second factor was depressive disorder (present versus absent). A total of 125 unmedicated patients with social phobia, depressive disorder, or comorbid social phobia and depressive disorder and 44 healthy comparison subjects were tested on dichotic fused-words, consonant-vowel syllable, and complex tone tests. Patients with social phobia with or without a comorbid depressive disorder had a smaller left hemisphere advantage for processing words and syllables, compared with subjects without social phobia, whereas no difference between groups was found in the right hemisphere advantage for processing complex tones. Depressed women had a larger left hemisphere advantage for processing words, compared with nondepressed women, but this difference was not seen among men. The results support the hypothesis that social phobia is associated with dysfunction of left hemisphere regions mediating verbal processing. Given the importance of verbal processes in social interactions, this dysfunction may contribute to the stress and difficulty experienced by patients with social phobia in social situations.

The use of imagery in phase 1 treatment of clients with complex dissociative disorders

PubMed Central

van der Hart, Onno

2012-01-01

The “standard of care” for clients with complex dissociative disorders and other complex trauma-related disorders is phase-oriented treatment. Within this frame, therapeutic progress can be enhanced by the use of imagery-based therapeutic techniques. In this article, the emphasis is on their application in phase 1 treatment, stabilization, symptom reduction, and skills training, but attention is also paid to applications in phase 2 and phase 3 treatment. Many of the existing imagery techniques are geared toward clients becoming more able to function in a more adaptive way in daily life, which, however, requires the involvement of various dissociative parts of the personality. Such collaborative involvement is also essential in the later treatment phases. Therefore, understanding the dissociative nature of these disorders is helpful in the judicious application of these techniques. PMID:22893843

Biology and genetics of oculocutaneous albinism and vitiligo - common pigmentation disorders in southern Africa.

PubMed

Manga, Prashiela; Kerr, Robyn; Ramsay, Michèle; Kromberg, Jennifer G R

2013-07-29

Pigmentation disorders span the genetic spectrum from single-gene autosomal recessive disorders such as oculocutaneous albinism (OCA), the autosomal dominant disorder piebaldism to X-linked ocular albinism and multifactorial vitiligo. OCA connotes a group of disorders that result in hypopigmented skin due to decreased melanin production in melanocytes and loss of visual acuity. There are four non-syndromic forms, OCA1-4, which are classified based on the gene that is mutated (tyrosinase, OCA2, tyrosinase-related protein 1 and SLC45A2, respectively). Despite the fact that multiple genes account for the various forms of OCA, the phenotypes of all four forms result from disruption in the maturation and trafficking of the enzyme tyrosinase. OCA2 is the most prevalent autosomal recessive disorder among southern African blacks, affecting 1/3 900 individuals; while OCA3, although rare, is most prevalent in southern Africa. Another common pigmentation disorder in southern Africa is vitiligo, which affects 1 - 2% of people worldwide. Vitiligo is a complex, acquired disorder in which melanocytes are destroyed due to an autoimmune response. The aetiology underlying this disorder is poorly understood, although recent genetic association studies have begun to shed light on the contributing factors. Pigmentation disorders have significant psychosocial implications and co-morbidities, yet therapies are still lacking. Recent progress in our understanding of the pathobiology of both albinism and vitiligo may herald novel treatment strategies for these disorders. 

Reducing Adverse Polypharmacy in Patients With Borderline Personality Disorder: An Empirical Case Study

PubMed Central

Oldham, John M.; Gonzalez, Sylvia; Fowler, J. Christopher

2015-01-01

Objective: Polypharmacy is common and especially challenging in the context of borderline personality disorder in light of impulsivity and self-harm associated with the disorder, risk of adverse drug-drug interactions, and financial burden. Reduction in polypharmacy could be conceptualized as a high priority in the treatment of borderline personality disorder. This case aims to demonstrate that potential. Method: This case report presents outcomes data for an individual with borderline personality disorder during the course of an extended psychiatric hospitalization. Symptomatic change is based on the Patient Health Questionnaire Somatic, Anxiety, and Depression Symptoms scales and World Health Organization 5-Item Well-Being Index. Change in polypharmacy is presented both in terms of absolute number and complexity of the medication regimen. Clinical outcomes data are provided at 2, 12, and 24 weeks postdischarge. Results: During a 56-day hospitalization, the patient demonstrated clinical improvement across clinical domains—all occurred within the context of reduced number (43%) and complexity (40%) of her medication regimen. Symptomatic improvement was sustained up to 6 months postdischarge. Conclusions: Despite good intentions, polypharmacy can be associated with iatrogenic harm and contribute to functional impairment, especially in the context of borderline personality disorder, in which symptomatic fluctuations are part of the illness itself. A reduction in the patient’s high-risk polypharmacy during treatment represents a noteworthy treatment outcome in and of itself. Additional measures of medication risk and liability have the potential to become markers of clinical effectiveness. PMID:26693036

Clinical importance of personality difficulties: diagnostically sub-threshold personality disorders.

PubMed

Karukivi, Max; Vahlberg, Tero; Horjamo, Kalle; Nevalainen, Minna; Korkeila, Jyrki

2017-01-14

Current categorical classification of personality disorders has been criticized for overlooking the dimensional nature of personality and that it may miss some sub-threshold personality disturbances of clinical significance. We aimed to evaluate the clinical importance of these conditions. For this, we used a simple four-level dimensional categorization based on the severity of personality disturbance. The sample consisted of 352 patients admitted to mental health services. All underwent diagnostic assessments (SCID-I and SCID-II) and filled in questionnaires concerning their social situation and childhood adversities, and other validated tools, including the Beck Depression Inventory (BDI), Alcohol Use Disorders Identification Test (AUDIT), health-related quality of life (15D), and the five-item Mental Health Index (MHI-5). The patients were categorized into four groups according to the level of personality disturbance: 0 = No personality disturbance, 1 = Personality difficulty (one criterion less than threshold for one or more personality disorders), 2 = Simple personality disorder (one personality disorder), and 3 = Complex/Severe personality disorder (two or more personality disorders or any borderline and antisocial personality disorder). The proportions of the groups were as follows: no personality disturbance 38.4% (n = 135), personality difficulty 14.5% (n = 51), simple personality disorder 19.9% (n = 70), and complex/severe personality disorder 24.4% (n = 86). Patients with no personality disturbance were significantly differentiated (p < 0.05) from the other groups regarding the BDI, 15D, and MHI-5 scores as well as the number of Axis I diagnoses. Patients with complex/severe personality disorders stood out as being worst off. Social dysfunction was related to the severity of the personality disturbance. Patients with a personality difficulty or a simple personality disorder had prominent symptoms and difficulties, but the differences between these groups were mostly non-significant. An elevated severity level of personality disturbance is associated with an increase in psychiatric morbidity and social dysfunction. Diagnostically sub-threshold personality difficulties are of clinical significance and the degree of impairment corresponds to actual personality disorders. Since these two groups did not significantly differ from each other, our findings also highlight the complexity related to the use of diagnostic thresholds for separate personality disorders.

[Management of children with headache in a Pediatric Emergency Department before and after the introduction of the Second International Classification of Headache Disorders (ICHD-II)].

PubMed

Gioachin, Anna; Fiumana, Elisa; Tarocco, Anna; Verzola, Adriano; Forini, Elena; Guerra, Valentina; Salani, Manuela; Faggioli, Raffaella

2013-03-01

The aim of this study was to evaluate how the management of children admitted with headache to a Pediatric Emergency Department, was modified by the introduction of the Second International Classification of Headache Disorders ( ICHD-II) published in 2004. The complexity and average costs of the services provided to patients in 2002 and 2011 were compared. The results revealed a decrease in the number of tests performed and in-hospital admissions. However, tests were more complex, and an increase in requests of specialist advice was observed. We hypothesized that this change may be related to the introduction of ICHD-II, which suggests a more rational approach to the child with headache and a better use of hospital resources.

Order-disorder phase transition in the peroxidovanadium complex NH4[VO(O2)2(NH3)].

PubMed

Schwendt, Peter; Gyepes, Róbert; Chrappová, Jana; Němec, Ivan; Vaněk, Přemysl

2018-07-05

Complex NH 4 [VO(O 2 ) 2 (NH 3 )] (1) undergoes an order-disorder phase transition at T c ~258K. This transition is accompanied by change in the space group of the orthorhombic lattice and also by significant structural rearrangements of the constituent molecules, which are pertinent mostly to their NH 4 + ions and their ammonia ligands. The low-temperature solid state IR and Raman spectra of 1 were corroborated by solid-state computations that employed Gaussian functions as the basis set. Results of these computations yielded excellent agreement with experimental data. On the curves of temperature dependence of vibrational modes, the phase transition is expressed by an abrupt change of the slope above T c . Copyright © 2018 Elsevier B.V. All rights reserved.

Functional advantages of dynamic protein disorder.

PubMed

Berlow, Rebecca B; Dyson, H Jane; Wright, Peter E

2015-09-14

Intrinsically disordered proteins participate in many important cellular regulatory processes. The absence of a well-defined structure in the free state of a disordered domain, and even on occasion when it is bound to physiological partners, is fundamental to its function. Disordered domains are frequently the location of multiple sites for post-translational modification, the key element of metabolic control in the cell. When a disordered domain folds upon binding to a partner, the resulting complex buries a far greater surface area than in an interaction of comparably-sized folded proteins, thus maximizing specificity at modest protein size. Disorder also maintains accessibility of sites for post-translational modification. Because of their inherent plasticity, disordered domains frequently adopt entirely different structures when bound to different partners, increasing the repertoire of available interactions without the necessity for expression of many different proteins. This feature also adds to the faithfulness of cellular regulation, as the availability of a given disordered domain depends on competition between various partners relevant to different cellular processes. Copyright © 2015 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.

Overview of the Genetics of Alcohol Use Disorder

PubMed Central

Tawa, Elisabeth A.; Hall, Samuel D.; Lohoff, Falk W.

2016-01-01

Aims Alcohol Use Disorder (AUD) is a chronic psychiatric illness characterized by harmful drinking patterns leading to negative emotional, physical, and social ramifications. While the underlying pathophysiology of AUD is poorly understood, there is substantial evidence for a genetic component; however, identification of universal genetic risk variants for AUD has been difficult. Recent efforts in the search for AUD susceptibility genes will be reviewed in this article. Methods In this review, we provide an overview of genetic studies on AUD, including twin studies, linkage studies, candidate gene studies, and genome-wide association studies (GWAS). Results Several potential genetic susceptibility factors for AUD have been identified, but the genes of alcohol metabolism, alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH), have been found to be protective against the development of AUD. GWAS have also identified a heterogeneous list of SNPs associated with AUD and alcohol-related phenotypes, emphasizing the complexity and heterogeneity of the disorder. In addition, many of these findings have small effect sizes when compared to alcohol metabolism genes, and biological relevance is often unknown. Conclusions Although studies spanning multiple approaches have suggested a genetic basis for AUD, identification of the genetic risk variants has been challenging. Some promising results are emerging from GWAS studies; however, larger sample sizes are needed to improve GWAS results and resolution. As the field of genetics is rapidly developing, whole genome sequencing could soon become the new standard of interrogation of the genes and neurobiological pathways which contribute to the complex phenotype of AUD. Short summary This review examines the genetic underpinnings of Alcohol Use Disorder (AUD), with an emphasis on GWAS approaches for identifying genetic risk variants. The most promising results associated with AUD and alcohol-related phenotypes have included SNPs of the alcohol metabolism genes ADH and ALDH. PMID:27445363

A systematic quality review of high-tech AAC interventions as an evidence-based practice.

PubMed

Morin, Kristi L; Ganz, Jennifer B; Gregori, Emily V; Foster, Margaret J; Gerow, Stephanie L; Genç-Tosun, Derya; Hong, Ee Rea

2018-06-01

Although high-tech augmentative and alternative communication (AAC) is commonly used to teach social-communication skills to people with autism spectrum disorder or intellectual disabilities who have complex communication needs, there is a critical need to evaluate the efficacy of this approach. The aim of this systematic review was to evaluate the quality of single-case experimental design research on the use of high-tech AAC to teach social-communication skills to individuals with autism spectrum disorder or intellectual disabilities who have complex communication needs, to determine if this intervention approach meets the criteria for evidence-based practices as outlined by the What Works Clearinghouse. Additionally, information on the following extended methodological standards is reported on all included studies: participant description, description of setting and materials, interventionist description, baseline and intervention description, maintenance, generalization, procedural integrity, and social validity. The results from 18 multiple-baseline or multiple-probe experiments across 17 studies indicate that using high-tech AAC to teach social-communication skills to individuals with autism spectrum disorder or intellectual disabilities and complex communication needs can be considered an evidence-based practice, although the review of comparison (i.e., alternating treatment) design studies did not indicate that high-tech AAC is significantly better than low-tech AAC.

Targeted treatment trials for tuberous sclerosis and autism: no longer a dream.

PubMed

Sahin, Mustafa

2012-10-01

Genetic disorders that present with a high incidence of autism spectrum disorders (ASD) offer tremendous potential both for elucidating the underlying neurobiology of ASD and identifying therapeutic drugs and/or drug targets. As a result, clinical trials for genetic disorders associated with ASD are no longer a hope for the future but rather an exciting reality whose time has come. Tuberous sclerosis complex (TSC) is one such genetic disorder that presents with ASD, epilepsy, and intellectual disability. Cell culture and mouse model experiments have identified the mTOR pathway as a therapeutic target in this disease. This review summarizes the advantages of using TSC as model of ASD and the recent advances in the translational and clinical treatment trials in TSC. Copyright © 2012 Elsevier Ltd. All rights reserved.

Teaching Students with Autism Spectrum Disorders: Technology, Curriculum, and Common Sense

ERIC Educational Resources Information Center

Ennis-Cole, Demetria

2012-01-01

Autism is a spectrum of disorders which comprises Asperger's Syndrome, Pervasive Developmental Delay-Not Otherwise Specified (PDD-NOS), Rett's Syndrome, Childhood Disintegrative Disorder, and Autistic Disorder. It affects 1 in 110 children (Center for Disease Control and Prevention, [CDC], 2011), and it is a complex neurological disorder that is…

Developmental disorders of the hypothalamus and pituitary gland associated with congenital hypopituitarism.

PubMed

Mehta, Ameeta; Dattani, Mehul T

2008-02-01

The pituitary gland is a complex organ secreting six hormones from five different cell types. It is the end product of a carefully orchestrated pattern of expression of signalling molecules and transcription factors. Naturally occurring and transgenic murine models have demonstrated a role for many of these molecules in the aetiology of congenital hypopituitarism. These include the transcription factors HESX1, PROP1, POU1F1, LHX3, LHX4, PITX1, PITX2, SOX2 and SOX3. The expression pattern of these transcription factors dictates the phenotype that results when the gene encoding the relevant transcription factor is mutated. The highly variable phenotype may consist of isolated hypopituitarism or more complex disorders such as septo-optic dysplasia and holoprosencephaly. However, the overall incidence of mutations in known transcription factors in patients with hypopituitarism is low, indicating that many genes remain to be identified; characterization of these will further elucidate the pathogenesis of this complex condition and also shed light on normal pituitary development and function.

Complexity Variability Assessment of Nonlinear Time-Varying Cardiovascular Control

NASA Astrophysics Data System (ADS)

Valenza, Gaetano; Citi, Luca; Garcia, Ronald G.; Taylor, Jessica Noggle; Toschi, Nicola; Barbieri, Riccardo

2017-02-01

The application of complex systems theory to physiology and medicine has provided meaningful information about the nonlinear aspects underlying the dynamics of a wide range of biological processes and their disease-related aberrations. However, no studies have investigated whether meaningful information can be extracted by quantifying second-order moments of time-varying cardiovascular complexity. To this extent, we introduce a novel mathematical framework termed complexity variability, in which the variance of instantaneous Lyapunov spectra estimated over time serves as a reference quantifier. We apply the proposed methodology to four exemplary studies involving disorders which stem from cardiology, neurology and psychiatry: Congestive Heart Failure (CHF), Major Depression Disorder (MDD), Parkinson’s Disease (PD), and Post-Traumatic Stress Disorder (PTSD) patients with insomnia under a yoga training regime. We show that complexity assessments derived from simple time-averaging are not able to discern pathology-related changes in autonomic control, and we demonstrate that between-group differences in measures of complexity variability are consistent across pathologies. Pathological states such as CHF, MDD, and PD are associated with an increased complexity variability when compared to healthy controls, whereas wellbeing derived from yoga in PTSD is associated with lower time-variance of complexity.

Anomalous Structural Disorder in Supported Pt Nanoparticles

DOE PAGES

Vila, Fernando D.; Rehr, John J.; Nuzzo, Ralph G.; ...

2017-07-02

Supported Pt nanocatalysts generally exhibit anomalous behavior, including negative thermal expansion and large structural disorder. Finite temperature DFT/MD simulations reproduce these properties, showing that they are largely explained by a combination of thermal vibrations and low-frequency disorder. We show in this paper that a full interpretation is more complex and that the DFT/MD mean-square relative displacements (MSRD) can be further separated into vibrational disorder, “dynamic structural disorder” (DSD), and long-time equilibrium fluctuations of the structure dubbed “anomalous structural disorder” (ASD). We find that the vibrational and DSD components behave normally, increasing linearly with temperature while the ASD decreases, reflecting themore » evolution of mean nanoparticle geometry. Finally, as a consequence the usual procedure of fitting the MSRD to normal vibrations plus temperature-independent static disorder results in unphysical bond strengths and Grüneisen parameters.« less

Arts, Science, Engineering and Medicine Collaborate to Educate Public on Bioenergetics.

PubMed

Tompkins, Emily; Faris, Sarah; Hughes, Laura; Maurakis, Eugene; Lesnefsky, Edward Joseph; Rao, Raj Raghavendra; Iyer, Shilpa

2017-01-01

Mitochondrial dysfunction has correlated with a rise in energy deficiency disorders (EDD). The EDDs include mitochondrial disorders, obesity, metabolic disorders, cardiovascular and neurodegenerative disorders. Many individuals in our communities are at high risk of developing these disorders, yet are unaware of it. Our goal was to increase public awareness of mitochondrial health, whilst providing students with an innovative educational experience. We designed a 'Bioenergetics exhibition' by introducing Arts into traditional STEM (Science, Technology, Engineering & Mathematics) disciplines to create a new STEAM-(Health) initiative. Results indicated ~120,000 guests visited the exhibition, including many school-aged children, teachers and families. Comparative analysis of random first-time vs. repeat visitor surveys demonstrated a statistically significant (8.25% at p-value = 0.006) increase in knowledge of mitochondrial disease and bioenergetics. Our findings clearly support the power of the STEAM-H initiative in creatively communicating the complex science to a broader community.

Attentional blink in young people with high-functioning autism and Asperger's disorder.

PubMed

Rinehart, Nicole; Tonge, Bruce; Brereton, Avril; Bradshaw, John

2010-01-01

The aim of the study was to examine the temporal characteristics of information processing in individuals with high-functioning autism and Asperger's disorder using a rapid serial visual presentation paradigm. The results clearly showed that such people demonstrate an attentional blink of similar magnitude to comparison groups. This supports the proposition that the social processing difficulties experienced by these individuals are not underpinned by a basic temporal-cognitive processing deficit, which is consistent with Minshew's complex information processing theory. This is the second study to show that automatic inhibitory processes are intact in both autism and Asperger's disorder, which appears to distinguish these disorders from some other frontostriatal disorders. The finding that individuals with autism were generally poorer than the comparison group at detecting black Xs, while being as good in responding to white letters, was accounted for in the context of a potential dual-task processing difficulty or visual search superiority.

No objectively measured sleep disturbances in children with attention-deficit/hyperactivity disorder.

PubMed

Bergwerff, Catharina E; Luman, Marjolein; Oosterlaan, Jaap

2016-10-01

The main goal of this study was to gain more insight into sleep disturbances in children with attention-deficit/hyperactivity disorder, using objective measures of sleep quality and quantity. The evidence for sleep problems in children with attention-deficit/hyperactivity disorder thus far is inconsistent, which might be explained by confounding influences of comorbid internalizing and externalizing problems and low socio-economic status. We therefore investigated the mediating and moderating role of these factors in the association between attention-deficit/hyperactivity disorder and sleep problems. To control for the effects of stimulant medication use, all participants were tested free of medication. Sixty-three children with attention-deficit/hyperactivity disorder and 61 typically developing children, aged 6-13 years, participated. Sleep was monitored for one to three school nights using actigraphy. Parent and teacher questionnaires assessed symptoms of attention-deficit/hyperactivity disorder, internalizing behaviour, oppositional defiant disorder and conduct disorder. Results showed no differences between the attention-deficit/hyperactivity disorder and typically developing group in any sleep parameter. Within the attention-deficit/hyperactivity disorder group, severity of attention-deficit/hyperactivity disorder symptoms was not related to sleep quality or quantity. Moderation analyses in the attention-deficit/hyperactivity disorder group showed an interaction effect between attention-deficit/hyperactivity disorder symptoms and internalizing and externalizing behaviour on total sleep time, time in bed and average sleep bout duration. The results of our study suggest that having attention-deficit/hyperactivity disorder is not a risk factor for sleep problems. Internalizing and externalizing behaviour moderate the association between attention-deficit/hyperactivity disorder and sleep, indicating a complex interplay between psychiatric symptoms and sleep. © 2016 European Sleep Research Society.

Use of evidence-based assessments for childhood anxiety disorders within a regional medical system.

PubMed

Sattler, Adam F; Ale, Chelsea M; Nguyen, Kristin; Gregg, Melissa S; Geske, Jennifer R; Whiteside, Stephen P H

2016-11-01

Anxiety disorders represent a common and serious threat to mental health in children and adolescents. To effectively treat anxiety in children, clinicians must conduct accurate assessment of patients' symptoms. However, despite the importance of assessment in the treatment of childhood anxiety disorders, the literature lacks a thorough analysis of the practices used by clinicians' when evaluating such disorders in community settings. Thus, the current study examines the quality of assessment for childhood anxiety disorders in a large regional health system. The results suggest that clinicians often provide non-specific diagnoses, infrequently document symptoms according to diagnostic criteria, and rarely administer rating scales and structured diagnostic interviews. Relatedly, diagnostic agreement across practice settings was low. Finally, the quality of assessment differed according to the setting in which the assessment was conducted and the complexity of the patient's symptomatology. These results highlight the need to develop and disseminate clinically feasible evidence-based assessment practices that can be implemented within resource-constrained service settings. (PsycINFO Database Record (c) 2016 APA, all rights reserved).

The Endosome Localized Arf-GAP AGAP1 Modulates Dendritic Spine Morphology Downstream of the Neurodevelopmental Disorder Factor Dysbindin

PubMed Central

Arnold, Miranda; Cross, Rebecca; Singleton, Kaela S.; Zlatic, Stephanie; Chapleau, Christopher; Mullin, Ariana P.; Rolle, Isaiah; Moore, Carlene C.; Theibert, Anne; Pozzo-Miller, Lucas; Faundez, Victor; Larimore, Jennifer

2016-01-01

AGAP1 is an Arf1 GTPase activating protein that interacts with the vesicle-associated protein complexes adaptor protein 3 (AP-3) and Biogenesis of Lysosome Related Organelles Complex-1 (BLOC-1). Overexpression of AGAP1 in non-neuronal cells results in an accumulation of endosomal cargoes, which suggests a role in endosome-dependent traffic. In addition, AGAP1 is a candidate susceptibility gene for two neurodevelopmental disorders, autism spectrum disorder (ASD) and schizophrenia (SZ); yet its localization and function in neurons have not been described. Here, we describe that AGAP1 localizes to axons, dendrites, dendritic spines and synapses, colocalizing preferentially with markers of early and recycling endosomes. Functional studies reveal overexpression and down-regulation of AGAP1 affects both neuronal endosomal trafficking and dendritic spine morphology, supporting a role for AGAP1 in the recycling endosomal trafficking involved in their morphogenesis. Finally, we determined the sensitivity of AGAP1 expression to mutations in the DTNBP1 gene, which is associated with neurodevelopmental disorder, and found that AGAP1 mRNA and protein levels are selectively reduced in the null allele of the mouse ortholog of DTNBP1. We postulate that endosomal trafficking contributes to the pathogenesis of neurodevelopmental disorders affecting dendritic spine morphology, and thus excitatory synapse structure and function. PMID:27713690

A novel mutation of the NDUFS7 gene leads to activation of a cryptic exon and impaired assembly of mitochondrial complex I in a patient with Leigh syndrome.

PubMed

Lebon, Sophie; Minai, Limor; Chretien, Dominique; Corcos, Johanna; Serre, Valérie; Kadhom, Noman; Steffann, Julie; Pauchard, Jean-Yves; Munnich, Arnold; Bonnefont, Jean-Paul; Rötig, Agnès

2007-01-01

Complex I deficiency is a frequent cause of mitochondrial disease as it accounts for one third of these disorders. By genotyping several putative disease loci using microsatellite markers we were able to describe a new NDUFS7 mutation in a consanguineous family with Leigh syndrome and isolated complex I deficiency. This mutation lies in the first intron of the NDUFS7 gene (c.17-1167 C>G) and creates a strong donor splice site resulting in the generation of a cryptic exon. This mutation is predicted to result in a shortened mutant protein of 41 instead of 213 amino acids containing only the first five amino acids of the normal protein. Analysis of the assembly state of the respiratory chain complexes under native condition revealed a marked decrease of fully assembled complex I while the quantity of the other complexes was not altered. These results report the first intronic NDUFS7 gene mutation and demonstrate the crucial role of NDUFS7 in the biogenesis of complex I.

Green Space and Childhood Autism

EPA Science Inventory

Autism, a group of complex neurodevelopmental disorders typically identified in early childhood, affects more than 3 million people in the U.S. To date, the cause of autism is unclear. It is believed that autism results from a combination of genetic and environmental factors incl...

Partial trisomy 16p in an adolescent with autistic disorder and Tourette`s syndrome

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

Hebebrand, J.; Martin, M.; Remschmidt, H.

A partial trisomy 16p was identified in a 14-year-old male adolescent with autistic disorder. He additionally showed complex motor and vocal phenomena, including some simple tics which had first appeared in childhood. Whereas these simple tics were of subclinical significance, an additional diagnosis of Tourette`s syndrome (TS) appears justified. The case report illustrates the diagnostic difficulties in assessing psychiatric symptomatology associated with both disorders, especially complex motor and vocal phenomena. The cytogenetic finding is discussed critically in the light of other chromosome abnormalities reported in both TS and autistic disorder. Chromosome 16p should be considered as a candidate region especiallymore » for autistic disorder. 21 refs.« less

[The effect of a short-term group stabilisation training in patients with complex posttraumatic stress disorder].

PubMed

Beldman, G; Kessels, H H L M; de Groot, I W

The international guideline for complex posttraumatic stress disorder (ptsd) from the International Society for Traumatic Stress Studies (istss) recommends treatment in phases, starting with stabilisation treatment. Different forms of stabilisation training have been developed the past few years, one being short-term group stabilisation training.
AIM: To map out the effects of the short-term group training.
METHOD: The research implemented a pre-post design. The training consisted of five group sessions. Questionnaires (bsi, OQ 45 and svl-15) were completed both prior to and after the training. Four domains were assessed: psychosymptomatology in general, depressive symptoms, problems with interpersonal functioning and ptsd-related symptoms. The effect of the training was calculated by paired t-tests.
RESULTS: The questionnaires of the 47 participants who had completed the training were analysed. No significant decrease was observed during the stabilisation training concerning the symptoms of the four evaluated domains.
CONCLUSION: Contrary our expectations, a short-term group-based stabilisation training does not seem to have added value when treating patients with complex ptsd. The results correspond with a recent trend in which the effectiveness of other stabilising methods is questioned. Alternative treatment options are discussed.

Dissociation, shame, complex PTSD, child maltreatment and intimate relationship self-concept in dissociative disorder, chronic PTSD and mixed psychiatric groups.

PubMed

Dorahy, Martin J; Middleton, Warwick; Seager, Lenaire; McGurrin, Patrick; Williams, Mary; Chambers, Ron

2015-02-01

Whilst a growing body of research has examined dissociation and other psychiatric symptoms in severe dissociative disorders (DDs), there has been no systematic examination of shame and sense of self in relationships in DDs. Chronic child abuse often associated with severe DDs, like dissociative identity disorder, is likely to heighten shame and relationship concerns. This study investigated complex posttraumatic stress disorder (PTSD), borderline and Schneiderian symptoms, dissociation, shame, child abuse, and various markers of self in relationships (e.g., relationship esteem, relationship depression, fear of relationships). Participants were assessed via clinical interview with psychometrically sound questionnaires. They fell into three diagnostic groups, dissociative disorder (n=39; primarily dissociative identity disorder), chronic PTSD (Chr-PTSD; n=13) or mixed psychiatric presentations (MP; n=21; primarily mood and anxiety disorders). All participants had a history of child abuse and/or neglect, and the groups did not differ on age and gender. The DD group was higher on nearly all measured variables than the MP group, and had more severe dissociative, borderline and Schneiderian symptoms than the Chr-PTSD sample. Shame and complex PTSD symptoms fell marginally short of predicting reductions in relationship esteem, pathological dissociative symptoms predicted increased relationship depression, and complex PTSD symptoms predicted fear of relationships. The representativeness of the samples was unknown. Severe psychiatric symptoms differentiate DDs from chronic PTSD, while dissociation and shame have a meaningful impact on specific markers of relationship functioning in psychiatric patients with a history of child abuse and neglect. Copyright © 2014 Elsevier B.V. All rights reserved.

Retrospective, nonrandomized controlled study on autoadjusting, dual-pressure positive airway pressure therapy for a consecutive series of complex insomnia disorder patients

PubMed Central

Krakow, Barry; McIver, Natalia D; Ulibarri, Victor A; Nadorff, Michael R

2017-01-01

Purpose Emerging evidence shows that positive airway pressure (PAP) treatment of obstructive sleep apnea (OSA) and upper airway resistance syndrome (UARS) in chronic insomnia patients (proposed “complex insomnia” disorder) leads to substantial decreases in insomnia severity. Although continuous PAP (CPAP) is the pressure mode most widely researched, intolerance to fixed pressurized air is rarely investigated or described in comorbidity patients. This retrospective study examined dual pressure, autoadjusting PAP modes in chronic, complex insomnia disorder patients. Patients and methods Chronic insomnia disorder patients (mean [SD] insomnia severity index [ISI] =19.11 [3.34]) objectively diagnosed with OSA or UARS and using either autobilevel PAP device or adaptive servoventilation (ASV) device after failing CPAP therapy (frequently due to intolerance to pressurized air, poor outcomes, or emergence of CSA) were divided into PAP users (≥20 h/wk) and partial users (<20 h/wk) for comparison. Subjective and objective baseline and follow-up measures were analyzed. Results Of the 302 complex insomnia patients, PAP users (n=246) averaged 6.10 (1.78) nightly hours and 42.71 (12.48) weekly hours and partial users (n=56) averaged 1.67 (0.76) nightly hours and 11.70 (5.31) weekly hours. For mean (SD) decreases in total ISI scores, a significant (group × time) interaction was observed (F[1,300]=13.566; P<0.0001) with PAP users (–7.59 [5.92]; d=1.63) showing superior results to partial users (−4.34 [6.13]; d=0.81). Anecdotally, patients reported better tolerability with advanced PAP compared to previous experience with CPAP. Both adaptive servoventilation and autobilevel PAP showed similar ISI score improvement without statistical differences between devices. Total weekly hours of PAP use correlated inversely with change in insomnia symptoms (r=−0.256, P<0.01). Conclusion Insomnia severity significantly decreased in patients using autoadjusting PAP devices, but the study design restricts interpretation to an association. Future research must elucidate the interaction between insomnia and OSA/UARS as well as the adverse influence of pressure intolerance on PAP adaptation in complex insomnia patients. Randomized controlled studies must determine whether advanced PAP modes provide benefits over standard CPAP modes in these comorbidity patients. PMID:28331381

Auditory-Motor Interactions in Pediatric Motor Speech Disorders: Neurocomputational Modeling of Disordered Development

PubMed Central

Terband, H.; Maassen, B.; Guenther, F.H.; Brumberg, J.

2014-01-01

Background/Purpose Differentiating the symptom complex due to phonological-level disorders, speech delay and pediatric motor speech disorders is a controversial issue in the field of pediatric speech and language pathology. The present study investigated the developmental interaction between neurological deficits in auditory and motor processes using computational modeling with the DIVA model. Method In a series of computer simulations, we investigated the effect of a motor processing deficit alone (MPD), and the effect of a motor processing deficit in combination with an auditory processing deficit (MPD+APD) on the trajectory and endpoint of speech motor development in the DIVA model. Results Simulation results showed that a motor programming deficit predominantly leads to deterioration on the phonological level (phonemic mappings) when auditory self-monitoring is intact, and on the systemic level (systemic mapping) if auditory self-monitoring is impaired. Conclusions These findings suggest a close relation between quality of auditory self-monitoring and the involvement of phonological vs. motor processes in children with pediatric motor speech disorders. It is suggested that MPD+APD might be involved in typically apraxic speech output disorders and MPD in pediatric motor speech disorders that also have a phonological component. Possibilities to verify these hypotheses using empirical data collected from human subjects are discussed. PMID:24491630

Disorder in Complex Human System

NASA Astrophysics Data System (ADS)

Akdeniz, K. Gediz

2011-11-01

Since the world of human and whose life becomes more and more complex every day because of the digital technology and under the storm of knowledge (media, internet, governmental and non-governmental organizations, etc...) the simulation is rapidly growing in the social systems and in human behaviors. The formation of the body and mutual interactions are left to digital technological, communication mechanisms and coding the techno genetics of the body. Deconstruction begins everywhere. The linear simulation mechanism with modern realities are replaced by the disorder simulation of human behaviors with awareness realities. In this paper I would like to introduce simulation theory of "Disorder Sensitive Human Behaviors". I recently proposed this theory to critique the role of disorder human behaviors in social systems. In this theory the principle of realty is the chaotic awareness of the complexity of human systems inside of principle of modern thinking in Baudrillard's simulation theory. Proper examples will be also considered to investigate the theory.

Development and Validation of a Decision Tool for Early Identification of Adult Patients with Severe and Complex Eating Disorder Psychopathology in Need of Highly Specialized Care.

PubMed

Dingemans, Alexandra E; Goorden, Maartje; Lötters, Freek J B; Bouwmans, Clazien; Danner, Unna N; van Elburg, Annemarie A; van Furth, Eric F; Hakkaart-van Roijen, Leona

2017-09-01

Patients with complex and severe eating disorders often receive a number of ineffective or/and insufficient treatments. Direct referral of these patients to highly specialized tertiary treatment facilities in an earlier stage of the disorder is likely to be more (cost)-effective. The aim of the study was to develop a decision tool that aids clinicians in early identification of these patients. After identification of criteria that were indicative of severity and complexity of eating disorder psychopathology by means of a systematic review of literature and consultation of a focus group, a Delphi method was applied to obtain consensus from experts on the list of relevant criteria. Finally, the decision tool was validated in clinical practice, and cut-off criteria were established. The tool demonstrated good feasibility and validity to identify patients for highly specialized tertiary care. The final decision tool consisted of five criteria that can easily be implemented in clinical practice. Copyright © 2017 John Wiley & Sons, Ltd and Eating Disorders Association. Copyright © 2017 John Wiley & Sons, Ltd and Eating Disorders Association.

Assessment of complex dissociative disorder patients and simulated dissociation in forensic contexts.

PubMed

Brand, Bethany L; Webermann, Aliya R; Frankel, A Steven

Few assessors receive training in assessing dissociation and complex dissociative disorders (DDs). Potential differential diagnoses include anxiety, mood, psychotic, substance use, and personality disorders, as well as exaggeration and malingering. Individuals with DDs typically elevate on many clinical and validity scales on psychological tests, yet research indicates that they can be distinguished from DD simulators. Becoming informed about the testing profiles of DD individuals and DD simulators can improve the accuracy of differential diagnoses in forensic settings. In this paper, we first review the testing profiles of individuals with complex DDs and contrast them with DD simulators on assessment measures used in forensic contexts, including the Minnesota Multiphasic Personality Inventory-2 (MMPI-2), Personality Assessment Inventory (PAI), and the Structured Inventory of Reported Symptoms (SIRS), as well as dissociation-specific measures such as the Dissociative Experiences Scale (DES) and Structured Clinical Interview for DSM-IV Dissociative Disorders (SCID-D-R). We then provide recommendations for assessing complex trauma and dissociation through the aforementioned assessments. Copyright © 2016 Elsevier Ltd. All rights reserved.

Modeling the Complexity of Post-Treatment Drinking: It’s a Rocky Road to Relapse

PubMed Central

Witkiewitz, Katie; Marlatt, G. Alan

2007-01-01

The most widely cited road block to successful treatment outcomes for psychological and substance use disorders has been described as the return to the previous behavior, or “relapse.” The operational definition of “relapse” varies from study to study and between clinicians, but in general the term is used to indicate the return to previous levels of symptomatic behavior. One explanation for the variation in the operationalization of relapse is the wide variety of behaviors for which the term is applied, including (but not limited to): depression, substance abuse, schizophrenia, mania, sexual offending, risky sexual behavior, dieting, and the anxiety disorders. A second explanation for the multitude of definitions for relapse is the inherent complexity in the process of behavior change. In this paper we present the most recent treatment outcome research evaluating relapse rates, with a special focus on the substance use disorders. Following this review of the literature we present an argument for the operationalization of relapse as a dynamic process, which can be empirically characterized using dynamical systems theory. We support this argument by presenting results from the analysis of alcohol treatment outcomes using catastrophe modeling techniques. These results demonstrate the utility of catastrophe theory in modeling the alcohol relapse process. The implications of these analyses for the treatment of alcohol use disorders, as well as a discussion of future research incorporating nonlinear dynamical systems theory is provided. PMID:17355897

Consequences of inducing intrinsic disorder in a high-affinity protein-protein interaction.

PubMed

Papadakos, Grigorios; Sharma, Amit; Lancaster, Lorna E; Bowen, Rebecca; Kaminska, Renata; Leech, Andrew P; Walker, Daniel; Redfield, Christina; Kleanthous, Colin

2015-04-29

The kinetic and thermodynamic consequences of intrinsic disorder in protein-protein recognition are controversial. We address this by inducing one partner of the high-affinity colicin E3 rRNase domain-Im3 complex (K(d) ≈ 10(-12) M) to become an intrinsically disordered protein (IDP). Through a variety of biophysical measurements, we show that a single alanine mutation at Tyr507 within the hydrophobic core of the isolated colicin E3 rRNase domain causes the enzyme to become an IDP (E3 rRNase(IDP)). E3 rRNase(IDP) binds stoichiometrically to Im3 and forms a structure that is essentially identical to the wild-type complex. However, binding of E3 rRNase(IDP) to Im3 is 4 orders of magnitude weaker than that of the folded rRNase, with thermodynamic parameters reflecting the disorder-to-order transition on forming the complex. Critically, pre-steady-state kinetic analysis of the E3 rRNase(IDP)-Im3 complex demonstrates that the decrease in affinity is mostly accounted for by a drop in the electrostatically steered association rate. Our study shows that, notwithstanding the advantages intrinsic disorder brings to biological systems, this can come at severe kinetic and thermodynamic cost.

Connecting Malfunctioning Glial Cells and Brain Degenerative Disorders.

PubMed

Kaminsky, Natalie; Bihari, Ofer; Kanner, Sivan; Barzilai, Ari

2016-06-01

The DNA damage response (DDR) is a complex biological system activated by different types of DNA damage. Mutations in certain components of the DDR machinery can lead to genomic instability disorders that culminate in tissue degeneration, premature aging, and various types of cancers. Intriguingly, malfunctioning DDR plays a role in the etiology of late onset brain degenerative disorders such as Parkinson's, Alzheimer's, and Huntington's diseases. For many years, brain degenerative disorders were thought to result from aberrant neural death. Here we discuss the evidence that supports our novel hypothesis that brain degenerative diseases involve dysfunction of glial cells (astrocytes, microglia, and oligodendrocytes). Impairment in the functionality of glial cells results in pathological neuro-glial interactions that, in turn, generate a "hostile" environment that impairs the functionality of neuronal cells. These events can lead to systematic neural demise on a scale that appears to be proportional to the severity of the neurological deficit. Copyright © 2016 The Authors. Production and hosting by Elsevier Ltd.. All rights reserved.

Normal sensorimotor plasticity in complex regional pain syndrome with fixed posture of the hand.

PubMed

Morgante, Francesca; Naro, Antonino; Terranova, Carmen; Russo, Margherita; Rizzo, Vincenzo; Risitano, Giovanni; Girlanda, Paolo; Quartarone, Angelo

2017-01-01

Movement disorders associated with complex regional pain syndrome type I have been a subject of controversy over the last 10 years regarding their nature and pathophysiology, with an intense debate about the functional (psychogenic) nature of this disorder. The aim of this study was to test sensorimotor plasticity and cortical excitability in patients with complex regional pain syndrome type I who developed a fixed posture of the hand. Ten patients with complex regional pain syndrome type I in the right upper limb and a fixed posture of the hand (disease duration less than 24 months) and 10 age-matched healthy subjects were enrolled. The following parameters of corticospinal excitability were recorded from the abductor pollicis brevis muscle of both hands by transcranial magnetic stimulation: resting and active motor thresholds, short-interval intracortical inhibition and facilitation, cortical silent period, and short- and long-latency afferent inhibition. Sensorimotor plasticity was tested using the paired associative stimulation protocol. Short-interval intracortical inhibition and long-latency afferent inhibition were reduced only in the affected right hand of patients compared with control subjects. Sensorimotor plasticity was comparable to normal subjects, with a preserved topographic specificity. Our data support the view that motor disorder in complex regional pain syndrome type I is not associated with abnormal sensorimotor plasticity, and it shares pathophysiological abnormalities with functional (psychogenic) dystonia rather than with idiopathic dystonia. © 2016 International Parkinson and Movement Disorder Society. © 2016 International Parkinson and Movement Disorder Society.

Attention Deficit Hyperactivity Disorder and Tuberous Sclerosis Complex

MedlinePlus

... disorders (such as in reading, writing, spelling or math) or has global intellectual disability (IQ<70). Child ... specific learning disorders (such as reading, writing, spelling, math) may appear to have trouble concentrating or paying ...

Attentional but not pre-attentive neural measures of auditory discrimination are atypical in children with developmental language disorder.

PubMed

Kornilov, Sergey A; Landi, Nicole; Rakhlin, Natalia; Fang, Shin-Yi; Grigorenko, Elena L; Magnuson, James S

2014-01-01

We examined neural indices of pre-attentive phonological and attentional auditory discrimination in children with developmental language disorder (DLD, n = 23) and typically developing (n = 16) peers from a geographically isolated Russian-speaking population with an elevated prevalence of DLD. Pre-attentive phonological MMN components were robust and did not differ in two groups. Children with DLD showed attenuated P3 and atypically distributed P2 components in the attentional auditory discrimination task; P2 and P3 amplitudes were linked to working memory capacity, development of complex syntax, and vocabulary. The results corroborate findings of reduced processing capacity in DLD and support a multifactorial view of the disorder.

Opening-assisted coherent transport in the semiclassical regime

NASA Astrophysics Data System (ADS)

Zhang, Yang; Celardo, G. Luca; Borgonovi, Fausto; Kaplan, Lev

2017-02-01

We study quantum enhancement of transport in open systems in the presence of disorder and dephasing. Quantum coherence effects may significantly enhance transport in open systems even in the semiclassical regime (where the decoherence rate is greater than the intersite hopping amplitude), as long as the disorder is sufficiently strong. When the strengths of disorder and dephasing are fixed, there is an optimal opening strength at which the coherent transport enhancement is optimized. Analytic results are obtained in two simple paradigmatic tight-binding models of large systems: the linear chain and the fully connected network. The physical behavior is also reflected in the Fenna-Matthews-Olson (FMO) photosynthetic complex, which may be viewed as intermediate between these paradigmatic models.

Outcomes of Diagnostic Exome Sequencing in Patients With Diagnosed or Suspected Autism Spectrum Disorders.

PubMed

Rossi, Mari; El-Khechen, Dima; Black, Mary Helen; Farwell Hagman, Kelly D; Tang, Sha; Powis, Zöe

2017-05-01

Exome sequencing has recently been proved to be a successful diagnostic method for complex neurodevelopmental disorders. However, the diagnostic yield of exome sequencing for autism spectrum disorders has not been extensively evaluated in large cohorts to date. We performed diagnostic exome sequencing in a cohort of 163 individuals with autism spectrum disorder (66.3%) or autistic features (33.7%). The diagnostic yield observed in patients in our cohort was 25.8% (42 of 163) for positive or likely positive findings in characterized disease genes, while a candidate genetic etiology was reported for an additional 3.3% (4 of 120) of patients. Among the positive findings in the patients with autism spectrum disorder or autistic features, 61.9% were the result of de novo mutations. Patients presenting with psychiatric conditions or ataxia or paraplegia in addition to autism spectrum disorder or autistic features were significantly more likely to receive positive results compared with patients without these clinical features (95.6% vs 27.1%, P < 0.0001; 83.3% vs 21.2%, P < 0.0001, respectively). The majority of the positive findings were in recently identified autism spectrum disorder genes, supporting the importance of diagnostic exome sequencing for patients with autism spectrum disorder or autistic features as the causative genes might evade traditional sequential or panel testing. These results suggest that diagnostic exome sequencing would be an efficient primary diagnostic method for patients with autism spectrum disorders or autistic features. Moreover, our data may aid clinicians to better determine which subset of patients with autism spectrum disorder with additional clinical features would benefit the most from diagnostic exome sequencing. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

EDdb: a web resource for eating disorder and its application to identify an extended adipocytokine signaling pathway related to eating disorder.

