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While there is evidence that these drugs can be beneficial for cognition in selected patients, questions remain about their cardiovascular effects. Here, we tested whether heart rate variability (HRV) is altered in people with Parkinson\u2019s disease, following a single-dose challenge with the noradrenaline reuptake inhibitor atomoxetine (40\u2005mg, oral). Consistent with previous work, our cohort of people with idiopathic Parkinson\u2019s disease (n = 15) had lower HRV than healthy controls (n = 22). Select markers of decreased HRV in people with Parkinson\u2019s disease were associated with reduced integrity of the caudal locus coeruleus, measured using neuromelanin-sensitive ultra-high-field 7T magnetic resonance imaging. Following a randomized double-blind placebo-controlled crossover challenge in the Parkinson\u2019s disease group, short-term resting HRV was not significantly altered following atomoxetine. Using Bayesian statistical inference, we demonstrated confidence in the preservation of HRV across measures in the time, frequency and non-linear domains. Our findings are in favour of a safe cardiovascular profile for atomoxetine in Parkinson\u2019s disease, further supporting noradrenergic modulation as a viable treatment strategy for neuropsychiatric symptoms in Parkinson\u2019s disease and related disorders.<\/jats:p>","DOI":"10.1093\/braincomms\/fcag338","type":"journal-article","created":{"date-parts":[[2026,9,6]],"date-time":"2026-09-06T11:21:39Z","timestamp":1788693699000},"source":"Crossref","is-referenced-by-count":0,"title":["Short-term heart rate variability is preserved in Parkinson\u2019s disease under atomoxetine"],"prefix":"10.1093","volume":"8","author":[{"ORCID":"https:\/\/orcid.org\/0009-0001-4515-3479","authenticated-orcid":false,"given":"Isabella F","family":"Orlando","sequence":"first","affiliation":[{"name":"School of Medical Sciences, Faculty of Medicine and Health, University of Sydney , Sydney 2050, New South Wales ,","place":["Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frank H","family":"Hezemans","sequence":"additional","affiliation":[{"name":"MRC Cognition and Brain Sciences Unit, University of Cambridge , Cambridge CB2 7EF ,","place":["UK"]},{"name":"Department of Clinical Neurosciences and Cambridge University Hospitals NHS Trust, University of Cambridge , Cambridge CB2 0SZ ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kamen A","family":"Tsvetanov","sequence":"additional","affiliation":[{"name":"Department of Clinical Neurosciences and Cambridge University Hospitals NHS Trust, University of Cambridge , Cambridge CB2 0SZ ,","place":["UK"]},{"name":"Department of Psychology, University of Cambridge , Cambridge CB2 3EA ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2529-7755","authenticated-orcid":false,"given":"Rong","family":"Ye","sequence":"additional","affiliation":[{"name":"Department of Clinical Neurosciences and Cambridge University Hospitals NHS Trust, University of Cambridge , Cambridge CB2 0SZ ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Catarina","family":"Rua","sequence":"additional","affiliation":[{"name":"Department of Clinical Neurosciences and Cambridge University Hospitals NHS Trust, University of Cambridge , Cambridge CB2 0SZ ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ralf","family":"Regenthal","sequence":"additional","affiliation":[{"name":"Division of Clinical Pharmacology, Rudolf-Boehm-Institute for Pharmacology and Toxicology, University of Leipzig , Leipzig 69978 ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roger A","family":"Barker","sequence":"additional","affiliation":[{"name":"Department of Clinical Neurosciences and Cambridge University Hospitals NHS Trust, University of Cambridge , Cambridge CB2 0SZ ,","place":["UK"]},{"name":"John van Geest Centre for Brain Repair, Department of Clinical Neurosciences, University of Cambridge , Cambridge CB2 0SZ ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caroline H","family":"Williams-Gray","sequence":"additional","affiliation":[{"name":"John van Geest Centre for Brain Repair, Department of Clinical Neurosciences, University of Cambridge , Cambridge CB2 0SZ ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7937-0615","authenticated-orcid":false,"given":"Luca","family":"Passamonti","sequence":"additional","affiliation":[{"name":"Department of Clinical Neurosciences and Cambridge University Hospitals NHS Trust, University of Cambridge , Cambridge CB2 0SZ ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0642-5977","authenticated-orcid":false,"given":"Trevor W","family":"Robbins","sequence":"additional","affiliation":[{"name":"Department of Psychology, University of Cambridge , Cambridge CB2 3EA ,","place":["UK"]},{"name":"Behavioural and Clinical Neuroscience Institute, University of Cambridge , Cambridge CB2 3EA ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James B","family":"Rowe","sequence":"additional","affiliation":[{"name":"MRC Cognition and Brain Sciences Unit, University of Cambridge , Cambridge CB2 7EF ,","place":["UK"]},{"name":"Department of Clinical Neurosciences and Cambridge University Hospitals NHS Trust, University of Cambridge , Cambridge CB2 0SZ ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5698-6364","authenticated-orcid":false,"given":"Claire","family":"O\u2019Callaghan","sequence":"additional","affiliation":[{"name":"School of Medical Sciences, Faculty of Medicine and Health, University of Sydney , Sydney 2050, New South Wales 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ageing","volume":"149","author":"Orlando","year":"2023","journal-title":"Neurosci Biobehav Rev."},{"issue":"5","key":"2026091421165699700_fcag338-B4","doi-asserted-by":"crossref","first-page":"e1010079","DOI":"10.1371\/journal.pcbi.1010079","article-title":"Noradrenergic deficits contribute to apathy in Parkinson\u2019s disease through the precision of expected outcomes","volume":"18","author":"Hezemans","year":"2022","journal-title":"PLoS Comput Biol."},{"issue":"7","key":"2026091421165699700_fcag338-B5","doi-asserted-by":"crossref","first-page":"1986","DOI":"10.1093\/brain\/awu117","article-title":"Targeting impulsivity in Parkinson\u2019s disease using atomoxetine","volume":"137","author":"Kehagia","year":"2014","journal-title":"Brain."},{"issue":"1","key":"2026091421165699700_fcag338-B6","doi-asserted-by":"crossref","first-page":"1223","DOI":"10.1038\/s42003-025-08627-2","article-title":"Pharmacological and pupillary evidence for the noradrenergic contribution to reinforcement 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