Negative correlation between brain glutathione level and negative symptoms in schizophrenia: a 3T 1H-MRS study.
BACKGROUND
Glutathione (GSH), a major intracellular antioxidant, plays a role in NMDA receptor-mediated neurotransmission, which is involved in the pathophysiology of schizophrenia. In the present study, we aimed to investigate whether GSH levels are altered in the posterior medial frontal cortex of schizophrenic patients. Furthermore, we examined correlations between GSH levels and clinical variables in patients.


RESULTS
Twenty schizophrenia patients and 16 age- and gender-matched normal controls were enrolled to examine the levels of GSH in the posterior medial frontal cortex by using 3T SIGNA EXCITE (1)H-MRS with the spectral editing technique, MEGA-PRESS. Clinical variables of patients were assessed by the Global Assessment of Functioning (GAF), Scale for the Assessment of Negative Symptoms (SANS), Brief Psychiatric Rating Scale (BPRS), Drug-Induced Extra-Pyramidal Symptoms Scale (DIEPSS), and five cognitive performance tests (Word Fluency Test, Stroop Test, Trail Making Test, Wisconsin Card Sorting Test and Digit Span Distractibility Test). Levels of GSH in the posterior medial frontal cortex of schizophrenic patients were not different from those of normal controls. However, we found a significant negative correlation between GSH levels and the severity of negative symptoms (SANS total score and negative symptom subscore on BPRS) in patients. There were no correlations between brain GSH levels and scores on any cognitive performance test except Trail Making Test part A.


CONCLUSIONS
These results suggest that GSH levels in the posterior medial frontal cortex may be related to negative symptoms in schizophrenic patients. Therefore, agents that increase GSH levels in the brain could be potential therapeutic drugs for negative symptoms in schizophrenia.
Matsuzawa
Daisuke
D
Department of Psychiatry, Chiba University Graduate School of Medicine, Chiba, Japan.
Obata
Takayuki
T
Shirayama
Yukihiko
Y
Nonaka
Hiroi
H
Kanazawa
Yoko
Y
Yoshitome
Eiji
E
Takanashi
Junichi
J
Matsuda
Tsuyoshi
T
Shimizu
Eiji
E
Ikehira
Hiroo
H
Iyo
Masaomi
M
Hashimoto
Kenji
K
D000328:Adult; D000975:Antioxidants / Q000378:metabolism; D001921:Brain / Q000378:metabolism*; D016022:Case-Control Studies; D003071:Cognition; D005260:Female; D005838:Genotype; D005978:Glutathione / Q000378:metabolism*; D006801:Humans; D009682:Magnetic Resonance Spectroscopy / Q000379:methods*; D008297:Male; D018384:Oxidative Stress; D017397:Prefrontal Cortex / Q000378:metabolism; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism; D012559:Schizophrenia / Q000378:metabolism* / Q000473:pathology
D000975:Antioxidants; D016194:Receptors, N-Methyl-D-Aspartate; D005978:Glutathione