Proton Magnetic Resonance Spectroscopy Changes in a Longitudinal Schizophrenia Study: a Pilot Study in Eleven Patients

Purpose: Investigation of the longitudinal effect of schizophrenia on changes in various brain-metabolite levels and their relationships with cognitive deficits that have not been fully explained yet. Methods: Five years subsequent to their first examination for their first episode of schizophrenia, eleven patients from an original group of 30 were reexamined. Their cognitive functions were assessed with the Wisconsin Card Sorting Test. Magnetic resonance imaging and proton magnetic resonance spectroscopy were performed on a 1.5 T scanner. Voxels of 8 cm(3) were positioned in the left frontal lobe, left temporal lobe, and the left thalamus. The study had a naturalistic design, and patients were treated with various antipsychotics. Results: No significant statistical differences between the baseline and follow-up in N-acetylaspartate (NAA: creatine plus phosphocreatine [Cr] and NAA/H2O) levels were observed in any region of interest. We found a significant statistical correlation between 5-year difference in frontal NAA/Cr levels and duration of the last antipsychotic treatment in this period (R=0.908, P=0.012). We found a trend (P=0.068) toward lower choline-containing compounds (Cho/Cr ratio) in the temporal lobe over 5 years and a trend (P= 0.079) in higher glutamate-glutamine-GABA (Glx/H2O) levels in the left thalamus. The patients showed social and clinical improvement at follow-up examination, and there were no changes in Wisconsin Card Sorting Test results. Conclusion: The observed tendency toward decline in choline ratio might have been due to decreased temporal cell density or impaired neuron-membrane or myelin functions. A tendency for higher Glx levels suggest the involvement of thalamus dysfunction in the chronic schizophrenia process. The lack of NAA decrease might have been due to effective antipsychotic treatment. Further longitudinal studies on large patient groups are required to confirm these metabolic changes in schizophrenia.