The serotonin transporter gene locus in late-life major depressive disorder

Davide Seripa, Francesco Panza, Grazia D'Onofrio, Giulia Paroni, Alessandra Bizzarro, Andrea Fontana, Francesco Paris, Leandro Cascavilla, Massimiliano Copetti, Carlo Masullo, Alberto Pilotto

Research output: Contribution to journalArticlepeer-review


Objective: Polymorphism C in the solute carrier family 6 (neurotransmitter transporter, serotonin), member 4 (SLC6A4) gene has been variously associated with major depressive disorder (MDD). To the best of our knowledge, no data were reported regarding a role of SLC6A4 in late-life MDD. The aim of this study was to explore the possible involvement of the SLC6A4 locus in patients with late-life MDD by means of a haplotype-tagged approach. Design: Case-control study. Setting: Older patients attending a geriatric unit. Participants: A total of 218 patients with late-life MDD (61 men and 157 women) age 65 to 92 years (76.29 ± 6.53 years) and 363 depression-free healthy subjects (156 men and 207 women) age 41 to 65 years (48.33 ± 5.94 years). Measurements: Genotyping and haplotype estimation of the three markers rs4795541, rs140701, and rs3813034 spanning a 39-kb block the SLC6A4 locus. Diagnoses of late-life MDD, mild cognitive impairment, Alzheimer disease, vascular dementia, and other dementing diseases were made using current clinical criteria. Results: No significant differences were observed in allele or genotype distribution for the three SLC6A4 markers across the study groups. Because the comparison group could not be matched for age, a sensitivity analysis for the misclassification of controls was performed according to different scenarios. For each simulated scenario, the same nonsignificant result was observed. However, the results are limited to late-life MDD that is specifically not associated with cognitive impairment, and there was limited power for detecting very small effect sizes. Conclusions: Our findings suggested that the SLC6A4 locus play a minor role, if any, in the pathogenesis of late-life MDD. Also, tempering our conclusions, we were unable to account for population stratification, recurrence or chronicity of depression, nor the influence of coexisting medical, cognitive, and psychosocial stressors.

Original languageEnglish
Pages (from-to)67-77
Number of pages11
JournalAmerican Journal of Geriatric Psychiatry
Issue number1
Publication statusPublished - Jan 2013


  • Late-life MDD
  • Major depression
  • Serotonin
  • Serotonin transporter
  • SLC6A4

ASJC Scopus subject areas

  • Psychiatry and Mental health
  • Geriatrics and Gerontology


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