Childhood trauma moderates schizotypy-related brain morphology: analyses of 1182 healthy individuals from the ENIGMA schizotypy working group.

BACKGROUND: Schizotypy represents an index of psychosis-proneness in the general population, often associated with childhood trauma exposure. Both schizotypy and childhood trauma are linked to structural brain alterations, and it is possible that trauma exposure moderates the extent of brain morphological differences associated with schizotypy. METHODS: We addressed this question using data from a total of 1182 healthy adults (age range: 18-65 years old, 647 females/535 males), pooled from nine sites worldwide, contributing to the Enhancing NeuroImaging Genetics through Meta-Analysis (ENIGMA) Schizotypy working group. All participants completed both the Schizotypal Personality Questionnaire Brief version (SPQ-B), and the Childhood Trauma Questionnaire (CTQ), and underwent a 3D T1-weighted brain MRI scan from which regional indices of subcortical gray matter volume and cortical thickness were determined. RESULTS: A series of multiple linear regressions revealed that differences in cortical thickness in four regions-of-interest were significantly associated with interactions between schizotypy and trauma; subsequent moderation analyses indicated that increasing levels of schizotypy were associated with thicker left caudal anterior cingulate gyrus, right middle temporal gyrus and insula, and thinner left caudal middle frontal gyrus, in people exposed to higher (but not low or average) levels of childhood trauma. This was found in the context of morphological changes directly associated with increasing levels of schizotypy or increasing levels of childhood trauma exposure. CONCLUSIONS: These results suggest that alterations in brain regions critical for higher cognitive and integrative processes that are associated with schizotypy may be enhanced in individuals exposed to high levels of trauma.

Cumulative sociodemographic disadvantage partially mediates associations between childhood trauma and schizotypy.

OBJECTIVES: Risk for psychosis in the general population is characterized by a set of multidimensional traits that are referred to as schizotypy. Higher levels of schizotypy are associated with socioeconomic disadvantage and childhood trauma, just as these risk factors are associated with schizophrenia and bipolar disorder. Here, we set out to investigate whether cumulative sociodemographic disadvantage mediates associations between childhood trauma and schizotypy in adulthood. METHODS: A sociodemographic cumulative risk (SDCR) score was derived from six risk indices spanning employment, education, income, socioeconomic status, marital, and living circumstances for 197 participants that included both healthy (n = 57) and clinical samples with schizophrenia or schizoaffective disorder (n = 65) or bipolar disorder (n = 75). A series of multiple linear regressions was used to examine the direct and indirect associations among childhood trauma (measured with the Childhood Trauma Questionnaire), the SDCR index, and levels of schizotypy (measured with the Schizotypal Personality Questionnaire). RESULTS: Schizotypy was independently associated with trauma and the SDCR index. In addition, the SDCR index partially mediated associations between trauma and schizotypy. CONCLUSIONS: These findings in a mixed sample of healthy and clinical participants represent the full spectrum of schizotypy across health and illness and suggest that effects of childhood trauma on schizotypal personality organization may operate via cumulative socioeconomic disadvantage in adulthood. PRACTITIONER POINTS: The strong associations between trauma and schizotypy suggest that systematic health screening of children exposed to early life trauma may assist to identify those at risk of developing psychosis. Clinicians should pay attention to various indicators of sociodemographic disadvantage in patients prone to psychosis, in addition to any exposure to trauma during childhood.

Polygenic risk for schizophrenia as a moderator of associations between childhood trauma and schizotypy.

