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

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


J Psychiatry Neurosci 2009; 34(5): 352-360

Denise Bernier, PhD; Robert Bartha, PhD; Sivakumaran Devarajan, MD; Frank P. MacMaster, PhD; Matthias H. Schmidt, MD; Benjamin Rusak, PhD

Bernier, Schmidt, Rusak — Department of Psychiatry; Bernier, Rusak — Department of Psychology; Rusak — Department of Pharmacology; Schmidt — Department of Radiology, Dalhousie University, Halifax, NS; Bartha — the Robarts Research Institute; Devarajan — Department of Psychiatry, University of Western Ontario, London, Ont.; MacMaster — Department of Psychiatry and Behavioral Neurosciences, Wayne State University School of Medicine, Detroit, Mich.


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 (F1–16 = 5.07, p = 0.039, Cohen’s d = 0.54) and an 11.3% increase in prefrontal Cho (F1–21 = 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, t9 = –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.

Conclusions: 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.

Submitted Oct. 7, 2008; Revised Mar. 27, May 26, 2009; Accepted May 27, 2009.

Acknowledgements: This research was supported by grants from the Nova Scotia Capital District Health Authority Research Fund and the Department of Psychiatry, Dalhousie University. It was submitted in partial fulfillment of the requirements for a PhD degree (D.B.) at Dalhousie University. We thank Carl Helmick, Mark Given, Matthew Rogers and Gregory McLean for their invaluable technical assistance; the late Vivek Kusumakar for his support and encouragement; Sonia Chehil and Marina Sokolenko for clinical support; Mohamed Abdolell and Wade Blanchard for their useful advice on statistical analyses; and three anonymous reviewers for numerous
helpful suggestions.

Competing interests: None declared.

Contributors: Drs. Bernier, MacMaster and Rusak designed the study. Drs. Bernier, Devarajan, MacMaster and Schmidt acquired the data, which Drs. Bernier, Bartha, MacMaster, Schmidt and Rusak analyzed. Drs. Bernier, MacMaster and Rusak wrote the article, which all authors reviewed and approved for publication.

Correspondence to: Dr. B. Rusak, Department of Psychiatry, Dalhousie University, 8215 Lane Bldg., Queen Elizabeth II Health Sciences Centre, 5909 Veterans Memorial Lane, Halifax NS B3H 2E2; Benjamin.Rusak@dal.ca