Virtanen, SuviKuja-Halkola, RalfMataix-Cols, DavidJayaram-Lindström, NityaD'Onofrio, Brian M.Larsson, HenrikRuck, ChristianSuvisaari, JaanaLichtenstein, PaulLatvala, Antti2020-11-112020-11-112020-07Virtanen, S, Kuja-Halkola, R, Mataix-Cols, D, Jayaram-Lindström, N, D'Onofrio, B M, Larsson, H, Ruck, C, Suvisaari, J, Lichtenstein, P & Latvala, A 2020, 'Comorbidity of substance misuse with anxiety-related and depressive disorders : a genetically informative population study of 3 million individuals in Sweden', Psychological Medicine, vol. 50, no. 10, 0033291719001788, pp. 1706-1715. https://doi.org/10.1017/S0033291719001788ORCID: /0000-0002-2779-3384/work/89117818http://hdl.handle.net/10138/321278Background Causes of the comorbidity of substance misuse with anxiety-related and depressive disorders (anxiety/depression) remain poorly known. We estimated associations of substance misuse and anxiety/depression in the general population and tested them while accounting for genetic and shared environmental factors. Methods We studied individuals born in Sweden 1968–1997 (n = 2 996 398) with follow-up in nationwide register data for 1997–2013. To account for familial effects, stratified analyses were conducted within siblings and twin pairs. Substance misuse was defined as ICD-10 alcohol or drug use disorder or an alcohol/drug-related criminal conviction. Three dimensions of ICD-10 anxiety and depressive disorders and a substance misuse dimension were identified through exploratory factor analysis. Results Substance misuse was associated with a 4.5-fold (95% CI 4.50–4.58) elevated risk of lifetime generalized anxiety/depression, 4.7-fold (95% CI 4.63–4.82) elevated risk of panic disorder and agora/social phobia, and 2.9-fold elevated risk of phobias/OCD (95% CI 2.82–3.02) as compared to those without substance misuse. The associations were attenuated in within-family analyses but we found elevated risks in monozygotic twin pairs discordant for substance misuse as well as significant non-shared environmental correlations. The association between anxiety/depression and substance misuse was mainly driven by generalized anxiety/depression, whereas other anxiety/depression dimensions had minor or no independent associations with substance misuse. Conclusions Substance misuse and anxiety/depression are associated at the population level, and these associations are partially explained by familial liabilities. Our findings indicate a common genetic etiology but are also compatible with a potential partially causal relationship between substance misuse and anxiety/depression.10engcc_by_nc_ndinfo:eu-repo/semantics/openAccessNeurology and psychiatryPsychologyAlcoholanxietycohortdepressiondrugfamily studygeneticsubstance usetwinsALCOHOL-USE DISORDERSDRUG-USE DISORDERSPOSTTRAUMATIC-STRESS-DISORDERNATIONAL EPIDEMIOLOGIC SURVEYENVIRONMENTAL RISK-FACTORSDSM-IV MOODPSYCHIATRIC-DISORDERSMENTAL-HEALTHPREVALENCELIFETIMEArticleopenAccessf23342cb-1705-4d29-bdda-62545ffcb54f000559400500013