Stress axis as the locus of gene-environment interactions in major depressive disorder

K. G. Kahl, M. Reimann, M. Bauer, S. R. Bornstein, M. L. Wong, J. Licinio

Research output: Chapter in Book/Report/Conference proceedingChapter


Evidence from family, twin, and adoption studies indicates that there is a significant genetic contribution to major depressive disorder. However, the majority of individuals with a positive family history of depression do not develop depression. Thus, current hypotheses about the role of genes for the development of depression collectively favor the stress-diathesis theory. The latter postulates that repeated or chronic exposure of a vulnerable genotype to stressful life events may trigger the development of depression. The hypothalamic-pituitary-adrenal (HPA) axis is discussed as a missing link between genes, stress, and depression. The genetic variation of coping behavior in response to stress and the depression-related dysregulation of HPA axis confirm a strong impact of both genetic and environmental factors on the manifestation of depressive disorders. Such interactions would facilitate the manifestation of environmental effects in a depressive phenotype preferentially in the presence of a permissive genetic background.

Original languageEnglish (US)
Title of host publicationEncyclopedia of Environmental Health
Number of pages5
ISBN (Electronic)9780444639523
ISBN (Print)9780444639516
StatePublished - Jan 1 2019


  • Adrenocorticotropin-releasing hormone
  • Corticotropin-releasing hormone
  • Environmental factors
  • Genetic vulnerability
  • Heritability
  • Hypothalamic-pituitary-adrenal axis
  • Major depressive disorder
  • Serotonin
  • Serotonin transporter length region polymorphism
  • Stress

ASJC Scopus subject areas

  • Environmental Science(all)


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