Genetic insights into human cortical organization and development through genome-wide analyses of 2,347 neuroimaging phenotypes

Nature Genetics, Journal Year: 2023, Volume and Issue: 55(9), P. 1483 - 1493

Published: Aug. 17, 2023

Language: Английский

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Connectome architecture shapes large-scale cortical alterations in schizophrenia: a worldwide ENIGMA study

Molecular Psychiatry, Journal Year: 2024, Volume and Issue: 29(6), P. 1869 - 1881

Published: Feb. 9, 2024

Abstract Schizophrenia is a prototypical network disorder with widespread brain-morphological alterations, yet it remains unclear whether these distributed alterations robustly reflect the underlying layout. We tested large-scale structural in schizophrenia relate to normative and functional connectome architecture, systematically evaluated robustness generalizability of network-level alterations. Leveraging anatomical MRI scans from 2439 adults 2867 healthy controls 26 ENIGMA sites data Human Connectome Project ( n = 207), we against two susceptibility models: (i) hub vulnerability, which examines associations between regional centrality magnitude disease-related alterations; (ii) epicenter mapping, identifies regions whose typical connectivity profile most closely resembles morphological To assess specificity, contextualized influence site, disease stages, individual clinical factors compared that found affective disorders. Our findings show schizophrenia-related cortical thinning spatially associated hubs, suggesting highly interconnected are more vulnerable Predominantly temporo-paralimbic frontal emerged as epicenters profiles linked schizophrenia’s alteration patterns. Findings were robust across sites, related symptoms. Moreover, transdiagnostic comparisons revealed overlapping bipolar, but not major depressive disorder, suggestive pathophysiological continuity within schizophrenia-bipolar-spectrum. In sum, over course follow brain emphasizing marked temporo-frontal at both level group individual. Subtle variations stages suggest interacting pathological processes, while patient-specific symptoms support additional inter-individual variability vulnerability schizophrenia. work outlines potential pathways better understand macroscale inter-

Language: Английский

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Using brain structural neuroimaging measures to predict psychosis onset for individuals at clinical high-risk

Molecular Psychiatry, Journal Year: 2024, Volume and Issue: 29(5), P. 1465 - 1477

Published: Feb. 9, 2024

Abstract Machine learning approaches using structural magnetic resonance imaging (sMRI) can be informative for disease classification, although their ability to predict psychosis is largely unknown. We created a model with individuals at CHR who developed later (CHR-PS+) from healthy controls (HCs) that differentiate each other. also evaluated whether we could distinguish CHR-PS+ those did not develop (CHR-PS-) and uncertain follow-up status (CHR-UNK). T1-weighted brain MRI scans 1165 (CHR-PS+, n = 144; CHR-PS-, 793; CHR-UNK, 228), 1029 HCs, were obtained 21 sites. used ComBat harmonize measures of subcortical volume, cortical thickness surface area data corrected non-linear effects age sex general additive model. ( 120) HC 799) 20 sites served as training dataset, which build classifier. The remaining samples external validation datasets evaluate classifier performance (test, independent confirmatory, group [CHR-PS- CHR-UNK] datasets). accuracy the on confirmatory was 85% 73% respectively. Regional measures-including right superior frontal, temporal, bilateral insular cortices strongly contributed classifying HC. CHR-PS- CHR-UNK more likely classified compared (classification rate HC: CHR-PS+, 30%; 73%; 80%). multisite sMRI train onset in individuals, it showed promise predicting an sample. results suggest when considering adolescent development, baseline may helpful identify prognosis. Future prospective studies are required about actually clinical settings.

Language: Английский

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Brain-charting autism and attention deficit hyperactivity disorder reveals distinct and overlapping neurobiology

Biological Psychiatry, Journal Year: 2024, Volume and Issue: unknown

Published: Aug. 1, 2024

Autism and attention-deficit/hyperactivity disorder (ADHD) are heterogeneous neurodevelopmental conditions with complex underlying neurobiology that is still poorly understood. Despite overlapping presentation sex-biased prevalence, autism ADHD rarely studied together sex differences often overlooked. Population modeling, referred to as normative provides a unified framework for studying age-specific sex-specific divergences in brain development.

Language: Английский

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Examining the shared etiology of psychopathology with genome-wide association studies

Physiological Reviews, Journal Year: 2023, Volume and Issue: 103(2), P. 1645 - 1665

Published: Jan. 12, 2023

Genome-wide association studies (GWASs) have ushered in a new era of reproducible discovery psychiatric genetics. The field has now identified hundreds common genetic variants that are associated with mental disorders, and many them influence more than one disorder. By advancing the understanding causal biology underlying psychopathology, GWAS results poised to inform development novel therapeutics, stratification at-risk patients, perhaps even revision top-down classification systems psychiatry. Here, we provide concise review findings an emphasis on elucidated shared etiology summarizing insights at three levels analysis: 1) genome-wide architecture; 2) networks, pathways, gene sets; 3) individual variants/genes. Three themes emerge from these efforts. First, all phenotypes heritable, highly polygenic, influenced by pleiotropic incomplete penetrance. Second, highlight broad etiological roles neuronal biology, system-wide effects over localized effects, early neurodevelopment as critical period. Third, loci robustly multiple forms psychopathology harbor genes involved synaptic structure function. Finally, conclude our discussing implications hold for psychiatry, well expected challenges future directions next stage

