Neurobiology of non-REM sleep in depression: further evidence for hypofrontality and thalamic dysregulation

OBJECTIVE: Sleep disturbances characterize depression and may reflect the abnormal persistence of brain activity from wakefulness into non-REM sleep. The goal of this study was to investigate the functional neuroanatomical correlates of non-REM sleep relative to presleep wakefulness in depressed patients and healthy subjects. METHOD: Twelve medication-free depressed patients and 13 healthy subjects underwent polysomnography and (18)F]fluorodeoxyglucose positron emission tomography scans during presleep wakefulness and non-REM sleep. Statistical parametric mapping contrasts were performed to detect differences in relative regional cerebral glucose metabolism between presleep wakefulness and non-REM sleep in each group as well as interactions across states and between groups. RESULTS: Relative to healthy subjects, depressed patients showed less of a decrease in relative regional cerebral glucose metabolism from presleep wakefulness to non-REM sleep in the left and right laterodorsal frontal gyri, right medial prefrontal cortex, right superior and middle temporal gyri, insula, right posterior cingulate cortex, lingual gyrus, striate cortex, cerebellar vermis, and left thalamus. CONCLUSIONS: Patterns of relative regional cerebral glucose metabolism changes from presleep wakefulness to non-REM sleep differ in healthy subjects and depressed patients. Specifically, the transition from wakefulness to non-REM sleep was characterized by the relative persistence of elevated metabolic activity in frontoparietal regions and thalamus in depressed patients compared with healthy subjects. These findings suggest that abnormal thalamocortical network function may underlie sleep anomalies and complaints of nonrestorative sleep in depressed patients.