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UMD PSYC 434 - The Harvard Twin Study of Substance Abuse: What We Have Learned

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body of research has addressed several pertinent questionsconcerning this issue: Does substance abuse run in families?If so, is the risk inherited? If yes, just what is inherited—avulnerability for abuse of a specific substance, or vulnerabil-ity factors underlying the risk for development of a numberof substance use and addictive behavioral problems?Twin studies are particularly well suited for investigatingthese questions. The unique structure of twin data allowsthe relative effects of genetic, shared environmental, andunique environmental influences to be explicated. Monozy-gotic (MZ) twins share 100% of their genes, while dizygotic(DZ) twins share, on average, 50%. Both MZ and DZ twinpairs generally share 100% of their family environment;such influences are assumed to promote resemblanceequally in MZ and DZ pairs. Thus, greater similarity amongMZ twins compared with DZ twins suggests genetic influ-ences on the phenotype under investigation. By comparingMZ and DZ correlations, we can arrive at estimates for thesethree sets of influences. Over the past decade, we have stud-ied the genetic and environmental determinants of addic-REVIEWThe Harvard Twin Study of Substance Abuse:What We Have LearnedMing T. Tsuang, MD, PhD, Jessica L. Bar, MA, Rebecca M. Harley, PhD, and Michael J. Lyons, PhDThe Harvard Twin Study of Substance Abuse was carried out with the members of theVietnam Era Twin (VET) Registry. The VET Registry comprises over 8000 male twins whoserved in the United States military between 1965 and 1975 and were subsequently inter-viewed regarding their use of licit and illicit substances, as well as various typesof psychopathology. Our research has demonstrated significant influences by genetic,shared environmental, and unique environmental factors on the abuse of illicit substances.Multivariate analyses have indicated that the co-occurrence of abuse of various types ofillicit drugs reflects a common vulnerability, influenced by both genetic and environmentalfactors, that cuts across all categories of illicit drugs. We have also demonstrated thatsome drugs have unique determinants, both genetic and environmental, that are notshared with other drugs. In part, the genetic influence on marijuana abuse is mediatedby genetic influence on subjective effects in response to the drug. The determinants oftransitions from one stage of drug use to another differ depending on which drug or whichtransition is examined. We determined significant genetic influences on several aspectsof nicotine and alcohol use separately, as well as genetic influences shared by bothsubstances. We found that the co-occurrence of illicit drug abuse and major depressionis due to unique environmental influences. The phenotypic association between symptomsof conduct disorder and alcohol and marijuana dependence is due largely to sharedenvironmental influences. Our results, thus far, indicate a complex pattern of genetic andenvironmental influences on substance use and abuse. (HARVARDREVPSYCHIATRY2001;9:267–279.)Substance abuse is widely recognized as one of the most com-plex and problematic issues facing today’s society. A growingFrom the Harvard Institute of Psychiatric Epidemiology and Genet-ics (Drs. Tsuang and Lyons), Massachusetts Mental Health Center(Dr. Tsuang), and the Department of Psychology, Boston University(Ms. Bar, Drs. Harley and Lyons), Boston, Mass.Supported by a grant (DA04604) from the National Institute onDrug Abuse (Dr. Tsuang), and the Department of Veterans AffairsHealth Services Research and Development Service and Coopera-tive Studies Program (Study 992).Original manuscript received 20 March 2001; revised manuscriptreceived 20 June 2001, accepted for publication 25 June 2001.Reprint requests: Ming T. Tsuang, MD, PhD, Massachusetts MentalHealth Center, 74 Fenwood Rd., Boston, MA 02115 (e-mail:[email protected]).䉷 2001 President and Fellows of Harvard College267tive behaviors using a large national cohort of twins whoare members of the Vietnam Era Twin (VET) Registry.This paper reviews our findings in an attempt to summarizewhat has been learned from the VET Registry thus farabout the phenomenology and etiology of substance use dis-orders.THE VIETNAM ERA TWIN REGISTRYThe VET Registry consists of over 8000 male-male twinpairs born between 1939 and 1957 in which both siblingsserved on active military duty during the Vietnam era (May1965 to August 1975). Twins were originally identified in thelate 1980s through a search of the Department of Defensecomputer files of discharged servicemen.1,2Individuals withthe same last name and date of birth but different firstnames were identified as potential twins. From a list ofapproximately 5.5 million veterans, 15,711 potential twinpairs were identified. Military records of possible pairs werethen examined to confirm twinship. Zygosity was evalu-ated by analyzing responses of twin siblings to a series ofquestions on twin similarity and limited blood group typingobtained from military records.3This method achieved 95%accuracy.In 1992, information about drug and alcohol use and life-time prevalence of comorbid psychiatric disorders was col-lected from VET Registry members by telephone interview.Of 10,300 individuals (5150 pairs) determined to be eligiblefor the study, 47 were deceased or incapacitated. Data weresuccessfully collected from 8169 of the remaining 10,253individuals (response rate, 79.7%). The 1874 MZ and 1498DZ pairs in which both members responded to the drugabuse items constituted the final sample. Sociodemographicbreakdown of the group revealed the following character-istics:Age: Mean, 44.6 years (SD, 2.8; range,36–55 years)Race: Non-Hispanic white: 90.4%African-American: 4.9%Hispanic: 2.7%Native American: 1.3%“Other”: 0.7%Education: High school graduate: 33.3%Vocational school attendance: 15.8%College graduate: 38.6%Graduate training and/or a gradu-ate degree: 10.6%Other/data not available: 1.7%Employment: Employed full-time: 92.6%Employed part-time: 1.8%Unemployed: 5.6%Marital status: Married: 75%Never married: 11%Currently unmarried/data notavailable: 14%Residence: All 50 states of the U.S.Registry members are representative of all twins who servedin the military during the Vietnam War on a variety of socio-demographic and other variables.4A complete description ofVET Registry construction has been published elsewhere.1,2Subjects were interviewed using the Diagnostic Inter-view


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UMD PSYC 434 - The Harvard Twin Study of Substance Abuse: What We Have Learned

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