Offspring of parents with severe mental illness are at increased risk of developing psychopathology. Identifying endophenotypic markers in high-familial-risk individuals can aid in early detection and inform development of prevention strategies. Using generalized additive mixed models, we compared age trajectories of gyrification index (GI) and sulcal morphometric measures (i.e., sulcal depth, length and width) between individuals at familial risk for bipolar disorder or schizophrenia and controls. 300 T1-weighted MRI scans were obtained of 187 individuals (53 % female, age range: 8-23 years) at familial risk for bipolar disorder (n = 80, n families=55) or schizophrenia (n = 53, n families=36) and controls (n = 54, n families=33). 113 individuals underwent two scans. Globally, GI, sulcal depth and sulcal length decreased significantly with age, and sulcal width increased significantly with age in a (near-)linear manner. There were no differences between groups in age trajectories or mean values of gyrification or any of the sulcal measures. These findings suggest that, on average, young individuals at familial risk for bipolar disorder or schizophrenia have preserved developmental patterns of gyrification and sulcal morphometrics during childhood and adolescence.

• Klíčová slova
• Bipolar disorder, Gyrification, High familial risk, Longitudinal, Offspring, Schizophrenia,
• MeSH
• bipolární porucha * patologie   genetika   diagnostické zobrazování   MeSH
• dítě postižených rodičů MeSH
• dítě MeSH
• lidé MeSH
• magnetická rezonanční tomografie MeSH
• mladiství MeSH
• mladý dospělý MeSH
• mozková kůra * růst a vývoj   patologie   MeSH
• schizofrenie * patologie   genetika   diagnostické zobrazování   MeSH
• Check Tag
• dítě MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

First-degree relatives of patients diagnosed with schizophrenia (SZ-FDRs) show similar patterns of brain abnormalities and cognitive alterations to patients, albeit with smaller effect sizes. First-degree relatives of patients diagnosed with bipolar disorder (BD-FDRs) show divergent patterns; on average, intracranial volume is larger compared to controls, and findings on cognitive alterations in BD-FDRs are inconsistent. Here, we performed a meta-analysis of global and regional brain measures (cortical and subcortical), current IQ, and educational attainment in 5,795 individuals (1,103 SZ-FDRs, 867 BD-FDRs, 2,190 controls, 942 schizophrenia patients, 693 bipolar patients) from 36 schizophrenia and/or bipolar disorder family cohorts, with standardized methods. Compared to controls, SZ-FDRs showed a pattern of widespread thinner cortex, while BD-FDRs had widespread larger cortical surface area. IQ was lower in SZ-FDRs (d = -0.42, p = 3 × 10-5 ), with weak evidence of IQ reductions among BD-FDRs (d = -0.23, p = .045). Both relative groups had similar educational attainment compared to controls. When adjusting for IQ or educational attainment, the group-effects on brain measures changed, albeit modestly. Changes were in the expected direction, with less pronounced brain abnormalities in SZ-FDRs and more pronounced effects in BD-FDRs. To conclude, SZ-FDRs and BD-FDRs show a differential pattern of structural brain abnormalities. In contrast, both had lower IQ scores and similar school achievements compared to controls. Given that brain differences between SZ-FDRs and BD-FDRs remain after adjusting for IQ or educational attainment, we suggest that differential brain developmental processes underlying predisposition for schizophrenia or bipolar disorder are likely independent of general cognitive impairment.

• Klíčová slova
• bipolar disorder, education, intelligence, neuroimaging, relatives, schizophrenia,
• MeSH
• bipolární porucha komplikace   diagnostické zobrazování   patologie   MeSH
• genetická predispozice k nemoci * MeSH
• inteligence fyziologie   MeSH
• kognitivní dysfunkce diagnostické zobrazování   patologie   MeSH
• lidé MeSH
• magnetická rezonanční tomografie MeSH
• neurozobrazování * MeSH
• rodina MeSH
• schizofrenie komplikace   diagnostické zobrazování   etiologie   patologie   MeSH
• stupeň vzdělání * MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• metaanalýza MeSH
• multicentrická studie MeSH
• práce podpořená grantem MeSH
• Research Support, N.I.H., Extramural MeSH
• Research Support, U.S. Gov't, Non-P.H.S. MeSH

