Interaction between Neighborhood Exposome and Genetic Risk in Child Persistent Distressing Psychotic-like Experiences

The genetic risk of persistent distressing psychotic-like experiences (PLE) in the multi-ancestral population is under-investigated. The gene-neighborhood environment interaction in persistent distressing PLE is also unknown. This study included 6,449 participants from the Adolescent Brain and Cognitive Development Study. Genetic risk was measured by a multi-ancestral schizophrenia polygenic risk score (SCZ-PRS). Multi-dimensional neighborhood-level exposures were used to form the neighborhood exposome (NE). SCZ-PRS was not statistically significantly associated with odds of persistent distressing PLE (OR = 1.04, 95% CI: 0.97, 1.13, P = 0.280), whereas NE score was (OR = 1.15, 95% CI: 1.05, 1.26, P = 0.003). A significant negative multiplicative interaction between SCZ-PRS and NE was found (Estimate = -0.08, 95% CI: -0.15, -0.00, P = 0.039). The additive interaction followed the same direction but was statistically insignificant (Estimate = -0.06, 95% CI: -0.15, 0.03, P = 0.189). Persistent distressing PLE in children may be driven by detrimental neighborhood exposures in multi-ancestral populations, particularly among those with low genetic risk. The findings provide important evidence on persistent distressing PLE etiology attributed to genetic and environmental risks and identify potential susceptible populations for targeted interventions.