Childhood Adversity Determines the Syndemic Effects of Violence, Substance Misuse, and Sexual Behavior on Psychotic Spectrum Disorder Among Men

Background and hypothesis: Childhood adversity (CA) increases the risk for several adult psychiatric conditions. It is unclear why some exposed individuals experience psychotic symptoms and others do not. We investigated whether a syndemic explained a psychotic outcome determined by CA.Study design: We used self-reported cross-sectional data from 7461 British men surveyed in different population subgroups. Latent class analysis (LCA) identified categorical psychopathological outcomes. LCs were tested by interaction analysis between syndemic factors derived from confirmatory factor analysis according to CA experiences. Pathway analysis using partial least squares path modeling.Results: A 4-class model with excellent fit identified an LC characterized by both psychotic and anxiety symptoms (class 4). A syndemic model of joint effects, adducing a 3-component latent variable of substance misuse (SM), high-risk sexual behavior (SH), violence and criminality (VC) showed synergy between components and explained the psychotic outcome (class 4). We found significant interactions between factor scores on the multiplicative scale, specific only to class 4 (psychosis), including SM x SH, SH x VC, and SM x VC (OR > 1, P < .05); and on the additive scale SM x SH (relative excess risk due to interaction >0, P < .05), but only for men who experienced CA.Conclusion: Multiplicative synergistic interactions between SM, SH, and VC constituted a mechanism determining a psychotic outcome, but not for anxiety disorder, mixed anxiety disorder/depression, or depressive disorder. This was specific to men who had experienced CA along direct and syndemic pathways. Population interventions should target SM and VC in adulthood but prioritize primary prevention strategies for CA.