Time moderates the interplay between 5-HTTLPR and stress on depression risk: gene x environment interaction as a dynamic process.

The sensitivity analysis confirmed a significant 5-HTTLPR x stress effect on depressive outcome in the subgroup of studies on chronic stress only (OR 1.17, 95% CI 1.01–1.34, p = 0.03, I 2 = 60%, χ2 = 35.09, p = 0.001), despite the subgroup difference failed to reach statistical significance ( p = 0.13; Supplementary Table 3 ).

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The sensitivity analysis confirmed these results, and the subgroup difference did not reach statistical significance ( p = 0.53; Supplementary Table 6 ).

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3 ).The highly significant heterogeneity in the overall group of studies on chronic stress was no more significant after subgrouping for the two time intervals, corroborating the hypothesis that the 5-HTTLPR x stress interaction produces different and well defined effects on the risk of depression before and after 1 year from the end of the stress.

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