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Markers of glutamate signaling in cerebrospinal fluid and serum from patients with bipolar disorder and healthy controls

Journal article
Authors Erik Pålsson
Joel Jakobsson
Kristoffer Södersten
Y. Fujita
C. Sellgren
C. J. Ekman
Hans Ågren
K. Hashimoto
Mikael Landén
Published in European Neuropsychopharmacology
Volume 25
Issue 1
Pages 133-140
ISSN 0924-977X
Publication year 2015
Published at Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry
Pages 133-140
Language en
Links dx.doi.org/10.1016/j.euroneuro.2014...
Keywords Bipolar disorder, Glutamic acid, Serum, Cerebrospinal fluid, N-methyl-D-aspartate, MAGNETIC-RESONANCE-SPECTROSCOPY, NAIVE SCHIZOPHRENIC-PATIENTS, EXCITATORY AMINO-ACIDS, D-ASPARTATE RECEPTOR, D-SERINE, MOOD DISORDERS, MAJOR DEPRESSION, PLASMA GLYCINE, VALPROIC ACID, THERAPEUTICS, Clinical Neurology, Neurosciences, Pharmacology & Pharmacy, Psychiatry
Subject categories Pharmacology, Psychiatry, Neurosciences

Abstract

Glutamate is the major excitatory neurotransmitter in the brain. Aberrations in glutamate signaling have been linked to the pathophysiology of mood disorders. Increased plasma levels of glutamate as well as higher glutamine+glutamate levels in the brain have been demonstrated in patients with bipolar disorder as compared to healthy controls. In this study, we explored the glutamate hypothesis of bipolar disorder by examining peripheral and central levels of amino acids related to glutamate signaling. A total of 215 patients with bipolar disorder and 112 healthy controls from the Swedish St. Goran bipolar project were included in this study. Glutamate, glutamine, glycine, L-serine and D-serine levels were determined in serum and in cerebrospinal fluid using high performance liquid chromatography with fluorescence detection. Serum levels of glutamine, glycine and D-serine were significantly higher whereas L-serine levels were lower in patients with bipolar disorder as compared to controls. No differences between the patient and control group in amino acid levels were observed in cerebrospinal fluid. The observed differences in serum amino acid levels may be interpreted as a systemic aberration in amino acid metabolism that affects several amino acids related to glutamate signaling. (C) 2014 Elsevier B.V. and ECNP. All rights reserved.

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