Daily stress reactivity and serotonin transporter gene (5-HTTLPR) variation: internalizing responses to everyday stress as a possible transdiagnostic phenotype

Biology of Mood & Anxiety Disorders

Christopher C Conway¹  George M Slavich²  Constance Hammen² 

[1] Department of Psychology, University of California, Los Angeles, Box 951563, Los Angeles, CA 90095-1563, USA

[2] Department of Psychiatry and Biobehavioral Sciences, University of California , CA, Los Angeles, USA

关键词: Young adulthood;    Serotonin transporter gene;    RDoC;    Life events;    Intermediate phenotype;    Gene-environment interaction;    Daily diary;    Depression;    Anxiety;   

Others  :  791744
DOI  :  10.1186/2045-5380-4-2

 received in 2013-10-21, accepted in 2014-01-10,  发布年份 2014

【 摘 要 】

Background

Recent studies examining the interaction between the 5-HTTLPR locus in the serotonin transporter gene and life stress in predicting depression have yielded equivocal results, leading some researchers to question whether 5-HTTLPR variation indeed regulates depressive responses to stress. Two possible sources of inconsistent data in this literature are imprecise stress assessment methodologies and a restricted focus on depression phenotypes as the outcome of interest, as opposed to transdiagnostic emotional symptoms such as internalizing and externalizing dimensions. The present study aimed to address these critical limitations in prior research by examining how 5-HTTLPR acts in concert with idiographically assessed daily life stress to predict transdiagnostic emotional outcomes.

Results

One hundred and four healthy young adults genotyped for 5-HTTLPR reported on their life stress exposure and internalizing and externalizing experiences for 14 consecutive days. As hypothesized, daily stress levels were associated with severity of internalizing symptoms, but only for 5-HTTLPR S allele carriers. Additional analyses revealed that these interactive effects of 5-HTTLPR and daily life stress on internalizing symptoms extended to both the distress and fear subdomains of internalizing symptoms.

Conclusions

Considered together, these results support the validity of the 5-HTTLPR stress sensitivity hypothesis and suggest for the first time that variation at 5-HTTLPR moderates the effects of daily life stress on broadband symptom profiles.

【 授权许可】

   
2014 Conway et al.; licensee BioMed Central Ltd.

【 图 表 】

Figure 1.

