Alterations in regional cerebral glucose metabolism across waking and non-rapid eye movement sleep in depression

Background: Depression is associated with sleep disturbances, including alterations in non-rapid eye movement (NREM) sleep. Non-rapid eye movement sleep is associated with decreases in frontal, parietal, and temporal cortex metabolic activity compared with wakefulness. Objective: To show that depressed patients would have less of a decrease than controls in frontal metabolism between waking and NREM sleep and to show that during NREM sleep, they would have increased activity in structures that promote arousal. Design: Subjects completed electroencephalographic sleep and regional cerebral glucose metabolism assessments during both waking and NREM sleep using [F-18]fluoro-2-deoxy-D-glucose positron emission tomography. Setting: General clinical research center. Patients: The study included 29 unmedicated patients who met the Structured Clinical Interview for DSM-IV criteria for current major depression and who had a score of 15 or greater on a 17-item Hamilton Rating Scale for Depression and 28 medically healthy subjects of comparable age and sex who were free of mental disorders. Main Outcome Measures: Electroencephalographic sleep and regional cerebral metabolism during waking and NREM sleep. Results: Depressed patients showed smaller decreases than healthy subjects in relative metabolism in broad regions of the frontal, parietal, and temporal cortex from waking to NREM sleep. Depressed patients showed larger decreases than healthy subjects in relative metabolism in the left amygdala, anterior cingulate cortex, cerebellum, parahippocampal cortex, fusiform gyrus, and occipital cortex. However, in post hoc analyses, depressed patients showed hypermetabolism in these areas during both waking and NREM sleep. Conclusions: The smaller decrease in frontal metabolism from waking to NREM sleep in depressed patients is further evidence for a dynamic sleep-wake alteration in prefrontal cortex function in depression. Hypermetabolism in a ventral emotional neural system during waking in depressed patients persists into NREM sleep.