Center for the Genetics and Treatment of Antisocial Drug Dependence: Publications

1994-2001

current publications

In R. L. Hendren, J. M. Oldham, M. B. Riba (eds) 1999; Review of Psychiatry, Volume 18. pp. 155-198. Washington, DC: American Psychiatric Association Press.

Substance use disorders and disruptive behavior disorders.

Riggs, P. D., & Whitmore, E. A.

This chapter explores the recent emergence of new effective prevention programs and treatments for adolescent substance use disorders. Such treatments have been developed from an increasingly sophisticated understanding of adolescent substance use disorder as a multidimensional, developmental disorder influenced by many interrelated factors. Our increasing understanding of the relationship between adolescent substance use disorder and the disruptive behavior disorders – especially conduct disorder – has guided the development of new, effective treatment approaches for this very serious and common comorbidity. However, more advancement is needed in this area in evolving a unified, empirically supported treatment model that acknowledges a common conceptual framework and the interrelationships between addictive disorders and other psychiatric illnesses.

Whitmore, E. A., Mikulich, S. K., Ehlers, K. M., & Crowley, T. J. (2000). One-year outcome of adolescent females referred for conduct disorder and substance abuse/dependence. Drug and Alcohol Dependence, 59, 131-141. This study investigated whether substance abuse/dependence (SUD), conduct disorder(CD), and other psychiatric disorders improved in adolescent females who were referred to outpatient treatment and what variables were related to 1-year outcome. 46 conduct-disordered females with substance abuse or dependence were re-evaluated approximately 1 year after discharge. Significant improvements were seen in 3 areas: 1) criminality and CD, 2) Attention Deficit/Hyperactivity Disorder (ADHD), and 3) educational and vocational status. However, neither substance involvement nor depression improved, and these females demonstrated significant risky sexual behaviors. Only 2 post treatment factors (peer problems and number of ADHD symptoms at follow-up) were found to be related to CD and SUD outcomes. The overall lack of pre- and post-treatment predictors presents interesting challenges for future research on adolescent females with these disorders.

Whitmore, E. A., Mikulich, S. K., Ehlers, K. M., & Crowley, T. J. (2000). One-year outcome of adolescent females referred for conduct disorder and substance abuse/dependence. Drug and Alcohol Dependence, 59, 131-141.

Crowley, T. J., Mikulich, S. K., Ehlers, K. M., Whitmore, E. A., Macdonald, M. J. (submitted). Validity of structured clinical evaluations in adolescents with conduct and substance problems. Journal of the American Academy of Child and Adolescent Psychiatry, 2000.

Hopfer, C. J., Mikulich, S. K., & Crowley, T. J. (in press). Heroin Use Among Adolescents in Treatment for Substance Use Disorders. Journal of the American Academy of Child and Adolescent Psychiatry, 2000.

Hopfer, C. J., Mikulich, S. K., & Crowley, T. J. (submitted). A Pilot Study of Parent and Child Reports of Attention-Deficit/Hyperactivity disorder in Adolescents with Conduct and Substance Problems. Journal of Child and Adolescent Substance Abuse.

Mikulich, S. K., Hall, S. K., Whitmore, E. A., & Crowley, T. J. (in press). Concordance Between DSM-III-R AND DSM-IV Diagnosis of Substance Use Disorders in Adolescents. Drug and Alcohol Dependence, 2000.

Sham, P. C., Cherny, S. S., Purcell, S. & Hewitt, J. K. (in press). Power of Linkage versus Association Analysis of Quantitative Traits, by Use of Variance-Components Models, for Sibship Data. American Journal of Human Genetics.

Sham, P. C., Zhao, J. H., Cherny S. S., & Hewitt, J. K. (in review). Variance components QTL linkage analysis of selected and non-normal samples: conditioning on trait values.

Stallings, M. C., Hewitt, J. K., Beresford, T., Heath, A. C., and Eaves, L. J. (in press) A Twin Study of Drinking and Smoking: Onset and Latencies From First Use To Regular Use. Behavior Genetics.

