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NEUROSCIENCE OF PSYCHOACTIVE SUBSTANCE USE AND DEPENDENCE

Alcohol use and schizophrenia
Similar links are also observed between schizophrenia and alcohol
dependence as those between schizophrenia and nicotine or psychostimulant
use. As reported in one large study, an individual with alcohol dependence is
3.3 times more likely to also have schizophrenia, while a patient with
schizophrenia is 3.8 times more likely to exhibit alcohol dependence than in
the general population (Regier et al., 1990). Nonetheless, it is not clear what
the factors leading to this comorbidity are, and few hypotheses have been
advanced to explain this association.

Hypotheses to explain the high rate of alcohol use among patients with
schizophrenia
As with other psychoactive substances, it has been suggested that alcohol
use may be self-medication for symptoms of schizophrenia; however, the
available data do not support this self-medication hypothesis. Most clinical
studies, patient reports and anecdotal clinical observations indicate that
excessive use of alcohol leads to a clear exacerbation of schizophrenia
symptomatology (Soyka, 1994; Tsuang & Lohr 1994; Pristach & Smith, 1996;
Gerding et al., 1999). Furthermore, it appears that approximately 30% of
comorbid patients show harmful use of alcohol before the first signs of
schizophrenia emerge (Hambrecht & Hafner, 1996). In terms of schizophrenia
and alcohol dependence, the hypothesis that best explains the available data
is that alcohol dependence and schizophrenia are different symptomatic
expressions of the same underlying neurobiological abnormalities, with
alcohol use exacerbating symptoms of schizophrenia. The precise nature of
the neurobiological basis of this association is not known, but more research
will help to clarify the epidemiology, etiology and treatment of schizophrenia
and alcohol dependence. Hypotheses regarding the neurobiological basis of
this association are discussed below.

Neurobiological interactions between schizophrenia and the effects of
psychoactive substances
There are several brain systems where schizophrenia-related abnormalities
and the effects of psychoactive substances may interact to lead to the high
degree of comorbidity of schizophrenia with substance dependence. One of
these systems is the mesolimbic dopamine system together with its efferent
and afferent connections to other brain sites and systems. This system is
comprised of dopaminergic projections from an area in the midbrain, called
the ventral tegmental area (VTA), to the forebrain region of the nucleus
accumbens (also called the ventral striatum) (Mogenson et al., 1980) (see
Chapter 2). There is considerable evidence that increased activity of the
mesolimbic dopamine system is critically involved in mediating the

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