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Influence of Serotonin Transporter Gene Polymorphisms and Adverse Life Events on Depressive Symptoms in the Elderly: A Population-Based Study.

ABSTRACT: Depression is common in the elderly. The role of genetic and environmental factors in modulating depressive symptoms is not clear.We evaluated the influence of serotonin transporter gene polymorphisms and recent adverse life events on depressive symptoms in an elderly Italian population. We used data from "InveCe.Ab", a population-based study of 1321 subjects aged 70-74 years. We used the 15-item Geriatric Depression Scale (GDS) to assess depressive symptoms-a GDS score ≥5 points (GDS≥5) indicated the presence of clinically relevant symptoms-and performed 5-HTTLPR and rs25531 genotyping to obtain the triallelic polymorphism of the serotonin transporter. We used the Geriatric Adverse Life Events Scale to measure adverse life events, and logistic regression models to evaluate the role of genotype and recent adverse life events in depressive symptoms, controlling for potential confounders and independent predictors.Two hundred subjects (15.76%) had a GDS≥5. The 5-HTTLPR triallelic polymorphism was significantly associated with GDS≥5. Only S'S' carriers showed an increased risk of depressive symptoms (ORadj = 1.81, p = .022); one extra adverse life event increased this risk by 14% (p = .061) independently of genotype. Other factors significantly related to GDS≥5 were: female gender (ORadj = 2.49, p < .001), age (ORadj = 1.19, p = .007), a history of depression (ORadj = 4.73, p < .001), and comorbidity (ORadj = 1.23, p = .001). One extra adverse life event increased the risk of depressive symptoms by 57% (p = .005) only in the L'L' carriers, while antidepressant intake was directly related to GDS≥5 in the L'S' carriers (ORadj = 2.46, p = .036) and borderline significant in the S'S' carriers (ORadj = 2.41, p = .081).The S'S' genotype and recent exposure to adverse life events were independently associated with depressive symptoms. The S'S' genotype, compared with the environment, exerted a predominant effect on depressive symptoms, suggesting that it reduces the efficacy of antidepressant therapy. We conclude that genetics may be an important risk factor for depressive symptoms in late adulthood.

SUBMITTER: Davin A

PROVIDER: S-EPMC4658113 | biostudies-other | 2015

REPOSITORIES: biostudies-other

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Influence of Serotonin Transporter Gene Polymorphisms and Adverse Life Events on Depressive Symptoms in the Elderly: A Population-Based Study.

Davin Annalisa A Monti Maria Cristina MC Polito Letizia L Vaccaro Roberta R Abbondanza Simona S Gnesi Marco M Villani Simona S Guaita Antonio A

PloS one 20151123 11

<h4>Background</h4>Depression is common in the elderly. The role of genetic and environmental factors in modulating depressive symptoms is not clear.<h4>Methods</h4>We evaluated the influence of serotonin transporter gene polymorphisms and recent adverse life events on depressive symptoms in an elderly Italian population. We used data from "InveCe.Ab", a population-based study of 1321 subjects aged 70-74 years. We used the 15-item Geriatric Depression Scale (GDS) to assess depressive symptoms-a ...[more]

PMID: 26598970

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Project description:BackgroundThe serotonin transporter gene (5-HTT) is a key regulator of serotonergic neurotransmission and has been linked to various psychiatric disorders. Among the genetic variants, polymorphisms in the 5-HTT gene-linked polymorphic region (5-HTTLPR) and variable-number-of-tandem-repeat in the second intron (5-HTTVNTR) have functional consequences. However, their genetic impact on cortical oscillation remains unclear. This study examined the modulatory effects of 5-HTTLPR (L-allele carriers vs. non-carriers) and 5-HTTVNTR (10-repeat allele carriers vs. non-carriers) polymorphism on regional neural activity in a young female population.MethodsBlood samples and resting state eyes-closed electroencephalography (EEG) signals were collected from 195 healthy women and stratified into 2 sets of comparisons of 2 groups each: L-allele carriers (N=91) vs. non-carriers for 5-HTTLPR and 10-repeat allele carriers (N=25) vs. non-carriers for 5-HTTVNTR. The mean power of 18 electrodes across theta, alpha, beta, gamma, gamma1, and gamma2 frequencies was analyzed. Between-group statistics were performed by an independent t-test, and global trends of regional power were quantified by non-parametric analyses.ResultsAmong 5-HTTVNTR genotypes, 10-repeat allele carriers showed significantly low regional power at gamma frequencies across the brain. We noticed a consistent global trend that carriers with low transcription efficiency of 5-HTT possessed low regional powers, regardless of frequency bands. The non-parametric analyses confirmed this observation, with P values of 3.071×10-8 and 1.459×10-12 for 5-HTTLPR and 5-HTTVNTR, respectively.Conclusions and limitationsOur analyses showed that genotypes with low 5-HTT activity are associated with less local neural synchronization during relaxation. The implication with respect to genetic vulnerability of 5-HTT across a broad range of psychiatric disorders is discussed. Given the low frequency of 10-repeat allele of 5-HTTVNTR in our research sample, the possibility of false positive findings should also be considered.

Dataset Information

Influence of Serotonin Transporter Gene Polymorphisms and Adverse Life Events on Depressive Symptoms in the Elderly: A Population-Based Study.

Publications

Influence of Serotonin Transporter Gene Polymorphisms and Adverse Life Events on Depressive Symptoms in the Elderly: A Population-Based Study.

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