Whitmore, E. A. & Riggs, P. D. (in press). Addiction and how it works: The use ofbuproprion in patients with substance use disorders and related conditions. Professional Opinion Newsletter, Cambridge, UK: Bridgett Publications.

Young, S. E., Stallings, M. C., Corley, R. P., Krauter, K. S., & Hewitt, J. K (in press) Genetic and environmental influences on behavioral disinhibition. Neuropsychiatric Genetics.

Young, S. E., Stallings M. C., Hewitt, J. K., & Fulker, D. W. (submitted). The Familial Transmission of Conduct Disorder: Importance of Spousal and Sibling Effects. Journal of Abnormal Psychology.


	Division of Substance Dependence

Adams, J. B., Heath, A. J., Stallings, M. C., Hewitt, J. K., Corley, R., Young, S. E., & Fulker, D. W. (in review). Relationships Between Personality and Preferred Substance and Motivations For Use Among Adolescent Substance Abusers and Their Family Members. Journal of Substance Abuse. This study examined the utility of Cloninger's tridimensional personality theory in predicting preferred substance of abuse and self-reported motivations for use among a sample of adolescent substance abusers and their family members. It was found that individuals low in Novelty Seeking (NS) tended to prefer alcohol and marijuana, while those high in NS endorsed a wider range of preferred substances. High NS was associated with significantly greater stimulant use and motivations focused on obtaining positive rewards, while low NS was associated with greater sedative use and motivations related to avoiding negative emotions or negative life experiences. Crowley, T. J., Mikulich, S. K., Ehlers, K. M., Whitmore, E. A., Macdonald, M. J. (submitted). Validity of structured clinical evaluations in adolescents with conduct and substance problems. . Journal of the American Academy of Child and Adolescent Psychiatry, 2000. For this study we used standardized diagnostic interviews to assess 87 adolescent patients (both genders) in treatment for conduct and substance problems and 85 adolescent controls (both genders) from the patients' neighborhoods. We found that youths' self reports significantly discriminated patients from controls in DSM-IV conduct and substance use disorders (CD, SUD) and in numerous associated measures. Youths' self reports did not discriminate patients from controls in attention deficit hyperactivity disorder (ADHD) or major depression (MDD). Parent information raised prevalence rates of ADHD and MDD, which then discriminated patients from controls. However, patients and parents usually disagreed on MDD and ADHD diagnoses. We concluded that despite some dissimulation, patients' self reports of CD and SUD correlated highly and had superb discriminative validity, making them useful for treatment and research. Self-reports of ADHD and MDD, apparently lacking discriminative validity, are less useful. Hopfer, C. J., Mikulich, S. K., & Crowley, T. J. (in press). Heroin Use Among Adolescents in Treatment for Substance Use Disorders. Journal of the American Academy of Child and Adolescent Psychiatry, 2000. The objective of this article is to clarify prevalence rates and describe patterns of adolescent heroin users who are in treatment for Substance Use disorders. Nationally, there was an increasing number, but not percentage, of heroin-using youth in treatment between 1992-1996. In 1997 there was an increase in both the number and percent of heroin-using youth in treatment. Heroin-using adolescents have the highest rate of injection drug use when compared with youths using other substances. Because of their greater risk of contracting HIV through injection drug use, treatment trials for these adolescents are needed. Hopfer, C. J., Mikulich, S. K., & Crowley, T. J. (submitted). A Pilot Study of Parent and Child Reports of Attention-Deficit/Hyperactivity disorder in Adolescents with Conduct and Substance Problems. Journal of Child and Adolescent Substance Abuse. We present the results of a study which examined the agreement between parent and adolescent reports of Attention-Deficit/Hyperactivity Disorder (ADHD) in a sample of 50 adolescents with substance and conduct problems. It was found that parents reported a greater mean number of ADHD symptoms within the last six months compared to adolescent self-report. This