Journal
BIOLOGICAL PSYCHIATRY
Volume 54, Issue 2, Pages 96-104Publisher
ELSEVIER SCIENCE INC
DOI: 10.1016/S0006-3223(02)01740-7
Keywords
depression; hypocretin; sertraline; bupropion; circadian rhythms; sleep
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Funding
- NCRR NIH HHS [M01RR00095] Funding Source: Medline
- NIMH NIH HHS [MH40041] Funding Source: Medline
- NINDS NIH HHS [NS 33797, NS 23724] Funding Source: Medline
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Background: Hypocretins, excitatory neuropeptides at monoaminergic synapses, appear to regulate human sleep-wake cycles. Undetectable cerebrospinal fluid hypocretin-1 levels are seen in narcolepsy, which is frequently associated with secondary depression. Shortened rapid eye movement latency is observed in both narcolepsy and depression. Cerebrospinal fluid hypocretin-1 levels have not been reported in mood disorders. Methods: We examined hypocretin-1 levels in 14 control and 15 depressed subjects. Cerebrospinal fluid was drawn continuously in supine subjects for 24 hours with an indwelling intrathecal catheter under entrained light-dark conditions. Depressed subjects were studied before and after 5 weeks of sertraline (n = 10, three nonresponders) or bupropion (n = 5, two nonresponders). Results: Hypocretin-1 levels varied slightly (amplitude 10%) but significantly across the diurnal cycle in control subjects, with amplitude significantly reduced in depression (3%). Levels were lowest at midday, surprising for a hypothetically wake-promoting peptide. Mean hypocretin levels trended higher in depressive than in control subjects. Hypocretin-1 levels decreased modestly but significantly after sertraline (-14%) but not bupropion. Conclusions: Our results are consistent with previous physiologic findings in depression indicating dampened diurnal variations in hypocretin-1. The finding that sertraline but not bupropion slightly decreased cerebrospinal fluid hypocretin-1 indicates a serotoninergic influence on hypocretin tone. (C) 2003 Society of Biological Psychiatry.
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