Elsevier

Biological Psychiatry

Volume 62, Issue 11, 1 December 2007, Pages 1310-1316
Biological Psychiatry

Original Article
Increased Levels of Glutamate in Brains from Patients with Mood Disorders

https://doi.org/10.1016/j.biopsych.2007.03.017Get rights and content

Background

Glutamate has been thought to have a role in mental disorders. Because the postmortem interval (PMI) has such a pronounced effect on glutamate and other amino acids, it is important that a study be conducted to examine the effects of PMI on these amino acids in postmortem brains and that the analysis of intergroup differences be adjusted accordingly. We determined the levels of amino acids in postmortem brains from patients with major mental disorders by normalizing the effects of the postmortem interval with equations derived from control studies using rodent and primate postmortem brains.

Methods

First, we examined the influence of postmortem intervals on the levels of the amino acids by using rodent brains and derived equations for normalizing the raw data of the amino acids from human brains according to their postmortem intervals. Second, we measured the levels of the amino acids in postmortem human brains, normalized their raw data with the equations, and analyzed the normalized data.

Results

Increased levels of glutamate were observed in the frontal cortex from patients with bipolar disorder and major depression. In addition, positive correlations were observed between several pairs of amino acids, including D-serine and glutamate.

Conclusions

This study suggests that glutamate plays a role in the pathophysiology of bipolar disorder and major depression.

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

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    All authors have no conflict of interest.

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