Cortical and Subcortical Neuroanatomical Signatures of Schizotypy in 2,952 Individuals Assessed in a Worldwide ENIGMA Study

James Gilleen

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Importance: Neuroanatomical abnormalities have been reported along a continuum from at-risk stages to early and chronic psychosis. However, a comprehensive neuroanatomical mapping of schizotypy remains to be established.
Objective: To conduct the first large-scale meta-analyses of subcortical and cortical morphometric signatures of schizotypy in the general population. Second, to compare schizotypy-related morphometric patterns with structural abnormalities observed in other major psychiatric disorders.
Design: Subcortical and cortical effect size maps related to different schizotypy scores in healthy individuals were generated using T1-weighted magnetic resonance images from cross-sectional data. Pattern similarity of schizotypy-related subcortical and cortical maps with corresponding maps in schizophrenia, bipolar disorder and depression was assessed. Data analysis was conducted between September 2018 and August 2020.
Setting: Meta-analysis using standardized methods of 26 cohorts from the worldwide ENIGMA Schizotypy working group.
Participants: 2,952 unmedicated healthy individuals (12 to 68 years, 46.5% male) with varying levels of schizotypy contributed to the meta-analysis.
Main outcomes and measures: Partial correlation effect size of subcortical volume, cortical thickness and surface area changes related to schizotypy scores.
Results: Thickness of prefrontal cortex, in particular right medial orbitofrontal cortex (mOFC), was positively associated with schizotypy ratings (r = .067, pFDR = .02, 95% CI [.03 - .10]), while schizotypy-related cortical surface area and subcortical volume changes were only subtle. All neuroanatomical findings were independent from disease chronicity or antipsychotic medication. The schizotypy-related cortical thickness map was positively correlated with cortical abnormalities in schizophrenia (r = .33, pspin = .008), but not bipolar disorder (r = .187, pspin = .156) or major depression (r = -.22, pspin = .095). Schizotypy-related subcortical volume changes were negatively correlated with subcortical volume abnormalities in schizophrenia (rho = -.651, pspin = .006), bipolar disorder (rho = -.627, pspin = .009), and major depression (rho = -.688, pspin = .004).
Conclusion: This neuroimaging meta-analysis comprehensively maps the morphometric signatures of schizotypy in the general population. The relationship of higher schizotypy to thicker mOFC yields new insights into the neurobiology of schizotypy. Finally, the cortical pattern similarity of schizotypy and schizophrenia provides neuroanatomical evidence for a dimensional continuity across the extended psychosis phenotype.
Original languageEnglish
JournalBiological Psychiatry
Publication statusSubmitted - 11 Oct 2020

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