Role In Mental Disorders Research Articles

The effects of Kctd12, an auxiliary subunit of GABAB receptor in dentate gyrus on behavioral response to chronic social defeat stress in mice

Adaptive responses to stress are critical to enhance physical and mental well-being, but excessive or prolonged stress may cause inadaptability and increase the risks of psychiatric disorders, such as depression. GABABR signaling is fundamental to brain function and has been identified in neuropsychiatric disorders. KCTD12 is a critical auxiliary subunit in GABABR signaling, but its role in mental disorders, such as depression is unclear. In the present study, we used a well-validated mice model, chronic social defeat stress (CSDS) to investigate behavioral responses to stress and explore the role of Kctd12 in stress response, as well as the relevant mechanisms. We found that CSDS increased the expression of Kctd12 in the dentate gyrus (DG), a subregion of hippocampus. Overexpression of Kctd12 in DG induced higher responsiveness to acute stress and increased vulnerability to social stress in mice, whereas knock-down of Kctd12 in DG prevented the social avoidance. Furthermore, an increased expression of GABAB receptor 2 (GB2) in the DG of CSDS-treated mice was observed, and CGP35348, an antagonist of GABABR, improved the stress-induced behavior responses along with suppressing the excess expression of Kctd12. In addition, Kctd12 regulated the excitability of granule cell in DG, and the stimulation of neuronal activity by silencing Kctd12 contributed to the antidepressant-like effect of fluoxetine. These findings identify that the Kctd12 in DG works as a critical mediator of stress responses, providing a promising therapeutic target in stress-related psychiatric disorders, including depression.

Short strides to important findings: A short interval longitudinal study of sleep quality, psychological distress and microstructure changes to the uncinate fasciculus in early adolescents.

Developmental studies have shown adolescence is a period of ongoing white matter (WM) development, reduced sleep quality and the onset of many mental disorders. Findings indicate the WM development of the uncinate fasciculus (UF), a WM tract suggested to play a key role in mental disorders, continues throughout adolescence. While these studies provide valuable information, they are limited by long intervals between scans (1 to 4years) leaving researchers and clinicians to infer what may be occurring between time-points. To allow inferences to be made regarding the impact that sleep quality may be having on WM development, longitudinal studies with much shorter between-scan intervals are required. The current study reports longitudinal data of self-reported sleep quality (PSQI), diffusion tensor imaging (DTI) measures of WM development and psychological distress (K10) for n=64 early adolescents spanning the first twelve months (four time-points; Baseline, 4, 8, & 12months) of the Longitudinal Adolescent Brain Study (LABS) study currently underway at the Thompson Institute. Generalised Estimating Equation analysis showed a significant relationship between sleep quality and psychological distress over the four time-points. Reduced radial diffusivity and increased fractional anisotropy of the UF is also reported with increasing age suggesting that ongoing myelination is occurring. Adding sleep quality to the model, however, negatively impacted this myelination process. These findings represent an important step towards elucidating how sleep, psychological distress and maturation of the UF may co-develop during early adolescence.

Severe Mental Disorder and Terrorism:When Psychosis, PTSD and Addictions Become a Vulnerability

ABSTRACT There is no empirical evidence to suggest that terrorism is driven by mental illness in the majority of cases. However, when terrorist acts are planned or executed by individuals with mental disorder, possible functional links between the two need to be explored in order to delineate risk and inform approaches to risk management and reduction. This paper explores such functional links, their complexities and implications for clinical interventions, with a focus on psychosis, PTSD and addictions. The challenges of establishing the precise role of mental disorder, especially where there is co-morbidity and a range of complex interacting symptoms, are explored. Finally, the limitations of the existing research in the field of mental disorder and terrorism, and the challenges of extrapolating from such research to practice, are addressed.

Dynamic frontostriatal functional peak connectivity (in alcohol use disorder).

