TY - JOUR
T1 - The serotonin transporter gene locus in late-life major depressive disorder
AU - Seripa, Davide
AU - Panza, Francesco
AU - D'Onofrio, Grazia
AU - Paroni, Giulia
AU - Bizzarro, Alessandra
AU - Fontana, Andrea
AU - Paris, Francesco
AU - Cascavilla, Leandro
AU - Copetti, Massimiliano
AU - Masullo, Carlo
AU - Pilotto, Alberto
PY - 2013/1
Y1 - 2013/1
N2 - 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.
AB - 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.
KW - Late-life MDD
KW - Major depression
KW - Serotonin
KW - Serotonin transporter
KW - SLC6A4
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U2 - 10.1016/j.jagp.2012.10.012
DO - 10.1016/j.jagp.2012.10.012
M3 - Article
C2 - 23290204
VL - 21
SP - 67
EP - 77
JO - American Journal of Geriatric Psychiatry
JF - American Journal of Geriatric Psychiatry
SN - 1064-7481
IS - 1
ER -