Association between CYP2C19 polymorphism and depressive symptoms

Abstract

Cytochrome P450 2C19 (CYP2C19) is a polymorphic enzyme active in the metabolism of for example diazepam and the antidepressants sertraline, citalopram, and escitalopram, whereby allelic variants cause increased (CYP2C19*17) or abolished (mainly CYP2C19*2) enzymatic activity in drug metabolism. In light of the importance of CYP2C19 in the metabolism of psychoactive substances we considered it of interest to investigate the relationship between CYP2C19 polymorphisms and depressive symptoms in 1,472 subjects of European ancestry (45-98 years old) from the Swedish Twin Registry. Depressive symptoms were assessed using the Center of Epidemiologic Studies Depression (CES-D) scale. We found that poor metabolizers lacking CYP2C19 activity (PMs, CYP2C19*2/*2) had significantly lower levels of depressive symptoms than extensive metabolizers (EMs, CYP2C19*1/*1) (P = 0.0018). The size of this difference was in the same range as that between subjects reported taking antidepressants (n = 104) and those without antidepressant treatment (P < 0.0001). Our results suggest for the first time that the CYP2C19 polymorphism might be of importance for depressive symptoms, as here shown for older European adults.

Genetic variability of drug-metabolizing enzymes: the dual impact on psychiatric therapy and regulation of brain function

“…155,156 Of possible significance to this association are data suggesting increased frequency of the CYP2D6 UM phenotype in depression more generally. 158 In a recent study of a large Swedish twins cohort, Sim et al 159 identified an association of the CYP2C19 functional polymorphism with depressive symptoms, more marked in males. The sexual dimorphism observed in this study is consistent with its dimorphic sexual expression in a humanized mice model.…”

Polymorphic Expression of Cyp2C19 and Cyp2D6 in the Developing and Adult Human Brain Causing Variability in Cognition, Risk for Depression and Suicide: The Search for the Endogenous Substrates

“…Twins carrying allelic variants causing high activity of the enzyme (CYP2C19*1) showed more depressive symptoms than the subjects carrying a defective allelic variant (CYP2C19*2), based on their significantly lower T1 scores in the center for epidemiologic studies depression (CES-D) scale and lower scores on the subscales depressed mood, psychomotor retardation, and somatic complaints, compared with extensive metabolizers [18].…”

Direct inhibition of retinoic acid catabolism by fluoxetine

“…While most of these isozymes are known from their involvement in hepatic xenobiotic metabolism, it is important to note that some of them are also expressed in specific brain regions (Ghosh et al 2011;Voirol et al 2000;Gilbert et al 2003). Interestingly, functionally relevant polymorphisms of RA-degrading CYP450 isozymes have recently been linked with major depression and response to antidepressant treatment (Sim et al 2010;Ruano et al 2011). Most interestingly in this context is a study recently published by Persson and colleagues (Persson et al 2014), demonstrating hippocampal atrophy and depressive-like symptoms in a mouse model expressing the human CYP2C19 gene.…”