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.
Highlights
Schizophrenia (SZ) and related psychotic disorders are increasingly recognized as clinical manifestations of quantitative characteristics that are continuously distributed in the general population
We found a positive association between the schizotypy-related cortical thickness (CT) pattern and the pattern of CT abnormalities observed in SZ, but not with that of bipolar disorder (BD) or MDD, supporting the notion of neurobiological continuity across the extended psychosis phenotype
Different anatomical trajectories have been reported in schizotypy [35], between different at-risk states [83] and in clinical-high risk (CHR) individuals who subsequently of prefrontal cortical thinning commonly observed in medicated patients with SZ [28, 47] and first-episode psychosis [27, 43]
Summary
Schizophrenia (SZ) and related psychotic disorders are increasingly recognized as clinical manifestations of quantitative characteristics that are continuously distributed in the general population. Our second aim was to examine the shared morphometric characteristics of schizotypy with previously reported structural abnormalities in SZ, bipolar disorder (BD) and major depression To this end, we correlated subcortical and cortical effect size maps derived from the present meta-analysis with recently published effect size maps from the ENIGMA left and right DK atlas regions with total schizotypy scores including age, sex, and global mean CT (or total SA) as covariates (continuous model 1) and secondarily excluding global mean CT (or total SA) (continuous model 2, Tables S7 and S8). Similar to the cortical analyses, continuous models mOFC/vmPFC thickness and higher schizotypy remained significant were applied to examine the relationship between schizotypy scores and subcortical volume for each ROI in each sample To this end, partial correlation analysis was used to test correlations between the left and right subcortical volumes with total schizotypy scores.
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