Gene-environment interactions predict cortisol responses after acute stress: implications for the etiology of depression.
BACKGROUND
Growing evidence suggests that the serotonin transporter polymorphism (5-HTTLPR) interacts with adverse environmental influences to produce an increased risk for the development of depression while the underlying mechanisms of this association remain largely unexplored. As one potential intermediate phenotype, we investigated alterations of hypothalamic-pituitary-adrenal (HPA) axis responses to stress in individuals with no history of psychopathology depending on both 5-HTTLPR and stressful life events.


METHODS
Healthy male adults (N=100) were genotyped and completed a questionnaire on severe stressful life events (Life Events Checklist). To test for gene-by-environment interactions on endocrine stress reactivity, subjects were exposed to a standardized laboratory stress task (Public Speaking). Saliva cortisol levels were obtained at 6 time points prior to the stressor and during an extended recovery period.


RESULTS
Subjects homozygous for the s-allele with a significant history of stressful life events exhibited markedly elevated cortisol secretions in response to the stressor compared to all other groups, indicating a significant gene-by-environment interaction on endocrine stress reactivity. No main effect of either 5-HTTLPR (biallelic and triallelic) or stressful life events on cortisol secretion patterns appeared.


CONCLUSIONS
This is the first study reporting that 5-HTTLPR and stressful life events interact to predict endocrine stress reactivity in a non-clinical sample. Our results underpin the potential moderating role of HPA-axis hyper-reactivity as a premorbid risk factor to increase the vulnerability for depression in subjects with low serotonin transporter efficiency and a history of severe life events.
Alexander
Nina
N
Center for Psychobiology and Behavioral Medicine, University of Giessen, Department of Psychology, FRG, Otto-Behaghel-Str. 10, D-35394 Giessen, Germany. nina.alexander@psychol.uni-giessen.de
Kuepper
Yvonne
Y
Schmitz
Anja
A
Osinsky
Roman
R
Kozyra
Eva
E
Hennig
Juergen
J
D000328:Adult; D003863:Depression / Q000209:etiology*; D005838:Genotype; D006801:Humans; D006854:Hydrocortisone / Q000378:metabolism*; D007030:Hypothalamo-Hypophyseal System / Q000378:metabolism; D008016:Life Change Events; D008297:Male; D010913:Pituitary-Adrenal System / Q000378:metabolism; D012463:Saliva / Q000378:metabolism; D050486:Serotonin Plasma Membrane Transport Proteins / Q000235:genetics*; D013060:Speech; D013315:Stress, Psychological / Q000378:metabolism*
C493230:SLC6A4 protein, human; D050486:Serotonin Plasma Membrane Transport Proteins; D006854:Hydrocortisone