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

Christopher C Conway1*, George M Slavich23 and Constance Hammen13

Author Affiliations

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

2 Department of Psychology, Cousins Center for Psychoneuroimmunology, University of California, CA, Los Angeles , USA

3 Department of Psychiatry and Biobehavioral Sciences, University of California , CA, Los Angeles, USA

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Biology of Mood & Anxiety Disorders 2014, 4:2  doi:10.1186/2045-5380-4-2

Published: 24 January 2014



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.


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.


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.

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