PubMed

Zhao, Min; Li, XiaoMo; Qu, Hong

2013-12-01

Eating disorder is a group of physiological and psychological disorders affecting approximately 1% of the female population worldwide. Although the genetic epidemiology of eating disorder is becoming increasingly clear with accumulated studies, the underlying molecular mechanisms are still unclear. Recently, integration of various high-throughput data expanded the range of candidate genes and started to generate hypotheses for understanding potential pathogenesis in complex diseases. This article presents EDdb (Eating Disorder database), the first evidence-based gene resource for eating disorder. Fifty-nine experimentally validated genes from the literature in relation to eating disorder were collected as the core dataset. Another four datasets with 2824 candidate genes across 601 genome regions were expanded based on the core dataset using different criteria (e.g., protein-protein interactions, shared cytobands, and related complex diseases). Based on human protein-protein interaction data, we reconstructed a potential molecular sub-network related to eating disorder. Furthermore, with an integrative pathway enrichment analysis of genes in EDdb, we identified an extended adipocytokine signaling pathway in eating disorder. Three genes in EDdb (ADIPO (adiponectin), TNF (tumor necrosis factor) and NR3C1 (nuclear receptor subfamily 3, group C, member 1)) link the KEGG (Kyoto Encyclopedia of Genes and Genomes) "adipocytokine signaling pathway" with the BioCarta "visceral fat deposits and the metabolic syndrome" pathway to form a joint pathway. In total, the joint pathway contains 43 genes, among which 39 genes are related to eating disorder. As the first comprehensive gene resource for eating disorder, EDdb ( http://eddb.cbi.pku.edu.cn ) enables the exploration of gene-disease relationships and cross-talk mechanisms between related disorders. Through pathway statistical studies, we revealed that abnormal body weight caused by eating disorder and obesity may both be related to dysregulation of the novel joint pathway of adipocytokine signaling. In addition, this joint pathway may be the common pathway for body weight regulation in complex human diseases related to unhealthy lifestyle.

Obsessive-compulsive spectrum disorders: a comorbidity and family history perspective.

PubMed

Brakoulias, Vlasios; Starcevic, Vladan; Sammut, Peter; Berle, David; Milicevic, Denise; Moses, Karen; Hannan, Anthony

2011-04-01

The concept of obsessive-compulsive spectrum disorders (OCSDs) has become so influential that there are proposals to introduce it into new diagnostic classificatory systems. The aim of this paper was to assess whether rates of comorbidity and family history of OCSDs in patients with obsessive-compulsive disorder (OCD) supported this concept. Comorbidity and family history were assessed in a group of participants with a primary diagnosis of OCD, using structured clinical interviews. Rates of OCSDs and other anxiety disorders (OADs), excluding OCD, were compared. Of the 77 OCD participants assessed, the most prevalent comorbid conditions were OADs: generalized anxiety disorder (34.6%), specific phobia (26.9%), social phobia (21.8%) and panic disorder (19.2%). The proposed OCSDs were less frequently comorbid: tic disorder (12.8%), trichotillomania (5.1%), hypochondriasis (3.8%) and body dysmorphic disorder (BDD) (3.8%). Similar trends were observed for a family history of these disorders. No participant reported a family history of an OCSD without a family history of an OAD. Although the concept of OCSDs has invigorated thinking in this complex diagnostic field, these results support the current association of OCD with OADs rather than with OCSDs.

Altered Neuronal and Circuit Excitability in Fragile X Syndrome.

PubMed

Contractor, Anis; Klyachko, Vitaly A; Portera-Cailliau, Carlos

2015-08-19

Fragile X syndrome (FXS) results from a genetic mutation in a single gene yet produces a phenotypically complex disorder with a range of neurological and psychiatric problems. Efforts to decipher how perturbations in signaling pathways lead to the myriad alterations in synaptic and cellular functions have provided insights into the molecular underpinnings of this disorder. From this large body of data, the theme of circuit hyperexcitability has emerged as a potential explanation for many of the neurological and psychiatric symptoms in FXS. The mechanisms for hyperexcitability range from alterations in the expression or activity of ion channels to changes in neurotransmitters and receptors. Contributions of these processes are often brain region and cell type specific, resulting in complex effects on circuit function that manifest as altered excitability. Here, we review the current state of knowledge of the molecular, synaptic, and circuit-level mechanisms underlying hyperexcitability and their contributions to the FXS phenotypes. Copyright © 2015 Elsevier Inc. All rights reserved.

An Intrinsically Disordered APLF Links Ku, DNA-PKcs, and XRCC4-DNA Ligase IV in an Extended Flexible Non-homologous End Joining Complex

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

Hammel, Michal; Yu, Yaping; Radhakrishnan, Sarvan K.

DNA double-strand break (DSB) repair by non-homologous end joining (NHEJ) in human cells is initiated by Ku heterodimer binding to a DSB, followed by recruitment of core NHEJ factors including DNA-dependent protein kinase catalytic subunit (DNA-PKcs), XRCC4-like factor (XLF), and XRCC4 (X4)-DNA ligase IV (L4). Ku also interacts with accessory factors such as aprataxin and polynucleotide kinase/phosphatase-like factor (APLF). But, how these factors interact to tether, process, and ligate DSB ends while allowing regulation and chromatin interactions remains enigmatic. Here, small angle X-ray scattering (SAXS) and mutational analyses show APLF is largely an intrinsically disordered protein that binds Ku, Ku/DNA-PKcsmore » (DNA-PK), and X4L4 within an extended flexible NHEJ core complex. X4L4 assembles with Ku heterodimers linked to DNA-PKcs via flexible Ku80 C-terminal regions (Ku80CTR) in a complex stabilized through APLF interactions with Ku, DNA-PK, and X4L4. Our collective results unveil the solution architecture of the six-protein complex and suggest cooperative assembly of an extended flexible NHEJ core complex that supports APLF accessibility while possibly providing flexible attachment of the core complex to chromatin. The resulting dynamic tethering furthermore, provides geometric access of L4 catalytic domains to the DNA ends during ligation and of DNA-PKcs for targeted phosphorylation of other NHEJ proteins as well as trans-phosphorylation of DNA-PKcs on the opposing DSB without disrupting the core ligation complex. Overall the results shed light on evolutionary conservation of Ku, X4, and L4 activities, while explaining the observation that Ku80CTR and DNA-PKcs only occur in a subset of higher eukaryotes.« less

An Intrinsically Disordered APLF Links Ku, DNA-PKcs, and XRCC4-DNA Ligase IV in an Extended Flexible Non-homologous End Joining Complex

DOE PAGES

Hammel, Michal; Yu, Yaping; Radhakrishnan, Sarvan K.; ...

2016-11-14

DNA double-strand break (DSB) repair by non-homologous end joining (NHEJ) in human cells is initiated by Ku heterodimer binding to a DSB, followed by recruitment of core NHEJ factors including DNA-dependent protein kinase catalytic subunit (DNA-PKcs), XRCC4-like factor (XLF), and XRCC4 (X4)-DNA ligase IV (L4). Ku also interacts with accessory factors such as aprataxin and polynucleotide kinase/phosphatase-like factor (APLF). But, how these factors interact to tether, process, and ligate DSB ends while allowing regulation and chromatin interactions remains enigmatic. Here, small angle X-ray scattering (SAXS) and mutational analyses show APLF is largely an intrinsically disordered protein that binds Ku, Ku/DNA-PKcsmore » (DNA-PK), and X4L4 within an extended flexible NHEJ core complex. X4L4 assembles with Ku heterodimers linked to DNA-PKcs via flexible Ku80 C-terminal regions (Ku80CTR) in a complex stabilized through APLF interactions with Ku, DNA-PK, and X4L4. Our collective results unveil the solution architecture of the six-protein complex and suggest cooperative assembly of an extended flexible NHEJ core complex that supports APLF accessibility while possibly providing flexible attachment of the core complex to chromatin. The resulting dynamic tethering furthermore, provides geometric access of L4 catalytic domains to the DNA ends during ligation and of DNA-PKcs for targeted phosphorylation of other NHEJ proteins as well as trans-phosphorylation of DNA-PKcs on the opposing DSB without disrupting the core ligation complex. Overall the results shed light on evolutionary conservation of Ku, X4, and L4 activities, while explaining the observation that Ku80CTR and DNA-PKcs only occur in a subset of higher eukaryotes.« less

Novel homozygous variants in ATCAY, MCOLN1, and SACS in complex neurological disorders.

PubMed

Manzoor, Humera; Brüggemann, Norbert; Hussain, Hafiz Muhammad Jafar; Bäumer, Tobias; Hinrichs, Frauke; Wajid, Muhammad; Münchau, Alexander; Naz, Sadaf; Lohmann, Katja

2018-06-01

Neurological disorders comprise a large group of clinically and genetically heterogeneous disorders, many of which have a genetic cause. In addition to a detailed neurological examination, exome sequencing is being increasingly used as a complementary diagnostic tool to identify the underlying genetic cause in patients with unclear, supposedly genetically determined disorders. To identify the genetic cause of a complex movement disorder in five consanguineous Pakistani families. We included five consanguineous Pakistani families with complex recessively inherited movement disorders. Clinical investigation including videotaping was carried out in a total of 59 family members (4-21 per family) and MRI in six patients. Exome sequencing was performed in 4-5 family members per pedigree to explore the underlying genetic cause. Patients presented a wide spectrum of neurological symptoms including ataxia and/or dystonia. We identified three novel homozygous, segregating variants in ATCAY (p.Pro200Profs*20), MCOLN1 (p.Ile184Thr), and SACS (p.Asn3040Lysfs*4) in three of the families. Thus, we were able to identify the likely cause of the disease in a considerable number of families (60%) with the relatively simple and nowadays widely available method of exome sequencing. Of note, close collaboration of neurologists and geneticists was instrumental for proper data interpretation. We expand the phenotypic, genotypic, and ethnical spectrum of mutations in these genes. Our findings alert neurologists that rare genetic causes should be considered in complex phenotypes regardless of ethnicity. Copyright © 2018 Elsevier Ltd. All rights reserved.

Electroencephalography signatures of attention-deficit/hyperactivity disorder: clinical utility.

PubMed

Alba, Guzmán; Pereda, Ernesto; Mañas, Soledad; Méndez, Leopoldo D; González, Almudena; González, Julián J

2015-01-01

The techniques and the most important results on the use of electroencephalography (EEG) to extract different measures are reviewed in this work, which can be clinically useful to study subjects with attention-deficit/hyperactivity disorder (ADHD). First, we discuss briefly and in simple terms the EEG analysis and processing techniques most used in the context of ADHD. We review techniques that both analyze individual EEG channels (univariate measures) and study the statistical interdependence between different EEG channels (multivariate measures), the so-called functional brain connectivity. Among the former ones, we review the classical indices of absolute and relative spectral power and estimations of the complexity of the channels, such as the approximate entropy and the Lempel-Ziv complexity. Among the latter ones, we focus on the magnitude square coherence and on different measures based on the concept of generalized synchronization and its estimation in the state space. Second, from a historical point of view, we present the most important results achieved with these techniques and their clinical utility (sensitivity, specificity, and accuracy) to diagnose ADHD. Finally, we propose future research lines based on these results.

Approach to the genetics of alcoholism: a review based on pathophysiology.

PubMed

Köhnke, Michael D

2008-01-01

Alcohol dependence is a common disorder with a heterogenous etiology. The results of family, twin and adoption studies on alcoholism are reviewed. These studies have revealed a heritability of alcoholism of over 50%. After evaluating the results, it was epidemiologically stated that alcoholism is heterogenous complex disorder with a multiple genetic background. Modern molecular genetic techniques allow examining specific genes involved in the pathophysiology of complex diseases such as alcoholism. Strategies for gene identification are introduced to the reader, including family-based and association studies. The susceptibility genes that are in the focus of this article have been chosen because they are known to encode for underlying mechanisms that are linked to the pathophysiology of alcoholism or that are important for the pharmacotherapeutic approaches in the treatment of alcohol dependence. Postulated candidate genes of the metabolism of alcohol and of the involved neurotransmitter systems are introduced. Genetic studies on alcoholism examining the metabolism of alcohol and the dopaminergic, GABAergic, glutamatergic, opioid, cholinergic and serotonergic neurotransmitter systems as well as the neuropeptide Y are presented. The results are critically discussed followed by a discussion of possible consequences.

Parents Psychopathology of Children with Attention Deficit Hyperactivity Disorder

ERIC Educational Resources Information Center

Margari, Francesco; Craig, Francesco; Petruzzelli, Maria Giuseppina; Lamanna, Annalinda; Matera, Emilia; Margari, Lucia

2013-01-01

Attention Deficit Hyperactivity Disorder (ADHD) is a disorder with extremely complex etiology, not yet well defined but certainly multi-factorial. This study investigated the possible etiopathogenetic role of ADHD symptoms and psychopathology disorders in parents of children with ADHD. We present a case-control study of parents of 50 children…

Tourette Syndrome: Information for School Nurses

ERIC Educational Resources Information Center

Golder, Tracy

2010-01-01

Tourette syndrome (TS) is a neurobehavioral disorder that consists of simple and complex tics. This disorder can significantly affect a child's self-esteem and academic success. Although some believe that only adults are affected, this disorder occurs most frequently in early childhood and symptoms decrease with age. Diagnosis of this disorder can…

Temperature Controlled Electrostatic Disorder and Polymorphism in Ultrathin Films of α-Sexithiophene

NASA Astrophysics Data System (ADS)

Hoffman, Benjamin; Jafari, Sara; McAfee, Terry; Apperson, Aubrey; O'Connor, Brendan; Dougherty, Daniel

Competing phases in well-ordered alpha-sexithiophene (α-6T) are shown to contribute to electrostatic disorder observed by differences in surface potential between mono- and bi-layer crystallites. Ultrathin films are of key importance to devices in which charge transport occurs in the first several monolayers nearest to a dielectric interface (e.g. thin film transistors) and complex structures in this regime impact the general electrostatic landscape. This study is comprised of 1.5 ML sample crystals grown via organic molecular beam deposition onto a temperature controlled hexamethyldisilazane (HMDS) passivated SiO2 substrate to produce well-ordered layer-by-layer type growth. Sample topography and surface potential were characterized simultaneously using Kelvin Probe Force Microscopy to then isolate contact potential differences by first and second layer α-6T regions. Films grown on 70° C, 120° C substrates are observed to have a bilayer with lower, higher potential than the monolayer, respectively. Resulting interlayer potential differences are a clear source of electrostatic disorder and are explained as subtle shifts in tilt-angles between layers relative to the substrate. These empirical results continue our understanding of how co-existing orientations contribute to the complex electrostatics influencing charge transport. NSF CAREER award DMR-1056861.

Symbolic dynamics of heart rate variability - a promising tool to investigate cardiac sympathovagal control in attention deficit/hyperactivity disorder (ADHD)?

PubMed

Tonhajzerova, Ingrid; Farsky, Ivan; Mestanik, Michal; Visnovcova, Zuzana; Mestanikova, Andrea; Hrtanek, Igor; Ondrejka, Igor

2016-06-01

We aimed to evaluate complex cardiac sympathovagal control in attention deficit/hyperactivity disorder (ADHD) by using heart rate variability (HRV) nonlinear analysis - symbolic dynamics. We examined 29 boys with untreated ADHD and 25 healthy boys (age 8-13 years). ADHD symptoms were evaluated by ADHD-RS-IV scale. ECG was recorded in 3 positions: baseline supine position, orthostasis, and clinostasis. Symbolic dynamics indices were used for the assessment of complex cardiac sympathovagal regulation: normalised complexity index (NCI), normalised unpredictability index (NUPI), and pattern classification measures (0V%, 1V%, 2LV%, 2UV%). The results showed that HRV complexity was significantly reduced at rest (NUPI) and during standing position (NCI, NUPI) in ADHD group compared to controls. Cardiac-linked sympathetic index 0V% was significantly higher during all posture positions and cardiovagal index 2LV% was significantly lower to standing in boys suffering from ADHD. Importantly, ADHD symptom inattention positively correlated with 0V%, and negatively correlated with NCI, NUPI. Concluding, symbolic dynamics revealed impaired complex neurocardiac control characterised by potential cardiac beta-adrenergic overactivity and vagal deficiency at rest and to posture changes in boys suffering from ADHD that is correlated with inattention. We suggest that symbolic dynamics indices could represent promising cardiac biomarkers in ADHD.

Threat Sensitivity in Bipolar Disorder

PubMed Central

Muhtadie, Luma; Johnson, Sheri L.

2015-01-01

Life stress is a major predictor of the course of bipolar disorder. Few studies have used laboratory paradigms to examine stress reactivity in bipolar disorder, and none have assessed autonomic reactivity to laboratory stressors. In the present investigation we sought to address this gap in the literature. Participants, 27 diagnosed with bipolar I disorder and 24 controls with no history of mood disorder, were asked to complete a complex working memory task presented as “a test of general intelligence.” Self-reported emotions were assessed at baseline and after participants were given task instructions; autonomic physiology was assessed at baseline and continuously during the stressor task. Compared to controls, individuals with bipolar disorder reported greater increases in pretask anxiety from baseline and showed greater cardiovascular threat reactivity during the task. Group differences in cardiovascular threat reactivity were significantly correlated with comorbid anxiety in the bipolar group. Our results suggest that a multimethod approach to assessing stress reactivity—including the use of physiological parameters that differentiate between maladaptive and adaptive profiles of stress responding— can yield valuable information regarding stress sensitivity and its associations with negative affectivity in bipolar disorder. PMID:25688436

Diagnosis and molecular basis of mitochondrial respiratory chain disorders: exome sequencing for disease gene identification.

PubMed

Ohtake, A; Murayama, K; Mori, M; Harashima, H; Yamazaki, T; Tamaru, S; Yamashita, Y; Kishita, Y; Nakachi, Y; Kohda, M; Tokuzawa, Y; Mizuno, Y; Moriyama, Y; Kato, H; Okazaki, Y

2014-04-01

Mitochondrial disorders have the highest incidence among congenital metabolic diseases, and are thought to occur at a rate of 1 in 5000 births. About 25% of the diseases diagnosed as mitochondrial disorders in the field of pediatrics have mitochondrial DNA abnormalities, while the rest occur due to defects in genes encoded in the nucleus. The most important function of the mitochondria is biosynthesis of ATP. Mitochondrial disorders are nearly synonymous with mitochondrial respiratory chain disorder, as respiratory chain complexes serve a central role in ATP biosynthesis. By next-generation sequencing of the exome, we analyzed 104 patients with mitochondrial respiratory chain disorders. The results of analysis to date were 18 patients with novel variants in genes previously reported to be disease-causing, and 27 patients with mutations in genes suggested to be associated in some way with mitochondria, and it is likely that they are new disease-causing genes in mitochondrial disorders. This article is part of a Special Issue entitled Frontiers of Mitochondrial Research. Copyright © 2014 The Authors. Published by Elsevier B.V. All rights reserved.

Identification of neuromotor deficits common to autism spectrum disorder and attention deficit/hyperactivity disorder, and imitation deficits specific to autism spectrum disorder.

PubMed

Biscaldi, Monica; Rauh, Reinhold; Müller, Cora; Irion, Lisa; Saville, Christopher W N; Schulz, Eberhard; Klein, Christoph

2015-12-01

Deficits in motor and imitation abilities are a core finding in autism spectrum disorders (ASD), but impaired motor functions are also found in attention deficit/hyperactivity disorder (ADHD). Given recent theorising about potential aetiological overlap between the two disorders, the present study aimed to assess difficulties in motor performance and imitation of facial movements and meaningless gestures in a sample of 24 ADHD patients, 22 patients with ASD, and 20 typically developing children, matched for age (6-13 years) and similar in IQ (>80). Furthermore, we explored the impact of comorbid ADHD symptoms on motor and imitation performance in the ASD sample and the interrelationships between the two groups of variables in the clinical groups separately. The results show motor dysfunction was common to both disorders, but imitation deficits were specific to ASD. Together with the pattern of interrelated motor and imitation abilities, which we found exclusively in the ASD group, our findings suggest complex phenotypic, and possibly aetiological, relationships between the two neurodevelopmental conditions.

Structural Basis for Inactivation of the Human Pyruvate Dehydrogenase Complex by Phosphorylation: Role of Disordered Phosphorylation Loops

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

Kato, Masato; Wynn, R. Max; Chuang, Jacinta L.

2009-09-11

We report the crystal structures of the phosporylated pyruvate dehydrogenase (E1p) component of the human pyruvate dehydrogenase complex (PDC). The complete phosphorylation at Ser264-{alpha} (site 1) of a variant E1p protein was achieved using robust pyruvate dehydrogenase kinase 4 free of the PDC core. We show that unlike its unmodified counterpart, the presence of a phosphoryl group at Ser264-{alpha} prevents the cofactor thiamine diphosphate-induced ordering of the two loops carrying the three phosphorylation sites. The disordering of these phosphorylation loops is caused by a previously unrecognized steric clash between the phosphoryl group at site 1 and a nearby Ser266-{alpha}, whichmore » nullifies a hydrogen-bonding network essential for maintaining the loop conformations. The disordered phosphorylation loops impede the binding of lipoyl domains of the PDC core to E1p, negating the reductive acetylation step. This results in the disruption of the substrate channeling in the PDC, leading to the inactivation of this catalytic machine.« less

Personality assessment of patients with complex regional pain syndrome type I.

PubMed

Monti, D A; Herring, C L; Schwartzman, R J; Marchese, M

1998-12-01

There is controversy regarding the importance of psychological/psychiatric factors in the development of the Complex Regional Pain Syndrome (CRPS). Our objective was to determine whether CRPS type I patients were psychiatrically different from other chronic pain patients, with particular attention to personality pathology. A standardized clinical assessment of all major psychiatric categories, including personality disorders, was performed on 25 CRPS type I patients and a control group of 25 patients with chronic low back pain from disc-related radiculopathy. Both sections of the Structured Clinical Interview for the Diagnostic and Statistical Manual (3rd ed., rev.) and the visual analog scale. Both groups were similar in terms of pain intensity and duration. Statistical analysis showed both groups to have a significant amount of major psychiatric comorbidity, in particular major depressive disorder, and a high incidence of personality disorders. Therefore, intense chronic pain was associated with significant psychiatric comorbidity in both groups and in similar proportions. The high incidence of personality pathology in both groups may represent an exaggeration of maladaptive personality traits and coping styles as a result of a chronic, intense, state of pain.

Paediatric acid-base disorders: A case-based review of procedures and pitfalls

PubMed Central

Carmody, J Bryan; Norwood, Victoria F

2013-01-01

Acid-base disorders occur frequently in paediatric patients. Despite the perception that their analysis is complex and difficult, a straightforward set of rules is sufficient to interpret even the most complex disorders – provided certain pitfalls are avoided. Using a case-based approach, the present article reviews the fundamental concepts of acid-base analysis and highlights common mistakes and oversights. Specific topics include the proper identification of the primary disorder; distinguishing compensatory changes from additional primary disorders; use of the albumin-corrected anion gap to generate a differential diagnosis for patients with metabolic acidosis; screening for mixed disorders with the delta-delta formula; recognizing the limits of compensation; use of the anion gap to identify ‘hidden’ acidosis; and the importance of using information from the history and physical examination to identify the specific cause of a patient’s acid-base disturbance. PMID:24381489

Fluorescence anisotropy reveals order and disorder of protein domains in the nuclear pore complex.

PubMed

Mattheyses, Alexa L; Kampmann, Martin; Atkinson, Claire E; Simon, Sanford M

2010-09-22

We present a new approach for studying individual protein domains within the nuclear pore complex (NPC) using fluorescence polarization microscopy. The NPC is a large macromolecular complex, the size and complexity of which presents experimental challenges. Using fluorescence anisotropy and exploiting the symmetry of the NPC and its organization in the nuclear envelope, we have resolved order and disorder of individual protein domains. Fluorescently tagging specific domains of individual nucleoporins revealed both rigid and flexible domains: the tips of the FG domains are disordered, whereas the NPC-anchored domains are ordered. Our technique allows the collection of structural information in vivo, providing the ability to probe the organization of protein domains within the NPC. This has particular relevance for the FG domain nucleoporins, which are crucial for nucleocytoplasmic transport. Copyright © 2010 Biophysical Society. Published by Elsevier Inc. All rights reserved.

Unified analysis of ensemble and single-complex optical spectral data from light-harvesting complex-2 chromoproteins for gaining deeper insight into bacterial photosynthesis

NASA Astrophysics Data System (ADS)

Pajusalu, Mihkel; Kunz, Ralf; Rätsep, Margus; Timpmann, Kõu; Köhler, Jürgen; Freiberg, Arvi

2015-11-01

Bacterial light-harvesting pigment-protein complexes are very efficient at converting photons into excitons and transferring them to reaction centers, where the energy is stored in a chemical form. Optical properties of the complexes are known to change significantly in time and also vary from one complex to another; therefore, a detailed understanding of the variations on the level of single complexes and how they accumulate into effects that can be seen on the macroscopic scale is required. While experimental and theoretical methods exist to study the spectral properties of light-harvesting complexes on both individual complex and bulk ensemble levels, they have been developed largely independently of each other. To fill this gap, we simultaneously analyze experimental low-temperature single-complex and bulk ensemble optical spectra of the light-harvesting complex-2 (LH2) chromoproteins from the photosynthetic bacterium Rhodopseudomonas acidophila in order to find a unique theoretical model consistent with both experimental situations. The model, which satisfies most of the observations, combines strong exciton-phonon coupling with significant disorder, characteristic of the proteins. We establish a detailed disorder model that, in addition to containing a C2-symmetrical modulation of the site energies, distinguishes between static intercomplex and slow conformational intracomplex disorders. The model evaluations also verify that, despite best efforts, the single-LH2-complex measurements performed so far may be biased toward complexes with higher Huang-Rhys factors.

Unified analysis of ensemble and single-complex optical spectral data from light-harvesting complex-2 chromoproteins for gaining deeper insight into bacterial photosynthesis.

PubMed

Pajusalu, Mihkel; Kunz, Ralf; Rätsep, Margus; Timpmann, Kõu; Köhler, Jürgen; Freiberg, Arvi

2015-01-01

Bacterial light-harvesting pigment-protein complexes are very efficient at converting photons into excitons and transferring them to reaction centers, where the energy is stored in a chemical form. Optical properties of the complexes are known to change significantly in time and also vary from one complex to another; therefore, a detailed understanding of the variations on the level of single complexes and how they accumulate into effects that can be seen on the macroscopic scale is required. While experimental and theoretical methods exist to study the spectral properties of light-harvesting complexes on both individual complex and bulk ensemble levels, they have been developed largely independently of each other. To fill this gap, we simultaneously analyze experimental low-temperature single-complex and bulk ensemble optical spectra of the light-harvesting complex-2 (LH2) chromoproteins from the photosynthetic bacterium Rhodopseudomonas acidophila in order to find a unique theoretical model consistent with both experimental situations. The model, which satisfies most of the observations, combines strong exciton-phonon coupling with significant disorder, characteristic of the proteins. We establish a detailed disorder model that, in addition to containing a C_{2}-symmetrical modulation of the site energies, distinguishes between static intercomplex and slow conformational intracomplex disorders. The model evaluations also verify that, despite best efforts, the single-LH2-complex measurements performed so far may be biased toward complexes with higher Huang-Rhys factors.

[Smartphone application for blood gas interpretation].

PubMed

Obiols, Julien; Bardo, Pascale; Garnier, Jean-Pierre; Brouard, Benoît

2013-01-01

Ninety four per cent of health professionals use their smartphone for business purposes and more than 50% has medical applications. The «Blood Gas» application was created to be part of this dynamic and participate to e-health development in France. The «Blood Gas» application facilitates interpretation of the results of blood gas analysis using an algorithm developed with reference to a medical bibliography. It can detect some complex or intricate acid-base disorders in evaluating the effectiveness of the secondary response. The application also studied the respiratory status of the patient by calculating the PaO2/FiO2 ratio and the alveol-arterial gradient. It also indicates the presence of a shunt effect. Finally, a specific module to calculate the SID (strong ion difference) depending on the model of Stewart can detect complex acid-base disorders.

DIAGNOSIS AND TREATMENT OF ADHD DURING ADOLESCENCE IN THE PRIMARY CARE SETTING: REVIEW AND FUTURE DIRECTIONS

PubMed Central

Brahmbhatt, Khyati; Hilty, Donald M.; Hah, Mina; Han, Jaesu; Angkustsiri, Kathy; Schweitzer, Julie

2017-01-01

Introduction Attention deficit hyperactivity disorder (ADHD) is a chronic neurodevelopmental disorder with a worldwide prevalence of about 5% in school age children. Objective The goal of this review is to assist primary care providers (PCPs) in diagnosing and treating ADHD in adolescents. Methods PubMed, PsychInfo and Science Citation Index databases were searched from March 1990–2015 with the key words: attention deficit hyperactivity disorder, primary care/pediatrics and children/adolescents, abstracts addressing diagnosis and/or treatment with 105 citations identified including supplementary treatment guidelines/books. Results Adolescent ADHD presents with significant disturbances in attention, academic performance and family relationships with unique issues associated with this developmental period. Diagnostic challenges include the variable symptom presentation during adolescence, complex differential diagnosis and limited training and time for PCPs to conduct thorough evaluations. The evidence-base for treatments in adolescence in comparison to those in children or adults with ADHD is relatively weak. Providers should be cognizant of prevention, early identification and treatment of conditions associated with ADHD that emerge during adolescence as substance use disorders. Conclusions Adolescent ADHD management for the PCP is complex, requires further research, and perhaps new primary care-psychiatric models, to assist in determining the optimal care for patients at this critical period. PMID:27209327

Mutations in chromatin regulators functionally link Cornelia de Lange syndrome and clinically overlapping phenotypes.

PubMed

Parenti, Ilaria; Teresa-Rodrigo, María E; Pozojevic, Jelena; Ruiz Gil, Sara; Bader, Ingrid; Braunholz, Diana; Bramswig, Nuria C; Gervasini, Cristina; Larizza, Lidia; Pfeiffer, Lutz; Ozkinay, Ferda; Ramos, Feliciano; Reiz, Benedikt; Rittinger, Olaf; Strom, Tim M; Watrin, Erwan; Wendt, Kerstin; Wieczorek, Dagmar; Wollnik, Bernd; Baquero-Montoya, Carolina; Pié, Juan; Deardorff, Matthew A; Gillessen-Kaesbach, Gabriele; Kaiser, Frank J

2017-03-01

The coordinated tissue-specific regulation of gene expression is essential for the proper development of all organisms. Mutations in multiple transcriptional regulators cause a group of neurodevelopmental disorders termed "transcriptomopathies" that share core phenotypical features including growth retardation, developmental delay, intellectual disability and facial dysmorphism. Cornelia de Lange syndrome (CdLS) belongs to this class of disorders and is caused by mutations in different subunits or regulators of the cohesin complex. Herein, we report on the clinical and molecular characterization of seven patients with features overlapping with CdLS who were found to carry mutations in chromatin regulators previously associated to other neurodevelopmental disorders that are frequently considered in the differential diagnosis of CdLS. The identified mutations affect the methyltransferase-encoding genes KMT2A and SETD5 and different subunits of the SWI/SNF chromatin-remodeling complex. Complementary to this, a patient with Coffin-Siris syndrome was found to carry a missense substitution in NIPBL. Our findings indicate that mutations in a variety of chromatin-associated factors result in overlapping clinical phenotypes, underscoring the genetic heterogeneity that should be considered when assessing the clinical and molecular diagnosis of neurodevelopmental syndromes. It is clear that emerging molecular mechanisms of chromatin dysregulation are central to understanding the pathogenesis of these clinically overlapping genetic disorders.

The Interaction of Ambient Frequency and Feature Complexity in the Diphthong Errors of Children with Phonological Disorders.

ERIC Educational Resources Information Center

Stokes, Stephanie F.; Lau, Jessica Tse-Kay; Ciocca, Valter

2002-01-01

This study examined the interaction of ambient frequency and feature complexity in the diphthong errors produced by 13 Cantonese-speaking children with phonological disorders. Perceptual analysis of 611 diphthongs identified those most frequently and least frequently in error. Suggested treatment guidelines include consideration of three factors:…

Addressing the Needs of Adolescents with Autism Spectrum Disorder: Considerations and Complexities for High School Interventions

ERIC Educational Resources Information Center

Kucharczyk, Suzanne; Reutebuch, Colleen K.; Carter, Erik W.; Hedges, Susan; El Zein, Farah; Gustafson, Jenny R.

2015-01-01

The outcomes of students with autism spectrum disorder (ASD) are driving the field to address how secondary education might be optimally designed and delivered. We conducted 28 focus groups across four states to explore the contexts, considerations, and complexities associated with delivering and combining evidence-based interventions to meet the…

Supporting Individuals with Autism Spectrum Disorder in Understanding and Coping with Complex Social Emotional Issues

ERIC Educational Resources Information Center

Ahlers, Kaitlyn P.; Gabrielsen, Terisa P.; Lewis, Danielle; Brady, Anna M.; Litchford, April

2017-01-01

Core deficits in autism spectrum disorder (ASD) center around social communication and behavior. For those with ASD, these deficits complicate the task of learning how to cope with and manage complex social emotional issues. Although individuals with ASD may receive sufficient academic and basic behavioral support in school settings, supports for…

Complex Psychiatric Comorbidity of Treatment-Seeking Youth with Autism Spectrum Disorder and Anxiety Symptoms

ERIC Educational Resources Information Center

Hepburn, Susan L.; Stern, Jessica A.; Blakeley-Smith, Audrey; Kimel, Lila K.; Reaven, Judith A.

2014-01-01

This descriptive study examines the complexity of psychiatric comorbidity in treatment-seeking youth with ASD and anxiety symptoms. Forty-two parents of youth with ASD and anxiety (ages 8-14) completed a structured diagnostic interview (Schedule for Affective Disorders and Schizophrenia for School-Age Children-Present and Lifetime Version). Youth…

Interaction of Social and Play Behaviors in Preschoolers With and Without Pervasive Developmental Disorder

ERIC Educational Resources Information Center

Pierce-Jordan, Sandra; Lifter, Karin

2005-01-01

This study investigated the relationship between the social and play behaviors of young children with pervasive developmental disorder (PDD) and without PDD. Videotaped observations of 21 preschool children (12 with PDD and 9 without PDD) were examined independently for (a) social complexity and (b) play complexity that was assessed on an…

Harnessing the Power of Play: Opportunities for Children with Autism Spectrum Disorders

ERIC Educational Resources Information Center

Mastrangelo, Sonia

2009-01-01

Play is a complex phenomenon that occurs naturally for most children; they move through the various stages of play development and are able to add complexity, imagination, and creativity to their thought processes and actions. However, for many children with autism spectrum disorders (ASD), the various stages of play never truly develop, or occur…

How Stimulus and Task Complexity Affect Monitoring in High-Functioning Adults with Autism Spectrum Disorder

ERIC Educational Resources Information Center

Koolen, Sophieke; Vissers, Constance Th. W. M.; Egger, Jos I. M.; Verhoeven, Ludo

2014-01-01

The present study examined whether individuals with autism spectrum disorder (ASD) are able to update and monitor working memory representations of visual input, and whether performance is influenced by stimulus and task complexity. 15 high-functioning adults with ASD and 15 controls were asked to allocate either elements of abstract figures or…

Cohesin and Human Disease

PubMed Central

Liu, Jinglan; Krantz, Ian D.

2016-01-01

Cornelia de Lange syndrome (CdLS) is a dominant multisystem disorder caused by a disruption of cohesin function. The cohesin ring complex is composed of four protein subunits and more than 25 additional proteins involved in its regulation. The discovery that this complex also has a fundamental role in long-range regulation of transcription in Drosophila has shed light on the mechanism likely responsible for its role in development. In addition to the three cohesin proteins involved in CdLS, a second multisystem, recessively inherited, developmental disorder, Roberts-SC phocomelia, is caused by mutations in another regulator of the cohesin complex, ESCO2. Here we review the phenotypes of these disorders, collectively termed cohesinopathies, as well as the mechanism by which cohesin disruption likely causes these diseases. PMID:18767966

Redefining the endophenotype concept to accommodate transdiagnostic vulnerabilities and etiological complexity.

PubMed

Beauchaine, Theodore P; Constantino, John N

2017-09-11

In psychopathology research, endophenotypes are a subset of biomarkers that indicate genetic vulnerability independent of clinical state. To date, an explicit expectation is that endophenotypes be specific to single disorders. We evaluate this expectation considering recent advances in psychiatric genetics, recognition that transdiagnostic vulnerability traits are often more useful than clinical diagnoses in psychiatric genetics, and appreciation for etiological complexity across genetic, neural, hormonal and environmental levels of analysis. We suggest that the disorder-specificity requirement of endophenotypes be relaxed, that neural functions are preferable to behaviors as starting points in searches for endophenotypes, and that future research should focus on interactive effects of multiple endophenotypes on complex psychiatric disorders, some of which are 'phenocopies' with distinct etiologies.

How people evaluate others with social anxiety disorder: A comparison to depression and general mental illness stigma.

PubMed

Anderson, Kristin N; Jeon, Andrew B; Blenner, Jordan A; Wiener, Richard L; Hope, Debra A

2015-03-01

Despite the availability of effective interventions, most individuals with social anxiety disorder do not seek treatment. Given their fear of negative evaluation, socially anxious individuals might be especially susceptible to stigma concerns, a recognized barrier for mental health treatment. However, very little is known about the stigma specific to social anxiety disorder. In a design similar to Feldman and Crandall (2007), university undergraduate students read vignettes about target individuals with a generic mental illness label, major depressive disorder, and social anxiety disorder. Subjects rated each of 3 people in the vignettes on social distance and 17 dimensions including dangerousness, heritability and prevalence of the disorder, and gender ratio. Results indicated that being male and not having experience with mental health treatment was associated with somewhat greater preferred social distance. Multiple regression analyses revealed that being embarrassed by the disorder and dangerousness predicted social distance across all 3 vignettes. The vignette for social anxiety disorder had the most complex model and included work impairment, more common among women, and more avoidable. These results have implications for understanding the specific aspects of the stigma associated with social anxiety disorder. Public service messages to reduce stigma should focus on more accurate information about dangerousness and mental illness, given this is an established aspect of mental illness stigma. More nuanced messages about social anxiety might be best incorporated into the treatment referral process and as part of treatment. (c) 2015 APA, all rights reserved).

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

Vila, Fernando D.; Rehr, John J.; Nuzzo, Ralph G.

Supported Pt nanocatalysts generally exhibit anomalous behavior, including negative thermal expansion and large structural disorder. Finite temperature DFT/MD simulations reproduce these properties, showing that they are largely explained by a combination of thermal vibrations and low-frequency disorder. We show in this paper that a full interpretation is more complex and that the DFT/MD mean-square relative displacements (MSRD) can be further separated into vibrational disorder, “dynamic structural disorder” (DSD), and long-time equilibrium fluctuations of the structure dubbed “anomalous structural disorder” (ASD). We find that the vibrational and DSD components behave normally, increasing linearly with temperature while the ASD decreases, reflecting themore » evolution of mean nanoparticle geometry. Finally, as a consequence the usual procedure of fitting the MSRD to normal vibrations plus temperature-independent static disorder results in unphysical bond strengths and Grüneisen parameters.« less

Grammatical processing in schizophrenia: Evidence from morphology

PubMed Central

Walenski, Matthew; Weickert, Thomas W.; Maloof, Christopher J.; Ullman, Michael T.

2009-01-01

Patients with psychiatric disorders such as schizophrenia commonly present with impaired language. Here we investigate language in schizophrenia with a focus on inflectional morphology, using an intensively-studied and relatively well-understood linguistic paradigm. Patients with schizophrenia (n=43) and age-matched healthy control subjects (n=42) were asked to produce past-tenses of regular (slip), irregular (swim), and novel (plag) English verbs. Patients were impaired at regulars and novels (slipped, plagged), with relative sparing of irregulars (swam), controlling for numerous subject- and item-specific factors (e.g., IQ, phonological complexity). Additionally, patients’ thought-disorder scores significantly predicted their performance at regular and novel (but not irregular) past-tense production. The results support grammatical deficits in schizophrenia, with a relative sparing of lexical memory, and suggest that thought disorder may be linked with grammatical impairments in the disorder. PMID:19766129

Nonlinear analysis of EEG in major depression with fractal dimensions.

PubMed

Akar, Saime A; Kara, Sadik; Agambayev, Sumeyra; Bilgic, Vedat

2015-01-01

Major depressive disorder (MDD) is a psychiatric mood disorder characterized by cognitive and functional impairments in attention, concentration, learning and memory. In order to investigate and understand its underlying neural activities and pathophysiology, EEG methodologies can be used. In this study, we estimated the nonlinearity features of EEG in MDD patients to assess the dynamical properties underlying the frontal and parietal brain activity. EEG data were obtained from 16 patients and 15 matched healthy controls. A wavelet-chaos methodology was used for data analysis. First, EEGs of subjects were decomposed into 5 EEG sub-bands by discrete wavelet transform. Then, both the Katz's and Higuchi's fractal dimensions (KFD and HFD) were calculated as complexity measures for full-band and sub-bands EEGs. Last, two-way analyses of variances were used to test EEG complexity differences on each fractality measures. As a result, a significantly increased complexity was found in both parietal and frontal regions of MDD patients. This significantly increased complexity was observed not only in full-band activity but also in beta and gamma sub-bands of EEG. The findings of the present study indicate the possibility of using the wavelet-chaos methodology to discriminate the EEGs of MDD patients from healthy controls.

EEG complexity as a biomarker for autism spectrum disorder risk

PubMed Central

2011-01-01

Background Complex neurodevelopmental disorders may be characterized by subtle brain function signatures early in life before behavioral symptoms are apparent. Such endophenotypes may be measurable biomarkers for later cognitive impairments. The nonlinear complexity of electroencephalography (EEG) signals is believed to contain information about the architecture of the neural networks in the brain on many scales. Early detection of abnormalities in EEG signals may be an early biomarker for developmental cognitive disorders. The goal of this paper is to demonstrate that the modified multiscale entropy (mMSE) computed on the basis of resting state EEG data can be used as a biomarker of normal brain development and distinguish typically developing children from a group of infants at high risk for autism spectrum disorder (ASD), defined on the basis of an older sibling with ASD. Methods Using mMSE as a feature vector, a multiclass support vector machine algorithm was used to classify typically developing and high-risk groups. Classification was computed separately within each age group from 6 to 24 months. Results Multiscale entropy appears to go through a different developmental trajectory in infants at high risk for autism (HRA) than it does in typically developing controls. Differences appear to be greatest at ages 9 to 12 months. Using several machine learning algorithms with mMSE as a feature vector, infants were classified with over 80% accuracy into control and HRA groups at age 9 months. Classification accuracy for boys was close to 100% at age 9 months and remains high (70% to 90%) at ages 12 and 18 months. For girls, classification accuracy was highest at age 6 months, but declines thereafter. Conclusions This proof-of-principle study suggests that mMSE computed from resting state EEG signals may be a useful biomarker for early detection of risk for ASD and abnormalities in cognitive development in infants. To our knowledge, this is the first demonstration of an information theoretic analysis of EEG data for biomarkers in infants at risk for a complex neurodevelopmental disorder. PMID:21342500

Gambling disorder: a side effect of an off-label prescription of baclofen-literature review.

PubMed

Guillou-Landreat, Morgane; Victorri Vigneau, Caroline; Gerardin, Marie

2017-01-10

The use of high-dose baclofen emerged in 2008 in the treatment of alcohol-use disorders. Its prescription is still off-label in France, but recent trials have suggested the interest of using high doses for alcohol dependence, so we have to deal with an increase in its use. However, we still have few data about the adverse effects of a high-dose baclofen prescription, especially in complex addictive disorders. We present a case of a 32-year-old man who sought treatment for gambling disorders (GDs). He had complex addictive disorders, including alcohol-use disorders and GDs. He developed a severe GD, after treatment with a high dose of baclofen. The maximum dose was 160 mg/day, prescribed for his alcohol-use disorders. According to the Naranjo algorithm, the score was +7, it enabled to conclude that problem of gambling was probably imputable to baclofen. We discuss this case with reference to literature. 2017 BMJ Publishing Group Ltd.

Targeted treatments for cognitive and neurodevelopmental disorders in tuberous sclerosis complex.

