Hostname: page-component-8448b6f56d-mp689 Total loading time: 0 Render date: 2024-04-18T20:37:33.204Z Has data issue: false hasContentIssue false

Clinical features of drug abuse that reflect genetic risk

Published online by Cambridge University Press:  24 January 2014

K. S. Kendler*
Affiliation:
Virginia Institute for Psychiatric and Behavioral Genetics, Virginia Commonwealth University, Richmond, VA, USA Department of Psychiatry, Virginia Commonwealth University, Richmond, VA, USA Department of Human and Molecular Genetics, Virginia Commonwealth University, Richmond, VA, USA
H. Ohlsson
Affiliation:
Center for Primary Health Care Research, Lund University, Malmö, Sweden
K. Sundquist
Affiliation:
Center for Primary Health Care Research, Lund University, Malmö, Sweden Stanford Prevention Research Center, Stanford University School of Medicine, Stanford, CA, USA
J. Sundquist
Affiliation:
Center for Primary Health Care Research, Lund University, Malmö, Sweden Stanford Prevention Research Center, Stanford University School of Medicine, Stanford, CA, USA
*
*Address for correspondence: K. S. Kendler, M.D., Virginia Institute for Psychiatric and Behavioral Genetics of VCU, Box 980126, Richmond, VA 23298-0126, USA. (Email: kendler@vcu.edu)

Abstract

Background

Drug abuse (DA) is a clinically heterogeneous syndrome. Can we, in a large epidemiological sample, identify clinical features of DA cases that index genetic risk?

Method

Using registration in medical, legal or pharmacy records, we identified four kinds of relative pairs (n = 935 854) starting with a proband with DA: monozygotic co-twins; full siblings; half-siblings; and cousins. Using linear hazard regression, we examined the interaction between three clinical features of DA in the proband and risk for DA in these four relative pairs, ordered by degree of genetic relationship.

Results

Increased risk for DA in relatives was robustly predicted by early age at first registration, total number of registrations, and ascertainment in the criminal versus the medical or pharmacy registry. In multivariate models, all three of these variables remained significant and in aggregate strongly predicted DA risk in relatives. The risk for DA in siblings of DA probands in the highest decile of genetic risk predicted by our three indices was more than twice as great as that predicted in siblings of probands in the lowest decile of risk.

Conclusions

In an epidemiological sample, genetic risk for DA can be substantially indexed by simple clinical and historical variables.

