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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.

METHOD: We recruited adults with schizophrenia (n=122) who had not received pharmacological treatment for at least one 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 (LC-MS).

RESULTS: Metabolites with the greatest change, when comparing pre- and post-treatment levels, were identified revealing fourteen water-soluble metabolites of interest. The composition of these metabolites were amino acids (n=6), carnitines (n=4), polar lipids (n=3), and organic acid (n=1). All amino acids and Lysophosphatidylcholines (LysoPCs) were increased, while the four carnitines, including Oleoylcarnitine, L-Palmitoylcarnitine, Linoleyl carnitine and L-Acetylcarnitine were decreased post-treatment. Of these metabolite biomarkers, a set of six, including Oleoylcarnitine, Linoleyl carnitine, L-Acetylcarnitine, LysoPC(15:0), D-Glutamic acid and L-Arginine, were identified that most consistently and predictably changed after 8 weeks of treatment.

CONCLUSION: Taken together, 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. This article is protected by copyright. All rights reserved.

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