Yichun Fan ^1,2* Wenping Yang ^3* Weilan Wu ^1,2* Xinjing Wang ^2* Yuxin Lin ^1,2* Linlin Wu ^4* Jun Wang ^2,5 Fei Huan ^2,5* Haixia Ding ^3* Rong Gao ^1,2*

• ¹ Department of Hygienic Analysis and Detection, Key Laboratory of Modern Toxicology, School of Public Health, Nanjing Medical University, Nanjing, Jiangsu Province, China
• ² Global Health Center, School of Public Health, Nanjing Medical University, Nanjing, Jiangsu Province, China
• ³ First Affiliated Hospital, Nanjing Medical University, Nanjing, Jiangsu Province, China
• ⁴ Wuxi Center for Disease Control and Prevention, Wuxi, Jiangsu Province, China
• ⁵ Department of Toxicology, Key Laboratory of Modern Toxicology, School of Public Health, Nanjing Medical University, Nanjing, Jiangsu Province, China

The clinical symptoms of Parkinson's disease (PD) are classified as motor and non-motor symptoms. Mental disorders, especially depression, is one of the major PD's non-motor signs. However, the underlying mechanisms remained poorly understood. In the present study, 21 neurotransmitters pertaining mental disorders were measured in serum samples from patients and controls via the ultra-high performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) assay. Besides, five clinical scale scores of MDS Unified-Parkinson Disease Rating Scale (UPDRS), Non-Motor Symptoms Scale (NMSS), Mini-Mental State Examination (MMSE), Hamilton Anxiety Scale (HAMA) and Hamilton Depression Scale (HAMD) in PD patients were assessed, which reflected the severity of motor and non-motor symptoms. For the neurotransmitter metabolism, it displayed pronounced changes of the tryptophan (Trp) metabolic pathway in PD patients, the Trp, kynurenine (KYN), kynurenic acid (KA), nicotinamide (NAM) and 5-methoxyltryptamine (MeOTA) were substantially decreased. Meanwhile, three other excitation/inhibiting amino acids, glutamic acid (Glu), 4-aminobutyric acid (GABA), and aspartic acid (Asp) were declined as well. Moreover, the neurotransmitter conversion such as KA/KYN, nicotinamide/niacin (NAM/NA), 5-hydroxytryptophan/tryptophan (5-HTP/Trp) and quinolinic acid/kynurenic acid (QA/KA), provided more dynamic information of the perturbed neurotransmitter metabolism. Correlation analyses between scale scores and neurotransmitter levels showed that the concentrations of xanthurenic acid (XA) and the turnover rate of 3-hydroxykynurenine (3-HK), were negatively correlated with UPDRS scores; while 5-hydroxytryptamine (5-HT) and GABA were negatively correlated with the non-motor symptoms of PD patients. Taken together, the present study, for the first time, elucidated the potential association and dynamics between the disturbed neurotransmitter metabolism and the etiology of PD in a motor and non-motor function, providing novel biomarkers and therapeutic targets for PD treatment.