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Objective: Three thalamic nuclei--the mediodorsal nucleus, pulvinar, and centromedian nucleus--each have unique reciprocal circuitry with cortical and sub-cortical areas known to be affected in schizophrenia. To determine if the disorder is also associated with dysfunction in the mediodorsal nucleus, pulvinar, and centromedian nucleus, relative glucose metabolism in these regions was measured in a large group of unmedicated patients with schizophrenia. Method: [[sup.18]F]-deoxyglucose positron emission tomography (PET) and matching [T.sub.1]-weighted magnetic resonance imaging (MRI) scans were obtained for 41 unmedicated patients with schizophrenia and 60 age-and sex-matched healthy subjects. The PET and MRI images for each subject were coregistered, and the whole thalamus, mediodorsal nucleus, pulvinar, and centromedian nucleus were traced on the MRI image. Relative glucose metabolism in these regions was assessed. Results: Patients with schizophrenia showed significantly lower relative glucose metabolism in the mediodorsal nucleus and the centromedian nucleus and significantly higher relative glucose metabolism in the pulvinar, compared with the healthy subjects. Lower relative glucose metabolism in the total thalamus, mediodorsal nucleus, and pulvinar was associated with greater overall clinical symptoms as measured by the Brief Psychiatric Rating Scale. Lower relative glucose metabolism in the pulvinar was associated with more hallucinations and more positive symptoms, while lower relative glucose metabolism in the mediodorsal nucleus was associated with more negative symptoms. Conclusions: The findings suggest that patients with schizophrenia exhibit dysfunction in thalamic subdivisions with distinct cortical connections and that these thalamic subdivisions have specific associations with clinical symptoms.