Serum Metabolic Profiling Using Small Molecular Water-soluble Metabolites in Individuals with Schizophrenia: A Longitudinal Study Using a Pre-post-treatment Design

Aim: We sought to compare alterations in serum bioenergetic markers within a well-characterized sample of adults with schizophrenia at baseline and after 8 weeks of pharmacological treatment with the hypothesis that treatment would be associated with significant changes in bioenergetic markers given the role of bioenergetic dysfunction in schizophrenia.

Methods: We recruited adults with schizophrenia (n = 122) who had not received pharmacological treatment for at least 1 month prior to enrollment, including drug-naïve (i.e., first-episode) participants and treatment non-adherent participants. Pre- and post-treatment serum samples were analyzed using liquid chromatography-tandem mass spectrometry.

Results: Metabolites with the greatest change, when comparing pre- and post-treatment levels, were identified revealing 14 water-soluble metabolites of interest. The composition of these metabolites was: amino acids (n = 6), carnitines (n = 4), polar lipids (n = 3), and organic acid (n = 1). All amino acids and lysophosphatidylcholines (LysoPC) were increased, while the four carnitines - oleoylcarnitine, L-palmitoylcarnitine, linoleyl carnitine, and L-acetylcarnitine - were decreased post-treatment. Of these metabolite biomarkers, six - oleoylcarnitine, linoleyl carnitine, L-acetylcarnitine, LysoPC(15:0), D-glutamic acid, and L-arginine - were identified as having most consistently and predictably changed after 8 weeks of treatment.

Conclusion: The current study identified several bioenergetic markers that consistently change with pharmacological treatment. These bioenergetic changes may provide further insights into the pathophysiology of schizophrenia along with furthering our understanding of the mechanisms subserving both the effects (e.g., antipsychotic effects) and side-effects (e.g., metabolic syndrome) of antipsychotics.