title: Markers of glutamate signaling in cerebrospinal fluid and serum from patients with bipolar disorder and healthy controls.
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. Göran 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.
authors.affiliation: Institute of Neuroscience and Physiology, Section of Psychiatry and Neurochemistry, University of Gothenburg, Sweden. Electronic address: erik.palsson@neuro.gu.se.
authors.forename: Erik
authors.initials: E
authors.lastname: Pålsson
authors.affiliation: Institute of Neuroscience and Physiology, Section of Psychiatry and Neurochemistry, University of Gothenburg, Sweden.
authors.forename: Joel
authors.initials: J
authors.lastname: Jakobsson
authors.affiliation: Institute of Neuroscience and Physiology, Section of Psychiatry and Neurochemistry, University of Gothenburg, Sweden.
authors.forename: Kristoffer
authors.initials: K
authors.lastname: Södersten
authors.affiliation: Division of Clinical Neuroscience, Chiba University Center for Forensic Mental Health, Chiba, Japan.
authors.forename: Yuko
authors.initials: Y
authors.lastname: Fujita
authors.affiliation: Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Carl
authors.initials: C
authors.lastname: Sellgren
authors.affiliation: Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Carl-Johan
authors.initials: CJ
authors.lastname: Ekman
authors.affiliation: Institute of Neuroscience and Physiology, Section of Psychiatry and Neurochemistry, University of Gothenburg, Sweden.
authors.forename: Hans
authors.initials: H
authors.lastname: Ågren
authors.affiliation: Division of Clinical Neuroscience, Chiba University Center for Forensic Mental Health, Chiba, Japan.
authors.forename: Kenji
authors.initials: K
authors.lastname: Hashimoto
authors.affiliation: Institute of Neuroscience and Physiology, Section of Psychiatry and Neurochemistry, University of Gothenburg, Sweden; Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Mikael
authors.initials: M
authors.lastname: Landén
mesh_terms: D000328:Adult; D001714:Bipolar Disorder / Q000097:blood* / Q000134:cerebrospinal fluid*; D005260:Female; D018698:Glutamic Acid / Q000097:blood* / Q000134:cerebrospinal fluid*; D005973:Glutamine / Q000097:blood / Q000134:cerebrospinal fluid; D005998:Glycine / Q000097:blood / Q000134:cerebrospinal fluid; D006801:Humans; D008297:Male; D008875:Middle Aged; D011569:Psychiatric Status Rating Scales; D012694:Serine / Q000097:blood / Q000134:cerebrospinal fluid
chemical_list: D005973:Glutamine; D018698:Glutamic Acid; D012694:Serine; D005998:Glycine
keywords: Bipolar disorder; Cerebrospinal fluid; Glutamic acid; N-methyl-d-aspartate; Serum