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NEUROSCIENCE OF PSYCHOACTIVE SUBSTANCE USE AND DEPENDENCE

2002). However for people with alcohol dependence with inactive ALDH2,
but not for those with active ALDH2, there was an association with the 5HT1B
receptor variant (G861GC), suggesting its involvement in the development
of some type of alcohol dependence (Hasegawa et al., 2002).

Serotonin Receptor 2A. Data suggest that there may be a relatively small
genetic variability in the HTR2A receptor gene involved in the development
of alcohol dependence (Nakamura et al., 1999; Hwu & Chen, 2000; Preuss et
al., 2001; Hasegawa et al., 2002).

Serotonin Receptor 2C. There is no evidence of HTR2C allele association with
alcohol dependence (Lappalainen et al., 1999; Schuckit et al., 1999; Fehr et
al., 2000; Parsian & Cloninger, 2001).

Serotonin Receptor 5. There was no evidence of HTR 5 allele differences in a
Finnish study of people with alcohol dependence and controls (Iwata et al.,
1998).

Serotonin Receptor 7. The HTR 7 L279 variant was not significantly associated
with alcohol dependence or impulsivity, however it may be a predisposing
allele in a subgroup of people with alcohol dependence and multiple
behavioural problems (Pesonen et al., 1998).

Tryptophan Hydroxylase. Genetic variation in tryptophan hydroxylase (TPH)
could significantly alter serotonergic neurotransmission and thus alter the
risk for dependence.
No association of TPH alleles with smoking status has been found (Lerman
et al., 2001), however, individuals with a specific genotype start smoking at
an earlier age (Lerman et al, 2001). In addition, another study found an
association with smoking initiation but not with progression to nicotine
dependence (Sullivan et al., 2001). These data suggest that variation in the
production of serotonin may be involved in the etiology of smoking initiation.
A higher frequency of the TPH A allele was found in Japanese people with
alcohol dependence and histories of drinking-related antisocial behaviours
(Ishiguro et al., 1999) and in Finnish people with alcohol dependence who
were also criminal offenders (Nielsen et al., 1998). However, no association
was found between the TPH A allele and alcohol dependence without
personality disorders (Han et al., 1999b; Ishiguro et al., 1999; Fehr et al., 2001).

Serotonin transporter. The serotonin transporter (5-HTT) gene (SLC6A4) is a
plausible candidate gene for smoking and predisposition to alcohol
dependence because of its association with psychological traits relevant to
smoking and drinking behaviour. A specific polymorphism of this gene has
been associated with numerous psychiatric disorders (e.g. depression, anxiety
disorders, bipolar disorders and schizophrenia).

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