Metabolomics analysis of cerebrospinal fluid suggests citric acid cycle aberrations in bipolar disorder

Mounting evidence indicates mitochondrial dysfunction in bipolar disorder pathophysiology. Here, we employed Proton Nuclear Magnetic Resonance Spectroscopy (¹H NMR) of cerebrospinal fluid (CSF) samples from well-characterized bipolar disorder patients (n ​= ​67) and healthy controls (n ​= ​55) in order to measure absolute concentrations of multiple metabolites. Focusing on four citric acid cycle metabolites - citrate, glucose, lactate, and pyruvate - we found higher concentrations of both citrate and glucose in patients compared with controls after correcting for age, sex and body mass index, but only the difference in CSF citrate survived correction for multiple comparisons. Within the patient group, CSF citrate concentrations were higher among lithium users than non-users. In conclusion, this report adds further evidence for a mitochondrial dysfunction in bipolar disorder.