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Cited by 558Stress Responses and CortisolNeurotransmitter Receptor Influence on BehaviorGenetic Associations and Epidemiology

HPA Axis Reactivity: A Mechanism Underlying the Associations Among 5-HTTLPR, Stress, and Depression

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Gotlib, Ian H., Joormann, Jutta, Minor, Kelly L., Hallmayer, Joachim·2008·Biological Psychiatry
DOI 10.1016/j.biopsych.2007.10.008PMC PMC2373542
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Abstract

Background Recent evidence indicates that individuals who are homozygous for the short (s) allele in the promoter region of the serotonin transporter gene have higher rates of depression and other psychiatric disorders as a function of exposure to increasing levels of stressful life events than do individuals who have one or two copies of the long (l) allele. Despite the reliability of this association, the mechanism by which this polymorphism confers risk for psychopathology in the presence of stress is not understood. This study was designed to examine the formulation that individuals who are homozygous for the s allele are characterized by a greater biological reactivity to stress than are their counterparts who have one or two copies of the l allele. Methods Girls at high (n = 25) and low (n = 42) risk for depression by virtue of the presence or absence of a family history of this disorder were genotyped and exposed to a standardized laboratory stress task. Cortisol levels were assessed before the stressor, after the stressor, and during an extended recovery period. Results Girls who were homozygous for the s allele produced higher and more prolonged levels of cortisol in response to the stressor than did girls with an l allele. Conclusions These findings indicate that the 5-HTTLPR polymorphism is associated with biological stress reactivity, which may increase susceptibility to depression in the face of stressful life events.

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  • The s′ allele of 5-HTTLPR has been associated with an exaggerated cortisol response to a standardized psychosocial stressor in children and adults.

    “Consistent with this, the s′ allele of 5-HTTLPR has been associated with an exaggerated cortisol response to a standardized psychosocial stressor in children and adults (Alexander et al. 2009; Gotlib et al. 2008).”

    From Gene–environment interactions: early life stress and risk for depressive and anxiety disorders (2011) · cites this paper as Gotlib et al. 2008

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Cited by

Sorted by citations

Authors
Gotlib, I. H., Joormann, J., Minor, K. L., & Hallmayer, J.
Affiliations
  • Stanford University (US)
  • University of Miami (US)
  • Stanford Medicine (US)
Corresponding author
Gotlib, Ian H.
ORCID
Venue
Biological Psychiatry
Publisher
Elsevier BV
Published
2008-05
Volume
63
Issue
9
Pages
847-851
ISSN
0006-3223 (ISSN-L)
DOI
10.1016/j.biopsych.2007.10.008
PMC
PMC2373542
OpenAlex
W1994628299
Cited by
558
References
11
Citations by year
2026: 2 · 2025: 5 · 2024: 12 · 2023: 9 · 2022: 15 · 2021: 12 · 2020: 60 · 2019: 31 · 2018: 24 · 2017: 21 · 2016: 22 · 2015: 27 · 2014: 41 · 2013: 38 · 2012: 57
FWCI
15.07
Type
journal article
Language
en
Open access
Licence
www.elsevier.com/tdm/userlicense/1.0/ (tdm)
Locations
  • Biological Psychiatry (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
Funders
National Institute of Mental Health (MH74849, R01MH074849)
Topics
  • Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
Keywords
5-HTTLPR, serotonin transporter gene, short allele, genetic polymorphism, hypothalamic-pituitary-adrenal axis, cortisol, stress reactivity, depression vulnerability, life events, family history of depression, girls
MeSH terms
Adolescent, Alleles, Arousal, Child, Major Depressive Disorder, Female, Genotype, Homozygote, Humans, Hydrocortisone, Hypothalamo-Hypophyseal System, Pituitary-Adrenal System, Promoter Regions, Genetic, Risk Factors, Stress, Psychological, Genetic Predisposition to Disease, Serotonin Plasma Membrane Transport Proteins

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