The mirror-gazing task (MGT) experimentally induces illusions, ranging from simple color changes in the specular image of oneself, to depersonalization-like anomalous self-experiences (ASE) as in experiencing one's specular image as someone else. The objective was to characterize how connectivity in resting-state networks (RSNs) differed in adolescents reporting such depersonalization-like ASEs during the MGT, in a cross-sectional (Y1) and in a longitudinal manner (a year after). 75 adolescents were recruited; for the cross-sectional analysis, participants were split into 2 groups: those who reported depersonalization-like ASEs on the MGT (ASE), and those who did not (NoASE). For the longitudinal analysis, participants were split into 3 groups whether they experienced MGT depersonalization-like ASEs: only at Y1 (Remitters), both times (Persisters), or never (Controls). Participants also filled out self-reports assessing schizotypal personality (Schizotypal Personality Questionnaire [SPQ]), and underwent resting-state functional MRI procedure (rs-fMRI). A group level Independent Component Analysis (ICA) was conducted and voxel-wise inter-group differences within RSNs were examined. The rs-fMRI analysis revealed lower connectivity of specific visual areas within the primary visual network (PVN), and higher connectivity of regions within the Default Mode Network (DMN) when contrasting the ASE and NoASE groups. The areas that were atypically connected within the PVN further presented differential pattern of connectivity in the longitudinal analysis. Atypical connectivity of visual area within the DMN at Y1 was associated with higher scores on the disorganized dimension of schizotypy at the second evaluation. The present study uncovers a subtle signature in the RSNs of non-clinical adolescents who experienced task-induced ASEs.

Investigating potential gray matter differences in adolescents presenting higher levels of schizotypy personality traits could bring further insights into the development of schizophrenia spectrum disorders. Research has yet to examine the morphological correlates of schizotypy features during adolescence prospectively, and no information is available on the developmental trajectories from adolescence to adulthood. We employed mixed model regression analysis to investigate developmental trajectories of cortical thickness (CT) in relation to schizotypy dimensions in a cohort of 109 adolescents from the general population for whom MRI-scans were acquired over a 5-year period, culminating in a total of 271 scans. Structural data were processed with FreeSurfer software, statistical analyses were conducted using mixed regression models following a ROI-based approach, and schizotypy was assessed with the Schizotypal Personality Questionnaire (SPQ). Accelerated thinning was observed in the posterior cingulate cortex in relation to high levels of positive schizotypy, whereas high levels of disorganized schizotypy were associated with a similar trajectory pattern in the anterior cingulate cortex. The developmental course of CT in the prefrontal, occipital, and cingulate cortices differed between adolescents expressing higher vs lower levels of negative schizotypy. Participants reporting high scores on all schizotypy dimensions were associated with differential trajectories of CT in posterior cingulate cortex and occipital cortex. Consistently with prospective developmental studies of clinical risk conversion, the negative schizotypy dimension appears to constitute the most informative dimension for psychosis-related psychopathology, as its cerebral correlates in adolescents most closely overlap with results found in clinical high risk for psychosis studies.

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.

Morphological abnormalities of subcortical structures have been consistently reported along the schizophrenia clinical spectrum, and they may play an important role in the pathophysiology of psychosis. However, the question arises whether these subcortical features are consequences of medication and illness chronicity, or if they contribute to the vulnerability to develop schizophrenia spectrum disorders. If some of the subcortical abnormalities could be evidenced in community adolescents expressing higher schizotypal traits (psychometric schizotypy), they could potentially shed light on vulnerability markers. To date, very few studies have examined the link between psychometric schizotypy and volumes of subcortical regions, and none of them have used a longitudinal design. This study sets out to investigate developmental trajectories of subcortical volumes in 110 community adolescents (12 to 20 years old), for whom MRI-scans were acquired over a period of 5 years, reaching a total of 297 scans. Analyses were conducted using Freesurfer, and schizotypal traits were measured with the Schizotypal Personality Questionnaire (SPQ). Using mixed model regression analyses following a region-of-interest approach, we observed differential linear developmental trajectories in four subcortical structures when comparing higher versus lower scorers on the disorganized schizotypy dimension (bilateral hippocampus, left-lateral ventricle and left-pallidum) and the negative schizotypy dimension (bilateral pallidum, and right-thalamus). All results survived a threshold of p<.05 (FDR-corrected) while covarying for the effect of other psychological problems (externalized and internalized psychopathology). These results indicate that expression of higher levels of negative and disorganized schizotypy during adolescence was associated with neural markers linking schizotypy personality features to schizophrenia spectrum disorders.