Metabolomics and Cytokine Analysis for Identification of Schizophrenia with Auditory Hallucination

Purpose: To investigate the metabolic profile and biomarkers of schizophrenia with auditory hallucinations (AHs).

Methods: A total of 18 schizophrenic patients with the symptom of pure AHs (pAHs), 28 without AH (nAHs) and 43 age-matched healthy persons (Con) were enrolled in this study. Participants in pAHs and nAHs groups had relapsed into exacerbations of psychosis after self-discontinuing antipsychotics for at least one month; blood samples were drawn prior to restarting anti-psychotic treatment. Participants with history of recreational substance use were excluded. Positive and Negative Syndrome Scale (PANSS) and Auditory Hallucinations Rating Scale (AHRS) were used to assess the clinical mental state of all samples. Enzyme-linked immunosorbent assay (ELISA) was used to estimate the level of cytokines, and metabolomics analysis to identify potential biomarkers and pathways in the three groups. Graphpad 8.0 software was used to calculate the area under the receiver operating characteristic (ROC) curve. The relationship between metabolites and cytokines were determined using correlation analysis.

Results: Questionnaire scores showed significant differences in the positive symptom scale and PANSS total between nAHs and pAHs groups. Four cytokines (BDNF, IL-2, NGF-β and TNF-α) differed significantly among the three groups. Six molecules in the nAHs group (phenylalanine, hippurate, serine, glutamate, valine and cystine) and four in the pAHs group (phenylalanine, serine, glutamate and cystine) were identified as potential biomarkers. In addition, phenylalanine was shown as a potential independent diagnostic biomarker for pAHs. Correlation analysis revealed that cystine and serine were significantly negatively correlated with IL-2 in the pAHs group.

Conclusions: This study revealed the metabolic profile of patients with schizophrenia with AHs and provided new information to support the diagnosis. The identification of unique biomarkers would contribute to objective and reliable diagnoses of patients with schizophrenia with AH.