Anatomic, Functional, and Clinical Studies of Neuroendocrine Function in Bipolar Disorder

The neuroendocrine system, which plays an integral role in regulation of mood, is dysfunctional in patients with affective disorders. This paper reviews data from anatomic, functional, and clinical studies elucidating neuroendocrine function in patients with bipolar disorder. In an anatomic study using magnetic resonance imaging, patients with bipolar disorder had significantly smaller pituitary volumes compared with healthy controls or patients with unipolar depression. In functional studies, bipolar disorder is characterized by abnormalities of hypothalamicpituitary-adrenal function as reflected primarily in a blunted response to the dexamethasone suppression test; blunted release of thyrotropin-stimulating hormone in response to administration of exogenous thyrotropin-releasing hormone; and blunted prolactin and growth hormone responses. Some or all of these abnormalities may be attributed at least partly to central serotonergic dysfunction. In clinical studies, a high incidence of menstrual irregularities reflecting dysregulation of the hypothalamic-pituitary-gonadal axis was observed in patients with bipolar disorder. The degree to which these functional, anatomic, and clinical neuroendocrine abnormalities cause or result from mood pathology—or both—is difficult to determine on the basis of available data. It is likely that the primary clinical manifestation of neuroendocrine dysfunction in bipolar disorder is the illness itself. That is, abnormalities in the neuroendocrine system with or without other central or peripheral nervous system pathologies may constitute the pathophysiologic basis of bipolar disorder. Much work remains before the clinical significance of the neuroendocrine abnormalities in bipolar disorder is understood. To improve the quality of care for patients, additional research is needed to define the clinical implications of specific aspects of neuroendocrine dysfunction in bipolar disorder. Research should assess the degree to which specific hormonal responses that are blunted in bipolar disorder contribute to mood symptoms and the impact on mood symptoms of medications that normalize specific aspects of neuroendocrine function. (Adv Stud Med. 2003;3(8A):S726-S732)