Cortical and subcortical neuroanatomical signatures of schizotypy in 3004 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 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.

Local molecular and global connectomic contributions to cross-disorder cortical abnormalities

“…We collected thirteen spatial maps of cortical abnormalities from the ENIGMA consortium for the following diseases, disorders, and conditions: 22q11.2 deletion syndrome 26 , attention-deficit/hyperactivity disorder (ADHD) 27 , autism spectrum disorder (ASD) 28 , idiopathic generalised epilepsy 29 , right temporal lobe epilepsy 29 , left temporal lobe epilepsy 29 , depression 30 , obsessive-compulsive disorder (OCD) 31 , schizophrenia 32 , bipolar disorder 33 , obesity 34 , schizotypy 35 , and Parkinson's disease 36 . For simplicity, we refer to diseases, disorders, and conditions as "disorders" throughout the text.…”

“…Furthermore, we find a similar trend of increased connectomic influence for severity of psychotic symptoms: namely, schizotypy and schizophrenia. Although schizotypy is not an earlier stage of schizophrenia (indeed, schizotypy is not a disorder per se but rather a multidimensional continuum of traits related to psychosis), individuals with schizotypy exhibit similar, albeit attenuated, characteristics as schizophrenia patients 35 . We find that the connectomic influence is considerably greater in schizophrenia compared to schizotypy, which may suggest that the structural network gradually becomes more implicated in disease progression.…”

“…Patterns of cortical thickness were collected for the available thirteen neurological, neurodevelopmental, and psychiatric disorders from the ENIGMA consortium and the enigma toolbox (https://github.com/ MICA-MNI/ENIGMA 96 ), including: 22q11.2 deletion syndrome (N = 474 participants, N = 315 controls) 26 , attention-deficit/hyperactivity disorder (ADHD; N = 733 participants, N = 539 controls) 27 , autism spectrum disorder (ASD; N = 1571 participants, N = 1651 controls) 28 , idiopathic generalised (N = 367 participants), right temporal lobe (N = 339 participants), and left temporal lobe (N = 415 participants) epilepsies (N = 1727 controls) 29 , depression (N = 2148 participants, N = 7957 controls) 30 , obsessive-compulsive disorder (OCD; N = 1905 participants, N = 1760 controls) 31 , schizophrenia (N = 4474 participants, N = 5098 controls) 32 , bipolar disorder (N = 1837 participants, N = 2582 controls) 33 , obesity (N = 1223 participants, N = 2917 controls) 34 , schizotypy (N = 3004 participants) 35 , and Parkinson's disease (N = 2367 participants, N = 1183 controls) 36 . The ENIGMA (Enhancing Neuroimaging Genetics through Meta-Analysis) Consortium is a data-sharing initiative that relies on standardised processing and analysis pipelines, such that disorder maps are comparable 25 .…”

Childhood trauma moderates schizotypy-related brain morphology: Analyses of 1,182 healthy individuals from the ENIGMA Schizotypy working group

“…12 A recent meta-analysis from the Enhancing NeuroImaging Genetics through Meta-Analysis (ENIGMA) Schizotypy working group has identified that higher schizotypy scores, assessed using different questionnaires, were associated with thicker right medial orbitofrontal/ventromedial prefrontal cortex. 15 In studies which used only the Schizotypal Personality Questionnaire (SPQ), 11, 16 increasing schizotypy levels have been inconsistently associated with smaller thalamus 17 and larger striatum (pallidum/putamen), 18 as well as thinner pars orbitalis , rostral middle frontal and parahippocampal gyri 19 and thicker right dorsolateral prefrontal cortex and dorsal premotor cortex/frontal eye fields. 17…”

“…12 A recent meta-analysis from the Enhancing NeuroImaging Genetics through Meta-Analysis (ENIGMA) Schizotypy working group has identified that higher schizotypy scores, assessed using different questionnaires, were associated with thicker right medial orbitofrontal/ventromedial prefrontal cortex. 15 In studies which used only the Schizotypal Personality Questionnaire (SPQ), 11,16 increasing schizotypy levels . CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.…”