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

<div><p>Background</p><p>Depression is common in the elderly. The role of genetic and environmental factors in modulating depressive symptoms is not clear.</p><p>Methods</p><p>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.</p><p>Results</p><p>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 (OR_adj = 1.81, <i>p</i> = .022); one extra adverse life event increased this risk by 14% (<i>p</i> = .061) independently of genotype. Other factors significantly related to GDS≥5 were: female gender (OR_adj = 2.49, <i>p</i> < .001), age (OR_adj = 1.19, <i>p</i> = .007), a history of depression (OR_adj = 4.73, <i>p</i> < .001), and comorbidity (OR_adj = 1.23, <i>p</i> = .001). One extra adverse life event increased the risk of depressive symptoms by 57% (<i>p</i> = .005) only in the L′L′ carriers, while antidepressant intake was directly related to GDS≥5 in the L′S′ carriers (OR_adj = 2.46, <i>p</i> = .036) and borderline significant in the S′S′ carriers (OR_adj = 2.41, <i>p</i> = .081).</p><p>Discussion</p><p>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.</p></div

Multivariable GLMMs results.

<p>Multivariable GLMMs results.</p

Scree plots of the principal component analysis (with and without copper).

<p>Scree plots of the principal component analysis (with and without copper).</p

The 25 municipalities forming the study area, the sampling sites and the ore bodies.

<p>The 25 municipalities forming the study area, the sampling sites and the ore bodies.</p

Results of principal component analysis (PCA).

<p>Results of principal component analysis (PCA).</p

Mutually adjusted associations of depressive symptoms^* (relevant vs not relevant) with genotype, adverse life events, pharmacological treatment for depression, history of depression, marital status, comorbidity index, gender and age distribution.

<p>* Depressive symptomatology was defined using GDS: relevant = GDS≥5 points, not relevant = GDS<5 points.</p><p>^ Unconditional logistic regression analysis was applied to estimate adjusted OR with 95%CI and p-value.</p><p><b>Adjusted odds ratios (OR</b>_<b>adj</b><b>) with confidence intervals (95%CI) and p-values are reported^{<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0143395#t002fn002" target="_blank">^</a>}</b>.</p

Overview of the baseline characteristics of the cohort.

<p>The summary statistics (mean and standard deviation) or the frequency distribution of each variable are shown in the overall population and by the presence/absence of clinically relevant depressive symptoms (GDS≥5 vs GDS<5).The statistical tests and p-values relative to analyses by GDS categories are also reported.</p