Virtual Histology of Cortical Thickness and Shared Neurobiology in 6 Psychiatric Disorders.

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  • Additional Information
    • Corporate Authors:
      Writing Committee for the Attention-Deficit/Hyperactivity Disorder; Autism Spectrum Disorder; Bipolar Disorder; Major Depressive Disorder; Obsessive-Compulsive Disorder; and Schizophrenia ENIGMA Working Groups
    • Source:
      Publisher: American Medical Association Country of Publication: United States NLM ID: 101589550 Publication Model: Print Cited Medium: Internet ISSN: 2168-6238 (Electronic) Linking ISSN: 2168622X NLM ISO Abbreviation: JAMA Psychiatry Subsets: MEDLINE
    • Publication Information:
      Original Publication: Chicago, IL : American Medical Association, [2013]-
    • Subject Terms:
      Attention Deficit Disorder with Hyperactivity/*pathology ; Autism Spectrum Disorder/*pathology ; Bipolar Disorder/*pathology ; Cerebral Cortex/*pathology ; Depressive Disorder, Major/*pathology ; Fetal Development/*physiology ; Gene Expression/*physiology ; Human Development/*physiology ; Obsessive-Compulsive Disorder/*pathology ; Schizophrenia/*pathology; Adolescent ; Adult ; Aged ; Aged, 80 and over ; Attention Deficit Disorder with Hyperactivity/diagnostic imaging ; Autism Spectrum Disorder/diagnostic imaging ; Bipolar Disorder/diagnostic imaging ; Case-Control Studies ; Cerebral Cortex/cytology ; Cerebral Cortex/diagnostic imaging ; Cerebral Cortex/growth & development ; Child ; Child, Preschool ; Cohort Studies ; Computational Biology ; Depressive Disorder, Major/diagnostic imaging ; Female ; Humans ; Magnetic Resonance Imaging ; Male ; Middle Aged ; Obsessive-Compulsive Disorder/diagnostic imaging ; Principal Component Analysis ; Schizophrenia/diagnostic imaging ; Young Adult
    • Abstract:
      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.
    • Comments:
      Erratum in: JAMA Psychiatry. 2021 Jan 1;78(1):112. doi: 10.1001/jamapsychiatry.2020.3094. (PMID: 32936223)
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    • Grant Information:
      P50 MH094268 United States MH NIMH NIH HHS; R01 EB015611 United States EB NIBIB NIH HHS; T32 AG058507 United States AG NIA NIH HHS; MC_PC_17209 United Kingdom MRC_ Medical Research Council; IK6 CX002519 United States CX CSRD VA; K01 MH112774 United States MH NIMH NIH HHS; K23 MH115206 United States MH NIMH NIH HHS; UL1 TR001863 United States TR NCATS NIH HHS; G0802594 United Kingdom MRC_ Medical Research Council; U01 DA041148 United States DA NIDA NIH HHS; R01 MH119219 United States MH NIMH NIH HHS; R01 MH115357 United States MH NIMH NIH HHS; S10 OD023696 United States OD NIH HHS
    • Publication Date:
      Date Created: 20200829 Date Completed: 20220117 Latest Revision: 20240813
    • Publication Date:
      20240813
    • Accession Number:
      PMC7450410
    • Accession Number:
      10.1001/jamapsychiatry.2020.2694
    • Accession Number:
      32857118