Alcohol use disorder (AUD) is associated with changes in frontostriatal connectivity, but functional magnetic resonance imaging (fMRI) functional connectivity (FC) approaches are usually not adapted to these circuits. We developed a circuit‐specific fMRI analysis approach to detect dynamic changes in frontostriatal FC inspired by medial‐ventral‐rostral to lateral‐dorsal‐caudal frontostriatal gradients originally identified in nonhuman primate tract‐tracing data. In our PeaCoG (“peak connectivity on a gradient”) approach we use information about the location of strongest FC on empirical frontostriatal connectivity gradients. We have recently described a basic PeaCoG version with conventional FC, and now developed a dynamic PeaCoG approach with sliding‐window FC. In resting state data of n = 66 AUD participants and n = 40 healthy controls we continue here the analyses that we began with the basic version. Our former result of an AUD‐associated ventral shift in right orbitofrontal cortex PeaCoG is consistently detected in the dynamic approach. Temporospatial variability of dynamic PeaCoG in the left dorsolateral prefrontal cortex is reduced in AUD and associated with self‐efficacy to abstain and days of abstinence. Our method has the potential to provide insight into the dynamics of frontostriatal circuits, which has so far been relatively unexplored, and into their role in mental disorders and normal cognition.

Examination of plasma zonulin levels in bipolar I disorder: a case-control study with follow-up.

There is an accumulation in studies which strive to reveal zonulin's potential role in mental disorders. To date, one cross-sectional recent study examined zonulin in patients with bipolar disorders (BDs); however, its role still remains vague due to high fluctuation. Our aims are to determine plasma zonulin levels in exacerbation and treatment response periods, and to examine the associations between zonulin and symptom severity in BD. 30 patients with BD type I and 29 healthy controlsparticipated in the current study. Socio-demographic form, Young Mania Rating Scale (YMRS), and Hamilton Depression Rating Scale (HAM-D) were administered. Enzyme-linked immune assay (ELISA) method was used to measure the plasma zonulin levels of the participants. The groups did not differ in plasma zonulin-level comparisons. Plasma zonulin did not alter between the exacerbation and treatment response periods of the patients. Besides, no associations were found between plasma zonulin-level and disease symptoms. Intestinal barrier integrity was not found to be altered among patients with BD type I. The lack of alterations in plasma zonulin level between different periods may be attributable to several factors. One possible factor might be the ELISA method which can detect other proteins (e.g., properdin) rather than zonulin. Therefore, it might fail to indicate direct observation of intestinal permeability. However, future study designs with more accurate estimation of zonulin in a larger sample may provide a different perspective on intestinal permeability's possible role in BD etiology.

M56. ASSORTATIVE MATING IN SCHIZOPHRENIA AND BIPOLAR DISORDER: A NATIONWIDE COHORT STUDY EXPLORING THE CHARACTERISTICS OF INDIVIDUALS WHO HAVE CHILDREN BY PARTNERS WITH SCHIZOPHRENIA OR BIPOLAR DISORDER

