The "glucocorticoid hypothesis of depression" posits that chronic stress leads to altered neuronal function/circuitry in the brain, leading to depressive symptoms. This implies:
1) that cortisol secreted by the adrenal glands must function as a neurotransmitter as well as a hormone.
2) that neurons in the brain must express cortisol receptors.
3) that people with depression would be predicted to have low circulating cortisol levels.
4) that people who tend to naturally secrete less CRH from their hypothalamus may be at elevated risk for depression.