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.

Keywords: Prodromal questionnaire; Psychological distress; Psychosis risk; Psychotic-like experiences.

Fig. 1

Distribution of psychotic-like experiences (PLE) captured by the German version of the Prodromal Questionnaire 16 (PQ-16) in 104 nonclinical subjects. Most PLE were assigned to three categories reflecting positive (Delusional, Perceptual) and Negative PLE based on a comparison to the Structured Interview for Prodromal Syndromes (SIPS). Note: Item descriptions are abbreviated for display purposes. This figure was created using ggplot2 [94]

Fig. 2

Upper panel shows statistical significance (thresholded at FDR-corrected p < 0.05) and effect size (thresholded at uncorrected peak-level p < 0.001) maps for structural correlates of total psychotic-like experiences (PLE), assessed by the Prodromal Questionnaire (PQ-16). Mean volumes of interest (VOI) were extracted from two prefrontal regions: right superior (rSFG) and middle frontal gyri (rMFG), which enclose the largest cluster of size k = 246. Lower panel shows the effect of distress and PLE interaction on predicted rSFG volume. At higher Perceptual PLE distress severity (scale score ≥ 2.75), overall PLE are associated with predicted rSFG volume reductions. This figure was created using MRIcroGL (https://www.mccauslandcenter.sc.edu/mricrogl/), ggplot2 [94], 3D Slicer (https://www.slicer.org) [95] and GNU Image Manipulation Program (GIMP, https://www.gimp.org/)