Dataset Information

The serotonin transporter polymorphism (5-HTTLPR): allelic variation and links with depressive symptoms.

ABSTRACT:

Background

We compare the genotype distribution for the serotonin transporter polymorphism (5-HTTLPR) in a sample of older Taiwanese adults with samples of various racial and ethnic groups collected in other studies. We also explore interactions among sex, stressors, and 5-HTTLPR genotype on depressive symptoms in our sample.

Methods

Using a nationally representative sample of 984 Taiwanese aged 53 and older, we model depressive symptoms as a function of 5-HTTLPR genotype and two classes of stressors: lifetime trauma and recent major life events. We test two- and three-way interactions among stressors, 5-HTTLPR, and sex.

Results

This sample exhibits higher frequency of S/S and lower frequency of L/L genotype than Western samples, but the distribution is comparable to those in East Asian populations. Nearly 9% carry an allele (XL) that has rarely been reported in the literature. Although the gene-environment (GxE) interaction with recent major life events is not significant, our results suggest that trauma has a worse effect on depressive symptoms for those with S/S or S/L genotype than for those who do not carry the S allele (P<0.05). We find no evidence that this GxE interaction varies by sex.

Conclusions

Previous studies of this GxE interaction have been inconclusive, perhaps because interactions between genotype and stressful events are more prominent under extreme stressors. Our findings underscore the need to move beyond a bi-allelic parameterization of the 5-HTTLPR polymorphism and raise questions about why East Asian populations exhibit low rates of depression despite a high frequency of the S allele.

SUBMITTER: Goldman N

PROVIDER: S-EPMC2841212 | biostudies-literature | 2010 Mar

REPOSITORIES: biostudies-literature

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Publications

The serotonin transporter polymorphism (5-HTTLPR): allelic variation and links with depressive symptoms.

Goldman Noreen N Glei Dana A DA Lin Yu-Hsuan YH Weinstein Maxine M

Depression and anxiety 20100301 3

<h4>Background</h4>We compare the genotype distribution for the serotonin transporter polymorphism (5-HTTLPR) in a sample of older Taiwanese adults with samples of various racial and ethnic groups collected in other studies. We also explore interactions among sex, stressors, and 5-HTTLPR genotype on depressive symptoms in our sample.<h4>Methods</h4>Using a nationally representative sample of 984 Taiwanese aged 53 and older, we model depressive symptoms as a function of 5-HTTLPR genotype and two ...[more]

PMID: 20196101

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Project description:Depending on genetic sensitivity to it, stress may affect depressive symptomatology differentially. Applying the stress-diathesis hypothesis to older adults, we postulate: (1) recent stress will associate with increased depressive symptom levels and (2) this effect will be greater for individuals with at least one short allele of the serotonin transporter gene promoter region (5-HTTLPR). Further, we employ a design that addresses specific limitations of many prior studies that have examined the 5-HTTLPR × SLE relation, by: (a) using a within-person repeated-measures design to address fluctuations that occur within individuals over time, increase power for detecting G × E, and address GE correlation; (b) studying reports of exogenous stressful events (those unlikely to be caused by depression) to help rule out reverse causation and negativity bias, and in order to assess stressors that are more etiologically relevant to depressive symptomatology in older adults. The sample is drawn from the Health and Retirement Study, a U.S. population-based study of older individuals (N = 28,248; mean age = 67.5; 57.3 % female; 80.7 % Non-Hispanic White, 14.9 % Hispanic/Latino, 4.5 % African American; genetic subsample = 12,332), from whom measures of depressive symptoms and exogenous stressors were collected biannually (1994-2010). Variation in the 5-HTTLPR was characterized via haplotype, using two single nucleotide polymorphisms (SNPs). Ordered logit models were constructed to predict levels of depressive symptoms from 5-HTTLPR and stressors, comparing results of the most commonly applied statistical approaches (i.e., comparing allelic and genotypic models, and continuous and categorical predictors) used in the literature. All models were stratified by race/ethnicity. Overall, results show a main effect of recent stress for all ethnic groups, and mixed results for the variation in 5-HTTLPR × stress interaction, contingent upon statistical model used. Findings suggest there may be a differential effect of stressors and 5-HTTLPR on depressive symptoms by ethnicity, but further research is needed, particularly when using a haplotype to characterize variation in 5-HTTLPR in population-based sample with a diverse ethnic composition.

Project description:BACKGROUND:The serotonin (5-HT) transporter-linked polymorphic region (5-HTTLPR) moderates the relationship between stressful life events and depression. Given the high prevalence of depression in chronic pain, the primary aim of this preliminary study was to investigate the associations between the 5-HTTLPR and the severity of depressive symptoms in a cohort of adults with chronic pain. METHODS:Adults with chronic pain who were consecutively admitted to an outpatient pain rehabilitation program and met inclusion criteria were recruited for study participation (n=277). Individuals were genotyped for the 5-HTTLPR (including rs25531) and categorized as high, intermediate, or low expressors of the 5-HT transporter. The severity of depressive symptoms at admission was measured by using the Center for Epidemiologic Depression scale (CES-D). RESULTS:The distribution of the high-, intermediate-, and low-expressing genotypes was 61 (22%), 149 (54%), and 67 (24%), respectively. The Hardy-Weinberg P-value was 0.204, which indicated no departure from equilibrium. A main effect of 5-HTTLPR was observed for depressive symptoms (P=0.040) where Center for Epidemiologic Depression scale (CES-D) scores were significantly greater in the low-expressing group compared to the high- (P=0.019) and intermediate (P=0.029)-expressing groups. In multivariate multinomial logistic regression analysis adjusted for age, sex, pain severity, pain catastrophizing, and pain anxiety, greater CES-D scores were significantly associated with the 5-HTTLPR low-expressing group compared to the high-expressing group (P=0.023), but not for the low-expressing group compared to the intermediate-expressing group (P=0.056). CONCLUSION:These preliminary findings suggest that the triallelic 5-HTTLPR could influence the severity of depressive symptoms in adults with chronic pain. Individuals with chronic pain may be particularly vulnerable to the moderating effects of 5-HTTLPR due to high levels of pain-related stress that are inherently present in this population.

Dataset Information

The serotonin transporter polymorphism (5-HTTLPR): allelic variation and links with depressive symptoms.

Background

Methods

Results

Conclusions

Publications

The serotonin transporter polymorphism (5-HTTLPR): allelic variation and links with depressive symptoms.

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