Collaborative meta-analysis finds no evidence of a strong interaction between stress and 5-HTTLPR genotype contributing to the development of depression

Culverhouse, R. C. and Saccone, N. L. and Horton, A. C. and Ma, Y. and Anstey, K. J. and Banaschewski, T. and Burmeister, M. and Cohen-Woods, S. and Etain, B. and Fisher, H. L. and Goldman, N. and Guillaume, S. and Horwood, J. and Juhász, Gabriella and Lester, David and Mandelli, L. and Middeldorp, C. M. and Olié, E. and VIllafuerte, S. and Air, T. M. and Araya, R. and Bowes, L. and Burns, R. and Byrne, E. M. and Coffey, C. and Coventry, W. L. and Gawronski, K. A. B. and Glei, D. and Hatzimanolis, A. and Hottenga, J. J. and Jaussent, I. and Jawahar, C. and Jennen-Steinmetz, C. and Kramer, J. R. and Lainef, M. and Little, K. and Zu Schwabedissen, H. M. and Nauck, M. and Nederhof, E. and Petschner, Péter and Peyrot, W. J. and Schwahn, C. and Sinnamon, G. and Stacey, D. and Tian, Y. and Toben, C. and Van der Auwera, S. and Wainwright, N. and Wang, J. C. and Willemsen, Gonneke and Anderson, I. M. and Arolt, V. and Aslund, C. and Bagdy, György and Baune, B. T. and Bellivier, F. and Boomsma, D. I. and Courtet, P. and Dannlowski, U. and de Geus, E. J. C. and Deakin, J. F. W. and Easteal, S. and Eley, T. and Fergusson, D. M. and Goate, A. M. and Gonda, Xénia and Grabe, H. J. and Holzman, C. and Johnson, E. O. and Kennedy, M. and Laucht, M. and Martin, N. G. and Munafó, M. R. and Nilsson, K. W. and Oldehinkel, A. J. and Olsson, C. A. and Ormel, J. and Otte, C. and Patton, G. C. and Penninx, B. W. H. J. and Ritchie, K. and Sarchiapone, M. and Scheid, J. M. and Serretti, A. and Smit, J. H. and Stefanis, N. C. and Surtees, P. G. and Völtzke, H. and Weinstein, M. and Whooley, M. and Nurnberger, J. I. Jr. and Breslau, N. and Bierut, L. J. (2018) Collaborative meta-analysis finds no evidence of a strong interaction between stress and 5-HTTLPR genotype contributing to the development of depression. Molecular Psychiatry, 23. pp. 133-142. ISSN 1359-4184

[img] Text
Restricted to Registered users only

Download (1MB)


The hypothesis that the S allele of the 5-HTTLPR serotonin transporter promoter region is associated with increased risk of depression, but only in individuals exposed to stressful situations, has generated much interest, research and controversy since first proposed in 2003. Multiple meta-analyses combining results from heterogeneous analyses have not settled the issue. To determine the magnitude of the interaction and the conditions under which it might be observed, we performed new analyses on 31 data sets containing 38 802 European ancestry subjects genotyped for 5-HTTLPR and assessed for depression and childhood maltreatment or other stressful life events, and meta-analysed the results. Analyses targeted two stressors (narrow, broad) and two depression outcomes (current, lifetime). All groups that published on this topic prior to the initiation of our study and met the assessment and sample size criteria were invited to participate. Additional groups, identified by consortium members or self-identified in response to our protocol (published prior to the start of analysis) with qualifying unpublished data, were also invited to participate. A uniform data analysis script implementing the protocol was executed by each of the consortium members. Our findings do not support the interaction hypothesis. We found no subgroups or variable definitions for which an interaction between stress and 5-HTTLPR genotype was statistically significant. In contrast, our findings for the main effects of life stressors (strong risk factor) and 5-HTTLPR genotype (no impact on risk) are strikingly consistent across our contributing studies, the original study reporting the interaction and subsequent meta-analyses. Our conclusion is that if an interaction exists in which the S allele of 5-HTTLPR increases risk of depression only in stressed individuals, then it is not broadly generalisable, but must be of modest effect size and only observable in limited situations.

Item Type: Article
Subjects: R Medicine / orvostudomány > RC Internal medicine / belgyógyászat > RC0321 Neuroscience. Biological psychiatry. Neuropsychiatry / idegkórtan, neurológia, pszichiátria
Depositing User: Dr Xenia Gonda
Date Deposited: 25 Sep 2018 14:32
Last Modified: 25 Sep 2018 14:32

Actions (login required)

Edit Item Edit Item