PubMed

de Vries, Petrus J

2010-07-01

Until recently, the neuropsychiatric phenotype of tuberous sclerosis complex (TSC) was presumed to be caused by the structural brain abnormalities and/or seizures seen in the disorder. However, advances in the molecular biology of the disorder have shown that TSC is a mammalian target of rapamycin (mTOR) overactivation syndrome, and that direct molecular pathways exist between gene mutation and cognitive/neurodevelopmental phenotype. Molecularly-targeted treatments using mTOR inhibitors (such as rapamycin) are showing great promise for the physical and neurological phenotype of TSC. Pre-clinical and early-phase clinical studies of the cognitive and neurodevelopmental features of TSC suggest that some of the neuropsychiatric phenotypes might also be reversible, even in adults with the disorder. TSC, fragile X, neurofibromatosis type 1, and disorders associated with phosphatase and tensin homo (PTEN) mutations, all signal through the mTOR signaling pathway, with the TSC1-TSC2 protein complex as a molecular switchboard at its center. Together, these disorders represent as much as 14% of autism spectrum disorders (ASD). Therefore, we suggest that this signaling pathway is a key to the underlying pathophysiology of a significant subset of individuals with ASD. The study of molecularly targeted treatments in TSC and related disorders, therefore, may be of scientific and clinical value not only to those with TSC, but to a larger population that may have a neuropsychiatric phenotype attributable to mTOR overactivation or dysregulation. (c) 2010 The American Society for Experimental NeuroTherapeutics, Inc. Published by Elsevier Inc. All rights reserved.

Second Language Acquisition and Schizophrenia

ERIC Educational Resources Information Center

Dugan, James E.

2014-01-01

Schizophrenia is a complex mental disorder that results in language-related symptoms at various discourse levels, ranging from semantics (e.g. inventing words and producing nonsensical strands of similar-sounding words) to pragmatics and higher-level functioning (e.g. too little or too much information given to interlocutors, and tangential…

Feeding and Swallowing Dysfunction in Genetic Syndromes

ERIC Educational Resources Information Center

Cooper-Brown, Linda; Copeland, Sara; Dailey, Scott; Downey, Debora; Petersen, Mario Cesar; Stimson, Cheryl; Van Dyke, Don C.

2008-01-01

Children with genetic syndromes frequently have feeding problems and swallowing dysfunction as a result of the complex interactions between anatomical, medical, physiological, and behavioral factors. Feeding problems associated with genetic disorders may also cause feeding to be unpleasant, negative, or even painful because of choking, coughing,…

Fuzzy regions in an intrinsically disordered protein impair protein-protein interactions.

PubMed

Gruet, Antoine; Dosnon, Marion; Blocquel, David; Brunel, Joanna; Gerlier, Denis; Das, Rahul K; Bonetti, Daniela; Gianni, Stefano; Fuxreiter, Monika; Longhi, Sonia; Bignon, Christophe

2016-02-01

Despite the partial disorder-to-order transition that intrinsically disordered proteins often undergo upon binding to their partners, a considerable amount of residual disorder may be retained in the bound form, resulting in a fuzzy complex. Fuzzy regions flanking molecular recognition elements may enable partner fishing through non-specific, transient contacts, thereby facilitating binding, but may also disfavor binding through various mechanisms. So far, few computational or experimental studies have addressed the effect of fuzzy appendages on partner recognition by intrinsically disordered proteins. In order to shed light onto this issue, we used the interaction between the intrinsically disordered C-terminal domain of the measles virus (MeV) nucleoprotein (NTAIL ) and the X domain (XD) of the viral phosphoprotein as model system. After binding to XD, the N-terminal region of NTAIL remains conspicuously disordered, with α-helical folding taking place only within a short molecular recognition element. To study the effect of the N-terminal fuzzy region on NTAIL /XD binding, we generated N-terminal truncation variants of NTAIL , and assessed their binding abilities towards XD. The results revealed that binding increases with shortening of the N-terminal fuzzy region, with this also being observed with hsp70 (another MeV NTAIL binding partner), and for the homologous NTAIL /XD pairs from the Nipah and Hendra viruses. Finally, similar results were obtained when the MeV NTAIL fuzzy region was replaced with a highly dissimilar artificial disordered sequence, supporting a sequence-independent inhibitory effect of the fuzzy region. © 2015 Federation of European Biochemical Societies.

Cation disorder in shocked orthopyroxene.

NASA Technical Reports Server (NTRS)

Dundon, R. W.; Hafner, S. S.

1971-01-01

The study of cation distributions over nonequivalent lattice sites in minerals may reveal information on the history of temperature and pressure in rocks. Chemically homogeneous orthopyroxene specimens were shocked under well-controlled conditions in the laboratory in order to provide a basis for the interpretation of more complex natural materials. As a result of the investigation it is concluded that the distribution of magnesium and iron over the M1 and M2 positions in Bamle enstatite shocked at 1 megabar is highly disordered. It corresponds to an equilibrium distribution of at least 1000 C.

HERVs Expression in Autism Spectrum Disorders

PubMed Central

Balestrieri, Emanuela; Arpino, Carla; Matteucci, Claudia; Sorrentino, Roberta; Pica, Francesca; Alessandrelli, Riccardo; Coniglio, Antonella; Curatolo, Paolo; Rezza, Giovanni; Macciardi, Fabio; Garaci, Enrico; Gaudi, Simona; Sinibaldi-Vallebona, Paola

2012-01-01

Background Autistic Spectrum Disorder (ASD) is a heterogeneous neurodevelopmental disorder, resulting from complex interactions among genetic, genomic and environmental factors. Here we have studied the expression of Human Endogenous Retroviruses (HERVs), non-coding DNA elements with potential regulatory functions, and have tested their possible implication in autism. Methods The presence of retroviral mRNAs from four HERV families (E, H, K and W), widely implicated in complex diseases, was evaluated in peripheral blood mononuclear cells (PBMCs) from ASD patients and healthy controls (HCs) by qualitative RT-PCR. We also analyzed the expression of the env sequence from HERV-H, HERV-W and HERV-K families in PBMCs at the time of sampling and after stimulation in culture, in both ASD and HC groups, by quantitative Real-time PCR. Differences between groups were evaluated using statistical methods. Results The percentage of HERV-H and HERV-W positive samples was higher among ASD patients compared to HCs, while HERV-K was similarly represented and HERV-E virtually absent in both groups. The quantitative evaluation shows that HERV-H and HERV-W are differentially expressed in the two groups, with HERV-H being more abundantly expressed and, conversely, HERV-W, having lower abundance, in PBMCs from ASDs compared to healthy controls. PMBCs from ASDs also showed an increased potential to up-regulate HERV-H expression upon stimulation in culture, unlike HCs. Furthermore we report a negative correlation between expression levels of HERV-H and age among ASD patients and a statistically significant higher expression in ASD patients with Severe score in Communication and Motor Psychoeducational Profile-3. Conclusions Specific HERV families have a distinctive expression profile in ASD patients compared to HCs. We propose that HERV-H expression be explored in larger samples of individuals with autism spectrum in order to determine its utility as a novel biological trait of this complex disorder. PMID:23155411

Evaluation of Oxidative Stress in Bipolar Disorder in terms of Total Oxidant Status, Total Antioxidant Status, and Oxidative Stress Index.

PubMed

Cingi Yirün, Merve; Ünal, Kübranur; Altunsoy Şen, Neslihan; Yirün, Onur; Aydemir, Çiğdem; Göka, Erol

2016-09-01

Bipolar disorder is one of the most debilitating psychiatric disorders characterized by disruptive episodes of mania/hypomania and depression. Considering the complex role of biological and environmental factors in the etiology of affective disorders, recent studies have focused on oxidative stress, which may damage nerve cell components and take part in pathophysiology. The aim of the present study was to contribute to the data about oxidative stress in bipolar disorder by detecting the total antioxidant status (TAS), total oxidant status (TOS), and oxidative stress index (OSI) levels of manic episode (ME) and euthymic (EU) patients and by comparing these results with those of healthy controls (HCs). The study population consisted of 28 EU outpatients meeting the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) criteria for bipolar disorder I and 23 inpatients who were currently hospitalized in a psychiatry ward with the diagnosis of the bipolar disorder ME according to the DSM-5 criteria. Forty-three healthy subjects were included in the study as the control group (HC). Serum TAS, TOS, and OSI levels of all the participants were determined. Statistical analysis of serum TAS, TOS, and OSI levels did not show any significant differences between the ME patients, EU patients, and HCs. Comparison between the bipolar disorder patients (ME+EU) and HC also did not reveal any statistically significant difference between these two groups in terms of serum TAS, TOS, and OSI levels. To date, studies on oxidative stress in bipolar disorder have led to controversial results. In the present study, no statistically significant difference was detected between the oxidative parameters of bipolar disorder patients and HCs. In order to comprehensively evaluate oxidative stress in bipolar disorder, further studies are needed.

How perfectionism and ineffectiveness influence growth of eating disorder risk in young adolescent girls.

PubMed

Wade, Tracey D; Wilksch, Simon M; Paxton, Susan J; Byrne, Susan M; Austin, S Bryn

2015-03-01

While perfectionism is widely considered to influence risk for eating disorders, results of longitudinal studies are mixed. The goal of the current study was to investigate a more complex model of how baseline perfectionism (both high personal standards and self-critical evaluative concerns) might influence change in risk status for eating disorders in young adolescent girls, through its influence on ineffectiveness. The study was conducted with 926 girls (mean age of 13 years), and involved three waves of data (baseline, 6- and 12-month follow-up). Latent growth curve modelling, incorporating the average rate at which risk changed over time, the intercept (initial status) of ineffectiveness, and baseline perfectionism, was used to explore longitudinal mediation. Personal standards was not supported as contributing to risk but results indicated that the higher mean scores on ineffectiveness over the three waves mediated the relationship between higher baseline self-critical evaluative concerns and both measures of eating disorder risk. The relationship between concern over mistakes and change in risk was small and negative. These results suggest the usefulness of interventions related to self-criticism and ineffectiveness for decreasing risk for developing an eating disorder in young adolescent girls. Copyright © 2015 Elsevier Ltd. All rights reserved.

Teacher Support in the Implementation of Classroom Interventions for Middle School Children with Autism Spectrum Disorder

ERIC Educational Resources Information Center

Pantoja, Danitza

2014-01-01

Autism spectrum disorder is generally regarded as complex, neurologically based, developmental disability that typically has its onset early in life (Myles & Simpson, 2001). Autism spectrum disorder is considered a universal disorder that affects children across all socioeconomic and educational levels (Wilkinson, 2010). Autism spectrum…

LPHN3 and Attention-Deficit/Hyperactivity Disorder: Interaction with Maternal Stress during Pregnancy

ERIC Educational Resources Information Center

Choudhry, Zia; Sengupta, Sarojini M.; Grizenko, Natalie; Fortier, Marie-Eve; Thakur, Geeta A.; Bellingham, Johanne; Joober, Ridha

2012-01-01

Background: Attention-deficit/hyperactivity disorder (ADHD) is a heterogeneous behavioral disorder, complex both in etiology and clinical expression. Both genetic and environmental factors have been implicated, and it has been suggested that gene-environment interactions may play a pivotal role in the disorder. Recently, a significant association…

Classification of Depressive Disorders in DSM-V: Proposal for a Two-Dimension System

PubMed Central

Klein, Daniel N.

2011-01-01

The number of categories and specifiers for mood disorders has increased with each successive edition of the Diagnostic and Statistical Manual for Mental Disorders (DSM). Many of these categories and specifiers can be viewed as an effort to map the various permutations of severity and chronicity that characterize the depressive disorders. However, this has resulted in a system that is unnecessarily complex and unwieldy, and created problems with artificial distinctions between categories and artifactual comorbidity, and at the same time obscures what may be more fundamental distinctions. A potentially useful and more parsimonious approach to capturing much of the heterogeneity of depressive disorders is to classify the depressive disorders along two dimensions, one reflecting severity and the other chronicity. Considerations in the development of these dimensions are discussed, and a set of examples is presented. Although further research and discussion are needed to determine the optimal form of these dimensions, the next edition of the DSM should consider replacing many of the existing categories and specifiers for depressive disorders with the simpler approach of classifying depressive disorders using the two dimensions of severity and chronicity. PMID:18729608

Electrostatically Accelerated Encounter and Folding for Facile Recognition of Intrinsically Disordered Proteins

PubMed Central

Ganguly, Debabani; Zhang, Weihong; Chen, Jianhan

2013-01-01

Achieving facile specific recognition is essential for intrinsically disordered proteins (IDPs) that are involved in cellular signaling and regulation. Consideration of the physical time scales of protein folding and diffusion-limited protein-protein encounter has suggested that the frequent requirement of protein folding for specific IDP recognition could lead to kinetic bottlenecks. How IDPs overcome such potential kinetic bottlenecks to viably function in signaling and regulation in general is poorly understood. Our recent computational and experimental study of cell-cycle regulator p27 (Ganguly et al., J. Mol. Biol. (2012)) demonstrated that long-range electrostatic forces exerted on enriched charges of IDPs could accelerate protein-protein encounter via “electrostatic steering” and at the same time promote “folding-competent” encounter topologies to enhance the efficiency of IDP folding upon encounter. Here, we further investigated the coupled binding and folding mechanisms and the roles of electrostatic forces in the formation of three IDP complexes with more complex folded topologies. The surface electrostatic potentials of these complexes lack prominent features like those observed for the p27/Cdk2/cyclin A complex to directly suggest the ability of electrostatic forces to facilitate folding upon encounter. Nonetheless, similar electrostatically accelerated encounter and folding mechanisms were consistently predicted for all three complexes using topology-based coarse-grained simulations. Together with our previous analysis of charge distributions in known IDP complexes, our results support a prevalent role of electrostatic interactions in promoting efficient coupled binding and folding for facile specific recognition. These results also suggest that there is likely a co-evolution of IDP folded topology, charge characteristics, and coupled binding and folding mechanisms, driven at least partially by the need to achieve fast association kinetics for cellular signaling and regulation. PMID:24278008

How Robust Is the Mechanism of Folding-Upon-Binding for an Intrinsically Disordered Protein?

PubMed

Bonetti, Daniela; Troilo, Francesca; Brunori, Maurizio; Longhi, Sonia; Gianni, Stefano

2018-04-24

The mechanism of interaction of an intrinsically disordered protein (IDP) with its physiological partner is characterized by a disorder-to-order transition in which a recognition and a binding step take place. Even if the mechanism is quite complex, IDPs tend to bind their partner in a cooperative manner such that it is generally possible to detect experimentally only the disordered unbound state and the structured complex. The interaction between the disordered C-terminal domain of the measles virus nucleoprotein (N TAIL ) and the X domain (XD) of the viral phosphoprotein allows us to detect and quantify the two distinct steps of the overall reaction. Here, we analyze the robustness of the folding of N TAIL upon binding to XD by measuring the effect on both the folding and binding steps of N TAIL when the structure of XD is modified. Because it has been shown that wild-type XD is structurally heterogeneous, populating an on-pathway intermediate under native conditions, we investigated the binding to 11 different site-directed variants of N TAIL of one particular variant of XD (I504A XD) that populates only the native state. Data reveal that the recognition and the folding steps are both affected by the structure of XD, indicating a highly malleable pathway. The experimental results are briefly discussed in the light of previous experiments on other IDPs. Copyright © 2018 Biophysical Society. Published by Elsevier Inc. All rights reserved.

Modulation of attentional processing by deep brain stimulation of the pedunculopontine nucleus region in patients with parkinsonian disorders.

PubMed

Fischer, Julia; Schwiecker, Kati; Bittner, Verena; Heinze, Hans-Jochen; Voges, Jürgen; Galazky, Imke; Zaehle, Tino

2015-07-01

Low-frequency electrical stimulation of the pedunculopontine nucleus (PPN) is a therapeutic approach aiming to improve motor symptoms such as freezing of gate and postural instability in parkinsonian disorders. Because the PPN is a component of the reticular activating system, we tested whether PPN stimulation directly affects attention and consciousness. Eight patients with parkinsonian disorders and implanted with electrodes in the bilateral PPN underwent computerized assessment of attention. Performance in 3 standard reaction time (RT) tasks was assessed at 5 different stimulation frequencies in 5 consecutive sessions. Stimulation of the PPN at low (8 Hz) and therapeutic (20 Hz) frequencies led to a significant improvement of performance in a simple RT task. Patients' RTs were significantly faster at stimulation frequencies of 8 Hz and 20 Hz relative to no stimulation. Stimulation did not affect patients' performance in more complex attentional tasks. Low-frequent stimulation of PPN improves basal attentional processing in patients with parkinsonian disorders, leading to an improved tonic alertness. As successful performance in this task requires the intrinsic ability to build up and keep a certain level of attention, this might be interpreted as attentional augmentation related to stimulation features. Stimulation had no effect on more complex attentional processing. Our results suggest an influence of the PPN on certain aspects of attention, supporting attentional augmentation as one possible mechanism to improve motor action and gait in patients with parkinsonian disorders. (c) 2015 APA, all rights reserved).

Mutsβ generates both expansions and contractions in a mouse model of the Fragile X-associated disorders

PubMed Central

Zhao, Xiao-Nan; Kumari, Daman; Gupta, Shikha; Wu, Di; Evanitsky, Maya; Yang, Wei; Usdin, Karen

2015-01-01

Fragile X-associated disorders are Repeat Expansion Diseases that result from expansion of a CGG/CCG-repeat in the FMR1 gene. Contractions of the repeat tract also occur, albeit at lower frequency. However, these contractions can potentially modulate disease symptoms or generate an allele with repeat numbers in the normal range. Little is known about the expansion mechanism and even less about contractions. We have previously demonstrated that the mismatch repair (MMR) protein MSH2 is required for expansions in a mouse model of these disorders. Here, we show that MSH3, the MSH2-binding partner in the MutSβ complex, is required for 98% of germ line expansions and all somatic expansions in this model. In addition, we provide evidence for two different contraction mechanisms that operate in the mouse model, a MutSβ-independent one that generates small contractions and a MutSβ-dependent one that generates larger ones. We also show that MutSβ complexes formed with the repeats have altered kinetics of ATP hydrolysis relative to complexes with bona fide MMR substrates and that MutSβ increases the stability of the CCG-hairpins at physiological temperatures. These data may have important implications for our understanding of the mechanism(s) of repeat instability and for the role of MMR proteins in this process. PMID:26420841

Schizophrenia: an integrative approach to modelling a complex disorder

PubMed Central

Robertson, George S.; Hori, Sarah E.; Powell, Kelly J.

2006-01-01

The discovery of candidate susceptibility genes for schizophrenia and the generation of mice lacking proteins that reproduce biochemical processes that are disrupted in this mental illness offer unprecedented opportunities for improved modelling of this complex disorder. Several lines of evidence indicate that obstetrical complications, as well as fetal or neonatal exposure to viral infection, are predisposing events for some forms of schizophrenia. These environmental events can be modelled in animals, resulting in some of the characteristic features of schizophrenia; however, animal models have yet to be developed that encompass both environmental and genetic aspects of this mental illness. A large number of candidate schizophrenia susceptibility genes have been identified that encode proteins implicated in the regulation of synaptic plasticity, neurotransmission, neuronal migration, cell adherence, signal transduction, energy metabolism and neurite outgrowth. In support of the importance of these processes in schizophrenia, mice that have reduced levels or completely lack proteins that control glutamatergic neurotransmission, neuronal migration, cell adherence, signal transduction, neurite outgrowth and synaptic plasticity display many features reminiscent of schizophrenia. In the present review, we discuss strategies for modelling schizophrenia that involve treating mice that bear these mutations in a variety of ways to better model both environmental and genetic factors responsible for this complex mental illness according to a “two-hit hypothesis.” Because rodents are able to perform complex cognitive tasks using odour but not visual or auditory cues, we hypothesize that olfactory-based tests of cognitive performance should be used to search for novel therapeutics that ameliorate the cognitive deficits that are a feature of this devastating mental disorder. PMID:16699601

Individuals with bipolar disorder and their relationship with the criminal justice system: a critical review.

PubMed

Fovet, Thomas; Geoffroy, Pierre Alexis; Vaiva, Guillaume; Adins, Catherine; Thomas, Pierre; Amad, Ali

2015-04-01

Bipolar disorder is a severe and prevalent psychiatric disease. Poor outcomes include a high frequency of criminal acts, imprisonments, and repeat offenses. This critical review of the international literature examined several aspects of the complex relationship between individuals with bipolar disorder and the criminal justice system: risk factors for criminal acts, features of bipolar patients' incarceration, and their postrelease trajectories. Publications were obtained from the PubMed and Google Scholar electronic databases by using the following MeSH headings: prison, forensic psychiatry, criminal law, crime, and bipolar disorder. Among patients with bipolar disorder, the frequency of violent criminal acts is higher than in the general population (odds ratio [OR]=2.8, 95% confidence interval [CI]=1.8-4.3). The frequency is higher among patients with bipolar disorder and a comorbid substance use disorder than among those without either disorder (OR=10.1, CI=5.3-19.2). As a result, the prevalence of bipolar disorder among prisoners is high (2%-7%). In prison, patients' bipolar disorder symptoms can complicate their relationship with prison administrators, leading to an increased risk of multiple incarcerations. Moreover, the risk of suicide increases for these prisoners. Criminal acts are common among patients with bipolar disorder and are often associated with problems such as addiction. Thus it is important to improve the diagnosis and treatment of inmates with bipolar disorder.

Use of atypical antipsychotics for treatment-resistant major depressive disorder.

PubMed

Papakostas, George I; Shelton, Richard C

2008-12-01

Despite the progressive increase in the number of pharmacologic agents with potential antidepressant activity, many patients suffering from major depressive disorder (MDD) continue to be symptomatic. Clearly, an urgent need exists to develop safer, better tolerated, and more effective treatments for MDD. Use of atypical antipsychotic agents as adjunctive treatment for treatment-resistant MDD (TRD) represents one such effort toward novel pharmacotherapy development. Atypical antipsychotic agents have been hypothesized to be beneficial in treating mood disorders, including TRD, as a result of their complex mechanisms of action. After an initial series of positive case reports, series, and small clinical trials, subsequent larger-scale projects have yielded conflicting results. However, more recently, larger-scale clinical trials have supported the effectiveness of at least some of these medications. This review summarizes the existing data regarding the effectiveness of these medications in treating TRD, including biochemical rationale and clinical data.

Characterization of the Pathological and Biochemical Markers that Correlate to the Clinical Features of Autism

DTIC Science & Technology

2011-10-01

to oxidative stress and abnormal brain energy metabolism in autism . Autism spectrum disorders (ASDs) are complex neurodevelopmental disorders. The...heterogeneous disorder, belonging to a group of neurodevelopmental disorders, known as the autism spec- trum disorders (ASDs) that include Asperger...Postmortem assessments of the brains of individuals with autism have unveiled early neurodevelop - mental alterations, including reduced programed cell

Current limitations of SNP data from the public domain for studies of complex disorders: a test for ten candidate genes for obesity and osteoporosis.

PubMed

Dvornyk, Volodymyr; Long, Ji-Rong; Xiong, Dong-Hai; Liu, Peng-Yuan; Zhao, Lan-Juan; Shen, Hui; Zhang, Yuan-Yuan; Liu, Yong-Jun; Rocha-Sanchez, Sonia; Xiao, Peng; Recker, Robert R; Deng, Hong-Wen

2004-02-25

Public SNP databases are frequently used to choose SNPs for candidate genes in the association and linkage studies of complex disorders. However, their utility for such studies of diseases with ethnic-dependent background has never been evaluated. To estimate the accuracy and completeness of SNP public databases, we analyzed the allele frequencies of 41 SNPs in 10 candidate genes for obesity and/or osteoporosis in a large American-Caucasian sample (1,873 individuals from 405 nuclear families) by PCR-invader assay. We compared our results with those from the databases and other published studies. Of the 41 SNPs, 8 were monomorphic in our sample. Twelve were reported for the first time for Caucasians and the other 29 SNPs in our sample essentially confirmed the respective allele frequencies for Caucasians in the databases and previous studies. The comparison of our data with other ethnic groups showed significant differentiation between the three major world ethnic groups at some SNPs (Caucasians and Africans differed at 3 of the 18 shared SNPs, and Caucasians and Asians differed at 13 of the 22 shared SNPs). This genetic differentiation may have an important implication for studying the well-known ethnic differences in the prevalence of obesity and osteoporosis, and complex disorders in general. A comparative analysis of the SNP data of the candidate genes obtained in the present study, as well as those retrieved from the public domain, suggests that the databases may currently have serious limitations for studying complex disorders with an ethnic-dependent background due to the incomplete and uneven representation of the candidate SNPs in the databases for the major ethnic groups. This conclusion attests to the imperative necessity of large-scale and accurate characterization of these SNPs in different ethnic groups.

Efficacy of Cognitive Processes in Young People with High-Functioning Autism Spectrum Disorder Using a Novel Visual Information-Processing Task

ERIC Educational Resources Information Center

Speirs, Samantha J.; Rinehart, Nicole J.; Robinson, Stephen R.; Tonge, Bruce J.; Yelland, Gregory W.

2014-01-01

Autism spectrum disorders (ASD) are characterised by a unique pattern of preserved abilities and deficits within and across cognitive domains. The Complex Information Processing Theory proposes this pattern reflects an altered capacity to respond to cognitive demands. This study compared how complexity induced by time constraints on processing…

Play Complexity and Toy Engagement in Preschoolers with Autism Spectrum Disorder: Do Girls and Boys Differ?

ERIC Educational Resources Information Center

Harrop, Clare; Green, Jonathan; Hudry, Kristelle

2017-01-01

While sex differences in play have been extensively observed in typical development, only a handful of studies have explored this phenomenon in depth with children with autism spectrum disorders. This study explored sex differences in play complexity and toy engagement within caregiver-child interaction samples for preschool-aged children (2-5…

The Social Living Complex: A New, All Day, Yearlong Intervention Model for Individuals with Autism Spectrum Disorder and Their Parents

ERIC Educational Resources Information Center

Doenyas, Ceymi

2016-01-01

We propose an unprecedented intervention for individuals with autism spectrum disorder (ASD) and their parents: the social living complex. Unlike existing social skills interventions, peer-mediated interventions here are not limited to the school/experiment duration and setting. Whereas other supported living services house adults with ASD only,…

Capacity Building: Evidence-Based Practice and Adolescents on the Autism Spectrum

ERIC Educational Resources Information Center

Rue, Hanna C.; Knox, Maria

2013-01-01

Empirical research in the treatment of autism spectrum disorders (ASDs) has resulted in the identification of numerous evidence-based interventions (EBIs). Adolescents with an ASD are faced with unique academic challenges, complex social environments, and physiological changes. They often require interventions to aid in acclimating to their…

Overcoming Executive Function Deficits with Students with ADHD

ERIC Educational Resources Information Center

Johnson, Joseph; Reid, Robert

2011-01-01

Academic problems are common among students with attention deficit hyperactivity disorder (ADHD). One reason for academic problems is the difficulties in executive functions (EF) that are necessary for complex goal-oriented behaviors. Students with ADHD often exhibit EF deficits and as a result have difficulties with tasks that require planning,…

Prader-Willi Syndrome. ARC Q&A #101-52.

ERIC Educational Resources Information Center

Arc, Arlington, TX.

This fact sheet uses a question-and-answer format to summarize what is known about Prader-Willi Syndrome (PWS), a complex genetic disorder resulting in short stature, mental retardation or learning disabilities, incomplete sexual development, characteristic behavior problems, low muscle tone, and an involuntary urge to eat constantly, which…

Free Energy and Virtual Reality in Neuroscience and Psychoanalysis: A Complexity Theory of Dreaming and Mental Disorder.

PubMed

Hopkins, Jim

2016-01-01

The main concepts of the free energy (FE) neuroscience developed by Karl Friston and colleagues parallel those of Freud's Project for a Scientific Psychology. In Hobson et al. (2014) these include an innate virtual reality generator that produces the fictive prior beliefs that Freud described as the primary process. This enables Friston's account to encompass a unified treatment-a complexity theory-of the role of virtual reality in both dreaming and mental disorder. In both accounts the brain operates to minimize FE aroused by sensory impingements-including interoceptive impingements that report compliance with biological imperatives-and constructs a representation/model of the causes of impingement that enables this minimization. In Friston's account (variational) FE equals complexity minus accuracy, and is minimized by increasing accuracy and decreasing complexity. Roughly the brain (or model) increases accuracy together with complexity in waking. This is mediated by consciousness-creating active inference-by which it explains sensory impingements in terms of perceptual experiences of their causes. In sleep it reduces complexity by processes that include both synaptic pruning and consciousness/virtual reality/dreaming in REM. The consciousness-creating active inference that effects complexity-reduction in REM dreaming must operate on FE-arousing data distinct from sensory impingement. The most relevant source is remembered arousals of emotion, both recent and remote, as processed in SWS and REM on "active systems" accounts of memory consolidation/reconsolidation. Freud describes these remembered arousals as condensed in the dreamwork for use in the conscious contents of dreams, and similar condensation can be seen in symptoms. Complexity partly reflects emotional conflict and trauma. This indicates that dreams and symptoms are both produced to reduce complexity in the form of potentially adverse (traumatic or conflicting) arousals of amygdala-related emotions. Mental disorder is thus caused by computational complexity together with mechanisms like synaptic pruning that have evolved for complexity-reduction; and important features of disorder can be understood in these terms. Details of the consilience among Freudian, systems consolidation, and complexity-reduction accounts appear clearly in the analysis of a single fragment of a dream, indicating also how complexity reduction proceeds by a process resembling Bayesian model selection.

Phenoxide and alkoxide complexes of Mg, Al and Zn, and their use for the ring-opening polymerization of ℇ-caprolactone with initiators of different natures.

PubMed

Minyaev, Mikhail E; Nifant'ev, Ilya E; Shlyakhtin, Andrey V; Ivchenko, Pavel V; Lyssenko, Konstantin A

2018-05-01

A new packing polymorph of bis(2,6-di-tert-butyl-4-methylphenolato-κO)bis(tetrahydrofuran-κO)magnesium, [Mg(C 15 H 23 O) 2 (C 4 H 8 O) 2 ] or Mg(BHT) 2 (THF) 2 , (BHT is the 2,6-di-tert-butyl-4-methylphenoxide anion and THF is tetrahydrofuran), (1), has the same space group (P2 1 ) as the previously reported modification [Nifant'ev et al. (2017d). Dalton Trans. 46, 12132-12146], but contains three crystallographically independent molecules instead of one. The structure of (1) exhibits rotational disorder of the tert-butyl groups and positional disorder of a THF ligand. The complex of bis(2,6-di-tert-butyl-4-methylphenolato-κO)bis(μ 2 -ethyl glycolato-κ 2 O,O':κO)dimethyldialuminium, [Al 2 (CH 3 ) 2 (C 4 H 7 O 3 ) 2 (C 15 H 23 O) 2 ] or [(BHT)AlMe(OCH 2 COOEt)] 2 , (2), is a dimer located on an inversion centre and has an Al 2 O 2 rhomboid core. The 2-ethoxy-2-oxoethanolate ligand (OCH 2 COOEt) displays a μ 2 -κ 2 O,O':κO semi-bridging coordination mode, forming a five-membered heteronuclear Al-O-C-C-O ring. The same ligand exhibits positional disorder of the terminal methyl group. The redetermined structure of the heptanuclear complex octakis(μ 3 -benzyloxo-κO:κO:κO)hexaethylheptazinc, [Zn 7 (C 2 H 5 ) 6 (C 7 H 7 O) 8 ] or [Zn 7 (OCH 2 Ph) 8 Et 6 ], (3), possesses a bicubic Zn 7 O 8 core located at an inversion centre and demonstrates positional disorder of one crystallographically independent phenyl group. Cambridge Structural Database surveys are given for complexes structurally analogous to (2) and (3). Complexes (2) and (3), as well as derivatives of (1), are of interest as catalysts for the ring-opening polymerization of ℇ-caprolactone, and polymerization results are reported.

Molecular Level Design Principle behind Optimal Sizes of Photosynthetic LH2 Complex: Taming Disorder through Cooperation of Hydrogen Bonding and Quantum Delocalization.

PubMed

Jang, Seogjoo; Rivera, Eva; Montemayor, Daniel

2015-03-19

The light harvesting 2 (LH2) antenna complex from purple photosynthetic bacteria is an efficient natural excitation energy carrier with well-known symmetric structure, but the molecular level design principle governing its structure-function relationship is unknown. Our all-atomistic simulations of nonnatural analogues of LH2 as well as those of a natural LH2 suggest that nonnatural sizes of LH2-like complexes could be built. However, stable and consistent hydrogen bonding (HB) between bacteriochlorophyll and the protein is shown to be possible only near naturally occurring sizes, leading to significantly smaller disorder than for nonnatural ones. Extensive quantum calculations of intercomplex exciton transfer dynamics, sampled for a large set of disorder, reveal that taming the negative effect of disorder through a reliable HB as well as quantum delocalization of the exciton is a critical mechanism that makes LH2 highly functional, which also explains why the natural sizes of LH2 are indeed optimal.

Multivalency regulates activity in an intrinsically disordered transcription factor

PubMed Central

Clark, Sarah; Myers, Janette B; King, Ashleigh; Fiala, Radovan; Novacek, Jiri; Pearce, Grant; Heierhorst, Jörg; Reichow, Steve L

2018-01-01

The transcription factor ASCIZ (ATMIN, ZNF822) has an unusually high number of recognition motifs for the product of its main target gene, the hub protein LC8 (DYNLL1). Using a combination of biophysical methods, structural analysis by NMR and electron microscopy, and cellular transcription assays, we developed a model that proposes a concerted role of intrinsic disorder and multiple LC8 binding events in regulating LC8 transcription. We demonstrate that the long intrinsically disordered C-terminal domain of ASCIZ binds LC8 to form a dynamic ensemble of complexes with a gradient of transcriptional activity that is inversely proportional to LC8 occupancy. The preference for low occupancy complexes at saturating LC8 concentrations with both human and Drosophila ASCIZ indicates that negative cooperativity is an important feature of ASCIZ-LC8 interactions. The prevalence of intrinsic disorder and multivalency among transcription factors suggests that formation of heterogeneous, dynamic complexes is a widespread mechanism for tuning transcriptional regulation. PMID:29714690

Priorities for autism spectrum disorder risk communication and ethics.

PubMed

Yudell, Michael; Tabor, Holly K; Dawson, Geraldine; Rossi, John; Newschaffer, Craig

2013-11-01

Autism spectrum disorders are an issue of increasing public health significance. The incidence of autism spectrum disorders has been increasing in recent years, and they are associated with significant personal and financial impacts for affected persons and their families. In recent years, a large number of scientific studies have been undertaken, which investigate genetic and environmental risk factors for autism, with more studies underway. At present, much remains unknown regarding autism spectrum disorder risk factors, but the emerging picture of causation is in many cases complex, with multiple genes and gene-environment interactions being at play. The complexity and uncertainty surrounding autism spectrum disorder risk factors raise a number of questions regarding the ethical considerations that should be taken into account when undertaking autism spectrum disorder risk communication. At present, however, little has been written regarding autism spectrum disorder risk communication and ethics. This article summarizes the findings of a recent conference investigating ethical considerations and policy recommendations in autism spectrum disorder risk communication, which to the authors' knowledge is the first of its kind. Here, the authors discuss a number of issues, including uncertainty; comprehension; inadvertent harm; justice; and the appropriate roles of clinicians, scientists, and the media in autism spectrum disorder risk communication.

Attentional but not Pre-Attentive Neural Measures of Auditory Discrimination are Atypical in Children with Developmental Language Disorder

PubMed Central

Kornilov, Sergey A.; Landi, Nicole; Rakhlin, Natalia; Fang, Shin-Yi; Grigorenko, Elena L.; Magnuson, James S.

2015-01-01

We examined neural indices of pre-attentive phonological and attentional auditory discrimination in children with developmental language disorder (DLD, n=23) and typically developing (n=16) peers from a geographically isolated Russian-speaking population with an elevated prevalence of DLD. Pre-attentive phonological MMN components were robust and did not differ in two groups. Children with DLD showed attenuated P3 and atypically distributed P2 components in the attentional auditory discrimination task; P2 and P3 amplitudes were linked to working memory capacity, development of complex syntax, and vocabulary. The results corroborate findings of reduced processing capacity in DLD and support a multifactorial view of the disorder. PMID:25350759

Fine-scale mapping of a locus for severe bipolar mood disorder on chromosome 18p11.3 in the Costa Rican population

PubMed Central

McInnes, L. Alison; Service, Susan K.; Reus, Victor I.; Barnes, Glenn; Charlat, Olga; Jawahar, Satya; Lewitzky, Steve; Yang, Qing; Duong, Quyen; Spesny, Mitzi; Araya, Carmen; Araya, Xinia; Gallegos, Alvaro; Meza, Luis; Molina, Julio; Ramirez, Rolando; Mendez, Roxana; Silva, Sandra; Fournier, Eduardo; Batki, Steven L.; Mathews, Carol A.; Neylan, Thomas; Glatt, Charles E.; Escamilla, Michael A.; Luo, David; Gajiwala, Paresh; Song, Terry; Crook, Stephen; Nguyen, Jasmine B.; Roche, Erin; Meyer, Joanne M.; Leon, Pedro; Sandkuijl, Lodewijk A.; Freimer, Nelson B.; Chen, Hong

2001-01-01

We have searched for genes predisposing to bipolar disorder (BP) by studying individuals with the most extreme form of the affected phenotype, BP-I, ascertained from the genetically isolated population of the Central Valley of Costa Rica (CVCR). The results of a previous linkage analysis on two extended CVCR BP-I pedigrees, CR001 and CR004, and of linkage disequilibrium (LD) analyses of a CVCR population sample of BP-I patients implicated a candidate region on 18p11.3. We further investigated this region by creating a physical map and developing 4 new microsatellite and 26 single-nucleotide polymorphism markers for typing in the pedigree and population samples. We report the results of fine-scale association analyses in the population sample, as well as evaluation of haplotypes in pedigree CR001. Our results suggest a candidate region containing six genes but also highlight the complexities of LD mapping of common disorders. PMID:11572994

Dopamine and anorexia nervosa.

PubMed

Södersten, P; Bergh, C; Leon, M; Zandian, M

2016-01-01

We have suggested that reduced food intake increases the risk for anorexia nervosa by engaging mesolimbic dopamine neurons, thereby initially rewarding dieting. Recent fMRI studies have confirmed that dopamine neurons are activated in anorexia nervosa, but it is not clear whether this response is due to the disorder or to its resulting nutritional deficit. When the body senses the shortage of nutrients, it rapidly shifts behavior toward foraging for food as a normal physiological response and the mesolimbic dopamine neurons may be involved in that process. On the other hand, the altered dopamine status of anorexics has been suggested to result from a brain abnormality that underlies their complex emotional disorder. We suggest that the outcomes of the treatments that emerge from that perspective remain poor because they target the mental symptoms that are actually the consequences of the food deprivation that accompanies anorexia. On the other hand, a method that normalizes the disordered eating behavior of anorexics results in much better physiological, behavioral, and emotional outcomes. Copyright © 2015 Elsevier Ltd. All rights reserved.

The frequency modulated auditory evoked response (FMAER), a technical advance for study of childhood language disorders: cortical source localization and selected case studies

PubMed Central

2013-01-01

Background Language comprehension requires decoding of complex, rapidly changing speech streams. Detecting changes of frequency modulation (FM) within speech is hypothesized as essential for accurate phoneme detection, and thus, for spoken word comprehension. Despite past demonstration of FM auditory evoked response (FMAER) utility in language disorder investigations, it is seldom utilized clinically. This report's purpose is to facilitate clinical use by explaining analytic pitfalls, demonstrating sites of cortical origin, and illustrating potential utility. Results FMAERs collected from children with language disorders, including Developmental Dysphasia, Landau-Kleffner syndrome (LKS), and autism spectrum disorder (ASD) and also normal controls - utilizing multi-channel reference-free recordings assisted by discrete source analysis - provided demonstratrions of cortical origin and examples of clinical utility. Recordings from inpatient epileptics with indwelling cortical electrodes provided direct assessment of FMAER origin. The FMAER is shown to normally arise from bilateral posterior superior temporal gyri and immediate temporal lobe surround. Childhood language disorders associated with prominent receptive deficits demonstrate absent left or bilateral FMAER temporal lobe responses. When receptive language is spared, the FMAER may remain present bilaterally. Analyses based upon mastoid or ear reference electrodes are shown to result in erroneous conclusions. Serial FMAER studies may dynamically track status of underlying language processing in LKS. FMAERs in ASD with language impairment may be normal or abnormal. Cortical FMAERs can locate language cortex when conventional cortical stimulation does not. Conclusion The FMAER measures the processing by the superior temporal gyri and adjacent cortex of rapid frequency modulation within an auditory stream. Clinical disorders associated with receptive deficits are shown to demonstrate absent left or bilateral responses. Serial FMAERs may be useful for tracking language change in LKS. Cortical FMAERs may augment invasive cortical language testing in epilepsy surgical patients. The FMAER may be normal in ASD and other language disorders when pathology spares the superior temporal gyrus and surround but presumably involves other brain regions. Ear/mastoid reference electrodes should be avoided and multichannel, reference free recordings utilized. Source analysis may assist in better understanding of complex FMAER findings. PMID:23351174

Individualized Levels System and Systematic Stimulus Pairing to Reduce Multiply Controlled Aggression of a Child With Autism Spectrum Disorder.

PubMed

Randall, Kayla R; Lambert, Joseph M; Matthews, Mary P; Houchins-Juarez, Nealetta J

2018-05-01

Research has shown that physical aggression is common in individuals with autism spectrum disorder (ASD). Interventions for multiply controlled aggression may be complex and difficult to implement with fidelity. As a result, the probability of treatment efficacy for this class of behavior may suffer. We designed an individualized levels system to reduce the physical aggression of an 11-year-old female with ASD. We then employed a systematic stimulus pairing procedure to facilitate generalization. Results suggest individualized levels systems can suppress multiply controlled aggression and that systematic stimulus pairing is an effective way to transfer treatment effects from trained therapists to caregivers.

Combined prevalence of inherited skeletal disorders in dog breeds in Belgium.

PubMed

Coopman, F; Broeckx, B; Verelst, E; Deforce, D; Saunders, J; Duchateau, L; Verhoeven, G

2014-01-01

Canine hip dysplasia (CHD), canine elbow dysplasia (CED), and humeral head osteochondrosis (HHOC) are inherited traits with uneven incidence in dog breeds. Knowledge of the combined prevalence of these three disorders is necessary to estimate the effect of the currently applied breeding strategies, in order to improve the genetic health of the population. Official screening results of the Belgian National Committee for Inherited Skeletal Disorders (NCSID) revealed that an average of 31.8% (CHD, CED, or both; n = 1273 dogs) and 47.2% (CHD, CED, HHOC, or a combination of these three diseases; n = 250 dogs) of dogs are mildly to severely affected by at least one skeletal disorder. According to the current breeding recommendations in some dog breeds in Belgium, these animals should be restricted (mild signs) or excluded (moderate to severe signs) from breeding. The introduction of genetic parameters, such as estimated breeding values, might create a better approach to gradually reduce the incidence of these complex inherited joint disorders, without compromising genetic population health.

Correlation of chemical shifts predicted by molecular dynamics simulations for partially disordered proteins.

PubMed

Karp, Jerome M; Eryilmaz, Ertan; Erylimaz, Ertan; Cowburn, David

2015-01-01

There has been a longstanding interest in being able to accurately predict NMR chemical shifts from structural data. Recent studies have focused on using molecular dynamics (MD) simulation data as input for improved prediction. Here we examine the accuracy of chemical shift prediction for intein systems, which have regions of intrinsic disorder. We find that using MD simulation data as input for chemical shift prediction does not consistently improve prediction accuracy over use of a static X-ray crystal structure. This appears to result from the complex conformational ensemble of the disordered protein segments. We show that using accelerated molecular dynamics (aMD) simulations improves chemical shift prediction, suggesting that methods which better sample the conformational ensemble like aMD are more appropriate tools for use in chemical shift prediction for proteins with disordered regions. Moreover, our study suggests that data accurately reflecting protein dynamics must be used as input for chemical shift prediction in order to correctly predict chemical shifts in systems with disorder.

[Willingness of Psychotherapists in Private Practice to Treat Patients With Complex Post-Traumatic Stress and Dissociative Disorders].

PubMed

Schnell, T; von Katte, S; Gast, U

2015-09-01

Analyses of patient care with severe mental disorders. Psychotherapists in private praxis were interviewed about their willingness to treat patients with a range of diagnoses in the context of post-traumatic disorders. Therapists were found more willing to treat "less severe" disorders, independent of years in practice, school of psychotherapy, a rural or urban practice setting. Therapists criticized the quality of their training and the health insurance review process. Therapists are generally willing to treat patients with severe mental disorders, but experience limits of competency attributed to training deficits. They further experience the bureaucratic procedures of the health insurance review process as barriers to accepting these patients into treatment.These results indicate that recently developed concepts of psychotherapy for these patient groups should be more intensively integrated into the existing training curricula. Furthermore, a simplified health insurance review process ought to be considered. © Georg Thieme Verlag KG Stuttgart · New York.

