Advance in Stress for Depressive Disorder
1State Key Laboratory of Medical Neurobiology, Department of Laboratory Animal Sciences, Institutes of Brain Science, Fudan University, Shanghai, China. dingyuqiang@vip.163.com.
Advances in Experimental Medicine and Biology
|December 1, 2019
Summary
Chronic stress, particularly early life stress, increases depression risk by altering brain function. Genetic and epigenetic factors interact with stress to influence vulnerability to depressive disorders.
Area of Science:
- Neuroscience
- Psychiatry
- Genetics
Background:
- Stress is a common life experience, but chronic or early life stress negatively impacts mental health, increasing depression risk.
- The hypothalamic-pituitary-adrenal (HPA) axis plays a key role in mediating stress's effects on brain structure and function.
- Genetic factors, including polymorphisms in SERT, BDNF, GR, FKBP5, MR, and CRHR1, moderate the link between stress and depression.
Purpose of the Study:
- To explore the intricate relationship between stressful life events and the onset of depressive disorders.
- To elucidate the mediating role of HPA axis dysregulation in stress-induced brain alterations.
- To investigate the combined influence of genetic predisposition and epigenetic modifications on depression vulnerability.
Main Methods:
- Review of existing evidence linking stress, HPA axis activity, genetic factors, and epigenetic modifications to depressive disorders.
- Analysis of how stressful life experiences, especially early life stress, induce epigenetic changes (DNA methylation, miRNA regulation).
- Examination of the interplay between environmental stress, genetic risk, and epigenetic mechanisms in altering brain function.
Main Results:
- Strong association found between chronic/early life stress and depressive disorder development.
- Stress-induced epigenetic modifications in risk genes lead to long-lasting changes in gene expression.
- Interaction between environmental stress, genetic risk factors, and epigenetic modifications is crucial for predicting depression onset.
Conclusions:
- Stress, in conjunction with genetic and epigenetic factors, significantly influences brain structure, function, and physiological/psychological well-being.
- Understanding the gene-environment interaction is essential for predicting and potentially preventing depressive disorders.
- Epigenetic modifications mediated by early life stress represent a critical mechanism linking stress exposure to long-term depression vulnerability.
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