This Article  • Full text  • PDF  • Reply to article  • Send to a friend  • Save in My Folder  • Save to citation manager  • Permissions  Citing Articles  • Citation map  • Citing articles on HighWire  • Citing articles on ISI (193)  • Contact me when this article is cited  Related Content  • Related articles  • Similar articles in this journal  Topic Collections  • Public Health  • Substance Abuse/ Alcoholism  • Alert me on articles by topic  Social Bookmarking   What's this?

Kathleen R. Merikangas, PhD; Marilyn Stolar, MA; Denise E. Stevens, PhD; Joseph Goulet, MS; Martin A. Preisig, MD; Brenda Fenton, PhD; Heping Zhang, PhD; Stephanie S. O'Malley, PhD; Bruce J. Rounsaville, MD

Arch Gen Psychiatry. 1998;55:973-979.

Background  There is increasing evidence that substance use disorders are familial and that genetic factors explain a substantial degree of their familial aggregation. To perform a controlled family study of probands with several different predominant drugs of abuse, including opioids, cocaine, cannabis, and/or alcohol.

Methods  The subjects for the present study included 231 probands with dependence on opioids, cocaine, cannabis, and/or alcohol and 61 control probands, and their 1267 adult first-degree relatives. Diagnostic estimates were based on semistructured diagnostic interviews and/or structured family history interviews regarding each proband, spouse, and adult first-degree relative. The interview data were reviewed blindly and independently by clinicians with extensive experience in the evaluation and treatment of substance use disorders.

Results  There was an 8-fold increased risk of drug disorders among the relatives of probands with drug disorders across a wide range of specific substances, including opioids, cocaine, cannabis, and alcohol, which is largely independent from the familial aggregation of both alcoholism and antisocial personality disorder. There was also evidence of specificity of familial aggregation of the predominant drug of abuse.

Conclusions  Elevation in risk of this magnitude places a family history of drug disorder as one of the most potent risk factors for the development of drug disorders. These results suggest that there may be risk factors that are specific to particular classes of drugs as well as risk factors that underlie substance disorders in general.

From the Departments of Epidemiology and Public Health (Drs Merikangas, Stevens, and Zhang, Ms Stolar, and Mr Goulet) and Psychiatry (Drs Merikangas, O'Malley, and Rounsaville), Yale University School of Medicine, New Haven, Conn; Department of Psychiatry, University of Lausanne, Lausanne, Switzerland (Dr Preisig); and Department of Psychiatry, University of Geneva, Geneva, Switzerland (Dr Fenton).

CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati     What's this?

RELATED ARTICLES

General and Specific Inheritance of Substance Abuse and Alcoholism
David Goldman and Andrew Bergen
Arch Gen Psychiatry. 1998;55(11):964-965.
EXTRACT | FULL TEXT  

Co-occurrence of Abuse of Different Drugs in Men: The Role of Drug-Specific and Shared Vulnerabilities
Ming T. Tsuang, Michael J. Lyons, Joanne M. Meyer, Thomas Doyle, Seth A. Eisen, Jack Goldberg, William True, Nong Lin, Rosemary Toomey, and Lindon Eaves
Arch Gen Psychiatry. 1998;55(11):967-972.
ABSTRACT | FULL TEXT  

Familial Transmission of Substance Dependence: Alcohol, Marijuana, Cocaine, and Habitual Smoking: A Report From the Collaborative Study on the Genetics of Alcoholism
Laura Jean Bierut, Stephen H. Dinwiddie, Henri Begleiter, Raymond R. Crowe, Victor Hesselbrock, John I. Nurnberger, Jr, Bernice Porjesz, Marc A. Schuckit, and Theodore Reich
Arch Gen Psychiatry. 1998;55(11):982-988.
ABSTRACT | FULL TEXT  

THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES

Gene-Environment Interplay Between Cannabis and Psychosis
Henquet et al.
Schizophr Bull 2008;34:1111-1121.
ABSTRACT | FULL TEXT  

