Effects of overnight sleep restriction on brain chemistry and mood in women with unipolar depression and healthy controls.

BACKGROUND Partial or total overnight sleep deprivation produces immediate mood improvement in about 50% of patients with depression, but not in healthy controls. Our objectives were to compare the neurochemical changes that accompanied partial overnight sleep deprivation in healthy and depressed participants, and to compare baseline neurochemical profiles and overnight neurochemical changes between those depressed participants who did and did not respond to sleep loss with mood improvement. METHODS We studied 2 brain regions (left dorsal prefrontal area and pons) in 12 women with unipolar depression and in 15 healthy women using proton magnetic resonance spectroscopy acquired at 1.5 T. The scans took place at baseline and 24 hours later after a night with sleep restricted to a maximum of 2.5 hours (22:30-01:00). We assessed 3 neurochemical signals (referenced to internal water): N-acetylaspartate (NAA), choline compounds (Cho) and creatine-plus-phosphocreatine (tCr). RESULTS In both groups combined, sleep restriction caused a 20.1% decrease in pontine tCr (F(1-16) = 5.07, p = 0.039, Cohen's d = 0.54) and an 11.3% increase in prefrontal Cho (F(1-21) = 5.24, p = 0.033, Cohen's d = 0.46). Follow-up tests revealed that prefrontal Cho increases were significant only among depressed participants (17.9% increase, t(9) = -3.35, p = 0.008, Cohen's d = 1.06). Five depressed patients showed at least 30% improvement in mood, whereas 6 showed no change or worsening in mood after sleep restriction. Baseline pontine Cho levels distinguished subsequent responders from nonresponders to sleep restriction among depressed participants (z = 2.61, p = 0.008). LIMITATIONS A limitation of this study is the relatively small sample size. CONCLUSION Sleep restriction altered levels of pontine tCr and prefrontal Cho in both groups combined, suggesting effects on phospholipid and creatine metabolism. Baseline levels of pontine Cho were linked to subsequent mood responses to sleep loss, suggesting a role for pontine phospholipid metabolism in mood effects of sleep restriction.