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Virtual histology of cortical thickness and shared neurobiology in 6 psychiatric disorders

Harrison, Neil 2021. Virtual histology of cortical thickness and shared neurobiology in 6 psychiatric disorders. Journal of the American Medical Association 78 (1) , pp. 47-63. 10.1001/jamapsychiatry.2020.2694

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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 neurobiological correlates of group differences in cortical thickness between cases and controls in six disorders: attention-deficit/hyperactivity disorder (ADHD), autism spectrum disorder (ASD), bipolar disorder (BD), major depressive disorder (MDD), obsessive-compulsive disorder (OCD) and schizophrenia (SCZ). Design: Meta-analytic profiles of group differences in cortical thickness between cases and controls were generated using T1-weighted magnetic resonance images. Similarity between inter-regional 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. Gene co-expression, clustering and enrichment for genes associated with these disorders were conducted. Data analysis was conducted between June and December 2019. Setting: A meta-analysis including 145 cohorts across 6 psychiatric disorders drawn from the ENIGMA Consortium. Participants: The number of cases/controls in each of the six disorders were as follows: ADHD: 1,814/1,602; ASD: 1,748/1,770; BD: 1,547/3,405; MDD: 2,658/3,572; OCD: 2,266/2,007; and SCZ: 2,688/3,244. Main outcomes and measures: Inter-regional profiles of group difference in cortical thickness between cases and controls. Results: Inter-regional profiles of group differences in cortical thickness for each of the six psychiatric disorders were associated with profiles of gene expression specific to pyramidal (CA1) cells, astrocytes (except for BD) and microglia (except for OCD). Principal component analysis revealed a shared profile of difference in cortical thickness across the six disorders (48% variance explained); inter-regional profile of this principal component 1 was related to that of the pyramidal-cell gene expression. Co-expression analyses of these genes revealed two clusters: (1) a prenatal cluster enriched with genes involved in neurodevelopmental (axon guidance) processes; and (2) a post-natal cluster enriched with genes involved in synaptic activity & plasticity-related processes. These clusters were enriched with genes associated with all six psychiatric disorders. Conclusion: There are shared neurobiological processes underlying 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.

Item Type: Article
Date Type: Publication
Status: Published
Schools: MRC Centre for Neuropsychiatric Genetics and Genomics (CNGG)
Medicine
Publisher: American Medical Association (AMA)
ISSN: 0098-7484
Date of Acceptance: 13 June 2020
Last Modified: 28 Jan 2021 15:01
URI: http://orca.cf.ac.uk/id/eprint/132600

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