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Updated: May 18, 2026
06:55
An Unpredictable Chronic Mild Stress Protocol for Instigating Depressive Symptoms, Behavioral Changes and Negative Health Outcomes in Rodents
Published on: December 2, 2015
[The hypothalamic-pituitary-adrenal axis and depressive disorder: recent progress]
Hiroshi Kunugi1, Hiroaki Hori, Tadahiro Numakawa
1Department of Mental Disorder Research, National Institute of Neuroscience, National Center of Neurology and Psychiatry, 4-1-1, Ogawahigashi, Kodaira, Tokyo, 187-8502 Japan. hkunugi@ncnp.go.jp
Nihon Shinkei Seishin Yakurigaku Zasshi = Japanese Journal of Psychopharmacology
|September 28, 2012
Summary
Depression involves abnormal stress responses. This study shows how excessive cortisol (hypercortisolism) and low cortisol (hypocortisolism) impact brain function and neural networks, affecting depression symptoms.
Area of Science:
- Neuroendocrinology
- Neurobiology
- Psychiatry
Context:
- Depression is linked to stress and hypothalamic-pituitary-adrenal (HPA) axis dysfunction.
- Chronic HPA axis hyperactivity and hypercortisolism are implicated in depression.
- Brain-derived neurotrophic factor (BDNF) also plays a role in depression.
Purpose:
- To investigate the role of HPA axis abnormalities, including hypercortisolism and hypocortisolism, in depression.
- To explore the molecular mechanisms by which glucocorticoids affect BDNF signaling and neuronal function.
- To examine the neuroanatomical and neural network correlates of HPA axis dysfunction in depression.
Summary:
- The dexamethasone (DEX)/CRH test effectively monitors HPA axis abnormalities, which normalize with treatment response.
- Glucocorticoids suppress BDNF-induced neuronal growth and synaptic formation by blocking MAPK and PLC-gamma pathways.
- Hypercortisolism correlates with gray matter volume loss and reduced neural network integrity (MRI/DTI), while hypocortisolism is associated with distress and personality traits.
Impact:
- This research elucidates molecular and macroscopic mechanisms linking HPA axis dysregulation to depression.
- Findings highlight the dual role of cortisol imbalance (hyper- and hypocortisolism) in the spectrum of depression disorders.
- The study provides insights into potential therapeutic targets for depression by understanding glucocorticoid-BDNF interactions and neurobiological changes.
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