Elevated Brain Glutamate Levels in Bipolar Disorder and Pyruvate Carboxylase-Mediated Anaplerosis

In vivo H-1 magnetic resonance spectroscopy studies have found elevated brain glutamate or glutamate + glutamine levels in bipolar disorder with surprisingly high reproducibility. We propose that the elevated glutamate levels in bipolar disorder can be explained by increased pyruvate carboxylase-mediated anaplerosis in brain. Multiple independent lines of evidence supporting increased pyruvate carboxylase-mediated anaplerosis as a common mechanism underlying glutamatergic hyperactivity in bipolar disorder and the positive association between bipolar disorder and obesity are also described.

Automated summary

Elevated brain glutamate levels in bipolar disorder may be explained by increased pyruvate carboxylase-mediated anaplerosis. Supporting evidence suggests that this mechanism is common in glutamatergic hyperactivity in bipolar disorder, as well as a positive association between bipolar disorder and obesity.