Type
Original Articles
Copyright
Copyright © Cambridge University Press 2014 

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

Agrawal, A, Lynskey, MT, Pergadia, ML, Bucholz, KK, Heath, AC, Martin, NG, Madden, PA (2008). Early cannabis use and DSM-IV nicotine dependence: a twin study. Addiction 103, 18961904.CrossRefGoogle ScholarPubMed
Agrawal, A, Sartor, CE, Lynskey, MT, Grant, JD, Pergadia, ML, Grucza, R, Bucholz, KK, Nelson, EC, Madden, PA, Martin, NG, Heath, AC (2009). Evidence for an interaction between age at first drink and genetic influences on DSM-IV alcohol dependence symptoms. Alcohol Clinical Experimental Research 33, 20472056.CrossRefGoogle ScholarPubMed
APA (1987). Diagnostic and Statistical Manual of Mental Disorders, 3rd edn, revised. American Psychiatric Association: Washington, DC.Google Scholar
Babor, TF, Hofmann, M, DelBoca, FK, Hesselbrock, V, Meyer, RE, Dolinsky, ZS, Rounsaville, B (1992). Types of alcoholics, I. Evidence for an empirically derived typology based on indicators of vulnerability and severity. Archives of General Psychiatry 49, 599608.CrossRefGoogle ScholarPubMed
Ball, SA, Carroll, KM, Babor, TF, Rounsaville, BJ (1995). Subtypes of cocaine abusers: support for a type A–type B distinction. Journal of Consulting and Clinical Psychology 63, 115124.CrossRefGoogle ScholarPubMed
Butler, RJ, Heron, J (2008). The prevalence of infrequent bedwetting and nocturnal enuresis in childhood. A large British cohort. Scandinavian Journal of Urology and Nephrology 42, 257264.CrossRefGoogle ScholarPubMed
Cloninger, CR (1987). Neurogenetic adaptive mechanisms in alcoholism. Science 236, 410416.CrossRefGoogle ScholarPubMed
Gillespie, NA, Neale, MC, Jacobson, K, Kendler, KS (2009). Modeling the genetic and environmental association between peer group deviance and cannabis use in male twins. Addiction 104, 420429.CrossRefGoogle ScholarPubMed
Heath, AC, Martin, NG, Lynskey, MT, Todorov, AA, Madden, PA (2002). Estimating two-stage models for genetic influences on alcohol, tobacco or drug use initiation and dependence vulnerability in twin and family data. Twin Research 5, 113124.CrossRefGoogle ScholarPubMed
Heston, LL, Mastri, AR, Anderson, VE, White, J (1981). Dementia of the Alzheimer type. Clinical genetics, natural history, and associated conditions. Archives of General Psychiatry 38, 10851090.CrossRefGoogle ScholarPubMed
Hibell, B, Guttormsson, U, Ahlstrom, S, Balakireva, O, Bjarnason, T, Kokkevi, A, Kraus, L (2007). The 2007 ESPAD Report: Substance Use Among Students in 35 European Countries. The Swedish Council for Information on Alcohol and Other Drugs (CAN): Stockholm.Google Scholar
Kendler, KS, Gatz, M, Gardner, CO, Pedersen, NL (2007). Clinical indices of familial depression in the Swedish Twin Registry. Acta Psychiatrica Scandinavica 115, 214220.CrossRefGoogle ScholarPubMed
Kendler, KS, Jacobson, K, Myers, JM, Eaves, LJ (2008). A genetically informative developmental study of the relationship between conduct disorder and peer deviance in males. Psychological Medicine 38, 10011011.CrossRefGoogle ScholarPubMed
Kendler, KS, Karkowski, LM, Neale, MC, Prescott, CA (2000). Illicit psychoactive substance use, heavy use, abuse, and dependence in a US population-based sample of male twins. Archives of General Psychiatry 57, 261269.CrossRefGoogle Scholar
Kendler, KS, Maes, H, Sundquist, K, Lichtenstein, P, Ohlsson, H, Sundquist, JA (2012 a). Genetic and family and community environmental effects on drug abuse in adolescence: a Swedish national twin and sibling study. American Journal of Psychiatry. Published online 30 September 2013 . doi:10.1176/appi.ajp.2013.12101300.Google Scholar
Kendler, KS, Ohlsson, H, Sundquist, K, Sundquist, J (2013 a). A latent class analysis of drug abuse in a national Swedish sample. Psychological Medicine 43, 21692178.CrossRefGoogle Scholar
