Is there heterogeneity among syndromes of substance use disorder for illicit drugs?

The use of DSM criteria to evaluate liability to substance use disorders (SUDs) and to identify SUD phenotypes may not provide the sensitivity required to identify genes associated with vulnerability to SUDs. The purpose of this study is to evaluate a number of basic aspects of substance use that may be more proximal than full SUDs to risk genes, some of which may thus have greater potential utility as phenotypes in subsequent molecular genetic analyses. In this paper we present results from the first stage of our planned analyses, focusing on how individual symptoms of abuse and dependence may be used to create alternate phenotypes for SUDs. Specifically, we used factor analysis and biometrical modeling on each symptom of illicit substance abuse and dependence within different types of substances, and compared and contrasted factor patterns and heritabilities across the different substances. These analyses were carried out using a population-based sample of 3372 male-male twin pairs from the Vietnam Era Twin Registry who participated in the Harvard Twin Study of Substance Abuse. We obtained extensive data from these participants on substance use and SUDs via telephone interview in 1992, including data on the illicit substances: opiates, cocaine, cannabis, sedatives, stimulants, and psychedelics. The results indicate that: A) although a one-factor model assuming a single underlying liability for abuse and dependence symptoms and behaviors can be rejected for most substances, there is no uniform support for a two-factor model differentiating between abuse versus dependence; B) patterns of symptoms or behaviors reported by substance users vary across substances; C) not all symptoms or behaviors contribute equally to the presentation of an SUD; and D) the heritability of symptoms or behaviors of substance users varies both within and between substances. These results represent important first steps in facilitating the search for SUD-risk genes in subsequent high-throughput molecular genetic analyses by providing alternate phenotypes that may have both optimal validity and increased heritability.