Elevated glutamine/glutamate ratio in cerebrospinal fluid of first episode and drug naive schizophrenic patients

BackgroundRecent magnetic resonance spectroscopy (MRS) studies report that glutamine is altered in the brains of schizophrenic patients. There were also conflicting findings on glutamate in cerebrospinal fluid (CSF) of schizophrenic patients, and absent for glutamine. This study aims to clarify the question of glutamine and glutamate in CSF of first episode and drug naive schizophrenic patients.MethodLevels of glutamine and glutamate in CSF of 25 first episode and drug-naive male schizophrenic patients and 17 age-matched male healthy controls were measured by a high performance liquid chromatography.ResultsThe ratio (126.1 (median), 117.7 ± 27.4 (mean ± S.D.)) of glutamine to glutamate in the CSF of patients was significantly (z = -3.29, p = 0.001) higher than that (81.01 (median), 89.1 ± 22.5 (mean ± S.D.)) of normal controls although each level of glutamine and glutamate in patients was not different from that of normal controls.ConclusionOur data suggests that a disfunction in glutamate-glutamine cycle in the brain may play a role in the pathophysiology of schizophrenia.

[1]  K. Blennow,et al.  Kynurenic acid levels are elevated in the cerebrospinal fluid of patients with schizophrenia , 2001, Neuroscience Letters.

[2]  J. Coyle,et al.  The emerging role of glutamate in the pathophysiology and treatment of schizophrenia. , 2001, The American journal of psychiatry.

[3]  Kenji Hashimoto,et al.  Dysfunction of Glia-Neuron Communication in Pathophysiology of Schizophrenia , 2005 .

[4]  Ravi S. Menon,et al.  Glutamate and glutamine in the anterior cingulate and thalamus of medicated patients with chronic schizophrenia and healthy comparison subjects measured with 4.0-T proton MRS. , 2003, The American journal of psychiatry.

[5]  F. Holsboer,et al.  γ‐Glutamylglutamine and Taurine Concentrations Are Decreased in the Cerebrospinal Fluid of Drug‐Naive Patients with Schizophrenic Disorders , 1995, Journal of neurochemistry.

[6]  K. Davis,et al.  Implications for altered glutamate and GABA metabolism in the dorsolateral prefrontal cortex of aged schizophrenic patients. , 2002, The American journal of psychiatry.

[7]  K. Hashimoto,et al.  Glutamate Hypothesis of Schizophrenia and Approach for Possible Therapeutic Drugs , 2004 .

[8]  Fahmeed Hyder,et al.  In vivo NMR studies of the glutamate neurotransmitter flux and neuroenergetics: implications for brain function. , 2003, Annual review of physiology.

[9]  J. Viña,et al.  Glutamine transport by the blood-brain barrier: a possible mechanism for nitrogen removal. , 1998, American journal of physiology. Cell physiology.

[10]  J. Coyle,et al.  Mind glue: implications of glial cell biology for psychiatry. , 2000, Archives of general psychiatry.

[11]  G. Burbaeva,et al.  Glutamine synthetase and glutamate dehydrogenase in the prefrontal cortex of patients with schizophrenia , 2003, Progress in Neuro-Psychopharmacology and Biological Psychiatry.

[12]  J. Coyle,et al.  Glutamatergic neurotransmission involves structural and clinical deficits of schizophrenia , 1998, Biological Psychiatry.

[13]  H. H. Kornhuber,et al.  Low cerebrospinal fluid glutamate in schizophrenic patients and a new hypothesis on schizophrenia , 1980, Neuroscience Letters.

[14]  T. Perry.  Normal cerebrospinal fluid and brain glutamate levels in schizophrenia do not support the hypothesis of glutamatergic neuronal dysfunction , 1982, Neuroscience Letters.

[15]  C. Kitada,et al.  A fully automated amino acid analyzer using NBD-F as a fluorescent derivatization reagent. , 2004, Biomedical chromatography : BMC.

[16]  R W Neufeld,et al.  Measurement of glutamate and glutamine in the medial prefrontal cortex of never-treated schizophrenic patients and healthy controls by proton magnetic resonance spectroscopy. , 1997, Archives of general psychiatry.

[17]  J. Viña,et al.  Na+ -dependent neutral amino acid transporters A, ASC, and N of the blood-brain barrier: mechanisms for neutral amino acid removal. , 2004, American journal of physiology. Endocrinology and metabolism.

[18]  J. Viña,et al.  Na+-dependent Glutamate Transporters (EAAT1, EAAT2, and EAAT3) of the Blood-Brain Barrier , 1999, The Journal of Biological Chemistry.

[19]  F. Wiesel,et al.  Glutamate and glutamine in cerebrospinal fluid and serum from healthy volunteers--analytical aspects. , 1988, Journal of chromatography.

[20]  D. Javitt,et al.  Recent advances in the phencyclidine model of schizophrenia. , 1991, The American journal of psychiatry.

[21]  J. Olney,et al.  Glutamate receptor dysfunction and schizophrenia. , 1995, Archives of general psychiatry.

[22]  Ravi S. Menon,et al.  Glutamate and glutamine measured with 4.0 T proton MRS in never-treated patients with schizophrenia and healthy volunteers. , 2002, The American journal of psychiatry.