Electroencephalogram complexity analysis in children with attention-deficit/hyperactivity disorder during a visual cognitive task.

PubMed

Zarafshan, Hadi; Khaleghi, Ali; Mohammadi, Mohammad Reza; Moeini, Mahdi; Malmir, Nastaran

2016-01-01

The aim of this study was to investigate electroencephalogram (EEG) dynamics using complexity analysis in children with attention-deficit/hyperactivity disorder (ADHD) compared with healthy control children when performing a cognitive task. Thirty 7-12-year-old children meeting Diagnostic and Statistical Manual of Mental Disorders-Fifth Edition (DSM-5) criteria for ADHD and 30 healthy control children underwent an EEG evaluation during a cognitive task, and Lempel-Ziv complexity (LZC) values were computed. There were no significant differences between ADHD and control groups on age and gender. The mean LZC of the ADHD children was significantly larger than healthy children over the right anterior and right posterior regions during the cognitive performance. In the ADHD group, complexity of the right hemisphere was higher than that of the left hemisphere, but the complexity of the left hemisphere was higher than that of the right hemisphere in the normal group. Although fronto-striatal dysfunction is considered conclusive evidence for the pathophysiology of ADHD, our arithmetic mental task has provided evidence of structural and functional changes in the posterior regions and probably cerebellum in ADHD.

Targeting the FKBP51/GR/Hsp90 Complex to Identify Functionally Relevant Treatments for Depression and PTSD.

PubMed

Sabbagh, Jonathan J; Cordova, Ricardo A; Zheng, Dali; Criado-Marrero, Marangelie; Lemus, Andrea; Li, Pengfei; Baker, Jeremy D; Nordhues, Bryce A; Darling, April L; Martinez-Licha, Carlos; Rutz, Daniel A; Patel, Shreya; Buchner, Johannes; Leahy, James W; Koren, John; Dickey, Chad A; Blair, Laura J

2018-06-19

Genetic and epigenetic alterations in FK506-binding protein 5 ( FKBP5) have been associated with increased risk for psychiatric disorders, including post-traumatic stress disorder (PTSD). Some of these common variants can increase the expression of FKBP5, the gene that encodes FKBP51. Excess FKBP51 promotes hypothalamic-pituitary-adrenal (HPA) axis dysregulation through altered glucocorticoid receptor (GR) signaling. Thus, we hypothesized that GR activity could be restored by perturbing FKBP51. Here, we screened 1280 pharmacologically active compounds and identified three compounds that rescued FKBP51-mediated suppression of GR activity without directly activating GR. One of the three compounds, benztropine mesylate, disrupted the association of FKBP51 with the GR/Hsp90 complex in vitro. Moreover, we show that removal of FKBP51 from this complex by benztropine restored GR localization in ex vivo brain slices and primary neurons from mice. In conclusion, we have identified a novel disruptor of the FKBP51/GR/Hsp90 complex. Targeting this complex may be a viable approach to developing treatments for disorders related to aberrant FKBP51 expression.

Discontinuous Patterns of Brain Activation in the Psychotherapy Process of Obsessive-Compulsive Disorder: Converging Results from Repeated fMRI and Daily Self-Reports

PubMed Central

Schiepek, Günter; Tominschek, Igor; Heinzel, Stephan; Aigner, Martin; Dold, Markus; Unger, Annemarie; Lenz, Gerhard; Windischberger, Christian; Moser, Ewald; Plöderl, Martin; Lutz, Jürgen; Meindl, Thomas; Zaudig, Michael; Pogarell, Oliver; Karch, Susanne

2013-01-01

This study investigates neuronal activation patterns during the psychotherapeutic process, assuming that change dynamics undergo critical instabilities and discontinuous transitions. An internet-based system was used to collect daily self-assessments during inpatient therapies. A dynamic complexity measure was applied to the resulting time series. Critical phases of the change process were indicated by the maxima of the varying complexity. Repeated functional magnetic resonance imaging (fMRI) measurements were conducted over the course of the therapy. The study was realized with 9 patients suffering from obsessive-compulsive disorder (subtype: washing/contamination fear) and 9 matched healthy controls. For symptom-provocative stimulation individualized pictures from patients’ personal environments were used. The neuronal responses to these disease-specific pictures were compared to the responses during standardized disgust-provoking and neutral pictures. Considerably larger neuronal changes in therapy-relevant brain areas (cingulate cortex/supplementary motor cortex, bilateral dorsolateral prefrontal cortex, bilateral insula, bilateral parietal cortex, cuneus) were observed during critical phases (order transitions), as compared to non-critical phases, and also compared to healthy controls. The data indicate that non-stationary changes play a crucial role in the psychotherapeutic process supporting self-organization and complexity models of therapeutic change. PMID:23977168

Peroxisome Biogenesis Disorders: Biological, Clinical and Pathophysiological Perspectives

ERIC Educational Resources Information Center

Braverman, Nancy E.; D'Agostino, Maria Daniela; MacLean, Gillian E.

2013-01-01

The peroxisome biogenesis disorders (PBD) are a heterogeneous group of autosomal recessive disorders in which peroxisome assembly is impaired, leading to multiple peroxisome enzyme deficiencies, complex developmental sequelae and progressive disabilities. Mammalian peroxisome assembly involves the protein products of 16 "PEX" genes;…

Bipolar Disorder in Adolescence: Diagnosis and Treatment.

ERIC Educational Resources Information Center

Wilkinson, Great Buyck; Taylor, Priscilla; Holt, Jan R.

2002-01-01

Due to developmental issues and overlapping symptoms with other disorders, diagnosing bipolar disorder in adolescents is often a confusing and complex process. This article highlights diagnostic criteria, symptoms and behaviors, and the differential diagnosis process. Treatment options are also discussed. (Contains 17 references.) (GCP)

Deciphering the Dynamic Interaction Profile of an Intrinsically Disordered Protein by NMR Exchange Spectroscopy.

PubMed

Delaforge, Elise; Kragelj, Jaka; Tengo, Laura; Palencia, Andrés; Milles, Sigrid; Bouvignies, Guillaume; Salvi, Nicola; Blackledge, Martin; Jensen, Malene Ringkjøbing

2018-01-24

Intrinsically disordered proteins (IDPs) display a large number of interaction modes including folding-upon-binding, binding without major structural transitions, or binding through highly dynamic, so-called fuzzy, complexes. The vast majority of experimental information about IDP binding modes have been inferred from crystal structures of proteins in complex with short peptides of IDPs. However, crystal structures provide a mainly static view of the complexes and do not give information about the conformational dynamics experienced by the IDP in the bound state. Knowledge of the dynamics of IDP complexes is of fundamental importance to understand how IDPs engage in highly specific interactions without concomitantly high binding affinity. Here, we combine rotating-frame R 1ρ , Carr-Purcell-Meiboom Gill relaxation dispersion as well as chemical exchange saturation transfer to decipher the dynamic interaction profile of an IDP in complex with its partner. We apply the approach to the dynamic signaling complex formed between the mitogen-activated protein kinase (MAPK) p38α and the intrinsically disordered regulatory domain of the MAPK kinase MKK4. Our study demonstrates that MKK4 employs a subtle combination of interaction modes in order to bind to p38α, leading to a complex displaying significantly different dynamics across the bound regions.

Impact of environment on dynamics of exciton complexes in a WS2 monolayer

NASA Astrophysics Data System (ADS)

Jakubczyk, Tomasz; Nogajewski, Karol; Molas, Maciej R.; Bartos, Miroslav; Langbein, Wolfgang; Potemski, Marek; Kasprzak, Jacek

2018-07-01

Scientific curiosity to uncover original optical properties and functionalities of atomically thin semiconductors, stemming from unusual Coulomb interactions in the two-dimensional geometry and multi-valley band structure, drives the research on monolayers of transition metal dichalcogenides (TMDs). While recent works ascertained the exotic energetic schemes of exciton complexes in TMDs, we here infer their unusual coherent dynamics occurring on subpicosecond time scale. The dynamics is largely affected by the disorder landscape on the submicron scale, thus can be uncovered using four-wave mixing in the frequency domain, which enables microscopic investigations and imaging. Focusing on a WS2 monolayer, we observe that exciton coherence is lost primarily due to interaction with phonons and relaxation processes towards optically dark excitonic states. Notably, when temperature is low and disorder weak, excitons large coherence volume results in enhanced oscillator strength, allowing to reach the regime of radiatively limited dephasing. Additionally, we observe long valley coherence for the negatively charged exciton complex. We therefore elucidate the crucial role of exciton environment in the TMDs on its dynamics and show that revealed mechanisms are ubiquitous within this family.

The Neuroanatomy of Autism Spectrum Disorder: An Overview of Structural Neuroimaging Findings and Their Translatability to the Clinical Setting

ERIC Educational Resources Information Center

Ecker, Christine

2017-01-01

Autism spectrum disorder is a complex neurodevelopmental disorder, which is accompanied by differences in brain anatomy, functioning and brain connectivity. Due to its neurodevelopmental character, and the large phenotypic heterogeneity among individuals on the autism spectrum, the neurobiology of autism spectrum disorder is inherently difficult…

Eating Disorders among Athletes: Public Policy To Promote Social and Individual Behavioral Change.

ERIC Educational Resources Information Center

Moriarty, Dick; Moriarty, Mary

Eating disorders are a complex physiological, psychological, and social illness. Since teachers and coaches should know the signs of eating disorders, some of the ways in which educators can recognize or prevent eating disorders are presented in this paper. Emphasis is placed on teachers and coaches familiarizing themselves with the five…

Comparing Service Use and Costs among Adolescents with Autism Spectrum Disorders, Special Needs and Typical Development

ERIC Educational Resources Information Center

Barrett, Barbara; Mosweu, Iris; Jones, Catherine R. G.; Charman, Tony; Baird, Gillian; Simonoff, Emily; Pickles, Andrew; Happé, Francesca; Byford, Sarah

2015-01-01

Autism spectrum disorder is a complex condition that requires specialised care. Knowledge of the costs of autism spectrum disorder, especially in comparison with other conditions, may be useful to galvanise policymakers and leverage investment in education and intervention to mitigate aspects of autism spectrum disorder that negatively impact…

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.

An introduction to the clinical phenomenology of Tourette syndrome.

PubMed

Martino, Davide; Madhusudan, Namrata; Zis, Panagiotis; Cavanna, Andrea E

2013-01-01

Tourette syndrome (TS) is the primary tic disorder that reaches most commonly medical attention and monitoring, with an estimated prevalence close to 1% between 5 and 18 years of age. Motor and phonic tics are the core features of TS. In addition to their well-characterized phenomenology, tics display a peculiar variability over time, which is strongly influenced by a variety of contextual factors. The sensory phenomena of TS are increasingly recognized as another crucial symptom of TS and consist of premonitory urges and somatic hypersensitivity. A relevant proportion of patients with TS display complex, tic-like, repetitive behaviors that include echophenomena, coprophenomena, and nonobscene socially inappropriate behaviors (NOSIBs). The burden of behavioral comorbidities is very important in determining the degree of disability of TS patients. Only a small minority of TS patients presents exclusively with a tic disorder. Obsessive-compulsive symptoms and related disorder (OCD) are common in TS, and the clinical distinction between compulsions and complex tics may be difficult in some cases. Probably, the presence of comorbid attention deficit hyperactivity disorder (ADHD) is the main determinant of cognitive dysfunction in TS patients and influences heavily also the risk of developing disruptive behaviors. Affective disorders, impulse control disorders, autism spectrum disorders, and personality disorders complete the wide psychopathological spectrum of this condition, but have been less investigated than OCD and ADHD. The complexity of the Tourette spectrum has been confirmed by cluster and factor analytical approaches, and is likely to inform the study of the genetic basis of this disorder, as well as future reappraisal of its nosography, with the development of novel clinical subtypes. © 2013 Elsevier Inc. All rights reserved.

Clinical differences between cocaine-dependent patients with and without antisocial personality disorder.

PubMed

Comín, Marina; Redondo, Santiago; Daigre, Constanza; Grau-López, Lara; Casas, Miguel; Roncero, Carlos

2016-12-30

The aim of this study is to compare the features of two groups of cocaine dependent patients in treatment, one of them with co-morbid diagnosis of antisocial personality disorder and the other not. Cross-sectional design, with 143 cocaine-dependent patients attending a drug unit, distributed in two groups: patients with and without Antisocial Personality Disorder. As results, we found that the 15.38% of the sample were diagnosed with an Antisocial Personality Disorder. In relation to socio-demographic variables, Antisocial Personality Disorder patients have less probability of being working or studying (9.1% vs. 47.9%). After multivariate analysis it was found that significantly Antisocial Personality Disorder patients have more opiates dependence (OR: 0.219; 95% IC 0.072-0.660), sedative dependence (OR: 0.203; 95% IC 0.062-0.644) and in more cases show Borderline Personality Disorder (OR: 0.239; 95% IC 0.077-0.746). This study highlights significant differences between cocaine addicts with or without an Antisocial Personality Disorder. All these differences are good indicators of the complexity of the patients with this personality disorder. Better knowledge of their profile will help us to improve the design of specific treatment programs. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Ictal visual hallucinations due to frontal lobe epilepsy in a patient with bipolar disorder☆

PubMed Central

Manfioli, Valeria; Saladini, Marina; Cagnin, Annachiara

2013-01-01

In ictal psychosis with complex visual hallucinations (VHs), widespread functional changes of cortical networks have been suggested. We describe the clinical and EEG findings of a patient with bipolar disorder who manifested complex VHs associated with intense emotional symptoms caused by frontal epileptic seizures. This description highlights the challenges of diagnosing the epileptic nature of new psychotic phenomena in patients with previous psychiatric disorders and shines light into the role of the frontal cortex in the genesis of complex VHs. PMID:25667849

Stability and change in personality disorders.

PubMed

Morey, Leslie C; Hopwood, Christopher J

2013-01-01

Stability is thought to be one of the major distinguishing features between personality disorders (PDs) and other forms of psychopathology. The development of more reliable PD assessments and the implementation of four major longitudinal studies on PD stability have provided critical data with which to evaluate the stability of PD features. Results from these and other studies reveal significant complexity in the interpretation of PD stability because of several issues that can impact stability estimates. Such estimates will vary as a function of the type of constructs being assessed, the type of stability being considered, the modality and reliability of the assessments being used, and the impacts of sampling. In this article, longitudinal research on PD stability is reviewed in the context of these issues. It is concluded that no single answer can be given to the question, "How stable are PDs?" and that future research and classification need to consider carefully and account for the complexity of this question.

Toxicosis in Helicobacter Pylori infection - a hypothesis

PubMed Central

BELASCU, MIHAI

2013-01-01

Background and aim We present a new clinical entity in relation to the Helicobacter pylori infection characterized by complex and varied clinical extra-digestive manifestations. Clinical findings such as asthenia, adynamia, sleep disorders, hair and nails modifications, digestive symptoms and heart rhythm disorders describe the clinical aspect of toxicosis associated with Helicobacter pylori infection. Methods The clinical presentation and therapy of patients with Helicobacter pylori infection were analyzed. Results Combined drug therapy: antibiotics + proton pump inhibitors + colloidal bismuth compound determinate remission of the symptoms in the first 3 to 5 days. The characteristic of the relation between Helicobacter pylori and the mucus-epithelial cell complex, the properties of the bacterial cell components, and the inflammatory and immunological response targeting other organs describe the immuno-pathological outbreak of Helicobacter pylori. Conclusion We support the term of toxicosis associated with Helicobacter pylori infection in selected cases. PMID:26527950

Decision Making: from Neuroscience to Psychiatry

PubMed Central

Lee, Daeyeol

2013-01-01

Adaptive behaviors increase the likelihood of survival and reproduction and improve the quality of life. However, it is often difficult to identify optimal behaviors in real life due to the complexity of the decision maker’s environment and social dynamics. As a result, although many different brain areas and circuits are involved in decision making, evolutionary and learning solutions adopted by individual decision makers sometimes produce suboptimal outcomes. Although these problems are exacerbated in numerous neurological and psychiatric disorders, their underlying neurobiological causes remain incompletely understood. In this review, theoretical frameworks in economics and machine learning and their applications in recent behavioral and neurobiological studies are summarized. Examples of such applications in clinical domains are also discussed for substance abuse, Parkinson’s disease, attention-deficit/hyperactivity disorder, schizophrenia, mood disorders, and autism. Findings from these studies have begun to lay the foundations necessary to improve diagnostics and treatment for various neurological and psychiatric disorders. PMID:23622061

Congenital Hypoglycemia Disorders: New Aspects of Etiology, Diagnosis, Treatment and Outcomes: Highlights of the Proceedings of the Congenital Hypoglycemia Disorders Symposium, Philadelphia April 2016.

PubMed

De Leon, Diva D; Stanley, Charles A

2017-02-01

Hypoglycemia continues to be an important cause of morbidity in neonates and children. Prompt diagnosis and management of the underlying hypoglycemia disorder is critical for preventing brain damage and improving outcomes. Congenital hyperinsulinism (HI) is the most common and severe cause of persistent hypoglycemia in neonates and children. Recent discoveries of the genetic causes of HI have improved our understanding of the pathophysiology, but its management is complex and requires the integration of clinical, biochemical, molecular, and imaging findings to establish the appropriate treatment according to the subtype. Here we present a summary of a recent international symposium on congenital hypoglycemia disorders with emphasis on novel molecular mechanisms resulting in HI, genetic diagnosis, overall approach to management, novel therapies under development, and current outcomes. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Genetic overlap between polycystic ovary syndrome and bipolar disorder: the endophenotype hypothesis.

PubMed

Jiang, Bowen; Kenna, Heather A; Rasgon, Natalie L

2009-12-01

Polycystic Ovary Syndrome (PCOS) is a polygenic disorder caused by the interaction of susceptible genomic polymorphisms with environmental factors. PCOS, characterized by hyperandrogenism and menstrual abnormalities, has a higher prevalence in women with Bipolar Disorder (BD). Theories explaining this high prevalence have included the effect of PCOS itself or the effect of drugs such as Valproate, which may cause PCOS either directly or indirectly. Incidentally, metabolic abnormalities are observed in both bipolar and PCOS patients. Endophenotypes such as insulin resistance, obesity, and hyperglycemia are common among BD and PCOS patients, suggesting some degree of pathophysiological overlap. Since both BD and PCOS are complex polygenetic diseases, the endophenotype overlap may be the result of common genetic markers. This paper postulates that shared clinical endophenotypes between PCOS and BD indicate common pathophysiological platforms and will review these for the potential of genetic overlap between the two disorders.

Hand stereotypies distinguish Rett syndrome from autism disorder.

PubMed

Goldman, Sylvie; Temudo, Teresa

2012-07-01

Rett syndrome (RTT) and autism disorder (AD) are 2 neurodevelopmental disorders of early life that share phenotypic features, one being hand stereotypies. Distinguishing RTT from AD often represents a challenge, and given their distinct long-term prognoses, this issue may have far-reaching implications. With the advances in genetic testing, the contribution of clinical manifestations in distinguishing RTT from AD has been overlooked. A comparison of hand stereotypies in 20 children with RTT and 20 with AD was performed using detailed analyses of videotaped standardized observations. Striking differences are observed between RTT and AD children. In RTT, hand stereotypies are predominantly complex, continuous, localized to the body midline, and involving mouthing. Conversely, in AD children, hand stereotypies are simple, bilateral, intermittent, and often involving objects. These results provide important clinical signs useful to the differential diagnosis of RTT versus AD, especially when genetic testing for RTT is not an option. Copyright © 2012 Movement Disorder Society.

Children with central and peripheral neurologic disorders have distinguishable patterns of dysphagia on videofluoroscopic swallow study.

PubMed

van den Engel-Hoek, Lenie; Erasmus, Corrie E; van Hulst, Karen C M; Arvedson, Joan C; de Groot, Imelda J M; de Swart, Bert J M

2014-05-01

To determine whether findings on videofluoroscopic swallow studies reveal different patterns of dysphagia between children with central and peripheral neurologic disorders, a retrospective study of 118 videofluoroscopic swallow studies was completed. There were 3 groups: cerebral palsy with only spastic features (n = 53), cerebral palsy with dyskinetic features (n = 34), and neuromuscular disorders (myotonic dystrophy I, n = 5; spinal muscular atrophy I-II, n = 8; Duchenne muscular dystrophy, n = 8; other neuromuscular disorder, n = 10). Interpretation of the videofluoroscopic swallow studies was not blinded. The video fluoroscopic swallow study findings were compared dichotomously between the groups. Children with cerebral palsy demonstrated dysphagia in 1 or all phases of swallowing. In neuromuscular disorder, muscle weakness results in pharyngeal residue after swallow. The underlying swallowing problem in neuromuscular disorder is muscle weakness whereas that in cerebral palsy is more complex, having to do with abnormal control of swallowing. This study serves as a first exploration on specific characteristics of swallowing in different neurologic conditions and will help clinicians anticipate what they might expect.

Genetics of hereditary neurological disorders in children.

PubMed

Huang, Yue; Yu, Sui; Wu, Zhanhe; Tang, Beisha

2014-04-01

Hereditary neurological disorders (HNDs) are relatively common in children compared to those occurring in adulthood. Recognising clinical manifestations of HNDs is important for the selection of genetic testing, genetic testing results interpretation, and genetic consultation. Meanwhile, advances in next generation sequencing (NGS) technologies have significantly enabled the discovery of genetic causes of HNDs and also challenge paediatricians on applying genetic investigation. Combination of both clinical information and advanced technologies will enhance the genetic test yields in clinical setting. This review summarises the clinical presentations as well as genetic causes of paediatric neurological disorders in four major areas including movement disorders, neuropsychiatric disorders, neuron peripheral disorders and epilepsy. The aim of this review is to help paediatric neurologists not only to see the clinical features but also the complex genetic aspect of HNDs in order to utilise genetic investigation confidently in their clinical practice. A smooth transition from research based to clinical use of comprehensive genetic testing in HNDs in children could be foreseen in the near future while genetic testing, genetic counselling and genetic data interpretation are in place appropriately.

The role of psychiatrists in diagnosing conversion disorder: a mixed-methods analysis

PubMed Central

Kanaan, Richard A; Armstrong, David; Wessely, Simon

2016-01-01

Objective Since DSM-5 removed the requirement for a psychosocial formulation, neurologists have been able to make the diagnosis of conversion disorder without psychiatric input. We sought to examine whether neurologists and specialist psychiatrists concurred with this approach. Design We used mixed methods, first surveying all the neurologists in the UK and then interviewing the neuropsychiatrists in a large UK region on the role of psychiatrists in diagnosing conversion disorder. Results Of the surveyed neurologists, 76% did not think that psychiatrists were essential for the diagnosis and 71% thought that psychiatrists did not even consider conversion disorder when referred a case. The neuropsychiatrists who were interviewed held complex models of conversion disorder. They believed all cases could be explained psychosocially in theory, but the nature of the diagnostic encounter often prevented it in practice; all felt that psychosocial formulation could be very helpful and some felt that it was essential to diagnosis. Conclusion Although neurologists do not think psychiatrists are required for diagnosing conversion disorder, specialist psychiatrists disagree, at least in some cases. PMID:27274253

Disorder-induced transition from grain boundary to bulk dominated ionic diffusion in pyrochlores

DOE PAGES

Perriot, Romain; Dholabhai, Pratik P.; Uberuaga, Blas P.

2017-05-04

In this paper, we use molecular dynamics simulations to investigate the role of grain boundaries (GBs) on ionic diffusion in pyrochlores, as a function of the GB type, chemistry of the compound, and level of cation disorder. We observe that the presence of GBs promotes oxygen transport in ordered and low-disordered systems, as the GBs are found to have a higher concentration of mobile carriers with higher mobilities than in the bulk. Thus, in ordered samples, the ionic diffusion is 2D, localized along the grain boundary. When cation disorder is introduced, bulk carriers begin to contribute to the overall diffusion,more » while the GB contribution is only slightly enhanced. In highly disordered samples, the diffusive behavior at the GBs is bulk-like, and the two contributions (bulk vs. GB) can no longer be distinguished. There is thus a transition from 2D/GB dominated oxygen diffusivity to 3D/bulk dominated diffusivity versus disorder in pyrochlores. Finally, these results provide new insights into the possibility of using internal interfaces to enhance ionic conductivity in nanostructured complex oxides.« less

Assessment of degree of disorder (amorphicity) of lyophilized formulations of growth hormone using isothermal microcalorimetry.

PubMed

Mosharraf, Mitra

2004-05-01

When determining the degree of disorder of a lyophilized cake of a protein, it is important to use an appropriate analytical technique. Differential scanning calorimetry (DSC) and X-ray powder diffraction (XRPD) are the most commonly used thermoanalytical techniques for characterizing freeze-dried protein formulations. Unfortunately, these methods are unable to detect solid-state disorder at levels < 10%. Also, interpretation of DSC results for freeze-dried protein formulations can be difficult, as a result of the more complex thermal events occurring with this technique. For example, proteins can inhibit the thermally induced recrystallization of the lyophilized cake, resulting in potential misinterpretation of DSC degree of disorder results. The aim of this investigation was to study the use of isothermal microcalorimetry (IMC) in the assessment of degree of solid-state disorder (amorphicity) of lyophilized formulations of proteins. For this purpose, two formulations of growth hormone were prepared by lyophilization. These formulations consisted of the same amounts of protein, mannitol, glycine, and phosphate buffer, but differed in the freeze-drying procedure. After lyophilization, the recrystallization of the samples was studied using IMC at 25 degrees C under different relative humidities (58-75%). The effect of available surface area was studied by determining the heat of recrystallization (Q) of the samples before and after disintegration of the cakes. The results showed that, in contrast to DSC, IMC allowed detection of the recrystallization event in the formulations. Although both formulations were completely disordered and indistinguishable according to XRPD method, IMC revealed that formulation B had a different solid-sate structure than formulation A. This difference was the result of differences in the freeze-drying parameters, demonstrating the importance of choosing appropriate analytical methodology.

Ability of the Child Behavior Checklist-Dysregulation Profile and the Youth Self Report-Dysregulation Profile to identify serious psychopathology and association with correlated problems in high-risk children and adolescents.

PubMed

Dölitzsch, Claudia; Kölch, Michael; Fegert, Jörg M; Schmeck, Klaus; Schmid, Marc

2016-11-15

The current analyses examined whether the dysregulation profile (DP) 1) could be used to identify children and adolescents at high risk for complex and serious psychopathology and 2) was correlated to other emotional and behavioral problems (such as delinquent behavior or suicide ideation). DP was assessed using both the Child Behavior Checklist (CBCL) and the Youth Self Report (YSR) in a residential care sample. Children and adolescents (N=374) aged 10-18 years living in residential care in Switzerland completed the YSR, and their professional caregivers completed the CBCL. Participants meeting criteria for DP (T-score ≥67 on the anxious/‌depressed, attention problems, and aggressive behavior scales of the YSR/CBCL) were compared against those who did not for the presence of complex psychopathology (defined as the presence of both emotional and behavioral disorders), and also for the prevalence of several psychiatric diagnoses, suicidal ideation, traumatic experiences, delinquent behaviors, and problems related to quality of life. The diagnostic criteria for CBCL-DP and YSR-DP were met by just 44 (11.8%) and 25 (6.7%) of participants. Only eight participants (2.1%) met the criteria on both instruments. Further analyses were conducted separately for the CBCL-DP and YSR-DP groups. DP was associated with complex psychopathology in only 34.4% of cases according to CBCL and in 60% of cases according to YSR. YSR-DP was somewhat more likely to be associated with psychiatric disorders and associated problems than was the CBCL-DP. Because of the relatively small overlap between the CBCL-DP and YSR-DP, analyses were conducted largely with different samples, likely contributing to the different results. Despite a high rate of psychopathology in the population studied, both the YSR-DP and the CBCL-DP were able to detect only a small proportion of those with complex psychiatric disorders. This result questions the validity of YSR-DP and the CBCL-DP in detecting subjects with complex and serious psychopathology. It is possible that different screening instruments may be more effective. Copyright © 2016 Elsevier B.V. All rights reserved.

Reproductive Disorders in Snakes.

PubMed

Di Girolamo, Nicola; Selleri, Paolo

2017-05-01

Reproduction of snakes is one of the challenging aspects of herpetology medicine. Due to the complexity of reproduction, several disorders may present before, during, or after this process. This article describes the physical examination, and radiographic, ultrasonographic, and endoscopic findings associated with reproductive disorders in snakes. Surgical techniques used to resolve reproductive disorders in snakes are described. Finally, common reproductive disorders in snakes are individually discussed. Copyright © 2017 Elsevier Inc. All rights reserved.

Truncating Variants in NAA15 Are Associated with Variable Levels of Intellectual Disability, Autism Spectrum Disorder, and Congenital Anomalies.

PubMed

Cheng, Hanyin; Dharmadhikari, Avinash V; Varland, Sylvia; Ma, Ning; Domingo, Deepti; Kleyner, Robert; Rope, Alan F; Yoon, Margaret; Stray-Pedersen, Asbjørg; Posey, Jennifer E; Crews, Sarah R; Eldomery, Mohammad K; Akdemir, Zeynep Coban; Lewis, Andrea M; Sutton, Vernon R; Rosenfeld, Jill A; Conboy, Erin; Agre, Katherine; Xia, Fan; Walkiewicz, Magdalena; Longoni, Mauro; High, Frances A; van Slegtenhorst, Marjon A; Mancini, Grazia M S; Finnila, Candice R; van Haeringen, Arie; den Hollander, Nicolette; Ruivenkamp, Claudia; Naidu, Sakkubai; Mahida, Sonal; Palmer, Elizabeth E; Murray, Lucinda; Lim, Derek; Jayakar, Parul; Parker, Michael J; Giusto, Stefania; Stracuzzi, Emanuela; Romano, Corrado; Beighley, Jennifer S; Bernier, Raphael A; Küry, Sébastien; Nizon, Mathilde; Corbett, Mark A; Shaw, Marie; Gardner, Alison; Barnett, Christopher; Armstrong, Ruth; Kassahn, Karin S; Van Dijck, Anke; Vandeweyer, Geert; Kleefstra, Tjitske; Schieving, Jolanda; Jongmans, Marjolijn J; de Vries, Bert B A; Pfundt, Rolph; Kerr, Bronwyn; Rojas, Samantha K; Boycott, Kym M; Person, Richard; Willaert, Rebecca; Eichler, Evan E; Kooy, R Frank; Yang, Yaping; Wu, Joseph C; Lupski, James R; Arnesen, Thomas; Cooper, Gregory M; Chung, Wendy K; Gecz, Jozef; Stessman, Holly A F; Meng, Linyan; Lyon, Gholson J

2018-05-03

N-alpha-acetylation is a common co-translational protein modification that is essential for normal cell function in humans. We previously identified the genetic basis of an X-linked infantile lethal Mendelian disorder involving a c.109T>C (p.Ser37Pro) missense variant in NAA10, which encodes the catalytic subunit of the N-terminal acetyltransferase A (NatA) complex. The auxiliary subunit of the NatA complex, NAA15, is the dimeric binding partner for NAA10. Through a genotype-first approach with whole-exome or genome sequencing (WES/WGS) and targeted sequencing analysis, we identified and phenotypically characterized 38 individuals from 33 unrelated families with 25 different de novo or inherited, dominantly acting likely gene disrupting (LGD) variants in NAA15. Clinical features of affected individuals with LGD variants in NAA15 include variable levels of intellectual disability, delayed speech and motor milestones, and autism spectrum disorder. Additionally, mild craniofacial dysmorphology, congenital cardiac anomalies, and seizures are present in some subjects. RNA analysis in cell lines from two individuals showed degradation of the transcripts with LGD variants, probably as a result of nonsense-mediated decay. Functional assays in yeast confirmed a deleterious effect for two of the LGD variants in NAA15. Further supporting a mechanism of haploinsufficiency, individuals with copy-number variant (CNV) deletions involving NAA15 and surrounding genes can present with mild intellectual disability, mild dysmorphic features, motor delays, and decreased growth. We propose that defects in NatA-mediated N-terminal acetylation (NTA) lead to variable levels of neurodevelopmental disorders in humans, supporting the importance of the NatA complex in normal human development. Copyright © 2018 American Society of Human Genetics. All rights reserved.

MAOA Variants and Genetic Susceptibility to Major Psychiatric Disorders.

PubMed

Liu, Zichao; Huang, Liang; Luo, Xiong-Jian; Wu, Lichuan; Li, Ming

2016-09-01

Monoamine oxidase A (MAOA) is a mitochondrial enzyme involved in the metabolism of several biological amines such as dopamine, norepinephrine, and serotonin, which are important neurochemicals in the pathogenesis of major psychiatric illnesses. MAOA is regarded as a functional plausible susceptibility gene for psychiatric disorders, whereas previous hypothesis-driven association studies obtained controversial results, a reflection of small sample size, genetic heterogeneity, or true negative associations. In addition, MAOA is not analyzed in most of genome-wide association studies (GWAS) on psychiatric disorders, since it is located on Chromosome Xp11.3. Therefore, the effects of MAOA variants on genetic predisposition to psychiatric disorders remain obscure. To fill this gap, we collected psychiatric phenotypic (schizophrenia, bipolar disorder, and major depressive disorder) and genetic data in up to 18,824 individuals from diverse ethnic groups. We employed classical fixed (or random) effects inverse variance weighted methods to calculate summary odds ratios (OR) and 95 % confidence intervals (CI). We identified a synonymous SNP rs1137070 showing significant associations with major depressive disorder (p = 0.00067, OR = 1.263 for T allele) and schizophrenia (p = 0.0039, OR = 1.225 for T allele) as well as a broad spectrum of psychiatric phenotype (p = 0.000066, OR = 1.218 for T allele) in both males and females. The effect size was similar between different ethnic populations and different gender groups. Collectively, we confirmed that MAOA is a risk gene for psychiatric disorders, and our results provide useful information toward a better understanding of genetic mechanism involving MAOA underlying risk of complex psychiatric disorders.

CONVULSIVE DISORDERS IN CHILDREN WITH REFERENCE TO TREATMENT WITH KETOGENIC DIET.

ERIC Educational Resources Information Center

KEITH, HADDOW M.

WRITTEN FOR THE MEDICAL PROFESSION, THIS BOOK PROVIDES INFORMATION ON CHILDHOOD CONVULSIONS (EPILEPSY) AND METHODS OF TREATMENT. VARIOUS CONVULSIVE DISORDERS, INCLUDING HYPSARHYTHMIA, AUTONOMIC SEIZURES, SYMPTOM COMPLEXES, FEBRILE CONVULSIONS, AND "PHOTOGENIC" DISORDERS, ARE DISCUSSED IN TERMS OF CAUSES, SYMPTOMS, AND TREATMENT.…

Eating Disorders as Coping Mechanisms

ERIC Educational Resources Information Center

Wagener, Amy M.; Much, Kari

2010-01-01

This article focuses on the complex nature of eating disorders, specifically highlighting their use as coping mechanisms for underlying emotional and psychological concerns. Case examples of college counseling center clients are discussed in order to illustrate common ways in which eating disorders are utilized by clients with varying…

Tourette syndrome and other neurodevelopmental disorders: a comprehensive review.

PubMed

Cravedi, Elena; Deniau, Emmanuelle; Giannitelli, Marianna; Xavier, Jean; Hartmann, Andreas; Cohen, David

2017-01-01

Gilles de la Tourette syndrome (TS) is a complex developmental neuropsychiatric condition in which motor manifestations are often accompanied by comorbid conditions that impact the patient's quality of life. In the DSM-5, TS belongs to the "neurodevelopmental disorders" group, together with other neurodevelopmental conditions, frequently co-occurring. In this study, we searched the PubMed database using a combination of keywords associating TS and all neurodevelopmental diagnoses. From 1009 original reports, we identified 36 studies addressing TS and neurodevelopmental comorbidities. The available evidence suggests the following: (1) neurodevelopmental comorbidities in TS are the rule, rather than the exception; (2) attention deficit/hyperactivity disorder (ADHD) is the most frequent; (3) there is a continuum from a simple (TS + ADHD or/and learning disorder) to a more complex phenotype (TS + autism spectrum disorder). We conclude that a prompt diagnosis and a detailed description of TS comorbidities are necessary not only to understand the aetiological basis of neurodevelopmental disorders but also to address specific rehabilitative and therapeutic approaches.

The Disordered C-Terminus of Yeast Hsf1 Contains a Cryptic Low-Complexity Amyloidogenic Region.

PubMed

Pujols, Jordi; Santos, Jaime; Pallarès, Irantzu; Ventura, Salvador

2018-05-06

Response mechanisms to external stress rely on networks of proteins able to activate specific signaling pathways to ensure the maintenance of cell proteostasis. Many of the proteins mediating this kind of response contain intrinsically disordered regions, which lack a defined structure, but still are able to interact with a wide range of clients that modulate the protein function. Some of these interactions are mediated by specific short sequences embedded in the longer disordered regions. Because the physicochemical properties that promote functional and abnormal interactions are similar, it has been shown that, in globular proteins, aggregation-prone and binding regions tend to overlap. It could be that the same principle applies for disordered protein regions. In this context, we show here that a predicted low-complexity interacting region in the disordered C-terminus of the stress response master regulator heat shock factor 1 (Hsf1) protein corresponds to a cryptic amyloid region able to self-assemble into fibrillary structures resembling those found in neurodegenerative disorders.

Convergent dysregulation of frontal cortical cognitive and reward systems in eating disorders.

PubMed

Stefano, George B; Ptáček, Radek; Kuželová, Hana; Mantione, Kirk J; Raboch, Jiří; Papezova, Hana; Kream, Richard M

2013-05-10

A substantive literature has drawn a compelling case for the functional involvement of mesolimbic/prefrontal cortical neural reward systems in normative control of eating and in the etiology and persistence of severe eating disorders that affect diverse human populations. Presently, we provide a short review that develops an equally compelling case for the importance of dysregulated frontal cortical cognitive neural networks acting in concert with regional reward systems in the regulation of complex eating behaviors and in the presentation of complex pathophysiological symptoms associated with major eating disorders. Our goal is to highlight working models of major eating disorders that incorporate complementary approaches to elucidate functionally interactive neural circuits defined by their regulatory neurochemical phenotypes. Importantly, we also review evidence-based linkages between widely studied psychiatric and neurodegenerative syndromes (e.g., autism spectrum disorders and Parkinson's disease) and co-morbid eating disorders to elucidate basic mechanisms involving dopaminergic transmission and its regulation by endogenously expressed morphine in these same cortical regions.

Dynamic protein interaction networks and new structural paradigms in signaling

PubMed Central

Csizmok, Veronika; Follis, Ariele Viacava; Kriwacki, Richard W.; Forman-Kay, Julie D.

2017-01-01

Understanding signaling and other complex biological processes requires elucidating the critical roles of intrinsically disordered proteins and regions (IDPs/IDRs), which represent ~30% of the proteome and enable unique regulatory mechanisms. In this review we describe the structural heterogeneity of disordered proteins that underpins these mechanisms and the latest progress in obtaining structural descriptions of ensembles of disordered proteins that are needed for linking structure and dynamics to function. We describe the diverse interactions of IDPs that can have unusual characteristics such as “ultrasensitivity” and “regulated folding and unfolding”. We also summarize the mounting data showing that large-scale assembly and protein phase separation occurs within a variety of signaling complexes and cellular structures. In addition, we discuss efforts to therapeutically target disordered proteins with small molecules. Overall, we interpret the remodeling of disordered state ensembles due to binding and post-translational modifications within an expanded framework for allostery that provides significant insights into how disordered proteins transmit biological information. PMID:26922996

How Can Music Influence the Autonomic Nervous System Response in Patients with Severe Disorder of Consciousness?

PubMed

Riganello, Francesco; Cortese, Maria D; Arcuri, Francesco; Quintieri, Maria; Dolce, Giuliano

2015-01-01

Activations to pleasant and unpleasant musical stimuli were observed within an extensive neuronal network and different brain structures, as well as in the processing of the syntactic and semantic aspects of the music. Previous studies evidenced a correlation between autonomic activity and emotion evoked by music listening in patients with Disorders of Consciousness (DoC). In this study, we analyzed retrospectively the autonomic response to musical stimuli by mean of normalized units of Low Frequency (nuLF) and Sample Entropy (SampEn) of Heart Rate Variability (HRV) parameters, and their possible correlation to the different complexity of four musical samples (i.e., Mussorgsky, Tchaikovsky, Grieg, and Boccherini) in Healthy subjects and Vegetative State/Unresponsive Wakefulness Syndrome (VS/UWS) patients. The complexity of musical sample was based on Formal Complexity and General Dynamics parameters defined by Imberty's semiology studies. The results showed a significant difference between the two groups for SampEn during the listening of Mussorgsky's music and for nuLF during the listening of Boccherini and Mussorgsky's music. Moreover, the VS/UWS group showed a reduction of nuLF as well as SampEn comparing music of increasing Formal Complexity and General Dynamics. These results put in evidence how the internal structure of the music can change the autonomic response in patients with DoC. Further investigations are required to better comprehend how musical stimulation can modify the autonomic response in DoC patients, in order to administer the stimuli in a more effective way.

Unique Challenges for Modeling Defect Dynamics in Concentrated Solid-Solution Alloys

NASA Astrophysics Data System (ADS)

Zhao, Shijun; Weber, William J.; Zhang, Yanwen

2017-11-01

Recently developed concentrated solid solution alloys (CSAs) are shown to have improved performance under irradiation that depends strongly on the number of alloying elements, alloying species, and their concentrations. In contrast to conventional dilute alloys, CSAs are composed of multiple principal elements situated randomly in a simple crystalline lattice. As a result, the intrinsic disorder has a profound influence on energy dissipation pathways and defect evolution when these CSAs are subjected to energetic particle irradiation. Extraordinary irradiation resistance, including suppression of void formation by two orders of magnitude at an elevated temperature, has been achieved with increasing compositional complexity in CSAs. Unfortunately, the loss of translational invariance associated with the intrinsic chemical disorder poses great challenges to theoretical modeling at the electronic and atomic levels. Based on recent computer simulation results for a set of novel Ni-containing, face-centered cubic CSAs, we review theoretical modeling progress in handling disorder in CSAs and underscore the impact of disorder on defect dynamics. We emphasize in particular the unique challenges associated with the description of defect dynamics in CSAs.

A Network Approach to Environmental Impact in Psychotic Disorder: Brief Theoretical Framework.

PubMed

Isvoranu, Adela-Maria; Borsboom, Denny; van Os, Jim; Guloksuz, Sinan

2016-07-01

The spectrum of psychotic disorder represents a multifactorial and heterogeneous condition and is thought to result from a complex interplay between genetic and environmental factors. In the current paper, we analyze this interplay using network analysis, which has been recently proposed as a novel psychometric framework for the study of mental disorders. Using general population data, we construct network models for the relation between 3 environmental risk factors (cannabis use, developmental trauma, and urban environment), dimensional measures of psychopathology (anxiety, depression, interpersonal sensitivity, obsessive-compulsive disorder, phobic anxiety, somatizations, and hostility), and a composite measure of psychosis expression. Results indicate the existence of specific paths between environmental factors and symptoms. These paths most often involve cannabis use. In addition, the analyses suggest that symptom networks are more strongly connected for people exposed to environmental risk factors, implying that environmental exposure may lead to less resilient symptom networks. © The Author 2016. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center. All rights reserved. For permissions, please email: journals.permissions@oup.com.

Psychosocial aspects of resistance in complex treatment of depressive disorder.

PubMed

Sedlackova, Zuzana; Prasko, Jan; Latalova, Klara; Kamaradova, Dana; Ociskova, Marie; Grambal, Ales; Sigmundova, Zuzana; Kasalova, Petra; Cakirpaloglu, Snezana

2015-01-01

Treatment of major depressive disorder can be affected by a broad range of factors. In our study, we focused on the relationships of demographic, psychological, clinical and social factors to the course of treatment of depression. The study included 151 patients (finally 140 patients were evaluated) hospitalized for major depressive disorder. They were assessed for demographic characteristics, the rates of depression and anxiety, quality of life, the rates of dissociation and insomnia, and subjective and objective disease severity at different times during treatment. Patients were treated with standard doses of antidepressants or other psychiatric medication. They also completed a 6-week long daily cognitive-behavioural therapy. Data were statistically analyzed. There were significant decreases in the overall severity of the disorder, anxiety level and depression rate during treatment. Improvement measured by objective Clinical Global Impression (oCGI-I) at the end of treatment was not significantly correlated with any of the measured parameters (age of patient, onset of illness, duration of disease, doses of medication etc.). It only significantly positively correlated with the initial evaluation of the patient by oCGI. However, the improvement in subjective assessment (using sCGI-I) correlated with many parameters (increased age, later onset of the disease, greater disease severity at baseline in both overall and subjective evaluation of the severity, anxiety and depressive symptomatology). Furthermore, it was negatively correlated with most quality of life parameters, such as H (Home), F (Feelings), L (Leisure), Sr (Social relations) and G (General). The results suggest that individual variables, such as the degree of psychopathology, particularly depression and anxiety, most quality of life parameters, higher patient age and age of disorder onset may be associated with poorer subjective response to complex treatment of patients with major depressive disorder.

