![]() ![]() We reexamined subjects 2 years later to determine whether they developed overt hypothyroidism. We analyzed HPT activity, including serum thyrotropin bioactivity, during SD in patients with MDD and normal subjects and measured serum concentrations of cortisol to determine whether changes were specific to the HPT. We postulated that the nocturnal pattern of serum thyrotropin concentration in patients with MDD differs from that of normal subjects and that the clinical response to SD correlates with this altered pattern. Thyroxine administration during SD can facilitate complete and sustained remission after SD, 28 suggesting that altered HPT function also mediates behavioral effects of SD. ![]() Therefore, little is known about detailed thyrotropin secretion during SD in depression. However, most investigators measured serum thyrotropin level infrequently or only compared hormone levels before and after SD. 21, 22 Thyrotropin secretion normally demonstrates a circadian rhythm, peaking during early sleep, 23 but nocturnal serum thyrotropin level continues to rise during SD, 24 - 27 associated with clinical improvement in some 25, 26 but not all 24, 27 studies. Protirelin causes acute changes in sleep electroencephalograms in normal volunteers. The HPT also may be involved in the mood response to SD. These observations support HPT involvement in MDD, with endocrinologically distinct MDD subgroups. 10, 11 Finally, protirelin has been shown to have antidepressant effects in some 10, 17 but not all 18, 19 patients. However, rather than having the exaggerated thyrotropin response to protirelin characteristic of hypothyroidism, about 30% of depressed euthyroid patients have blunted responses to protirelin. 10 - 13 Major depressive disorder is common in hypothyroid patients, 10 and some 12 - 14 but not all 15, 16 studies indicate that some patients with MDD have subclinical primary hypothyroidism. 6 - 9 Alterations in hypothalamic-pituitary-thyroid axis (HPT) function may be involved in MDD. Some findings suggest a relationship between diurnal rhythm and the effects of SD: SD has been shown to alter the sleep-wake cycle, 3, 4 diurnal mood variability predicts the antidepressant effect of SD, 1, 2, 5 and phase advance and light therapy are sometimes effective in MDD. ONE NIGHT of sleep deprivation (SD) induces a rapid, albeit transient, remission in about 60% of patients with major depressive disorder (MDD), 1, 2 but the mechanism by which SD exerts its antidepressant effect is unknown. ![]() Sleep deprivation responders compensate by secreting more thyrotropin with normal bioactivity nonresponders compensate by secreting thyrotropin with increased bioactivity. Other thyroid indexes and serum cortisol concentrations were similar among groups.Ĭonclusions Depressed patients have mild compensated thyroid resistance to thyrotropin action, not subclinical autoimmune primary hypothyroidism. The bioactivity of thyrotropin in nonresponders was significantly greater than in responders (F 1,8.99 = 7.52 P =. Responders had exaggerated responses to protirelin the next afternoon. Results Nocturnal serum thyrotropin concentrations were consistently higher in responders, entirely because of elevated levels in the women reponders. To determine if the changes were limited to the hypothalamic-pituitary-thyroid axis, we measured serum cortisol, which also has a circadian secretory pattern. We measured serum thyrotropin every 15 minutes during the night of sleep deprivation, thyrotropin bioactivity, the thyrotropin response to protirelin the next afternoon, and other indexes of hypothalamic-pituitary-thyroid function. Methods We studied 18 patients with major depressive disorder and 10 normal volunteers. We wished to define precisely the status of the hypothalamic-pituitary-thyroid axis of depressed patients during sleep deprivation and the possible relationship of hypothalamic-pituitary-thyroid function to the mood response. Subclinical hypothyroidism may be associated with depression, and changes in hypothalamic-pituitary-thyroid function may affect the mood response to sleep deprivation.
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