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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: suvi.virtanen@helsinki.fi
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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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References

Bejerot, S and Humble, M (1999) Low prevalence of smoking among patients with obsessive-compulsive disorder. Comprehensive Psychiatry 40, 268–272.CrossRefGoogle ScholarPubMed
Blanco, C, Xu, Y, Brady, K, Pérez-Fuentes, G, Okuda, M and Wang, S (2013) Comorbidity of posttraumatic stress disorder with alcohol dependence among US adults: results from National Epidemiological Survey on Alcohol and Related Conditions. Drug and Alcohol Dependence 132, 630–638.CrossRefGoogle ScholarPubMed
Burns, L and Teesson, M (2002) Alcohol use disorders comorbid with anxiety, depression and drug use disorders: findings from the Australian National Survey of Mental Health and Well Being. Drug and Alcohol Dependence 68, 299–307.CrossRefGoogle ScholarPubMed
Conway, KP, Compton, W, Stinson, FS and Grant, BF (2006) Lifetime comorbidity of DSM-IV mood and anxiety disorders and specific drug use disorders: results from the National Epidemiologic Survey on Alcohol and Related Conditions. Journal of Clinical Psychiatry 67, 247–257.CrossRefGoogle ScholarPubMed
De Bellis, MD (2002) Developmental traumatology: a contributory mechanism for alcohol and substance use disorders. Psychoneuroendocrinology 27, 155–170.CrossRefGoogle ScholarPubMed
de Graaf, R, Bijl, RV, Smit, F, Vollebergh, WA and Spijker, J (2002) Risk factors for 12-month comorbidity of mood, anxiety, and substance use disorders: findings from the Netherlands Mental Health Survey and Incidence Study. American Journal of Psychiatry 159, 620–629.CrossRefGoogle ScholarPubMed
D'Onofrio, BM, Lahey, BB, Turkheimer, E and Lichtenstein, P (2013) Critical need for family-based, quasi-experimental designs in integrating genetic and social science research. American Journal of Public Health 103, 46–55.CrossRefGoogle ScholarPubMed
Ekbom, A (2011) The Swedish multi-generation register. Methods in Molecular Biology 675, 215–220.CrossRefGoogle ScholarPubMed
Farrell, M, Howes, S, Bebbington, P, Brugha, T, Jenkins, R, Lewis, G and Meltzer, H (2001) Nicotine, alcohol and drug dependence and psychiatric comorbidity: results of a national household survey. British Journal of Psychiatry 179, 432–437.CrossRefGoogle ScholarPubMed
Flensborg-Madsen, T, Mortensen, EL, Knop, J, Becker, U, Sher, L and Grønbæk, M (2009) Comorbidity and temporal ordering of alcohol use disorders and other psychiatric disorders: results from a Danish register-based study. Comprehensive Psychiatry 50, 307–314.CrossRefGoogle ScholarPubMed
Fröjd, S, Ranta, K, Kaltiala-Heino, R and Marttunen, M (2011) Associations of social phobia and general anxiety with alcohol and drug use in a community sample of adolescents. Alcohol and Alcoholism 46, 192–199.CrossRefGoogle Scholar
Galea, S and Tracy, M (2007) Participation rates in epidemiologic studies. Annals of Epidemiology 17, 643–653.CrossRefGoogle ScholarPubMed
Gunasekara, F, Richardson, K, Carter, K and Blakely, T (2014) Fixed effects analysis of repeated measures data. International Journal of Epidemiology 43, 264–269.CrossRefGoogle ScholarPubMed
Kasteenpohja, T, Marttunen, M, Aalto-Setälä, T, Perälä, J, Saarni, SI and Suvisaari, J (2016) Treatment adequacy of anxiety disorders among young adults in Finland. BMC Psychiatry 16, 63–76.CrossRefGoogle ScholarPubMed