BackgroundAssortative mating is common in patients with mental disorders, both for specific disorders and across the spectrum of mental disorders. Assortative mating may play a key role in mental disorders because the person with the close relation to an individual with a mental disorder is also likely to have mental disorders, poorer cognitive abilities or lower social functioning, which may further intensify problems for both partners and their offspring. When one parent is ill, the care for the child will often depend on the other parent. Thus, assortative mating will most likely contribute to outcomes in the offspring. Therefore, the objective of this study was to investigate possible diagnoses of a mental illness, cognitive ability and social functioning in individuals who have biological children by partners with schizophrenia or bipolar disorder. Further, we also aimed to explore differences in polygenic risk scores derived from genome-wide association studies for schizophrenia, bipolar disorder, and depression.MethodsThis study was based on data from The Danish High Risk and Resilience Study - VIA7, a population-based cohort study conducted in Denmark between 2013 and 2016. Subjects were identified through the Danish Civil registration System and the Danish Psychiatric Central Research register. The VIA7 cohort consists of 522 children aged 7 years with parents diagnosed with schizophrenia or bipolar disorder in the Danish registries (index parents) and their partners (non-index parents). This study focuses on the non-index parents (N = 492) without schizophrenia or bipolar disorder in the Danish registries. All participants were interviewed with a diagnostic interview (SCAN 2.0). Main outcomes were intelligence, processing speed, verbal working memory, and social functioning. A linear mixed effect model was applied for each of the outcomes, including parent status (index parent or non-index parent), group (schizophrenia, bipolar disorder, and control), and interaction between parent status and group.ResultsNon-index parents having children by a partner with schizophrenia or bipolar disorder more often fulfilled the criteria for a mental disorder compared to non-index parents in the control group. Non-index parents having children by a partner with schizophrenia or bipolar disorder had lower levels of social functioning compared to non-index parents in the control group and performed poorer on intelligence and processing speed.DiscussionIndividuals who have children by partners with schizophrenia or bipolar disorder are more likely to have a mental disorder and to have lower levels of cognitive and social functioning compared to individuals who have children by partners without schizophrenia or bipolar disorder. Assortative mating may have important implications for our understanding of the familial transmission of these disorders. The findings presented in this study should be considered in future genetic research in psychiatry, specifically in the investigation of potential risk factors for children with a parent with schizophrenia or bipolar disorder.

Baseline income, follow-up income, income mobility and their roles in mental disorders: a longitudinal intra-generational community-based study

BackgroundAlthough a number of studies have found that income mobility associated with an elevated risk of mental disorders, existing research does not provide sufficient evidence of how exactly individuals’ experience of income mobility per se affects their risk of mental health outcomes. This present study aimed to explore roles of baseline income, follow-up income, and income mobility in the development of mental disorders using an intra-generational, longitudinal follow-up study.MethodsWe used data from the Montreal South-West Longitudinal Catchment Area Study. A total of 1117 participants with complete information both on income and past 12-month diagnoses of mental disorders were selected for this study. Diagonal Reference Models were used to simultaneously examine roles of income at baseline, income at follow-up, and income mobility in mental disorders during a 4-year follow-up.ResultsBoth baseline and follow-up income were important predictors for any mental disorder and major depression among males and females. Those with low income had a higher risk of any mental disorders and major depression. No evidence was found to support an association between income mobility (neither downwards nor upwards) and mental disorders. Marital status was uniquely associated with any mental disorder among males. Having a pre-existing diagnosis of any mental disorder at origin was associated with any mental disorder and major depression at the end of the 4-year follow-up.ConclusionsThis study first simultaneously examined roles of income at baseline, at follow-up, and mobility in mental disorders among a large-scale intra-generational community-based study. This present study provides additional evidence on how income is associated with an individuals’ likelihood of mental disorders.

Previous suicide attempt and subsequent risk of re-attempt and suicide: Are there differences in immigrant subgroups compared to Swedish-born individuals?

BackgroundStudies investigating how suicide attempting refugees and non-refugee migrants differ from Swedish-born individuals in terms of re-attempts and suicide are missing. It remains unknown how mental disorders and labour market marginalization (LMM) impact on these associations. MethodsThis longitudinal cohort study included Swedish residents aged 20–64 with suicide attempt in 2004–2012. In total, 42,684 individuals including 2017 refugees, and 2544 non-refugee migrants were included and followed until December 31, 2016. Risks of re-attempt and suicide were calculated as hazard ratios (HR) with 95% confidence intervals (CI), and adjusted for important confounders. Stratified analyses were to assess if mental disorders or LMM modified these associations. ResultsIn the adjusted models, refugees had an adjusted HR (aHR) of suicide re-attempt of 0.74 (CI: 0.67–0.81), and an aHR of 0.67 (CI: 0.53–0.86) for suicide death. These estimates were very similar to those of non-refugee migrants. Refugees and non-refugee migrants with suicide attempt had a lower prevalence of specialised health care due to mental disorders compared to Swedish-born attempters (48%, 44% and 61%, respectively). Mental disorders and LMM in terms of long-term sickness absence and disability pension increased the risk of re-attempt and suicide in all three groups. LimitationsOnly suicide attempts and mental disorders resulting in specialized in-and outpatient care were registered. ConclusionMigrants show considerably lower risks of re-attempt and suicide than Swedish-born individuals, with no differences between migrant groups. Despite vast differences in the prevalence of specific mental disorders, the role of mental disorders in the pathways to re-attempt and suicide does not appear to differ considerably between these groups.

