Abstract
Neuroanatomical abnormalities have been reported along a continuum from at-risk stages, including high schizotypy, to early and chronic psychosis. However, a comprehensive neuroanatomical mapping of schizotypy remains to be established. The authors conducted the first large-scale meta-analyses of cortical and subcortical morphometric patterns of schizotypy in healthy individuals, and compared these patterns with neuroanatomical abnormalities observed in major psychiatric disorders. The sample comprised 3004 unmedicated healthy individuals (12–68 years, 46.5% male) from 29 cohorts of the worldwide ENIGMA Schizotypy working group. Cortical and subcortical effect size maps with schizotypy scores were generated using standardized methods. Pattern similarities were assessed between the schizotypy-related cortical and subcortical maps and effect size maps from comparisons of schizophrenia (SZ), bipolar disorder (BD) and major depression (MDD) patients with controls. Thicker right medial orbitofrontal/ventromedial prefrontal cortex (mOFC/vmPFC) was associated with higher schizotypy scores (r = 0.067, pFDR = 0.02). The cortical thickness profile in schizotypy was positively correlated with cortical abnormalities in SZ (r = 0.285, pspin = 0.024), but not BD (r = 0.166, pspin = 0.205) or MDD (r = −0.274, pspin = 0.073). The schizotypy-related subcortical volume pattern was negatively correlated with subcortical abnormalities in SZ (rho = −0.690, pspin = 0.006), BD (rho = −0.672, pspin = 0.009), and MDD (rho = −0.692, pspin = 0.004). Comprehensive mapping of schizotypy-related brain morphometry in the general population revealed a significant relationship between higher schizotypy and thicker mOFC/vmPFC, in the absence of confounding effects due to antipsychotic medication or disease chronicity. The cortical pattern similarity between schizotypy and schizophrenia yields new insights into a dimensional neurobiological continuity across the extended psychosis phenotype.
Original language | English |
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Pages (from-to) | 1167-1176 |
Number of pages | 10 |
Journal | Molecular Psychiatry |
Volume | 27 |
Issue number | 2 |
Early online date | 27 Oct 2021 |
DOIs | |
Publication status | Published - Feb 2022 |
Bibliographical note
Funding Information:PMT received partial grant support from Biogen, Inc. (Boston, USA) for work unrelated to this paper. SK received speaker honoraria from Janssen, Takeda, Lundbeck and Roche. Royalties for cognitive test and training software from Schuhfried. In the past 3 years, CP served on an advisory board for Lundbeck, Australia Pty Ltd. He has received honoraria for talks presented at educational meetings organized by Lundbeck. No other disclosures were reported.
Funding Information:
Core funding for ENIGMA was provided by the NIH Big Data to Knowledge (BD2K) program under consortium grant U54 EB020403 (PI: PMT). This research was funded in whole, or in part, by the Wellcome Trust [Sir Henry Dale Fellowship 202397/Z/16/Z to GM]. For the purpose of open access, the author has applied a CC BY public copyright licence to any Author Accepted Manuscript version arising from this submission. MK acknowledges funding from the Swiss National Science Foundation (P2SKP3_178175). Acknowledgments and funding details for the various participating data contributors are listed in at the end of the Supplementary Material.
Publisher Copyright:
© 2021, The Author(s).
Funding
PMT received partial grant support from Biogen, Inc. (Boston, USA) for work unrelated to this paper. SK received speaker honoraria from Janssen, Takeda, Lundbeck and Roche. Royalties for cognitive test and training software from Schuhfried. In the past 3 years, CP served on an advisory board for Lundbeck, Australia Pty Ltd. He has received honoraria for talks presented at educational meetings organized by Lundbeck. No other disclosures were reported. Core funding for ENIGMA was provided by the NIH Big Data to Knowledge (BD2K) program under consortium grant U54 EB020403 (PI: PMT). This research was funded in whole, or in part, by the Wellcome Trust [Sir Henry Dale Fellowship 202397/Z/16/Z to GM]. For the purpose of open access, the author has applied a CC BY public copyright licence to any Author Accepted Manuscript version arising from this submission. MK acknowledges funding from the Swiss National Science Foundation (P2SKP3_178175). Acknowledgments and funding details for the various participating data contributors are listed in at the end of the Supplementary Material.
Funders | Funder number |
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Biogen, Inc. | |
National Institutes of Health | |
National Institute of Biomedical Imaging and Bioengineering | U54EB020403 |
Wellcome Trust | 202397/Z/16/Z |
Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung | P2SKP3_178175 |