Posttraumatic Stress Disorder and Complex Posttraumatic Stress Disorder in DSM-5 and ICD-11: Clinical and Behavioral Correlates.

PubMed

Hyland, Philip; Shevlin, Mark; Fyvie, Claire; Karatzias, Thanos

2018-04-01

The American Psychiatric Association and the World Health Organization provide distinct trauma-based diagnoses in the fifth edition of the Diagnostic and Statistical Manual (DSM-5), and the forthcoming 11th version of the International Classification of Diseases (ICD-11), respectively. The DSM-5 conceptualizes posttraumatic stress disorder (PTSD) as a single, broad diagnosis, whereas the ICD-11 proposes two "sibling" disorders: PTSD and complex PTSD (CPTSD). The objectives of the current study were to: (a) compare prevalence rates of PTSD/CPTSD based on each diagnostic system; (b) identify clinical and behavioral variables that distinguish ICD-11 CPTSD and PTSD diagnoses; and (c) examine the diagnostic associations for ICD-11 CPTSD and DSM-5 PTSD. Participants in a predominately female clinical sample (N = 106) completed self-report scales to measure ICD-11 PTSD and CPTSD, DSM-5 PTSD, and depression, anxiety, borderline personality disorder, dissociation, destructive behaviors, and suicidal ideation and self-harm. Significantly more people were diagnosed with PTSD according to the DSM-5 criteria (90.4%) compared to those diagnosed with PTSD and CPTSD according to the ICD-11 guidelines (79.8%). An ICD-11 CPTSD diagnosis was distinguished from an ICD-11 PTSD diagnosis by higher levels of dissociation (d = 1.01), depression (d = 0.63), and borderline personality disorder (d = 0.55). Diagnostic associations with depression, anxiety, and suicidal ideation and self-harm were higher for ICD-11 CPTSD compared to DSM-5 PTSD (by 10.7%, 4.0%, and 7.0%, respectively). These results have implications for differential diagnosis and for the development of targeted treatments for CPTSD. Copyright © 2018 International Society for Traumatic Stress Studies.

Mouse Models of Genomic Syndromes as Tools for Understanding the Basis of Complex Traits: An Example with the Smith-Magenis and the Potocki-Lupski Syndromes

PubMed Central

Carmona-Mora, P; Molina, J; Encina, C.A; Walz, K

2009-01-01

Each human's genome is distinguished by extra and missing DNA that can be “benign” or powerfully impact everything from development to disease. In the case of genomic disorders DNA rearrangements, such as deletions or duplications, correlate with a clinical specific phenotype. The clinical presentations of genomic disorders were thought to result from altered gene copy number of physically linked dosage sensitive genes. Genomic disorders are frequent diseases (~1 per 1,000 births). Smith-Magenis syndrome (SMS) and Potocki-Lupski syndrome (PTLS) are genomic disorders, associated with a deletion and a duplication, of 3.7 Mb respectively, within chromosome 17 band p11.2. This region includes 23 genes. Both syndromes have complex and distinctive phenotypes including multiple congenital and neurobehavioral abnormalities. Human chromosome 17p11.2 is syntenic to the 32-34 cM region of murine chromosome 11. The number and order of the genes are highly conserved. In this review, we will exemplify how genomic disorders can be modeled in mice and the advantages that such models can give in the study of genomic disorders in particular and gene copy number variation (CNV) in general. The contributions of the SMS and PTLS animal models in several aspects ranging from more specific ones, as the definition of the clinical aspects of the human clinical spectrum, the identification of dosage sensitive genes related to the human syndromes, to the more general contributions as the definition of genetic locus impacting obesity and behavior and the elucidation of general mechanisms related to the pathogenesis of gene CNV are discussed. PMID:19949547

Proposal for classifying the severity of speech disorder using a fuzzy model in accordance with the implicational model of feature complexity.

PubMed

Brancalioni, Ana Rita; Magnago, Karine Faverzani; Keske-Soares, Marcia

2012-09-01

The objective of this study is to create a new proposal for classifying the severity of speech disorders using a fuzzy model in accordance with a linguistic model that represents the speech acquisition of Brazilian Portuguese. The fuzzy linguistic model was run in the MATLAB software fuzzy toolbox from a set of fuzzy rules, and it encompassed three input variables: path routing, level of complexity and phoneme acquisition. The output was the Speech Disorder Severity Index, and it used the following fuzzy subsets: severe, moderate severe, mild moderate and mild. The proposal was used for 204 children with speech disorders who were monolingual speakers of Brazilian Portuguese. The fuzzy linguistic model provided the Speech Disorder Severity Index for all of the evaluated phonological systems in a fast and practical manner. It was then possible to classify the systems according to the severity of the speech disorder as severe, moderate severe, mild moderate and mild; the speech disorders could also be differentiated according to the severity index.

Identification and Characterization of FAM124B as a Novel Component of a CHD7 and CHD8 Containing Complex

PubMed Central

Batsukh, Tserendulam; Schulz, Yvonne; Wolf, Stephan; Rabe, Tamara I.; Oellerich, Thomas; Urlaub, Henning; Schaefer, Inga-Marie; Pauli, Silke

2012-01-01

Background Mutations in the chromodomain helicase DNA binding protein 7 gene (CHD7) lead to CHARGE syndrome, an autosomal dominant multiple malformation disorder. Proteins involved in chromatin remodeling typically act in multiprotein complexes. We previously demonstrated that a part of human CHD7 interacts with a part of human CHD8, another chromodomain helicase DNA binding protein presumably being involved in the pathogenesis of neurodevelopmental (NDD) and autism spectrum disorders (ASD). Because identification of novel CHD7 and CHD8 interacting partners will provide further insights into the pathogenesis of CHARGE syndrome and ASD/NDD, we searched for additional associated polypeptides using the method of stable isotope labeling by amino acids in cell culture (SILAC) in combination with mass spectrometry. Principle findings The hitherto uncharacterized FAM124B (Family with sequence similarity 124B) was identified as a potential interaction partner of both CHD7 and CHD8. We confirmed the result by co-immunoprecipitation studies and showed a direct binding to the CHD8 part by direct yeast two hybrid experiments. Furthermore, we characterized FAM124B as a mainly nuclear localized protein with a widespread expression in embryonic and adult mouse tissues. Conclusion Our results demonstrate that FAM124B is a potential interacting partner of a CHD7 and CHD8 containing complex. From the overlapping expression pattern between Chd7 and Fam124B at murine embryonic day E12.5 and the high expression of Fam124B in the developing mouse brain, we conclude that Fam124B is a novel protein possibly involved in the pathogenesis of CHARGE syndrome and neurodevelopmental disorders. PMID:23285124

Tuning and Freezing Disorder in Photonic Crystals using Percolation Lithography.

PubMed

Burgess, Ian B; Abedzadeh, Navid; Kay, Theresa M; Shneidman, Anna V; Cranshaw, Derek J; Lončar, Marko; Aizenberg, Joanna

2016-01-21

Although common in biological systems, synthetic self-assembly routes to complex 3D photonic structures with tailored degrees of disorder remain elusive. Here we show how liquids can be used to finely control disorder in porous 3D photonic crystals, leading to complex and hierarchical geometries. In these optofluidic crystals, dynamically tunable disorder is superimposed onto the periodic optical structure through partial wetting or evaporation. In both cases, macroscopic symmetry breaking is driven by subtle sub-wavelength variations in the pore geometry. These variations direct site-selective infiltration of liquids through capillary interactions. Incorporating cross-linkable resins into our liquids, we developed methods to freeze in place the filling patterns at arbitrary degrees of partial wetting and intermediate stages of drying. These percolation lithography techniques produced permanent photonic structures with adjustable disorder. By coupling strong changes in optical properties to subtle differences in fluid behavior, optofluidic crystals may also prove useful in rapid analysis of liquids.

The Big Role of Small RNAs in Anxiety and Stress-Related Disorders.

PubMed

Malan-Müller, S; Hemmings, S M J

2017-01-01

In the study of complex, heterogeneous disorders, such as anxiety and stress-related disorders, epigenetic factors provide an additional level of heritable complexity. MicroRNAs (miRNAs) are a class of small, noncoding RNAs that function as epigenetic modulators of gene expression by binding to target messenger RNAs (mRNAs) and subsequently blocking translation or accelerating their degradation. In light of their abundance in the central nervous system (CNS) and their involvement in synaptic plasticity and neuronal differentiation, miRNAs represent an exciting frontier to be explored in the etiology and treatment of anxiety and stress-related disorders. This chapter will present a thorough review of miRNAs, their functions, and mRNA targets in the CNS, focusing on their role in anxiety and stress-related disorders as described by studies performed in animals and human subjects. © 2017 Elsevier Inc. All rights reserved.

Self-perceived coping resources of middle-aged and older adults - results of a large population-based study.

PubMed

Boehlen, Friederike H; Herzog, Wolfgang; Schellberg, Dieter; Maatouk, Imad; Saum, Kai-Uwe; Brenner, Hermann; Wild, Beate

2017-12-01

Psychosocial resources (personal resources, social resources, and other) are important for coping with aging and impairment. The aim of this study was to describe the resources of older adults and to compare subgroups with frailty, complex health care needs, and/or mental disorders. At the third follow-up of the large population-based German ESTHER study, 3124 elderly persons (aged 55-85) were included. Psychosocial resources were assessed during a home visit by trained study doctors by using a list of 26 different items. Resources were described for the total group, separated by sex, and for the three subgroups of persons with frailty, complex health care needs, and mental disorders. Family, self-efficacy, and financial security were the most frequently reported resources of older adults. Women and men showed significant differences in their self-perceived resources. Personal resources (self-efficacy, optimism, mastery), social resources, and financial security were reported significantly less frequently by frail persons, persons with complex health care needs, and mentally ill older adults compared to non-impaired participants. Apart from external support, patients who experienced complex health care needs reported resources less frequently compared to frail and mentally ill patients. Coping resources in older adults are associated with sex and impairment. Evaluation and support of personal resources of frail or mentally ill persons or individuals with complex health care needs should be integrated in the therapeutic process.

[Screening interview for early detection of high-functioning autism spectrum disorders].

PubMed

Hoffmann, Wiebke; Heinzel-Gutenbrunner, Monika; Becker, Katja; Kamp-Becker, Inge

2015-05-01

Various different questionnaires are available for the screening of autism spectrum disorders (ASD). These screening instruments show high sensitivity and are able to identify a large number of individuals with ASD, but they lack the specificity to differentiate individuals with ASD from those children and adolescents with other complex neurobehavioural disorders (such as attention-deficit/hyperactivity disorder, emotional disorders, and others), especially for those without intellectual disabilities. The present study evaluates the data of 309 individuals (153 with high-functioning ASD, 156 with other psychiatric disorders, IQ > 70) to find out whether selected items of the ADI-R can be used for an economic and sensitive screening of high-functioning ASD. The results show that 8 items of the ADI-R can be used to discriminate high-functioning ASD and other psychiatric disorders. A cutoff of 5 led to a sensitivity of 0.93 and a cutoff of 6 to a specificity of 0.74. The combination of early onset, serious abnormalities in social contact with stereotyped or compulsive-ritualized behaviour or interests can be detected with few interview questions for screening of ASD. Nevertheless, a more detailed and specific assessment in an expert setting should follow the screening process.

[Development of sexuality and motivational aspects of sexual behavior in men with obsessive-compulsive disorders].

PubMed

2014-09-01

Sexual behavior and formation of sexuality in men with obsessive-compulsive disorder is one of the pressing issues in contemporary medicine. Obsessive-compulsive disorder is characterized by the development of intrusive thoughts, memories, movements and actions, as well as a variety of pathological fears (phobias). Increase in the number of patients with this pathology in modern clinical practice of neurotic disorders, the young age of the patients and as a result violation of interpersonal, communicational and sexual nature is quite apparent. The study involved 35 men aged 23 to 47 years with clinical signs of OCD. We determined the severity of obsessive-compulsive symptoms using the Yale-Brown scale. We established the presence of a mild degree of disorder in 34,3% of cases; in 48,6% of cases disorder of moderate severity was diagnosed; remaining 17.1% were assessed subclinical condition of OCD at the applicable scale. The system of motivational maintenance of sexual behavior in men with obsessive-compulsive disorders is investigated. Motives of sexual behavior of the investigated men with the pathology are determined. The presented research in men with OCD have established multidimensionality and complexity of motivational ensuring of sexual behavior.

New Communitarianism Movements and Complex Utopia

NASA Astrophysics Data System (ADS)

Akdeniz, K. Gediz

Simulation is a rapidly growing field in social sciences. Simulation theories in social sciences are considered to critique social dynamics and societies which are mostly simulated by media, cinema, TV, internet, etc. Recently we (Akdeniz KG, Disorder in complex human system. In: Fritzsch H, Phua KK (eds) Singapore: proceedings of the conference in Honour of Murray Gell-Mann's 80th birthday quantum mechanics, elementary particles, quantum cosmology and complexity. World Scientific Publishing, Hackensack, pp 630-637, 2009) purposed a simulation theory as a critique theory to investigate disordered human behaviors. In this theory, "Disorder-Sensitive Human Behaviors (DSHB) Simulation Theory", chaotic awareness is also considered as a reality principle in simulation world to complete Baudrillard Simulation Theory (Baudrillard J, Simulacra and simulation. University of Michigan Press, Michigan, 1995). We call the emergence of this reality as zuhur which is different than simulacra. More recently we proposed the complex utopia (Akdeniz KG, From Simulacra to Zuhur in Complex Utopia. 11th International Conference of the Utopian Studies Society, Lublin, 2010; Akdeniz KG, The new identities of the physicist: cyborg-physicist and post-physicist. In: Proceedings of the conference of world international conference of technology and education, Beirut, 2010) to critique the complex societies and communities in simulation world. The challenging agents in the complex utopia are both simulacra and zuhur. In this paper we would like to review "What is the complex utopia?" And we shall critique some global events in framework of complex utopia with particular examples in socio-economic and political contexts.

Post-traumatic stress disorder in children and adolescents: epidemiology, diagnosis and treatment options.

PubMed

Donnelly, Craig L; Amaya-Jackson, Lisa

2002-01-01

Post-traumatic stress disorder (PTSD) is a common psychiatric condition in childhood and adolescence. Rates vary widely depending upon the type of trauma exposure. Interpersonal traumas, such as rape or physical abuse, are more likely to result in PTSD than exposure to natural or technological disaster. Clinical presentations are exceedingly complex and children with PTSD are at increased risk of having comorbid psychiatric diagnoses. Because of its complexity and frequent occurrence with other disorders, assessment of PTSD necessitates a broad-based evaluation utilizing multiple informations and structured instruments specific to the symptoms of PTSD in youth. Cognitive-behavioral therapy (CBT) is the treatment of first choice. Pharmacological agents for PTSD treatment have received little empirical investigation in childhood. Pharmacological treatment is used to target disabling symptoms of the disorder, which limit psychotherapy or life functioning, by helping children to tolerate working through distressful material in therapy and life. Pharmacological treatment should be based on a stepwise approach utilizing broad spectrum medications such as the selective serotonin reuptake inhibitors as first-line agents. Comorbid conditions should be identified and treated with appropriate medication or psychosocial interventions. Treatment algorithms are provided to guide rational medication strategies for children and adolescents with PTSD, subsyndromal PTSD, and in PTSD that is comorbid with other psychiatric conditions of childhood. Reduction in even one debilitating symptom of PTSD can improve a child's overall functioning across multiple domains.

The neuropsychiatry of hyperkinetic movement disorders: insights from neuroimaging into the neural circuit bases of dysfunction.

PubMed

Hayhow, Bradleigh D; Hassan, Islam; Looi, Jeffrey C L; Gaillard, Francesco; Velakoulis, Dennis; Walterfang, Mark

2013-01-01

Movement disorders, particularly those associated with basal ganglia disease, have a high rate of comorbid neuropsychiatric illness. We consider the pathophysiological basis of the comorbidity between movement disorders and neuropsychiatric illness by 1) reviewing the epidemiology of neuropsychiatric illness in a range of hyperkinetic movement disorders, and 2) correlating findings to evidence from studies that have utilized modern neuroimaging techniques to investigate these disorders. In addition to diseases classically associated with basal ganglia pathology, such as Huntington disease, Wilson disease, the neuroacanthocytoses, and diseases of brain iron accumulation, we include diseases associated with pathology of subcortical white matter tracts, brain stem nuclei, and the cerebellum, such as metachromatic leukodystrophy, dentatorubropallidoluysian atrophy, and the spinocerebellar ataxias. Neuropsychiatric symptoms are integral to a thorough phenomenological account of hyperkinetic movement disorders. Drawing on modern theories of cortico-subcortical circuits, we argue that these disorders can be conceptualized as disorders of complex subcortical networks with distinct functional architectures. Damage to any component of these complex information-processing networks can have variable and often profound consequences for the function of more remote neural structures, creating a diverse but nonetheless rational pattern of clinical symptomatology.

The Genetics of Stress-Related Disorders: PTSD, Depression, and Anxiety Disorders

PubMed Central

Smoller, Jordan W

2016-01-01

Research into the causes of psychopathology has largely focused on two broad etiologic factors: genetic vulnerability and environmental stressors. An important role for familial/heritable factors in the etiology of a broad range of psychiatric disorders was established well before the modern era of genomic research. This review focuses on the genetic basis of three disorder categories—posttraumatic stress disorder (PTSD), major depressive disorder (MDD), and the anxiety disorders—for which environmental stressors and stress responses are understood to be central to pathogenesis. Each of these disorders aggregates in families and is moderately heritable. More recently, molecular genetic approaches, including genome-wide studies of genetic variation, have been applied to identify specific risk variants. In this review, I summarize evidence for genetic contributions to PTSD, MDD, and the anxiety disorders including genetic epidemiology, the role of common genetic variation, the role of rare and structural variation, and the role of gene–environment interaction. Available data suggest that stress-related disorders are highly complex and polygenic and, despite substantial progress in other areas of psychiatric genetics, few risk loci have been identified for these disorders. Progress in this area will likely require analysis of much larger sample sizes than have been reported to date. The phenotypic complexity and genetic overlap among these disorders present further challenges. The review concludes with a discussion of prospects for clinical translation of genetic findings and future directions for research. PMID:26321314

Protein intrinsic disorder in plants.

PubMed

Pazos, Florencio; Pietrosemoli, Natalia; García-Martín, Juan A; Solano, Roberto

2013-09-12

To some extent contradicting the classical paradigm of the relationship between protein 3D structure and function, now it is clear that large portions of the proteomes, especially in higher organisms, lack a fixed structure and still perform very important functions. Proteins completely or partially unstructured in their native (functional) form are involved in key cellular processes underlain by complex networks of protein interactions. The intrinsic conformational flexibility of these disordered proteins allows them to bind multiple partners in transient interactions of high specificity and low affinity. In concordance, in plants this type of proteins has been found in processes requiring these complex and versatile interaction networks. These include transcription factor networks, where disordered proteins act as integrators of different signals or link different transcription factor subnetworks due to their ability to interact (in many cases simultaneously) with different partners. Similarly, they also serve as signal integrators in signaling cascades, such as those related to response to external stimuli. Disordered proteins have also been found in plants in many stress-response processes, acting as protein chaperones or protecting other cellular components and structures. In plants, it is especially important to have complex and versatile networks able to quickly and efficiently respond to changing environmental conditions since these organisms cannot escape and have no other choice than adapting to them. Consequently, protein disorder can play an especially important role in plants, providing them with a fast mechanism to obtain complex, interconnected and versatile molecular networks.

Protein intrinsic disorder in plants

PubMed Central

Pazos, Florencio; Pietrosemoli, Natalia; García-Martín, Juan A.; Solano, Roberto

2013-01-01

To some extent contradicting the classical paradigm of the relationship between protein 3D structure and function, now it is clear that large portions of the proteomes, especially in higher organisms, lack a fixed structure and still perform very important functions. Proteins completely or partially unstructured in their native (functional) form are involved in key cellular processes underlain by complex networks of protein interactions. The intrinsic conformational flexibility of these disordered proteins allows them to bind multiple partners in transient interactions of high specificity and low affinity. In concordance, in plants this type of proteins has been found in processes requiring these complex and versatile interaction networks. These include transcription factor networks, where disordered proteins act as integrators of different signals or link different transcription factor subnetworks due to their ability to interact (in many cases simultaneously) with different partners. Similarly, they also serve as signal integrators in signaling cascades, such as those related to response to external stimuli. Disordered proteins have also been found in plants in many stress-response processes, acting as protein chaperones or protecting other cellular components and structures. In plants, it is especially important to have complex and versatile networks able to quickly and efficiently respond to changing environmental conditions since these organisms cannot escape and have no other choice than adapting to them. Consequently, protein disorder can play an especially important role in plants, providing them with a fast mechanism to obtain complex, interconnected and versatile molecular networks. PMID:24062761

Predicting stabilizing treatment outcomes for complex posttraumatic stress disorder and dissociative identity disorder: an expertise-based prognostic model.

PubMed

Baars, Erik W; van der Hart, Onno; Nijenhuis, Ellert R S; Chu, James A; Glas, Gerrit; Draijer, Nel

2011-01-01

The purpose of this study was to develop an expertise-based prognostic model for the treatment of complex posttraumatic stress disorder (PTSD) and dissociative identity disorder (DID). We developed a survey in 2 rounds: In the first round we surveyed 42 experienced therapists (22 DID and 20 complex PTSD therapists), and in the second round we surveyed a subset of 22 of the 42 therapists (13 DID and 9 complex PTSD therapists). First, we drew on therapists' knowledge of prognostic factors for stabilization-oriented treatment of complex PTSD and DID. Second, therapists prioritized a list of prognostic factors by estimating the size of each variable's prognostic effect; we clustered these factors according to content and named the clusters. Next, concept mapping methodology and statistical analyses (including principal components analyses) were used to transform individual judgments into weighted group judgments for clusters of items. A prognostic model, based on consensually determined estimates of effect sizes, of 8 clusters containing 51 factors for both complex PTSD and DID was formed. It includes the clusters lack of motivation, lack of healthy relationships, lack of healthy therapeutic relationships, lack of other internal and external resources, serious Axis I comorbidity, serious Axis II comorbidity, poor attachment, and self-destruction. In addition, a set of 5 DID-specific items was constructed. The model is supportive of the current phase-oriented treatment model, emphasizing the strengthening of the therapeutic relationship and the patient's resources in the initial stabilization phase. Further research is needed to test the model's statistical and clinical validity.

Hyperkinetic Impulse Disorder in Children's Behavior Problems

ERIC Educational Resources Information Center

Laufer, Maurice W.; Denhoff, Eric; Solomons, Gerald

2011-01-01

A very common cause of children's behavior disorder disturbance is an entity described as the hyperkinetic impulse disorder. This is characterized by hyperactivity, short attention span and poor powers of concentration, irritability, impulsiveness, variability, and poor schoolwork. The existence of this complexity may lead to many psychological…

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

Perriot, Romain; Uberuaga, Blas P.

We use molecular dynamics simulations to investigate the role of cation disorder on oxygen diffusion in Gd 2Zr 2O 7 (GZO) and Gd 2Ti 2O 7 (GTO) pyrochlores, a class of complex oxides which contain a structural vacancy relative to the basic fluorite structure. The introduction of disorder has distinct effects depending on the chemistry of the material, increasing the mobility of structural carriers by up to four orders of magnitude in GZO. In contrast, in GTO, there is no mobility at zero or low disorder on the ns timescale, but higher disorder liberates the otherwise immobile carriers, allowing diffusionmore » with rates comparable to GZO for the fully disordered material. Here, we show that the cation disorder enhances the diffusivity by both increasing the concentration of mobile structural carriers and their individual mobility. The disorder also influences the diffusion in materials containing intrinsic carriers, such as additional vacancies VO or oxygen interstitials OI. And while in ordered GZO and GTO the contribution of the intrinsic carriers dominates the overall diffusion of oxygen, OI in GZO contributes along with structural carriers, and the total diffusion rate can be calculated by assuming simple additive contributions from the two sources. Although the disorder in the materials with intrinsic defects usually enhances the diffusivity as in the defect-free case, in low concentrations, cation antisites AB or BA, where A = Gd and B = Zr or Ti, can act as traps for fast intrinsic defects. The trapping results in a lowering of the diffusivity, and causes a non-monotonic behavior of the diffusivity with disorder. Conversely, in the case of slow intrinsic defects, the main effect of the disorder is to liberate the structural carriers, resulting in an increase of the diffusivity regardless of the defect trapping.« less

Gene-Environment Interactions in Genome-Wide Association Studies: Current Approaches and New Directions

ERIC Educational Resources Information Center

Winham, Stacey J.; Biernacka, Joanna M.

2013-01-01

Background: Complex psychiatric traits have long been thought to be the result of a combination of genetic and environmental factors, and gene-environment interactions are thought to play a crucial role in behavioral phenotypes and the susceptibility and progression of psychiatric disorders. Candidate gene studies to investigate hypothesized…

Simple Identification of Complex ADHD Subtypes Using Current Symptom Counts

ERIC Educational Resources Information Center

Volk, Heather E.; Todorov, Alexandre A.; Hay, David A.; Todd, Richard D.

2009-01-01

The results of the assessment of the accuracy of simple rules based on symptom count for assigning youths to attention deficit hyperactivity disorder subtypes show that having six or more total symptoms and fewer than three hyperactive-impulsive symptoms is an accurate predictor for the latent class sever inattentive subtype.

Genetics, environmental factors and the emerging role of epigenetics in neurodegenerative diseases.

PubMed

Migliore, Lucia; Coppedè, Fabio

2009-07-10

In the present review we summarize recent advances in the understanding of the interaction between genetics and environmental factors involved in complex multi-factorial neurodegenerative disorders such as Alzheimer's disease (AD), Parkinson's disease (PD) and Amyotrophic Lateral Sclerosis (ALS). The discovery of several genes responsible for the familial forms has led to a better comprehension of the molecular pathways involved in the selective neuronal degeneration which is specific for each of these disorders. However, the vast majority of the cases occurs as sporadic forms, likely resulting from complex gene-gene and gene-environment interplay. Several environmental factors, including, pesticides, metals, head injuries, lifestyles and dietary habits have been associated with increased disease risk or even with protection. Hundreds of genetic variants have been investigated as possible risk factors for the sporadic forms, but results are often conflicting, not repeated or inconclusive. New approaches to environmental health research are revealing us that at the basis there could be chemically induced changes in gene regulation and emphasise the importance of understanding the susceptibility of the human epigenome to dietary and other environmental effects.

Gene-gene and gene-environment interactions defining lipid-related traits.

PubMed

Ordovás, José M; Robertson, Ruairi; Cléirigh, Ellen Ní

2011-04-01

Steps towards reducing chronic disease progression are continuously being taken through the form of genomic research. Studies over the last year have highlighted more and more polymorphisms, pathways and interactions responsible for metabolic disorders such as cardiovascular disease, obesity and dyslipidemia. Many of these chronic illnesses can be partially blamed by altered lipid metabolism, combined with individual genetic components. Critical evaluation and comparison of these recent studies is essential in order to comprehend the results, conclusions and future prospects in the field of genomics as a whole. Recent literature elucidates significant gene--diet and gene--environment interactions resulting in altered lipid metabolism, inflammation and other metabolic imbalances leading to cardiovascular disease and obesity. Epigenetic and epistatic interactions are now becoming more significantly associated with such disorders, as genomic research digs deeper into the complex nature of genetic individuality and heritability. The vast array of data collected from genome-wide association studies must now be empowered and explored through more complex interaction studies, using standardized methods and larger sample sizes. In doing so the etiology of chronic disease progression will be further understood.

Caenorhabditis elegans as an experimental tool for the study of complex neurological diseases: Parkinson's disease, Alzheimer's disease and autism spectrum disorder.

PubMed

Calahorro, Fernando; Ruiz-Rubio, Manuel

2011-12-01

The nematode Caenorhabditis elegans has a very well-defined and genetically tractable nervous system which offers an effective model to explore basic mechanistic pathways that might be underpin complex human neurological diseases. Here, the role C. elegans is playing in understanding two neurodegenerative conditions, Parkinson's and Alzheimer's disease (AD), and a complex neurological condition, autism, is used as an exemplar of the utility of this model system. C. elegans is an imperfect model of Parkinson's disease because it lacks orthologues of the human disease-related genes PARK1 and LRRK2 which are linked to the autosomal dominant form of this disease. Despite this fact, the nematode is a good model because it allows transgenic expression of these human genes and the study of the impact on dopaminergic neurons in several genetic backgrounds and environmental conditions. For AD, C. elegans has orthologues of the amyloid precursor protein and both human presenilins, PS1 and PS2. In addition, many of the neurotoxic properties linked with Aβ amyloid and tau peptides can be studied in the nematode. Autism spectrum disorder is a complex neurodevelopmental disorder characterised by impairments in human social interaction, difficulties in communication, and restrictive and repetitive behaviours. Establishing C. elegans as a model for this complex behavioural disorder is difficult; however, abnormalities in neuronal synaptic communication are implicated in the aetiology of the disorder. Numerous studies have associated autism with mutations in several genes involved in excitatory and inhibitory synapses in the mammalian brain, including neuroligin, neurexin and shank, for which there are C. elegans orthologues. Thus, several molecular pathways and behavioural phenotypes in C. elegans have been related to autism. In general, the nematode offers a series of advantages that combined with knowledge from other animal models and human research, provides a powerful complementary experimental approach for understanding the molecular mechanisms and underlying aetiology of complex neurological diseases.

Sleep in childhood and adolescence: age-specific sleep characteristics, common sleep disturbances and associated difficulties.

PubMed

Barclay, Nicola L; Gregory, Alice M

2014-01-01

Sleep changes throughout the lifespan, with particularly salient alterations occurring during the first few years of life, as well as during the transition from childhood to adolescence. Such changes are partly the result of brain maturation; complex changes in the organisation of the circadian system; as well as changes in daily routine, environmental demands and responsibilities. Despite the automaticity of sleep, given that it is governed by a host of complex mechanisms, there are times when sleep becomes disturbed. Sleep disturbances in childhood are common and may stem from behavioural difficulties or abnormalities in physiological processes-and, in some cases manifest into diagnosable sleep disorders. As well as occurring exclusively, childhood sleep disturbances often co-occur with other difficulties. The purpose of this chapter is to outline the neurobiology of typical sleep/wake processes, and describe changes in sleep physiology and architecture from birth to adulthood. Furthermore, common childhood sleep disorders are described as are their associations with other traits, including all of the syndromes presented in this handbook: ASDs, ADHD, schizophrenia and emotional/behavioural difficulties. Throughout, we attempt to explain possible mechanisms underlying these disorders and their associations.

Anomalous subjective experience and psychosis risk in young depressed patients.

PubMed

Szily, Erika; Kéri, Szabolcs

2009-01-01

Help-seeking young people often display depressive symptoms. In some patients, these symptoms may co-exist with clinically high-risk mental states for psychosis. The aim of this study was to determine differences in subjective experience and social perception in young depressed patients with and without psychosis risk. Participants were 68 young persons with major depressive disorder. Twenty-six patients also met the criteria of attenuated or brief limited intermittent psychotic symptoms according to the Comprehensive Assessment of At Risk Mental States (CAARMS) criteria. Subjective experiences were assessed with the Bonn Scale for the Assessment of Basic Symptoms (BSABS). Recognition of complex social emotions and mental states was assessed using the 'Reading the Mind in the Eyes' test. Perplexity, self-disorder, and diminished affectivity significantly predicted psychosis risk. Depressed patients without psychosis risk displayed impaired recognition performance for negative social emotions, whereas patients with psychosis risk were also impaired in the recognition of cognitive expressions. In the high-risk group, self-disorder was associated with impaired recognition of facial expressions. These results suggest that anomalous subjective experience and impaired recognition of complex emotions may differentiate between young depressed patients with and without psychosis risk. 2009 S. Karger AG, Basel.

A new view of “dream enactment” in REM sleep behavior disorder

PubMed Central

Blumberg, Mark S.; Plumeau, Alan M.

2015-01-01

SUMMARY REM sleep behavior disorder (RBD) is a disorder in which patients exhibit increased muscle tone and exaggerated myoclonic twitching during REM sleep. In addition, violent movements of the limbs, and complex behaviors that can sometimes appear to involve the enactment of dreams, are associated with RBD. These behaviors are widely thought to result from a dysfunction involving atonia-producing neural circuitry in the brainstem, thereby unmasking cortically generated dreams. Here we scrutinize the assumptions that led to this interpretation of RBD. In particular, we challenge the assumption that motor cortex produces twitches during REM sleep, thus calling into question the related assumption that motor cortex is primarily responsible for all of the pathological movements of RBD. Moreover, motor cortex is not even necessary to produce complex behavior; for example, stimulation of some brainstem structures can produce defensive and aggressive behaviors in rats and monkeys that are striking similar to those reported in human patients with RBD. Accordingly, we suggest an interpretation of RBD that focuses increased attention on the brainstem as a source of the pathological movements and that considers sensory feedback from moving limbs as an important influence on the content of dream mentation. PMID:26802823

Force-induced bone growth and adaptation: A system theoretical approach to understanding bone mechanotransduction

NASA Astrophysics Data System (ADS)

Maldonado, Solvey; Findeisen, Rolf

2010-06-01

The modeling, analysis, and design of treatment therapies for bone disorders based on the paradigm of force-induced bone growth and adaptation is a challenging task. Mathematical models provide, in comparison to clinical, medical and biological approaches an structured alternative framework to understand the concurrent effects of the multiple factors involved in bone remodeling. By now, there are few mathematical models describing the appearing complex interactions. However, the resulting models are complex and difficult to analyze, due to the strong nonlinearities appearing in the equations, the wide range of variability of the states, and the uncertainties in parameters. In this work, we focus on analyzing the effects of changes in model structure and parameters/inputs variations on the overall steady state behavior using systems theoretical methods. Based on an briefly reviewed existing model that describes force-induced bone adaptation, the main objective of this work is to analyze the stationary behavior and to identify plausible treatment targets for remodeling related bone disorders. Identifying plausible targets can help in the development of optimal treatments combining both physical activity and drug-medication. Such treatments help to improve/maintain/restore bone strength, which deteriorates under bone disorder conditions, such as estrogen deficiency.

The Role of Temperament in the Etiopathogenesis of Bipolar Spectrum Illness.

PubMed

Fountoulakis, Konstantinos N; Gonda, Xenia; Koufaki, Ioanna; Hyphantis, Thomas; Cloninger, C Robert

2016-01-01

Bipolar disorder constitutes a challenge for clinicians in everyday clinical practice. Our knowledge concerning this clinical entity is incomplete, and contemporary classification systems are unable to reflect the complexity of this disorder. The concept of temperament, which was first described in antiquity, provides a helpful framework for synthesizing our knowledge on how the human body works and what determines human behavior. Although the concept of temperament originally included philosophical and sociocultural approaches, the biomedical model is dominant today. It is possible that specific temperaments might constitute vulnerability factors, determine the clinical picture, or modify the course of illness. Temperaments might even act as a bridge between genes and clinical manifestations, thus giving rise to the concept of the bipolar spectrum, with major implications for mental health research and treatment. More specifically, it has been reported that the hyperthymic and the depressive temperaments are related to the more "classic" bipolar disorder, whereas cyclothymic, anxious, and irritable temperaments are related to more complex manifestations and might predict poor response to treatment, violent or suicidal behavior, and high comorbidity. Incorporating of the concept of temperament and the bipolar spectrum into the standard training of psychiatric residents might well result in an improvement of everyday clinical practice.

The search for mechanisms of change in behavioral treatments for alcohol use disorders: a commentary.

PubMed

Longabaugh, Richard

2007-10-01

Definitive results from efforts to identify mechanisms of change in behavioral treatments for alcohol use disorders have been elusive. The working hypothesis guiding this paper is that one of the reasons for this elusiveness is that the models we hypothesize to account for treatments effectiveness are unnecessarily restricted and too simple. This paper aims to accomplish 3 things. First, a typography for locating potential mediators of change will be presented. In the course of doing so, a nomenclature will be proposed with the hope that this will facilitate communications among alcohol treatment researchers studying mechanisms of change. Second, alternatives to the classic test of mediation of alcohol treatment effects will be considered and one such alternative described. Third, alternative ways of conceptualizing, constructing and analyzing variables to measure mediators will be suggested. It is hoped that this commentary will facilitate research on mechanisms of change in behavioral treatments for alcohol use disorders. Behavioral change is a complex process, and the models that we develop to account for this process need to reflect this complexity. Advances in statistical approaches for testing mediation, along with a better understanding as to how to use these tools should help in moving toward this goal.

The possible interplay of synaptic and clock genes in autism spectrum disorders.

PubMed

Bourgeron, T

2007-01-01

Autism spectrum disorders (ASD) are complex neurodevelopmental conditions characterized by deficits in social communication, absence or delay in language, and stereotyped and repetitive behaviors. Results from genetic studies reveal one pathway associated with susceptibility to ASD, which includes the synaptic cell adhesion molecules NLGN3, NLGN4, and NRXN1 and a postsynaptic scaffolding protein SHANK3. This protein complex is crucial for the maintenance of functional synapses as well as the adequate balance between neuronal excitation and inhibition. Among the factors that could modulate this pathway are the genes controlling circadian rhythms. Indeed, sleep disorders and low melatonin levels are frequently observed in ASD. In this context, an alteration of both this synaptic pathway and the setting of the clock would greatly increase the risk of ASD. In this chapter, I report genetic and neurobiological findings that highlight the major role of synaptic and clock genes in the susceptibility to ASD. On the basis of these lines of evidence, I propose that future studies of ASD should investigate the circadian modulation of synaptic function as a focus for functional analyses and the development of new therapeutic strategies.

Low-Level Laser Irradiation Improves Depression-Like Behaviors in Mice.

PubMed

Xu, Zhiqiang; Guo, Xiaobo; Yang, Yong; Tucker, Donovan; Lu, Yujiao; Xin, Ning; Zhang, Gaocai; Yang, Lingli; Li, Jizhen; Du, Xiangdong; Zhang, Quanguang; Xu, Xingshun

2017-08-01

Major depressive disorder (MDD) is one of the leading forms of psychiatric disorders, characterized by aversion to mobility, neurotransmitter deficiency, and energy metabolic decline. Low-level laser therapy (LLLT) has been investigated in a variety of neurodegenerative disorders associated with mitochondrial dysfunction and functional impairments. The goal of this study was to examine the effect of LLLT on depression-like behaviors and to explore the potential mechanism by detecting mitochondrial function following LLLT. Depression models in space restriction mice and Abelson helper integration site-1 (Ahi1) knockout (KO) mice were employed in this work. Our results revealed that LLLT effectively improved depression-like behaviors, in the two depression mice models, by decreasing immobility duration in behavioral despair tests. In addition, ATP biosynthesis and the level of mitochondrial complex IV expression and activity were significantly elevated in prefrontal cortex (PFC) following LLLT. Intriguingly, LLLT has no effects on ATP content and mitochondrial complex I-IV levels in other tested brain regions, hippocampus and hypothalamus. As a whole, these findings shed light on a novel strategy of transcranial LLLT on depression improvement by ameliorating neurotransmitter abnormalities and promoting mitochondrial function in PFC. The present work provides concrete groundwork for further investigation of LLLT for depression treatment.

Combination therapies - the next logical step for the treatment of synucleinopathies?

PubMed Central

Valera, E.; Masliah, E.

2015-01-01

Currently there are no disease-modifying alternatives for the treatment of most neurodegenerative disorders. The available therapies for diseases such as Parkinson’s disease (PD), PD dementia (PDD), Dementia with Lewy bodies (DLB) and Multiple system atrophy (MSA), in which the protein alpha-synuclein (α-syn) accumulates within neurons and glial cells with toxic consequences, are focused on managing the disease symptoms. However, utilizing strategic drug combinations and/or multi-target drugs might increase the treatment efficiency when compared to monotherapies. Synucleinopathies are complex disorders that progress through several stages, and toxic α-syn aggregates exhibit prion-like behavior spreading from cell to cell. Therefore, it follows that these neurodegenerative disorders might require equally complex therapeutic approaches in order to obtain significant and long-lasting results. Hypothetically, therapies aimed at reducing α-syn accumulation and cell-to-cell transfer, such as immunotherapy against α-syn, could be combined with agents that reduce neuroinflammation with potential synergistic outcomes. Here we review the current evidence supporting this type of approach, suggesting that such rational therapy combinations, together with the use of multi-target drugs, may hold promise as the next logical step for the treatment of synucleinopathies. PMID:26388203

Stress, epigenetics, and alcoholism.

PubMed

Moonat, Sachin; Pandey, Subhash C

2012-01-01

Acute and chronic stressors have been associated with alterations in mood and increased anxiety that may eventually result in the development of stress-related psychiatric disorders. Stress and associated disorders, including anxiety, are key factors in the development of alcoholism because alcohol consumption can temporarily reduce the drinker's dysphoria. One molecule that may help mediate the relationship between stress and alcohol consumption is brain-derived neurotrophic factor (BDNF), a protein that regulates the structure and function of the sites where two nerve cells interact and exchange nerve signals (i.e., synapses) and which is involved in numerous physiological processes. Aberrant regulation of BDNF signaling and alterations in synapse activity (i.e., synaptic plasticity) have been associated with the pathophysiology of stress-related disorders and alcoholism. Mechanisms that contribute to the regulation of genetic information without modification of the DNA sequence (i.e., epigenetic mechanisms) may play a role in the complex control of BDNF signaling and synaptic plasticity-for example, by modifying the structure of the DNA-protein complexes (i.e., chromatin) that make up the chromosomes and thereby modulating the expression of certain genes. Studies regarding the epigenetic control of BDNF signaling and synaptic plasticity provide a promising direction to understand the mechanisms mediating the interaction between stress and alcoholism.

Helium defectoscopy of cerium gadolinium ceramics Ce0.8Gd0.2O1.9 with a submicrocrystalline structure in the impurity disorder region

NASA Astrophysics Data System (ADS)

Koromyslov, A. V.; Zhiganov, A. N.; Kovalenko, M. A.; Kupryazhkin, A. Ya.

2013-12-01

The concentration of impurity anion vacancies formed upon the dissociation of gadolinium-vacancy complexes has been determined using helium defectoscopy of the cerium gadolinium ceramics Ce0.8Gd0.2O1.9 with a submicrocrystalline structure in the temperature range T = 740-1123 K and at saturation pressures ranging from 0.05 to 15 MPa. It has been found that the energy of dissociation of gadoliniumvacancy complexes is E {eff/ D }= 0.26 ± 0.06 eV, and the energy of dissolution of helium in anion vacancies in the impurity disorder region is E P = -0.31 ± 0.09 eV. The proposed mechanism of dissolution has been confirmed by the investigation of the electrical conductivity of the cerium gadolinium ceramics, as well as by the high-speed molecular dynamics simulation of the dissociation of gadolinium-vacancy complexes. It has been assumed that a decrease in the effective dissolution energy in comparison with the results of the previously performed low-temperature investigations is caused by the mutual repulsion of vacancies formed upon the dissociation of gadolinium-vacancy complexes in highly concentrated solutions of gadolinium in CeO2 with increasing temperature.

Embracing Complexity: Using Technology to Develop a Life-Long Learning Model for Non-Working Time in the Interdependent Homes for Adults with Autism Spectrum Disorders

ERIC Educational Resources Information Center

Chiang, I-Tsun; Chen, Mei-Li

2011-01-01

The purpose of this study was to employ complexity theory as a theoretical framework and technology to facilitate the development of a life-long learning model for non-working time in the interdependent homes for adults with Autism Spectrum Disorders (ASD). A "Shining Star Sustainable Action Project" of the ROC Foundation for Autistic…

[Effects of therapeutic complexes including balneoradonokinesitherapy, electromyostimulation and low-frequency magnetotherapy on regional blood flow in patients with postrraumatic gonarthritis].

PubMed

Raspopova, E A; Udartsev, E Iu

2006-01-01

Balneoradonokinesitherapy alone and its combination with electrostimulation and low-frequency magnetotherapy were used for the treatment of regional blood flow disorders in 76 patients with posttraumatic gonarthritis. Balneoradonokinesitherapy in combination with electromyostimulation improved blood circulation. When low-frequency magnetotherapy was added to the latter complex, the regress of regional blood flow disorders of a damaged extremity was most significant.

Empirical support for the definition of a complex trauma event in children and adolescents.

PubMed

Wamser-Nanney, Rachel; Vandenberg, Brian R

2013-12-01

Complex trauma events have been defined as chronic, interpersonal traumas that begin early in life (Cook, Blaustein, Spinazzola, & van der Kolk, 2003). The complex trauma definition has been examined in adults, as indicated by the Diagnostic and Statistical Manual of Mental Disorders (4th ed.; DSM-IV) field trial; however, this research was lacking in child populations. The symptom presentations of complexly traumatized children were contrasted with those exposed to other, less severe trauma ecologies that met 1 or 2 features of the complex trauma definition. Included in this study were 346 treatment-seeking children and adolescents (ages 3–18 years) who had experienced atraumatic event. Results indicated that child survivors of complex trauma presented with higher levels of generalized behavior problems and trauma-related symptoms than those who experienced (a) acute noninterpersonal trauma, (b) chronic interpersonal trauma that begins later in life, and (c) acute interpersonal trauma. Greater levels of behavioral problems were observed in children exposed to complex trauma as compared to those who experienced a traumatic event that begins early in life. These results provide support for the complex trauma event definition and suggest the need for a complex trauma diagnostic construct for children and adolescents.

