Association of Obsessive-Compulsive Disorder and Obsessive-Compulsive Symptoms With Substance Misuse in 2 Longitudinal Cohorts in Sweden.

Importance: Neurobiological models have postulated shared neural mechanisms between obsessive-compulsive disorder (OCD) and substance use disorders, but results from clinical and epidemiological studies are conflicting or even suggest that OCD may be protective against substance misuse. Objective: To investigate whether OCD and obsessive-compulsive symptoms are associated with substance misuse and the extent to which shared genetic and/or environmental factors account for this association. Design, Setting, and Participants: In this cohort study, individuals in the general population of Sweden born between January 1, 1932, and December 31, 1997 (population cohort), were followed up through Swedish nationwide registers from January 1, 1997, to December 31, 2013. The second cohort included twin participants in the Child and Adolescent Twin Study in Sweden (CATSS) followed up from ages 18 to 24 years. Data were analyzed from March 1, 2021, to March 31, 2022. Exposures: Lifetime International Statistical Classification of Diseases and Related Health Problems, Tenth Revision, diagnosis of OCD in the National Patient Register (population cohort 1), and self-reported obsessive-compulsive symptoms at 18 years of age (CATSS cohort). Main Outcomes and Measures: Substance misuse was defined as registered substance use-related disorder, criminal conviction, or death (population cohort), and self-reported alcohol and drug dependence symptoms at 18 and 24 years of age (CATSS cohort). Results: The general population cohort included 6 304 188 individuals (48.9% women and 51.1% men; median baseline age, 30.5 [IQR, 15.0-46.4] years), of whom 27 342 had an OCD diagnosis. Obsessive-compulsive disorder was associated with an elevated risk of substance misuse (hazard ratio, 3.68 [95% CI, 3.52-3.85]). In the 9230 individuals in the CATSS cohort (5551 women [60.1%] and 3679 men [39.9%]), obsessive-compulsive symptoms at 18 years of age were associated with increased symptoms of alcohol dependence (concurrent [n = 9219], β = 0.18 [95% CI, 0.16-0.20]; longitudinal [n = 3381], β = 0.10 [95% CI, 0.06-0.14]) and drug dependence (concurrent [n = 749], β = 0.19 [95% CI, 0.11-0.27]; longitudinal [n = 452], β = 0.15 [95% CI, 0.04-0.25]). Comorbid anxiety and depression did not entirely explain the associations in either cohort. Using data from full siblings and maternal half-siblings (population cohort) and monozygotic and dizygotic twins (CATSS cohort) provided estimates of the relative contribution of genetic and environmental influences to the covariance between OCD and obsessive-compulsive symptoms and substance misuse or dependence. The associations were explained by genetic (56%-68%) and nonshared environmental (32%-44%) factors. Conclusions and Relevance: The findings of this Swedish population-based cohort study challenge the notion that OCD is protective against developing substance misuse. The association of OCD and obsessive-compulsive symptoms with substance misuse was largely explained by shared genetics but was also compatible with partial environmental mediation.