CYP2C9 gene and susceptibility to major depressive disorder

Abstract

Alteration of monoaminergic neurotransmission has been implicated in the pathophysiology of mood disorders, and CYP2C9 enzyme activity has been shown to be modulated by serotonin in vitro. The present study was aimed at analysing the frequency of CYP2C9 alleles (*1, *2, *3) among patients suffering from major depressive disorder. In all, 70 such suffering psychiatric outpatients were studied. The CYP2C9 genotypes were determined by allelespecific PCR. The CYP2C9*3 allele frequency was higher (Po0.01) among the patients suffering from major depression than in a population of 89 schizophrenic patients (odds ratio¼3.3) and 138 healthy volunteers (odds ratio¼2.8). The results suggest that CYP2C9 genetic polymorphism may be related to a major depressive disorder due to an alteration in endogenous metabolism, although a linkage between CYP2C9 and some other gene related to depression cannot be ruled out.

Evaluation of the Relationship between Sex, Polymorphisms in CYP2C8 and CYP2C9, and Pharmacokinetics of Angiotensin Receptor Blockers

“…The frequencies of CYP2C9 and CYP2C8 alleles were similar to that found in other studies performed in Spanish subjects Llerena et al, 2003;López-Rodríguez et al, 2008).…”

Increased risk for major depression associated with the short allele of the serotonin transporter promoter region (5‐HTTLPR‐S) and the CYP2C9*3 allele

“…Additionally, we showed the influence of CYP2C9 genotypes on fluoxetine plasma concentration during steady-state conditions in MDD patients [8], and also the relationship between CYP2C9*3 allele and the risk of MDD [9]. In support of this result, previous findings showed that CYP2C9 is implicated in the metabolism of arachidonic acid [10] which has been related to depression [11].…”

Novel Drug Metabolism Indices for Pharmacogenetic Functional Status Based on Combinatory Genotyping of CYP2C9 , CYP2C19 and CYP2D6 Genes

“…This approach to CYP2C9 , CYP2C19 and CYP2D6 analyses provides clinically relevant overarching and drug-specific measures of liver enzyme metabolism capacity. Currently, we have chosen CYP2C9, CYP2C19 and CYP2D6 because they each play a critical role in psychotropic metabolism, they have been linked with endogenous metabolism of neuro-active substrates, they have each been associated with depressive symptoms or personality traits, and their allelic variations, interindividual differences and resulting enzyme functions are well-documented [17,19,45,46]. By contrast, other isoenzymes known to play a role in the metabolism of many psychotropics, for instance those coded by CYP1A2 and CYP3A4 have been excluded due to the lack of sufficient evidence at present to characterize interindividual variations and relevance to drug metabolism [47].…”

“…CYP2C9 is involved in the metabolism of multiple antidepressants, including fluoxetine and sertraline, for which its isoenzyme product constitutes a major metabolic pathway [10,13]. In addition, CYP2C9 activity may be modulated by endogenous substrates such as adrenaline and serotonin, and polymorphism of CYP2C9 has been associated with major depressive disorder [14,15]. CYP2C19 is involved in the metabolism of citalopram, escitalopram, sertraline and several tricyclic antidepressants [13,16].…”