Language: Английский

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Combining Transdiagnostic and Disorder-Level GWAS Enhances Precision of Psychiatric Genetic Risk Profiles in a Multi-Ancestry Sample

medRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: May 10, 2024

Abstract The etiology of substance use disorders (SUDs) and psychiatric reflects a combination both transdiagnostic (i.e., common) disorder-level independent) genetic risk factors. We applied genomic structural equation modeling to examine these factors across SUDs, psychotic, mood, anxiety using genome-wide association studies (GWAS) European-(EUR) African-ancestry (AFR) individuals. In EUR individuals, represented SUDs (143 lead single nucleotide polymorphisms [SNPs]), psychotic (162 SNPs), mood/anxiety (112 SNPs). identified two novel SNPs for that have probable regulatory roles on FOXP1 , NECTIN3 BTLA genes. AFR (1 SNP) (no significant SUD factor SNP, although previously in EUR- cross-ancestry GWAS, is finding Shared variance accounted overlap between their comorbidities, with second-order GWAS identifying up 12 not significantly associated either first-order Finally, common independent effects showed different associations psychiatric, sociodemographic, medical phenotypes. For example, the components schizophrenia bipolar disorder had distinct affective risk-taking behaviors, phenome-wide conditions tobacco broader factor. Thus, combining approaches can improve our understanding co-occurring increase specificity discovery, which critical demonstrate considerable symptom etiological overlap.

Language: Английский

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Characterizing the phenotypic and genetic structure of psychopathology in UK Biobank

Nature Mental Health, Journal Year: 2024, Volume and Issue: 2(8), P. 960 - 974

Published: July 4, 2024

Language: Английский

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Molecular genetic influences on attentional control and other executive processes and their links with psychopathology in the AFFECT study

medRxiv (Cold Spring Harbor Laboratory), Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 20, 2025

Abstract Background Attentional control is a critical component of executive functioning involved in numerous psychiatric and neurological disorders, yet its etiological relationships with many cognitive behavioral phenotypes remain underexplored. Methods We conducted the first multivariate characterization molecular genetic influences on attentional other processes cohort more than 20,000 individuals enriched for mood disorders. used Genomic Structural Equation Modeling to formally model patterns covariance among these task-based measures cognition, as well their cognitive, clinical, imaging-derived phenotypes. Results identified two independent latent factors: one broadly influencing function narrowly control. Both Common Executive Function (CEF) Control (AC) factors were genetically correlated clinical phenotypes, each factor uniquely linked liability For example, we observed myriad between psychopathology, including robust conditionally associations ADHD. However, despite clear links brain-related correlations themselves modest non-significant after correcting multiple comparisons. Conclusions Overall, results our study suggest that are generally distinct from those influence broader aspects function. The CEF AC show overlap outcomes, underscoring need detailed phenotyping cognition generate new insights into etiology psychopathology.

Language: Английский

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Insights into the genetic architecture of cerebellar lobules derived from the UK Biobank

Scientific Reports, Journal Year: 2024, Volume and Issue: 14(1)

Published: April 25, 2024

In this work we endeavor to further understand the genetic architecture of cerebellum by examining underpinnings different cerebellar lob(ul)es, identifying their relation cortical and subcortical regions, as well psychiatric disorders, traces evolutionary trajectories. We confirm moderate heritability volumes, reveal clustering variability across substructures, which warranted a detailed analysis using higher structural resolution. replicated known correlations with several report new cortico-cerebellar correlations, including negative between anterior lobules cingulate, positive ones lateral Crus I lobule VI measures in fusiform region. Heritability partitioning for annotations highlighted that vermis II has depleted genomic regions "archaic introgression deserts", but no enrichment/depletion any other regions. Taken together, these findings novel insights into lobules.

Language: Английский

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Dataset factors associated with age‐related changes in brain structure and function in neurodevelopmental conditions

Human Brain Mapping, Journal Year: 2024, Volume and Issue: 45(13)

Published: Sept. 1, 2024

With brain structure and function undergoing complex changes throughout childhood adolescence, age is a critical consideration in neuroimaging studies, particularly for those of individuals with neurodevelopmental conditions. However, despite the increasing use large, consortium-based datasets to examine neurotypical neurodivergent populations, it unclear whether age-related are consistent between inconsistencies related differences sample characteristics, such as demographics phenotypic features, exist. To address this, we built models (regional cortical thickness regional surface area; N = 1218) (resting-state functional connectivity strength; 1254) two neurodiverse datasets: Province Ontario Neurodevelopmental Network Healthy Brain Network. We examined deviations from these differed datasets, explored were associated demographic clinical variables. found significant measures area strength brain. For area, patterns race/ethnicity, while strength, positive associations observed head motion. Our findings highlight that may be influenced by thus future studies should consider when examining or controlling effects analyses.

Language: Английский

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