Subtypes of major depression in substance dependence.

Major depressive disorder (MDD) and substance dependence (SD) are highly prevalent in the general population and frequently co-occur, both in clinical samples [1–4] and the general population [5–10]. Explanations for the high rate of mood symptoms among individuals with SD include the presence of an independent mood disorder with concomitant substance use, secondary mood symptoms induced by protracted intoxication or withdrawal, or a combination of independent and substance-induced mood symptoms. The DSM-IV [11] stipulates that a mood disorder can be considered independent if the signs and symptoms of the disorder predate the onset of substance use, exceed that attributable to substance use alone, or persist for more than four weeks beyond the period of acute substance intoxication or withdrawal. Although patients with mood symptoms and substance misuse should be carefully interviewed to establish the chronology of signs and symptoms of the two disorders [12,13], it is often difficult to obtain this information reliably, particularly at the earliest ages of onset, due to frequent periods of intoxication and possible cognitive impairment from protracted substance misuse. The use of temporal markers, e.g., major life events, and the availability of knowledgeable collateral informants may help to establish a valid psychiatric history in substance-abusing patients with affective symptoms [14]. However, studies that have systematically analyzed the sociodemographic, psychiatric and substance-related features of independent or substance-induced depressive episodes have yielded conflicting results concerning the extent of psychopathology in patients with independent or substance-induced depression [12, 15–19]. Some studies show that individuals with co-morbid depression and SD have a worse course of psychiatric illness [17–19], though in other studies independent depression among alcoholics was associated with more suicide attempts [15] or the psychiatric symptom burden during the worst episode of substance-induced depression was similar to the burden of independent depression [16]. Two studies from the Collaborative Study on the Genetics of Alcoholism (COGA) underscore the clinical utility of subtyping depression among individuals with SD [15,16]. In an initial study of 2,945 alcoholics, the lifetime prevalence of an independent major depressive episode (MDE) was 15.2%, similar to that in the general population, and 26.4% of participants endorsed a lifetime diagnosis of substance-induced MDE [15]. Alcoholics with independent MDE were more likely than those with substance-induced MDE to be female, European-American, and married. They were also more likely to have attempted suicide and to have a family history of independent mood disorders, but were less likely to have co-morbid drug abuse or to have received treatment for an alcohol use disorder [15]. Recently, Schuckit et al. [16] reported findings from a second COGA sample of 2,548 subjects that overlapped partly with the earlier study sample. Individuals with substance-induced depression were more likely to be male, probands, from alcohol dependence families, and to have an alcohol use disorder, antisocial personality disorder (ASPD), and more illicit drug use disorders. In contrast, subjects with independent depression were more likely to be older, female and white; to have co-morbid ASPD and a family history of primary depression; and to smoke at least 10 cigarettes per day. To characterize more fully the subtypes of MDE, we conducted a secondary analysis of data obtained using a semi-structured instrument designed to assess SD and co-morbid psychiatric disorders in a large sample of subjects with SD [20–24]. Subjects were divided into four groups: those with no lifetime history of MDE (“no MDE”), those with only a lifetime diagnosis of one or more episodes of MDE not attributable to substance use (“independent MDE”), those with only a lifetime history of one or more episodes of MDE in the context of substance use (“substance-induced MDE”), and those endorsing a lifetime history of both independent and substance-induced MDEs (“both types of MDE”). Analyses compared these groups on a variety of sociodemographic and clinical measures, to identify risk factors for the development of MDE in the context of SD and the features that differentiate the MDE subtypes. The predictors were chosen based on their prior association with either depression or SD [7,10], or to ensure that they did not confound the analysis of the MDE subtypes.