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David N. Orth, MD; Richard C. Shelton, MD; Wendell E. Nicholson, BS; Paolo Beck-Peccoz, MD; Andrew J. Tomarken, PhD; Luca Persani, MD; Peter T. Loosen, MD, PhD

Arch Gen Psychiatry. 2001;58:77-83.

Background  One night of sleep deprivation induces a brief remission in about half of depressed patients. Subclinical hypothyroidism may be associated with depression, and changes in hypothalamic-pituitary-thyroid function may affect the mood response to sleep deprivation. 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.

Methods  We studied 18 patients with major depressive disorder and 10 normal volunteers. We assessed mood before and after sleep. 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. To determine if the changes were limited to the hypothalamic-pituitary-thyroid axis, we measured serum cortisol, which also has a circadian secretory pattern.

Results  Nocturnal serum thyrotropin concentrations were consistently higher in responders, entirely because of elevated levels in the women reponders. Responders had exaggerated responses to protirelin the next afternoon. The bioactivity of thyrotropin in nonresponders was significantly greater than in responders (F_1,8.99 = 7.52; P = .02). Other thyroid indexes and serum cortisol concentrations were similar among groups.

Conclusions  Depressed patients have mild compensated thyroid resistance to thyrotropin action, not subclinical autoimmune primary hypothyroidism. Sleep deprivation responders compensate by secreting more thyrotropin with normal bioactivity; nonresponders compensate by secreting thyrotropin with increased bioactivity.

From the Departments of Medicine (Drs Orth and Loosen and Mr Nicholson) and Psychiatry (Drs Shelton and Loosen), Vanderbilt University Medical Center, Nashville, Tenn; Istituto di Scienze Endocrine, Ospedale Maggiore Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS), Milan, Italy (Dr Beck-Peccoz); Department of Psychology, Vanderbilt University, Nashville (Dr Tomarken); Universitá di Milano, Istituto Auxologico Italiano IRCCS, Milan (Dr Persani); and Psychiatry Service,Veterans Affairs Hospital, Nashville (Dr Loosen).

Corresponding author: Peter T. Loosen, MD, PhD, Psychiatry Service (116A), Department of Veterans Affairs Medical Center, 1310 24th Ave S, Nashville, TN 37212-2637 (e-mail: ptloosen{at}aol.com).