Abstract
Converging evidence from molecular to neuroimaging studies suggests brain energy metabolism abnormalities in both schizophrenia and bipolar disorder. One emerging hypothesis is: decreased oxidative phosphorylation leading to accumulation of lactic acid from glycolysis and subsequent acidification of tissue. In this regard, integrating lactate and pH data from magnetic resonance spectroscopy (MRS) studies in both diseases may help us understand underlying neurobiological mechanisms. In order to achieve this goal, we performed a systematic search of case–control studies examining brain lactate or pH among schizophrenia and/or bipolar patients by using MRS. Medline/Pubmed and EBSCO databases were searched separately for both diseases and outcomes. Our search yielded 33 studies in total composed of 7 lactate and 26 pH studies. In bipolar disorder, 5 out of 6 studies have found elevated lactate levels especially in the cingulate cortex and 4 out of 13 studies reported reduced pH in the frontal lobe. In contrast, in schizophrenia a single study has examined lactate and reported elevation, while only 2 out of 13 studies examining pH have reported reduction in this measure. There were no consistent patterns for the relationship between lactate or pH levels and medication use, disease type, mood state, and other clinical variables. We highlight the need for future studies combining 1H-MRS and 31P-MRS approaches, using longitudinal designs to examine lactate and pH in disease progression across both schizophrenia and bipolar disorders.
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Acknowledgements
We thank to Dr. Zafer Dogan for his contribution to the manuscript. This review was funded by MH104449(DO) to Dost Ongur, R21MH114020 to Fei Du, NIMH 5T32MH016259(MS) to Virginie-Anne Chouinard and Maria Lorenz Pope Fellowship Award to Cagri Yuksel. No funding body had any involvement in the interpretation of the data, writing of the manuscript or decision to publish.
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Dogan, A.E., Yuksel, C., Du, F. et al. Brain lactate and pH in schizophrenia and bipolar disorder: a systematic review of findings from magnetic resonance studies. Neuropsychopharmacol 43, 1681–1690 (2018). https://doi.org/10.1038/s41386-018-0041-9
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DOI: https://doi.org/10.1038/s41386-018-0041-9
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