title: Genetic and hormonal sensitivity to threat: testing a serotonin transporter genotype × testosterone interaction.
abstract: BACKGROUND
  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.
  
  
  METHODS
  Three studies tested the hypothesis that higher T, S carriers would show increased cortisol responses to threat.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors: Department of Psychology, The University of Texas at Austin, Austin, TX 78756, USA. josephs@mail.psy.utexas.edu
authors: Robert A
authors: RA
authors: Josephs
authors: Michael J
authors: MJ
authors: Telch
authors: J Gregory
authors: JG
authors: Hixon
authors: Jacqueline J
authors: JJ
authors: Evans
authors: Hanjoo
authors: H
authors: Lee
authors: Valerie S
authors: VS
authors: Knopik
authors: John E
authors: JE
authors: McGeary
authors: Ahmad R
authors: AR
authors: Hariri
authors: Christopher G
authors: CG
authors: Beevers
mesh_terms: D002245:Carbon Dioxide; D004247:DNA / Q000235:genetics; D003863:Depression / Q000235:genetics / Q000523:psychology; D005006:Ethnicity; D005260:Female; D005838:Genotype; D006579:Heterozygote; D006801:Humans; D006854:Hydrocortisone / Q000097:blood; D008297:Male; D008889:Military Personnel; D011569:Psychiatric Status Rating Scales; D011597:Psychomotor Performance / Q000502:physiology; D012463:Saliva / Q000737:chemistry; D050486:Serotonin Plasma Membrane Transport Proteins / Q000235:genetics* / Q000378:metabolism*; D012931:Social Environment; D013315:Stress, Psychological / Q000235:genetics* / Q000378:metabolism*; D011795:Surveys and Questionnaires; D013739:Testosterone / Q000097:blood*; D055815:Young Adult
chemical_list: C493230:SLC6A4 protein, human; D050486:Serotonin Plasma Membrane Transport Proteins; D002245:Carbon Dioxide; D013739:Testosterone; D004247:DNA; D006854:Hydrocortisone