Neuroanatomical Correlates of Psychotic-Like Experiences Assessed in 2,695 Individuals via the ENIGMA Consortium

Abstract

Background: Recent meta-analytical evidence indicates that cortical thickness abnormalities in schizophrenia are influenced by illness severity and antipsychotic medication exposure. Schizotypy research allows investigating the neuroanatomical correlates of psychotic-like experiences without illness- and treatment-related confounders. Here we present the first large-scale meta-analysis of cortical thickness in schizotypy across 23 datasets worldwide. Methods: The study involved structural MRI scans from 2,695 healthy individuals (mean [range] age, 29.1 [17-55.8], 46.3% male) who also completed self-report schizotypy questionnaires. Each site used FreeSurfer to extract cortical thickness for 70 Desikan-Killiany atlas regions (34 regions per hemisphere + left and right hemisphere mean thickness), and performed partial correlation analyses with total schizotypy scores in R to predict left, right and mean cortical thickness by region, adjusting by sex and age. Random-effects meta-analyses of partial correlation effect sizes for each region were performed using R’s metafor package. Results: Schizotypy scores were positively associated with mean cortical thickness of the medial orbitofrontal cortex (r=0.077; pFDR=0.006) and the frontal pole (r=0.073; pFDR=0.006). By hemisphere, schizotypy was associated with cortical thickness of the left medial orbitofrontal cortex (r=0.066; pFDR=0.044), and at trend-level with the right medial orbitofrontal cortex and left frontal pole (both r=0.062; pFDR=0.053). Conclusions: Worldwide cooperative analyses of neuroimaging data shows that subclinical psychotic-like experiences are associated with greater prefrontal cortical thickness. The directionality of the effects is opposite to that of thinner cortex in schizophrenia. Given that accelerated prefrontal thinning has been associated with progression to psychosis in at-risk individuals, our findings may reflect mechanisms of resilience in schizotypy.