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NEUROSCIENCE OF PSYCHOACTIVE SUBSTANCE USE AND DEPENDENCE

symptomatic manifestations of the same underlying neuropathologies? These
are topics of considerable recent interest and research at both the clinical
and preclinical levels.
The purpose of this chapter is to present several hypotheses that may
explain the high degree of comorbidity between mental illness and substance
dependence. Emphasis will be placed on the comorbidity of schizophrenia
and depression with illicit drug dependence, tobacco smoking and alcohol
use, with particular reference to dependence on psychostimulants and
tobacco. Schizophrenia and depression were selected on the basis of high
societal and economic costs of these two disorders (Rupp & Keith, 1993;
Mauskopf et al., 1999; Meltzer, 1999; Wong & Licinio, 2001), and on the fact
that they appear to be highly associated with substance use disorders.
Generally, research findings over the past decade will be highlighted, although
older findings will also be referred to where relevant. Finally, directions for
future clinical and preclinical research will be discussed, as well as
considerations for treatment and prevention of substance use disorders.
It is also important to recognize that the effects of many psychoactive
substances can produce psychiatric-like syndromes. For example, as
discussed in Chapter 4, amphetamines and cocaine can induce psychotic-
like symptoms, and some drugs can produce hallucinations, which are an
aspect of some psychoses. Furthermore, psychoactive substances alter mood
states, producing either euphoria and feelings of well-being, or inducing
depression, especially during substance withdrawal. Psychoactive substances
can alter cognitive functioning, which is also a core feature of many mental
illnesses. These factors all suggest common neurobiological mechanisms to
both mental illnesses and substance dependence.
Research into the comorbidity of mental illness with substance dependence
will provide new insights into both disorders, and may provide improved
treatment and prevention strategies for both disorders independently, and
when they co-occur. Research in developing countries, among the general
population, and among people seeking or receiving treatment is also of extreme
importance for better understaning the relationship between biological and
environmental factors related to comorbidity.

Hypotheses that may explain the observed comorbidity
As discussed above, the high comorbidity between any mental illness and
substance dependence in humans in certain populations (Rounsaville et
al., 1982; Robins et al., 1984; Rounsaville et al., 1987; Robins & Regier, 1991;
Rounsaville et al., 1991; Kessler et al., 1994; Kosten, Markou & Koob, 1998)
is likely to reflect similarities in the neurobiology of these psychiatric
disorders.
Four neurobiological hypotheses can be postulated to explain this
comorbidity.

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