Historical aspects of studying craniocervical dystonia

The study of dystonic hyperkinesias has a thousand-year-old history. Beginning with drawings and sculptures from antiquity and up to the present day, modern ideas gradually developed about the phenomenology, origin, and treatment methods of dystonia. Mentions of spastic torticollis, blepharospasm and Meige syndrome can even be found in the writings of Hippocrates and Celsus. Images and monuments from antiquity and ancient civilizations indicate the existence of focal dystonias in those times. The Middle Ages left science with records of cervical dystonia and numerous illustrations in religious images. The first well-known mention of the term ‘torticollis’ belongs to Francois Rabelais. The term started to appear in medical texts later on. One of the earliest medical records on cervical dystonia was made by the Swiss physician Felix Platerus. During the Age of Enlightenment, dystonias became a separate class in disease classification. Modern tendencies in studying dystonia are characterized by identifying the genes responsible for different forms of primary dystonia along with description of their phenotypes. There is an ongoing research on the role of mental disorders in the clinical presentation of dystonia.

Gut Microbiota in Bipolar Depression and Its Relationship to Brain Function: An Advanced Exploration.

The mechanism of bipolar disorder is unclear. Growing evidence indicates that gut microbiota plays a pivotal role in mental disorders. This study aimed to find out changes in the gut microbiota in bipolar depression (BD) subjects following treatment with quetiapine and evaluate their correlations with the brain and immune function. Totally 36 subjects with BD and 27 healthy controls (HCs) were recruited. The severity of depression was evaluated with the Montgomery-Asberg depression rating scale (MADRS). At baseline, fecal samples were collected and analyzed by quantitative polymerase chain reaction (qPCR). T lymphocyte subsets were measured to examine immune function. Near-infrared spectroscopy (NIRS) was used to assess brain function. All BD subjects received quetiapine treatment (300 mg/d) for four weeks, following which the fecal microbiota and immune profiles were reexamined. Here, we first put forward the new concept of brain-gut coefficient of balance (B-GCB), which referred to the ratio of [oxygenated hemoglobin]/(Bifidobacteria to Enterobacteriaceae ratio), to analyze the linkage between the gut microbiota and brain function. At baseline, the CD3+ T cell proportion was positively correlated with log10 Enterobacter spp count, whereas the correlativity between the other bacteria and immune profiles were negative. Log10 B-GCB was positively correlated with CD3+ T cell proportion. In subjects with BD, counts of Faecalibacterium prausnitzii, Bacteroides–Prevotella group, Atopobium Cluster, Enterobacter spp, and Clostridium Cluster IV were higher, whereas the log10 (B/E) were lower than HCs (B/E refers to Bifidobacteria to Enterobacteriaceae ratio and represents microbial colonization resistance). After treatment, MADRS scores were reduced, whereas the levels of Eubacterium rectale, Bifidobacteria, and B/E increased. The composition of the gut microbiota and its relationship to brain function were altered in BD subjects. Quetiapine treatment was effective for depression and influenced the composition of gut microbiota in patients. Clinical Trial Registration: http://www.chictr.org.cn/index.aspx, identifier ChiCTR-COC-17011401, URL: http://www.chictr.org.cn/listbycreater.aspx.

