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. 2022 Jun 30:1:100108.
doi: 10.1016/j.nsa.2022.100108. eCollection 2022.

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

Erik Smedler  1 , Alireza M Salehi  2   3 , Aurimantas Pelanis  1 , Ana Andreazza  4 , Erik Pålsson  1 , Timea Sparding  1 , Mikael Landén  1   2
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Metabolomics analysis of cerebrospinal fluid suggests citric acid cycle aberrations in bipolar disorder

Erik Smedler et al. Neurosci Appl. .

Abstract

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.

Keywords: Cerebrospinal fluid; Citric acid cycle; MeSH): bipolar disorder; Metabolome.

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Figures

Fig. 1
Fig. 1
CSF concentration of citrate for all patients, controls, patients with lithium treatment at those without lithium treatment.
See this image and copyright information in PMC

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