Schizophrenia has a heritability of 60-80%1, much of which is attributable to common risk alleles. Here, in a two-stage genome-wide association study of up to 76,755 individuals with schizophrenia and 243,649 control individuals, we report common variant associations at 287 distinct genomic loci. Associations were concentrated in genes that are expressed in excitatory and inhibitory neurons of the central nervous system, but not in other tissues or cell types. Using fine-mapping and functional genomic data, we identify 120 genes (106 protein-coding) that are likely to underpin associations at some of these loci, including 16 genes with credible causal non-synonymous or untranslated region variation. We also implicate fundamental processes related to neuronal function, including synaptic organization, differentiation and transmission. Fine-mapped candidates were enriched for genes associated with rare disruptive coding variants in people with schizophrenia, including the glutamate receptor subunit GRIN2A and transcription factor SP4, and were also enriched for genes implicated by such variants in neurodevelopmental disorders. We identify biological processes relevant to schizophrenia pathophysiology; show convergence of common and rare variant associations in schizophrenia and neurodevelopmental disorders; and provide a resource of prioritized genes and variants to advance mechanistic studies.

• MeSH
• alely MeSH
• celogenomová asociační studie * MeSH
• genetická predispozice k nemoci genetika   MeSH
• genomika MeSH
• jednonukleotidový polymorfismus genetika   MeSH
• lidé MeSH
• schizofrenie * genetika   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Research Support, N.I.H., Extramural MeSH

IMPORTANCE: Large-scale neuroimaging studies have revealed group differences in cortical thickness across many psychiatric disorders. The underlying neurobiology behind these differences is not well understood. OBJECTIVE: To determine neurobiologic correlates of group differences in cortical thickness between cases and controls in 6 disorders: attention-deficit/hyperactivity disorder (ADHD), autism spectrum disorder (ASD), bipolar disorder (BD), major depressive disorder (MDD), obsessive-compulsive disorder (OCD), and schizophrenia. DESIGN, SETTING, AND PARTICIPANTS: Profiles of group differences in cortical thickness between cases and controls were generated using T1-weighted magnetic resonance images. Similarity between interregional profiles of cell-specific gene expression and those in the group differences in cortical thickness were investigated in each disorder. Next, principal component analysis was used to reveal a shared profile of group difference in thickness across the disorders. Analysis for gene coexpression, clustering, and enrichment for genes associated with these disorders were conducted. Data analysis was conducted between June and December 2019. The analysis included 145 cohorts across 6 psychiatric disorders drawn from the ENIGMA consortium. The numbers of cases and controls in each of the 6 disorders were as follows: ADHD: 1814 and 1602; ASD: 1748 and 1770; BD: 1547 and 3405; MDD: 2658 and 3572; OCD: 2266 and 2007; and schizophrenia: 2688 and 3244. MAIN OUTCOMES AND MEASURES: Interregional profiles of group difference in cortical thickness between cases and controls. RESULTS: A total of 12 721 cases and 15 600 controls, ranging from ages 2 to 89 years, were included in this study. Interregional profiles of group differences in cortical thickness for each of the 6 psychiatric disorders were associated with profiles of gene expression specific to pyramidal (CA1) cells, astrocytes (except for BD), and microglia (except for OCD); collectively, gene-expression profiles of the 3 cell types explain between 25% and 54% of variance in interregional profiles of group differences in cortical thickness. Principal component analysis revealed a shared profile of difference in cortical thickness across the 6 disorders (48% variance explained); interregional profile of this principal component 1 was associated with that of the pyramidal-cell gene expression (explaining 56% of interregional variation). Coexpression analyses of these genes revealed 2 clusters: (1) a prenatal cluster enriched with genes involved in neurodevelopmental (axon guidance) processes and (2) a postnatal cluster enriched with genes involved in synaptic activity and plasticity-related processes. These clusters were enriched with genes associated with all 6 psychiatric disorders. CONCLUSIONS AND RELEVANCE: In this study, shared neurobiologic processes were associated with differences in cortical thickness across multiple psychiatric disorders. These processes implicate a common role of prenatal development and postnatal functioning of the cerebral cortex in these disorders.

• MeSH
• analýza hlavních komponent MeSH
• bipolární porucha diagnostické zobrazování   patologie   MeSH
• depresivní porucha unipolární diagnostické zobrazování   patologie   MeSH
• dítě MeSH
• dospělí MeSH
• exprese genu fyziologie   MeSH
• hyperkinetická porucha diagnostické zobrazování   patologie   MeSH
• kohortové studie MeSH
• lidé středního věku MeSH
• lidé MeSH
• magnetická rezonanční tomografie MeSH
• mladiství MeSH
• mladý dospělý MeSH
• mozková kůra cytologie   diagnostické zobrazování   růst a vývoj   patologie   MeSH
• obsedantně kompulzivní porucha diagnostické zobrazování   patologie   MeSH
• poruchy autistického spektra diagnostické zobrazování   patologie   MeSH
• předškolní dítě MeSH
• schizofrenie diagnostické zobrazování   patologie   MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• studie případů a kontrol MeSH
• výpočetní biologie MeSH
• vývoj člověka fyziologie   MeSH
• vývoj plodu fyziologie   MeSH
• Check Tag
• dítě MeSH
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• předškolní dítě MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

