title: Abnormality in glutamine-glutamate cycle in the cerebrospinal fluid of cognitively intact elderly individuals with major depressive disorder: a 3-year follow-up study.
abstract: Major depressive disorder (MDD), common in the elderly, is a risk factor for dementia. Abnormalities in glutamatergic neurotransmission via the N-methyl-D-aspartate receptor (NMDA-R) have a key role in the pathophysiology of depression. This study examined whether depression was associated with cerebrospinal fluid (CSF) levels of NMDA-R neurotransmission-associated amino acids in cognitively intact elderly individuals with MDD and age- and gender-matched healthy controls. CSF was obtained from 47 volunteers (MDD group, N=28; age- and gender-matched comparison group, N=19) at baseline and 3-year follow-up (MDD group, N=19; comparison group, N=17). CSF levels of glutamine, glutamate, glycine, L-serine and D-serine were measured by high-performance liquid chromatography. CSF levels of amino acids did not differ across MDD and comparison groups. However, the ratio of glutamine to glutamate was significantly higher at baseline in subjects with MDD than in controls. The ratio decreased in individuals with MDD over the 3-year follow-up, and this decrease correlated with a decrease in the severity of depression. No correlations between absolute amino-acid levels and clinical variables were observed, nor were correlations between amino acids and other biomarkers (for example, amyloid-β42, amyloid-β40, and total and phosphorylated tau protein) detected. These results suggest that abnormalities in the glutamine-glutamate cycle in the communication between glia and neurons may have a role in the pathophysiology of depression in the elderly. Furthermore, the glutamine/glutamate ratio in CSF may be a state biomarker for depression.
authors.affiliation: Division of Clinical Neuroscience, Chiba University Center for Forensic Mental Health, Chiba, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Hashimoto
authors.affiliation: Department of Psychology, Liverpool Hope University, Liverpool, UK.
authors.forename: D
authors.initials: D
authors.lastname: Bruno
authors.affiliation: Nathan S. Kline Institute for Psychiatric Research, Orangeburg, NY, USA.|Department of Psychiatry, New York University Langone Medical Center, New York, NY, USA.
authors.forename: J
authors.initials: J
authors.lastname: Nierenberg
authors.affiliation: Department of Psychiatry, New York University Langone Medical Center, New York, NY, USA.
authors.forename: C R
authors.initials: CR
authors.lastname: Marmar
authors.affiliation: Clinical Neurochemistry Laboratory, Institute of Neuroscience and Physiology, The Sahlgrenska Academy at the University of Gothenburg, Mölndal, Sweden.|Department of Molecular Neuroscience, UCL Institute of Neurology, London, UK.
authors.forename: H
authors.initials: H
authors.lastname: Zetterberg
authors.affiliation: Clinical Neurochemistry Laboratory, Institute of Neuroscience and Physiology, The Sahlgrenska Academy at the University of Gothenburg, Mölndal, Sweden.
authors.forename: K
authors.initials: K
authors.lastname: Blennow
authors.affiliation: Nathan S. Kline Institute for Psychiatric Research, Orangeburg, NY, USA.|Department of Psychiatry, New York University Langone Medical Center, New York, NY, USA.
authors.forename: N
authors.initials: N
authors.lastname: Pomara
mesh_terms: D000368:Aged; D000375:Aging / Q000134:cerebrospinal fluid / Q000502:physiology; D002851:Chromatography, High Pressure Liquid; D003071:Cognition; D003865:Major Depressive Disorder / Q000134:cerebrospinal fluid* / Q000503:physiopathology; D005260:Female; D005500:Follow-Up Studies; D018698:Glutamic Acid / Q000134:cerebrospinal fluid*; D005973:Glutamine / Q000134:cerebrospinal fluid*; D006801:Humans; D008297:Male; D011569:Psychiatric Status Rating Scales; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism; D009435:Synaptic Transmission / Q000502:physiology*
chemical_list: D016194:Receptors, N-Methyl-D-Aspartate; D005973:Glutamine; D018698:Glutamic Acid