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6. CONCURRENT DISORDERS

1992; Sandyk, 1993; Ziedonis et al., 1994). Nicotine could help to decrease
these side-effects through its stimulatory effects on dopamine, and it could
also reduce them through its effects on acetylcholine, which acts in the basal
ganglia (see Chapter 2) and other brain areas to help coordinate movements.
However, the exact mechanism is not currently known. This will be discussed
in more detail at the end of this section.
The second hypothesis regarding tobacco dependence and schizophrenia
postulates that nicotine administration through tobacco smoking ameliorates
the sensory gating deficits and perhaps even more generalized cognitive
deficits (Dalack, Healy & Meador-Woodruff, 1998) that are characteristic of
patients with schizophrenia. (Freedman et al., 1997). Again, the exact
mechanisms responsible for this are not currently known, but the stimulatory
effects of nicotine on dopaminergic and cholinergic systems are strong
candidates.
The third hypothesis postulates that nicotine administration through
tobacco smoking ameliorates the negative symptoms of schizophrenia that
are most resistant to the majority of currently available antipsychotic
treatments (Marder, Wirshing & Van Putten, 1991; Dalack, Healy & Meador-
Woodruff, 1998; Jibson & Tandon, 1998; Moller, 1998). Schizophrenia is
characterized by the so-called positive and negative symptoms (American
Psychiatric Association, 1994). Positive symptoms reflect an excess or
distortion of normal functions, such as hallucinations, delusions and
disorganized thought and speech. Negative symptoms reflect a diminution
or loss of normal functions, such as loss of pleasure in normally pleasurable
activities, loss of motivation, reluctance to speak or impoverished speech,
and flattening of emotions. These symptoms appear to result from alterations
in reward and motivational processes associated with mesolimbic and
mesocortical dopamine. Accruing clinical evidence over the past decade
provides some support for the hypothesis that patients with schizophrenia
self-medicate negative symptoms with cigarette smoking (Marder, Wirshing
& Van Putten, 1991; Dalack, Healy & Meador-Woodruff, 1998; Jibson & Tandon,
1998; Moller, 1998). In a study of 182 patients with schizophrenia, heavy
smokers had significantly fewer negative symptoms than non-smokers with
schizophrenia (Ziedonis et al., 1994). Further, patients with negative
symptoms were less likely to quit smoking than other schizophrenia patients
who exhibited few negative symptoms, while no such relationship was shown
for positive symptoms and smoking cessation (Hall et al., 1995). Interestingly,
patients treated with atypical antipsychotic drugs such as clozapine,
risperidone and olanzapine, which are considered to be more effective against
the negative symptoms than traditional neuroleptic antipsychotic
medications such as haloperidol (Claghorn et al., 1987), reduced their
smoking by 25–30% compared with patients who received traditional typical
medications (George et al., 1995; McEvoy et al., 1995; McEvoy et al., 1999;
George et al., 2000). If indeed atypical antipsychotic drugs are more effective
against the negative symptoms than neuroleptic medications (Claghorn et

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