Cortical complexity in bipolar disorder applying a spherical harmonics approach.

PubMed

Nenadic, Igor; Yotter, Rachel A; Dietzek, Maren; Langbein, Kerstin; Sauer, Heinrich; Gaser, Christian

2017-05-30

Recent studies using surface-based morphometry of structural magnetic resonance imaging data have suggested that some changes in bipolar disorder (BP) might be neurodevelopmental in origin. We applied a novel analysis of cortical complexity based on fractal dimensions in high-resolution structural MRI scans of 18 bipolar disorder patients and 26 healthy controls. Our region-of-interest based analysis revealed increases in fractal dimensions (in patients relative to controls) in left lateral orbitofrontal cortex and right precuneus, and decreases in right caudal middle frontal, entorhinal cortex, and right pars orbitalis, and left fusiform and posterior cingulate cortices. While our analysis is preliminary, it suggests that early neurodevelopmental pathologies might contribute to bipolar disorder, possibly through genetic mechanisms. Copyright © 2017 Elsevier Ireland Ltd. All rights reserved.

Bupropion Augmentation in a Case of Compulsive Buying Disorder.

PubMed

Sepede, Gianna; Di Iorio, Giuseppe; Sarchione, Fabiola; Fiori, Federica; Di Giannantonio, Massimo

Compulsive buying disorder (CBD) is a condition characterized by excessive preoccupations, impulses, and behaviors regarding buying, resulting in serious psychological, social, and financial problems. Even though it has not been included in Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, "behavioral addictions" section, CBD is a hot topic in current clinical psychiatry, because of its relevant prevalence (at least 5% in adult populations) and severe effect on quality of life.The CBD shares some clinical features with substance-related and behavioral addictions, impulse control disorders, and obsessive compulsive disorder, and it is often comorbid with other psychiatric illnesses (especially depressive and anxiety disorders). The treatment of CBD is therefore difficult, and clear therapeutic guidelines are not yet available. Treating the comorbid disorders as the first-line approach, or combining drugs with different pharmacodynamic profiles, has been suggested to address this challenging condition. A 60-year-old woman affected by a severe form of CBD with comorbid major depressive disorder, resistant/intolerant to previous selective serotonin reuptake inhibitor treatments and only partially responder to mirtazapine, achieved a good clinical improvement adding bupropion. Combining 2 agents with different pharmacological profiles and mechanisms of action, such as bupropion and mirtazapine, could be a useful strategy in the management of complex CBD cases.

Assessment and Treatment of Personality Disorders: A Behavioral Perspective

ERIC Educational Resources Information Center

Nelson-Gray, Rosemery O.; Lootens, Christopher M.; Mitchell, John T.; Robertson, Christopher D.; Hundt, Natalie E.; Kimbrel, Nathan A.

2009-01-01

Personality disorders are complex and highly challenging to treatment providers; yet, for clients with these problems, there exist very few treatment options that have been supported by research. Given the lack of empirically-supported therapies for personality disorders, it can be difficult to make treatment decisions for this population. The…

Tourette Syndrome: School-Based Interventions for Tics and Associated Conditions

ERIC Educational Resources Information Center

Koutsoklenis, Athanasios; Theodoridou, Zoe

2012-01-01

Tourette syndrome (TS) is a neurological disorder characterized by motor and phonic tics that follow a fluctuating pattern of severity, intensity and frequency. TS is often associated with other conditions such as attention-deficit/hyperactivity disorder, obsessive-compulsive disorder and learning difficulties. This complex phenotype affects the…

Accommodating Asperger's: An Autoethnography on the Learning Experience in an E-Learning Music Education Program

ERIC Educational Resources Information Center

Farrell, Riley Jarrett

2013-01-01

A student with Asperger's Syndrome faces a complex myriad of learning disabilities and social difficulties. The co-morbid conditions of dyslexia, Obsessive Compulsive Disorder, Attention Deficit Disorder, Attention Deficit Hyperactive Disorder and anxiety further complicate Asperger's Syndrome. Asperger's Syndrome and these conditions, singularly…

Multimodal Brain Imaging in Autism Spectrum Disorder and the Promise of Twin Research

ERIC Educational Resources Information Center

Mevel, Katell; Fransson, Peter; Bölte, Sven

2015-01-01

Current evidence suggests the phenotype of autism spectrum disorder to be driven by a complex interaction of genetic and environmental factors impacting onto brain maturation, synaptic function, and cortical networks. However, findings are heterogeneous, and the exact neurobiological pathways of autism spectrum disorder still remain poorly…

The Neurobiology of Autism: Theoretical Applications

ERIC Educational Resources Information Center

Schroeder, Jessica H.; Desrocher, Mary; Bebko, James M.; Cappadocia, M. Catherine

2010-01-01

Autism spectrum disorders (ASD) are complex neurological disorders characterized by heterogeneity in skills and impairments. A variety of models have been developed to describe the disorders and a wide range of brain processes have been implicated. This review attempts to integrate some of the consistent neurological findings in the research with…

Targeted Treatments in Autism and Fragile X Syndrome

ERIC Educational Resources Information Center

Gurkan, C. Kagan; Hagerman, Randi J.

2012-01-01

Autism is a neurodevelopmental disorder consisting of a constellation of symptoms that sometimes occur as part of a complex disorder characterized by impairments in social interaction, communication and behavioral domains. It is a highly disabling disorder and there is a need for treatment targeting the core symptoms. Although autism is accepted…

The Role of Sleep in Childhood Psychiatric Disorders

ERIC Educational Resources Information Center

Alfano, Candice A.; Gamble, Amanda L.

2009-01-01

Although sleep problems often comprise core features of psychiatric disorders, inadequate attention has been paid to the complex, reciprocal relationships involved in the early regulation of sleep, emotion, and behavior. In this paper, we review the pediatric literature examining sleep in children with primary psychiatric disorders as well as…

The Role of Mitochondrial Dysfunction in Psychiatric Disease

ERIC Educational Resources Information Center

Scaglia, Fernando

2010-01-01

Mitochondrial respiratory chain disorders are a group of genetically and clinically heterogeneous disorders caused by the biochemical complexity of mitochondrial respiration and the fact that two genomes, one mitochondrial and one nuclear, encode the components of the respiratory chain. These disorders can manifest at birth or present later in…

Narratives Reflecting the Lived Experiences of People with Brain Disorders: Common Psychosocial Difficulties and Determinants

PubMed Central

Hartley, Sally; McArthur, Maggie; Coenen, Michaela; Cabello, Maria; Covelli, Venusia; Roszczynska-Michta, Joanna; Pitkänen, Tuuli; Bickenbach, Jerome; Cieza, Alarcos

2014-01-01

Background People with brain disorders - defined as both, mental disorders and neurological disorders experience a wide range of psychosocial difficulties (PSDs) (e.g., concentrating, maintaining energy levels, and maintaining relationships). Research evidence is required to show that these PSDs are common across brain disorders. Objectives To explore and gain deeper understanding of the experiences of people with seven brain disorders (alcohol dependency, depression, epilepsy, multiple sclerosis, Parkinson’s disease, schizophrenia, stroke). It examines the common PSDs and their influencing factors. Methods Seventy seven qualitative studies identified in a systematic literature review and qualitative data derived from six focus groups are used to generate first-person narratives representing seven brain disorders. A theory-driven thematic analysis of these narratives identifies the PSDs and their influencing factors for comparison between the seven disorders. Results First-person narratives illustrate realities for people with brain disorders facilitating a deeper understanding of their every-day life experiences. Thematic analysis serves to highlight the commonalities, both of PSDs, such as loneliness, anger, uncertainty about the future and problems with work activities, and their determinants, such as work opportunities, trusting relationships and access to self-help groups. Conclusions The strength of the methodology and the narratives is that they provide the opportunity for the reader to empathise with people with brain disorders and facilitate deeper levels of understanding of the complexity of the relationship of PSDs, determinants and facilitators. The latter reflect positive aspects of the lives of people with brain disorders. The result that many PSDs and their influencing factors are common to people with different brain disorders opens up the door to the possibility of using cross-cutting interventions involving different sectors. This strengthens the message that ‘a great deal can be done’ to improve the lived experience of persons with brain disorders when medical interventions are exhausted. PMID:24805128

CONGENITAL HYPOGLYCEMIA DISORDERS: NEW ASPECTS OF ETIOLOGY, DIAGNOSIS, TREATMENT AND OUTCOMES

PubMed Central

De Leon, Diva D.; Stanley, Charles A.

2017-01-01

Hypoglycemia continues to be an important cause of morbidity in neonates and children. Prompt diagnosis and management of the underlying hypoglycemia disorder is critical for preventing brain damage and improving outcomes. Congenital hyperinsulinism is the most common and severe cause of persistent hypoglycemia in neonates and children. Recent discoveries of the genetic causes of hyperinsulinism have improved our understanding of the pathophysiology, but its management is complex and requires the integration of clinical, biochemical, molecular and imaging findings to establish the appropriate treatment according to the subtype. Here we present a summary of a recent international symposium on congenital hypoglycemia disorders with emphasis on novel molecular mechanisms resulting in hyperinsulinism, genetic diagnosis, overall approach to management, novel therapies under development, and current outcomes. PMID:27753189

Random electric field instabilities of relaxor ferroelectrics

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

Arce-Gamboa, Jose R.; Guzman-Verri, Gian G.

Relaxor ferroelectrics are complex oxide materials which are rather unique to study the effects of compositional disorder on phase transitions. Here, we study the effects of quenched cubic random electric fields on the lattice instabilities that lead to a ferroelectric transition and show that, within a microscopic model and a statistical mechanical solution, even weak compositional disorder can prohibit the development of long-range order and that a random field state with anisotropic and power-law correlations of polarization emerges from the combined effect of their characteristic dipole forces and their inherent charge disorder. As a result, we compare and reproduce severalmore » key experimental observations in the well-studied relaxor PbMg 1/3Nb 2/3O 3–PbTiO 3.« less

Random electric field instabilities of relaxor ferroelectrics

DOE PAGES

Arce-Gamboa, Jose R.; Guzman-Verri, Gian G.

2017-06-13

Relaxor ferroelectrics are complex oxide materials which are rather unique to study the effects of compositional disorder on phase transitions. Here, we study the effects of quenched cubic random electric fields on the lattice instabilities that lead to a ferroelectric transition and show that, within a microscopic model and a statistical mechanical solution, even weak compositional disorder can prohibit the development of long-range order and that a random field state with anisotropic and power-law correlations of polarization emerges from the combined effect of their characteristic dipole forces and their inherent charge disorder. As a result, we compare and reproduce severalmore » key experimental observations in the well-studied relaxor PbMg 1/3Nb 2/3O 3–PbTiO 3.« less

[What is the contribution of Stewart's concept in acid-base disorders analysis?].

PubMed

Quintard, H; Hubert, S; Ichai, C

2007-05-01

To explain the different approaches for interpreting acid-base disorders; to develop the Stewart model which offers some advantages for the pathophysiological understanding and the clinical interpretation of acid-base imbalances. Record of french and english references from Medline data base. The keywords were: acid-base balance, hyperchloremic acidosis, metabolic acidosis, strong ion difference, strong ion gap. Data were selected including prospective and retrospective studies, reviews, and case reports. Acid-base disorders are commonly analysed by using the traditional Henderson-Hasselbalch approach which attributes the variations in plasma pH to the modifications in plasma bicarbonates or PaCO2. However, this approach seems to be inadequate because bicarbonates and PaCO2 are completely dependent. Moreover, it does not consider the role of weak acids such as albuminate, in the determination of plasma pH value. According to the Stewart concept, plasma pH results from the degree of plasma water dissociation which is determined by 3 independent variables: 1) strong ion difference (SID) which is the difference between all the strong plasma cations and anions; 2) quantity of plasma weak acids; 3) PaCO2. Thus, metabolic acid-base disorders are always induced by a variation in SID (decreased in acidosis) or in weak acids (increased in acidosis), whereas respiratory disorders remains the consequence of a change in PaCO2. These pathophysiological considerations are important to analyse complex acid-base imbalances in critically ill patients. For example, due to a decrease in weak acids, hypoalbuminemia increases SID which may counter-balance a decrease in pH and an elevated anion gap. Thus if using only traditional tools, hypoalbuminemia may mask a metabolic acidosis, because of a normal pH and a normal anion gap. In this case, the association of metabolic acidosis and alkalosis is only expressed by respectively a decreased SID and a decreased weak acids concentration. This concept allows to establish the relationship between hyperchloremic acidosis and infusion of solutes which contain large concentration of chloride such as NaCl 0.9%. Finally, the Stewart concept permits to understand that sodium bicarbonate as well as sodium lactate induces plasma alkalinization. In fact, sodium remains in plasma, whereas anion (lactate or bicarbonate) are metabolized leading to an increase in plasma SID. Due to its simplicity, the traditional Henderson-Hasselbalch approach of acid-base disorders, remains commonly used. However, it gives an inadequate pathophysiological analysis which may conduct to a false diagnosis, especially with complex acid-base imbalances. Despite its apparent complexity, the Stewart concept permits to understand precisely the mechanisms of acid-base disorders. It has to become the most appropriate approach to analyse complex acid-base abnormalities.

Low pacemaker incidence with continuous-sutured valves: a retrospective analysis.

PubMed

Niclauss, Lars; Delay, Dominique; Pfister, Raymond; Colombier, Sebastien; Kirsch, Matthias; Prêtre, René

2017-06-01

Background Permanent pacemaker implantation after surgical aortic valve replacement depends on patient selection and risk factors for conduction disorders. We aimed to identify risk criteria and obtain a selected group comparable to patients assigned to transcatheter aortic valve implantation. Methods Isolated sutured aortic valve replacements in 994 patients treated from 2007 to 2015 were reviewed. Demographics, hospital stay, preexisting conduction disorders, surgical technique, and etiology in patients with and without permanent pacemaker implantation were compared. Reported outcomes after transcatheter aortic valve implantation were compared with those of a subgroup including only degenerative valve disease and first redo. Results The incidence of permanent pacemaker implantation was 2.9%. Longer hospital stay ( p = 0.01), preexisting rhythm disorders ( p < 0.001), complex prosthetic endocarditis ( p = 0.01), and complex redo ( p < 0.001) were associated with permanent pacemaker implantation. Although prostheses were sutured with continuous monofilament in the majority of cases (86%), interrupted pledgetted sutures were used more often in the pacemaker group ( p = 0.002). In the subgroup analysis, the incidence of permanent pacemaker implantation was 2%; preexisting rhythm disorders and the suture technique were still major risk factors. Conclusion Permanent pacemaker implantation depends on etiology, preexisting rhythm disorders, and suture technique, and the 2% incidence compares favorably with the reported 5- to 10-fold higher incidence after transcatheter aortic valve implantation. Cost analysis should take this into account. Often dismissed as minor complication, permanent pacemaker implantation increases the risks of endocarditis, impaired myocardial recovery, and higher mortality if associated with prosthesis regurgitation.

Mental health, concurrent disorders, and health care utilization in homeless women.

PubMed

Strehlau, Verena; Torchalla, Iris; Kathy, Li; Schuetz, Christian; Krausz, Michael

2012-09-01

This study assessed lifetime and current prevalence rates of mental disorders and concurrent mental and substance use disorders in a sample of homeless women. Current suicide risk and recent health service utilization were also examined in order to understand the complex mental health issues of this population and to inform the development of new treatment strategies that better meet their specific needs. A cross-sectional survey of 196 adult homeless women in three different Canadian cities was done. Participants were assessed using DSM-IV-based structured clinical interviews. Current diagnoses were compared to available mental health prevalence rates in the Canadian female general population. Current prevalence rates were 63% for any mental disorder, excluding substance use disorders; 17% for depressive episode; 10% for manic episode; 7% for psychotic disorder; 39% for anxiety disorders, 28% for posttraumatic stress disorder; and 19% for obsessive-compulsive disorder; 58% had concurrent substance dependence and mental disorders. Lifetime prevalence rates were notably higher. Current moderate or high suicide risk was found in 22% of the women. Participants used a variety of health services, especially emergency rooms, general practitioners, and walk-in clinics. Prevalence rates of mental disorders among homeless participants were substantially higher than among women from the general Canadian population. The percentage of participants with moderate or high suicide risk and concurrent disorders indicates a high severity of mental health symptomatology. Treatment and housing programs need to be accompanied by multidisciplinary, specialized interventions that account for high rates of complex mental health conditions.

Dissociative identity disorder: An empirical overview.

PubMed

Dorahy, Martin J; Brand, Bethany L; Sar, Vedat; Krüger, Christa; Stavropoulos, Pam; Martínez-Taboas, Alfonso; Lewis-Fernández, Roberto; Middleton, Warwick

2014-05-01

Despite its long and auspicious place in the history of psychiatry, dissociative identity disorder (DID) has been associated with controversy. This paper aims to examine the empirical data related to DID and outline the contextual challenges to its scientific investigation. The overview is limited to DID-specific research in which one or more of the following conditions are met: (i) a sample of participants with DID was systematically investigated, (ii) psychometrically-sound measures were utilised, (iii) comparisons were made with other samples, (iv) DID was differentiated from other disorders, including other dissociative disorders, (v) extraneous variables were controlled or (vi) DID diagnosis was confirmed. Following an examination of challenges to research, data are organised around the validity and phenomenology of DID, its aetiology and epidemiology, the neurobiological and cognitive correlates of the disorder, and finally its treatment. DID was found to be a complex yet valid disorder across a range of markers. It can be accurately discriminated from other disorders, especially when structured diagnostic interviews assess identity alterations and amnesia. DID is aetiologically associated with a complex combination of developmental and cultural factors, including severe childhood relational trauma. The prevalence of DID appears highest in emergency psychiatric settings and affects approximately 1% of the general population. Psychobiological studies are beginning to identify clear correlates of DID associated with diverse brain areas and cognitive functions. They are also providing an understanding of the potential metacognitive origins of amnesia. Phase-oriented empirically-guided treatments are emerging for DID. The empirical literature on DID is accumulating, although some areas remain under-investigated. Existing data show DID as a complex, valid and not uncommon disorder, associated with developmental and cultural variables, that is amenable to psychotherapeutic intervention.

Yet More Lessons From Complexity. Unity the key for Peace.

NASA Astrophysics Data System (ADS)

Puente, C. E.

2004-12-01

The last few decades have witnessed the development of a host of ideas aimed at understanding and predicting nature's ever present complexity. It is shown that such a work provides, through its detailed study of order and disorder, a suitable framework for visualizing the dynamics and consequences of mankind's ever present divisive traits. Specifically, this work explains how recent universal results pertaining to power-laws, self-organized criticality and space-filling transformations provide additional and pertinent reminders that point us to unity as an essential element for us to achieve peace.

The gut microbiota and the emergence of autoimmunity: relevance to major psychiatric disorders

PubMed Central

Severance, EG; Tveiten, D; Lindström, LH; Yolken, RH; Reichelt, KL

2017-01-01

Background Autoimmune phenotypes are prevalent in major psychiatric disorders. Disequilibria of cellular processes occurring in the gastrointestinal (GI) tract likely contribute to immune dysfunction in psychiatric disorders. As the venue of a complex community of resident microbes, the gut in a homeostatic state equates with a functional digestive system, cellular barrier stability and properly regulated recognition of self and non-self antigens. When gut processes become disrupted as a result of environmental or genetic factors, autoimmunity may ensue. Methods Here, we review the issues pertinent to autoimmunity and the microbiome in psychiatric disorders and show that many of the reported immune risk factors for the development of these brain disorders are in fact related and consistent with dysfunctions occurring in the gut. We review the few human microbiome studies that have been done in people with psychiatric disorders and supplement this information with mechanistic data gleaned from experimental rodent studies. Results These investigations demonstrate changes in behavior and brain biochemistry directly attributable to alterations in the gut microbiome. We present a model by which autoantigens are produced by extrinsically-derived food and microbial factors bound to intrinsic components of the gut including receptors present in the enteric nervous system. Conclusion This new focus on examining activities outside of the CNS for relevance to the etiology and pathophysiology of psychiatric disorders may require new modalities or a re-evaluation of pharmaceutical targets found in peripheral systems. PMID:27634185

Similar local order in disordered fluorite and aperiodic pyrochlore structures

DOE PAGES

Shamblin, Jacob; Tracy, Cameron; Palomares, Raul; ...

2017-10-01

A major challenge to understanding the response of materials to extreme environments (e.g., nuclear fuels/waste forms and fusion materials) is to unravel the processes by which a material can incorporate atomic-scale disorder, and at the same time, remain crystalline. While it has long been known that all condensed matter, even liquids and glasses, possess short-range order, the relation between fully-ordered, disordered, and aperiodic structures over multiple length scales is not well understood. For example, when defects are introduced (via pressure or irradiation) into materials adopting the pyrochlore structure, these complex oxides either disorder over specific crystallographic sites, remaining crystalline, ormore » become aperiodic. Here we present neutron total scattering results characterizing the irradiation response of two pyrochlores, one that is known to disorder (Er2Sn2O7) and the other to amorphize (Dy2Sn2O7) under ion irradiation. The results demonstrate that in both cases, the local pyrochlore structure is transformed into similar short range configurations that are best fit by the orthorhombic weberite structure, even though the two compositions have distinctly different structures, aperiodic vs. disordered-crystalline, at longer length scales. Thus, a material's resistance to amorphization may not depend primarily on local defect formation energies, but rather on the structure's compatibility with meso-scale modulations of the local order in a way that maintains long-range periodicity.« less

Novel linkage disequilibrium clustering algorithm identifies new lupus genes on meta-analysis of GWAS datasets.

PubMed

Saeed, Mohammad

2017-05-01

Systemic lupus erythematosus (SLE) is a complex disorder. Genetic association studies of complex disorders suffer from the following three major issues: phenotypic heterogeneity, false positive (type I error), and false negative (type II error) results. Hence, genes with low to moderate effects are missed in standard analyses, especially after statistical corrections. OASIS is a novel linkage disequilibrium clustering algorithm that can potentially address false positives and negatives in genome-wide association studies (GWAS) of complex disorders such as SLE. OASIS was applied to two SLE dbGAP GWAS datasets (6077 subjects; ∼0.75 million single-nucleotide polymorphisms). OASIS identified three known SLE genes viz. IFIH1, TNIP1, and CD44, not previously reported using these GWAS datasets. In addition, 22 novel loci for SLE were identified and the 5 SLE genes previously reported using these datasets were verified. OASIS methodology was validated using single-variant replication and gene-based analysis with GATES. This led to the verification of 60% of OASIS loci. New SLE genes that OASIS identified and were further verified include TNFAIP6, DNAJB3, TTF1, GRIN2B, MON2, LATS2, SNX6, RBFOX1, NCOA3, and CHAF1B. This study presents the OASIS algorithm, software, and the meta-analyses of two publicly available SLE GWAS datasets along with the novel SLE genes. Hence, OASIS is a novel linkage disequilibrium clustering method that can be universally applied to existing GWAS datasets for the identification of new genes.

Genetic variations in the Dravidian population of South West coast of India: Implications in designing case-control studies.

PubMed

D'Cunha, Anitha; Pandit, Lekha; Malli, Chaithra

2017-06-01

Indian data have been largely missing from genome-wide databases that provide information on genetic variations in different populations. This hinders association studies for complex disorders in India. This study was aimed to determine whether the complex genetic structure and endogamy among Indians could potentially influence the design of case-control studies for autoimmune disorders in the south Indian population. A total of 12 single nucleotide variations (SNVs) related to genes associated with autoimmune disorders were genotyped in 370 healthy individuals belonging to six different caste groups in southern India. Allele frequencies were estimated; genetic divergence and phylogenetic relationship within the various caste groups and other HapMap populations were ascertained. Allele frequencies for all genotyped SNVs did not vary significantly among the different groups studied. Wright's FSTwas 0.001 per cent among study population and 0.38 per cent when compared with Gujarati in Houston (GIH) population on HapMap data. The analysis of molecular variance results showed a 97 per cent variation attributable to differences within the study population and <1 per cent variation due to differences between castes. Phylogenetic analysis showed a separation of Dravidian population from other HapMap populations and particularly from GIH population. Despite the complex genetic origins of the Indian population, our study indicated a low level of genetic differentiation among Dravidian language-speaking people of south India. Case-control studies of association among Dravidians of south India may not require stratification based on language and caste.

Free Energy and Virtual Reality in Neuroscience and Psychoanalysis: A Complexity Theory of Dreaming and Mental Disorder

PubMed Central

Hopkins, Jim

2016-01-01

The main concepts of the free energy (FE) neuroscience developed by Karl Friston and colleagues parallel those of Freud's Project for a Scientific Psychology. In Hobson et al. (2014) these include an innate virtual reality generator that produces the fictive prior beliefs that Freud described as the primary process. This enables Friston's account to encompass a unified treatment—a complexity theory—of the role of virtual reality in both dreaming and mental disorder. In both accounts the brain operates to minimize FE aroused by sensory impingements—including interoceptive impingements that report compliance with biological imperatives—and constructs a representation/model of the causes of impingement that enables this minimization. In Friston's account (variational) FE equals complexity minus accuracy, and is minimized by increasing accuracy and decreasing complexity. Roughly the brain (or model) increases accuracy together with complexity in waking. This is mediated by consciousness-creating active inference—by which it explains sensory impingements in terms of perceptual experiences of their causes. In sleep it reduces complexity by processes that include both synaptic pruning and consciousness/virtual reality/dreaming in REM. The consciousness-creating active inference that effects complexity-reduction in REM dreaming must operate on FE-arousing data distinct from sensory impingement. The most relevant source is remembered arousals of emotion, both recent and remote, as processed in SWS and REM on “active systems” accounts of memory consolidation/reconsolidation. Freud describes these remembered arousals as condensed in the dreamwork for use in the conscious contents of dreams, and similar condensation can be seen in symptoms. Complexity partly reflects emotional conflict and trauma. This indicates that dreams and symptoms are both produced to reduce complexity in the form of potentially adverse (traumatic or conflicting) arousals of amygdala-related emotions. Mental disorder is thus caused by computational complexity together with mechanisms like synaptic pruning that have evolved for complexity-reduction; and important features of disorder can be understood in these terms. Details of the consilience among Freudian, systems consolidation, and complexity-reduction accounts appear clearly in the analysis of a single fragment of a dream, indicating also how complexity reduction proceeds by a process resembling Bayesian model selection. PMID:27471478

Final Report: Continuation Study: A Systems Approach to Understanding Post-Traumatic Stress Disorder

DTIC Science & Technology

2017-01-31

Research Office P.O. Box 12211 Research Triangle Park, NC 27709-2211 Post Traumatic Stress Disorder, HPA-Circadian-metabolic pathway, methylation...17150 remaining probes were located in coding regions. Linear additive models were used to test the interactions among the quantitative loci and...SECURITY CLASSIFICATION OF: Post -Traumatic Stress Disorder (PTSD) is a complex anxiety disorder affecting many combat-exposed soldiers. Current

The spectrum of clinical presentation, diagnosis, and management of mitochondrial forms of diabetes.

PubMed

Karaa, Amel; Goldstein, Amy

2015-02-01

Primary mitochondrial diseases refer to a group of heterogeneous and complex genetic disorders affecting 1:5000 people. The true prevalence is anticipated to be even higher because of the complexity of achieving a diagnosis in many patients who present with multisystemic complaints ranging from infancy to adulthood. Diabetes is a prominent feature of several of these disorders which might be overlooked by the endocrinologist. We here review mitochondrial disorders and describe the phenotypic and pathogenetic differences between mitochondrial diabetes mellitus (mDM) and other more common forms of diabetes mellitus. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Malleable machines in transcription regulation: the mediator complex.

PubMed

Tóth-Petróczy, Agnes; Oldfield, Christopher J; Simon, István; Takagi, Yuichiro; Dunker, A Keith; Uversky, Vladimir N; Fuxreiter, Monika

2008-12-01

The Mediator complex provides an interface between gene-specific regulatory proteins and the general transcription machinery including RNA polymerase II (RNAP II). The complex has a modular architecture (Head, Middle, and Tail) and cryoelectron microscopy analysis suggested that it undergoes dramatic conformational changes upon interactions with activators and RNAP II. These rearrangements have been proposed to play a role in the assembly of the preinitiation complex and also to contribute to the regulatory mechanism of Mediator. In analogy to many regulatory and transcriptional proteins, we reasoned that Mediator might also utilize intrinsically disordered regions (IDRs) to facilitate structural transitions and transmit transcriptional signals. Indeed, a high prevalence of IDRs was found in various subunits of Mediator from both Saccharomyces cerevisiae and Homo sapiens, especially in the Tail and the Middle modules. The level of disorder increases from yeast to man, although in both organisms it significantly exceeds that of multiprotein complexes of a similar size. IDRs can contribute to Mediator's function in three different ways: they can individually serve as target sites for multiple partners having distinctive structures; they can act as malleable linkers connecting globular domains that impart modular functionality on the complex; and they can also facilitate assembly and disassembly of complexes in response to regulatory signals. Short segments of IDRs, termed molecular recognition features (MoRFs) distinguished by a high protein-protein interaction propensity, were identified in 16 and 19 subunits of the yeast and human Mediator, respectively. In Saccharomyces cerevisiae, the functional roles of 11 MoRFs have been experimentally verified, and those in the Med8/Med18/Med20 and Med7/Med21 complexes were structurally confirmed. Although the Saccharomyces cerevisiae and Homo sapiens Mediator sequences are only weakly conserved, the arrangements of the disordered regions and their embedded interaction sites are quite similar in the two organisms. All of these data suggest an integral role for intrinsic disorder in Mediator's function.

Context processing in adolescents with autism spectrum disorder: How complex could it be?

PubMed

Ben-Yosef, Dekel; Anaki, David; Golan, Ofer

2017-03-01

The ability of individuals with Autism Spectrum Disorder (ASD) to process context has long been debated: According to the Weak Central Coherence theory, ASD is characterized by poor global processing, and consequently-poor context processing. In contrast, the Social Cognition theory argues individuals with ASD will present difficulties only in social context processing. The complexity theory of autism suggests context processing in ASD will depend on task complexity. The current study examined this controversy through two priming tasks, one presenting human stimuli (facial expressions) and the other presenting non-human stimuli (animal faces). Both tasks presented visual targets, preceded by congruent, incongruent, or neutral auditory primes. Local and global processing were examined by presenting the visual targets in three spatial frequency conditions: High frequency, low frequency, and broadband. Tasks were administered to 16 adolescents with high functioning ASD and 16 matched typically developing adolescents. Reaction time and accuracy were measured for each task in each condition. Results indicated that individuals with ASD processed context for both human and non-human stimuli, except in one condition, in which human stimuli had to be processed globally (i.e., target presented in low frequency). The task demands presented in this condition, and the performance deficit shown in the ASD group as a result, could be understood in terms of cognitive overload. These findings provide support for the complexity theory of autism and extend it. Our results also demonstrate how associative priming could support intact context processing of human and non-human stimuli in individuals with ASD. Autism Res 2017, 10: 520-530. © 2016 International Society for Autism Research, Wiley Periodicals, Inc. © 2016 International Society for Autism Research, Wiley Periodicals, Inc.

Prevalence of mental disorders among depressed coronary patients with and without Type D personality. Results of the multi-center SPIRR-CAD trial.

PubMed

Lambertus, Frank; Herrmann-Lingen, Christoph; Fritzsche, Kurt; Hamacher, Stefanie; Hellmich, Martin; Jünger, Jana; Ladwig, Karl-Heinz; Michal, Matthias; Ronel, Joram; Schultz, Jobst-Hendrik; Vitinius, Frank; Weber, Cora; Albus, Christian

Type D personality, as with formal mental disorders, is linked to increased mortality in coronary heart disease (CHD). Our aim was to determine the prevalence of mental disorders among depressed CHD patients with and without Type D personality. Depressive symptoms (HADS, HAM-D), Type D personality (DS-14) and mental disorders based on DSM-IV (SCID I and II) were assessed. Results were calculated by Kruskal-Wallis tests, Fisher's exact tests and logistic regression analyses. 570 CHD patients were included (age 59.2±9.5years; male 78.9%, HADS-D depression 10.4±2.5; HAM-D 11.3±6.6; Type D 60.1%). 84.8% of patients with Type D personality and 79.3% of non-Type D patients suffered from at least one mental disorder (p=0.092), while 41.8% of Type D positives and 27.8% of Type D negatives had at least two mental disorders (p=0.001). Patients with Type D personality significantly more often had social phobia [odds ratio (95% confidence interval): 3.79 (1.1 to 13.12); p=0.035], dysthymia [1.78 (1.12 to 2.84); p=0.015], compulsive [2.25 (1.04 to 4.86); p=0.038] or avoidant [8.95 (2.08 to 38.49); p=0.003] personality disorder. Type D personality among depressed CHD patients is associated with more complex and enduring mental disorders. This implies higher treatment demands. ISRCTN 76240576; NCT00705965. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

Can Classification Tree Analyses Help Improve Decision Making About Treatments for Depression and Anxiety Disorders? A Preliminary Investigation

PubMed Central

Rhodes, Louisa; Naumann, Ulrike M.

2011-01-01

Objective: To identify how decisions about treatment are being made in secondary services for anxiety disorders and depression and, specifically, whether it was possible to predict the decisions to refer for evidence-based treatments. Method: Post hoc classification tree analysis was performed using a sample from an audit on implementation of the National Institute for Health and Clinical Excellence Guidelines for Depression and Anxiety Disorders. The audit was of 5 teams offering secondary care services; they included psychiatrists, psychologists, community psychiatric nurses, social workers, dual-diagnosis workers, and vocational workers. The patient sample included all of those with a primary problem of depression (n = 56) or an anxiety disorder (n = 16) who were offered treatment from February 16 to April 3, 2009. The outcome variable was whether or not evidence-based treatments were offered, and the predictor variables were presenting problem, risk, comorbid problem, social problems, and previous psychiatric history. Results: Treatment decisions could be more accurately predicted for anxiety disorders (93% correct) than for depression (55%). For anxiety disorders, the presence or absence of social problems was a good predictor for whether evidence-based or non–evidence-based treatments were offered; 44% (4/9) of those with social problems vs 100% (6/6) of those without social problems were offered evidence-based treatments. For depression, patients’ risk rating had the largest impact on treatment decisions, although no one variable could be identified as individually predictive of all treatment decisions. Conclusions: Treatment decisions were generally consistent for anxiety disorders but more idiosyncratic for depression, making the development of a decision-making model very difficult for depression. The lack of clarity of some terms in the clinical guidelines and the more complex nature of depression could be factors contributing to this difficulty. Further research is needed to understand the complex nature of decision making with depressed patients. PMID:22295255

Assessing the causal role of adiposity on disordered eating in childhood, adolescence, and adulthood: a Mendelian randomization analysis

PubMed Central

2017-01-01

Background: Observational studies have shown that higher body mass index (BMI) is associated with increased risk of developing disordered eating patterns. However, the causal direction of this relation remains ambiguous. Objective: We used Mendelian randomization (MR) to infer the direction of causality between BMI and disordered eating in childhood, adolescence, and adulthood. Design: MR analyses were conducted with a genetic score as an instrumental variable for BMI to assess the causal effect of BMI at age 7 y on disordered eating patterns at age 13 y with the use of data from the Avon Longitudinal Study of Parents and Children (ALSPAC) (n = 4473). To examine causality in the reverse direction, MR analyses were used to estimate the effect of the same disordered eating patterns at age 13 y on BMI at age 17 y via a split-sample approach in the ALSPAC. We also investigated the causal direction of the association between BMI and eating disorders (EDs) in adults via a two-sample MR approach and publically available genome-wide association study data. Results: MR results indicated that higher BMI at age 7 y likely causes higher levels of binge eating and overeating, weight and shape concerns, and weight-control behavior patterns in both males and females and food restriction in males at age 13 y. Furthermore, results suggested that higher levels of binge eating and overeating in males at age 13 y likely cause higher BMI at age 17 y. We showed no evidence of causality between BMI and EDs in adulthood in either direction. Conclusions: This study provides evidence to suggest a causal effect of higher BMI in childhood and increased risk of disordered eating at age 13 y. Furthermore, higher levels of binge eating and overeating may cause higher BMI in later life. These results encourage an exploration of the ways to break the causal chain between these complex phenotypes, which could inform and prevent disordered eating problems in adolescence. PMID:28747331

Assessing the causal role of adiposity on disordered eating in childhood, adolescence, and adulthood: a Mendelian randomization analysis.

PubMed

Reed, Zoe E; Micali, Nadia; Bulik, Cynthia M; Davey Smith, George; Wade, Kaitlin H

2017-09-01

Background: Observational studies have shown that higher body mass index (BMI) is associated with increased risk of developing disordered eating patterns. However, the causal direction of this relation remains ambiguous. Objective: We used Mendelian randomization (MR) to infer the direction of causality between BMI and disordered eating in childhood, adolescence, and adulthood. Design: MR analyses were conducted with a genetic score as an instrumental variable for BMI to assess the causal effect of BMI at age 7 y on disordered eating patterns at age 13 y with the use of data from the Avon Longitudinal Study of Parents and Children (ALSPAC) ( n = 4473). To examine causality in the reverse direction, MR analyses were used to estimate the effect of the same disordered eating patterns at age 13 y on BMI at age 17 y via a split-sample approach in the ALSPAC. We also investigated the causal direction of the association between BMI and eating disorders (EDs) in adults via a two-sample MR approach and publically available genome-wide association study data. Results: MR results indicated that higher BMI at age 7 y likely causes higher levels of binge eating and overeating, weight and shape concerns, and weight-control behavior patterns in both males and females and food restriction in males at age 13 y. Furthermore, results suggested that higher levels of binge eating and overeating in males at age 13 y likely cause higher BMI at age 17 y. We showed no evidence of causality between BMI and EDs in adulthood in either direction. Conclusions: This study provides evidence to suggest a causal effect of higher BMI in childhood and increased risk of disordered eating at age 13 y. Furthermore, higher levels of binge eating and overeating may cause higher BMI in later life. These results encourage an exploration of the ways to break the causal chain between these complex phenotypes, which could inform and prevent disordered eating problems in adolescence.

Risk factors in autism: Thinking outside the brain

PubMed Central

Matelski, Lauren; Van de Water, Judy

2017-01-01

Autism spectrum disorders (ASD) are complex neurodevelopmental conditions that have been rising markedly in prevalence for the past 30 years, now thought to affect 1 in 68 in the United States. This has prompted the search for possible explanations, and has even resulted in some controversy regarding the “true” prevalence of autism. ASD are influenced by a variety of genetic, environmental, and possibly immunological factors that act during critical periods to alter key developmental processes. This can affect multiple systems and manifests as the social and behavioral deficits that define these disorders. The interaction of environmental exposures in the context of an individual’s genetic susceptibilities manifests differently in each case, leading to heterogeneous phenotypes and varied comorbid symptoms within the disorder. This has also made it very difficult to elucidate underlying genes and exposure profiles, but progress is being made in this area. Some pharmaceutical drugs, toxicants, and metabolic and nutritional factors have been identified in epidemiological studies as increasing autism risk, especially during the prenatal period. Immunologic risk factors, including maternal infection during pregnancy, autoantibodies to fetal brain proteins, and familial autoimmune disease, have consistently been observed across multiple studies, as have immune abnormalities in individuals with ASD. Mechanistic research using animal models and patient-derived stem cells will help researchers to understand the complex etiology of these neurodevelopmental disorders, which will lead to more effective therapies and preventative strategies. Proposed therapies that need more investigation include special diets, probiotics, immune modulation, oxytocin, and personalized pharmacogenomic targets. The ongoing search for biomarkers and better treatments will result in earlier identification of ASD and provide much needed help and relief for afflicted families. PMID:26725748

Repeat-mediated genetic and epigenetic changes at the FMR1 locus in the Fragile X-related disorders

PubMed Central

Usdin, Karen; Hayward, Bruce E.; Kumari, Daman; Lokanga, Rachel A.; Sciascia, Nicholas; Zhao, Xiao-Nan

2014-01-01

The Fragile X-related disorders are a group of genetic conditions that include the neurodegenerative disorder, Fragile X-associated tremor/ataxia syndrome (FXTAS), the fertility disorder, Fragile X-associated primary ovarian insufficiency (FXPOI) and the intellectual disability, Fragile X syndrome (FXS). The pathology in all these diseases is related to the number of CGG/CCG-repeats in the 5′ UTR of the Fragile X mental retardation 1 (FMR1) gene. The repeats are prone to continuous expansion and the increase in repeat number has paradoxical effects on gene expression increasing transcription on mid-sized alleles and decreasing it on longer ones. In some cases the repeats can simultaneously both increase FMR1 mRNA production and decrease the levels of the FMR1 gene product, Fragile X mental retardation 1 protein (FMRP). Since FXTAS and FXPOI result from the deleterious consequences of the expression of elevated levels of FMR1 mRNA and FXS is caused by an FMRP deficiency, the clinical picture is turning out to be more complex than once appreciated. Added complications result from the fact that increasing repeat numbers make the alleles somatically unstable. Thus many individuals have a complex mixture of different sized alleles in different cells. Furthermore, it has become apparent that the eponymous fragile site, once thought to be no more than a useful diagnostic criterion, may have clinical consequences for females who inherit chromosomes that express this site. This review will cover what is currently known about the mechanisms responsible for repeat instability, for the repeat-mediated epigenetic changes that affect expression of the FMR1 gene, and for chromosome fragility. It will also touch on what current and future options are for ameliorating some of these effects. PMID:25101111

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

ADHD latent class clusters: DSM-IV subtypes and comorbidity

PubMed Central

Elia, Josephine; Arcos-Burgos, Mauricio; Bolton, Kelly L.; Ambrosini, Paul J.; Berrettini, Wade; Muenke, Maximilian

2014-01-01

ADHD (Attention Deficit Hyperactivity Disorder) has a complex, heterogeneous phenotype only partially captured by Diagnostic and Statistical Manual of Mental Disorders (DSM-IV) criteria. In this report, latent class analyses (LCA) are used to identify ADHD phenotypes using K-SADS-IVR (Schedule for Affective Disorders & Schizophrenia for School Age Children-IV-Revised) symptoms and symptom severity data from a clinical sample of 500 ADHD subjects, ages 6–18, participating in an ADHD genetic study. Results show that LCA identified six separate ADHD clusters, some corresponding to specific DSM-IV subtypes while others included several subtypes. DSM-IV comorbid anxiety and mood disorders were generally similar across all clusters, and subjects without comorbidity did not aggregate within any one cluster. Age and gender composition also varied. These results support findings from population-based LCA studies. The six clusters provide additional homogenous groups that can be used to define ADHD phenotypes in genetic association studies. The limited age ranges aggregating in the different clusters may prove to be a particular advantage in genetic studies where candidate gene expression may vary during developmental phases. DSM-IV comorbid mood and anxiety disorders also do not appear to increase cluster heterogeneity; however, longitudinal studies that cover period of risk are needed to support this finding. PMID:19900717

Augmentative and alternative communication supports for adults with autism spectrum disorders.

PubMed

Trembath, David; Iacono, Teresa; Lyon, Katie; West, Denise; Johnson, Hilary

2014-11-01

Many adults with autism spectrum disorders have complex communication needs and may benefit from the use of augmentative and alternative communication. However, there is a lack of research examining the specific communication needs of these adults, let alone the outcomes of interventions aimed at addressing them. The aim of this study was to explore the views and experiences of support workers and family members regarding the outcomes of providing low-technology communication aids to adults with autism spectrum disorders. The participants were six support workers and two family members of six men and women with autism spectrum disorders, who had received low-technology communication aids. Using semi-structured, in-depth interviews and following thematic analysis, the results revealed strong support for, and the potential benefits of, augmentative and alternative communication for both adults with autism spectrum disorders and their communication partners. The results also revealed inconsistencies in the actions taken to support the use of the prescribed augmentative and alternative communication systems, pointing to the clinical need to address common barriers to the provision of augmentative and alternative communication support. These barriers include organisational practices and limitations in the knowledge and skills of key stakeholders, as well as problematic attitudes. © The Author(s) 2013.

Gene Expression Profiling in Rodent Models for Schizophrenia

PubMed Central

Schijndel, Jessica E. Van; Martens, Gerard J.M

2010-01-01

The complex neurodevelopmental disorder schizophrenia is thought to be induced by an interaction between predisposing genes and environmental stressors. In order to get a better insight into the aetiology of this complex disorder, animal models have been developed. In this review, we summarize mRNA expression profiling studies on neurodevelopmental, pharmacological and genetic animal models for schizophrenia. We discuss parallels and contradictions among these studies, and propose strategies for future research. PMID:21629445

Mental capacity, diagnosis and insight in psychiatric in-patients: a cross-sectional study.