Kendler, KS, Walters, EE, Neale, MC, Kessler, RC, Heath, AC and Eaves, LJ (1995) The structure of the genetic and environmental risk factors for six major psychiatric disorders in women: phobia, generalized anxiety disorder, panic disorder, bulimia, major depression, and alcoholism. Archives of General Psychiatry 52, 374–383.CrossRefGoogle ScholarPubMed
Kendler, KS, Prescott, CA, Myers, J and Neale, MC (2003) The structure of genetic and environmental risk factors for common psychiatric and substance use disorders in men and women. Archives of General Psychiatry 60, 929–937.CrossRefGoogle ScholarPubMed
Kessler, RC, McGonagle, KA, Zhao, S, Nelson, CB, Hughes, M, Eshleman, S and Kendler, KS (1994) Lifetime and 12-month prevalence of DSM-III-R psychiatric disorders in the United States: results from the National Comorbidity Survey. Archives of General Psychiatry 51, 8–19.CrossRefGoogle ScholarPubMed
Kessler, RC, Berglund, P, Demler, O, Jin, R, Merikangas, KR and Walters, EE (2005 a) Lifetime prevalence and age-of-onset distributions of DSM-IV disorders in the National Comorbidity Survey Replication. Archives of General Psychiatry 62, 593–602.CrossRefGoogle ScholarPubMed
Kessler, RC, Chiu, WT, Demler, O and Walters, EE (2005 b) Prevalence, severity, and comorbidity of 12-month DSM-IV disorders in the National Comorbidity Survey Replication. Archives of General Psychiatry 62, 617–627.CrossRefGoogle ScholarPubMed
Kranzler, HR and Rosenthal, RN (2003) Dual diagnosis: alcoholism and co-morbid psychiatric disorders. American Journal on Addictions 12, 26–40.CrossRefGoogle ScholarPubMed
Lahey, BB and D'Onofrio, BM (2010) All in the family: comparing siblings to test causal hypotheses regarding environmental influences on behavior. Current Directions in Psychological Science 19, 319–323.CrossRefGoogle ScholarPubMed
Lai, HMX, Cleary, M, Sitharthan, T and Hunt, GE (2015) Prevalence of comorbid substance use, anxiety and mood disorders in epidemiological surveys, 1990–2014: a systematic review and meta-analysis. Drug and Alcohol Dependence 154, 1–13.CrossRefGoogle ScholarPubMed
Langas, AM, Malt, UF and Opjordsmoen, S (2012) In-depth study of personality disorders in first-admission patients with substance use disorders. BMC Psychiatry 12, 180–190.CrossRefGoogle ScholarPubMed
Laramee, P, Leonard, S and Buchanan-Hughes, A (2015) Risk of all-cause mortality in alcohol-dependent individuals: a systematic literature review and meta-analysis. EBioMedicine 2, 1394–1404.CrossRefGoogle ScholarPubMed
Ludvigsson, JF, Otterblad-Olausson, P, Pettersson, BU and Ekbom, A (2009) The Swedish personal identity number: possibilities and pitfalls in healthcare and medical research. European Journal of Epidemiology 24, 659–667.CrossRefGoogle ScholarPubMed
Ludvigsson, JF, Andersson, E, Ekbom, A, Feychting, M, Kim, JL, Reuterwall, C, Heurgren, M and Otterblad Olausson, P (2011) External review and validation of the Swedish National Inpatient Register. BMC Public Health 11, 450–466.CrossRefGoogle ScholarPubMed
Markkula, N, Suvisaari, J, Saarni, SI, Pirkola, S, Peña, S, Saarni, S, Ahola, K, Mattila, AK, Viertiö, S, Strehle, J, Koskinen, S and Härkänen, T (2015) Prevalence and correlates of major depressive disorder and dysthymia in an eleven-year follow-up – results from the Finnish Health 2011 Survey. Journal of Affective Disorders 1, 73–80.CrossRefGoogle Scholar
McGue, M, Osler, M and Christensen, K (2010) Causal inference and observational research: the utility of twins. Perspectives in Psychological Science 5, 546–556.CrossRefGoogle Scholar
