Diurnal variation of cerebrospinal fluid hypocretin-1 (Orexin-A) levels in control and depressed subjects

Biol Psychiatry. 2003 Jul 15;54(2):96-104. doi: 10.1016/s0006-3223(02)01740-7.

Abstract

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.

Publication types

  • Clinical Trial
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adult
  • Antidepressive Agents / therapeutic use
  • Antidepressive Agents, Second-Generation / therapeutic use
  • Bupropion / therapeutic use
  • Carrier Proteins / cerebrospinal fluid*
  • Carrier Proteins / drug effects
  • Case-Control Studies
  • Circadian Rhythm* / drug effects
  • Depressive Disorder / cerebrospinal fluid*
  • Depressive Disorder / drug therapy*
  • Dopamine Uptake Inhibitors / therapeutic use
  • Female
  • Humans
  • Intracellular Signaling Peptides and Proteins*
  • Male
  • Neuropeptides / cerebrospinal fluid*
  • Neuropeptides / drug effects
  • Orexins
  • Radioimmunoassay
  • Serotonin Uptake Inhibitors / therapeutic use
  • Sertraline / therapeutic use

Substances

  • Antidepressive Agents
  • Antidepressive Agents, Second-Generation
  • Carrier Proteins
  • Dopamine Uptake Inhibitors
  • HCRT protein, human
  • Intracellular Signaling Peptides and Proteins
  • Neuropeptides
  • Orexins
  • Serotonin Uptake Inhibitors
  • Bupropion
  • Sertraline