BRAIN GLUCOSE-METABOLISM DURING NON-RAPID EYE-MOVEMENT SLEEP IN MAJORDEPRESSION - A POSITRON EMISSION TOMOGRAPHY STUDY

Background: Depression is characterized by several sleep-related abnor malities shortly before and after sleep onset, such as prolonged sleep latency, loss of stage 3-4 sleep, reduced rapid eye movement (REM) la tency, increased nocturnal core body temperature, and abnormal hormone secretion patterns. Sleep deprivation is associated with a temporary improvement in depression. We hypothesized that depressed patients may be ''overaroused'' and that absolute cerebral glucose metabolism woul d be elevated during the first nocturnal non-REM sleep period in depre ssed patients compared with normal controls. In addition, since hypofr ontality (greater metabolic activity in occipital compared with fronta l cortical activity) has been reported in waking positron emission tom ographic studies of depressed patients compared with controls, we pred icted significant hypofrontality in depressed patients during the firs t non-REM period. Methods: Positron emission tomography with fludeoxyg lucose F 18 was used to compare 10 unmedicated men with unipolar depre ssion with 12 normal men during the first non-REM sleep period at norm al bedtime. Results: Whole-brain absolute metabolic rate during non-RE M sleep was significantly elevated (+47%) in patients compared with co ntrols. Mean absolute cerebral glucose metabolic rate was also higher in every area of the brain in patients compared with normal controls. The greatest significant mean increases were in the posterior cingulat e and amygdala (+44%), hippocampus (+37% to +43%), occipital and tempo ral cortex (+33% to +34%), and pons (+33%). Relative metabolic rates i n specific neroanatomical areas, however, varied considerably both wit hin the patient group and between patients and controls. Patients show ed significant hypofrontality, particularly in the medio-orbital front al cortex, compared with controls. Patients also showed significant re ductions of relative metabolic rate in the anterior cingulate, caudate , and medial thalamus compared with controls. Conclusions: These findi ngs provide further support for the hyperarousal hypothesis of some ty pes of major depressive disorder. Abnormal patterns of cerebral metabo lism during non-REM sleep in depressed patients confirmed earlier waki ng findings of decreased relative frontal and abnormal limbic metaboli c activity and striatal metabolism in association with posterior corti cal increases.