Rapid antidepressant changes with sleep deprivation in major depressive disorder are associated with changes in vascular endothelial growth factor (VEGF): a pilot study

Brain Res Bull. 2011 Aug 10;86(1-2):129-33. doi: 10.1016/j.brainresbull.2011.06.003. Epub 2011 Jun 16.


While conventional antidepressants benefit many patients with major depressive disorder (MDD), as much as eight to 12 weeks can elapse before significant improvements in depressive symptoms are seen. Treatments that act more rapidly in MDD are urgently needed. Sleep deprivation (SD) has been shown to produce a rapid antidepressant response within one day in 50-60% of patients with MDD; thus, identifying its antidepressant mechanism may contribute to the development of antidepressants that act more rapidly. The present study evaluated the effects of 39 h of SD on mood, as well as on plasma levels of brain derived neurotrophic factor (BDNF) and vascular endothelial growth factor (VEGF) in patients with MDD. After a drug-free period of at least two weeks, 11 patients (6 males, 5 females; ages 25-62) who met DSM-IV criteria for MDD underwent total SD. Plasma samples for BDNF and VEGF assays were collected on Days 1 (baseline) and 2. The six-item Hamilton Rating Scale for Depression (HAMD-6) was the primary outcome measure. HAMD-6 scores decreased significantly after SD (Day 2). SD was negatively correlated with change in HAMD-6 score and change in VEGF levels, indicating that as depression scores decreased following SD, VEGF plasma levels increased. In contrast, SD did not alter plasma BDNF concentrations, nor was an association found between BDNF levels and clinical improvement on the HAMD-6. These results suggest that SD is associated with mood-related changes in plasma VEGF levels, but not plasma BDNF levels. Further studies using larger sample sizes are needed to confirm these preliminary findings.

Trial registration: ClinicalTrials.gov NCT00078715.

Publication types

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

MeSH terms

  • Adult
  • Animals
  • Antidepressive Agents / therapeutic use*
  • Brain-Derived Neurotrophic Factor / blood
  • Depressive Disorder, Major / blood
  • Depressive Disorder, Major / drug therapy*
  • Depressive Disorder, Major / physiopathology*
  • Female
  • Humans
  • Male
  • Middle Aged
  • Neuropsychological Tests
  • Pilot Projects
  • Sleep Deprivation*
  • Vascular Endothelial Growth Factor A / blood*


  • Antidepressive Agents
  • Brain-Derived Neurotrophic Factor
  • Vascular Endothelial Growth Factor A

Associated data

  • ClinicalTrials.gov/NCT00078715