Lactate in bipolar disorder: A systematic review and meta-analysis

Bipolar disorder (BD) is a debilitating mood disorder with no specific biological marker. No novel treatment has been developed specifically for BD in the last several decades. Although the pathophysiology of BD remains unclear, there is strong evidence in the literature supporting the role of mitochondrial dysfunction in BD. In this systematic review, we identified and investigated 12 studies that measure lactate, which is a direct marker for mitochondrial dysfunction, in BD patients and healthy controls. Six studies measured lactate levels in the brain through proton echo-planar spectroscopy or magnetic resonance spectroscopy and five of these studies reported significantly elevated lactate levels in patients with BD. Two studies reporting cerebrospinal fluid lactate levels also found significantly elevated lactate in BD compared to healthy controls. Two other studies that reported peripheral lactate levels did not demonstrate significant findings. The meta-analysis, using standardized means and a random-effect model for five studies that measured brain lactate levels, corroborated the findings of the systematic review. Although the meta-analysis had a nearly significant overall effect (Z = 1.97, P = 0.05), high statistical heterogeneity (I²  = 86%) and possible publication bias suggest that the results should be interpreted with caution. To validate lactate abnormalities in BD, further studies should be carried out, including larger sample sizes, not excluding female patients, and using standardized methodologies. Peripheral lactate levels and other bioenergetic markers should be thoroughly studied to better understand the role of mitochondrial dysfunction in BD and to help develop more objective diagnostic tools.