The emerging role of exosomes in mental disorders

Exosomes are a class of extracellular vesicles of endocytic origin, which are released by cells and are accessible in biofluids, such as saliva, urine, and plasma. These vesicles are enriched with small RNA, and they play a role in many physiological processes. In the brain, they are involved in processes including synaptic plasticity, neuronal stress response, cell-to-cell communication and neurogenesis. While exosomes have been implicated previously in cancer and neurodegenerative diseases, research regarding their role in mental disorders remains scarce. Given their functional significance in the brain, investigation in this field is warranted. Additionally, because exosomes can cross the blood–brain barrier, they may serve as accessible biomarkers of neural dysfunction. Studying exosomes may provide information towards diagnosis and therapeutic intervention, and specifically those derived from the brain may provide a mechanistic view of the disease phenotype. This review will discuss the roles of exosomes in the brain, and relate novel findings to current insights into mental disorders.

Agmatine modulates spontaneous activity in neurons of the rat medial habenular complex\u2014a relevant mechanism in the pathophysiology and treatment of depression?

The dorsal diencephalic conduction system connects limbic forebrain structures to monaminergic mesencephalic nuclei via a distinct relay station, the habenular complexes. Both habenular nuclei, the lateral as well as the medial nucleus, are considered to play a prominent role in mental disorders like major depression. Herein, we investigate the effect of the polyamine agmatine on the electrical activity of neurons within the medial habenula in rat. We present evidence that agmatine strongly decreases spontaneous action potential firing of medial habenular neurons by activating I1-type imidazoline receptors. Additionally, we compare the expression patterns of agmatinase, an enzyme capable of inactivating agmatine, in rat and human habenula. In the medial habenula of both species, agmatinase is similarly distributed and observed in neurons and, in particular, in distinct neuropil areas. The putative relevance of these findings in the context of depression is discussed. It is concluded that increased activity of the agmatinergic system in the medial habenula may strengthen midbrain dopaminergic activity. Consequently, the habenular–interpeduncular axis may be dysregulated in patients with major depression.

Maternal suicide - Register based study of all suicides occurring after delivery in Sweden 1974-2009.

BackgroundRecent research suggests that having a newborn child is associated with substantially reduced risk for maternal suicide. We studied postpartum suicides in a national cohort of mothers and the role of mental disorder, self-harm and delivery related factors.MethodsWe used a nested case-control design with data from Swedish registries. The cohort consisted of all women given birth in Sweden 1974–2009. Mothers who died by suicide during follow-up were considered cases (n = 1,786) and risk of suicide was estimated with proximity to delivery as the explanatory variable. In a second step, association between suicide during the first year following delivery (n = 145) and mental disorder, self-harm and delivery related variables risk factors were analyzed.ResultsThe first postpartum year was associated with a lower risk of suicide, compared to later (RR 0.80, 95%CI 0.66–0.96), which was unaltered after adjustment for socio-economic status and history of self-harm (aRR 0.82, 95%CI 0.68–0.99). Compared to living mothers, suicide victims of the postpartum year more often had affective disorders (aRR 133.94, 95%CI 45.93–390.61), psychotic disorders (aRR 83.69, 95%CI 36.99–189.31) and history of self-harm (aRR 47.56, 95%CI 18.24–124.02). The aRR of stillbirth was 2.66 (95%CI 0.63–11.30).ConclusionsWe found only a weak negative association between childbirth during the preceding year and suicide, when using mothers as controls. A severe mental disorder after delivery and a history of self-harm was strongly associated with increased risk of suicide in the postpartum year and may inform the clinical assessment postpartum.

Circuits regulating pleasure and happiness: evolution and role in mental disorders.

