Etiology of Mood Disorders: Hormone factors

Alterations of Hormonal Regulation estimated be etiology of mood disorders. Lasting alterations in neuroendocrine and behavioral responses can result from severe early stress.  Prolactin, growth hormone,Thyroid Axis Activity has been studied and associated with mood disorders exactly incident of depression.

Animal studies indicate that even transient periods of maternal deprivation can alter subsequent responses to stress. Activity of the gene coding for the neurokinin brain-derived neurotrophic growth factor (BDNF) is decreased after chronic stress, as is the process of neurogenesis. Protracted stress thus can induce changes in the functional status of neurons and, eventually, cell death. Recent studies in depressed humans indicate that a history of early trauma is associated with increased HPA activity accompanied by structural changes (i.e., atrophy or decreased volume) in the cerebral cortex.

Elevated HPA activity is a hallmark of mammalian stress responses and one of the clearest links between depression and the biology of chronic stress. Hypercortisolema in depression suggests one or more of the following central disturbances: decreased inhibitory serotonin tone; increased drive from norepinephrine (NE), ACh, or corticotropin releasing hormone (CRH); or decreased feedback inhibition from the hippocampus.

Evidence of increased HPA activity is apparent in 20 to 40 percent of depressed outpatients and 40 to 60 percent of depressed inpatients.

Elevated HPA activity in depression has been documented via excretion of urinary-free cortisol (UFC), 24-hour (or shorter time segments) intravenous (IV) collections of plasma cortisol levels, salivary cortisol levels, and tests of the integrity of feedback inhibition. A disturbance of feedback inhibition is tested by administration of dexamethasone (Decadron) (0.5 to 2.0 mg), a potent synthetic glucocorticoid, which normally suppresses HPA axis activity for 24 hours. Nonsuppression of cortisol secretion at 8:00 AM the following morning or subsequent escape from suppression at 4:00 PM or 11:00 PM is indicative of impaired feedback inhibition. Hypersecretion of cortisol and dexamethasone nonsuppression are imperfectly correlated (approximately 60 percent concordance). A more recent development to improve the sensitivity of the test involves infusion of a test dose of CRH after dexamethasone suppression.

These tests of feedback inhibition are not used as a diagnostic test because adrenocortical hyperactivity (albeit usually less prevalent) is observed in mania, schizophrenia, dementia, and other psychiatric disorders.

Thyroid Axis Activity.
Approximately 5 to 10 percent of people evaluated for depression have previously undetected thyroid dysfunction. What this can reason that thyroid axis activity can be cause of mood disorders?. As reflected by an elevated basal thyroid-stimulating hormone (TSH) level or an increased TSH response to a 500-mg infusion of the hypothalamic neuropeptide thyroid-releasing hormone (TRH). Such abnormalities are often associated with elevated antithyroid antibody levels and, unless corrected with hormone replacement therapy, can compromise response to treatment mood disorders. An even larger subgroup of depressed patients (e.g., 20 to 30 percent) shows a blunted TSH response to TRH challenge. To date, the major therapeutic implication of a blunted TSH response is evidence of an increased risk of relapse despite preventive antidepressant therapy. Of note, unlike the dexamethasone suppression test (DST), blunted TSH response to TRH does not usually normalize with effective treatment.

Growth Hormone
Growth hormone (GH) is secreted from the anterior pituitary after stimulation by NE and Dopamine (DA). Secretion is inhibited by somatostatin, a hypothalamic neuropeptide, and CRH. Decreased CSF somatostatin levels have been reported in depression, and increased levels have been observed in mania.

Prolactin
Prolactin is released from the pituitary by serotonin stimulation and inhibited by DA. Most studies have not found significant abnormalities of basal or circadian prolactin secretion in depression, although a blunted prolactin response to various serotonin agonists has been described. This response is uncommon among premenopausal women, suggesting that estrogen has a moderating effect.