Original ArticleIncreased Levels of Glutamate in Brains from Patients with Mood Disorders
Section snippets
Postmortem Human Brain Tissues
The human postmortem frontal cortex samples (Brodmann area [BA] 6) from normal control subjects (n = 15) as well as patients with schizophrenia (n = 15), bipolar disorder (n = 15), and major depression (n = 15) were obtained from the Stanley Foundation Brain Collection (Bethesda, Maryland). The specimens are collected by medical examiners. Permission from the next of kin was obtained in all cases. The demographic, clinical, and storage characteristics for the cases have been published
Amino Acid Levels in Animal Brains After PMIs of Different Length
First, we examined changes in the levels of amino acids of the frontal cortices of mouse brains after PMIs of different length (from 0 to 72 hours). The levels of L-serine and glycine were increased with increasing length of PMI, whereas the levels of D-serine and glutamate were decreased with increasing length of PMI (Figure 1). In contrast, the levels of glutamine were not altered at any of the PMIs (Figure 1). Consistent trends of changes in all these amino acids depending on the PMI were
Discussion
The present study examined amino acid levels in autopsied brains from patients with major mental illnesses. There were two major findings in the present study. Because the levels of amino acids in the raw human data and rodent brain data are influenced by the PMI, we introduced equations derived from control studies with rodent postmortem brains to normalize the raw data from human autopsied brains according to the PMI. In the raw data for the human sample set, we found significant negative
References (43)
The human brain revisited: Opportunities and challenges in postmortem studies of psychiatric disorders
Neuropsychopharmacology
(2002)- et al.
The Stanley Foundation brain collection and neuropathology consortium
Schizophr Res
(2000) Normal cerebrospinal fluid and brain glutamate levels in schizophrenia do not support the hypothesis of glutamatergic neuronal dysfunction
Neurosci Lett
(1982)- et al.
Identification of multiple serine racemase (SRR) mRNA isoforms and genetic analyses of SRR and DAO in schizophrenia and D-serine levels
Biol Psychiatry
(2005) - et al.
Signaling: Cellular insights into the pathophysiology of bipolar disorder
Biol Psychiatry
(2000) - et al.
Lithium increases N-acetyl-aspartate in the human brain: In vivo evidence in support of bcl-2’s neurotrophic effects?
Biol Psychiatry
(2000) - et al.
Lithium-induced increase in human brain grey matter
Lancet
(2000) - et al.
Lithium and valproic acid treatment effects on brain chemistry in bipolar disorder
Biol Psychiatry
(2004) - et al.
Reduced glutamate in the anterior cingulate cortex in depression: An in vivo proton magnetic resonance spectroscopy study
Biol Psychiatry
(2000) - et al.
Reduced anterior cingulate glutamate in pediatric major depression: A magnetic resonance spectroscopy study
Biol Psychiatry
(2005)
Antidepressant effects of ketamine in depressed patients
Biol Psychiatry
Preliminary evidence of riluzole efficacy in antidepressant-treated patients with residual depressive symptoms
Biol Psychiatry
Alterations in the N-methyl-D-aspartate (NMDA) receptor complex in the frontal cortex of suicide victims
Brain Res
Neurotransmitter amino acids in post-mortem brains of chronic schizophrenic patients
Psychiatry Res
Reduced D-serine to total serine ratio in the cerebrospinal fluid of drug naive schizophrenic patients
Prog Neuropsychopharmacol Biol Psychiatry
Recent advances in the phencyclidine model of schizophrenia
Am J Psychiatry
Subanesthetic effects of the noncompetitive NMDA antagonist, ketamine, in humansPsychotomimetic, perceptual, cognitive, and neuroendocrine responses
Arch Gen Psychiatry
Schizophrenia and glutamatergic transmission
Crit Rev Neurobiol
The emerging role of glutamate in the pathophysiology and treatment of schizophrenia
Am J Psychiatry
Schizophrenia: Diverse approaches to a complex disease
Science
Decreased serum levels of D-serine in patients with schizophrenia: Evidence in support of the NMDA receptor hypofunction hypothesis of schizophrenia
Arch Gen Psychiatry
Cited by (0)
All authors have no conflict of interest.