title: 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.
authors.affiliation: Section of Pharmacogenetics, Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden. sarah.sim@ki.se
authors.forename: Sarah C
authors.initials: SC
authors.lastname: Sim
authors.forename: Linn
authors.initials: L
authors.lastname: Nordin
authors.forename: Therese M-L
authors.initials: TM
authors.lastname: Andersson
authors.forename: Susanne
authors.initials: S
authors.lastname: Virding
authors.forename: Marita
authors.initials: M
authors.lastname: Olsson
authors.forename: Nancy L
authors.initials: NL
authors.lastname: Pedersen
authors.forename: Magnus
authors.initials: M
authors.lastname: Ingelman-Sundberg
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000235:genetics / Q000523:psychology; D000928:Antidepressive Agents / Q000627:therapeutic use; D001189:Aryl Hydrocarbon Hydroxylases / Q000235:genetics*; D065731:Cytochrome P-450 CYP2C19; D003863:Depression / Q000175:diagnosis / Q000188:drug therapy / Q000235:genetics*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D012720:Severity of Illness Index; D013548:Sweden; D044465:White People / Q000235:genetics
chemical_list: D000928:Antidepressive Agents; D001189:Aryl Hydrocarbon Hydroxylases; C045793:CYP2C19 protein, human; D065731:Cytochrome P-450 CYP2C19