【 参考文献 】

• [1]Caspi A, Sugden K, Moffitt TE, Taylor A, Craig IW, Harrington H, McClay J, Mill J, Martin J, Braithwaite A, Poulton R: Influence of life stress on depression: moderation by a polymorphism in the 5HTT gene. Science 2003, 301:386-389.
• [2]Risch N, Herell R, Lehner T, Liang KY, Eaves L, Hoh J, Griem A, Kovacs M, Ott J, Merikangas KR: Interaction between the serotonin transporter gene (5-HTTLPR), stressful life events, and risk of depression: a meta-analysis. JAMA 2009, 30123:2462-2471.
• [3]Karg K, Burmeister M, Shedden K, Sen S: The serotonin transporter promoter variant (5 HTTLPR), stress, and depression meta-analysis revisited: evidence of genetic moderation. Arch Gen Psychiatry 2011, 68:444-454.
• [4]Munafò MR, Brown SM, Hariri AR: Serotonin transporter (5-HTTLPR) genotype and amygdala activation: a meta-analysis. Biol Psychiatry 2008, 63:852-857.
• [5]Pergamin-Hight L, Bakermans-Kranenburg MJ, van Ijzendoorn MH, Bar-Haim Y: Variations in the promoter region of the serotonin transporter gene and biased attention for emotional information: a meta-analysis. Biol Psychiatry 2012, 71:373-379.
• [6]Way BM, Taylor SE: The serotonin transporter promoter polymorphism is associated with cortisol response to psychosocial stress. Biol Psychiatry 2010, 67:487-492.
• [7]Caspi A, Hariri AR, Holmes A, Uher R, Moffitt TE: Genetic sensitivity to the environment: the case of the serotonin transporter gene and its implications for studying complex diseases and traits. Am J Psychiatry 2010, 167:509-527.
• [8]Kendler KS, Kuhn JW, Vittum J, Prescott CA, Riley B: The interaction of stressful life events and a serotonin transporter polymorphism in the prediction of episodes of major depression: a replication. Arch Gen Psychiatry 2005, 62:529-535.
• [9]Hariri AR, Holmes A: Genetics of emotional regulation: the role of the serotonin transporter in neural function. Trends Cogn Sci 2006, 10:182-191.
• [10]Wright AG, Krueger RF, Hobbs MJ, Markon KE, Eaton NR, Slade T: The structure of psychopathology: toward an expanded quantitative mode. J Abnorm Psychol 2013, 122:281-294.
• [11]Ofrat S, Krueger RF: How research on the meta-structure of psychopathology aids in understanding biological correlates of mood and anxiety disorders. Biol Mood Anxiety Disord 2012, 2:13-17. BioMed Central Full Text
• [12]Achenbach TM: Manual for the Young Adult Self-Report and Young Adult Behavior Checklist. Burlington: University of Vermont Department of Psychiatry; 1997.
• [13]Seidlitz L, Diener E: Memory for positive versus negative life events: theories for the differences between happy and unhappy persons. J Pers Soc Psychol 1993, 64:654-663.
• [14]Shahar G, Henrich CC, Reiner IC, Little TD: Development and initial validation of the brief adolescent life event scale (BALES). Anxiety Stress Coping 2003, 16:119-128.
• [15]Gunthert KC, Conner TS, Armeli S, Tennen H, Covault J, Kranzler HR: Serotonin transporter gene polymorphism (5-HTTLPR) and anxiety reactivity in daily life: a daily process approach to gene-environment interaction. Psychosom Med 2007, 69:762-768.
• [16]Watson D, O’Hara MW, Simms LJ, Kotov R, Chmielewski M, McDade-Montez EA, Gamez W, Scott S: Development and validation of the Inventory of Depression and Anxiety Symptoms (IDAS). Psychol Assess 2007, 19:253-268.
• [17]Wendland JR, Lesch KP, Newman TK, Timme A, Gachot-Neveu H, Thierry B, Suomi SJ: Differential functional variability of serotonin transporter and monoamine oxidase a genes in macaque species displaying contrasting levels of aggression-related behavior. Behav Genet 2006, 36:163-172.
• [18]Wray NR, James MR, Gordon SD, Dumenil T, Ryan L, Coventry WL, Statham DJ, Pergadia ML, Madden PA, Heath AC, Montgomery GW, Martin NG: Accurate, large-scale genotyping of 5HTTLPR and flanking single nucleotide polymorphisms in an association study of depression, anxiety, and personality measures. Biol Psychiatry 2009, 66:468-476.
• [19]Dasch KB, Cohen LJ, Sahl JC, Gunthert KC: Moderating effects of sociotropy and autonomy on affective and self-esteem reactivity to daily stressors. Cognit Ther Res 2008, 32:177-195.
• [20]Hox J: Multilevel Analysis: Techniques and Applications. New York: Routlage; 2010.
• [21]Sahl JC, Cohen LH, Dasch KB: Hostility, interpersonal competence, and daily dependent stress: a daily model of stress generation. Cognit Ther Res 2009, 33:199-210.
• [22]Shih JH, Eberhart NK, Hammen CL, Brennan PA: Differential exposure and reactivity to interpersonal stress predict sex differences in adolescent depression. J Clin Child Adolesc Psychol 2006, 35:103-115.
• [23]Cuthbert BN, Insel TR: Toward the future of psychiatric diagnosis: the seven pillars of RDoC. BMC Med 2013, 11:126-134. BioMed Central Full Text
• [24]Kendler KS: ‘A gene for…’: the nature of gene action in psychiatric disorders. Am J Psychiatry 2005, 162:1243-1252.
• [25]Uher R, McGuffin P: The moderation by the serotonin transporter gene of environmental adversity in the etiology of depression: 2009 update. Mol Psychiatry 2010, 15:18-22.
• [26]Strauss ME, Smith GT: Construct validity: advances in theory and methodology. Annu Rev Clin Psychol 2009, 5:1-25.
• [27]Cardon LR, Palmer LJ: Population stratification and spurious allelic association. Lancet 2003, 361:598-604.