Objective: The objective of this work was to determine whether plasma serotonin levels in Parkinson’s disease (PD) are related to iron levels in the brain, and particularly in the substantia nigra pars compacta (SNc).

Background: PD involves iron and serotonin co-pathologies, including elevated iron levels in the SNc and low serotonin levels in the brain and periphery. Several findings in studies using animal models suggest serotonin dysfunction and iron dyshomeostasis may be closely related. Yet, the relationship between serotonin and iron co-pathologies in PD remains unclear.

Method: We obtained clinical and MRI data from 97 PD and 89 control subjects who participated in an NIH-funded PD biomarker program. We measured serotonin concentrations in available plasma samples using ultra performance liquid chromatography. We compared these concentrations between PD and controls and investigated associations with clinical metrics and nigral quantitative susceptibility mapping (QSM, an MRI metric reflecting iron) after adjusting for age, sex, and disease duration.

Results: Plasma serotonin was significantly lower in PD subjects compared to controls. Lower plasma serotonin in PD was associated with higher iron in the brain as reflected both by QSM in the SNc (rs(58)=-0.444, p=0.000) and H-ferritin in CSF (rs(16) =-0.597, p = 0.009). Subgroup analyses revealed that mean QSM in the SNc was only significantly elevated compared to controls in PD patients within the lowest plasma serotonin tertile (p=0.000). Clinically, plasma serotonin was not significantly correlated with disease duration, but was correlated with non-motor symptom severity (MDS-UPDRS I; rs(90) = -0.240, p = 0.012), quality of life (QoL; Parkinson’s Disease Questionnaire 39 (PDQ-39); rs(90) =0.300, p=0.007), and, in females, freezing of gait (FOG-Q; rs(44)=-.459, p=.001). Low plasma serotonin was also strongly associated with SSRI/SNRI use (p=0.000).

Conclusion: Low plasma serotonin is strongly associated with elevated levels of nigral iron and CSF H-ferritin in PD, and this association may be influenced by anti-depressant medication. In addition, low plasma serotonin is correlated with worse non-motor symptoms, QoL, and, in females, freezing of gait in PD. An iron-serotonin link in PD could have important clinical and pathoetiological implications and warrants further exploration in pre-clinical and clinical studies.

« Back to MDS Virtual Congress 2020

MDS Abstracts - https://www.mdsabstracts.org/abstract/elevated-nigral-iron-is-associated-with-low-plasma-serotonin-in-parkinsons-disease/