Elevated Cerebrospinal Fluid Lactate Concentrations in Patients with Bipolar Disorder and Schizophrenia: Implications for the Mitochondrial Dysfunction Hypothesis

William T. Regenold, Pornima Phatak, Christopher M. Marano, Amritpal Sassan, Robert R. Conley, Mitchel A. Kling

Research output: Contribution to journalArticle

Abstract

Background: Evidence is accumulating that mitochondrial dysfunction is involved in the pathophysiology of bipolar disorder and schizophrenia. Cerebrospinal fluid (CSF) concentration of lactate, a product of extra-mitochondrial glucose metabolism, is commonly elevated in individuals with mitochondrial disorders, especially those with neuropsychiatric symptoms. We tested the hypothesis that patients with bipolar disorder and schizophrenia would, on average, have elevated CSF lactate concentrations compared with healthy control subjects. Methods: The CSF lactate and CSF and plasma glucose concentrations were measured with a YSI (YSI, Yellow Springs, Ohio) 2300 STAT Plus Glucose & Lactate Analyzer in 15 samples from each of three groups of subjects: bipolar I disorder patients, schizophrenic patients, and healthy control subjects. Results: Mean CSF lactate concentrations were significantly higher in bipolar (1.76 ± .38) and schizophrenic subjects (1.61 ± .31) compared with control subjects (1.31 ± .21 mmol/L). These differences persisted after adjusting means for CSF glucose concentration, which correlated positively with CSF lactate concentration. Conclusions: This is the first report of increased CSF lactate concentrations in patients with bipolar disorder and schizophrenia. Elevated CSF lactate indicates increased extra-mitochondrial and anaerobic glucose metabolism and is consistent with impaired mitochondrial metabolism. Measuring CSF lactate concentration might help identify bipolar and schizophrenic patients with mitochondrial dysfunction who might benefit from research to elucidate and ultimately rectify possible mitochondrial pathology underlying these disorders.

Original languageEnglish (US)
Pages (from-to)489-494
Number of pages6
JournalBiological Psychiatry
Volume65
Issue number6
DOIs
StatePublished - Mar 15 2009
Externally publishedYes

Fingerprint

Bipolar Disorder
Cerebrospinal Fluid
Lactic Acid
Schizophrenia
Glucose
Healthy Volunteers
Anaerobiosis
Mitochondrial Diseases
Pathology

Keywords

  • Bipolar
  • cerebrospinal fluid
  • lactate
  • metabolism
  • mitochondrial
  • schizophrenia

ASJC Scopus subject areas

  • Biological Psychiatry

Cite this

Elevated Cerebrospinal Fluid Lactate Concentrations in Patients with Bipolar Disorder and Schizophrenia : Implications for the Mitochondrial Dysfunction Hypothesis. / Regenold, William T.; Phatak, Pornima; Marano, Christopher M.; Sassan, Amritpal; Conley, Robert R.; Kling, Mitchel A.

In: Biological Psychiatry, Vol. 65, No. 6, 15.03.2009, p. 489-494.

Research output: Contribution to journalArticle

Regenold, William T. ; Phatak, Pornima ; Marano, Christopher M. ; Sassan, Amritpal ; Conley, Robert R. ; Kling, Mitchel A. / Elevated Cerebrospinal Fluid Lactate Concentrations in Patients with Bipolar Disorder and Schizophrenia : Implications for the Mitochondrial Dysfunction Hypothesis. In: Biological Psychiatry. 2009 ; Vol. 65, No. 6. pp. 489-494.
@article{7d5f0574579c4a388adc9b1fbabcb653,
title = "Elevated Cerebrospinal Fluid Lactate Concentrations in Patients with Bipolar Disorder and Schizophrenia: Implications for the Mitochondrial Dysfunction Hypothesis",
abstract = "Background: Evidence is accumulating that mitochondrial dysfunction is involved in the pathophysiology of bipolar disorder and schizophrenia. Cerebrospinal fluid (CSF) concentration of lactate, a product of extra-mitochondrial glucose metabolism, is commonly elevated in individuals with mitochondrial disorders, especially those with neuropsychiatric symptoms. We tested the hypothesis that patients with bipolar disorder and schizophrenia would, on average, have elevated CSF lactate concentrations compared with healthy control subjects. Methods: The CSF lactate and CSF and plasma glucose concentrations were measured with a YSI (YSI, Yellow Springs, Ohio) 2300 STAT Plus Glucose & Lactate Analyzer in 15 samples from each of three groups of subjects: bipolar I disorder patients, schizophrenic patients, and healthy control subjects. Results: Mean CSF lactate concentrations were significantly higher in bipolar (1.76 ± .38) and schizophrenic subjects (1.61 ± .31) compared with control subjects (1.31 ± .21 mmol/L). These differences persisted after adjusting means for CSF glucose concentration, which correlated positively with CSF lactate concentration. Conclusions: This is the first report of increased CSF lactate concentrations in patients with bipolar disorder and schizophrenia. Elevated CSF lactate indicates increased extra-mitochondrial and anaerobic glucose metabolism and is consistent with impaired mitochondrial metabolism. Measuring CSF lactate concentration might help identify bipolar and schizophrenic patients with mitochondrial dysfunction who might benefit from research to elucidate and ultimately rectify possible mitochondrial pathology underlying these disorders.",
keywords = "Bipolar, cerebrospinal fluid, lactate, metabolism, mitochondrial, schizophrenia",
author = "Regenold, {William T.} and Pornima Phatak and Marano, {Christopher M.} and Amritpal Sassan and Conley, {Robert R.} and Kling, {Mitchel A.}",
year = "2009",
month = "3",
day = "15",
doi = "10.1016/j.biopsych.2008.11.010",
language = "English (US)",
volume = "65",
pages = "489--494",
journal = "Biological Psychiatry",
issn = "0006-3223",
publisher = "Elsevier USA",
number = "6",

