Antidepressants - Glucocorticoi Theory of Depression Flashcards
What is the hypothalamic-pituitary-adrenal axis (HPA)?
An important part of the neuroendocrine system that controls the body’s response to stress.
What is the most influential environmental factor that predisposes an individual to depression?
Stress.
How does HPA-axis respond to stress?
Through a hierarchical organization so that the physiological changes that take place are like a domino effect.
Describe the stress response physiologically.
The neurons in the hypothalamus secrete corticotropin-releasing hormone (CRH). This initiates the release of adrenocorticotropic hormone (ACTH) from the anterior pituitary, which ultimately stimulates the secretion of glucocorticoids (cortisol in humans) from the cortex of the adrenal glands, which sit above the kidneys.
When and how does the stress response stop?
Once stressful experience ends, the HPA-axis response terminates. This is achieved through series of negative-feedback loops - cortisol binds to glucocorticoid receptors in the pituitary, hypothalamus, and especially in the hippocampus, which then sends a signal to the hypothalamus to stop releasing CRH.
What can happen in individuals who experience frequent or chronic stress?
The HPA-axis may become overactive (hyperactive).
What causes HPA-axis hyperactivity?
Downregulation of glucocorticoid receptors in the hippocampus.
What levels and activity of HPA axis and CRH and corisol are found in depressed and suicidal individuals?
Over-activity of HPA axis and high levels of CRH and cortisol.
Where are neurons that contain CRH present?
Hypothalamus
Areas of the limbic system (which plays an important role in emotion and mood)
- Prefrontal cortex contains receptor sites for CRH and cortisol and sends inhibitory projecctions to the hypothalamus.
- Amygdala (fear and anxiety) contains receptors for HPA-axis stress hormones, but sends excitatory projections to the hypothalamus.
What are some structural changes that are found in the limbic areas in depressed individuals?
Both PFC and hippocampus lose volume (i.e. atrophy), and amygdala increases in volume.
What causes structural changes in the limbic system?
Believed to result from high levels of cortisol circulating through the bloodstream and entering the brain.
Severity of depressive symptoms positively correlate to what changes in the amygdala?
Metabolism and blood flow to the amygdala.
Structural changes in these structures leads to what?
PFC, hippocampus and amygdala (which are interconnected to the hypothalamus)
Leads to a loss of balance between inhibition and excitation of the stress system, resulting in heightened stress hormone release.
What substantially increases one’s risk of depression and suicide?
Heightened HPA-axis activity and resulting elevation of stress hormone levels.
Explain the mixed results of Glucocorticoid theory of depression.
- Some clinical trials have found that patients with major depressive disorder experienced significant reduction of depressive symptoms with CRH antagonists.
- Other trials found that CRH receptor antagonists fared no better than a placebo.
- Could be that CRH antagonists benefit only those individuals whose depression is brought on by stress and resulting hyperactivity of the HPA axis.
