Elevated Cerebrospinal Fluid Lactate Concentrations in Patients with Bipolar Disorder and Schizophrenia: Implications for the Mitochondrial Dysfunction Hypothesis

Background: Evidence is accumulating that mitochondrial dysfunction is involved in the pathophysiology of bipolar disorder and schizophrenia. Cerebrospinal fluid (CSF) concentration of lactate, a product of extra-mitochondrial glucose metabolism, is commonly elevated in individuals with mitochondrial disorders, especially those with neuropsychiatric symptoms. We tested the hypothesis that patients with bipolar disorder and schizophrenia would, on average, have elevated CSF lactate concentrations compared with healthy control subjects. Methods: The CSF lactate and CSF and plasma glucose concentrations were measured with a YSI (YSI, Yellow Springs, Ohio) 2300 STAT Plus Glucose & Lactate Analyzer in 15 samples from each of three groups of subjects: bipolar I disorder patients, schizophrenic patients, and healthy control subjects. Results: Mean CSF lactate concentrations were significantly higher in bipolar (1.76 +/- .38) and schizophrenic subjects (1.61 +/- .31) compared with control subjects (1.31 +/- .21 mmol/L). These differences persisted after adjusting means for CSF glucose concentration, which correlated positively with CSF lactate concentration. Conclusions: This is the first report of increased CSF lactate concentrations in patients with bipolar disorder and schizophrenia. Elevated CSF lactate indicates increased extra-mitochondrial and anaerobic glucose metabolism and is consistent with impaired mitochondrial metabolism. Measuring CSF lactate concentration might help identify bipolar and schizophrenic patients with mitochondrial dysfunction who might benefit from research to elucidate and ultimately rectify possible mitochondrial pathology underlying these disorders.