Elsevier

Biological Psychiatry

Volume 63, Issue 9, 1 May 2008, Pages 847-851
Biological Psychiatry

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

https://doi.org/10.1016/j.biopsych.2007.10.008Get rights and content

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.

Section snippets

Participants

Participants were 67 girls aged 9 to 14 with no current or past Axis I disorder. Forty-two girls had biological mothers with no current or past Axis I disorder (low-risk daughters), and 25 girls had biological mothers with a history of recurrent episodes of MDD during their daughter’s lifetime (high-risk daughters). Participants were recruited through advertisements posted in numerous locations within the local community (e.g., Internet bulletin boards, university kiosks, supermarkets) and

Participant Characteristics

Demographic and clinical characteristics of the high-risk (RSK) and low-risk (CTL) groups are presented in Table 1. There were no significant group differences in age, t(65) < 1, proportion of girls who were postmenarcheal, χ2(1,67) < 1, WISC vocabulary scores, t(57) = 1.56, ethnicity, χ2(1,67) < 1, or mothers’ education, χ2(1,66) = 1.76, all ps > .05; the CTL group had a higher percentage of married mothers, χ2(1,66) = 12.58, p < .01. The RSK girls obtained slightly but significantly higher

Discussion

The pattern of findings reported here both provides an explanation for the results of studies documenting associations among genotype, exposure to stress, and probability of depression and extends our understanding of the relation between the 5-HTTLPR polymorphism and stress reactivity. Investigators have known for decades that exposure to severe life stressors increases the likelihood of subsequent depression (35). We also know, however, that many individuals who experience life stress do not

References (39)

  • A. Caspi et al.

    Influence of life stress on depression: Moderation by a polymorphism in the 5-HTT gene

    Science

    (2003)
  • J.-M. Kim et al.

    Interactions between life stressors and susceptibility genes (5-HTTLPR and BDNF) on depression in Korean elders

    Biol Psychiat

    (2007)
  • G. Zalsman et al.

    Association of a triallelic serotonin transporter gene promoter region (5-HTTLPR) polymorphism with stressful life events and severity of depression

    Am J Psychiatry

    (2006)
  • J. Kaufman et al.

    Social supports and serotonin transporter gene moderate depression in maltreated children

    Proc Natl Acad Sci U S A

    (2004)
  • Q. Li et al.

    Reduction of 5-HT1A binding sites in 5-HT transporter knockout mice

    J Pharmacol Exp Ther

    (1999)
  • K.S. Kendler et al.

    The interaction of stressful life events and a serotonin transporter polymorphism in the prediction of episodes of major depression

    Arch Gen Psychiatry

    (2005)
  • A.R. Hariri et al.

    A susceptibility gene for affective disorders and the response of the human amygdala

    Arch Gen Psychiatry

    (2005)
  • L. Pezawas et al.

    5-HTTLPR polymorphism impacts human cingulate-amygdala interactions: A genetic susceptibility mechanism for depression

    Nature Neurosci

    (2005)
  • I.S. Federenko et al.

    The heritability of hypothalamus pituitary adrenal axis responses to psychosocial stress is context dependent

    J Clin Endocrinol Metab

    (2004)
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