TY - JOUR
T1 - Time moderates the interplay between 5-HTTLPR and stress on depression risk
T2 - gene x environment interaction as a dynamic process
AU - Delli Colli, Claudia
AU - Borgi, Marta
AU - Poggini, Silvia
AU - Chiarotti, Flavia
AU - Cirulli, Francesca
AU - Penninx, Brenda W. J. H.
AU - Benedetti, Francesco
AU - Vai, Benedetta
AU - Branchi, Igor
N1 - Funding Information: Alessandro Giuliani, Ph.D. (Istituto Superiore di Sanità) helped in data analysis and interpretation and Nadia Francia and Antonio Maione (Istituto Superiore di Sanità) provided editorial support. The research was supported by the grant from the Italian Ministry of Health Ricerca Finalizzata RF-2018-12367249 to IB. Publisher Copyright: © 2022, The Author(s).
PY - 2022/12/1
Y1 - 2022/12/1
N2 - The serotonin-transporter-linked promoter region (5-HTTLPR) has been widely investigated as contributing to depression vulnerability. Nevertheless, empirical research provides wide contrasting findings regarding its involvement in the etiopathogenesis of the disorder. Our hypothesis was that such discrepancy can be explained considering time as moderating factor. We explored this hypothesis, exploiting a meta analytic approach. We searched PubMed, PsychoINFO, Scopus and EMBASE databases and 1096 studies were identified and screened, resulting in 22 studies to be included in the meta-analyses. The effect of the 5-HTTLPR x stress interaction on depression risk was found to be moderated by the following temporal factors: the duration of stress (i.e. chronic vs. acute) and the time interval between end of stress and assessment of depression (i.e. within 1 year vs. more than 1 year). When stratifying for the duration of stress, the effect of the 5-HTTLPR x stress interaction emerged only in the case of chronic stress, with a significant subgroup difference (p = 0.004). The stratification according to time interval revealed a significant interaction only for intervals within 1 year, though no difference between subgroups was found. The critical role of time interval clearly emerged when considering only chronic stress: a significant effect of the 5-HTTLPR and stress interaction was confirmed exclusively within 1 year and a significant subgroup difference was found (p = 0.01). These results show that the 5-HTTLPR x stress interaction is a dynamic process, producing different effects at different time points, and indirectly confirm that s-allele carriers are both at higher risk and more capable to recover from depression. Overall, these findings expand the current view of the interplay between 5-HTTLPR and stress adding the temporal dimension, that results in a three-way interaction: gene x environment x time.
AB - The serotonin-transporter-linked promoter region (5-HTTLPR) has been widely investigated as contributing to depression vulnerability. Nevertheless, empirical research provides wide contrasting findings regarding its involvement in the etiopathogenesis of the disorder. Our hypothesis was that such discrepancy can be explained considering time as moderating factor. We explored this hypothesis, exploiting a meta analytic approach. We searched PubMed, PsychoINFO, Scopus and EMBASE databases and 1096 studies were identified and screened, resulting in 22 studies to be included in the meta-analyses. The effect of the 5-HTTLPR x stress interaction on depression risk was found to be moderated by the following temporal factors: the duration of stress (i.e. chronic vs. acute) and the time interval between end of stress and assessment of depression (i.e. within 1 year vs. more than 1 year). When stratifying for the duration of stress, the effect of the 5-HTTLPR x stress interaction emerged only in the case of chronic stress, with a significant subgroup difference (p = 0.004). The stratification according to time interval revealed a significant interaction only for intervals within 1 year, though no difference between subgroups was found. The critical role of time interval clearly emerged when considering only chronic stress: a significant effect of the 5-HTTLPR and stress interaction was confirmed exclusively within 1 year and a significant subgroup difference was found (p = 0.01). These results show that the 5-HTTLPR x stress interaction is a dynamic process, producing different effects at different time points, and indirectly confirm that s-allele carriers are both at higher risk and more capable to recover from depression. Overall, these findings expand the current view of the interplay between 5-HTTLPR and stress adding the temporal dimension, that results in a three-way interaction: gene x environment x time.
UR - http://www.scopus.com/inward/record.url?scp=85133921707&partnerID=8YFLogxK
U2 - https://doi.org/10.1038/s41398-022-02035-4
DO - https://doi.org/10.1038/s41398-022-02035-4
M3 - Article
C2 - 35821204
SN - 2158-3188
VL - 12
JO - Translational psychiatry
JF - Translational psychiatry
IS - 1
M1 - 274
ER -