Meier, SM, Mattheisen, M, Mors, O, Mortensen, PB, Laursen, TM and Penninx, BW (2016) Increased mortality among people with anxiety disorders: total population study. British Journal of Psychiatry 209, 216–221.CrossRefGoogle ScholarPubMed
Merikangas, KR, Mehta, RL, Molnar, BE, Walters, EE, Swendsen, JD, Aguilar-Gaziola, S, Kolody, B, Vega, WA, Wittchen, HU and Kessler, RC (1998 a) Comorbidity of substance use disorders with mood and anxiety disorders: results of the International Consortium in Psychiatric Epidemiology. Addictive Behaviors 23, 893–907.CrossRefGoogle Scholar
Merikangas, KR, Stevens, DE, Fenton, B, Stolar, M, O'Malley, S, Woods, SW and Risch, N (1998 b) Co-morbidity and familial aggregation of alcoholism and anxiety disorders. Psychological Medicine 28, 773–788.CrossRefGoogle ScholarPubMed
Neale, MCCL and Cardon, LR (1992) Methodology for Genetic Studies of Twins and Families. Dordrecht, The Netherlands: Kluwer Academic Publishers.CrossRefGoogle Scholar
Pickens, RW, Svikis, DS, McGue, M and LaBuda, MC (1995) Common genetic mechanisms in alcohol, drug, and mental disorder comorbidity. Drug and Alcohol Dependence 39, 129–138.CrossRefGoogle ScholarPubMed
Pirkola, SP, Isometsä, E, Suvisaari, J, Aro, H, Joukamaa, M, Poikolainen, K, Koskinen, S, Aromaa, A and Lönnqvist, JK (2005) DSM-IV mood-, anxiety- and alcohol use disorders and their comorbidity in the Finnish general population. Social Psychiatry and Psychiatric Epidemiology 40, 1–10.CrossRefGoogle ScholarPubMed
Plana-Ripoll, O, Pedersen, CB, Holtz, Y, Benros, ME, Dalsgaard, S, de Jonge, P, Fan, CC, Degenhardt, L, Ganna, A, Greve, AN, Gunn, J, Iburg, KM, Kessing, LV, Lee, BK, Lim, CCW, Mors, O, Nordentoft, M, Prior, A, Roest, AM, Saha, S, Schork, A, Scott, JG, Scott, KM, Stedman, T, Sørensen, HJ, Werge, T, Whiteford, HA, Laursen, TM, Agerbo, E, Kessler, RC, Mortensen, PB and McGrath, JJ (2019) Exploring comorbidity within mental disorders among a Danish National Population. JAMA Psychiatry. Published online January 16, 2019. doi: 10.1001/jamapsychiatry.2018.3658.CrossRefGoogle ScholarPubMed
Regier, DA, Farmer, ME, Rae, DS, Locke, BZ, Keith, SJ, Judd, LL and Goodwin, FK (1990) Comorbidity of mental disorders with alcohol and other drug abuse: results from the Epidemiologic Catchment Area (ECA) study. JAMA 264, 2511–2518.CrossRefGoogle ScholarPubMed
Revelle, W (2018) Psych: Procedures for Personality and Psychological Research. Northwestern University, Evanston, Illinois, USA. Available at https://CRAN.R-project.org/package=psych; Version = 1.8.4.Google Scholar
Rijsdijk, FV and Sham, PC (2002) Analytic approaches to twin data using structural equation models. Briefings in Bioinformatics 3, 119–133.CrossRefGoogle ScholarPubMed
Saraceno, B (2002) The WHO world health report 2001 on mental health. Epidemiologia e Psichiatria Sociale 11, 83–87.CrossRefGoogle ScholarPubMed
Saraceno, L, Munafó, M, Heron, J, Craddock, N and Van Den Bree, MB (2009) Genetic and non-genetic influences on the development of co-occurring alcohol problem use and internalizing symptomatology in adolescence: a review. Addiction 104, 1100–1121.CrossRefGoogle ScholarPubMed
Sartor, CE, McCutcheon, VV, Pommer, NE, Nelson, EC, Grant, JD, Duncan, A, Waldron, M, Bucholz, KK, Madden, PA and Heath, AC (2011) Common genetic and environmental contributions to post-traumatic stress disorder and alcohol dependence in young women. Psychological Medicine 41, 1497–1505.CrossRefGoogle ScholarPubMed
Savage, JE, Kaprio, J, Korhonen, T, Pulkkinen, L, Rose, RJ, Verhulst, B and Dick, DM (2016) The effects of social anxiety on alcohol and cigarette use across adolescence: results from a longitudinal twin study in Finland. Psychology of Addictive Behaviors 30, 462–474.CrossRefGoogle ScholarPubMed
