Altered Patterns of Brain Glucose Metabolism Involve More Extensive and Discrete Cortical Areas in Treatment-resistant Schizophrenia Patients Compared to Responder Patients and Controls: Results From a Head-to-Head 2-[18F]-FDG-PET Study

Background and Hypothesis Treatment resistant schizophrenia (TRS) affects almost 30% of patients with schizophrenia and has been considered a different phenotype of the disease. In vivo characterization of brain metabolic patterns associated with treatment response could contribute to elucidate the neurobiological underpinnings of TRS. Here, we used 2-[F-18]-fluorodeoxyglucose (FDG) positron emission tomography (PET) to provide the first head-to-head comparative analysis of cerebral glucose metabolism in TRS patients compared to schizophrenia responder patients (nTRS), and controls. Additionally, we investigated, for the first time, the differences between clozapine responders (Clz-R) and non-responders (Clz-nR). Study Design 53 participants underwent FDG-PET studies (41 patients and 12 controls). Response to conventional antipsychotics and to clozapine was evaluated using a standardized prospective procedure based on PANSS score changes. Maps of relative brain glucose metabolism were processed for voxel-based analysis using Statistical Parametric Mapping software. Study Results Restricted areas of significant bilateral relative hypometabolism in the superior frontal gyrus characterized TRS compared to nTRS. Moreover, reduced parietal and frontal metabolism was associated with high PANSS disorganization factor scores in TRS (P < .001 voxel level uncorrected, P < .05 cluster level FWE-corrected). Only TRS compared to controls showed significant bilateral prefrontal relative hypometabolism, more extensive in CLZ-nR than in CLZ-R (P < .05 voxel level FWE-corrected). Relative significant hypermetabolism was observed in the temporo-occipital regions in TRS compared to nTRS and controls. Conclusions These data indicate that, in TRS patients, altered metabolism involved discrete brain regions not found affected in nTRS, possibly indicating a more severe disrupted functional brain network associated with disorganization symptoms.