The Impact of the Parental Patterns of Morbidity and Comorbidity in the Cross‐Generational Transmission of Risk for Major Depression and Alcohol Use Disorder

To further understand the inter-relationship of the familial transmission of major depression (MD) and alcohol use disorder (AUD), we examine, via a multivariable Cox proportional hazards model, risks for AUD and MD in 1,244,516 individuals born in Sweden from 1970 to 1990 to intact mother-father pairs as a function of parental diagnoses of MD and/or AUD. Across the nine possible mating types, we see both direct transmission (MD → MD, AUD → AUD) and also, less strongly, indirect transmission: MD → AUD and AUD → MD. Risks in offspring accumulate with multiple affected parents, which reveals the impact of interactive effects in risk prediction. Interestingly, the risk for comorbid AUD/MD in offspring is higher when one parent has MD and the other AUD rather than when one parent has both disorders. Modest sex effects are seen, with maternal-offspring transmission sometimes significantly stronger than paternal-offspring transmission. In most comparisons, parental-offspring transmission was modestly stronger for same-sex versus opposite-sex parent-offspring pairs. These results suggest that MD/AUD comorbidity in Sweden is due, at least in part, to correlated familial liability transmitted by direct and indirect paths across generations. We could reject the hypothesis that an AUD/MD syndrome was specifically transmitted from parents to offspring.