Schizotypy represents an index of psychosis-proneness in the general population often associated with childhood trauma exposure. Both schizotypy and childhood trauma are linked to structural brain alterations, and it is possible that trauma exposure moderates the extent of brain morphological differences associated with schizotypy. We addressed this question using data from a total of 1,182 healthy adults (age range: 18-65 years old, 647 females/535 males), pooled from nine sites worldwide, contributing to the Enhancing NeuroImaging Genetics through Meta-Analysis (ENIGMA) Schizotypy working group. All participants completed both the Schizotypal Personality Questionnaire Brief version (SPQ-B), and the Childhood Trauma Questionnaire (CTQ), and underwent a 3D T1-weighted brain MRI scan from which regional indices of subcortical grey matter volume and cortical thickness were determined. A series of multiple linear regressions revealed that differences in cortical thickness in four regions-of-interest were significantly associated with interactions between schizotypy and trauma; subsequent moderation analyses indicated that increasing levels of schizotypy were associated with thicker left caudal anterior cingulate gyrus, right middle temporal gyrus and insula, and thinner left caudal middle frontal gyrus, in people exposed to higher (but not low or average) levels of childhood trauma. This was found in the context of thicker bilateral medial orbitofrontal gyri, right rostral anterior cingulate gyrus, left temporal pole, left insula, and thinner left paracentral lobule directly associated with increasing levels of schizotypy. In addition, thinner left postcentral, superior parietal and lingual gyri, as well as thicker left caudal middle frontal gyrus and smaller left thalamus and right caudate were associated with increasing levels of childhood trauma exposure. These results suggest that alterations in brain regions critical for higher cognitive and integrative processes that are associated with schizotypy may be enhanced in individuals exposed to high levels of trauma.

Paul M. Thompson received partial grant support from Biogen, Inc., for research unrelated to this manuscript. James Gilleen has received remuneration from Takeda Pharmaceuticals in the past 3 years for consultancy work unrelated to this research.

The ENIGMA-Schizotypy working group gratefully acknowledges support from the NIH Big Data to Knowledge (BD2K) award (U54 EB020403 to Paul M. Thompson). FOR2107 Marburg: This work was funded by the German Research Foundation (DFG grant FOR2107, KI588/14-1 and FOR2107, KI588/14-2 to Tilo Kircher). Igor Nenadić was supported by Deutsche Forschungsgemeinschaft (DFG), grants NE2254/2-1, NE2254/3-1, NDE2254/4-1. FOR2107 Muenster: This work was funded by the German Research Foundation (DFG, grant FOR2107 DA1151/5-1 and DA1151/5-2 to Udo Dannlowski; SFB-TRR58, Projects C09 and Z02 to Udo Dannlowski) and the Interdisciplinary Centre for Clinical Research (IZKF) of the medical faculty of Muenster (grant Dan3/012/17 to Udo Dannlowski). Tim Hahn was funded by the German Research Foundation (DFG grants HA7070/2-2, HA7070/3, HA7070/4). IGP: The Imaging Genetics in Psychosis (IGP) study was funded by Project Grants from the Australian National Health and Medical Research council (NHMRC; #630471 and #1081603), and the Macquarie University Australian Research Council Centre of Excellence in Cognition and its Disorders (CE110001021) awarded to Melissa J. Green. Emiliana Tonini was supported by the Australian Government Research Training Program (RTP) Scholarship (administered by the University of New South Wales), and a supplementary scholarship administered by Neuroscience Research Australia (NeuRA). Zurich: This study was financially supported by the Donald C. Cooper-Fonds. Paris: This study was supported by the French ANR Agence Nationale pour la Recherche (ANR MNP VIP and Labex BioPsy). London: This work was supported by a Brain and Behavior Research Foundation NARSAD Young Investigator Grant (#21200, Lieber Investigator) and a Sir Henry Dale Fellowship jointly funded by the Wellcome Trust and the Royal Society (#202397/Z/16/Z), both awarded to Gemma Modinos. Roehampton: This work was supported by a British Academy grant awarded to Dr James Gilleen (#SG150457).

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