Taking the evolutionary development of the forebrain as a starting point, the authors developed a biological framework for the subcortical regulation of human emotional behaviour which may offer an explanation for the pathogenesis of the principle symptoms of mental disorders. Appetitive-searching (reward-seeking) and distress-avoiding (misery-fleeing) behaviour are essential for all free-moving animals to stay alive and to have offspring. Even the oldest ocean-dwelling animal creatures, living about 560 million years ago and human ancestors, must therefore have been capable of generating these behaviours. Our earliest vertebrate ancestors, with a brain comparable with the modern lamprey, had a sophisticated extrapyramidal system generating and controlling all motions as well as a circuit including the habenula for the evaluation of the benefits of their actions. Almost the complete endbrain of the first land animals with a brain comparable with that of amphibians became assimilated into the human amygdaloid and hippocampal complex, whereas only a small part of the dorsal pallium and striatum developed into the ventral extrapyramidal circuits and the later insular cortex. The entire neocortex covering the hemispheres is of recent evolutionary origin, appearing first in early mammals. During the entire evolution of vertebrates, the habenular system was well conserved and maintained its function in regulating the intensity of reward-seeking (pleasure-related) and misery-fleeing (happiness-related) behaviour. The authors propose that the same is true in humans. Symptomatology of human mental disorders can be considered to result from maladaptation within a similar amygdalo/hippocampal-habenular-mesencephalic-ventral striatal system.

Analysis of microbiota in first episode psychosis identifies preliminary associations with symptom severity and treatment response

The effects of gut microbiota on the central nervous system, along its possible role in mental disorders, have received increasing attention. Here we investigated differences in fecal microbiota between 28 patients with first-episode psychosis (FEP) and 16 healthy matched controls and explored whether such differences were associated with response after up to 12months of treatment. Numbers of Lactobacillus group bacteria were elevated in FEP-patients and significantly correlated with severity along different symptom domains. A subgroup of FEP patients with the strongest microbiota differences also showed poorer response after up to 12months of treatment. The present findings support the involvement of microbiota alterations in psychotic illness and may provide the basis for exploring the benefit of their modulation on treatment response and remission.

Can gut microbes play a role in mental disorders and their treatment?

The gut microbes, collectively called microbiota, are linked to the brain through a bidirectional system that involves the vagus nerve, the immune system, and various neurotransmitters. Stress response, memory functions, social behavior, and mood are modulated by microbiota. Furthermore, microbiota play a role in the development of the central nervous system. These features, established largely in rodent studies, have informed hypotheses about the role of microbiota in human psychiatric disorders. Microbiota affect phenomena that are known to be parts of the depression phenotype, such as exaggerated response to stress and inflammatory features. Furthermore, the role of microbiota in neurodevelopment and in the modulation of social behavior suggests the possibility of its role in autism spectrum disorder and in schizophrenia. If altered, microbiota play a role in psychiatric disorders, then efforts to normalize the gut microbial population by the ingestion of probiotics (live bacteria) could have antidepresssant or antipsychotic effects. Testing such hypotheses in translational human studies is a matter of future research.

Клинико-психологические аспекты вхождения подростков в экстремистскую и террористическую деятельность

The article deals with the clinical and psychological aspects of including minors in terrorist and extremist activities. In the historical perspective, it was traced how the views on the role of mental disorders in the genesis of such crimes changed. It is shown that terrorist and extremist activity must be viewed as a complex multi-factor phenomenon, in which socio-psychological components play a leading role. It is noted that the psychopathological process can act as a prerequisite for inclusion in such radical groups. Psychoanalytic, sociological, cognitive approaches, theories of social learning and the concept of diffuse ego-identity making attempts to explain the mechanisms of terrorist and extremist activity in minors are analyzed. The problem of insufficient study of the influence of the Internet and social networks on the formation of readiness for admission to adolescents in radical organizations is posed.

Effectiveness of a Cognitive Behavioral Therapy-Based Indicated Prevention Program for Children with Elevated Anxiety Levels: a Randomized Controlled Trial

Childhood anxiety is a problem not only because of its negative consequences on the well-being of children but also because of its adverse effects on society and its role in mental disorders later in life. Adequate prevention might be the key in tackling this problem. The effectiveness of Coping Cat, as an indicated CBT-based prevention program in Dutch primary school children, was assessed by means of a randomized controlled trial. In total, 141 children aged 7–13 with elevated levels of anxiety and their mothers were included and randomly assigned to an intervention group and a waiting list control group. After screening, all participants completed baseline, post-intervention, and 3-month follow-up assessments. The results showed that Coping Cat, as an indicated prevention program, reduces children’s self-reported anxiety symptoms, with Cohen’s effect size d of 0.66 at the 3-month follow-up. A moderating effect was found for baseline anxiety level; specifically, children with high levels of baseline anxiety who received the Coping Cat program had lower anxiety levels at follow-up compared to children with high levels of anxiety in the control condition. No moderating effects of gender or age were found. An unexpected decline in anxiety levels from screening to pre-assessment was found in both groups, and this decline was stronger in the experimental group. These promising results warrant the implementation of Coping Cat as an indicated prevention program.

