Brain glutamate levels measured by MRS in patients with bipolar disorder: a meta-analysis

Abstract

Objectives: Bipolar disorder (BD) is a relatively common highly disabling disease characterized by substantial cognitive and functional impairment. The investigation of its causes has identified abnormalities in neurotransmission and neuroplasticity. In this context, there is growing evidence that glutamate plays an important role in the neurobiology of the disease. Proton magnetic resonance spectroscopy (1H-MRS) is a non-invasive method that produces in vivo assessments and has corroborated to this investigation, although contrasting results have been found. The objective of this study was to undertake a review and meta-analysis of the literature on measurement of glutamate by 1H-MRS in BD. Methods: A review of the literature was conducted to identify published studies that used 1H-MRS to compare Glx (glutamate + glutamine), Glx/Creatine (Cr) ratio, glutamate (Glu), or Glu/Cr ratio in adult or child/adolescent patients with BD and healthy subjects in any brain region. A meta-analysis of pooled data was conducted. Results: BD patients have increased Glx compared to healthy subjects with all brain areas combined, in medicated and non-medicated patients, and in the combined frontal areas in adults. A non-significant trend (p = 0.09) suggested an increase in both Glx/Cr and Glu in patients compared to healthy subjects. No significant difference was found in Glu/Cr. Conclusion: Overall, these findings support the notion that elevated glutamate levels play an important role in the pathophysiology of BD.