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. 2008 Mar 30;169(1):208-13.
doi: 10.1016/j.jneumeth.2007.11.017. Epub 2007 Nov 29.

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

Nader D Halim  1 , Barbara K Lipska, Thomas M Hyde, Amy Deep-Soboslay, E Michael Saylor, Mary M Herman, Jay Thakar, Ajay Verma, Joel E Kleinman
Affiliations

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

Nader D Halim et al. J Neurosci Methods. .

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 (0.8mg/kg/day) and clozapine (5mg/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.

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Figures

Figure 1
Figure 1
A scatter plot of lactate levels (mmol/L) in the cerebellum of control subjects (n = 42) and schizophrenic patients (n = 35). Lactate levels are significantly higher in patients with schizophrenia than control subjects (p = 0.001).
Figure 2
Figure 2
(A) Lactate levels are highly correlated with pH (r = −0.53), (B) weakly correlated with age (r = 0.29), (C) and not significantly correlated with postmortem interval (PMI; r = 0.04).
Figure 3
Figure 3
Lactate levels are not significantly correlated with last (A), daily (B), or lifetime (C) chlorpromazine (CPZ) equivalents (0 < r < 0.1).
Figure 4
Figure 4
Lactate concentrations (mean ± SD) in the frontal cortex of rats treated with clozapine (5 mg/kg), haloperidol (0.8 mg/kg), or vehicle (0.1% lactic acid) for 28 days. Chronic intraperitoneal injections of haloperidol or clozapine significantly increased post mortem lactate levels relative to vehicle-treated animals (*p < 0.01, significantly different from vehicle control).
See this image and copyright information in PMC

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