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

被引：206

作者：

Culverhouse, R. C. ^{[1
,2
]}

Saccone, N. L. ^{[2
,3
]}

Horton, A. C. ^{[4
]}

Ma, Y. ^{[4
]}

Anstey, K. J. ^{[5
]}

Banaschewski, T. ^{[6
]}

Burmeister, M. ^{[7
,8
]}

Cohen-Woods, S. ^{[9
]}

Etain, B. ^{[10
,11
,12
]}

Fisher, H. L. ^{[13
]}

Goldman, N. ^{[14
]}

Guillaume, S. ^{[15
,16
,17
]}

Horwood, J. ^{[18
]}

Juhasz, G. ^{[19
,20
,21
,22
]}

Lester, K. J. ^{[23
]}

Mandelli, L. ^{[24
]}

Middeldorp, C. M. ^{[25
,26
]}

Olie, E. ^{[15
,16
,17
]}

Villafuerte, S. ^{[7
]}

Air, T. M. ^{[27
]}

Araya, R. ^{[28
]}

Bowes, L. ^{[29
]}

Burns, R. ^{[5
]}

Byrne, E. M. ^{[30
]}

Coffey, C. ^{[31
]}

Coventry, W. L. ^{[32
]}

Gawronski, K. A. B. ^{[33
]}

Glei, D. ^{[34
]}

Hatzimanolis, A. ^{[35
,36
]}

Hottenga, J-J ^{[25
,37
]}

Jaussent, I. ^{[16
]}

Jawahar, C. ^{[27
]}

Jennen-Steinmetz, C. ^{[38
]}

Kramer, J. R. ^{[39
]}

Lajnef, M. ^{[40
]}

Little, K. ^{[41
,42
,43
]}

zu Schwabedissen, H. M. ^{[44
]}

Nauck, M. ^{[45
]}

Nederhof, E. ^{[46
]}

Petschner, P. ^{[20
,22
,47
]}

Peyrot, W. J. ^{[48
,49
]}

Schwahn, C. ^{[50
]}

Sinnamon, G. ^{[27
]}

Stacey, D. ^{[27
]}

Tian, Y. ^{[51
]}

Toben, C. ^{[27
]}

Van der Auwera, S. ^{[52
]}

Wainwright, N. ^{[53
]}

Wang, J-C ^{[54
]}

Willemsen, G. ^{[25
,37
]}

机构：

[1] Washington Univ, Sch Med, Dept Med, St Louis, MO 63110 USA

[2] Washington Univ, Sch Med, Div Biostat, St Louis, MO 63110 USA

[3] Washington Univ, Sch Med, Dept Genet, St Louis, MO 63110 USA

[4] Washington Univ, Sch Med, Dept Psychiat, St Louis, MO 63110 USA

[5] Australian Natl Univ, Ctr Res Ageing Hlth & Wellbeing, Canberra, ACT, Australia

[6] Heidelberg Univ, Med Fac Mannheim, Cent Inst Mental Hlth, Dept Child & Adolescent Psychiat & Psychotherapy, Mannheim, Germany

[7] Univ Michigan, Dept Psychiat, Ann Arbor, MI 48109 USA

[8] Univ Michigan, Dept Human Genet, Ann Arbor, MI 48109 USA

[9] Flinders Univ S Australia, Sch Psychol, Fac Social & Behav Sci, Adelaide, SA, Australia

[10] Univ Paris Diderot, Sorbonne Paris Cite, UMR S 1144, Paris, France

[11] AP HP, Grp St Louis Lariboisiere F, Paris, France

[12] INSERM, U1144, Paris, France

[13] Kings Coll London, Inst Psychiat Psychol & Neurosci, Social Genet & Dev Psychiat Ctr, London, England

[14] Princeton Univ, Off Populat Res, Princeton, NJ 08544 USA

[15] Univ Montpellier, Montpellier, France

[16] INSERM, Neuropsychiat U1061, Montpellier, France

[17] CHU Montpellier, Dept Emergency Psychiat & Acute Care, Montpellier, France

[18] Univ Otago Christchurch, Dept Psychol Med, Christchurch, New Zealand

[19] Semmelweis Univ, Hungarian Acad Sci, MTA SE NAP Genet Brain Imaging Migraine Res Grp B, Budapest, Hungary

