title: The serotonin transporter gene locus in late-life major depressive disorder.
abstract: 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.
  
  
  METHODS
  Case-control study.
  
  
  METHODS
  Older patients attending a geriatric unit.
  
  
  METHODS
  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).
  
  
  METHODS
  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.
authors.affiliation: Geriatric Unit & Gerontology-Geriatric Research Laboratory, Department of Medical Sciences, Institute of Care and Scientific Research Casa Sollievo della Sofferenza, San Giovanni Rotondo, Foggia, Italy. dseripa@operapadrepio.it
authors.forename: Davide
authors.initials: D
authors.lastname: Seripa
authors.forename: Francesco
authors.initials: F
authors.lastname: Panza
authors.forename: Grazia
authors.initials: G
authors.lastname: D'Onofrio
authors.forename: Giulia
authors.initials: G
authors.lastname: Paroni
authors.forename: Alessandra
authors.initials: A
authors.lastname: Bizzarro
authors.forename: Andrea
authors.initials: A
authors.lastname: Fontana
authors.forename: Francesco
authors.initials: F
authors.lastname: Paris
authors.forename: Leandro
authors.initials: L
authors.lastname: Cascavilla
authors.forename: Massimiliano
authors.initials: M
authors.lastname: Copetti
authors.forename: Carlo
authors.initials: C
authors.lastname: Masullo
authors.forename: Alberto
authors.initials: A
authors.lastname: Pilotto
mesh_terms: D000328:Adult; D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D000544:Alzheimer Disease / Q000235:genetics; D016022:Case-Control Studies; D060825:Cognitive Dysfunction / Q000235:genetics; D003704:Dementia / Q000235:genetics; D015140:Dementia, Vascular; D003865:Major Depressive Disorder / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic / Q000235:genetics; D050486:Serotonin Plasma Membrane Transport Proteins / Q000235:genetics*
chemical_list: C493230:SLC6A4 protein, human; D050486:Serotonin Plasma Membrane Transport Proteins