The Hypothalamic-Pituitary-Adrenal Axis in Affective Disorders and Schizophrenia
Adrenocorticotropin Hormone (ACTH) or corticotropin stimulates the adrenal cortex. More directly, it stimulates secretion of aldosterone. ACTH is secreted from the pituitary in response to corticotropin-releasing factor (CRF) from the hypothalamus. (1)
Research in the past five to ten years suggests that patients with affective disorder, particularly some types of depression, may be suffering from an imbalance in the hypothalamic-pituitary-adrenal axis. (4)
Many of the symptoms of affective disorders are consistent with these types of neuroendocrine abnormalities; since they involve changes in appetite, sleep regulation, and adaptability to stress and change. (4)
The dexamethasone-suppression test (DST) is used commonly to evaluate patients suffering from depression. The DST is specifically designed to determine where the communication system between the brain and the adrenal glands has broken down. (4)
Patients tested take a tablet containing dexamethasone, a potent synthetic hormone very similar to cortisol. As the dexamethasone circulates in the blood and travels to the brain, the hypothalamus in normal individuals “reads” plasma cortisol levels as being high because it interprets the dexamethasone as equivalent to cortisol. It stops sending out CRF to the pituitary, and in turn the pituitary stops sending out ACTH to the adrenals. Thus, taking the dexamethasone tablet “suppresses” the hypothalamic-pituitary-adrenal axis, and within twelve hours the blood levels of cortisol drop to low levels. This is known as “normal suppression.” (4)
Many patients with depressive illness fail to suppress in this normal pattern; something has gone wrong in the hypothalamic-pituitary-adrenal communication system, and cortisol continues to pour out. Even though the patient took the dexamethasone the night before in order to “fool” the hypothalamus, when blood samples are taken the next morning and in the middle of the afternoon or evening, plasma cortisol levels continue to be high. Therefore, the patient’s DST is said to be “abnormal.” (4)
The DST is important because it not only helps illuminate neuroendocrine abnormalities in depression, but also is sometimes used to diagnose depression. (4)
Neuropeptide corticotropin is a releasing factor (CRF) typically secreted in response to stress, common in anxiety and depressive disorders. (2)
SSIs are the recommended first-line pharmacotherapy for anxiety disorders, and their efficacy for depression suggests they should do well for the treatment of anxiety and comorbid depression. (2)
Naloxone reverses both exogenous and endogenous opioids (endorphins, enkephalins, and dynorphins) (3), which are secreted in the hypothalamic-pituitary-adrenal axis. (4)
From Fig. 2
Lipotropin: Originally described as having weak lipolytic effects, its major importance is the precursor to beta-endorphin.
Beta-endorphin and Meta-enkephalin: Opioid peptides with pain-alleviation and euphoric effects.
Melanocyte: Stimulating hormone (MSH): Known to control melanin pigmentation in the skin of most vertabrate. (1)
Related: Psychosis, Antipsychotics, and Estrogen
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