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.