Genome-Wide Association for Methamphetamine Dependence: Convergent Results From 2 Samples
Uhl et al.
Arch Gen Psychiatry 2008;65:345-355.
ABSTRACT | FULL TEXT  

Familial Risk Analyses of Attention Deficit Hyperactivity Disorder and Substance Use Disorders
Biederman et al.
Am. J. Psychiatry 2008;165:107-115.
ABSTRACT | FULL TEXT  

Neurexin 3 polymorphisms are associated with alcohol dependence and altered expression of specific isoforms
Hishimoto et al.
Hum Mol Genet 2007;16:2880-2891.
ABSTRACT | FULL TEXT  

Association of Maternal Smoking and Alcohol Consumption with Young Adults' Cannabis Use: A Prospective Study
Hayatbakhsh et al.
Am J Epidemiol 2007;166:592-598.
ABSTRACT | FULL TEXT  

Identification of Functional Polymorphisms in the Promoter Region of the Human PICK1 Gene and Their Association With Methamphetamine Psychosis
Matsuzawa et al.
Am. J. Psychiatry 2007;164:1105-1114.
ABSTRACT | FULL TEXT  

Genomewide suggestive linkage of opioid dependence to chromosome 14q
Lachman et al.
Hum Mol Genet 2007;16:1327-1334.
ABSTRACT | FULL TEXT  

Addiction: A Disease of Learning and Memory
Hyman
Focus 2007;5:220-228.
ABSTRACT | FULL TEXT  

Commentary: Understanding pathways to cannabis use and from use to harm.
Macleod and Hickman
Int J Epidemiol 2006;35:680-682.
FULL TEXT  

A dopamine transporter gene functional variant associated with cocaine abuse in a Brazilian sample
Guindalini et al.
Proc. Natl. Acad. Sci. USA 2006;103:4552-4557.
ABSTRACT | FULL TEXT  

Increased Vulnerability to Nicotine Self-Administration and Relapse in Alcohol-Naive Offspring of Rats Selectively Bred for High Alcohol Intake
Le et al.
J. Neurosci. 2006;26:1872-1879.
ABSTRACT | FULL TEXT  

Caffeine Dependence in Combination With a Family History of Alcoholism as a Predictor of Continued Use of Caffeine During Pregnancy
Svikis et al.
Am. J. Psychiatry 2005;162:2344-2351.
ABSTRACT | FULL TEXT  

Early Predictors of Adult Drinking: A Birth Cohort Study
Alati et al.
Am J Epidemiol 2005;162:1098-1107.
ABSTRACT | FULL TEXT  

Pooled association genome scanning: Validation and use to identify addiction vulnerability loci in two samples
Liu et al.
Proc. Natl. Acad. Sci. USA 2005;102:11864-11869.
ABSTRACT | FULL TEXT  

Addiction: A Disease of Learning and Memory
Hyman
Am. J. Psychiatry 2005;162:1414-1422.
ABSTRACT | FULL TEXT  

Developments in the Epidemiology of Drug Use and Drug Use Disorders
Compton et al.
Am. J. Psychiatry 2005;162:1494-1502.
ABSTRACT | FULL TEXT  

Pharmacogenetics and Human Molecular Genetics of Opiate and Cocaine Addictions and Their Treatments
Kreek et al.
Pharmacol. Rev. 2005;57:1-26.
ABSTRACT | FULL TEXT  

A Family Study of Alcohol Dependence: Coaggregation of Multiple Disorders in Relatives of Alcohol-Dependent Probands
Nurnberger et al.
Arch Gen Psychiatry 2004;61:1246-1256.
ABSTRACT | FULL TEXT  

Family Transmission and Heritability of Externalizing Disorders: A Twin-Family Study
Hicks et al.
Arch Gen Psychiatry 2004;61:922-928.
ABSTRACT | FULL TEXT  

The Effect of Parental Alcohol and Drug Disorders on Adolescent Personality
Elkins et al.
Am. J. Psychiatry 2004;161:670-676.
ABSTRACT | FULL TEXT  

The Burden of Complex Genetics in Brain Disorders
Uhl and Grow
Arch Gen Psychiatry 2004;61:223-229.
ABSTRACT | FULL TEXT  

