Causal Discovery Analysis Reveals Insights into Psychosis Proneness, Brain Function, and Environmental Factors among...

Experiencing mild symptoms of psychosis, like delusions and hallucinations, occurs sometimes in general, nonclinical populations, often termed psychosis proneness (PP), potentially part of the psychosis continuum. Understanding the neural and environmental factors contributing to PP in young individuals during critical developmental periods remains unclear. We aimed to explore these directional relationships using causal discovery analysis (CDA). Participants were 194 healthy adolescent and young adult twin and sibling pairs aged between 14-24 years. They completed comprehensive assessments evaluating sociodemographic status, environmental risk, general intelligence, self-schema, psychosis proneness score (PPS), and working memory (WM) performance during fMRI (37 variables). CDA, a novel machine learning algorithm, was applied to understand the causal relationships of PPS. The analysis identified negative self-schema as having the largest potential causal effect among all assessments in PPS. Secondly, experiencing low levels of social cohesion and trust had a potential causal effect on PPS. Although our analysis could not exclude the possibility that other unmeasured factors may confound these relationships, the effect sizes (ES) were substantial, negative self-schema & PPS (ES= 0.54) and social cohesion and trust & PPS (ES= -0.18). PPS, on the other hand, was identified as a direct cause of greater activation in DLPFC (ES= 0.12). CDA provided simultaneous directionality for 37 variables collected on the same individuals. The findings highlight the significance of negative self-schema and social cohesion and trust in the general population with PP, emphasizing the potential for preventive interventions targeting these factors. These findings also suggest a role for DLPFC as a potential target in this regard. This study represents the first data-driven analysis to model causal mechanisms in PP in the general population.