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.
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.
Cervilla
Jorge A
JA
Departamento de Medicina Legal, Toxicología y Psiquiatría, Facultad de Medicina, Universidad de Granada, Granada, Spain. jacb@ugr.es
Rivera
Margarita
M
Molina
Esther
E
Torres-González
Francisco
F
Bellón
Juan A
JA
Moreno
Berta
B
de Dios Luna
Juan
J
Lorente
José A
JA
de Diego-Otero
Yolanda
Y
King
Michael
M
Nazareth
Irwin
I
Gutiérrez
Blanca
B
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
D017931:DNA Primers; C493230:SLC6A4 protein, human; D050486:Serotonin Plasma Membrane Transport Proteins