Heterogeneity of Drug Abuse

United States

NIDA Organizer(s): Kevin P. Conway, Ph.D., DESPR/ERB 

Purpose & Intent

The purpose of the meeting is to bring together diverse researchers to discuss and identify ways to better describe, discriminate, and predict the nature and course of drug use disorders so as to offer more precise phenotypic indicators of underlying genetic and environmental risk. Like many other relatively common human diseases, drug abuse is a phenotypically complex disorder believed to arise from multiple genes exerting small effects, gene-by-gene interactions, gene-by-environment interactions, and a host of environmental factors and risk-conferring behaviors. As a consequence of the multifactorial nature of drug abuse, the phenotypic expression is highly heterogeneous - in terms of risk factors, gender distribution and expression, comorbid conditions, types and number of drugs of abuse, symptom expression, severity, course, age of onset, and rate of progression from initial drug use to persistent use, abuse, and dependence. Although contemporary theoretical models depict drug abuse as a heterogeneous and dynamic construct, this information has been comparatively less integrated into quantitative approaches to the study of drug abuse. Ultimately, the identification of specific genes and related mechanisms, underlying physiologic systems, and other etiological processes hinges on precise and specific phenotypic definitions and greater understanding of how such phenotypes influence and are shaped by environmental factors, developmental course, and individual characteristics. It is hoped that the Heterogeneity of Drug Abuse Meeting will inform these issues and guide future research towards greater clarity of the drug abuse phenotype(s). 

Invited Participants

James Anthony, Ph.D.
Kathlee, K. Bucholz, Ph.D.
Duncan B. Clark, M.D., Ph.D.
Lindon J. Eaves, Ph.D.
Deborah Hasin, Ph.D.
James J. Hudziak, M.D.
Douglas R. Langbehn, M.D., Ph.D.
James L. Langenbucher, Ph.D.
Kathleen Merikangas, Ph.D.
Bengt O. Muthen, Ph.D.
Robert J. Pandina, Ph.D.
John P. Rice, Ph.D.
Michael C. Stallings, Ph.D.
Ming Tsuang, M.D., Ph.D.

Meeting Outcome

Highlights of key issues appear below.

• Reliance on DSM as a conglomerate clinical tool can overlook important features of the disorder.
• Empirical research on current and past DSM versions can inform subsequent versions.
• The association between abuse and dependence is not fully understood, and may vary by drug of abuse.
• The process of identifying severity phenotypes may differ across drugs of abuse.
• Psychiatric comorbidity is a critical feature of the phenotype, yet the issue of confounding versus intermediary factor is poorly understood.
• Endophenotypes are intriguing, yet their systems of measurement vary by discipline.
• Definitions of the phenotype should consider risk history in addition to current manifestation.
• Future studies should concern gene and environmental interactions.
• To date, molecular genetic studies of drug abuse have been difficult to replicate.
• The concept of the gene state is evolving. One aspect involves moving towards a dynamic model of genes, as human variation involves how genes interact with the environment, and how this process changes over time.
• The frontier of statistical analyses is expanding. Success requires that drug abuse researchers work cooperatively with methodologists and statisticians.
• Heterogeneity can be efficiently captured by categorical and continuous latent variables. Promising techniques are severity latent class modeling, growth mixture modeling, and hybrid models.
• Cross-cultural research is needed.
• Research on developmental, dynamic phenotypes is lacking.
• Large, longitudinal studies are exceptionally valuable for investigating drug abuse heterogeneity, and offer unique opportunities for nesting novel approaches.

Expected Follow-up

Information generated by this science meeting will be used to inform future initiatives designed to support research that will better describe, discriminate, and predict the nature and course of drug use disorders so as to offer more precise phenotypic indicators of underlying genetic and environmental risk.

Resulting Publications

Information generated by this meeting will be disseminated in a Special Issue of an appropriate peer-reviewed journal.