Diurnal variation of cerebrospinal fluid hypocretin-1 (Orexin-A) levels in control and depressed subjects.
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.
Salomon
Ronald M
RM
Department of Psychiatry, Vanderbilt University School of Medicine, Nashville, Tennessee 37212, USA.
Ripley
Beth
B
Kennedy
John S
JS
Johnson
Benjamin
B
Schmidt
Dennis
D
Zeitzer
Jamie M
JM
Nishino
Seiji
S
Mignot
Emmanuel
E
D000328:Adult; D000928:Antidepressive Agents / Q000627:therapeutic use; D018687:Antidepressive Agents, Second-Generation / Q000627:therapeutic use; D016642:Bupropion / Q000627:therapeutic use; D002352:Carrier Proteins / Q000134:cerebrospinal fluid* / Q000187:drug effects; D016022:Case-Control Studies; D002940:Circadian Rhythm / Q000187:drug effects; D003866:Depressive Disorder / Q000134:cerebrospinal fluid* / Q000188:drug therapy*; D018765:Dopamine Uptake Inhibitors / Q000627:therapeutic use; D005260:Female; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D008297:Male; D009479:Neuropeptides / Q000134:cerebrospinal fluid* / Q000187:drug effects; D000068797:Orexins; D011863:Radioimmunoassay; D017367:Selective Serotonin Reuptake Inhibitors / Q000627:therapeutic use; D020280:Sertraline / Q000627:therapeutic use
D000928:Antidepressive Agents; D018687:Antidepressive Agents, Second-Generation; D016642:Bupropion; D002352:Carrier Proteins; D018765:Dopamine Uptake Inhibitors; D047908:Intracellular Signaling Peptides and Proteins; D009479:Neuropeptides; D000068797:Orexins; D017367:Selective Serotonin Reuptake Inhibitors; D020280:Sertraline; C000596229:HCRT protein, human