Kendler, KS, Ohlsson, H, Sundquist, K, Sundquist, J (2013 b). Within-family environmental transmission of drug abuse: a Swedish national study. Archives of General Psychiatry 70, 235242.Google ScholarPubMed
Kendler, KS, Ohlsson, H, Sundquist, K, Sundquist, J (2014). Environmental influences on familial resemblance for drug abuse in first-cousin pairs: a Swedish national study. Psychological Medicine 44, 371379.CrossRefGoogle ScholarPubMed
Kendler, KS, Prescott, CA (1998). Cannabis use, abuse, and dependence in a population-based sample of female twins. American Journal of Psychiatry 155, 10161022.CrossRefGoogle Scholar
Kendler, KS, Sundquist, K, Ohlsson, H, Palmer, K, Maes, H, Winkleby, MA, Sundquist, J (2012 b). Genetic and familial–environmental influences on risk for drug abuse: a national Swedish adoption study. Archives of General Psychiatry 69, 690697.CrossRefGoogle ScholarPubMed
Kraus, L, Augustin, R, Frischer, M, Kummler, P, Uhl, A, Wiessing, L (2003). Estimating prevalence of problem drug use at national level in countries of the European Union and Norway. Addiction 98, 471485.CrossRefGoogle ScholarPubMed
Kringlen, E, Torgersen, S, Cramer, V (2001). A Norwegian psychiatric epidemiological study. American Journal of Psychiatry 158, 10911098.CrossRefGoogle ScholarPubMed
Lichtenstein, P, de Faire, U, Floderus, B, Svartengren, M, Svedberg, P, Pedersen, NL (2002). The Swedish Twin Registry: a unique resource for clinical, epidemiological and genetic studies. Journal of Internal Medicine 252, 184205.CrossRefGoogle ScholarPubMed
Lynskey, MT, Heath, AC, Nelson, EC, Bucholz, KK, Madden, PA, Slutske, WS, Statham, DJ, Martin, NG (2002). Genetic and environmental contributions to cannabis dependence in a national young adult twin sample. Psychological Medicine 32, 195207.CrossRefGoogle Scholar
Marenberg, ME, Risch, N, Berkman, LF, Floderus, B, de Faire, U (1994). Genetic susceptibility to death from coronary heart disease in a study of twins. New England Journal of Medicine 330, 10411046.CrossRefGoogle Scholar
McGue, M, Pickens, RW, Svikis, DS (1992). Sex and age effects on the inheritance of alcohol problems: a twin study. Journal of Abnormal Psychology 101, 317.CrossRefGoogle ScholarPubMed
Merikangas, K, Stolar, M, Stevens, DE, Goulet, J, Preisig, MA, Fenton, B, Zhang, H, O'Malley, SS, Rounsaville, BJ (1998). Familial transmission of substance use disorders. Archives of General Psychiatry 55, 973979.CrossRefGoogle ScholarPubMed
Schlaepfer, IR, Hoft, NR, Collins, AC, Corley, RP, Hewitt, JK, Hopfer, CJ, Lessem, JM, McQueen, MB, Rhee, SH, Ehringer, MA (2008). The CHRNA5/A3/B4 gene cluster variability as an important determinant of early alcohol and tobacco initiation in young adults. Biological Psychiatry 63, 10391046.CrossRefGoogle ScholarPubMed
Sinha, R (2001). How does stress increase risk of drug abuse and relapse? Psychopharmacology (Berlin) 158, 343359.CrossRefGoogle ScholarPubMed
Steele, CM (2002). Cancer of the breast and female reproductive tract. In Emery and Rimoin's Principles and Practice of Medical Genetics, 4th edn, vol. 2 (ed. Rimoin, D. L., Connor, J. M., Pyeritz, R. E. and Korf, B. R.), pp. 23522384. Churchill Livingstone: London.Google Scholar
Sullivan, PF, Neale, MC, Kendler, KS (2000). Genetic epidemiology of major depression: review and meta-analysis. American Journal of Psychiatry 157, 15521562.CrossRefGoogle ScholarPubMed
Tsuang, MT, Lyons, MJ, Eisen, SA, Goldberg, J, True, W, Lin, N, Meyer, JM, Toomey, R, Faraone, SV, Eaves, L (1996). Genetic influences on DSM-III-R drug abuse and dependence: a study of 3,372 twin pairs. American Journal of Medical Genetics 67, 473477.3.0.CO;2-L>CrossRefGoogle Scholar
Vanyukov, MM, Moss, HB, Yu, LM, Tarter, RE, Deka, R (1995). Preliminary evidence for an association of a dinucleotide repeat polymorphism at the MAOA gene with early onset alcoholism/substance abuse. American Journal of Medical Genetics 60, 122126.CrossRefGoogle ScholarPubMed