Serotonin transporter gene and stress reactivity in unipolar depression. Role of the HPA system as endophenotype of the SLC6A4 gene

BACKGROUND: A length polymorphism in the promoter region of the serotonin transporter gene (5-HTTLPR) is associated with both depression and hypothalamic-pituitary-adrenal (HPA) system activity. A dysregulation of the HPA system is considered to be a candidate endophenotype of depression. The objective of the present study was an investigation of a possible gene-endophenotype-interaction between 5-HTTLPR and HPA system activity in a sample of inpatients with major depression. MATERIALS AND METHODS: A total of 237 inpatients with major depression were genotyped for 5-HTTLPR and participated in a combined dexamethasone-corticotropin-releasing hormone test (Dex-CRH test) as well as using the Hamilton score (Hamilton rating scale for depression) to determine the severity of the psychopathology. RESULTS: Patients with the ss-genotype showed a significantly higher HPA -system activity in comparison to patients with the lI-genotype, but no association between 5-HTTLPR and the severity of psychopathology could be detected. CONCLUSIONS: The results of the current study demonstrate an influence of 5-HTTLPR on dysregulation of the HPA system in patients with major depression and support the hypothesis that 5-HTTLPR- and HPA-system-interaction constitutes an important component in the pathogenesis of depression.