title: The 5-HTTLPR s/s genotype at the serotonin transporter gene (SLC6A4) increases the risk for depression in a large cohort of primary care attendees: the PREDICT-gene study.
abstract: Previous reports and meta-analyses have yielded inconclusive results as to whether the s/s genotype at the 5-HTTLPR serotonin transporter polymorphism confers increased risk for depression. We tested the association between s/s genotype and depression in a large cohort (n = 737) of Spanish primary care consecutive attendees participating in a European study on predictors for depression in primary care (PREDICT study). Participants were administered the Composite International Diagnostic Interview (CIDI) depression subscale allowing diagnoses using ICD-10 criteria for depressive episodes. Participants were genotyped to establish 5HTTLPR genotype. Both univariable and multivariable associations between the s/s genotype and depression were tested twice using two different depressive outcomes (ICD-10 depressive episode and ICD-10 severe depressive episode). We found an association between the s/s genotype and both depressive outcomes that was independent of age, sex, family history of psychological problems among first degree relatives and presence of comorbid generalized anxiety disorder. When comparing s/s homozygous versus the rest, the adjusted odds ratio for any ICD-10 depressive episode and for severe ICD-10 depressive episode were 1.50 (95% CI: 1.0-2.2; P = 0.045) and 1.79 (95% CI: 1.1-2.8; P = 0.016), respectively. The association was significantly stronger with increasing severity of depression (chi2 for linear association=6.1; P = 0.013) suggesting a dose-dependent relationship. Our results are consistent with previous reports suggesting a small but independent effect by the s/s 5-HTTLPR genotype increasing the risk for depression.
authors.affiliation: Departamento de Medicina Legal, Toxicología y Psiquiatría, Facultad de Medicina, Universidad de Granada, Granada, Spain. jacb@ugr.es
authors.forename: Jorge A
authors.initials: JA
authors.lastname: Cervilla
authors.forename: Margarita
authors.initials: M
authors.lastname: Rivera
authors.forename: Esther
authors.initials: E
authors.lastname: Molina
authors.forename: Francisco
authors.initials: F
authors.lastname: Torres-González
authors.forename: Juan A
authors.initials: JA
authors.lastname: Bellón
authors.forename: Berta
authors.initials: B
authors.lastname: Moreno
authors.forename: Juan
authors.initials: J
authors.lastname: de Dios Luna
authors.forename: José A
authors.initials: JA
authors.lastname: Lorente
authors.forename: Yolanda
authors.initials: Y
authors.lastname: de Diego-Otero
authors.forename: Michael
authors.initials: M
authors.lastname: King
authors.forename: Irwin
authors.initials: I
authors.lastname: Nazareth
authors.forename: Blanca
authors.initials: B
authors.lastname: Gutiérrez
mesh_terms: D000328:Adult; D000368:Aged; D017931:DNA Primers; D003863:Depression / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D008957:Models, Genetic; D016017:Odds Ratio; D011110:Polymorphism, Genetic; D050486:Serotonin Plasma Membrane Transport Proteins / Q000235:genetics*; D013030:Spain
chemical_list: D017931:DNA Primers; C493230:SLC6A4 protein, human; D050486:Serotonin Plasma Membrane Transport Proteins