General and Specific Predictors of Behavioral and Emotional Problems Among Adolescents
Windle and Mason
Journal of Emotional and Behavioral Disorders 2004;12:49-61.
ABSTRACT  

Childhood and Adolescent Predictors of Major Depression in the Transition to Adulthood
Reinherz et al.
Am. J. Psychiatry 2003;160:2141-2147.
ABSTRACT | FULL TEXT  

ETHANOL-REINFORCED BEHAVIOUR PREDICTS ACQUISITION BUT NOT EXTINCTION OF COCAINE SELF-ADMINISTRATION IN THE RAT
Mierzejewski et al.
Alcohol Alcohol 2003;38:543-549.
ABSTRACT | FULL TEXT  

EVENT-RELATED POTENTIAL RESPONSES TO ALCOHOL-RELATED STIMULI IN AFRICAN-AMERICAN YOUNG ADULTS: RELATION TO FAMILY HISTORY OF ALCOHOLISM AND DRUG USAGE
Ehlers et al.
Alcohol Alcohol 2003;38:332-338.
ABSTRACT | FULL TEXT  

The Genetic Determinants of Smoking
Batra et al.
Chest 2003;123:1730-1739.
ABSTRACT | FULL TEXT  

Specificity of Genetic and Environmental Risk Factors for Use and Abuse/Dependence of Cannabis, Cocaine, Hallucinogens, Sedatives, Stimulants, and Opiates in Male Twins
Kendler et al.
Am. J. Psychiatry 2003;160:687-695.
ABSTRACT | FULL TEXT  

Family Study of Affective Spectrum Disorder
Hudson et al.
Arch Gen Psychiatry 2003;60:170-177.
ABSTRACT | FULL TEXT  

Shared Genetic Risk of Major Depression, Alcohol Dependence, and Marijuana Dependence: Contribution of Antisocial Personality Disorder in Men
Fu et al.
Arch Gen Psychiatry 2002;59:1125-1132.
ABSTRACT | FULL TEXT  

Are Personality Traits Familial Risk Factors for Substance Use Disorders? Results of a Controlled Family Study
Swendsen et al.
Am. J. Psychiatry 2002;159:1760-1766.
ABSTRACT | FULL TEXT  

A 28-Year-Old Man Addicted to Cocaine
Hyman
JAMA 2001;286:2586-2594.
FULL TEXT  

Twin Studies of Psychiatric Illness: An Update
Kendler
Arch Gen Psychiatry 2001;58:1005-1014.
ABSTRACT | FULL TEXT  

Risk Factors for Adolescent Substance Abuse
Weinberg
J Learn Disabil 2001;34:343-351.
ABSTRACT  

Pharmacogenetics of Alcohol Response and Alcoholism: The Interplay of Genes and Environmental Factors in Thresholds for Alcoholism
Radel and Goldman
Drug Metab. Dispos. 2001;29:489-494.
ABSTRACT | FULL TEXT  

Multivariate Logistic Regression for Familial Aggregation of Two Disorders. I. Development of Models and Methods
Hudson et al.
Am J Epidemiol 2001;153:500-505.
ABSTRACT | FULL TEXT  

Illicit Psychoactive Substance Use, Heavy Use, Abuse, and Dependence in a US Population-Based Sample of Male Twins
Kendler et al.
Arch Gen Psychiatry 2000;57:261-269.
ABSTRACT | FULL TEXT  

Toward the Identification of Core Psychopathological Processes?
Wittchen et al.
Arch Gen Psychiatry 1999;56:929-931.
FULL TEXT  

Cigarette Smoking
Bergen and Caporaso
JNCI J Natl Cancer Inst 1999;91:1365-1375.
ABSTRACT | FULL TEXT  

Genetic Factors in Substance Abuse
JWatch Psychiatry 1999;1999:3-3.
FULL TEXT  

General and Specific Inheritance of Substance Abuse and Alcoholism
Goldman and Bergen
Arch Gen Psychiatry 1998;55:964-965.
FULL TEXT