Association between CYP2C19 polymorphism and depressive symptoms

Am J Med Genet B Neuropsychiatr Genet. 2010 Sep;153B(6):1160-6. doi: 10.1002/ajmg.b.31081.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Twin Study

MeSH terms

  • Aged
  • Aged, 80 and over
  • Aging / genetics
  • Aging / psychology
  • Antidepressive Agents / therapeutic use
  • Aryl Hydrocarbon Hydroxylases / genetics*
  • Cytochrome P-450 CYP2C19
  • Depression / diagnosis
  • Depression / drug therapy
  • Depression / genetics*
  • European Continental Ancestry Group / genetics
  • Female
  • Humans
  • Male
  • Middle Aged
  • Polymorphism, Genetic*
  • Severity of Illness Index
  • Sweden

Substances

  • Antidepressive Agents
  • Aryl Hydrocarbon Hydroxylases
  • CYP2C19 protein, human
  • Cytochrome P-450 CYP2C19