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Comorbidity of substance misuse with anxiety-related and depressive disorders: a genetically informative population study of 3 million individuals in Sweden

Published online by Cambridge University Press:  22 July 2019

Suvi Virtanen Open the ORCID record for Suvi Virtanen [Opens in a new window] ,
Ralf Kuja-Halkola ,
David Mataix-Cols ,
Nitya Jayaram-Lindström ,
Brian M. D'Onofrio ,
Henrik Larsson ,
Christian Rück ,
Jaana Suvisaari ,
Paul Lichtenstein  and
Antti Latvala
Suvi Virtanen*
Affiliation:
Institute for Molecular Medicine Finland, University of Helsinki, Helsinki, Finland Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden
Ralf Kuja-Halkola
Affiliation:
Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden
David Mataix-Cols
Affiliation:
Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden Centre for Psychiatry Research, Stockholm Health Care Services, Stockholm County Council, Stockholm, Sweden
Nitya Jayaram-Lindström
Affiliation:
Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden Centre for Psychiatry Research, Stockholm Health Care Services, Stockholm County Council, Stockholm, Sweden
Brian M. D'Onofrio
Affiliation:
Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden Department of Psychological and Brain Sciences, Indiana University, Bloomington, IN, USA
Henrik Larsson
Affiliation:
Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden School of Medical Sciences, Örebro University, Örebro, Sweden
Christian Rück
Affiliation:
Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden Centre for Psychiatry Research, Stockholm Health Care Services, Stockholm County Council, Stockholm, Sweden
Jaana Suvisaari
Affiliation:
National Institute for Health and Welfare, Helsinki, Finland
Paul Lichtenstein
Affiliation:
Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden
Antti Latvala
Affiliation:
Institute for Molecular Medicine Finland, University of Helsinki, Helsinki, Finland Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden
*
Author for correspondence: Suvi Virtanen, E-mail: [email protected]
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Abstract

Background

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.

Keywords

Alcoholanxietycohortdepressiondrugfamily studygeneticsubstance usetwins
Type
Original Articles
Information
Psychological Medicine , Volume 50 , Issue 10 , July 2020 , pp. 1706 - 1715
Copyright
Copyright © Cambridge University Press 2019

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