Identification of the BRD1 interaction network and its impact on mental disorder risk.

BackgroundThe bromodomain containing 1 (BRD1) gene has been implicated with transcriptional regulation, brain development, and susceptibility to schizophrenia and bipolar disorder. To advance the understanding of BRD1 and its role in mental disorders, we characterized the protein and chromatin interactions of the BRD1 isoforms, BRD1-S and BRD1-L.MethodsStable human cell lines expressing epitope tagged BRD1-S and BRD1-L were generated and used as discovery systems for identifying protein and chromatin interactions. Protein-protein interactions were identified using co-immunoprecipitation followed by mass spectrometry and chromatin interactions were identified using chromatin immunoprecipitation followed by next generation sequencing. Gene expression profiles and differentially expressed genes were identified after upregulating and downregulating BRD1 expression using microarrays. The presented functional molecular data were integrated with human genomic and transcriptomic data using available GWAS, exome-sequencing datasets as well as spatiotemporal transcriptomic datasets from the human brain.ResultsWe present several novel protein interactions of BRD1, including isoform-specific interactions as well as proteins previously implicated with mental disorders. By BRD1-S and BRD1-L chromatin immunoprecipitation followed by next generation sequencing we identified binding to promoter regions of 1540 and 823 genes, respectively, and showed correlation between BRD1-S and BRD1-L binding and regulation of gene expression. The identified BRD1 interaction network was found to be predominantly co-expressed with BRD1 mRNA in the human brain and enriched for pathways involved in gene expression and brain function. By interrogation of large datasets from genome-wide association studies, we further demonstrate that the BRD1 interaction network is enriched for schizophrenia risk.ConclusionOur results show that BRD1 interacts with chromatin remodeling proteins, e.g. PBRM1, as well as histone modifiers, e.g. MYST2 and SUV420H1. We find that BRD1 primarily binds in close proximity to transcription start sites and regulates expression of numerous genes, many of which are involved with brain development and susceptibility to mental disorders. Our findings indicate that BRD1 acts as a regulatory hub in a comprehensive schizophrenia risk network which plays a role in many brain regions throughout life, implicating e.g. striatum, hippocampus, and amygdala at mid-fetal stages.Electronic supplementary materialThe online version of this article (doi:10.1186/s13073-016-0308-x) contains supplementary material, which is available to authorized users.

Homicide-suicide and the role of mental disorder: a national consecutive case series.

PurposeThere is a lack of robust empirical research examining mental disorder and homicide–suicide. Primary care medical records are seldom used in homicide–suicide research. The aims of this study were to describe the characteristics of offenders and victims; determine the prevalence of mental disorder and contact with mental health services and examine adverse events prior to the offence.MethodsThis was a mixed-methods study based on a consecutive case series of offences in England and Wales occurring between 2006 and 2008. 60 homicide–suicides were recorded. Data sources included coroner’s records, police files, General Practice (GP) and specialist mental health records, and newspaper articles.ResultsThe results show that most victims were spouse/partners and/or children. Most perpetrators were male (88 %) and most victims were female (77 %). The incidents were commonly preceded by relationship breakdown and separation. 62 % had mental health problems. A quarter visited a GP for emotional distress within a month of the incident. Few had been in recent contact with mental health services before the incident (12 %). Self-harm (26 %) and domestic violence (39 %) were common.ConclusionIn conclusion, GPs cannot be expected to prevent homicide–suicide directly, but they can reduce risk generally, via the treatment of depression and recognising the risks associated with domestic violence.