Elsevier

Biological Psychiatry

Volume 62, Issue 5, 1 September 2007, Pages 423-428
Biological Psychiatry

Original Article
Interactions Between Life Stressors and Susceptibility Genes (5-HTTLPR and BDNF) on Depression in Korean Elders

https://doi.org/10.1016/j.biopsych.2006.11.020Get rights and content

Background

It has been reported that the functional polymorphism in the serotonin transporter gene linked promoter region (5-HTTLPR) modifies the association between stressful life events (SLEs) and depression in child, adolescent, and adult populations. We sought to replicate this finding in elders and, additionally, to test modifying effects of the brain-derived neurotrophic factor (BDNF) val66met polymorphism.

Methods

In 732 Korean community residents ages 65+, diagnosis of depression (Geriatric Mental State Schedule), information on SLEs, and genotypes for 5-HTTLPR and BDNF val66met were ascertained. Of those without depression at baseline, 521 (88%) were followed up 2.5 years later. Interactions between SLEs and the two genotypes were investigated for both prevalent depression at baseline and incident depression at follow-up.

Results

Significant interactions of SLEs with both 5-HTTLPR and BDNF genotypes were observed on risk of depression after adjustment for age, gender, education, and disability. A significant three-way interaction between 5-HTTLPR, BDNF, and SLEs was also found. The same findings were observed for predictors of incident depression in the prospective analysis.

Conclusions

These findings suggest that environmental risk of depression is modified by at least two genes and that gene–environment interactions are found even into old age.

Section snippets

Sample and Measurements

This analysis was carried out on data from a prospective community-based study of late-life psychiatric morbidity carried out in Kwangju, South Korea from 2001 to 2003, in collaboration with the 10/66 International Research Program on Dementia in Developing Countries (Prince et al. 2003). All participants gave written formal informed consent at each examination. This study was approved by the Chonnam National University Hospital Institutional Review Board.

Cross-sectional data were analyzed from

Results

Of 732 participants at baseline, case-level depression was present in 101 (13.8%). Frequencies of SLEs and 5-HTTLPR/BDNF genotypes in the sample are displayed in the first column of Table 1. These are compared between those with and without depression in the second through fifth columns of Table 1. Depression was significantly associated with increased numbers of SLEs. Although associations between depression and the two genotypes were in the directions anticipated, these were not significant.

Discussion

The principal findings of this study of community elders were as follows: 1) previous findings of effect modification between 5-HTTLPR genotype and SLEs on risk of depression were confirmed; 2) similar effect modification between BDNF val66met genotype and SLEs on risk of depression was identified; and 3) three-way effect modification between these two genotypes and SLEs on risk of depression was found. These findings were largely confirmed when the analysis was repeated in a follow-up study of

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