Brain glutamate levels measured by magnetic resonance spectroscopy in patients with bipolar disorder: A meta-analysis

Objectives: Bipolar disorder (BD) is a common and highly disabling disease characterized by substantial cognitive and functional impairment. The exact neurobiological mechanisms underlying the expression of symptoms in this condition remain unknown but there is growing evidence that glutamate might play an important role. Using proton magnetic resonance spectroscopy (¹H-MRS), a number of studies have examined brain glutamate/glutamine levels in patients with bipolar disorder, but they have produced conflicting results. The objective of this paper was to conduct a systematic review and meta-analysis of the literature on brain glutamate/glutamine in BD as measured by ¹H-MRS. Methods: A Medline search for the period January 1980-April 2010 was conducted to identify published studies that used ¹H-MRS to measure glutamate+glutamine (Glx), the Glx/creatine (Cr) ratio, glutamate (Glu), or the Glu/Cr ratio in any brain region in adult or child/adolescent patients with BD and healthy subjects. A meta-analysis of the pooled data was conducted. Results: BD patients were found to have increased Glx compared to healthy subjects when all brain areas were combined. This finding remained true in medicated and non-medicated patients, and in frontal brain areas in adults. There was a non-significant trend (p=0.09) for an increase in whole-brain Glx/Cr and Glu in patients compared with healthy subjects. No significant difference was found in Glu/Cr. Conclusions: The results of this meta-analysis suggest that brain Glx levels are elevated in BD patients and support the idea that glutamate might play an important role in the pathophysiology of BD.