High
frequency of a CYP2C9 allele in major
depression
Cytochrome
P450 (CYP) enzymes, present in the liver but
also in other tissues such as the brain, play a
major role in drug metabolism. CYP2C9 is
involved in the metabolism of several
psychoactive compounds including fluoxetine and
amitryptyline and its activity is modulated by
the endogenous substrates, adrenaline and
serotonin. The frequency of CYP2C9 alleles among
patients with major depression has recently been
analysed.
The study included 70 patients suffering from a
major depressive disorder, 89 schizophrenic
patients and 138 healthy volunteers for
comparison. The CYP2C9 genotypes were determined
by the PCR method allowing identification of the
allelic variants CYP2C9*1, CYP2C9*2 and
CYP2C9*3. The frequency of the CYP2C9*3 allele
was higher in patients with major depression
than in schizophrenic patients or healthy
volunteers.
Alteration of monoaminergic neurotransmission is
involved in the pathophysiology of mood
disorders, and most antidepressant drugs act by
influencing serotonin in the brain. CYP2C9
enzyme has been suggested to be involved in the
metabolism of serotonin and would influence its
turnover. Thus, the data from this study suggest
that the high frequency of the CYP2C9*3 allele
in the depressed patients may be related to
modifications of serotonin metabolism resulting
from alterations of brain activity of the CYP2C9
enzyme. Llerena
et al., 2003 CYP2C9 gene and susceptibility to
major depressive
disorder. The
Pharmacogenomics Journal 3: 300-302.