Distress severity in perceptual anomalies moderates the relationship between prefrontal brain structure and psychosis proneness in nonclinical individuals

Abstract

In the general population, psychosis risk phenotypes occur independently of attenuated prodromal syndromes. Neurobiological correlates of vulnerability could help to understand their meaningfulness. Interactions between the occurrence of psychotic-like experiences (PLE) and other psychological factors e.g., distress related to PLE, may distinguish psychosis-prone individuals from those without risk of future psychotic disorder. We aimed to investigate whether (a) correlates of total PLE and distress, and (b) symptom dimension-specific moderation effects exist at the brain structural level in non-help-seeking adults reporting PLE below and above the screening criterion for clinical high-risk (CHR). We obtained T1-weighted whole-brain MRI scans from 104 healthy adults from the community without psychosis CHR states for voxel-based morphometry (VBM). Brain structural associations with PLE and PLE distress were analysed with multiple linear regression models. Moderation of PLE by distress severity of two types of positive symptoms from the Prodromal Questionnaire (PQ-16) screening inventory was explored in regions-of-interest after VBM. Total PQ-16 score was positively associated with grey matter volume (GMV) in prefrontal regions, occipital fusiform and lingual gyri (p < 0.05, FDR peak-level corrected). Overall distress severity and GMV were not associated. Examination of distress severity on the positive symptom dimensions as moderators showed reduced strength of the association between PLE and rSFG volume with increased distress severity for perceptual PLE. In this study, brain structural variation was related to PLE level, but not distress severity, suggesting specificity. In healthy individuals, positive relationships between PLE and prefrontal volumes may indicate protective features, which supports the insufficiency of PLE for the prediction of CHR. Additional indicators of vulnerability, such as distress associated with perceptual PLE, change the positive brain structure relationship. Brain structural findings may strengthen clinical objectives through disentanglement of innocuous and risk-related PLE.

Thoughts falling apart: disorganized schizotypy specifically predicts both psychotic- and stress-reactivity in daily life

“…We first established that greater-than-usual exposure to social, economic and health stressors predicted more intense PLEs within individuals. This is in line with previous studies (Evermann et al, 2021;Klippel et al, 2022;Taylor et al, 2019;Wilson et al, 2020) showing that distress is positively associated with psychosis-vulnerability. The association further underlies the role of the hypothalamic-pituitary-adrenal (HPA) axis in triggering and exacerbating psychotic symptoms in response to distress (for review see (Pruessner et al, 2017)): the HPA is responsible for the production and regulation of cortisol, and beyond elevated overall cortisol levels, cortisol reactivity was also increased in individuals with high genetic risk in response to unpleasant events compared to healthy controls (Collip et al, 2011).…”

Building up resilience in an uncertain world: mental health challenges in the aftermath of the first modern pandemic

“…On the contrary, lower premorbid cognitive functioning together with higher levels of emotion-focused coping were associated with increased perceived stress in controls [ 6 ]. Along these lines, the study by Evermann et al [ 7 ] in this issue shows that distress severity moderates the relationship between the presence of psychotic-like experiences and brain volumes in non-help-seeking individuals from the community. Furthermore, this study highlights the role of perceived stress in the interaction between psychotic-like experiences and prefrontal brain abnormalities that may lead to the development of psychotic disorders.…”