resulted in significantly more ADHD diagnoses based on parent report. Our finding of poor parent-adolescent agreement in reports of ADHD symptoms and diagnoses among patients with CD and SUD is consistent with and extends the results of previous studies with community and clinic-referred adolescents. Mikulich, S. K., Hall, S. K., Whitmore, E. A., & Crowley, T. J. (in press). Concordance Between DSM-III-R AND DSM-IV Diagnosis of Substance Use Disorders in Adolescents. Drug and Alcohol Dependence, 2000. We assessed a clinical sample of 102 adolescents using CIDI-SAM. Prevalence of either an abuse or dependence diagnosis was lower with DSM-IV than DSM-III-R except for cannabis and alcohol, and concordance rates were better for dependence that for abuse. For most substances, rates of DSM-IV withdrawal were lower than in DSM-III-R, but rates of DSM-IV physiological dependence remained high. Changes in DSM-IV criteria appear to have impacted diagnoses in these adolescents, particularly for the substances they use most – i.e. alcohol, tobacco and cannabis. Sham, P. C., Cherny, S. S., Purcell, S. & Hewitt, J. K. (in press). Power of Linkage versus Association Analysis of Quantitative Traits, by Use of Variance-Components Models, for Sibship Data. American Journal of Human Genetics. In this article, we investigate the power of quantitative-trait loci (QTL) linkage and association analyses for simple random sibship samples, under the variance-components model proposed by Fulker et al. We show that the powers of both linkage and association analyses are crucially dependent on the proportion of phenotypic variance attributable to the QTL. The main difference between the two tests is that, whereas the power of association is directly related to the QTL heritability, the power of linkage is related more closely to the square of the QTL heritability. We also describe both how the power of linkage is attenuated by incomplete linkage and incomplete marker information and how the power of association is attenuated by incomplete linkage disequilibrium. Sham, P. C., Zhao, J. H., Cherny S. S., & Hewitt, J. K. (in review). Variance components QTL linkage analysis of selected and non-normal samples: conditioning on trait values. Standard variance components QTL linkage analysis can produce an elevated rate of type 1 errors when applied to selected samples and non-normal data. Here, we describe an adjustment of the log-likelihood function based on conditioning on trait values that largely overcomes these problems. This method is shown by simulation studies on sib pairs to provide valid tests in selected samples and non-normal data, and to be as powerful as alternative methods for analyzing selected samples that require knowledge of the ascertainment procedure or the trait values of non-selected sib pairs. Stallings, M. C., Hewitt, J. K., Beresford, T., Heath, A. C., and Eaves, L. J. (in press) A Twin Study of Drinking and Smoking: Onset and Latencies From First Use To Regular Use. Behavior Genetics. This study investigated genetic and environmental influences on age-at-onset of alcohol and tobacco use by examining twin resemblance for several retrospectively reported onset milestones including: age at first use, age at first alcohol intoxication experience, and age at regular use. In addition, latency between age of first use and regular use of tobacco and alcohol was examined. Biometrical model fitting results confirmed that familial resemblance for age of first use for both alcohol and tobacco was largely the result of shared environmental factors, while the latency between first use and regular patterns of use were more genetically influenced. These findings add to a growing literature suggesting that initiation of substance use is primarily influenced by environmental rather that genetic factors. Whitmore, E. A. & Riggs, P. D. (in press). Addiction and how it works: The use of buproprion in patients with substance use disorders and related conditions. Professional Opinion Newsletter, Cambridge, UK: Bridgett Publications. Our recent open trial of buproprion for ADHD in adolescents with substance use disorders and conduct disorder suggested that it may be a helpful treatment. Adolescents treated with buproprion showed significant reductions in standard ratings