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

**Authors:** Hideo Hagihara, Kotaro Hattori, Hiroshi Kunugi, Tsuyoshi Miyakawa

PMC · DOI: 10.1002/npr2.70096 · Neuropsychopharmacology Reports · 2026-03-03

## TL;DR

This study found higher cerebrospinal fluid lactate levels in Japanese patients with schizophrenia and depression, suggesting a possible link to brain energy metabolism issues.

## Contribution

The study confirms elevated CSF lactate levels in schizophrenia and MDD in a Japanese population, independent of medication effects.

## Key findings

- CSF lactate levels were significantly higher in individuals with schizophrenia and MDD compared to controls.
- CSF glucose levels were elevated in MDD patients compared to controls.
- Lactate and glucose levels showed positive correlations with age.

## Abstract

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.

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.

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.

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.

This study demonstrated increased cerebrospinal fluid lactate levels in Japanese patients with schizophrenia and major depressive disorder, consistent with reports from other populations. This elevation is unlikely to be primarily driven by medication and may instead reflect intrinsic alterations in brain energy metabolism.

## Linked entities

- **Chemicals:** lactate (PubChem CID 61503), pyruvate (PubChem CID 107735), glucose (PubChem CID 5793), imipramine (PubChem CID 3696)
- **Diseases:** schizophrenia (MONDO:0005090), major depressive disorder (MONDO:0002009)

## Full-text entities

- **Diseases:** central nervous system disease (MESH:D002493), bronchial asthma (MESH:D001249), SZ (MESH:D012559), diabetes (MESH:D003920), AD (MESH:D000544), substance abuse (MESH:D019966), Mental Disorders (MESH:D001523), head injury (MESH:D006259), hyperlipidemia (MESH:D006949), MDD (MESH:D003865), seizure (MESH:D012640), mood disturbances (MESH:D019964), brain disorders (MESH:D001927), intellectual disability (MESH:D008607), hypertension (MESH:D006973), epileptic seizures (MESH:D004827), cognitive impairments (MESH:D003072), allergy (MESH:D004342), bipolar disorder (MESH:D001714), depression (MESH:D003866)
- **Chemicals:** Lactate (MESH:D019344), Pyruvate (MESH:D019289), imipramine (MESH:D007099), Cerebrospinal Fluid Lactate (-), Glucose (MESH:D005947), CPZ (MESH:D002746)
- **Species:** Homo sapiens (human, species) [taxon 9606]

## Full text

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## Figures

2 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12956547/full.md

## References

40 references — full list in the complete paper: https://tomesphere.com/paper/PMC12956547/full.md

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Source: https://tomesphere.com/paper/PMC12956547