Population-level preventive interventions are urgently needed and may be effective for psychosis due to social determinants. We tested three syndemic models along pathways from childhood adversity (CA) to psychotic spectrum disorder (PSD) and their implications for prevention.

Cross-sectional data from 7461 British men surveyed in 5 population subgroups. We tested interactions on both additive and multiplicative scales for a syndemic of violence/criminality (VC), sexual behavior (SH), and substance misuse (SM) according to the presence of CA and adult traumatic life events; mediation analysis of path models; and partial least squares path modeling, with PSD as outcome.

Multiplicative synergistic interactions were found between VC, SH, and SM among men, who experienced CA and traumatic adult life events. However, when disaggregated, only SM mediated the pathway from CA to PSD. Path modeling showed traumatic life events acted on PSD through the syndemic and had no direct effect on PSD. Higher syndemic scores and living in areas of deprivation characterized men with PSD and CA.

Our findings support a broad division of PSD into cases due to (i) biological/inherent causes, and (ii) social determinants, the latter including a syndemic pathway determined by CA. Preventive strategies should focus primarily on preventing adverse effects of CA on developmental pathways which result in PSD. Single component prevention strategies may prevent triggering effects of SM on PSD during adolescence/early adulthood among vulnerable individuals due to CA. Future research should determine applicability and transferability of interventions based on these findings to different populations, specifically those experiencing syndemics.