Cortical and Subcortical Neuroanatomical Signatures of Schizotypy in 3,004 Individuals Assessed in a Worldwide ENIGMA Study

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 3,004 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=.07, pFDR=.02). The cortical thickness profile in schizotypy was positively correlated with cortical abnormalities in SZ (r=.33, pspin=.01), but not BD (r=.19, pspin=.16) or MDD (r=-.22, pspin=.10). The schizotypy-related subcortical volume pattern was negatively correlated with subcortical abnormalities in SZ (rho=-.65, pspin=.01), BD (rho=-.63, pspin=.01), and MDD (rho=-.69, pspin=.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.

Mapping neurotransmitter systems to the structural and functional organization of the human neocortex

“…Patterns of cortical abnormality were collected for 13 neurological, neurodevelopmental and psychiatric disorders from the ENIGMA consortium and the Enigma toolbox (https://github.com/MICA-MNI/ENIGMA; ref. 118 ), including: 22q11.2 deletion syndrome (22q) 119 , ADHD 120 , ASD 121 , idiopathic generalized epilepsy 122 , right temporal lobe epilepsy 122 , left temporal lobe epilepsy 122 , depression 123 , OCD 124 , schizophrenia 125 , BD 126 , obesity 127 , schizotypy 128 and PD 129 . Although most disorders show decreases in cortical thickness, some (for example, 22q, ASD and schizotypy) also show regional increases in cortical thickness.…”

Schizophrenia polygenic risk during typical development reflects multiscale cortical organization

“…The neurodevelopmental hypothesis of schizophrenia posits that cortical maturation is perturbed, producing widespread cortical abnormalities (van Erp et al, 2018). Differences in cortical morphometry are consistently reported across different stages and clinical phenotypes of the schizophrenia spectrum (Wannan et al, 2019;Kirschner et al, 2020Kirschner et al, , 2021; ENIGMA Clinical High Risk for Psychosis Working Group et al, 2021). Investigating neurodevelopmental features of schizophrenia requires a departure from classic case-control designs, however.…”

The Enhancing NeuroImaging Genetics through Meta‐Analysis Consortium: 10 Years of Global Collaborations in Human Brain Mapping

“…A related paper by Gurholt et al (2020) examines intracranial and subcortical volumes in adolescents with early-onset psychosis-a severe and often progressive form of the disorder. Recently, ENIGMA working groups have been created to study various conditions on the schizophrenia spectrum-including the first large-scale international studies of schizotypy (Kirschner et al, 2021). These analyses will lend insight into the schizophrenia prodrome and factors that confer resilience to psychosis in unaffected relatives and in the general population.…”