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

Abstract

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
• r-Aminobutyric acid
• Neurotransmitters
• Schizophrenia
• Cognitive function
• Biomarker