Increased Levels of Glutamate in Brains from Patients with Mood Disorders

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.