Objective: To summarize current concepts on neuroendocrine and genetic principles underlying stress-related depression and to discuss the challenges of personalized treatment in depression.
Methods: Review of the literature pertaining to genetic and neuroendocrine basis of stress-related depression including aspects of treatment response with a focus on the hypothalamus-pituitary-adrenal (HPA) axis.
Results: There is increasing evidence that genetic polymorphisms and dysregulation of the HPA axis are associated with the pathophysiology of stress-related depression. Individual stress hormone reactivity seems to be determined by a combination of genetic and environmental factors, contributing to both, resilience or vulnerability.
Conclusions: Although substantial progress has been made, current knowledge is still limited. Further basic and clinical research is needed to identify specific subgroups and to minimize heterogeneity of the depression phenotype. A better characterization is essential to detect genetic and functional predictors of antidepressant treatment response to follow the vision of personalized therapy in psychiatry.