Serum 5-hydroxytryptamine levels as biomarkers for motor dysfunction and depression in Parkinson’s disease patients

Abstract

BACKGROUND

Two severely disabling complications - levodopa-induced dyskinesia and depression - commonly emerge in Parkinson’s disease (PD) patients, substantially diminishing their quality of life. Through mechanisms involving uncontrolled dopamine release and compromised mood regulation pathways, serotonergic dysfunction contributes critically to both conditions. The clinical community faces an ongoing need to identify easily accessible peripheral markers that enable early risk assessment.

AIM

To examines how serum 5-hydroxytryptamine (5-HT) concentrations relate to motor impairment (dyskinesia) and depressive symptoms in PD patients. Our goal is to assess whether serum 5-HT can function as a unified biomarker for these prevalent complications.

METHODS

Between January 2019 and August 2019, we enrolled 70 PD patients from our hospital’s inpatient and outpatient services in an observational investigation. Participants were divided into two groups: Those with dyskinesia (n = 33) and those without (n = 37). Using standardized assessment tools, we evaluated depression and subsequently classified patients according to whether depressive symptoms were present. High-performance liquid chromatography enabled measurement of serum 5-HT concentrations. We gathered clinical information encompassing Hoehn-Yahr (H-Y) staging, levodopa equivalent daily dose, dyskinesia severity scores, and depression scale ratings. SPSS version 22.0 software facilitated our statistical analyses.

RESULTS

The dyskinesia group exhibited significantly reduced serum 5-HT concentrations relative to the non-dyskinesia group. Analysis of 5-HT distribution revealed that 78.8% (26/33) of dyskinesia patients had concentrations falling below the median value, contrasting sharply with just 29.7% (11/37) in the non-dyskinesia group (χ² = 16.84, P < 0.001). Further stratification within the dyskinesia group utilized Abnormal Involuntary Movement Scale (AIMS) scores to assess dyskinesia severity. Patients with mild dyskinesia (AIMS 1-6, n = 14) demonstrated elevated 5-HT levels compared to those experiencing moderate-to-severe dyskinesia (AIMS ≥ 7, n = 19). While no significant association emerged between serum 5-HT concentrations and H-Y stages among dyskinesia patients (H-Y 2-2.5 vs H-Y 3-4: P = 0.073), the near-significant P value warrants cautious interpretation considering the constrained sample size. Similarly, maximum daily levodopa dosage showed no significant correlation.

CONCLUSION

PD patients presenting with dyskinesia and depression display markedly reduced serum 5-HT concentrations, indicating that serum 5-HT may represent a valuable marker for tracking both motor and non-motor complications. These results reinforce the contribution of serotonergic dysfunction to the underlying pathophysiology of dyskinesia and depression in PD, which may guide therapeutic approaches targeting serotonin-related pathways.

Keywords: Parkinson’s disease; Serum serotonin; Biomarkers; Dyskinesia; Depression; Non-motor symptoms; Serotonergic dysfunction

Core Tip: This study investigated the role of serum serotonin [5-hydroxytryptamine (5-HT)] as a biomarker for complications in Parkinson’s disease (PD). We found that reduced serum 5-HT levels were independently associated with both levodopa-induced dyskinesia and depression, two common motor and non-motor complications of PD. Serum 5-HT showed good discriminative ability for identifying at-risk patients and may provide a simple peripheral marker for early risk stratification and personalized management in PD.