Glutamatergic system involvement in BD supported

By Mark Cowen

Results from a systematic review and meta-analysis of published studies suggest that brain levels of glutamate plus glutamine (Glx) are elevated in bipolar disorder (BD) patients compared with mentally healthy individuals.

The team also found a nonsignificant trend for increased glutamate (Glu) levels and an increased Glx/creatine ratio in BD patients.

The findings, published in Bipolar Disorders, "support the idea that glutamate might play an important role in the pathophysiology of BD," say Alexandre Gigante (University of São Paulo Medical School, Brazil) and team.

The researchers searched the literature for the period 1980-2010 and identified 34 studies that compared BD patients with mentally healthy individuals (controls) for brain levels of Glx, Glu, Glx/creatine ratio, and Glu/creatine ratio using proton magnetic resonance spectroscopy.

In total, 17 studies met the criteria for inclusion in the final analysis.

Evaluation of data from nine studies indicated a significant increase in Glx levels among BD patients (n=162) compared with controls (n=165), at an effect size (ES) of 0.72.

This increase in Glx levels was evident in both medicated and unmedicated BD patients, although the association was stronger in the former than latter group, at an ES of 1.91 versus 0.31.

Pooled data from six studies showed a nonsignificant increase in the Glx/creatine ratio among BD patients (n=96) compared with controls (n=88), at an ES of 0.63.

Seven studies that involved 179 BD patients and 184 controls also showed a nonsignificant trend for increased Glu levels in patients with the mood disorder compared with controls, at an ES of 0.71.

There was no evidence for an increased Glu/creatine ratio in BD patients compared with controls.

"The results of this meta-analysis suggest that brain Glx levels are elevated in BD patients," conclude Gigante and team.

They add that the causes of this increase are unclear, "nonetheless, many mood-stabilizing medications modulate the glutamatergic system, and treatments that act specifically on the glutamatergic system are currently being tested and may become promising therapeutics for the future."

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