MRI-derived brain measures offer a link between genes, the environment and behavior and have been widely studied in bipolar disorder (BD). However, many neuroimaging studies of BD have been underpowered, leading to varied results and uncertainty regarding effects. The Enhancing Neuro Imaging Genetics through Meta-Analysis (ENIGMA) Bipolar Disorder Working Group was formed in 2012 to empower discoveries, generate consensus findings and inform future hypothesis-driven studies of BD. Through this effort, over 150 researchers from 20 countries and 55 institutions pool data and resources to produce the largest neuroimaging studies of BD ever conducted. The ENIGMA Bipolar Disorder Working Group applies standardized processing and analysis techniques to empower large-scale meta- and mega-analyses of multimodal brain MRI and improve the replicability of studies relating brain variation to clinical and genetic data. Initial BD Working Group studies reveal widespread patterns of lower cortical thickness, subcortical volume and disrupted white matter integrity associated with BD. Findings also include mapping brain alterations of common medications like lithium, symptom patterns and clinical risk profiles and have provided further insights into the pathophysiological mechanisms of BD. Here we discuss key findings from the BD working group, its ongoing projects and future directions for large-scale, collaborative studies of mental illness.

• Klíčová slova
• ENIGMA, MRI, bipolar disorder, cortical surface area, cortical thickness, mega-analysis, meta-analysis, neuroimaging, psychiatry, volume,
• MeSH
• bipolární porucha * diagnostické zobrazování   patologie   MeSH
• lidé MeSH
• magnetická rezonanční tomografie * MeSH
• metaanalýza jako téma MeSH
• mozková kůra * diagnostické zobrazování   patologie   MeSH
• multicentrické studie jako téma MeSH
• neurozobrazování * MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• přehledy MeSH
• Research Support, N.I.H., Extramural MeSH
• Research Support, N.I.H., Intramural MeSH

This review summarizes the last decade of work by the ENIGMA (Enhancing NeuroImaging Genetics through Meta Analysis) Consortium, a global alliance of over 1400 scientists across 43 countries, studying the human brain in health and disease. Building on large-scale genetic studies that discovered the first robustly replicated genetic loci associated with brain metrics, ENIGMA has diversified into over 50 working groups (WGs), pooling worldwide data and expertise to answer fundamental questions in neuroscience, psychiatry, neurology, and genetics. Most ENIGMA WGs focus on specific psychiatric and neurological conditions, other WGs study normal variation due to sex and gender differences, or development and aging; still other WGs develop methodological pipelines and tools to facilitate harmonized analyses of "big data" (i.e., genetic and epigenetic data, multimodal MRI, and electroencephalography data). These international efforts have yielded the largest neuroimaging studies to date in schizophrenia, bipolar disorder, major depressive disorder, post-traumatic stress disorder, substance use disorders, obsessive-compulsive disorder, attention-deficit/hyperactivity disorder, autism spectrum disorders, epilepsy, and 22q11.2 deletion syndrome. More recent ENIGMA WGs have formed to study anxiety disorders, suicidal thoughts and behavior, sleep and insomnia, eating disorders, irritability, brain injury, antisocial personality and conduct disorder, and dissociative identity disorder. Here, we summarize the first decade of ENIGMA's activities and ongoing projects, and describe the successes and challenges encountered along the way. We highlight the advantages of collaborative large-scale coordinated data analyses for testing reproducibility and robustness of findings, offering the opportunity to identify brain systems involved in clinical syndromes across diverse samples and associated genetic, environmental, demographic, cognitive, and psychosocial factors.

• MeSH
• depresivní porucha unipolární * genetika   MeSH
• lidé MeSH
• magnetická rezonanční tomografie MeSH
• mozek diagnostické zobrazování   MeSH
• neurozobrazování MeSH
• reprodukovatelnost výsledků MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• metaanalýza MeSH
• práce podpořená grantem MeSH
• přehledy MeSH
• Research Support, N.I.H., Extramural MeSH