Increased lactate levels and reduced pH in postmortem brains of schizophrenics: Medication confounds

Nader D. Halim, Barbara K. Lipska, Thomas Hyde, Amy Deep-Soboslay, E. Michael Saylor, Mary M. Herman, Jay Thakar, Ajay Verma, Joel Kleinman

Research output: Contribution to journalArticle

Abstract

A number of postmortem studies have found decreased pH in brains of patients with schizophrenia. Insofar as lower pH has been associated with decreased mRNA expression in postmortem human brain, decreased pH in schizophrenia may represent an important potential confound in comparisons between patients and controls. We hypothesized that decreased pH may be related to increased concentration of lactic acid. However, in contrast to the previous notion that an increase in lactic acid represents evidence for primary metabolic abnormalities in schizophrenia, we hypothesized that this increase is secondary to prior antipsychotic treatment. We have tested this by first demonstrating that lactate levels in the cerebellum of patients with schizophrenia (n = 35) are increased relative to control subjects (n = 42) by 28%, p = 0.001. Second, we have shown that there is an excellent correlation between lactate levels in the cerebellum and pH, and that this correlation is particularly strong in patients (r = -0.78, p = 3E-6). Third, we have shown in rats that chronic haloperidol (0.8 mg/kg/day) and clozapine (5 mg/kg/day) increase lactic acid concentration in the frontal cortex relative to vehicle (by 31% and 22% respectively, p < 0.01). These data suggest that lactate increases in postmortem human brain of patients with schizophrenia are associated with decreased pH and that these changes are possibly related to antipsychotic treatment rather than a primary metabolic abnormality in the prefrontal cortex of patients with schizophrenia.

Original languageEnglish (US)
Pages (from-to)208-213
Number of pages6
JournalJournal of Neuroscience Methods
Volume169
Issue number1
DOIs
StatePublished - Mar 30 2008
Externally publishedYes

Fingerprint

Lactic Acid
Schizophrenia
Brain
Cerebellum
Antipsychotic Agents
Clozapine
Frontal Lobe
Haloperidol
Prefrontal Cortex
Messenger RNA
Therapeutics

Keywords

  • Brain collection
  • Lactate
  • pH
  • Postmortem
  • Schizophrenia

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Increased lactate levels and reduced pH in postmortem brains of schizophrenics : Medication confounds. / Halim, Nader D.; Lipska, Barbara K.; Hyde, Thomas; Deep-Soboslay, Amy; Saylor, E. Michael; Herman, Mary M.; Thakar, Jay; Verma, Ajay; Kleinman, Joel.

In: Journal of Neuroscience Methods, Vol. 169, No. 1, 30.03.2008, p. 208-213.

Research output: Contribution to journalArticle

Halim, Nader D. ; Lipska, Barbara K. ; Hyde, Thomas ; Deep-Soboslay, Amy ; Saylor, E. Michael ; Herman, Mary M. ; Thakar, Jay ; Verma, Ajay ; Kleinman, Joel. / Increased lactate levels and reduced pH in postmortem brains of schizophrenics : Medication confounds. In: Journal of Neuroscience Methods. 2008 ; Vol. 169, No. 1. pp. 208-213.
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