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NEUROSCIENCE OF PSYCHOACTIVE SUBSTANCE USE AND DEPENDENCE

dependence are significant considering that 80% of people with alcohol
dependence have symptoms of depression, one-third of whom meet the
criteria for a major depressive episode (Schuckit, 1985; Regier et al., 1990;
Roy et al., 1991; Kessler et al., 1996).
In summary, epidemiological and clinical evidence suggests that
depression and alcohol dependence are associated. Nevertheless, the
majority of these clinical and epidemiological studies were unable to
determine whether the depression was primary (i.e. appearing before the
onset of alcohol dependence) or secondary (i.e. appearing after the initiation
of alcohol use) and thus potentially alcohol-induced. Such a distinction is
critical in establishing whether alcohol dependence and depression are
different symptomatic expressions of the same neurobiological
abnormalities, or whether the depression is alcohol-induced, and how self-
medication may lead to the observed comorbidity. A recent study designed
to examine this issue suggested that alcohol dependence and depression were
divided nearly evenly between primary and secondary disorders (Compton
et al., 2000a). Other data suggest that alcohol dependence leads to depression
(i.e. that depression is secondary) and that once the alcohol use ceases then
the symptoms of depression remit (Schuckit, 1994).
Considering the above summarized data and the various hypotheses put
forward that attempt to explain the comorbidity of psychiatric disorders with
substance use, in the case of alcohol and depression it appears that there is
some familiar aggregation that would support the first hypothesis of common
neurobiological substrates with different symptomatic expressions, although
there is much data that are not supportive of this genetic linkage. A self-
medication hypothesis is not supported because alcohol does not improve
symptoms of depression (Hendrie, Sairally & Starkey, 1998). In fact, there are
ample data to suggest that excessive alcohol use leads to depression (Schuckit,
1994), supporting the hypothesis of drug-induced depression that explains
the high degree of comorbidity observed between alcohol dependence and
depression.

Neurobiological interactions between depression and the effects
of psychoactive substances
Substance withdrawal, one of the syndromes that may be associated with
substance dependence (Himmelsbach, 1943; Wikler, 1973; Koob & LeMoal,
2001) (see Chapter 1), exhibits similarities with depression. Cessation of
chronic drug use induces the behavioural and physical expression of the
neuroadaptations that develop as a response to drug exposure. These are
expressed as withdrawal syndromes that are distinct for each class of
psychoactive substances (Koob et al., 1993; Markou, Kosten & Koob, 1998)
(see Chapter 4). Interestingly, however, depression is a common symptom of
withdrawal from substances from a variety of pharmacological classes
including psychostimulants (Gawin & Kleber, 1986; Weddington et al., 1990;

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