Effect of Clozapine on Proton Magnetic Resonance Spectroscopy Findings in Hippocampus

The purpose of this study was to investigate the effect of clozapine on proton magnetic resonance spectroscopy (1H-MRS) findings in hippocampus in patients with schizophrenia. In addition, the relationship between the change in 1H-MRS findings and the change in psychopathology and neurocognitive functions was evaluated. Patients with schizophrenia (n=16) were assessed with the Positive and Negative Syndrome Scale (PANSS), Clinical Global Impression Scale (CGI), a neurocognitive test battery and 1H-MRS at baseline, and twelve weeks after the initiation of clozapine. Healthy controls (n=8) were assessed once with a neurocognitive test battery and 1H-MRS. Bilateral multivoxel and left single voxel NAA/Cr, Cho/Cr, MI/Cr was calculated in the hippocampi. After 12 weeks of clozapine treatment, PANSS and CGI scores decreased; immediate recall, cumulative learning subtests of the Rey Auditory Verbal Learning Test, Category Verbal Fluency Test and Wechsler Memory Scale's visual reproduction delayed subtest scores increased significantly. Compared with healthy controls and patients after clozapine, hippocampi multivoxel and single voxel NAA/Cr, Cho/ Cr, MI/Cr ratios were not different in patients before clozapine. No significant correlations between change in 1H-MRS metabolite ratios and change in psychopathology, neurocognitive functions were detected. This study is the first longitudinal study to investigate the effect of clozapine in hippocampus with 1H-MRS. There were no significant changes in 1H-MRS findings in hippocampi after twelve weeks of clozapine treatment. Clozapine's effect in hippocampus should be investigated further in longer follow up studies with larger samples to reach a final conclusion.