of inattention and hyperactivity, as well as improved subjective reports of progress in substance treatment. Buproprion appears to be as effective for ADHD as the long-acting psychostimulants, with less abuse potential. Given buproprion's efficacy in treating smoking cessation and what is currently known about the neurobiology of addiction, controlled studies of buproprion for treatment of substance dependence other than nicotine dependence appear warranted. Young, S. E., Stallings, M. C., Corley, R. P., Krauter, K. S., & Hewitt, J. K (in press) Genetic and environmental influences on behavioral disinhibition. Neuropsychiatric Genetics. Comorbidity among childhood disruptive behavioral disorders is commonly reported. These problems are also associated with early substance abuse and other markers of behavioral disinhibition. 172 MZ and 162 DZ twin pairs were assessed using standardized psychiatric interviews and personality assessments. A common pathway model suggested that behavioral disinhibition is highly heritable (a2 = .84) and is not influenced significantly by shared environmental factors. The results suggest that a variety of adolescent problem behaviors may share a common underlying genetic risk. Young, S. E., Stallings M. C., Hewitt, J. K., & Fulker, D. W. (submitted). The Familial Transmission of Conduct Disorder: Importance of Spousal and Sibling Effects. Journal of Abnormal Psychology. This study of DSM-III-R conduct disorder tests an explicit model of familial resemblance including the estimation of parent-child transmission, assortative mating and sibling resemblance. We present 3 primary findings regarding the familial aggregation of CD using this model. First, we present compelling evidence of the elevated risk for DSM-III-R symptoms and diagnosis of CD in family members of adolescents identified with a history of substance use and conduct problems. Second, we provide evidence of significant direct (parent-child) transmission as well as significant indirect effects, transmitted through positive spouse correlations. Thirdly, these data suggest there is a unique sibling environmental effect contributing to family resemblance. Abstracts Gynther, L. Carey G., & Knesevich, J. (1989). A twin study of drug use. Behavior Genetics, 19, 760-761. Carey, G. (1992). Pedigree analysis of antisocial symptoms, alcohol abuse symptoms, and drug abuse symptoms in adolescent substance abusers and their families. Behavior Genetics, 22, 715. Wear, K., & Carey, G. (1992). The relationship among conduct disorder, antisocial personality disorder, and antisocial symptoms in the families of adolescent substance abusers. Behavior Genetics, 22, 761. Miles, D., & Carey, G. (1993). The genetics of antisocial personality disorder: A psychiatric sample. Behavior Genetics, 23, 558-559. Rhea, S. A., Corley, R., & Fulker, D. W. (1993). Familial resemblance for cognitive abilities in twin and Colorado Adoption Project control families. Behavior Genetics, 23, 562. Carey, G. (1994). Multivariate genetic relationships among substance abuse, alcohol abuse, and antisocial personality. Psychiatric Genetics, 3, 141. Cherny, S. S., Stallings, M. C., Carey, G., Fulker, D. W., & Hewitt, J. K. (1994). The familial transmission of depressive symptoms in adolescent substance abusing males. Behavior Genetics, 24, 509. Cherny, S. S., Stallings, M. C., Carey, G., Fulker. D. W., & Hewitt, J. K. (1994). The familial aggregation of depressive symptoms, antisocial personality, and substance abuse. Behavior Genetics, 24, 509. Corley, R., Rhea, S. A., & Young, S. (1994). Comparison of Drug Use and Symptoms of Psychopathology in Four Samples of Adolescents. Behavior Genetics, 24, 510. Stallings, M. C., Cherny, S. S, Carey, G, Fulker, D. W., & Hewitt, J. K. (1994). Familial aggregation of alcohol and drug problems in families of adolescent substance users. Behavior Genetics, 24, 531. Stallings, M. C., Cherny, S. S., Carey G., Fulker, D. W., & Hewitt, J. K. (1994). Personality risk factors in adolescent substance abuse. Behavior Genetics, 24, 531. Stallings, M. C., Cherny, S. S., Young, S. E., Miles, D. R., Carey, G., Hewitt, J. K., & Fulker, D. W. (1994). Familial aggregation of alcohol and drug problems in adolescent males. Behavior Genetics, 24, 531 Stallings, M. C., Hewitt, J. K., Fulker, D. W., Carey