OBJECTIVE: Polymorphism C in the solute carrier family 6 (neurotransmitter transporter, serotonin), member 4 (SLC6A4) gene has been variously associated with contrasting results with major depressive disorder (MDD). To the best of our knowledge, no data were reported regarding the locus SLC6A4 in late-life MDD. The aim of this study was to explore the possible involvement of the SLC6A4 locus in these patients 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 three investigated markers of 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. PMID: 22301456 [PubMed - as supplied by publisher]
Masullo, C., The serotonin transporter gene locus in late-life major depressive disorder, <<AMERICAN JOURNAL OF GERIATRIC PSYCHIATRY>>, 2013; 21 (1): 67-77. [doi:10.1016/j.jagp.2012.10.012] [http://hdl.handle.net/10807/8167]
The serotonin transporter gene locus in late-life major depressive disorder
Masullo, Carlo
2013
Abstract
OBJECTIVE: Polymorphism C in the solute carrier family 6 (neurotransmitter transporter, serotonin), member 4 (SLC6A4) gene has been variously associated with contrasting results with major depressive disorder (MDD). To the best of our knowledge, no data were reported regarding the locus SLC6A4 in late-life MDD. The aim of this study was to explore the possible involvement of the SLC6A4 locus in these patients 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 three investigated markers of 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. PMID: 22301456 [PubMed - as supplied by publisher]
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