Interface between hypothalamic-pituitary-adrenal axis and brain-derived neurotrophic factor in depression
Hiroshi Kunugi1, Hiroaki Hori, Naoki Adachi
1Department of Mental Disorder Research, National Institute of Neuroscience, National Center of Neurology and Psychiatry, Tokyo, Japan. hkunugi@ncnp.go.jp
Psychiatry and Clinical Neurosciences
|October 7, 2010
Summary
This review integrates research on the hypothalamic pituitary-adrenal (HPA) axis and brain-derived neurotrophic factor (BDNF) to explain depression. Findings suggest HPA axis and BDNF dysregulation contribute to depression pathophysiology and antidepressant treatment mechanisms.
Area of Science:
- Neuroscience
- Psychiatry
- Endocrinology
Background:
- The pathophysiology of depressive disorder is not fully understood.
- Two promising frameworks involve hypothalamic pituitary-adrenal (HPA) axis abnormalities and brain-derived neurotrophic factor (BDNF).
Purpose of the Study:
- To review research on HPA axis and BDNF in depression.
- To formulate an integrated theory of depressive disorder based on these frameworks.
Main Methods:
- Review of hormonal challenge tests (e.g., dexamethasone/corticotropin-releasing hormone test).
- Analysis of evidence from postmortem, animal, blood, and genetic studies on BDNF.
- Examination of the interaction between glucocorticoid receptors and BDNF signaling.
Main Results:
- Hormonal tests reveal both hypercortisolism and hypocortisolism in depression.
- Evidence links BDNF to depression pathogenesis and antidepressant treatment efficacy.
- Stress reduces BDNF expression, while antidepressants increase it.
- Glucocorticoids interfere with BDNF signaling, impacting brain structure and neurogenesis.
Conclusions:
- An integrated model of depression pathophysiology and recovery is proposed.
- HPA axis and BDNF dysregulation are central to depression.
- Understanding these interactions may inform novel therapeutic strategies.
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