Dries Bleys1, Patrick Luyten2, Bart Soenens3, Stephan Claes4. 1. KU Leuven, Faculty of Psychology and Educational Sciences, Tiensestraat 102, 3000 Leuven, Belgium. Electronic address: dries.bleys@kuleuven.be. 2. KU Leuven, Faculty of Psychology and Educational Sciences, Tiensestraat 102, 3000 Leuven, Belgium; University College London, Faculty of Brain Sciences, 1-19 Torrington Place, London WC1E7HB, United Kingdom. 3. Ghent University, Department of Developmental, Personality and Social Psychology, H. Dunantlaan 2, 9000 Ghent, Belgium. 4. KU Leuven, Research Group Psychiatry, Herestraat 49, 3000 Leuven, Belgium.
Abstract
BACKGROUND: Meta-analyses have yielded contradictory findings concerning the role of 5-HTTLPR in interaction with stress (GxE) in depression. The current meta-analysis investigates if these contradictory findings are a result of differences between studies in methodological approaches towards the assessment of stress and depression. METHODS: After performing a systematic database search (February to December 2016), first, a meta-analysis was used to investigate the total effect size and publication bias. Second, stratified meta-analyses were used to investigate the potential moderating influence of different methodological approaches on heterogeneity of study findings. Third, a meta-regression was used to investigate the combined influence of the methodological approaches on the overall effect size. RESULTS: Results showed a small but significant effect of 5-HTTLPR in interaction with stress in the prediction of depression (OR[95%CI] = 1.18[1.09; 1.28], n = 48 effect sizes from 51 studies, totaling 51,449 participants). There was no evidence of publication bias. Heterogeneity of effect sizes was a result of outliers and not due to different methodological approaches towards the assessment of stress and depression. Yet, there was some evidence that studies adopting a categorical and interview approach to the assessment of stress report higher GxE effects, but further replication of this finding is needed. LIMITATIONS: A large amount of heterogeneity (i.e., 46%) was not explained by the methodological factors included in the study and there was a low response rate of invited studies. CONCLUSIONS: The current meta-analysis provides new evidence for the robustness of the interaction between stress and 5-HTTLPR in depression.
BACKGROUND: Meta-analyses have yielded contradictory findings concerning the role of 5-HTTLPR in interaction with stress (GxE) in depression. The current meta-analysis investigates if these contradictory findings are a result of differences between studies in methodological approaches towards the assessment of stress and depression. METHODS: After performing a systematic database search (February to December 2016), first, a meta-analysis was used to investigate the total effect size and publication bias. Second, stratified meta-analyses were used to investigate the potential moderating influence of different methodological approaches on heterogeneity of study findings. Third, a meta-regression was used to investigate the combined influence of the methodological approaches on the overall effect size. RESULTS: Results showed a small but significant effect of 5-HTTLPR in interaction with stress in the prediction of depression (OR[95%CI] = 1.18[1.09; 1.28], n = 48 effect sizes from 51 studies, totaling 51,449 participants). There was no evidence of publication bias. Heterogeneity of effect sizes was a result of outliers and not due to different methodological approaches towards the assessment of stress and depression. Yet, there was some evidence that studies adopting a categorical and interview approach to the assessment of stress report higher GxE effects, but further replication of this finding is needed. LIMITATIONS: A large amount of heterogeneity (i.e., 46%) was not explained by the methodological factors included in the study and there was a low response rate of invited studies. CONCLUSIONS: The current meta-analysis provides new evidence for the robustness of the interaction between stress and 5-HTTLPR in depression.
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