}

TY - JOUR

T1 - Elevated Cerebrospinal Fluid Lactate Concentrations in Patients with Bipolar Disorder and Schizophrenia

T2 - Implications for the Mitochondrial Dysfunction Hypothesis

AU - Regenold, William T.

AU - Phatak, Pornima

AU - Marano, Christopher M.

AU - Sassan, Amritpal

AU - Conley, Robert R.

AU - Kling, Mitchel A.

PY - 2009/3/15

Y1 - 2009/3/15

N2 - Background: Evidence is accumulating that mitochondrial dysfunction is involved in the pathophysiology of bipolar disorder and schizophrenia. Cerebrospinal fluid (CSF) concentration of lactate, a product of extra-mitochondrial glucose metabolism, is commonly elevated in individuals with mitochondrial disorders, especially those with neuropsychiatric symptoms. We tested the hypothesis that patients with bipolar disorder and schizophrenia would, on average, have elevated CSF lactate concentrations compared with healthy control subjects. Methods: The CSF lactate and CSF and plasma glucose concentrations were measured with a YSI (YSI, Yellow Springs, Ohio) 2300 STAT Plus Glucose & Lactate Analyzer in 15 samples from each of three groups of subjects: bipolar I disorder patients, schizophrenic patients, and healthy control subjects. Results: Mean CSF lactate concentrations were significantly higher in bipolar (1.76 ± .38) and schizophrenic subjects (1.61 ± .31) compared with control subjects (1.31 ± .21 mmol/L). These differences persisted after adjusting means for CSF glucose concentration, which correlated positively with CSF lactate concentration. Conclusions: This is the first report of increased CSF lactate concentrations in patients with bipolar disorder and schizophrenia. Elevated CSF lactate indicates increased extra-mitochondrial and anaerobic glucose metabolism and is consistent with impaired mitochondrial metabolism. Measuring CSF lactate concentration might help identify bipolar and schizophrenic patients with mitochondrial dysfunction who might benefit from research to elucidate and ultimately rectify possible mitochondrial pathology underlying these disorders.

AB - Background: Evidence is accumulating that mitochondrial dysfunction is involved in the pathophysiology of bipolar disorder and schizophrenia. Cerebrospinal fluid (CSF) concentration of lactate, a product of extra-mitochondrial glucose metabolism, is commonly elevated in individuals with mitochondrial disorders, especially those with neuropsychiatric symptoms. We tested the hypothesis that patients with bipolar disorder and schizophrenia would, on average, have elevated CSF lactate concentrations compared with healthy control subjects. Methods: The CSF lactate and CSF and plasma glucose concentrations were measured with a YSI (YSI, Yellow Springs, Ohio) 2300 STAT Plus Glucose & Lactate Analyzer in 15 samples from each of three groups of subjects: bipolar I disorder patients, schizophrenic patients, and healthy control subjects. Results: Mean CSF lactate concentrations were significantly higher in bipolar (1.76 ± .38) and schizophrenic subjects (1.61 ± .31) compared with control subjects (1.31 ± .21 mmol/L). These differences persisted after adjusting means for CSF glucose concentration, which correlated positively with CSF lactate concentration. Conclusions: This is the first report of increased CSF lactate concentrations in patients with bipolar disorder and schizophrenia. Elevated CSF lactate indicates increased extra-mitochondrial and anaerobic glucose metabolism and is consistent with impaired mitochondrial metabolism. Measuring CSF lactate concentration might help identify bipolar and schizophrenic patients with mitochondrial dysfunction who might benefit from research to elucidate and ultimately rectify possible mitochondrial pathology underlying these disorders.

KW - Bipolar

KW - cerebrospinal fluid

KW - lactate

KW - metabolism

KW - mitochondrial

KW - schizophrenia

UR - http://www.scopus.com/inward/record.url?scp=60349098146&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=60349098146&partnerID=8YFLogxK

U2 - 10.1016/j.biopsych.2008.11.010

DO - 10.1016/j.biopsych.2008.11.010

M3 - Article

C2 - 19103439

AN - SCOPUS:60349098146

VL - 65

SP - 489

EP - 494

JO - Biological Psychiatry

JF - Biological Psychiatry

SN - 0006-3223

IS - 6

ER -