Sleep onset represents a highly evolved, dynamic biological process, involving the reduction and ultimate cessation of noradrenergic and serotonergic neuronal activity, the onset of cholinergic "bursts" of firing from pontine nuclei and the increased secretion of GH primarily through muscarinic inhibition of SOM, the GH secretagogue suppressant. During the early phases of sleep, increases of spontaneous GH secretion have been associated with slow wave (delta) sleep, the former subsiding several hours following sleep onset. The elevations of CRF and cortisol increases that are frequently evident in Mood Disorders are inhibitory towards GH secretion and imply a ratio increase of CRF to GRF in adult depression (Holsboer, 1994).
Thus, adults with acute Major Depressive Disorder (MDD) quite consistently hyposecrete GH around the time of sleep onset. Studies followed depressed subjects into a drug-free recovery phase and found persistence of sleep-related GH hyposecretion, suggesting that this may be a trait marker for MDD. Investigators have proposed that secretion of growth hormone at night may be phase advanced in depression such that secretion occurs just prior to sleep onset instead of during the first few hours of sleep. Of interest, one group of investigators has reported that the phase-advanced GH peak is phase-delayed into the normal range after recovery from the depressive state, in contrast to the persistent, trait-like nature of the blunted nocturnal GH secretion in adult depression.
Puig-Antich (1987) hypothesized that a serotonin deficit state with cholinergic dominance could lead to sleep-related GH hypersecretion in prepubertal depressives. Coplan and colleagues (2000) examined unperturbed serial GH measurements over a 24-hour period in depressed and normal control adolescents in light of 10 years of clinical follow-up data. A reanalysis of diagnoses demonstrated that lifetime-depressive subjects (subjects who were initially depressed and those who became depressed over the 10-year period) exhibited low levels of GH in the 100 minutes before sleep relative to lifetime depression-free subjects.
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