G., Prescott, C. A., Heath, A. C., & Eaves, L. J. (1994). Personality risk factors for alcohol, tobacco, and illicit substance abuse behavior. Psychiatric Genetics, 3:3, 142. Carey, G. (1995). Analytical methods for the application of molecular genetic strategies to quantitative phenotypes. Behavior Genetics, 25:3, 258. Carey, G., Stallings, M. C., Hewitt, J. K., & Fulker, D. W. (1995). The familial relationship among personality, substance abuse, and other problem behavior in adolescents. Behavior Genetics, 25:3, 258. Corley, R. P., Cherny, S. S., Stallings, M. C., & Young, S. E. (1995). Temperamental and familial factors in adolescent substance use. Poster presented at the Biennial Meeting of the Society for Research in Child Development, Indianapolis, Indiana, March 1995. Corley, R. P., & Wadsworth, S. J. (1995). Preliminary investigation of parental influences on age of first experimentation with illicit substances in the Colorado Adoption Project. Behavior Genetics, 25, 260 Harris, K. N., Wadsworth, S. J., Corley, R. P., & DeFries, J. C. (1995). Early academic achievement and adolescent substance abuse. National Institute of Mental Health COR Colloquium Program and Abstracts, F-11. Norflin, E. L., Corley, R. P., Wadsworth, S. J., & DeFries, J. C. (1995). Peer and family influences on substance experimentation. National Institute of Mental Health COR Colloquium Program and Abstracts, F-11. Rhea, S. A., & Corley, R. P. (1995). Genetic and environmental influences on television viewing in Colorado Adoption Project families. Behavior Genetics, 25, 284-285. Stallings, M. C., Cherny, S. S., Young, S. E., Carey, G., Hewitt, J. K., & Fulker, D. W. (1995). Personality factors in early-onset adolescent substance abuse. Behavior Genetics, 25, 289. Stallings, M. C., Cherny, S. S., Young, S. E., Corley, R. P., Fulker, D. W., & Hewitt, J. K. (1995). The coaggregation of alcohol abuse, depressive symptoms, and antisocial personality in the families of multiple-problem adolescents. Alcoholism: Clinical and Experimental Research, 19, 71A. Wadsworth, S. J., Corley, R., & DeFries, J. C. (1995). Substance use in the Colorado Adoption Project. Behavior Genetics, 25, 293. Young, S. E., Stallings, M. C., Cherny, S. S., Carey, G., Hewitt, J. K., & Fulker, D. W. (1995). Familial transmission of substance dependence and comorbid psychiatric problems in severely affected adolescent males and their relatives. Behavior Genetics, 25, 294. Stallings, M. C., Young, S. E., Hewitt, J. K., Crowley, T. J., and Fulker, D. W. (1996). Heterogeneous temperament profiles among early onset multi-problem substance abusing youth. Problems of Drug Dependence 1996: Proceedings of the 58th Annual Scientific Meeting of the College on Problems of Drug Dependence. National Institute on Drug Abuse Research Monograph, 174, 267. Young, S. E., Stallings, M. C., Corley, R. P., Hewitt, J. K., and Fulker, D. W. (1996). Parent-offspring transmission of substance abuse, antisocial behavior, and cognitive factors in selected, adoptive, and control families. Behavior Genetics, 26, 602-603. Cherny, S. S., Fulker, D. W., & Sham, P. (1998). Maximum-likelihood methods of association and linkage. Behavior Genetics, 28:6, 467 Crowley, T. J., Mikulich, S. K., Macdonald, M. J., Ehlers, K. M. (1998). Discriminant validity of self-report: Substance-involved delinquents vs. controls. Oral presentation accepted for the Sixtieth Annual Scientific Meeting of the College on Problems of Drug Dependence, Scottsdale, AZ.. June 13-18, 1998. Stallings, M. C., Young, S. E., Miles, D. R., Hewitt, J. K., Fulker, D. W., & Crowley, T. J. (1998). The familial aggregation of nicotine, alcohol, and marijuana dependence symptoms in families with substance-abusing adolescent probands and controls. Behavior Genetics, 28:6, 481-2. Wilson, S. M., Hewitt, J. K., Corley, R. P., Stallings, M. C., & Beresford, T. P. (1998). Genetic and environmental influences on adolescent drug and alcohol use in the Colorado Adolescent Twin Study (CATS). Behavior Genetics, 28:6, 485-6. Young, S. E., Stallings, M. C., Corley, R. P., Hewitt, J. K., & Fulker, D. W. (1998). Family factors underlying conduct disorder and attention deficit hyperactivity disorder: A sibling study of comorbidity. Behavior Genetics, 28:6, 486.