Elsevier

Biological Psychiatry

Volume 65, Issue 6, 15 March 2009, Pages 489-494
Biological Psychiatry

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

https://doi.org/10.1016/j.biopsych.2008.11.010Get rights and content

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.

Section snippets

Subjects and CSF Samples

Patients were recruited from the inpatient and outpatient psychiatric services of the University of Maryland Medical Center, and all provided written informed consent to participate in this Institutional Review Board (IRB)-approved study. Bipolar subjects (n = 15) had bipolar I disorder confirmed by a board-certified psychiatrist (WTR) on the basis of Structured Clinical Interview for the DSM-IV (SCID) criteria (25). Specific diagnoses were: manic, severe with catatonic features (n = 3); manic,

Results

Groups differed significantly by racial composition, CSF lactate, CSF glucose, and plasma glucose concentrations but not by age, gender, treatment resistance, illness duration, or family history of psychiatric illness (Table 1). Bipolar and schizophrenic groups had significantly higher mean CSF lactate concentrations compared with healthy control subjects—34% and 23% higher, respectively; however, group data distributions overlapped considerably (Figure 1). Bipolar subjects also had

Discussion

In this study we found evidence to support our hypothesis that CSF concentration of lactate is, on average, elevated in bipolar and schizophrenic patients compared with healthy control subjects. This novel finding indicates increased extra-mitochondrial, anaerobic glucose metabolism and is consistent with impaired mitochondrial metabolism in some patients with these disorders. We discuss this finding and others in the following text in relation to normal CNS glucose and lactate metabolism,

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