Serum levels of β-hydroxybutyrate and pyruvate, metabolic changes and cognitive function in patients with schizophrenia during antipsychotic treatment: a preliminary study

Abstract

Background: β-hydroxybutyrate (β-HB) and pyruvate have been associated with the brain energy utilization, which may play a role in the pathophysiology of schizophrenia. In this prospective study, we aim to investigate the trends of β-HB and pyruvate levels, metabolic changes, and cognitive function in schizophrenia patients receiving antipsychotic treatment.

Objective: We recruited 38 schizophrenia patients who had been treated with antipsychotics for 12 weeks, as well as 38 healthy age- and gender-matched subjects. Blood samples were taken from the patients at baseline and week 12 to determine the serum levels of β-HB, pyruvate, and metabolic parameters, while blood samples of the healthy controls were taken at baseline. We evaluated the psychopathology using the Positive and Negative Syndrome Scale and cognitive function using the Brief Assessment of Cognition in Schizophrenia.

Results: During the 12-week follow-up period, the β-HB levels in patients with schizophrenia showed a decreasing trend, particularly in those undergoing treatment with aripiprazole or ziprasidone. The serum levels of β-HB in patients at baseline and week 12 were both higher than the levels in the healthy controls. Among the schizophrenia patients, changes in β-HB were positively correlated with changes in executive function. On the other hand, serum pyruvate levels remained steady during the 12-week follow-up period, and we found no significant correlation between pyruvate changes and changes in cognitive function or clinical symptoms.

Conclusion: Our findings indicate that β-HB may possess a potential indicator of energy utilization and have a protective role in executive function in patients with schizophrenia. Additional longitudinal studies with a larger sample size and longer follow-up periods are necessary to identify the relationship of metabolite regulation and cognitive function during schizophrenia patients' exposure to antipsychotics.

Keywords: antipsychotic; cognition; energy; executive function; ketone body; metabolism; schizophrenia.

Figure 1

Changes of serum levels of β-HB (A) and pyruvate (B) in patients with schizophrenia during a 12-week antipsychotic treatment period, and comparison with healthy controls. Notes: *p<0.05, **p<0.01, ***p<0.001. β-HB levels in schizophrenia patients at baseline were significantly higher than β-HB levels in healthy controls (492.3±246.5 vs 327.4±100.0 μM, p<0.001). β-HB levels in patients at week 12 remained significantly higher than β-HB levels in the healthy controls (431.5±148.2 vs 327.4±100.0 μM, p=0.001; A). Pyruvate levels between baseline and week 12 in patients had no statistically significant difference (pyruvate at baseline and week 12: 30.0±18.9 vs 29.3±13.9 μM, p>0.05); pyruvate levels in patients at baseline and week 12 had no significant differences when compared with pyruvate levels in the healthy controls (25.7±9.0 μM, p>0.05; B). Abbreviations: AZ group, patients being treated with aripiprazole or ziprasidone; β-HB, β-hydroxybutyrate; OA group, patients being treated with any other antipsychotics; OC group, patients being treated with olanzapine or clozapine.

Figure 2

Scatterplot displaying the changes of β-HB and the changes of executive function during the 12-week antipsychotic treatment period (r=0.424, p=0.008). Abbreviations: AZ group, patients being treated with aripiprazole or ziprasidone; β-HB, β-hydroxybutyrate; OA group, patients being treated with any other antipsychotics; OC group, patients being treated with olanzapine or clozapine.