Increased Cerebrospinal Fluid Lactate Levels in Schizophrenia and Major Depressive Disorder: NCNP Biobank Study in Japan

日本NCNP生物库研究:精神分裂症和重度抑郁症患者脑脊液乳酸水平升高

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Abstract

AIM: Altered brain energy metabolism related to neural hyperexcitation, which leads to increased lactate levels in the brain and cerebrospinal fluid (CSF), has been implicated in several neuropsychiatric disorders. This study aimed to investigate CSF levels of lactate and related metabolites in Japanese individuals with schizophrenia and major depressive disorder (MDD), using samples from the National Center for Neurology and Psychiatry biobank. METHODS: CSF levels of lactate, pyruvate, and glucose were measured in 27 patients with schizophrenia, 26 patients with MDD, and 27 age-matched non-psychiatric controls. Analyses were conducted by diagnostic groups and demographic variables. RESULTS: CSF lactate levels were significantly higher in individuals with schizophrenia and MDD compared with controls. CSF glucose levels were significantly elevated in individuals with MDD compared with controls. Pyruvate levels showed no significant group differences. Across all individuals, CSF lactate, pyruvate, and glucose levels were positively correlated. Lactate and glucose levels showed positive correlations with age. No significant associations were found between the three metabolites' levels and medication dosages, except for an effect of imipramine on glucose levels. CONCLUSION: This study confirmed elevated CSF lactate levels in Japanese individuals with schizophrenia and MDD, consistent with findings in other populations. The elevation of CSF lactate is unlikely to reflect medication effects and instead may represent an underlying pathophysiology associated with altered brain energy metabolism in the brain.

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