A more limited literature inhibitor Bortezomib supports elevations of Gin in medial frontal regions, suggestive of increased glutamatergic neurotransmission. Treatment-related studies Treatment studies using 1H-MRS not surprisingly lag in number compared with cross-sectional investigations. Most of them have been naturalistic observations before and after treatment with antipsychotic

agents. Theberge et al10 examined antipsychotic-naïve Sz subjects at baseline, 10, and 30 months following antipsychotic Inhibitors,research,lifescience,medical treatment. Baseline thalamic Gin elevations were decreased at 30 months, and correlated with widespread temporal and parietal gray matter reductions. This was interpreted as evidence of glutamate-related disease progression, not as a medication effect (at 10 months, Gin did not change). Although a few studies have reported increases in NAA with treatment, the majority have failed to do so. Bertolino et al,11 in a retrospective study, reported higher NAA/Cre in the dorsolateral prefrontal cortex Inhibitors,research,lifescience,medical in patients while treated with antipsychotic Inhibitors,research,lifescience,medical medication compared with when they were medication-free. Fannon

et al12 reported reduced medial temporal NAA/Cre at baseline, which was no longer statistically different from healthy subjects after 3 months of atypical antipsychotic treatment. However, Choe et al13 found low frontal NAA/Cre at baseline with no changes after treatment

with typical and atypical agents (follow-up 1-6 months). We found frontal and striatal NAA reductions in minimally treated patients that did not change following 9-month randomized treatment with quetiapine or haloperidol.14 Szulc et al15 reported no NAA changes Inhibitors,research,lifescience,medical following treatment with various antipsychotics. Finally, Theberge et al10 found no NAA changes following a 30-month treatment. Inhibitors,research,lifescience,medical These clinical studies are generally consistent with largely negative findings in the animal TI-MRS literature examining antipsychotic exposure in rats. Lindquist et al16 found no reductions of frontal NAA after 1 week of haloperidol but a reduction with olanzapine. We found no changes in NAA AV-951 after 6 weeks of clozapine or haloperidol.17 Additionally, 6 months exposure to haloperidol produced no changes in NAA, Glu, Gin, or GABA.18 However, Ilarte et al19 did find increased NAA in the rat striatum with long-term haloperidol exposure, consistent with dendritic sprouting. Antipsychotic drugs are known to induce structural volume increases in the human striatum20 and cortical volume reductions,21 but no neuronal loss. Hence, the ability to detect changes in neuronal tissue concentration would depend on the spatial resolution of the 1H-MRS sellectchem technique (currently limited to 1 cc, clearly suboptimal for the 2- to 3-mm thick human cortex) as well as the timing of acquisition.