Autonomic and Depression Symptoms in Parkinson’s Disease: Clinical Evidence for Overlapping Physiology

Article type: Research Article

Authors: Sklerov, Miriam^{a; *} | Browner, Nina^a | Dayan, Eran^{b; c} | Rubinow, David^d | Frohlich, Flavio^{a; d; e; f; g; h}

Affiliations: [a] Department of Neurology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA | [b] Department of Radiology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA | [c] Biomedical Research Imaging Center, University of North Carolina at Chapel Hill, NC, USA | [d] Department of Psychiatry, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA | [e] Carolina Center for Neurostimulation, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA | [f] Department of Cell Biology and Physiology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA | [g] Department of Biomedical Engineering, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA | [h] Neuroscience Center, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA

Correspondence: [*] Correspondence to: Dr. Miriam Sklerov, MD MS, 170 Manning Drive CB#7025, Chapel Hill, NC, 27599, USA. Tel.: +1 914 413 5308; E-mail: [email protected].

Abstract: Background:Autonomic dysfunction and depression are common non-motor symptoms of Parkinson’s disease (PD) that confer poorer prognosis. These PD symptoms may have overlapping pathophysiologic underpinnings. Objective:To investigate associations between autonomic and depression symptoms in early PD, and their evolution over time. Methods:We obtained data from the Parkinson’s Progression Markers Initiative, a prospective open-access database of early PD. Regression analyses were used to model effects of depression on autonomic symptoms in controls and in PD at baseline, visit 6 (24 months after baseline), and visit 12 (60 months after baseline), correcting for multiple comparisons. Results:Data from 421 people with PD at baseline, 360 at visit 6, 300 at visit 12, and 193 controls were included. When controlling for age, depression, and anti-hypertensive medications, depression predicted autonomic symptoms in all groups. Accounting for motor symptoms did not alter these associations. When comparing groups, the influence of depression on autonomic symptoms was stronger in all PD groups compared to controls, and strongest in PD at visit 12. Depression predicted the presence of orthostatic hypotension only in the PD group at visit 12. Conclusion:We demonstrated the important impact of depression on autonomic symptoms in early and middle stages of PD, which are independent of motor symptoms. Though the physiologic basis of these two PD symptoms are not fully understood, our findings add to pathologic evidence of a shared mechanistic substrate, separate from that responsible for PD motor symptoms. These findings may influence clinical management and development of novel therapies.

Keywords: Parkinson’s disease, non-motor symptoms, depression, autonomic dysfunction, autonomic symptoms

DOI: 10.3233/JPD-213075

Journal: Journal of Parkinson's Disease, vol. 12, no. 3, pp. 1059-1067, 2022