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

Persistent distressing psychotic-like experiences (PLE) among children may be driven by genetics and neighborhood environmental exposures. However, the gene-environment interaction to persistent distressing PLE is unknown. The study included 6,449 participants from the Adolescent Brain and Cognitive Development Study. Genetic risk was measured by a multi-ancestry schizophrenia polygenic risk score (SCZ-PRS). Multi-dimensional neighborhood-level exposures were used to form a neighborhood exposome (NE) score. 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). The association between NE score and persistent distressing PLE was statistically significantly attenuated as SCZ-PRS increased (OR for interaction = 0.92, 95% CI: 0.86, 1.00, P = 0.039). The findings indicate that persistent distressing PLE may be driven by detrimental neighborhood exposures, particularly among children with low genetic risks.