PubMed

Owen, G S; David, A S; Richardson, G; Szmukler, G; Hayward, P; Hotopf, M

2009-08-01

Mental capacity is now a core part of UK mental health law and clinicians will increasingly be expected to assess it. Because it is a legal concept there is a need to clarify associations with variables that clinicians are more familiar with, especially insight. In this cross-sectional study we recruited consecutive psychiatric admissions to the Maudsley Hospital, London. We carried out structured assessments of decision making using the MacArthur Competence Assessment Tool for Treatment (MacCAT-T), resulting in a clinical judgement about capacity status. We analysed associations with a range of sociodemographic and clinical variables, including insight score on the Expanded Schedule for the Assessment of Insight (SAI-E). The same variables were compared in an analysis stratified according to diagnostic group: psychotic disorders/bipolar affective disorder (BPAD)/non-psychotic disorders. Psychotic disorders and manic episodes of BPAD are most strongly associated with incapacity. In such patients, insight is the best discriminator of capacity status. In patients with non-psychotic disorders, insight is less strongly associated with capacity; in this group depressed mood discriminates capacity status whereas it does not in psychotic disorders. Cognitive performance does not discriminate capacity status in patients with psychotic disorders. Mental capacity has complex relationships with psychopathological variables, and these relationships are different according to diagnostic group. Insight is the best discriminator of capacity status in psychotic disorders and BPAD but not in non-psychotic disorders.

Identification of the TFII-I family target genes in the vertebrate genome.

PubMed

Chimge, Nyam-Osor; Makeyev, Aleksandr V; Ruddle, Frank H; Bayarsaihan, Dashzeveg

2008-07-01

GTF2I and GTF2IRD1 encode members of the TFII-I transcription factor family and are prime candidates in the Williams syndrome, a complex neurodevelopmental disorder. Our previous expression microarray studies implicated TFII-I proteins in the regulation of a number of genes critical in various aspects of cell physiology. Here, we combined bioinformatics and microarray results to identify TFII-I downstream targets in the vertebrate genome. These results were validated by chromatin immunoprecipitation and siRNA analysis. The collected evidence revealed the complexity of TFII-I-mediated processes that involve distinct regulatory networks. Altogether, these results lead to a better understanding of specific molecular events, some of which may be responsible for the Williams syndrome phenotype.

The crystallography of correlated disorder.

PubMed

Keen, David A; Goodwin, Andrew L

2015-05-21

Classical crystallography can determine structures as complicated as multi-component ribosomal assemblies with atomic resolution, but is inadequate for disordered systems--even those as simple as water ice--that occupy the complex middle ground between liquid-like randomness and crystalline periodic order. Correlated disorder nevertheless has clear crystallographic signatures that map to the type of disorder, irrespective of the underlying physical or chemical interactions and material involved. This mapping hints at a common language for disordered states that will help us to understand, control and exploit the disorder responsible for many interesting physical properties.

Shame, pride and eating disorders.

PubMed

Goss, Kenneth; Allan, Steven

2009-01-01

This paper explores shame and shame-based responses in eating disorders. Research linking shame with eating disorders and the possible role of shame and pride in the onset and maintenance of eating disorders is reviewed. The experience of shame is likely to be complex, dynamic and variable. However, the key to identifying shame is often via the various coping strategies adopted, which in turn may form part of a maintenance cycle for eating disorder beliefs and behaviours. An outline model of shame and pride cycles in the maintenance of eating disorders is presented with clinical implications.

Treatment of obsessive-compulsive disorder complicated by comorbid eating disorders.

PubMed

Simpson, H Blair; Wetterneck, Chad T; Cahill, Shawn P; Steinglass, Joanna E; Franklin, Martin E; Leonard, Rachel C; Weltzin, Theodore E; Riemann, Bradley C

2013-01-01

Eating disorders and obsessive-compulsive disorder (OCD) commonly co-occur, but there is little data for how to treat these complex cases. To address this gap, we examined the naturalistic outcome of 56 patients with both disorders, who received a multimodal treatment program designed to address both problems simultaneously. A residential treatment program developed a cognitive-behavioral approach for patients with both OCD and an eating disorder by integrating exposure and response prevention (ERP) treatment for OCD with ERP strategies targeting eating pathology. Patients also received a supervised eating plan, medication management, and social support. At admission and discharge, patients completed validated measures of OCD severity (the Yale-Brown Obsessive-Compulsive Scale--Self Report [Y-BOCS-SR]), eating disorder severity (the Eating Disorders Examination-Questionnaire), and depressive severity (the Beck Depression Inventory II [BDI-II]). Body mass index (BMI) was also measured. Paired-sample t-tests examined change on these measures. Between 2006 and 2011, 56 individuals completed all study measures at admission and discharge. Mean length of stay was 57 days (SD = 27). Most (89%) were on psychiatric medications. Significant decreases were observed in OCD severity, eating disorder severity, and depression. Those with bulimia nervosa showed more improvement than those with anorexia nervosa. BMI significantly increased, primarily among those underweight at admission. Simultaneous treatment of OCD and eating disorders using a multimodal approach that emphasizes ERP techniques for both OCD and eating disorders can be an effective treatment strategy for these complex cases.

Addressing the Complex Needs of Students with Attachment Disorders

ERIC Educational Resources Information Center

Losinski, Mickey; Katsiyannis, Antonis; White, Sherry; Wiseman, Nicole

2016-01-01

Attachment disorders are a relatively rare condition affecting children. This is particularly true for those who are adopted or living in foster care, and are thought to be attributed to an interruption in the bonding between a child and his or her caregiver. Attachment disorders are divided into two distinct categories: a predominately withdrawn…

Clinical Reasoning in the Assessment and Planning for Intervention for Autism Spectrum Disorder

ERIC Educational Resources Information Center

McCrimmon, Adam W.; Yule, Ashleigh E.

2017-01-01

Autism spectrum disorder (ASD) is a complex neurodevelopmental disorder whose incidence is rising. School-based professionals are in an ideal position to provide the much-needed assessment and intervention supports for students with ASD, as the professionals' placement within a formal system affords the opportunity to observe and support children…

Executive Function, Social Emotional Learning, and Social Competence in School-Aged Boys with Autism Spectrum Disorder

ERIC Educational Resources Information Center

Berard, Nathalie; Loutzenhiser, Lynn; Sevigny, Phillip R.; Alfano, Dennis P.

2017-01-01

Autism Spectrum Disorder (ASD) is an aetiologically complex neurodevelopmental disorder characterized by deficits in social functioning. Children with ASD display a wide range of social competence and more variability in social domains as compared with either communication or repetitive behaviour domains. There is limited understanding of factors…

The Expression of Caspases Is Enhanced in Peripheral Blood Mononuclear Cells of Autism Spectrum Disorder Patients

ERIC Educational Resources Information Center

Siniscalco, Dario; Sapone, Anna; Giordano, Catia; Cirillo, Alessandra; de Novellis, Vito; de Magistris, Laura; Rossi, Francesco; Fasano, Alessio; Maione, Sabatino; Antonucci, Nicola

2012-01-01

Autism and autism spectrum disorders (ASDs) are heterogeneous complex neuro-developmental disorders characterized by dysfunctions in social interaction and communication skills. Their pathogenesis has been linked to interactions between genes and environmental factors. Consistent with the evidence of certain similarities between immune cells and…

Nonlinear Complexity Analysis of Brain fMRI Signals in Schizophrenia

PubMed Central

Sokunbi, Moses O.; Gradin, Victoria B.; Waiter, Gordon D.; Cameron, George G.; Ahearn, Trevor S.; Murray, Alison D.; Steele, Douglas J.; Staff, Roger T.

2014-01-01

We investigated the differences in brain fMRI signal complexity in patients with schizophrenia while performing the Cyberball social exclusion task, using measures of Sample entropy and Hurst exponent (H). 13 patients meeting diagnostic and Statistical Manual of Mental Disorders, 4th Edition (DSM IV) criteria for schizophrenia and 16 healthy controls underwent fMRI scanning at 1.5 T. The fMRI data of both groups of participants were pre-processed, the entropy characterized and the Hurst exponent extracted. Whole brain entropy and H maps of the groups were generated and analysed. The results after adjusting for age and sex differences together show that patients with schizophrenia exhibited higher complexity than healthy controls, at mean whole brain and regional levels. Also, both Sample entropy and Hurst exponent agree that patients with schizophrenia have more complex fMRI signals than healthy controls. These results suggest that schizophrenia is associated with more complex signal patterns when compared to healthy controls, supporting the increase in complexity hypothesis, where system complexity increases with age or disease, and also consistent with the notion that schizophrenia is characterised by a dysregulation of the nonlinear dynamics of underlying neuronal systems. PMID:24824731

The Accuracy of the ADOS-2 in Identifying Autism among Adults with Complex Psychiatric Conditions

ERIC Educational Resources Information Center

Maddox, Brenna B.; Brodkin, Edward S.; Calkins, Monica E.; Shea, Kathleen; Mullan, Katherine; Hostager, Jack; Mandell, David S.; Miller, Judith S.

2017-01-01

The Autism Diagnostic Observation Schedule, Second Edition (ADOS-2), Module 4 is considered a "gold-standard" instrument for diagnosing autism spectrum disorder (ASD) in adults. Although the ADOS-2 shows good sensitivity and specificity in lab-based settings, it is unknown whether these results hold in community clinics that serve a more…

Noonan Syndrome Complicated by Primary Pulmonary Lymphangiectasia.

PubMed

Ford, Jaclyn Jo; Trotter, Carol W

2015-01-01

Noonan syndrome is a genetic disorder that has several features common to other conditions, making diagnosis a challenge. This column summarizes the case of a neonate with an atypical presentation of Noonan syndrome involving a fatal type of lymphangiectasia resulting in persistent pleural effusions. Radiographic features of this condition are presented along with the complexities of diagnosis and treatment.

Familial Associations of Intense Preoccupations, an Empirical Factor of the Restricted, Repetitive Behaviors and Interests Domain of Autism

ERIC Educational Resources Information Center

Smith, Christopher J.; Lang, Colleen M.; Kryzak, Lauren; Reichenberg, Abraham; Hollander, Eric; Silverman, Jeremy M.

2009-01-01

Background: Clinical heterogeneity of autism likely hinders efforts to find genes associated with this complex psychiatric disorder. Some studies have produced promising results by restricting the sample according to the expression of specific familial factors or components of autism. Previous factor analyses of the restricted, repetitive…

[Attention deficit hyperactivity disorder and/or bipolar disorder?].

PubMed

Da Fonseca, D; Adida, M; Belzeaux, R; Azorin, J-M

2014-12-01

The attention deficit disorder and the bipolar disorder maintain a complex relation. Indeed, these two syndromes share numerous symptoms that engender numerous diagnostic difficulties. According to several studies, it seems that these two disorders are really different with significant differences at the functional and anatomical level. However, there are common cognitive deficits as well as relatively frequent co-morbidity which is necessary to know in order to adjust the treatment. Copyright © 2014 L’Encéphale. Published by Elsevier Masson SAS.. All rights reserved.

Treatment of complex dissociative disorders: a comparison of interventions reported by community therapists versus those recommended by experts.

PubMed

Myrick, Amie C; Chasson, Gregory S; Lanius, Ruth A; Leventhal, Barry; Brand, Bethany L

2015-01-01

There is a paucity of empirical data to assist clinicians in choosing interventions to use with patients with complex dissociative disorder (DD; i.e., dissociative identity disorder and dissociative disorder not otherwise specified) at different stages in treatment. This study compared interventions used by a sample of international outpatient therapists treating DD clients in the 1st 2 stages of treatment with those recommended by expert DD therapists. There were many similarities between therapists' and experts' interventions, including the use of several emotion regulation and dissociation-focused interventions. However, community therapists reported significantly less focus on relationally oriented interventions, teaching and using grounding and containment skills, and stabilizing patients after revictimization by alleged perpetrators. This study has important implications for the development and implementation of training opportunities for DD therapists.

Genetic aspects of autism spectrum disorders: insights from animal models

PubMed Central

Banerjee, Swati; Riordan, Maeveen; Bhat, Manzoor A.

2014-01-01

Autism spectrum disorders (ASDs) are a complex neurodevelopmental disorder that display a triad of core behavioral deficits including restricted interests, often accompanied by repetitive behavior, deficits in language and communication, and an inability to engage in reciprocal social interactions. ASD is among the most heritable disorders but is not a simple disorder with a singular pathology and has a rather complex etiology. It is interesting to note that perturbations in synaptic growth, development, and stability underlie a variety of neuropsychiatric disorders, including ASD, schizophrenia, epilepsy, and intellectual disability. Biological characterization of an increasing repertoire of synaptic mutants in various model organisms indicates synaptic dysfunction as causal in the pathophysiology of ASD. Our understanding of the genes and genetic pathways that contribute toward the formation, stabilization, and maintenance of functional synapses coupled with an in-depth phenotypic analysis of the cellular and behavioral characteristics is therefore essential to unraveling the pathogenesis of these disorders. In this review, we discuss the genetic aspects of ASD emphasizing on the well conserved set of genes and genetic pathways implicated in this disorder, many of which contribute to synapse assembly and maintenance across species. We also review how fundamental research using animal models is providing key insights into the various facets of human ASD. PMID:24605088

Facial recognition deficits as a potential endophenotype in bipolar disorder.

PubMed

Vierck, Esther; Porter, Richard J; Joyce, Peter R

2015-11-30

Bipolar disorder (BD) is considered a highly heritable and genetically complex disorder. Several cognitive functions, such as executive functions and verbal memory have been suggested as promising candidates for endophenotypes. Although there is evidence for deficits in facial emotion recognition in individuals with BD, studies investigating these functions as endophenotypes are rare. The current study investigates emotion recognition as a potential endophenotype in BD by comparing 36 BD participants, 24 of their 1st degree relatives and 40 healthy control participants in a computerised facial emotion recognition task. Group differences were evaluated using repeated measurement analysis of co-variance with age as a covariate. Results revealed slowed emotion recognition for both BD and their relatives. Furthermore, BD participants were less accurate than healthy controls in their recognition of emotion expressions. We found no evidence of emotion specific differences between groups. Our results provide evidence for facial recognition as a potential endophenotype in BD. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Tuberous Sclerosis: A New Frontier in Targeted Treatment of Autism.

PubMed

Davis, Peter E; Peters, Jurriaan M; Krueger, Darcy A; Sahin, Mustafa

2015-07-01

Tuberous sclerosis complex (TSC) is a genetic disorder with a high prevalence of autism spectrum disorder (ASD). Tremendous progress in understanding the pathogenesis of TSC has been made in recent years, along with initial trials of medical treatment aimed specifically at the underlying mechanism of the disorder. At the cellular level, loss of TSC1 or TSC2 results in upregulation of the mechanistic target of rapamycin (mTOR) pathway. At the circuitry level, TSC and mTOR play crucial roles in axonal, dendritic, and synaptic development and function. In this review, we discuss the molecular mechanism underlying TSC, and how this disease results in aberrant neural connectivity at multiple levels in the central nervous system, leading to ASD symptoms. We then review recent advances in mechanism-based treatments of TSC, and the promise that these treatments provide for future mechanism-based treatment of ASD. Because of these recent advances, TSC represents an ideal model for how to make progress in understanding and treating the mechanisms that underlie ASD in general.

A smart-phone application and a companion website for the improvement of the communication skills of children with autism: clinical rationale, technical development and preliminary results.

PubMed

De Leo, Gianluca; Gonzales, Carol H; Battagiri, Padmaja; Leroy, Gondy

2011-08-01

Autism is a complex neurobiological disorder that is part of a group of disorders known as autism spectrum disorders (ASD). Today, one in 150 individuals is diagnosed with autism. Lack of social interaction and problems with communication are the main characteristics displayed by children with ASD. The Picture Exchange Communication System (PECS) is a communication system where children exchange visual symbols as a form of communication. The visual symbols are laminated pictures stored in a binder. We have designed, developed and are currently testing a software application, called PixTalk which works on any Windows Mobile Smart-phone. Teachers and caregivers can access a web site and select from an online library the images to be downloaded on to the Smart-phone. Children can browse and select images to express their intentions, desires, and emotions using PixTalk. Case study results indicate that PixTalk can be used as part of ongoing therapy.

Interactive Metronome training in children with attention deficit and developmental coordination disorders.

PubMed

Cosper, Sharon M; Lee, Gregory P; Peters, Susan Beth; Bishop, Elizabeth

2009-12-01

The objective of this study was to examine the efficacy of Interactive Metronome (Interactive Metronome, Sunrise, Florida, USA) training in a group of children with mixed attentional and motor coordination disorders to further explore which subcomponents of attentional control and motor functioning the training influences. Twelve children who had been diagnosed with attention deficit hyperactivity disorder, in conjunction with either developmental coordination disorder (n=10) or pervasive developmental disorder (n=2), underwent 15 1-h sessions of Interactive Metronome training over a 15-week period. Each child was assessed before and after the treatment using measures of attention, coordination, and motor control to determine the efficacy of training on these cognitive and behavioral realms. As a group, the children made significant improvements in complex visual choice reaction time and visuomotor control after the training. There were, however, no significant changes in sustained attention or inhibitory control over inappropriate motor responses after treatment. These results suggest Interactive Metronome training may address deficits in visuomotor control and speed, but appears to have little effect on sustained attention or motor inhibition.

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

Perriot, Romain; Dholabhai, Pratik P.; Uberuaga, Blas P.

In this paper, we use molecular dynamics simulations to investigate the role of grain boundaries (GBs) on ionic diffusion in pyrochlores, as a function of the GB type, chemistry of the compound, and level of cation disorder. We observe that the presence of GBs promotes oxygen transport in ordered and low-disordered systems, as the GBs are found to have a higher concentration of mobile carriers with higher mobilities than in the bulk. Thus, in ordered samples, the ionic diffusion is 2D, localized along the grain boundary. When cation disorder is introduced, bulk carriers begin to contribute to the overall diffusion,more » while the GB contribution is only slightly enhanced. In highly disordered samples, the diffusive behavior at the GBs is bulk-like, and the two contributions (bulk vs. GB) can no longer be distinguished. There is thus a transition from 2D/GB dominated oxygen diffusivity to 3D/bulk dominated diffusivity versus disorder in pyrochlores. Finally, these results provide new insights into the possibility of using internal interfaces to enhance ionic conductivity in nanostructured complex oxides.« less

Ethical issues raised in addressing the needs of people with serious mental disorders in complex emergencies.

PubMed

Wissow, Lawrence S; Rutkow, Lainie; Kass, Nancy E; Rabins, Peter V; Vernick, Jon S; Hodge, James G

2012-03-01

Recent manmade and natural disasters highlight weaknesses in the public health systems designed to protect populations from harm and minimize disruption of the social and built environments. Emergency planning and response efforts have, as a result, focused largely on ensuring populations' physical well-being during and after a disaster. Many public health authorities, including the World Health Organization, have recognized the importance of addressing both mental and physical health concerns in emergency plans. Individuals with mental disorders represent a notable proportion of the overall population, and anticipating their needs is critical to comprehensive emergency planning and response efforts. Because people with serious mental disorders historically have been stigmatized, and many individuals with mental disorders may be unable to care for themselves, ethical guidance may be of assistance to those engaged in emergency planning and response. This article considers several broad categories of ethical issues that arise during emergencies for people with serious mental disorders and offers recommendations for ways in which emergency planners and other stakeholders can begin to address these ethical challenges.

Comorbid psychiatric and alcohol abuse/dependence disorders: psychosocial stress, abuse, and personal history factors of those in treatment.

PubMed

De Bernardo, Gina L; Newcomb, Michael; Toth, Amanda; Richey, Gary; Mendoza, Richard

2002-01-01

Factors related to comorbid versus only substance disorders are essential to understanding and treating these complex problems. Medical records of sixty-nine inpatients at a private rehabilitation hospital in Southern California were reviewed to determine the associations between personal history factors and (1) comorbid psychiatric and substance abuse disorders and (2) participant's self-assessed progress in treatment. Results revealed significant differences between dual diagnosis patients (alcohol abuse/dependence and an affective disorder) and alcohol abuse/dependence only in regard to gender, previous diagnosis, length of illness, suicide attempts, psychotropic medication history, maternal emotional, physical and sexual abuse, paternal abuse, legal difficulties, and psychosocial stressors. No significant differences between substance abusing patients and dually diagnosed patients were found in terms of self-assessment of progress in treatment. Significant correlations were found between self-assessed progress in treatment and major depression (versus bipolar disorder), use of psychotropic medication, and less abuse from mother or primary caretaker. Identification of these personal history factors may be useful in developing and implementing treatment plans.

A Common STEP in the Synaptic Pathology of Diverse Neuropsychiatric Disorders

PubMed Central

Johnson, Micah A.; Lombroso, Paul J.

2012-01-01

Synaptic function is critical for proper cognition, and synaptopathologies have been implicated in diverse neuropsychiatric disorders. STriatal-Enriched protein tyrosine Phosphatase (STEP) is a brain-enriched tyrosine phosphatase that normally opposes synaptic strengthening by dephosphorylating key neuronal signaling molecules. STEP targets include N-methyl D-aspartate receptors (NMDARs) and α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors (AMPARs), as well as extracellular signal-regulated kinase (ERK) and the tyrosine kinase Fyn. STEP-mediated dephosphorylation promotes the internalization of NMDARs and AMPARs and the inactivation of ERK and Fyn. Regulation of STEP is complex, and recent work has implicated STEP dysregulation in the pathophysiology of several neuropsychiatric disorders. Both high levels and low levels of STEP are found in a diverse group of illnesses. This review focuses on the role of STEP in three disorders in which STEP levels are elevated: Alzheimer’s disease, fragile X syndrome, and schizophrenia. The presence of elevated STEP in all three of these disorders raises the intriguing possibility that cognitive deficits resulting from diverse etiologies may share a common molecular pathway. PMID:23239949

Mirror me: Imitative responses in adults with autism.

PubMed

Schunke, Odette; Schöttle, Daniel; Vettorazzi, Eik; Brandt, Valerie; Kahl, Ursula; Bäumer, Tobias; Ganos, Christos; David, Nicole; Peiker, Ina; Engel, Andreas K; Brass, Marcel; Münchau, Alexander

2016-02-01

Dysfunctions of the human mirror neuron system have been postulated to underlie some deficits in autism spectrum disorders including poor imitative performance and impaired social skills. Using three reaction time experiments addressing mirror neuron system functions under simple and complex conditions, we examined 20 adult autism spectrum disorder participants and 20 healthy controls matched for age, gender and education. Participants performed simple finger-lifting movements in response to (1) biological finger and non-biological dot movement stimuli, (2) acoustic stimuli and (3) combined visual-acoustic stimuli with different contextual (compatible/incompatible) and temporal (simultaneous/asynchronous) relation. Mixed model analyses revealed slower reaction times in autism spectrum disorder. Both groups responded faster to biological compared to non-biological stimuli (Experiment 1) implying intact processing advantage for biological stimuli in autism spectrum disorder. In Experiment 3, both groups had similar 'interference effects' when stimuli were presented simultaneously. However, autism spectrum disorder participants had abnormally slow responses particularly when incompatible stimuli were presented consecutively. Our results suggest imitative control deficits rather than global imitative system impairments. © The Author(s) 2015.

Psychosocial factors, psychiatric illness and functional gastrointestinal disorders: a historical perspective.

PubMed

Van Oudenhove, Lukas; Vandenberghe, Joris; Demyttenaere, Koen; Tack, Jan

2010-01-01

A new classification of functional gastrointestinal disorders (FGID) became available recently, based on consensus in expert committees ('Rome III process'). It is widely accepted that these frequent disorders, although their pathophysiology remains incompletely understood, result from a complex reciprocal interaction between biological, psychological and social factors that can be predisposing, precipitating and/or perpetuating. Comorbidity with psychiatric disorders, especially mood and anxiety disorders, is high. Modern epidemiologic, psychophysiological and functional neuroimaging studies have partially elucidated the mechanisms underlying the relation between cognitive-affective processes on the one hand and GI function and symptom reporting on the other. The aim of this article is to provide a noncomprehensive historical review of the literature on FGID up to the mid-20th century, with special emphasis on the role of psychosocial factors and psychiatric comorbidity. We can conclude from this review that a lot of the knowledge that became available recently through modern research methodology can also be found in the historical psychosomatic and neuroscience literature, though obviously less empirically grounded. This provides further support for an integrative, multidisciplinary biopsychosocial approach to FGID.

Pervasive pleiotropy between psychiatric disorders and immune disorders revealed by integrative analysis of multiple GWAS

PubMed Central

Wang, Qian; Yang, Can; Gelernter, Joel; Zhao, Hongyu

2015-01-01

Although some existing epidemiological observations and molecular experiments suggested that brain disorders in the realm of psychiatry may be influenced by immune dysregulation, the degree of genetic overlap between psychiatric disorders and immune disorders has not been well established. We investigated this issue by integrative analysis of genome-wide association studies of 18 complex human traits/diseases (five psychiatric disorders, seven immune disorders, and others) and multiple genome-wide annotation resources (Central nervous system genes, immune-related expression-quantitative trait loci (eQTL) and DNase I hypertensive sites from 98 cell-lines). We detected pleiotropy in 24 of the 35 psychiatric-immune disorder pairs. The strongest pleiotropy was observed for schizophrenia-rheumatoid arthritis with MHC region included in the analysis (p = 3.9 × 10−285), and schizophrenia-Crohns disease with MHC region excluded (p = 1.1 × 10−36). Significant enrichment (>1.4 fold) of immune-related eQTL was observed in four psychiatric disorders. Genomic regions responsible for pleiotropy between psychiatric disorders and immune disorders were detected. The MHC region on chromosome 6 appears to be the most important with other regions, such as cytoband 1p13.2, also playing significant roles in pleiotropy. We also found that most alleles shared between schizophrenia and Crohns disease have the same effect direction, with similar trend found for other disorder pairs, such as bipolar-Crohn’s disease. Our results offer a novel birds-eye view of the genetic relationship and demonstrate strong evidence for pervasive pleiotropy between psychiatric disorders and immune disorders. Our findings might open new routes for prevention and treatment strategies for these disorders based on a new appreciation of the importance of immunological mechanisms in mediating risk of many psychiatric diseases. PMID:26340901

Anxiety in Children and Adolescents with Autism Spectrum Disorders

PubMed Central

White, Susan W.; Oswald, Donald; Ollendick, Thomas; Scahill, Lawrence

2009-01-01

Anxiety and poor stress management are common concerns in clinical samples of children with autism spectrum disorders (ASD). Anxiety may worsen during adolescence, as young people face an increasingly complex social milieu and often become more aware of their differences and interpersonal difficulties. This review summarizes the state of research on the prevalence, phenomenology, and treatment of anxiety in youth with autism and related conditions such as Asperger’s disorder. Using search words autism, asperger(s), or pervasive developmental disorder and anxiety or anxious to find reports published between 1990 and 2008, this review identified 40 papers. The results of the review suggest that anxiety, whether measured categorically or dimensionally, is indeed common in children and adolescents with autism spectrum disorders and may be a source of additional morbidity. The assessment of anxiety disorders in ASD should be conducted using multiple informants and modalities, as children with ASD often do not display age-typical symptoms of anxiety. To date, relatively few controlled intervention studies using well-characterized samples have been conducted despite preliminary evidence for efficacy of select pharmacological and psychosocial approaches. Recommendations for future applied research are presented and clinical implications are explored. PMID:19223098

Assessing Social Networks in Patients with Psychotic Disorders: A Systematic Review of Instruments

PubMed Central

Priebe, Stefan

2015-01-01

Background Evidence suggests that social networks of patients with psychotic disorders influence symptoms, quality of life and treatment outcomes. It is therefore important to assess social networks for which appropriate and preferably established instruments should be used. Aims To identify instruments assessing social networks in studies of patients with psychotic disorders and explore their properties. Method A systematic search of electronic databases was conducted to identify studies that used a measure of social networks in patients with psychotic disorders. Results Eight instruments were identified, all of which had been developed before 1991. They have been used in 65 studies (total N of patients = 8,522). They assess one or more aspects of social networks such as their size, structure, dimensionality and quality. Most instruments have various shortcomings, including questionable inter-rater and test-retest reliability. Conclusions The assessment of social networks in patients with psychotic disorders is characterized by a variety of approaches which may reflect the complexity of the construct. Further research on social networks in patients with psychotic disorders would benefit from advanced and more precise instruments using comparable definitions of and timescales for social networks across studies. PMID:26709513

[The Role of Physician In Enhancement of Rehabilitation of Disabled Children].

PubMed

Nizova, L M; Kislisyna, I G

2017-09-01

The national and international experience of rehabilitation of disabled children was investigated. On the basis of monitoring data problem of increasing of number of children with diagnosis of infantile cerebral paralysis, including necessity of development of new methods of their rehabilitation was established. The comparative dynamics of nosology of disabled children permitted to detect diseases of nervous system and congenital abnormalities (malformations), deformations and chromosomal disorders, psychological disorders and behavioral disorders mostly specific for urban and rural area. The model of institutional environment of rehabilitation of disabled children was developed including system of formal (state, legislative acts, health institutions, organizations of social support of population)and non-formal (public, non-commercial and social psychological organizations) institutions impacted by economic, social,legal and demographic factors. The role of physician is substantiated concerning increasing of quality of rehabilitation services: diagnostic of disordered functions, detection of optimal volume of medical, psychological and pedagogue activities in patients with severe speech disorders, motoric and and neuro-censorial disorders developed as a result of early organic damage of brain, neuro-infections, strokes, and other affection of brain. The adequate curative rehabilitative complex programs were developed of social everyday and social labor rehabilitation.

Interaction of saponin 1688 with phase separated lipid bilayers.

PubMed

Chen, Maohui; Balhara, Vinod; Jaimes Castillo, Ana Maria; Balsevich, John; Johnston, Linda J

2017-07-01

Saponins are a diverse family of naturally occurring plant triterpene or steroid glycosides that have a wide range of biological activities. They have been shown to permeabilize membranes and in some cases membrane disruption has been hypothesized to involve saponin/cholesterol complexes. We have examined the interaction of steroidal saponin 1688-1 with lipid membranes that contain cholesterol and have a mixture of liquid-ordered (L o ) and liquid-disordered (L d ) phases as a model for lipid rafts in cellular membranes. A combination of atomic force microscopy (AFM) and fluorescence was used to probe the effect of saponin on the bilayer. The results demonstrate that saponin forms defects in the membrane and also leads to formation of small aggregates on the membrane surface. Although most of the membrane damage occurs in the liquid-disordered phase, fluorescence results demonstrate that saponin localizes in both ordered and disordered membrane phases, with a modest preference for the disordered regions. Similar effects are observed for both direct incorporation of saponin in the lipid mixture used to make vesicles/bilayers and for incubation of saponin with preformed bilayers. The results suggest that the initial sites of interaction are at the interface between the domains and surrounding disordered phase. The preference for saponin localization in the disordered phase may reflect the ease of penetration of saponin into a less ordered membrane, rather than the actual cholesterol concentration in the membrane. Dye leakage assays indicate that a high concentration of saponin is required for membrane permeabilization consistent with the supported lipid bilayer experiments. Crown Copyright © 2017. Published by Elsevier B.V. All rights reserved.

Seeking Web-Based Information About Attention Deficit Hyperactivity Disorder: Where, What, and When

PubMed Central

2017-01-01

Background Attention Deficit Hyperactivity Disorder (ADHD) is a common neurodevelopmental disorder, prevalent among 2-10% of the population. Objective The objective of this study was to describe where, what, and when people search online for topics related to ADHD. Methods Data were collected from Microsoft’s Bing search engine and from the community question and answer site, Yahoo Answers. The questions were analyzed based on keywords and using further statistical methods. Results Our results revealed that the Internet indeed constitutes a source of information for people searching the topic of ADHD, and that they search for information mostly about ADHD symptoms. Furthermore, individuals personally affected by the disorder made 2.0 more questions about ADHD compared with others. Questions begin when children reach 2 years of age, with an average age of 5.1 years. Most of the websites searched were not specifically related to ADHD and the timing of searches as well as the query content were different among those prediagnosis compared with postdiagnosis. Conclusions The study results shed light on the features of ADHD-related searches. Thus, they may help improve the Internet as a source of reliable information, and promote improved awareness and knowledge about ADHD as well as quality of life for populations dealing with the complex phenomena of ADHD. PMID:28432038

Evidence of excited state localization and static disorder in LH2 investigated by 2D-polarization single-molecule imaging at room temperature.

PubMed

Tubasum, Sumera; Camacho, Rafael; Meyer, Matthias; Yadav, Dheerendra; Cogdell, Richard J; Pullerits, Tõnu; Scheblykin, Ivan G

2013-12-07

Two-dimensional polarization fluorescence imaging of single light harvesting complexes 2 (LH2) of Rps. acidophila was carried out to investigate the polarization properties of excitation and fluorescence emission simultaneously, at room temperature. In two separate experiments we excited LH2 with a spectrally narrow laser line matched to the absorption bands of the two chromophore rings, B800 and B850, thereby indirectly and directly triggering fluorescence of the B850 exciton state. A correlation analysis of the polarization modulation depths in excitation and emission for a large number of single complexes was performed. Our results show, in comparison to B800, that the B850 ring is a more isotropic absorber due to the excitonic nature of its excited states. At the same time, we observed a strong tendency for LH2 to emit with dipolar character, from which preferential localization of the emissive exciton, stable for minutes, is inferred. We argue that the observed effects can consistently be explained by static energetic disorder and/or deformation of the complex, with possible involvement of exciton self-trapping.

Nanoscale Charge Balancing Mechanism in Calcium-Silicate-Hydrate Gels: Novel Complex Disordered Materials from First-principles

NASA Astrophysics Data System (ADS)

Ozcelik, Ongun; White, Claire

Alkali-activated materials which have augmented chemical compositions as compared to ordinary Portland cement are sustainable technologies that have the potential to lower CO2 emissions associated with the construction industry. In particular, calcium-silicate-hydrate (C-S-H) gel is altered at the atomic scale due to changes in its chemical composition. Here, based on first-principles calculations, we predict a charge balancing mechanism at the molecular level in C-S-H gels when alkali atoms are introduced into their structure. This charge balancing process is responsible for the formation of novel structures which possess superior mechanical properties compared to their charge unbalanced counterparts. Different structural representations are obtained depending on the level of substitution and the degree of charge balancing incorporated in the structures. The impact of these charge balancing effects on the structures is assessed by analyzing their formation energies, local bonding environments, diffusion barriers and mechanical properties. These results provide information on the phase stability of alkali/aluminum containing C-S-H gels, shedding light on the fundamental mechanisms that play a crucial role in these complex disordered materials. We acknowledge funding from the Princeton Center for Complex Materials, a MRSEC supported by NSF.

Tuning and Freezing Disorder in Photonic Crystals using Percolation Lithography

PubMed Central

Burgess, Ian B.; Abedzadeh, Navid; Kay, Theresa M.; Shneidman, Anna V.; Cranshaw, Derek J.; Lončar, Marko; Aizenberg, Joanna

2016-01-01

Although common in biological systems, synthetic self-assembly routes to complex 3D photonic structures with tailored degrees of disorder remain elusive. Here we show how liquids can be used to finely control disorder in porous 3D photonic crystals, leading to complex and hierarchical geometries. In these optofluidic crystals, dynamically tunable disorder is superimposed onto the periodic optical structure through partial wetting or evaporation. In both cases, macroscopic symmetry breaking is driven by subtle sub-wavelength variations in the pore geometry. These variations direct site-selective infiltration of liquids through capillary interactions. Incorporating cross-linkable resins into our liquids, we developed methods to freeze in place the filling patterns at arbitrary degrees of partial wetting and intermediate stages of drying. These percolation lithography techniques produced permanent photonic structures with adjustable disorder. By coupling strong changes in optical properties to subtle differences in fluid behavior, optofluidic crystals may also prove useful in rapid analysis of liquids. PMID:26790372

[Movement disorders is psychiatric diseases].

PubMed

Hidasi, Zoltan; Salacz, Pal; Csibri, Eva

2014-12-01

Movement disorders are common in psychiatry. The movement disorder can either be the symptom of a psychiatric disorder, can share a common aetiological factor with it, or can be the consequence of psychopharmacological therapy. Most common features include tic, stereotypy, compulsion, akathisia, dyskinesias, tremor, hypokinesia and disturbances of posture and gait. We discuss characteristics and clinical importance of these features. Movement disorders are frequently present in mood disorders, anxiety disorders, schizophrenia, catatonia, Tourette-disorder and psychogenic movement disorder, leading to differential-diagnostic and therapeutical difficulties in everyday practice. Movement disorders due to psychopharmacotherapy can be classified as early-onset, late-onset and tardive. Frequent psychiatric comorbidity is found in primary movement disorders, such as Parkinson's disease, Wilson's disease, Huntington's disease, diffuse Lewy-body disorder. Complex neuropsychiatric approach is effective concerning overlapping clinical features and spectrums of disorders in terms of movement disorders and psychiatric diseases.

Liquid-gas phase transitions and C K symmetry in quantum field theories

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

Nishimura, Hiromichi; Ogilvie, Michael C.; Pangeni, Kamal

A general field-theoretic framework for the treatment of liquid-gas phase transitions is developed. Starting from a fundamental four-dimensional field theory at nonzero temperature and density, an effective three-dimensional field theory is derived. The effective field theory has a sign problem at finite density. Although finite density explicitly breaks charge conjugation C , there remains a symmetry under C K , where K is complex conjugation. Here, we consider four models: relativistic fermions, nonrelativistic fermions, static fermions and classical particles. The interactions are via an attractive potential due to scalar field exchange and a repulsive potential due to massive vector exchange.more » The field-theoretic representation of the partition function is closely related to the equivalence of the sine-Gordon field theory with a classical gas. The thermodynamic behavior is extracted from C K -symmetric complex saddle points of the effective field theory at tree level. In the cases of nonrelativistic fermions and classical particles, we find complex saddle point solutions but no first-order transitions, and neither model has a ground state at tree level. The relativistic and static fermions show a liquid-gas transition at tree level in the effective field theory. The liquid-gas transition, when it occurs, manifests as a first-order line at low temperature and high density, terminated by a critical end point. The mass matrix controlling the behavior of correlation functions is obtained from fluctuations around the saddle points. Due to the C K symmetry of the models, the eigenvalues of the mass matrix are not always real but can be complex. This then leads to the existence of disorder lines, which mark the boundaries where the eigenvalues go from purely real to complex. The regions where the mass matrix eigenvalues are complex are associated with the critical line. In the case of static fermions, a powerful duality between particles and holes allows for the analytic determination of both the critical line and the disorder lines. Depending on the values of the parameters, either zero, one, or two disorder lines are found. Our numerical results for relativistic fermions give a very similar picture.« less

Liquid-gas phase transitions and C K symmetry in quantum field theories

DOE PAGES

Nishimura, Hiromichi; Ogilvie, Michael C.; Pangeni, Kamal

2017-04-04

A general field-theoretic framework for the treatment of liquid-gas phase transitions is developed. Starting from a fundamental four-dimensional field theory at nonzero temperature and density, an effective three-dimensional field theory is derived. The effective field theory has a sign problem at finite density. Although finite density explicitly breaks charge conjugation C , there remains a symmetry under C K , where K is complex conjugation. Here, we consider four models: relativistic fermions, nonrelativistic fermions, static fermions and classical particles. The interactions are via an attractive potential due to scalar field exchange and a repulsive potential due to massive vector exchange.more » The field-theoretic representation of the partition function is closely related to the equivalence of the sine-Gordon field theory with a classical gas. The thermodynamic behavior is extracted from C K -symmetric complex saddle points of the effective field theory at tree level. In the cases of nonrelativistic fermions and classical particles, we find complex saddle point solutions but no first-order transitions, and neither model has a ground state at tree level. The relativistic and static fermions show a liquid-gas transition at tree level in the effective field theory. The liquid-gas transition, when it occurs, manifests as a first-order line at low temperature and high density, terminated by a critical end point. The mass matrix controlling the behavior of correlation functions is obtained from fluctuations around the saddle points. Due to the C K symmetry of the models, the eigenvalues of the mass matrix are not always real but can be complex. This then leads to the existence of disorder lines, which mark the boundaries where the eigenvalues go from purely real to complex. The regions where the mass matrix eigenvalues are complex are associated with the critical line. In the case of static fermions, a powerful duality between particles and holes allows for the analytic determination of both the critical line and the disorder lines. Depending on the values of the parameters, either zero, one, or two disorder lines are found. Our numerical results for relativistic fermions give a very similar picture.« less

Autism genetics: Methodological issues and experimental design.

PubMed

Sacco, Roberto; Lintas, Carla; Persico, Antonio M

2015-10-01

Autism is a complex neuropsychiatric disorder of developmental origin, where multiple genetic and environmental factors likely interact resulting in a clinical continuum between "affected" and "unaffected" individuals in the general population. During the last two decades, relevant progress has been made in identifying chromosomal regions and genes in linkage or association with autism, but no single gene has emerged as a major cause of disease in a large number of patients. The purpose of this paper is to discuss specific methodological issues and experimental strategies in autism genetic research, based on fourteen years of experience in patient recruitment and association studies of autism spectrum disorder in Italy.

Fiscal mapping autism spectrum disorder funds: a case study of Ohio.

PubMed

Joyce, Hilary D; Hoffman, Jill; Anderson-Butcher, Dawn; Moodie-Dyer, Amber

2014-01-01

Individuals with autism spectrum disorders (ASDs) have complex needs requiring regular service utilization. Policymakers, administrators, and community leaders are looking for ways to finance ASD services and systems. Understanding the fiscal resources that support ASD services is essential. This article uses fiscal mapping to explore ASD funding streams in Ohio. Fiscal mapping steps are overviewed to assist ASD stakeholders in identifying and examining ASD-related funding. Implications are drawn related to how fiscal mapping could be used to identify and leverage funding for ASD services. The resulting information is critical to utilizing existing resources, advocating for resources, and leveraging available funds.

Anorexia Nervosa and Bulimia: Problems of “The Pleasing Child”

PubMed Central

McSherry, J. A.

1984-01-01

Widespread media publicity has resulted in increased case findings of eating disorders such as anorexia nervosa and bulimia. The etiology of these conditions is complex and multifactorial, and they may have devastating effects on physical and psychological health. Family physicians have an important role to play in recognizing, evaluating and managing eating disorders. Severe anorexics—those who have lost 25% or more of the average weight for their age and height—require specialist management, but milder forms respond to treatment which can be undertaken by an interested family physician. Most cases of uncomplicated bulimia can be treated successfully in a family practice setting. PMID:21278973

Neurobiology of rodent self-grooming and its value for translational neuroscience

PubMed Central

Kalueff, Allan V.; Stewart, Adam Michael; Song, Cai; Berridge, Kent C.; Graybiel, Ann M.; Fentress, John C.

2016-01-01

Self-grooming is a complex innate behaviour with an evolutionary conserved sequencing pattern and is one of the most frequently performed behavioural activities in rodents. In this Review, we discuss the neurobiology of rodent self-grooming, and we highlight studies of rodent models of neuropsychiatric disorders — including models of autism spectrum disorder and obsessive compulsive disorder — that have assessed self-grooming phenotypes. We suggest that rodent self-grooming may be a useful measure of repetitive behaviour in such models, and therefore of value to translational psychiatry. Assessment of rodent self-grooming may also be useful for understanding the neural circuits that are involved in complex sequential patterns of action. PMID:26675822

Proceedings of the workshop on Cerebellum, Basal Ganglia and Cortical Connections Unmasked in Health and Disorder held in Brno, Czech Republic, October 17th, 2013.

PubMed

Bareš, Martin; Apps, Richard; Kikinis, Zora; Timmann, Dagmar; Oz, Gulin; Ashe, James J; Loft, Michaela; Koutsikou, Stella; Cerminara, Nadia; Bushara, Khalaf O; Kašpárek, Tomáš

2015-04-01

The proceedings of the workshop synthesize the experimental, preclinical, and clinical data suggesting that the cerebellum, basal ganglia (BG), and their connections play an important role in pathophysiology of various movement disorders (like Parkinson's disease and atypical parkinsonian syndromes) or neurodevelopmental disorders (like autism). The contributions from individual distinguished speakers cover the neuroanatomical research of complex networks, neuroimaging data showing that the cerebellum and BG are connected to a wide range of other central nervous system structures involved in movement control. Especially, the cerebellum plays a more complex role in how the brain functions than previously thought.

Autism Center First to Study Minimally Verbal Children

MedlinePlus

... on. Feature: Taste, Smell, Hearing, Language, Voice, Balance Autism Center First to Study Minimally Verbal Children Past ... research exploring the causes, diagnosis, and treatment of autism spectrum disorder (ASD), a complex developmental disorder that ...

Suffering in silence: why a developmental psychopathology perspective on selective mutism is needed.

