Hormonal Regulation
- Hypothalamus
- Releasing factor
- Anterior pituitary
- ACTH (through blood)
- Adrenal cortex
- Cortisol
Depression May Have Systemic Health Consequences
- Hypothalamus stimulates the pituitary gland to release excessive ACTH, continuously driving the adrenal gland
- The adrenal gland releases excessive amounts of catecholamines and cortisol
- Increase in catecholamines can lead to myocardial ischemia, diminished heart rate variability, and can contribute to ventricular arrhythmias
- Increase in catecholamines causes platelet activation; increase in cytokines and interleukins may also contribute to atherosclerosis and eventual hypertension
- Cortisol antagonizes insulin and contributes to dyslipidemia, type 2 diabetes, and obesity; increases in cortisol also suppress the immune system
MDD may not only be a “psychiatric disease,” as there is evidence of widespread systemic consequences. Neuroendocrine dysregulation and elevated sympathetic tone may result in cardiovascular morbidity and increased risk of metabolic syndrome. Immune response may be compromised in MDD. Major depression and depressive symptoms, although commonly encountered in medical populations, are frequently underdiagnosed and undertreated in patients with cardiovascular disease (CVD). This is of particular importance because several studies have shown depression and its associated symptoms to be a major risk factor for both the development of CVD and death after an index myocardial infarction. Treatment of depression in patients with CVD may be able to improve their dysphoria and other signs and symptoms of depression and improve quality of life.
Normal Stress Response: HPA Axis
- Stressor
- CRF released from hypothalamus (crossed out)
- ACTH released from pituitary
- Gluco-corticoids released from adrenal cortex
- Gluco-corticoids provide negative feedback to hypothalamus
Stress Sensitization and Brain Atrophy
- Prolonged Stress
- Prolonged Glucocorticoid Release
- Disinhibition of HPA Axis by Hippocampus
- Hippocampal Atrophy
- Hippocampal Atrophy
- Disinhibition of HPA Axis by Hippocampus
- Prolonged Glucocorticoid Release
Cellular Atrophy After Stress
- Rat hippocampal neurone before (A) and after (B)
3-week repeated stress
Structural Changes in Brain in Depression
- Stress
- Decrease in neurogenesis
- Decrease in hippocampal volume
- Cellular atrophy
