Skip to main content
Journal cover image

Genetic and hormonal sensitivity to threat: testing a serotonin transporter genotype × testosterone interaction.

Publication ,  Journal Article
Josephs, RA; Telch, MJ; Hixon, JG; Evans, JJ; Lee, H; Knopik, VS; McGeary, JE; Hariri, AR; Beevers, CG
Published in: Psychoneuroendocrinology
June 2012

Striking parallels are observed when comparing the literature on the 5-HTTLPR of the serotonin transporter gene (SLC6A4) to the testosterone (T) literature on measures of stress reactivity and neural activity. Short (S) allele carriers and individuals higher in testosterone levels show exaggerated stress responses, amygdala hyperactivity, and reduction of amygdala-prefrontal cortex coupling when exposed to threat.Three studies tested the hypothesis that higher T, S carriers would show increased cortisol responses to threat.Supporting the hypothesis, a T × 5-HTTLPR interaction was obtained across all studies. Threats to status via social exclusion (Study 1), cognitive/perceptual failure (Study 2), and physical competence (Study 3) all produced elevated cortisol levels in S carriers with higher T levels. An unexpected result was that 5-HTTLPR long (L) allele homozygotes with higher T showed lower cortisol levels in response to threat-a pattern of response that closely parallels that reported for psychopathic individuals. Finally, combining effect sizes across studies showed that the likelihood that these effects were due to Type 1 errors was quite low.What emerges from these studies is a novel yet reliable, and synergistic relationship between 5-HTTLPR genotype and testosterone on stress reactivity, possibly conferring vulnerability for multiple neuropsychiatric disorders.

Duke Scholars

Altmetric Attention Stats
Dimensions Citation Stats

Published In

Psychoneuroendocrinology

DOI

EISSN

1873-3360

ISSN

0306-4530

Publication Date

June 2012

Volume

37

Issue

6

Start / End Page

752 / 761

Related Subject Headings

  • Young Adult
  • Testosterone
  • Surveys and Questionnaires
  • Stress, Psychological
  • Social Environment
  • Serotonin Plasma Membrane Transport Proteins
  • Saliva
  • Psychomotor Performance
  • Psychiatry
  • Psychiatric Status Rating Scales
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Josephs, R. A., Telch, M. J., Hixon, J. G., Evans, J. J., Lee, H., Knopik, V. S., … Beevers, C. G. (2012). Genetic and hormonal sensitivity to threat: testing a serotonin transporter genotype × testosterone interaction. Psychoneuroendocrinology, 37(6), 752–761. https://doi.org/10.1016/j.psyneuen.2011.09.006
Josephs, Robert A., Michael J. Telch, J Gregory Hixon, Jacqueline J. Evans, Hanjoo Lee, Valerie S. Knopik, John E. McGeary, Ahmad R. Hariri, and Christopher G. Beevers. “Genetic and hormonal sensitivity to threat: testing a serotonin transporter genotype × testosterone interaction.Psychoneuroendocrinology 37, no. 6 (June 2012): 752–61. https://doi.org/10.1016/j.psyneuen.2011.09.006.
Josephs RA, Telch MJ, Hixon JG, Evans JJ, Lee H, Knopik VS, et al. Genetic and hormonal sensitivity to threat: testing a serotonin transporter genotype × testosterone interaction. Psychoneuroendocrinology. 2012 Jun;37(6):752–61.
Josephs, Robert A., et al. “Genetic and hormonal sensitivity to threat: testing a serotonin transporter genotype × testosterone interaction.Psychoneuroendocrinology, vol. 37, no. 6, June 2012, pp. 752–61. Epmc, doi:10.1016/j.psyneuen.2011.09.006.
Josephs RA, Telch MJ, Hixon JG, Evans JJ, Lee H, Knopik VS, McGeary JE, Hariri AR, Beevers CG. Genetic and hormonal sensitivity to threat: testing a serotonin transporter genotype × testosterone interaction. Psychoneuroendocrinology. 2012 Jun;37(6):752–761.
Journal cover image

Published In

Psychoneuroendocrinology

DOI

EISSN

1873-3360

ISSN

0306-4530

Publication Date

June 2012

Volume

37

Issue

6

Start / End Page

752 / 761

Related Subject Headings

  • Young Adult
  • Testosterone
  • Surveys and Questionnaires
  • Stress, Psychological
  • Social Environment
  • Serotonin Plasma Membrane Transport Proteins
  • Saliva
  • Psychomotor Performance
  • Psychiatry
  • Psychiatric Status Rating Scales