PubMed

Cohan, Sharon L; Price, Joseph M; Stein, Murray B

2006-08-01

A developmental psychopathology perspective is offered in an effort to organize the existing literature regarding the etiology of selective mutism (SM), a relatively rare disorder in which a child consistently fails to speak in 1 or more social settings (e.g., school) despite speaking normally in other settings (e.g., home). Following a brief description of the history, prevalence, and course of the disorder, multiple pathways to the development of SM are discussed, with a focus on the various genetic, temperamental, psychological, and social/environmental systems that may be important in conceptualizing this unusual childhood disorder. The authors propose that SM develops due to a series of complex interactions among the various systems reviewed (e.g., a strong genetic loading for anxiety interacts with an existing communication disorder, resulting in heightened sensitivity to verbal interactions and mutism in some settings). Suggestions are provided for future longitudinal, twin/adoption, molecular genetic, and neuroimaging studies that would be particularly helpful in testing the pathways perspective on SM.

Enhancement of the finite-frequency superfluid response in the pseudogap regime of strongly disordered superconducting films

PubMed Central

Mondal, Mintu; Kamlapure, Anand; Ganguli, Somesh Chandra; Jesudasan, John; Bagwe, Vivas; Benfatto, Lara; Raychaudhuri, Pratap

2013-01-01

The persistence of a soft gap in the density of states above the superconducting transition temperature Tc, the pseudogap, has long been thought to be a hallmark of unconventional high-temperature superconductors. However, in the last few years this paradigm has been strongly revised by increasing experimental evidence for the emergence of a pseudogap state in strongly-disordered conventional superconductors. Nonetheless, the nature of this state, probed primarily through scanning tunneling spectroscopy (STS) measurements, remains partly elusive. Here we show that the dynamic response above Tc, obtained from the complex ac conductivity, is highly modified in the pseudogap regime of strongly disordered NbN films. Below the pseudogap temperature, T*, the superfluid stiffness acquires a strong frequency dependence associated with a marked slowing down of critical fluctuations. When translated into the length-scale of fluctuations, our results suggest a scenario of thermal phase fluctuations between superconducting domains in a strongly disordered s-wave superconductor. PMID:23446946

Comparison of mapping quantitative theta encephalograms during directed and required visual-verbal activity and passive period in children with different disorders of speech-language functioning.

PubMed

Radicevic, Zoran; Jelicic Dobrijevic, Ljiljana; Sovilj, Mirjana; Barlov, Ivana

2009-06-01

Aim of the research was to examine similarities and differences between the periods of experiencing visually stimulated directed speech-language information and periods of undirected attention. The examined group comprised N = 64 children, aged 4-5, with different speech-language disorders (developmental dysphasia, hyperactive syndrome with attention disorder, children with borderline intellectual abilities, autistic complex). Theta EEG was registered in children in the period of watching and describing the picture ("task"), and in the period of undirected attention ("passive period"). The children were recorded in standard EEG conditions, at 19 points of EEG registration and in longitudinal bipolar montage. Results in the observed age-operative theta rhythm indicated significant similarities and differences in the prevalence of spatial engagement of certain regions between the two hemispheres at the input and output of processing, which opens the possibility for more detailed analysis of conscious control of speech-language processing and its disorders.

Are circadian rhythms new pathways to understand Autism Spectrum Disorder?

PubMed

Geoffray, M-M; Nicolas, A; Speranza, M; Georgieff, N

2016-11-01

Autism Spectrum Disorder (ASD) is a frequent neurodevelopmental disorder. ASD is probably the result of intricate interactions between genes and environment altering progressively the development of brain structures and functions. Circadian rhythms are a complex intrinsic timing system composed of almost as many clocks as there are body cells. They regulate a variety of physiological and behavioral processes such as the sleep-wake rhythm. ASD is often associated with sleep disorders and low levels of melatonin. This first point raises the hypothesis that circadian rhythms could have an implication in ASD etiology. Moreover, circadian rhythms are generated by auto-regulatory genetic feedback loops, driven by transcription factors CLOCK and BMAL1, who drive transcription daily patterns of a wide number of clock-controlled genes (CCGs) in different cellular contexts across tissues. Among these, are some CCGs coding for synapses molecules associated to ASD susceptibility. Furthermore, evidence emerges about circadian rhythms control of time brain development processes. Copyright © 2017 Elsevier Ltd. All rights reserved.

Enhancement of the finite-frequency superfluid response in the pseudogap regime of strongly disordered superconducting films.

PubMed

Mondal, Mintu; Kamlapure, Anand; Ganguli, Somesh Chandra; Jesudasan, John; Bagwe, Vivas; Benfatto, Lara; Raychaudhuri, Pratap

2013-01-01

The persistence of a soft gap in the density of states above the superconducting transition temperature Tc, the pseudogap, has long been thought to be a hallmark of unconventional high-temperature superconductors. However, in the last few years this paradigm has been strongly revised by increasing experimental evidence for the emergence of a pseudogap state in strongly-disordered conventional superconductors. Nonetheless, the nature of this state, probed primarily through scanning tunneling spectroscopy (STS) measurements, remains partly elusive. Here we show that the dynamic response above Tc, obtained from the complex ac conductivity, is highly modified in the pseudogap regime of strongly disordered NbN films. Below the pseudogap temperature, T*, the superfluid stiffness acquires a strong frequency dependence associated with a marked slowing down of critical fluctuations. When translated into the length-scale of fluctuations, our results suggest a scenario of thermal phase fluctuations between superconducting domains in a strongly disordered s-wave superconductor.

Exploring the Molecular Design of Protein Interaction Sites with Molecular Dynamics Simulations and Free Energy Calculations†

PubMed Central

Liang, Shide; Li, Liwei; Hsu, Wei-Lun; Pilcher, Meaghan N.; Uversky, Vladimir; Zhou, Yaoqi; Dunker, A. Keith; Meroueh, Samy O.

2009-01-01

The significant work that has been invested toward understanding protein–protein interaction has not translated into significant advances in structure-based predictions. In particular redesigning protein surfaces to bind to unrelated receptors remains a challenge, partly due to receptor flexibility, which is often neglected in these efforts. In this work, we computationally graft the binding epitope of various small proteins obtained from the RCSB database to bind to barnase, lysozyme, and trypsin using a previously derived and validated algorithm. In an effort to probe the protein complexes in a realistic environment, all native and designer complexes were subjected to a total of nearly 400 ns of explicit-solvent molecular dynamics (MD) simulation. The MD data led to an unexpected observation: some of the designer complexes were highly unstable and decomposed during the trajectories. In contrast, the native and a number of designer complexes remained consistently stable. The unstable conformers provided us with a unique opportunity to define the structural and energetic factors that lead to unproductive protein–protein complexes. To that end we used free energy calculations following the MM-PBSA approach to determine the role of nonpolar effects, electrostatics and entropy in binding. Remarkably, we found that a majority of unstable complexes exhibited more favorable electrostatics than native or stable designer complexes, suggesting that favorable electrostatic interactions are not prerequisite for complex formation between proteins. However, nonpolar effects remained consistently more favorable in native and stable designer complexes reinforcing the importance of hydrophobic effects in protein–protein binding. While entropy systematically opposed binding in all cases, there was no observed trend in the entropy difference between native and designer complexes. A series of alanine scanning mutations of hot-spot residues at the interface of native and designer complexes showed less than optimal contacts of hot-spot residues with their surroundings in the unstable conformers, resulting in more favorable entropy for these complexes. Finally, disorder predictions revealed that secondary structures at the interface of unstable complexes exhibited greater disorder than the stable complexes. PMID:19113835

Mobile Phone Application for Supporting Persons with Higher Brain Dysfunctions

NASA Astrophysics Data System (ADS)

Nakayama, Tsuyoshi; Miyaji, Yuka; Kato, Seishi; Sakurada, Nobuhisa; Ueda, Noriyuki; Nomura, Takayuki; Okaya, Kazunori; Uematsu, Hiroshi; Kimura, Eiji

This paper shows a mobile phone application for supporting persons with higher brain dysfunction (HBD) such as a cognitive disorder, a memory disorder, and an attention-deficit disorder. This application serves them as a schedule manager, an alarm and an instructor of work sequences. The development concept of this application is easy handling and simple display, because persons with HBD are easily bewildered by complex procedures in the work. Five persons with HBD participated in the experiments for assessing the application at the vocational training place. The use of the application resulted in the drastic decrease of the number of errors and the increase of the System Usability Score, indicating that the developed application is useful for persons with HBD especially in performing vocational training tasks such as the use of database software on PC.

Neuropsychiatric features associated with nutritional and metabolic status in a gastric bypass patient.

PubMed

Waserman, Jessica E; Hategan, Ana; Bourgeois, James A

2015-01-01

Bariatric patients may present for psychiatric evaluation due to exacerbation of preexisting psychiatric disorders, new onset psychiatric disorders and/or neuropsychiatric complications associated with abnormal nutritional and metabolic states following the surgical procedure. These neuropsychiatric complications can be insidious, and clinical manifestations may vary, possibly due to the individual central nervous system (CNS) vulnerability to nutritional decline. Lack of awareness of these complications and their symptoms can result in delays in diagnosis and treatment. Identifying and correcting underlying pathophysiologic processes that lead to such neuropsychiatric syndromes can be challenging. We report a case of a patient who developed a protracted course of mood and cognitive disorder after gastric bypass surgery, which illustrates some of the complexities encountered in diagnosing and managing these patients. Copyright © 2015 Elsevier Inc. All rights reserved.

Childhood family characteristics and prescription drug misuse in a national sample of Latino adults.

PubMed

Vaughan, Ellen L; Waldron, Mary; de Dios, Marcel A; Richter, James; Cano, Miguel Ángel

2017-08-01

Prescription drug misuse is a growing public health concern and has been understudied in Latino populations. The current study tests the relationships between childhood and family characteristics and prescriptions drug misuse among adult Latinos. A subsample of 8,308 Latinos from the National Epidemiologic Survey on Alcohol and Related Conditions (NESARC) were examined. Logistic regression analyses tested associations between parental alcoholism, parental divorce before age 18, and parental death before age 18 and prescription drug misuse and prescription drug use disorder. Parental alcoholism and parental divorce increased the odds of both prescription drug misuse and use disorder. Parental death increased the odds of prescription drug use disorders. The results have important implications for understanding the complex associations between family psychosocial history and prescription drug misuse. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

Clinical management of behavioral characteristics of Prader-Willi syndrome.

PubMed

Ho, Alan Y; Dimitropoulos, Anastasia

2010-05-06

Prader-Willi syndrome (PWS) is a complex neurodevelopmental disorder caused by an abnormality on the long arm of chromosome 15 (q11-q13) that results in a host of phenotypic characteristics, dominated primarily by hyperphagia and insatiable appetite. Characteristic behavioral disturbances in PWS include excessive interest in food, skin picking, difficulty with a change in routine, temper tantrums, obsessive and compulsive behaviors, and mood fluctuations. Individuals with PWS typically have intellectual disabilities (borderline to mild/moderate mental retardation) and exhibit a higher overall behavior disturbance compared to individuals with similar intellectual disability. Due to its multisystem disorder, family members, caregivers, physicians, dieticians, and speech-language pathologists all play an important role in the management and treatment of symptoms in an individual with PWS. This article reviews current research on behavior and cognition in PWS and discusses management guidelines for this disorder.

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

The neuropsychological rehabilitation of visual agnosia and Balint's syndrome.

PubMed

Heutink, Joost; Indorf, Dana L; Cordes, Christina

2018-01-24

Visual agnosia and Balint's syndrome are complex neurological disorders of the higher visual system that can have a remarkable impact on individuals' lives. Rehabilitation of these individuals is important to enable participation in everyday activities despite the impairment. However, the literature about the rehabilitation of these disorders is virtually silent. Therefore, the aim of this systematic review is to give an overview of available literature describing treatment approaches and their effectiveness with regard to these disorders. The search engines Psychinfo, Amed, and Medline were used, resulting in 22 articles meeting the criteria for inclusion. Only articles describing acquired disorders were considered. These articles revealed that there is some information available on the major subtypes of visual agnosia as well as on Balint's syndrome which practising clinicians can consult for guidance. With regard to the type of rehabilitation, compensatory strategies have proven to be beneficial in most of the cases. Restorative training on the other hand has produced mixed results. Concluding, although still scarce, a scientific foundation about the rehabilitation of visual agnosia and Balint's syndrome is evolving. The available approaches give valuable information that can be built upon in the future.

Norman Geschwind and the use of history in the (re)birth of behavioral neurology.

PubMed

Kushner, Howard I

2015-01-01

When Norman Geschwind (1926-1984) attended medical school in the 1940s, his psychiatry professors taught as if behavior were unrelated to neuropathology. The focus of neurology remained the diagnosis and treatment of aphasias and epilepsies, while cognitive impairments and developmental disorders were classified as functional (psychological) disorders. Geschwind was troubled by the fact that many of the patients he saw with neurological deficits also presented with behavioral (developmental) disorders. Geschwind's generation also had been taught that aphasias resulted from global rather than localized or focal neurological lesions. These holists, including the prepsychoanalytic Sigmund Freud, targeted the work of aphasiologist Carl Wernicke as an exemplar of the flaws of the localizationist hypothesis. Reading Wernicke in the original, Geschwind discovered a complex and multilayered explanation for aphasias that implicated lesions located in association pathways that, when extensive, resulted in behavioral disorders. Geschwind also reread the works of the holists, discovering that, while their rhetoric rejected Wernicke, their explanations of aphasias actually reinforced Wernicke's hypothesis. Building on his reading of these historical documents and his clinical experiences, Geschwind urged the resurrection of Wernicke's disconnection syndromes that Geschwind labeled as Behavioral Neurology.

Comorbidity Structure of Psychological Disorders in the Online e-PASS Data as Predictors of Psychosocial Adjustment Measures: Psychological Distress, Adequate Social Support, Self-Confidence, Quality of Life, and Suicidal Ideation

PubMed Central

Klein, Britt; Meyer, Denny

2014-01-01

Background A relative newcomer to the field of psychology, e-mental health has been gaining momentum and has been given considerable research attention. Although several aspects of e-mental health have been studied, 1 aspect has yet to receive attention: the structure of comorbidity of psychological disorders and their relationships with measures of psychosocial adjustment including suicidal ideation in online samples. Objective This exploratory study attempted to identify the structure of comorbidity of 21 psychological disorders assessed by an automated online electronic psychological assessment screening system (e-PASS). The resulting comorbidity factor scores were then used to assess the association between comorbidity factor scores and measures of psychosocial adjustments (ie, psychological distress, suicidal ideation, adequate social support, self-confidence in dealing with mental health issues, and quality of life). Methods A total of 13,414 participants were assessed using a complex online algorithm that resulted in primary and secondary Diagnostic and Statistical Manual of Mental Disorders (Fourth Edition, Text Revision) diagnoses for 21 psychological disorders on dimensional severity scales. The scores on these severity scales were used in a principal component analysis (PCA) and the resulting comorbidity factor scores were related to 4 measures of psychosocial adjustments. Results A PCA based on 17 of the 21 psychological disorders resulted in a 4-factor model of comorbidity: anxiety-depression consisting of all anxiety disorders, major depressive episode (MDE), and insomnia; substance abuse consisting of alcohol and drug abuse and dependency; body image–eating consisting of eating disorders, body dysmorphic disorder, and obsessive-compulsive disorders; depression–sleep problems consisting of MDE, insomnia, and hypersomnia. All comorbidity factor scores were significantly associated with psychosocial measures of adjustment (P<.001). They were positively related to psychological distress and suicidal ideation, but negatively related to adequate social support, self-confidence, and quality of life. Conclusions This exploratory study identified 4 comorbidity factors in the e-PASS data and these factor scores significantly predicted 5 psychosocial adjustment measures. Trial Registration Australian and New Zealand Clinical Trials Registry ACTRN121611000704998; http://www.anzctr.org.au/trial_view.aspx?ID=336143 (Archived by WebCite at http://www.webcitation.org/618r3wvOG). PMID:25351885

Structural vs. intrinsic carriers: contrasting effects of cation chemistry and disorder on ionic conductivity in pyrochlores

DOE PAGES

Perriot, Romain; Uberuaga, Blas P.

2015-04-21

We use molecular dynamics simulations to investigate the role of cation disorder on oxygen diffusion in Gd 2Zr 2O 7 (GZO) and Gd 2Ti 2O 7 (GTO) pyrochlores, a class of complex oxides which contain a structural vacancy relative to the basic fluorite structure. The introduction of disorder has distinct effects depending on the chemistry of the material, increasing the mobility of structural carriers by up to four orders of magnitude in GZO. In contrast, in GTO, there is no mobility at zero or low disorder on the ns timescale, but higher disorder liberates the otherwise immobile carriers, allowing diffusionmore » with rates comparable to GZO for the fully disordered material. Here, we show that the cation disorder enhances the diffusivity by both increasing the concentration of mobile structural carriers and their individual mobility. The disorder also influences the diffusion in materials containing intrinsic carriers, such as additional vacancies VO or oxygen interstitials OI. And while in ordered GZO and GTO the contribution of the intrinsic carriers dominates the overall diffusion of oxygen, OI in GZO contributes along with structural carriers, and the total diffusion rate can be calculated by assuming simple additive contributions from the two sources. Although the disorder in the materials with intrinsic defects usually enhances the diffusivity as in the defect-free case, in low concentrations, cation antisites AB or BA, where A = Gd and B = Zr or Ti, can act as traps for fast intrinsic defects. The trapping results in a lowering of the diffusivity, and causes a non-monotonic behavior of the diffusivity with disorder. Conversely, in the case of slow intrinsic defects, the main effect of the disorder is to liberate the structural carriers, resulting in an increase of the diffusivity regardless of the defect trapping.« less

The neural correlates of obsessive-compulsive disorder: a multimodal perspective.

PubMed

Moreira, P S; Marques, P; Soriano-Mas, C; Magalhães, R; Sousa, N; Soares, J M; Morgado, P

2017-08-29

Obsessive-compulsive disorder (OCD) is one of the most debilitating psychiatric conditions. An extensive body of the literature has described some of the neurobiological mechanisms underlying the core manifestations of the disorder. Nevertheless, most reports have focused on individual modalities of structural/functional brain alterations, mainly through targeted approaches, thus possibly precluding the power of unbiased exploratory approaches. Eighty subjects (40 OCD and 40 healthy controls) participated in a multimodal magnetic resonance imaging (MRI) investigation, integrating structural and functional data. Voxel-based morphometry analysis was conducted to compare between-group volumetric differences. The whole-brain functional connectome, derived from resting-state functional connectivity (FC), was analyzed with the network-based statistic methodology. Results from structural and functional analysis were integrated in mediation models. OCD patients revealed volumetric reductions in the right superior temporal sulcus. Patients had significantly decreased FC in two distinct subnetworks: the first, involving the orbitofrontal cortex, temporal poles and the subgenual anterior cingulate cortex; the second, comprising the lingual and postcentral gyri. On the opposite, a network formed by connections between thalamic and occipital regions had significantly increased FC in patients. Integrative models revealed direct and indirect associations between volumetric alterations and FC networks. This study suggests that OCD patients display alterations in brain structure and FC, involving complex networks of brain regions. Furthermore, we provided evidence for direct and indirect associations between structural and functional alterations representing complex patterns of interactions between separate brain regions, which may be of upmost relevance for explaining the pathophysiology of the disorder.

Working memory deficits in high-functioning adolescents with autism spectrum disorders: neuropsychological and neuroimaging correlates.

PubMed

Barendse, Evelien M; Hendriks, Marc Ph; Jansen, Jacobus Fa; Backes, Walter H; Hofman, Paul Am; Thoonen, Geert; Kessels, Roy Pc; Aldenkamp, Albert P

2013-06-04

Working memory is a temporary storage system under attentional control. It is believed to play a central role in online processing of complex cognitive information and may also play a role in social cognition and interpersonal interactions. Adolescents with a disorder on the autism spectrum display problems in precisely these domains. Social impairments, communication difficulties, and repetitive interests and activities are core domains of autism spectrum disorders (ASD), and executive function problems are often seen throughout the spectrum. As the main cognitive theories of ASD, including the theory of mind deficit hypotheses, weak central coherence account, and the executive dysfunction theory, still fail to explain the broad spectrum of symptoms, a new perspective on the etiology of ASD is needed. Deficits in working memory are central to many theories of psychopathology, and are generally linked to frontal-lobe dysfunction. This article will review neuropsychological and (functional) brain imaging studies on working memory in adolescents with ASD. Although still disputed, it is concluded that within the working memory system specific problems of spatial working memory are often seen in adolescents with ASD. These problems increase when information is more complex and greater demands on working memory are made. Neuroimaging studies indicate a more global working memory processing or connectivity deficiency, rather than a focused deficit in the prefrontal cortex. More research is needed to relate these working memory difficulties and neuroimaging results in ASD to the behavioral difficulties as seen in individuals with a disorder on the autism spectrum.

Efficacy of stimulants for cognitive enhancement in non-attention deficit hyperactivity disorder youth: a systematic review

PubMed Central

Bagot, Kara Simone; Kaminer, Yifrah

2015-01-01

Background and Aims Increasing prescription stimulant abuse among youth without diagnoses of attention deficit hyperactivity disorder (ADHD) is of concern. The most frequently cited motive for abuse is improved academic achievement via neurocognitive enhancement. Our aim in reviewing the literature was to identify neurocognitive effects of prescription stimulants in non-ADHD youth. Methods A systematic review was conducted for youth aged 12–25 years using Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Fourteen papers were included. Results Modafinil appears to improve reaction time (P ≤ 0.04), logical reasoning (P ≤ 0.05) and problem-solving. Methylphenidate appears to improve performance in novel tasks and attention-based tasks (P ≤ 0.05), and reduces planning latency in more complex tasks (P ≤ 0.05). Amphetamine has been shown to improve consolidation of information (0.02 ≥ P ≤ 0.05), leading to improved recall. Across all three types of prescription stimulants, research shows improved attention with lack of consensus on whether these improvements are limited to simple versus complex tasks in varying youth populations. Conclusions The heterogeneity of the non-attention deficit hyperactivity disorder youth population, the variation in cognitive task characteristics and lack of replication of studies makes assessing the potential global neurocognitive benefits of stimulants among non-attention deficit hyper-activity disorder youth difficult; however, some youth may derive benefit in specific cognitive domains. PMID:24749160

Aberrant expression of long noncoding RNAs in autistic brain.

PubMed

Ziats, Mark N; Rennert, Owen M

2013-03-01

The autism spectrum disorders (ASD) have a significant hereditary component, but the implicated genetic loci are heterogeneous and complex. Consequently, there is a gap in understanding how diverse genomic aberrations all result in one clinical ASD phenotype. Gene expression studies from autism brain tissue have demonstrated that aberrantly expressed protein-coding genes may converge onto common molecular pathways, potentially reconciling the strong heritability and shared clinical phenotypes with the genomic heterogeneity of the disorder. However, the regulation of gene expression is extremely complex and governed by many mechanisms, including noncoding RNAs. Yet no study in ASD brain tissue has assessed for changes in regulatory long noncoding RNAs (lncRNAs), which represent a large proportion of the human transcriptome, and actively modulate mRNA expression. To assess if aberrant expression of lncRNAs may play a role in the molecular pathogenesis of ASD, we profiled over 33,000 annotated lncRNAs and 30,000 mRNA transcripts from postmortem brain tissue of autistic and control prefrontal cortex and cerebellum by microarray. We detected over 200 differentially expressed lncRNAs in ASD, which were enriched for genomic regions containing genes related to neurodevelopment and psychiatric disease. Additionally, comparison of differences in expression of mRNAs between prefrontal cortex and cerebellum within individual donors showed ASD brains had more transcriptional homogeneity. Moreover, this was also true of the lncRNA transcriptome. Our results suggest that further investigation of lncRNA expression in autistic brain may further elucidate the molecular pathogenesis of this disorder.

[Therapeutic management of bipolar disorder in France and Europe: a multinational longitudinal study (WAVE-bd)].

PubMed

Bellivier, F; Delavest, M; Coulomb, S; Figueira, M L; Langosch, J M; Souery, D; Vieta, E

2014-10-01

Bipolar disorder is a complex disease which requires multiple healthcare resources and complex medical care programs including pharmacological and non pharmacological treatment. If mood stabilizers remain the corner stone for bipolar disorder treatment, the development of atypical antipsychotics and their use as mood stabilizers has significantly modified therapeutic care. At the present time, psychiatrists have a large variety of psychotropic drugs for bipolar disorder: mood stabilizers, atypical antipsychotics, antidepressants, anxiolytics… However, despite the publication of guidelines on pharmacological treatment, with a high degree of consensus, everyday clinical practices remain heterogeneous. Moreover, there are few longitudinal studies to describe therapeutic management of bipolar disorder, whatever the phase of the disease is. Indeed, most of the studies are carried out on a specific phase of the disease or treatment. And there is no study comparing French and European practices. In this paper, we aim to present the comparison of the management of pharmacological treatments of bipolar disorder between France and Europe, using the data of the observational Wide AmbispectiVE study of the clinical management and burden of bipolar disorder (WAVE-bd study). The WAVE-bd study is a multinational, multicentre and non-interventional cohort study of patients diagnosed with BD type I or type II, according to DSM IV-TR criteria, in any phase of the disorder, who have experienced at least one mood event during the 12 months before enrolment. In total, 2507 patients have been included across 8 countries of Europe (480 in France). Data collection was retrospective (from 3 to 12 months), but also prospective (from 9 to 15 months) for a total study length of 12 to 27 months. Main outcome measures were the healthcare resource use and pharmacological treatments. Our results show differences in the therapeutic management of bipolar disorder between France and other European countries. Regarding healthcare resource use, our results show that French patients consult more frequently a psychiatrist or a psychologist and less frequently a general practitioner or the emergency ward in comparison with patients from other European countries. In the whole European population, including France, atypical antipsychotics are widely used. Only 25% of the patients receive lithium and more than 50% of the patients receive antidepressants, while their use in bipolar disorder remains controversial. Most of the patients receive polymedication. Considering all phases of the disease pooled, less lithium and less atypical antipsychotics are prescribed to French patients, whereas they receive more antidepressants and more benzodiazepines than patients from other European countries. On the over hand, prescription of anticonvulsants and electroconvulsive therapy are equal. Moreover, data analyses by polarity of the episodes globally confirm these trends. There are a few exceptions: mixed states, in which lithium is twice more prescribed in France in comparison to other countries; depressive states, in which antidepressants are even more prescribed in other countries than in France; and less prescription of anticonvulsants in manic, mixed and euthymic phases in France. The WAVE-bd study is the first observational study conducted on a large sample of bipolar I and II patients that compares therapeutic management between France and other European countries. The differences observed in therapeutic care across the different phases of the disease show that treatments differ depending on the countries studied, but also according to the preventive or curative phases, polarity of the bipolar disorder, comorbidities, impact of guidelines, and care organization. Although French patients have been treated by less lithium and less atypical antipsychotics than other European patients, they receive more antidepressants and more benzodiazepines. Finally, patients generally receive polymedication and the diversity in prescriptions shows how bipolar disorder is a complex disorder. Copyright © 2014 L’Encéphale, Paris. Published by Elsevier Masson SAS. All rights reserved.

Laforin, a dual specificity phosphatase that dephosphorylates complex carbohydrates.

PubMed

Worby, Carolyn A; Gentry, Matthew S; Dixon, Jack E

2006-10-13

Laforin is the only phosphatase in the animal kingdom that contains a carbohydrate-binding module. Mutations in the gene encoding laforin result in Lafora disease, a fatal autosomal recessive neurodegenerative disorder, which is diagnosed by the presence of intracellular deposits of insoluble complex carbohydrates known as Lafora bodies. We demonstrate that laforin interacts with proteins known to be involved in glycogen metabolism and rule out several of these proteins as potential substrates. Surprisingly, we find that laforin displays robust phosphatase activity against a phosphorylated complex carbohydrate. Furthermore, this activity is unique to laforin, since several other phosphatases are unable to dephosphorylate polysaccharides. Finally, fusing the carbohydrate-binding module of laforin to the dual specific phosphatase VHR does not result in the ability of this phosphatase to dephosphorylate polysaccharides. Therefore, we hypothesize that laforin is unique in its ability to utilize a phosphorylated complex carbohydrate as a substrate and that this function may be necessary for the maintenance of normal cellular glycogen.

Use of Multivariate Linkage Analysis for Dissection of a Complex Cognitive Trait

PubMed Central

Marlow, Angela J.; Fisher, Simon E.; Francks, Clyde; MacPhie, I. Laurence; Cherny, Stacey S.; Richardson, Alex J.; Talcott, Joel B.; Stein, John F.; Monaco, Anthony P.; Cardon, Lon R.

2003-01-01

Replication of linkage results for complex traits has been exceedingly difficult, owing in part to the inability to measure the precise underlying phenotype, small sample sizes, genetic heterogeneity, and statistical methods employed in analysis. Often, in any particular study, multiple correlated traits have been collected, yet these have been analyzed independently or, at most, in bivariate analyses. Theoretical arguments suggest that full multivariate analysis of all available traits should offer more power to detect linkage; however, this has not yet been evaluated on a genomewide scale. Here, we conduct multivariate genomewide analyses of quantitative-trait loci that influence reading- and language-related measures in families affected with developmental dyslexia. The results of these analyses are substantially clearer than those of previous univariate analyses of the same data set, helping to resolve a number of key issues. These outcomes highlight the relevance of multivariate analysis for complex disorders for dissection of linkage results in correlated traits. The approach employed here may aid positional cloning of susceptibility genes in a wide spectrum of complex traits. PMID:12587094

A Contemporary Learning Theory Perspective on the Etiology of Anxiety Disorders: It's Not What You Thought it Was

ERIC Educational Resources Information Center

Mineka, Susan; Zinbarg, Richard

2006-01-01

The authors describe how contemporary learning theory and research provide the basis for perspectives on the etiology and maintenance of anxiety disorders that capture the complexity associated with individual differences in the development and course of these disorders. These insights from modern research on learning overcome the shortcomings of…

Teaching Children with Autistic Spectrum Disorder: A Preschool Teacher Survey to Determine Best Practice Approach

ERIC Educational Resources Information Center

Grossi-Kliss, Joanne

2006-01-01

Teaching children with Autistic Spectrum Disorder (ASD) can be the most challenging to preschool teachers because of the complexity of this brain disorder. A child s life is affected, whether its communication and language, social and play skills, activities of daily living, self-regulation behaviors, and sensory impairments. Therefore, a teacher…

Teaching Sam to Read: An Integrated Team Approach with One Child with Autism Spectrum Disorder

ERIC Educational Resources Information Center

Coulter, Gail; Sasnett, Roger

2016-01-01

Few evidence-based practices are available to guide educators in teaching reading to children with Autism Spectrum Disorder who have complex learning and behavioral needs associated with the symptoms of ASD and common co-occurring conditions, such as Attention Deficit/Hyperactive Disorder and Specific Learning Disability. Some researchers have…

A Systematic Review of Parenting in Relation to the Development of Comorbidities and Functional Impairments in Children with Attention-Deficit/Hyperactivity Disorder (ADHD)

ERIC Educational Resources Information Center

Deault, Louise C.

2010-01-01

This review synthesizes recent research evidence regarding the parenting characteristics associated with families with children with Attention-Deficit/Hyperactivity Disorder (ADHD). ADHD is a complex, heterogeneous disorder with a range of genetic and environmental factors that contribute to its behavioral expression and different developmental…

Identification of multiple genetic loci in the mouse controlling immobility time in the tail suspension and forced swimming tests.

PubMed

Abou-Elnaga, Ahmed F; Torigoe, Daisuke; Fouda, Mohamed M; Darwish, Ragab A; Abou-Ismail, Usama A; Morimatsu, Masami; Agui, Takashi

2015-05-01

Depression is one of the most famous psychiatric disorders in humans in all over the countries and considered a complex neurobehavioral trait and difficult to identify causal genes. Tail suspension test (TST) and forced swimming test (FST) are widely used for assessing depression-like behavior and antidepressant activity in mice. A variety of antidepressant agents are known to reduce immobility time in both TST and FST. To identify genetic determinants of immobility duration in both tests, we analyzed 101 F2 mice from an intercross between C57BL/6 and DBA/2 strains. Quantitative trait locus (QTL) mapping using 106 microsatellite markers revealed three loci (two significant and one suggestive) and five suggestive loci controlling immobility time in the TST and FST, respectively. Results of QTL analysis suggest a broad description of the genetic architecture underlying depression, providing underpinnings for identifying novel molecular targets for antidepressants to clear the complex genetic mechanisms of depressive disorders.

Intrinsic disorder mediates the diverse regulatory functions of the Cdk inhibitor p21

PubMed Central

Wang, Yuefeng; Fisher, John C.; Mathew, Rose; Ou, Li; Otieno, Steve; Sublett, Jack; Xiao, Limin; Chen, Jianhan; Roussel, Martine F.; Kriwacki, Richard W.

2011-01-01

Traditionally, well-defined three-dimensional structure was thought to be essential for protein function. However, myriad biological functions are performed by highly dynamic, intrinsically disordered proteins (IDPs). IDPs often fold upon binding their biological targets and frequently exhibit “binding diversity” by targeting multiple ligands. We sought to understand the physical basis of IDP binding diversity and herein report that the cyclin-dependent kinase (Cdk) inhibitor, p21Cip1, adaptively binds to and inhibits the various Cdk/cyclin complexes that regulate eukaryotic cell division. Based on results from NMR spectroscopy, and biochemical and cellular assays, we show that structural adaptability of a helical sub-domain within p21 termed LH enables two other sub-domains termed D1 and D2 to specifically bind conserved surface features of the cyclin and Cdk subunits, respectively, within otherwise structurally distinct Cdk/cyclin complexes. Adaptive folding upon binding is likely to mediate the diverse biological functions of the thousands of IDPs present in eukaryotes. PMID:21358637

An intrinsically disordered peptide from Ebola virus VP35 controls viral RNA synthesis by modulating nucleoprotein-RNA interactions

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

Leung, Daisy  W.; Borek, Dominika; Luthra, Priya

During viral RNA synthesis, Ebola virus (EBOV) nucleoprotein (NP) alternates between an RNA-template-bound form and a template-free form to provide the viral polymerase access to the RNA template. In addition, newly synthesized NP must be prevented from indiscriminately binding to noncognate RNAs. Here, we investigate the molecular bases for these critical processes. We identify an intrinsically disordered peptide derived from EBOV VP35 (NPBP, residues 20–48) that binds NP with high affinity and specificity, inhibits NP oligomerization, and releases RNA from NP-RNA complexes in vitro. The structure of the NPBP/ΔNP NTD complex, solved to 3.7 Å resolution, reveals how NPBP peptidemore » occludes a large surface area that is important for NP-NP and NP-RNA interactions and for viral RNA synthesis. Together, our results identify a highly conserved viral interface that is important for EBOV replication and can be targeted for therapeutic development.« less

An intrinsically disordered peptide from Ebola virus VP35 controls viral RNA synthesis by modulating nucleoprotein-RNA interactions

DOE PAGES

Leung, Daisy  W.; Borek, Dominika; Luthra, Priya; ...

2015-04-01

During viral RNA synthesis, Ebola virus (EBOV) nucleoprotein (NP) alternates between an RNA-template-bound form and a template-free form to provide the viral polymerase access to the RNA template. In addition, newly synthesized NP must be prevented from indiscriminately binding to noncognate RNAs. Here, we investigate the molecular bases for these critical processes. We identify an intrinsically disordered peptide derived from EBOV VP35 (NPBP, residues 20–48) that binds NP with high affinity and specificity, inhibits NP oligomerization, and releases RNA from NP-RNA complexes in vitro. The structure of the NPBP/ΔNP NTD complex, solved to 3.7 Å resolution, reveals how NPBP peptidemore » occludes a large surface area that is important for NP-NP and NP-RNA interactions and for viral RNA synthesis. Together, our results identify a highly conserved viral interface that is important for EBOV replication and can be targeted for therapeutic development.« less

An Intrinsically Disordered Peptide from Ebola Virus VP35 Controls Viral RNA Synthesis by Modulating Nucleoprotein-RNA Interactions.

PubMed

Leung, Daisy W; Borek, Dominika; Luthra, Priya; Binning, Jennifer M; Anantpadma, Manu; Liu, Gai; Harvey, Ian B; Su, Zhaoming; Endlich-Frazier, Ariel; Pan, Juanli; Shabman, Reed S; Chiu, Wah; Davey, Robert A; Otwinowski, Zbyszek; Basler, Christopher F; Amarasinghe, Gaya K

2015-04-21

During viral RNA synthesis, Ebola virus (EBOV) nucleoprotein (NP) alternates between an RNA-template-bound form and a template-free form to provide the viral polymerase access to the RNA template. In addition, newly synthesized NP must be prevented from indiscriminately binding to noncognate RNAs. Here, we investigate the molecular bases for these critical processes. We identify an intrinsically disordered peptide derived from EBOV VP35 (NPBP, residues 20-48) that binds NP with high affinity and specificity, inhibits NP oligomerization, and releases RNA from NP-RNA complexes in vitro. The structure of the NPBP/ΔNPNTD complex, solved to 3.7 Å resolution, reveals how NPBP peptide occludes a large surface area that is important for NP-NP and NP-RNA interactions and for viral RNA synthesis. Together, our results identify a highly conserved viral interface that is important for EBOV replication and can be targeted for therapeutic development. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

Demographic and clinical characteristics associated with comorbid cannabis use disorders (CUDs) in hospitalized patients with bipolar I disorder.

PubMed

Weinstock, Lauren M; Gaudiano, Brandon A; Wenze, Susan J; Epstein-Lubow, Gary; Miller, Ivan W

2016-02-01

Published data suggest that cannabis use is associated with several negative consequences for individuals with bipolar disorder (BD), including new manic episode onset, psychosis, and functional disability. Yet much less is known about cannabis use disorders (CUDs) in this population, especially in more acutely symptomatic groups. To evaluate correlates of CUD comorbidity in BD, a retrospective chart review was conducted for 230 adult patients with bipolar I disorder (BDI) who were admitted to a university-affiliated private psychiatric hospital. Using a computer algorithm, a hospital administrator extracted relevant demographic and clinical data from the electronic medical record for analysis. Thirty-six (16%) had a comorbid CUD. CUD comorbidity was significantly associated with younger age, manic/mixed episode polarity, presence of psychotic features, and comorbid nicotine dependence, alcohol use disorder (AUD), and other substance use disorders, but was associated with decreased likelihood of anxiety disorder comorbidity. With the exception of manic/mixed polarity and AUD comorbidity, results from multivariate analyses controlling for the presence of other SUDs were consistent with univariate findings. Patients with BD and comorbid CUDs appear to be a complex population with need for enhanced clinical monitoring. Given increasing public acceptance of cannabis use, and the limited availability of evidenced-based interventions targeted toward CUDs in BD, psychoeducation and other treatment development efforts appear to be warranted. Copyright © 2015 Elsevier Inc. All rights reserved.

Risk factors for suicide among children and youths with bipolar spectrum and early bipolar disorder.

PubMed

Rajewska-Rager, Aleksandra; Sibilski, Piotr; Lepczyńska, Natalia

2015-01-01

In recent years much attention has been given to determine risk factors for suicide among adults with bipolar disorder. Such studies concerning children and youths, which would also take into account the specificity of the developmental age, are still too few. The ability to identify risk factors for children and youths with mood disorders, as well as the possibility to monitor them, is an essential element in preventing suicidal behaviours. Previous studies have clearly indicated that in the group of patients with an early onset of the bipolar disorder the occurrence of suicidal thoughts and intentions were significantly increased. Identifying the risk of suicide is hindered further by the complexity of the phenomenon, which is a compound interaction of various factors: biological, environmental, sociological, psychological and clinical. This is especially true with young adults suffering from mental illness and presenting a number of other psychopathological symptoms. The following paper introduces and reviews the results of current studies, which analysed the risk factors for suicide among children and youths with bipolar spectrum or already diagnosed with bipolar disorder. For this purpose we conducted the overview of recent years literature available in PubMed/MEDLINE database, including the following search criteria: early onset bipolar disorder, bipolar disorder in children and young people, the spectrum of bipolar disorder, and suicidal ideation, suicidal intent, suicide.

Toward a Valid Animal Model of Bipolar Disorder: How the Research Domain Criteria Help Bridge the Clinical-Basic Science Divide.

PubMed

Cosgrove, Victoria E; Kelsoe, John R; Suppes, Trisha

2016-01-01

Bipolar disorder is a diagnostically heterogeneous disorder, although mania emerges as a distinct phenotype characterized by elevated mood and increased activity or energy. While bipolar disorder's cyclicity is difficult to represent in animals, models of mania have begun to decode its fundamental underlying neurobiology. When psychostimulants such as amphetamine or cocaine are administered to rodents, a resulting upsurge of motor activity is thought to share face and predictive validity with mania in humans. Studying black Swiss mice, which inherently exhibit proclivity for reward seeking and risk taking, also has yielded some insight. Further, translating the biology of bipolar disorder in humans into animal models has led to greater understanding of roles for candidate biological systems such as the GRIK2 and CLOCK genes, as well as the extracellular signal-related kinase pathway involved in the pathophysiology of the illness. The National Institute of Mental Health Research Domain Criteria initiative seeks to identify building blocks of complex illnesses like bipolar disorder in hopes of uncovering the neurobiology of each, as well as how each fits together to produce syndromes like bipolar disorder or why so many mental illnesses co-occur together. Research Domain Criteria-driven preclinical models of isolated behaviors and domains involved in mania and bipolar disorder will ultimately inform movement toward nosology supported by neurobiology. Copyright © 2016 Society of Biological Psychiatry. All rights reserved.

The structure of PTSD symptoms according to DSM-5 and IDC-11 proposal: A multi-sample analysis.

PubMed

Cyniak-Cieciura, M; Staniaszek, K; Popiel, A; Pragłowska, E; Zawadzki, B

2017-07-01

Posttraumatic stress disorder (PTSD) symptoms structure is a subject of ongoing debate since its inclusion in DSM-III classification in 1980. Different research on PTSD symptoms structure proved the better fit of four-factor and five-factor models comparing to the one proposed by DSM-IV. With the publication of DSM-5 classification, which introduced significant changes to PTSD diagnosis, the question arises about the adequacy of the proposed criteria to the real structure of disorder symptoms. Recent analyses suggest that seven-factor hybrid model is the best reflection of symptoms structure proposed to date. At the same time, some researchers and ICD-11 classification postulate a simplification of PTSD diagnosis restricting it to only three core criteria and adding additional diagnostic unit of complex-PTSD. This research aimed at checking symptoms' structure according to well-known and supported four-, five-, six- and seven-factor models based on DSM-5 symptoms and the conceptualization proposed by the ICD-11 as well as examining the relation between PTSD symptoms categories with borderline personality disorder. Four different trauma populations were examined with self-reported Posttraumatic Diagnostic Scale for DSM-5 (PDS-5) measure. The results suggest that six- and seven-factor hybrid model as well as three-factor ICD-11 concept fits the data better than other models. The core PTSD symptoms were less related to borderline personality disorder than other, broader, symptoms categories only in one sample. Combination of ICD-11 simplified PTSD diagnosis with the more complex approach (e.g. basing on a seven-factor model) may be an attractive proposal for both scientists and practitioners, however does not necessarily lower its comorbidity with borderline personality disorder. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Genome-wide association study of major depressive disorder: new results, meta-analysis, and lessons learned.

PubMed

Wray, N R; Pergadia, M L; Blackwood, D H R; Penninx, B W J H; Gordon, S D; Nyholt, D R; Ripke, S; MacIntyre, D J; McGhee, K A; Maclean, A W; Smit, J H; Hottenga, J J; Willemsen, G; Middeldorp, C M; de Geus, E J C; Lewis, C M; McGuffin, P; Hickie, I B; van den Oord, E J C G; Liu, J Z; Macgregor, S; McEvoy, B P; Byrne, E M; Medland, S E; Statham, D J; Henders, A K; Heath, A C; Montgomery, G W; Martin, N G; Boomsma, D I; Madden, P A F; Sullivan, P F

2012-01-01

Major depressive disorder (MDD) is a common complex disorder with a partly genetic etiology. We conducted a genome-wide association study of the MDD2000+ sample (2431 cases, 3673 screened controls and >1 M imputed single-nucleotide polymorphisms (SNPs)). No SNPs achieved genome-wide significance either in the MDD2000+ study, or in meta-analysis with two other studies totaling 5763 cases and 6901 controls. These results imply that common variants of intermediate or large effect do not have main effects in the genetic architecture of MDD. Suggestive but notable results were (a) gene-based tests suggesting roles for adenylate cyclase 3 (ADCY3, 2p23.3) and galanin (GAL, 11q13.3); published functional evidence relates both of these to MDD and serotonergic signaling; (b) support for the bipolar disorder risk variant SNP rs1006737 in CACNA1C (P=0.020, odds ratio=1.10); and (c) lack of support for rs2251219, a SNP identified in a meta-analysis of affective disorder studies (P=0.51). We estimate that sample sizes 1.8- to 2.4-fold greater are needed for association studies of MDD compared with those for schizophrenia to detect variants that explain the same proportion of total variance in liability. Larger study cohorts characterized for genetic and environmental risk factors accumulated prospectively are likely to be needed to dissect more fully the etiology of MDD.