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NEUROSCIENCE OF PSYCHOACTIVE SUBSTANCE USE AND DEPENDENCE

schizophrenia is 2–3 times higher than that in the general population and
considerably higher than the prevalence among any other psychiatric
population (Masterson & O’Shea, 1984; Goff, Henderson & Amico, 1992; de
Leon et al., 1995; Hughes, 1996). Estimates indicate that in some countries,
more than 80–90% of patients with schizophrenia smoke, compared to 20–
30% in the general population (Masterson & O’Shea, 1984; Goff, Henderson
& Amico, 1992; de Leon et al., 1995; Hughes, 1996; Diwan et al., 1998).
Furthermore, individuals with schizophrenia are commonly heavy smokers
(defined as an individual smoking more than 1.5 packs of cigarettes per day),
smoke high-tar cigarettes (which are also high in nicotine content), and
extract more nicotine from cigarettes than smokers without schizophrenia
(Masterson & O’Shea, 1984; Hughes et al., 1986; Olincy, Young & Freedman,
1997).

Hypotheses to explain the high incidence of cigarette smoking among
patients with schizophrenia
The first hypothesis postulates that the high prevalence of cigarette smoking
among patients with schizophrenia reflects an attempt to reduce neuroleptic-
induced side-effects, such as Parkinsonism (difficulty initiating movements)
and tardive dyskinesias (explained below) (Jarvik, 1991). Schizophrenia is
associated with excessive activity in mesolimbic and mesocortical dopamine
pathways (see Chapter 2). Neuroleptic drugs used to treat schizophrenia block
dopamine receptors; however, they block both the affected pathways
(mesolimbic, mesocortical) as well as unaffected pathways such as the
nigrostriatal pathway which is involved in motor function. Therefore,
neuroleptic medications can lead to side-effects such as Parkinsonism. Long-
term use of neuroleptics can also lead to side-effects associated with the
changes in the brain that occur in response to long-term blockade of
dopamine receptors, such as an increase in the number or sensitivity of these
receptors. Such changes result in excessive involuntary movements, most
often in the mouth and facial area and extremities, called tardive dyskinesias.
Anecdotal evidence indicates that a small proportion of patients with
schizophrenia report that smoking helps reduce the side-effects of their
antipsychotic medication (Glynn & Sussman, 1990). Patients with
schizophrenia who are smokers are usually prescribed higher levels of
neuroleptic medication compared with nonsmokers (Goff, Henderson
& Amico, 1992; Ziedonis et al., 1994) because cigarette smoking increases the
metabolism of these medications. This change in metabolism is caused not
by nicotine but by the “tar” (polynuclear aromatic hydrocarbons) in cigarettes
that induces hepatic microsomal enzymes (Glassman, 1993; Ziedonis et al.,
1994). Results from studies on smoking and the side-effects of antipsychotic
medications have been mixed, with reports of increased side-effects,
decreased side-effects, and no change in side-effects (Binder et al., 1987; Yassa
et al., 1987; Decina et al., 1990; Menza et al., 1991; Goff, Henderson & Amico,

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