Alteration levels of monoamine neurotransmitter related with non-motor symptoms and their fluctuation patterns during on/off periods in Parkinson’s patients

Abstract

Parkinson’s disease (PD) is the second most common neurodegenerative disorder. This study consisted of two parts. The purpose of part I was to investigate the difference in concentrations of DA, NE, 5-HT and their metabolites (3-methoxytyramine (3-MET), homovanillic acid (HVA), normetanephrine (NM), vanillylmandelic acid (VMA) and 5-hydroxyindoleacetic acid (5-HIAA)) in peripheral body fluids between control and PD groups. In addition, the correlation between these neurotransmitter levels and NMSs were evaluated. The purpose of part II was to investigate the fluctuation of plasma DA, NE and 5-HT concentrations during medication ON/OFF periods in advanced-PD patients. In part I, the control and PD patients (n=40/group), aged between 30-80 years were randomly recruited from the King Chulalongkorn Memorial Hospital. All participants were assessed anxiety and depression, sleep problems, and sexual dysfunction by using Hospital Anxiety and Depression Scale (HADS), Modified Parkinson’s disease sleep scale (MPDSS), and The Arizona Sexual Experience Scale (ASEX), respectively. Plasma, saliva, and urine were collected for determined the levels of monoamine and their metabolites by using high performance liquid chromatography with electrochemical detector. In part II, the plasma DA, NE and 5-HT levels were determined in advanced-PD patients at 3 points time during medication ON/OFF periods (5 minutes before, 45 and 120 minutes after drug taking). Plasma DA level did not show significant differences between two groups. However, there were significantly higher in plasma NE and lower plasma 5-HT levels in PD patients than control group. Levels of urinary 3-Met and HVA were significantly higher in the PD patients, while urinary NM and 5-HIAA levels were significantly lower in PD than control. Salivary DA and NE tend to increase in PD but do not show significant differences when compared to control. However, salivary 5-HT could not be detected in this study. PD patients were significantly higher in HADS (anxiety and depression) and ASEX score with lower in MPDSS score than in control. For the study of correlation, the results did not show any relationship between monoamines levels and NMSs in PD patients. In part II, we found that plasma DA, NE and 5-HT levels increase after medication taking for 45 minutes in ON comparing to the OFF period. Plasma DA and 5-HT levels tend to be decrease after medication taking for 120 minutes. Meanwhile, NE level in plasma was continuously increased. However, there were no significant difference among 3 time points of these plasma monoamine levels. From these findings, there is dysregulations of monoamines in peripheral body fluids. Additionally, PD patients exhibited anxiety, depression, sleep disturbances and sexual dysfunction. This knowledge could benefit appropriate pharmacological treatment planning in respect of monoamine changes and might also help predict subsequent clinical symptoms.