Schuckit, MA (2006) Comorbidity between substance use disorders and psychiatric conditions. Addiction 101, 76–88.CrossRefGoogle ScholarPubMed
Sundquist, J, Ohlsson, H, Sundquist, K and Kendler, KS (2017) Common adult psychiatric disorders in Swedish primary care where most mental health patients are treated. BMC Psychiatry 17, 234–244.CrossRefGoogle ScholarPubMed
Swendsen, JD, Merikangas, KR, Canino, GJ, Kessler, RC, Rubio-Stipec, M and Angst, J (1998) The comorbidity of alcoholism with anxiety and depressive disorders in four geographic communities. Comprehensive Psychiatry 39, 176–184.CrossRefGoogle ScholarPubMed
Takayanagi, Y, Spira, AP, Roth, KB, Gallo, JJ, Eaton, WW and Mojtabai, R (2014) Accuracy of reports of lifetime mental and physical disorders: results from the Baltimore Epidemiological Catchment Area study. JAMA Psychiatry 71, 273–280.CrossRefGoogle ScholarPubMed
Tambs, K, Harris, JR and Magnus, P (1997) Genetic and environmental contributions to the correlation between alcohol consumption and symptoms of anxiety and depression. Results from a bivariate analysis of Norwegian twin data. Behavior Genetics 27, 241–250.CrossRefGoogle ScholarPubMed
Teesson, M, Hall, W, Lynskey, M and Degenhardt, L (2000) Alcohol- and drug-use disorders in Australia: implications of the National Survey of Mental Health and Wellbeing. The Australian and New Zealand Journal of Psychiatry 34, 206–213.CrossRefGoogle ScholarPubMed
Toftdahl, NG, Nordentoft, M and Hjorthøj, C (2016) Prevalence of substance use disorders in psychiatric patients: a nationwide Danish population-based study. Social Psychiatry and Psychiatric Epidemiology 51, 129–140.CrossRefGoogle ScholarPubMed
Turner, S, Mota, N, Bolton, J and Sareen, J (2018) Self-medication with alcohol or drugs for mood and anxiety disorders: a narrative review of the epidemiological literature. Depression and Anxiety 35, 851–860.CrossRefGoogle ScholarPubMed
Westman, J, Wahlbeck, K, Laursen, TM, Gissler, M, Nordentoft, M, Hällgren, J and Ösby, U (2015) Mortality and life expectancy of people with alcohol use disorder in Denmark, Finland and Sweden. Acta Psychiatrica Scandinavica 131, 297–306.CrossRefGoogle ScholarPubMed
Whiteford, HA, Degenhardt, L, Rehm, J, Baxter, AJ, Ferrari, AJ, Erskine, HE, Charlson, FJ, Norman, RE, Flaxman, AD, Johns, N, Burstein, R, Murray, CJ and Vos, T (2013) Global burden of disease attributable to mental and substance use disorders: findings from the global burden of disease study 2010. Lancet 382, 1575–1586.CrossRefGoogle ScholarPubMed
Wittchen, HU, Jacobi, F, Rehm, J, Gustavsson, A, Svensson, M, Jönsson, B, Olesen, J, Allgulander, C, Alonso, J, Faravelli, C, Fratiglioni, L, Jennum, P, Lieb, R, Maercker, A, van Os, J, Preisig, M, Salvador-Carulla, L, Simon, R and Steinhausen, HC (2011) The size and burden of mental disorders and other disorders of the brain in Europe 2010. European Neuropsychopharmacology 21, 655–679.CrossRefGoogle ScholarPubMed
World Health Organization (1992) The ICD-10 Classification of Mental and Behavioural Disorders: Clinical Descriptions and Diagnostic Guidelines. Geneva, Switzerland: World Health Organization.Google Scholar
Xian, H, Chantarujikapong, SI, Scherrer, JF, Eisen, SA, Lyons, MJ, Goldberg, J and True, WR (2000) Genetic and environmental influences on posttraumatic stress disorder, alcohol and drug dependence in twin pairs. Drug and Alcohol Dependence 61, 95–102.CrossRefGoogle ScholarPubMed
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