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OBJECTIVE: The goal of this study was to assess brain glucose metabolism and its relationship to dissociation measures and clinical symptoms in DSM-IV depersonalization disorder. METHOD: Positron emission tomography scans coregistered with magnetic resonance images of eight subjects with depersonalization disorder were compared to those of 24 healthy comparison subjects. The two groups did not differ in age, sex, education, performance on a baseline neuropsychological battery, or performance on a verbal learning task administered during [18F]fluorodeoxyglucose uptake. A cortical analysis by individual Brodmann’s areas was performed. RESULTS: Compared to the healthy subjects, subjects with depersonalization disorder showed significantly lower metabolic activity in right Brodmann’s areas 22 and 21 of the superior and middle temporal gyri and had significantly higher metabolism in parietal Brodmann’s areas 7B and 39 and left occipital Brodmann’s area 19. Dissociation and depersonalization scores among the subjects with depersonalization disorder were significantly positively correlated with metabolic activity in area 7B. CONCLUSIONS: Depersonalization appears to be associated with functional abnormalities along sequential hierarchical areas, secondary and cross-modal, of the sensory cortex (visual, auditory, and somatosensory), as well as areas responsible for an integrated body schema. These findings are in good agreement with the phenomenological conceptualization of depersonalization as a dissociation of perceptions as well as with the subjective symptoms of depersonalization disorder.