Page 155 - Pagetit

NEUROSCIENCE OF PSYCHOACTIVE SUBSTANCE USE AND DEPENDENCE

significant evidence of linkage to the serotonin receptor 1B G861C (see below);
in a southwestern American Indian tribe, significant sib-pair linkage to
chromosome 6 was also seen (Lappalainen et al., 1998). The strongest
suggestions of linkage with susceptibility loci for alcohol dependence are on
chromosomes 1 and 7, and more modest evidence for a locus on chromo-
some 2 (Reich et al., 1998). The best evidence for linkage has been seen on
chromosome 11p (D11S1984), in close proximity to the dopamine receptor D4
(DRD4) and tyrosine hydroxylase (TH) genes (Long et al., 1998).

Candidate genes for alcohol dependence
Aldehyde dehydrogenase
Alcohol is metabolized to acetaldehyde, which in turn is metabolized to
acetate before elimination from the body. The mitochondrial form of aldehyde
dehydrogenase (ALDH2) is the enzyme primarily responsible for the
metabolism of acetaldehyde to acetate (for reviews of ethanol metabolism
and dependence see Agarwal (2001); Li (2000); Ramchandani et al. (2001).
ALDH2 deficiency leads to an aversive response to alcohol due to elevated
levels of acetaldehyde, resulting in increased hangover symptoms (Wall et
al., 2000) and the alcohol flushing response, or alcohol sensitivity (Box 5.2)
(Tanaka et al., 1997; Li, 2000). ALDH2 is found on chromosome 4p which has
been linked to alcohol dependence in Asians and Europeans.

BOX 5.2
Alcohol flushing response or “alcohol sensitivity”

Some individuals show a cluster of symptoms following alcohol consumption,
which have been related to elevated acetaldehyde levels. These elevations in
acetaldehyde are due to alterations in ethanol metabolism, and can lead to the
following symptoms:
– vasodilation, increased skin temperature, feeling of hotness, facial flushing
– increased heart rate and respiration
– decreased blood pressure
–bronchoconstriction
– nausea and headache
– euphoria or aversive reactions.
The neurotransmitters involved in this response are catecholamines, opioids,
prostaglandins, histamine and bradykinin.
Source: Eriksson, 2001.

134

Chapter_5 134 19.1.2004, 11:45