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Gene-environment interactions between stress and 5-HTTLPR in depression: A meta-analytic update
Dries Bleys1, Patrick Luyten2, Bart Soenens3
1KU Leuven, Faculty of Psychology and Educational Sciences, Tiensestraat 102, 3000 Leuven, Belgium.
Journal of Affective Disorders
|October 15, 2017
Summary
The serotonin transporter gene variant (5-HTTLPR) interacts with stress to predict depression, a finding robust across studies. Methodological differences did not explain prior contradictory results, though outliers contributed to heterogeneity.
Area of Science:
- Psychiatry
- Genetics
- Epidemiology
Background:
- Conflicting findings exist regarding the serotonin transporter gene-linked polymorphic region (5-HTTLPR) and its interaction with stress (GxE) in depression.
- This meta-analysis aimed to resolve discrepancies by examining methodological variations in stress and depression assessment.
Purpose of the Study:
- To investigate the overall effect size of the 5-HTTLPR x stress interaction on depression.
- To identify if methodological differences in assessing stress and depression explain heterogeneity in prior meta-analyses.
- To explore the moderating influence of specific methodological approaches on GxE effects.
Main Methods:
- A systematic literature search was conducted from February to December 2016.
- Meta-analysis and stratified meta-analyses were employed to assess total effect size, publication bias, and heterogeneity.
- Meta-regression was used to evaluate the combined impact of methodological factors.
Main Results:
- A significant, albeit small, effect of 5-HTTLPR x stress interaction was found in predicting depression (OR=1.18, 95% CI [1.09; 1.28], N=51,449).
- No evidence of publication bias was detected.
- Heterogeneity was primarily due to outliers, not methodological variations, although some evidence suggested higher GxE effects with categorical/interview stress assessment.
Conclusions:
- The interaction between stress and 5-HTTLPR remains a robust predictor of depression.
- While methodological differences did not fully explain prior inconsistencies, outliers contributed significantly to heterogeneity.
- Further research is needed to confirm the influence of specific stress assessment methods on GxE effects.