[20] Semmelweis Univ, Dept Pharmacodynam, Budapest, Hungary

[21] Univ Manchester, Neurosci & Psychiat Unit, Manchester, Lancs, England

[22] Semmelweis Univ, NAP A SE New Antidepressant Target Res Grp, Budapest, Hungary

[23] Univ Sussex, Sch Psychol, Brighton, E Sussex, England

[24] Univ Bologna, Dept Biomed & NeuroMotor Sci, Bologna, Italy

[25] Vrije Univ Amsterdam, Dept Biol Psychol, Amsterdam, Netherlands

[26] Vrije Univ Amsterdam, Neurosci Campus Amsterdam, Amsterdam, Netherlands

[27] Univ Adelaide, Discipline Psychiat, Adelaide, SA, Australia

[28] London Sch Hyg & Trop Med, Ctr Global Mental Hlth, London, England

[29] Univ Oxford, Dept Expt Psychol, Oxford, England

[30] Univ Queensland, Inst Mol Biosci, Brisbane, Qld, Australia

[31] Murdoch Childrens Res Inst, Ctr Adolescent Hlth, Melbourne, Vic, Australia

[32] Univ New England, Discipline Psychol, Armidale, NSW, Australia

[33] Univ Penn, Dept Genet, Perelman Sch Med, Philadelphia, PA 19104 USA

[34] Georgetown Univ, Ctr Populat & Hlth, Washington, DC USA

[35] Natl & Kapodistrian Univ Athens, Sch Med, Eginit Hosp, Dept Psychiat, Athens, Greece

[36] Theodor Theohari Cozzika Fdn, Neurobiol Res Inst, Athens, Greece

[37] VU Med Ctr Amsterdam, EMGO Inst Hlth & Care Res, Amsterdam, Netherlands

[38] Heidelberg Univ, Med Fac Mannheim, Cent Inst Mental Hlth, Dept Biostat, Mannheim, Germany

[39] Univ Iowa, Dept Psychiat, Carver Coll Med, Iowa City, IA 52242 USA

[40] INSERM, U955, Creteil, France

[41] Murdoch Childrens Res Inst, Melbourne, Vic, Australia

[42] Univ Melbourne, Dept Paediat, Melbourne, Vic, Australia

[43] Univ Melbourne, Sch Psychol Sci, Melbourne, Vic, Australia

[44] Univ Basel, Dept Pharmaceut Sci, Biopharm, Basel, Switzerland

[45] Univ Med Greifswald, Inst Clin Chem & Lab Med, Greifswald, Germany

[46] Univ Groningen, Univ Med Ctr Groningen, Interdisciplinary Ctr Psychopathol & Emot Regulat, Groningen, Netherlands

[47] Semmelweis Univ, Hungarian Acad Sci, MTA SE Neuropsychopharmacol & Neurochem Res Grp, Budapest, Hungary

[48] Vrije Univ Amsterdam Med Ctr, Dept Psychiat, Amsterdam, Netherlands

[49] GGZ InGeest, Amsterdam, Netherlands

[50] Univ Med Greifswald, Dept Prosthet Dent Gerostomatol & Dent Mat, Greifswald, Germany

来源：

MOLECULAR PSYCHIATRY | 2018年 / 23卷 / 01期

基金：

英国医学研究理事会; 美国国家卫生研究院; 英国经济与社会研究理事会; 澳大利亚研究理事会; 欧盟第七框架计划; 英国惠康基金;

关键词：

SEROTONIN TRANSPORTER GENE; MAJOR DEPRESSION; COHORT PROFILE; LIFE EVENTS; CHILDHOOD MALTREATMENT; POLYMORPHISM; 5-HTTLPR; ENVIRONMENT; RISK; DISORDER; RELIABILITY;

D O I：

10.1038/mp.2017.44

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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.

引用

页码：133 / 142

页数：10

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