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. 2025 Feb 18;25(1):142.
doi: 10.1186/s12888-025-06584-y.

Disturbance of neurotransmitter metabolites in peripheral blood of schizophrenia patients treated with olanzapine: a preliminary targeted metabolomic study

Jiajun Yin #  1 , Yansha Gan #  1 , Chenguang Jiang #  2 , Jun Wang  3 , Zhenhe Zhou  4
Affiliations

Disturbance of neurotransmitter metabolites in peripheral blood of schizophrenia patients treated with olanzapine: a preliminary targeted metabolomic study

Jiajun Yin et al. BMC Psychiatry. .

Abstract

Background: The aim of this research was to characterize changes in peripheral blood neurotransmitter metabolites in olanzapine-treated schizophrenia (SCZ) and to identify potential biomarkers for SCZ. Concurrently, the relationship between these differential neurotransmitters and cognitive function is explored.

Methods: We recruited 40 SCZ treated with single-agent olanzapine and 40 healthy controls (HC). Cognitive function and psychopathology were assessed using the MCCB and PANSS, respectively. Neurotransmitter levels were determined by targeted metabolomics approach using liquid chromatography-mass spectrometry (LC/MS).

Results: SCZ showed cognitive impairment in all domains of the MCCB compared to HC. Interestingly, a 4-neurotransmitter panel consisting of 3-Methoxytyramine hydrochloride (3-MT), 3,4-Dihydroxyphenylacetate (DOPAC), arginine, and r-aminobutyric acid (GABA) illustrated the highest determinative score between SCZ and HC. Arginine was positively correlated with PANSS general psychopathology scores. 3-MT independently predicted the verbal learning scores only in SCZ, whereas GABA independently predicted the social cognition scores only. Furthermore, GABA independently predicted the working memory scores only in HC.

Conclusions: The collective assessment of these four neurotransmitters (3-MT, DOPAC, arginine, and GABA) holds considerable promise as potential biomarkers for SCZ. Moreover, 3-MT and GABA may enhance our understanding of cognitive dysfunction in SCZ, particularly in areas of verbal learning and social cognitive dysfunction.

Keywords: 3-methoxytyramine; Biomarker; Cognitive function; Neurotransmitters; Schizophrenia; r-Aminobutyric acid.

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Conflict of interest statement

Declarations. Ethics approval and consent to participate: All participants provided written informed consent, and the study was approved by the Ethics Committee of the Wuxi Mental Health Center (WXMHCIRB2022LLky002). Consent for publication: Not applicable. Competing interests: The authors declare no competing interests.

Figures

Fig. 1
Fig. 1
ROC curve for the 4-neurotransmitter panel and each neurotransmitter
Fig. 2
Fig. 2
Correlation of clinical symptoms, cognition and OLZ total dose with neurotransmitters
Fig. 3
Fig. 3
General linear regression analysis results of 3-MT and GABA on cognitive performance in patients and healthy control
See this image and copyright information in PMC

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