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Eric A. Nofzinger, MD; Daniel J. Buysse, MD; Anne Germain, PhD; Cameron Carter, MD; Beatriz Luna, PhD; Julie C. Price, PhD; Carolyn C. Meltzer, MD; Jean M. Miewald, BA; Charles F. Reynolds III, MD; David J. Kupfer, MD

Arch Gen Psychiatry. 2004;61:695-702.

Background  Depression is associated with sleep disturbances, including alterations in rapid eye movement (REM) sleep, that may relate to the neurobiology of the disorder. Given that REM sleep activates limbic and anterior paralimbic cortex and that depressed patients demonstrate increases in electroencephalographic sleep measures of REM, we hypothesized greater activation of these structures during waking to REM sleep in depressed patients.

Design  Subjects completed electroencephalographic sleep and regional cerebral glucose metabolism assessments during both waking and REM sleep using [¹⁸F]fluoro-2-deoxy-D-glucose positron emission tomography.

Setting  Patients and healthy subjects recruited from the general community to participate in a research study of depression at an academic medical center.

Patients  Twenty-four unmedicated patients who met the Structured Clinical Interview for DSM-IV criteria for current major depression and who had a score of 15 or higher on a 17-item Hamilton Rating Scale for Depression; 14 medically healthy subjects of comparable age and sex who were free of mental disorders.

Main Outcome Measures  Electroencephalographic sleep, semiquantitative and relative regional cerebral metabolism during waking and REM sleep.

Results  Depressed patients showed greater REM sleep percentages. While both healthy and depressed patients activated anterior paralimbic structures from waking to REM sleep, the spatial extent of this activation was greater in the depressed patients. Additionally, depressed patients showed greater activation in bilateral dorsolateral prefrontal, left premotor, primary sensorimotor, and left parietal cortices, as well as in the midbrain reticular formation.

Conclusions  Increased anterior paralimbic activation from waking to REM sleep may be related to affective dysregulation in depressed patients. Increased activation of executive cortex may be related to a cognitive dysregulation. These results suggest that altered function of limbic/anterior paralimbic and prefrontal circuits in depression is accentuated during the REM sleep state. The characteristic sleep disturbances of depression may reflect this dysregulation.

From the Departments of Psychiatry (Drs Nofzinger, Buysse, Germain, Carter, Luna, Meltzer, Reynolds, and Kupfer and Ms Miewald), Psychology (Drs Carter and Luna), Neuroscience (Dr Carter), and Radiology (Drs Price and Meltzer), University of Pittsburgh School of Medicine, Pittsburgh, Pa; and the Department of Psychiatry and Behavioral Sciences, University of California–Davis (Dr Carter).

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