• MeSH
• lidé MeSH
• magnetická rezonanční tomografie MeSH
• mozek MeSH
• nemoci mozku * MeSH
• schizofrenie * MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• dopisy MeSH
• komentáře MeSH

BACKGROUND: The profile of cortical neuroanatomical abnormalities in schizophrenia is not fully understood, despite hundreds of published structural brain imaging studies. This study presents the first meta-analysis of cortical thickness and surface area abnormalities in schizophrenia conducted by the ENIGMA (Enhancing Neuro Imaging Genetics through Meta Analysis) Schizophrenia Working Group. METHODS: The study included data from 4474 individuals with schizophrenia (mean age, 32.3 years; range, 11-78 years; 66% male) and 5098 healthy volunteers (mean age, 32.8 years; range, 10-87 years; 53% male) assessed with standardized methods at 39 centers worldwide. RESULTS: Compared with healthy volunteers, individuals with schizophrenia have widespread thinner cortex (left/right hemisphere: Cohen's d = -0.530/-0.516) and smaller surface area (left/right hemisphere: Cohen's d = -0.251/-0.254), with the largest effect sizes for both in frontal and temporal lobe regions. Regional group differences in cortical thickness remained significant when statistically controlling for global cortical thickness, suggesting regional specificity. In contrast, effects for cortical surface area appear global. Case-control, negative, cortical thickness effect sizes were two to three times larger in individuals receiving antipsychotic medication relative to unmedicated individuals. Negative correlations between age and bilateral temporal pole thickness were stronger in individuals with schizophrenia than in healthy volunteers. Regional cortical thickness showed significant negative correlations with normalized medication dose, symptom severity, and duration of illness and positive correlations with age at onset. CONCLUSIONS: The findings indicate that the ENIGMA meta-analysis approach can achieve robust findings in clinical neuroscience studies; also, medication effects should be taken into account in future genetic association studies of cortical thickness in schizophrenia.

• MeSH
• čelní lalok diagnostické zobrazování   patologie   MeSH
• dítě MeSH
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• lineární modely MeSH
• magnetická rezonanční tomografie MeSH
• mladiství MeSH
• mladý dospělý MeSH
• mozek diagnostické zobrazování   patologie   MeSH
• neurozobrazování MeSH
• prefrontální mozková kůra diagnostické zobrazování   patologie   MeSH
• schizofrenie diagnostické zobrazování   patologie   MeSH
• senioři MeSH
• spánkový lalok diagnostické zobrazování   patologie   MeSH
• studie případů a kontrol MeSH
• stupeň závažnosti nemoci MeSH
• věk při počátku nemoci MeSH
• Check Tag
• dítě MeSH
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• metaanalýza MeSH
• Research Support, N.I.H., Extramural MeSH

Sponsored by the Adolescent Mental Health Initiative of the Annenberg Public Policy Center (APPC) of the University of Pennsylvania and the Annenberg Foundation Trust at Sunnylands Trust, Treating and Preventing Adolescent Mental Health Disorders, Second Edition, provides a major update since the first edition in 2005. It addresses the current state of knowledge about the major mental health disorders that emerge during adolescence, including updated DSM-5 diagnostic criteria. Here, six commissions established by the APPC and the Sunnylands Trust pool their expertise on adolescent anxiety, schizophrenia, substance use disorders, depression and bipolar disorders, eating disorders, and suicidal behavior in sections that thoroughly define each disorder, outline and assess available treatments, discuss prevention strategies, and suggest a research agenda based on what we know and don't yet know about these various conditions. Two additional behavioral disorders-gambling and internet addiction are covered in this second edition.

• MeSH
• duševní poruchy diagnóza   prevence a kontrola   terapie   MeSH
• psychologie adolescentů MeSH
• zdravotnické služby pro mladistvé organizace a řízení   MeSH
• Geografické názvy
• Spojené státy americké MeSH

• Konspekt
• Psychiatrie
• NLK Obory
• psychiatrie
• pediatrie
• NLK Publikační typ
• kolektivní monografie

• MeSH
• antipsychotika škodlivé účinky   terapeutické užití   MeSH
• benzodiazepiny škodlivé účinky   terapeutické užití   MeSH
• farmakologické účinky MeSH
• financování vládou MeSH
• haloperidol škodlivé účinky   terapeutické užití   MeSH
• interpretace statistických dat MeSH
• lidé MeSH
• longitudinální studie MeSH
• magnetická rezonanční tomografie využití   MeSH
• mozek fyziologie   patologie   MeSH
• multicentrické studie jako téma MeSH
• neurologické vyšetření metody   využití   MeSH
• schizofrenie farmakoterapie   terapie   MeSH
• Check Tag
• lidé MeSH