The role of loneliness and social isolation in mediating the relationship between childhood maltreatment and schizophrenia: A genetically informed approach.

Observational studies have found loneliness and social isolation to mediate the relationship between childhood maltreatment and schizophrenia. Limitations with observational studies (e.g., confounding and reverse causation), however, have meant the robustness of these relationships has thus far not been explored. To address this gap, the current study utilized genomic structural equation modeling (genomic SEM) and Mendelian randomization (MR) to perform a genetic mediation analysis between childhood maltreatment, loneliness/isolation, and schizophrenia, using summary statistics from three genome-wide association studies (sample sizes 105,318-487,647). While we observed a putative effect of both childhood maltreatment (inverse variance weighted