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

Abstract

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.

Fig. 1

Positions of the 2 spectroscopic volumes of interest (VOI): the left dorsal prefrontal region and the pons. We first acquired data from a 16 × 16 × 16–mm VOI in the left dorsal prefrontal region (left panels) and then from a 13 × 13 × 13–mm VOI in the pons (right panels). The VOIs are illustrated in the sagittal plane (above) and the coronal plane (below).

Fig. 2

Concentration levels of choline compounds in institutional units (IU) acquired in the left prefrontal region for both groups combined and for the control (n = 13) and depressed (n = 10) groups (inset) during the baseline scan and 24 h later after overnight sleep restriction. Levels increased significantly after sleep restriction for both groups combined (*p = 0.033, Cohen’s d = 0.46). There was no significant change in the control group alone, but a significant increase among depressed participants (#p = 0.008, Cohen’s d = 1.06). Error bars representing 1 standard deviation are shown in 1 direction only for clarity. The number of values varies because only participants with scans meeting quality criteria on both days are included.

Fig. 3

Concentration levels of creatine-plus-phosphocreatine (tCr) in the pons for both groups combined (n = 18) and separately for the control (n = 8) and depressed (n = 10) groups (inset) during the baseline scan and 24 hours later after overnight sleep restriction. In both groups combined, tCr levels declined by 20.1% after sleep restriction relative to baseline values (*p = 0.039, Cohen’s d = 0.54). We observed similar patterns in the 2 groups (inset), but neither group alone was statistically significant. Error bars representing 1 standard deviation are shown in 1 direction only for clarity. The number of values varies because only participants with scans meeting quality criteria on both days are included.

Fig. 4

Concentration levels of choline compounds (Cho) acquired in the pons during the baseline scan and 24 hours later after overnight sleep restriction. Data are shown for the control group (n = 10) and separately for depressed participants showing at least 30% mood improvement after sleep loss (responders, n = 5) and those failing to show such improvement (nonresponders, n = 5). The omnibus test showed a significant effect of group (p = 0.039). Follow-up tests showed that Cho levels were significantly lower at baseline for nonresponders compared with both responders (*p = 0.008) and controls (#p = 0.001). Error bars representing 1 standard deviation are shown in 1 direction only for clarity. The number of values varies because only participants with scans meeting quality criteria on both days are included.