Mitochondrial function is related to alterations at brain SPECT in depressed patients

ABSTRACT Objective: 99mTc-HMPAO retention in brain is proportional to cerebral blood flow (CBF) and related to both the local hemodynamic state and to the cellular content of reduced glutathione (GSH). Alterations of the regional distribution of 99mTc-HMPAO retention, with discrepant results, have been reported at functional brain imaging of unipolar depression. Since a mitochondrial involvement has been reported in depressed patients, the aim of the study was to explore whether the 99mTc-HMPAO retention at SPECT in depressed patients may relate to different levels of mitochondrial function. Methods: All patients had audiological and muscular symptoms, somatic symptoms which are common in depression. Citrate synthase activity (CS) assessed in muscle mitochondria correlated strongly with the activities of three mitochondrial respiratory chain enzymes and was used as a marker of mitochondrial function. K-means clustering performed on CS grouped 8 patients with low and 11 patients with normal CS. Voxel-based analysis (VBA) was performed on the two groups by statistical parametric mapping (SPM2). Results: VBA showed significantly higher 99mTc-HMPAO retention in the patients with low CS as compared to the patients with normal CS in the posterior and inferior frontal cortex, the superior and posterior temporal cortex, the somato-sensory cortex, and the associative parietal cortex. Conclusion: Low muscle CS in depressed patients is related to higher regional 99mTc-HMPAO retention that may reflect cerebrovascular adaptation to impaired intracellular metabolism and/or intracellular enzymatic changes, as previously reported in mitochondrial disorder. Mitochondrial dysfunction in varying proportions of the subjects may explain some of the discrepant results for 99mTc-HMPAO retention in depression.