Schizophrenia is a debilitating mental illness that places a large burden on patients, their families, and society-at-large. The glutamate hypothesis of schizophrenia puts forth a compelling mechanism to characterize features of the illness. To this end, we explored the neurometabolic and neuroanatomical profiles of patients with schizophrenia using magnetic resonance imaging, with a particular focus on the glutamatergic system. First, we explored associative striatum neurometabolite levels using proton magnetic resonance spectroscopy (1H-MRS) within a sample composed of antipsychotic-naïve patients experiencing their first-episode of psychosis (FEP) and age- and sex-matched healthy controls. The FEP group had elevated myo-inositol, choline, and glutamate levels compared to the healthy control group. Second, again within a sample of antipsychotic-naïve patients with FEP and age- and sex-matched healthy controls, we investigated whether elevated levels of glutamatergic neurometabolites within the precommissural dorsal caudate (PDC), as assessed by 1H-MRS, were related to measures of brain structure. In addition to widespread cortical thinning and suggestions of possible precommissural caudate volume (PCV) deficits within the patient group, a negative association between PDC glutamate+glutamine levels and PCV was found in the FEP group. Third, striatal neurometabolite levels were examined using 1H-MRS within a sample of patients with schizophrenia who had undergone long-term antipsychotic treatment and healthy controls. No group differences in neurometabolite levels were identified. Multiple study visits permitted a 1H-MRS reliability assessment. Taken together, the results from this body of work suggest elevated levels of striatal glutamatergic neurometabolites within the early, antipsychotic-naïve stages of schizophrenia, which are contrastingly shown to be comparable to those of healthy controls in the later, medicated stages of illness. Findings also provide evidence for glial activation that may resultantly disrupt glutamatergic tone, as well as a striatal excitotoxic mechanism that may account for some of the vast structural compromise that exists in patients with schizophrenia.Ph.D
