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6. CONCURRENT DISORDERS

1. Psychoactive substance use disorders and other mental illnesses are
different symptomatic expressions of the same pre-existing
neurobiological abnormalities.
2. Repeated substance administration leads – through possibly aberrant or
excessive neuroadaptations to acute substance effects – to biological
changes that have some common elements with the abnormalities
mediating other mental illnesses, such as depression.
3. Psychoactive substance use may reflect self-medication intended to reverse
some of the abnormalities associated with mental illness; these
abnormalities may have existed prior to substance use or may have been
caused by the substance use. This hypothesis is related closely to, and is
not independent of, the second hypothesis.
4. Substance dependence and other mental illnesses have different and
independent neurobiological mechanisms, and the observed comorbidity
is simply observed by chance. However, this hypothesis is unlikely,
considering the extensive epidemiological and neurobiological data
indicating the contrary.

There are also other possible non-neurobiological reasons for this
comorbidity, such as a common environmental factor; however, a detailed
discussion of these factors is beyond the scope of this report, which focuses
on neurobiological mechanisms. There is also strong neurobiological and
genetic evidence that at least some of the association has a neurobiological
basis, as discussed below.
It should be emphasized that the first three hypotheses are not necessarily
mutually exclusive: the first hypothesis may be true for one mental disorder
and one substance, while the second and third hypotheses may be true for
another disorder and another substance. Indeed, current neurobiological and
clinical data are consistent with the notion that different hypotheses may be
true for different mental disorders, as discussed below. Furthermore, the first
three hypotheses may be true in a single patient population. That is, a
particular mental illness and substance use disorder originally may be
symptomatic expressions of the same underlying neurobiological
abnormalities; while at the same time substance use may temporarily relieve
some symptoms (i.e. through self-medication), although in the long term the
same substance use may worsen the overall severity of the mental disorder.
These hypotheses will be explored in the context of schizophrenia and
depression.

Schizophrenia
Tobacco smoking and schizophrenia

There is a high degree of comorbidity of schizophrenia with tobacco smoking.
Where it has been studied, the prevalence of smoking among individuals with

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