Recent evidence shows that genetic and environmental risk factors for psychotic disorders are associated with higher levels of schizotypy (or psychosis proneness) in the general population. However, little is known about how these risk factors interact. We specifically examined whether genetic loading for schizophrenia moderates the association between childhood trauma severity and schizotypy. Schizotypy was measured using the Schizotypal Personality Questionnaire (SPQ), and childhood trauma severity was measured with the Childhood Trauma Questionnaire (CTQ) among a total of 168 participants (comprising 51 healthy individuals, 56 diagnosed with schizophrenia, and 61 with bipolar disorder). Polygenic risk scores (PRS) for schizophrenia were calculated for all participants and examined as a potential moderator of associations between total scores on the CTQ and schizotypy total scores and dimensions (i.e., cognitive-perceptual, interpersonal, disorganised). Multiple linear regression models revealed associations between childhood trauma and all dimensions of schizotypy, but no associations between PRS and schizotypy. A significant interaction between PRS and childhood trauma was evident for the interpersonal and disorganised dimensions of schizotypy, as well as the total score, reflecting positive associations between childhood trauma severity and these two schizotypal dimensions, only for individuals with low or average PRS for schizophrenia. This suggests that trauma may be able to increase risk for psychosis independently of any genetic vulnerability. The present findings are consistent with the idea of several risk pathways for the development of psychotic disorders.

Structural and functional neural correlates of schizotypy: A systematic review.

Schizotypy refers to a multidimensional construct that spans a range of cognitive, behavioral, and personality features, representing liability to psychosis on a continuum between health and illness. Schizotypy has been associated with functional and structural brain alterations as potential intermediate phenotypes on the developmental path to psychosis. We scanned the literature between February 2019 and August 1, 2020 using PubMed, Medline, APA PsycINFO, and ProQuest. We identified eligible articles conducted on participants assessed with psychometric schizotypy across the health-illness spectrum and reporting a direct statistic between schizotypy and a structural, task-related, or functional magnetic resonance imaging brain measure. Articles not peer-reviewed and not written in English were excluded. We systematically reviewed 84 studies that determined the changes in gray matter, brain activation, and connectivity associated with schizotypy in both healthy and clinical cohorts. Morphological and functional changes in the default and the frontoparietal networks, specifically frontal and temporal cortices, were most frequently associated with schizotypy. Yet, we were unable to identify consistent patterns of morphological or functional brain aberration associated with schizotypy, due to methodological differences between studies in the conceptualization and measurement of schizotypy. Efforts toward greater methodological concordance in future neuroimaging research of schizotypy are needed to improve the identification of brain-based endophenotypes for schizophrenia. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

Schizotypy, childhood trauma and brain morphometry.

BACKGROUND: Childhood trauma confers risk for psychosis and is associated with increased 'schizotypy' (a multi-dimensional construct reflecting risk for psychosis in the general population). Structural brain alterations are associated with both childhood trauma and schizotypy, but the potential role of trauma exposure in moderating associations between schizotypy and brain morphology has yet to be determined. METHODS: Participants were 160 healthy individuals (mean age: 40.08 years, SD = 13.64, range 18-64; 52.5% female). Childhood trauma exposure was assessed using the Childhood Adversity Questionnaire, and schizotypy was assessed using the Schizotypal Personality Questionnaire. Univariate voxel-based morphometry and multivariate analyses of grey matter volume covariation (GMC; derived from independent component analysis) were performed to determine the main effects of schizotypy, trauma exposure and their interaction on these indices of grey matter volume. Moderation analyses were performed following significant interaction. RESULTS: Levels of schizotypy, in particular the Cognitive-Perceptual and Interpersonal dimensions, were negatively associated with GMC in the striatum, the hippocampus/parahippocampal gyrus, thalamus and insulae. Trauma exposure was negatively associated with GMC of the middle frontal gyrus and parietal lobule, while negatively associated with GMC in the cerebellum. Levels of schizotypy (total scores, and the cognitive-perceptual dimension) were negatively associated with striatal GMC in individuals not exposed to trauma, but not in those exposed to trauma. CONCLUSIONS: Schizotypy and childhood trauma were independently associated with changes of grey matter in brain regions critical for cognition and social cognition. In individuals not exposed to trauma, increased schizotypy was associated with decreased striatal and limbic grey matter.

Developmental Trajectories of Cortical Thickness in Relation to Schizotypy During Adolescence.

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.