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Predicting beneficial effects of atomoxetine and citalopram on response inhibition in Parkinson's disease with clinical and neuroimaging measures
Ye, Zheng1,2; Rae, Charlotte L.1,3; Nombela, Cristina1; Ham, Timothy1; Rittman, Timothy1; Jones, Peter Simon1; Rodriguez, Patricia Vazquez1; Coyle-Gilchrist, Ian1; Regenthal, Ralf4; Altena, Ellemarije1; Housden, Charlotte R.1; Maxwell, Helen1; Sahakian, Barbara J.6,7; Barker, Roger A.1; Robbins, Trevor W.5,7; Rowe, James B.1,3,7
2016-03-01
Source PublicationHUMAN BRAIN MAPPING
ISSN1065-9471
SubtypeArticle
Volume37Issue:3Pages:1026-1037
AbstractRecent studies indicate that selective noradrenergic (atomoxetine) and serotonergic (citalopram) reuptake inhibitors may improve response inhibition in selected patients with Parkinson's disease, restoring behavioral performance and brain activity. We reassessed the behavioral efficacy of these drugs in a larger cohort and developed predictive models to identify patient responders. We used a double-blind randomized three-way crossover design to investigate stopping efficiency in 34 patients with idiopathic Parkinson's disease after 40mg atomoxetine, 30mg citalopram, or placebo. Diffusion-weighted and functional imaging measured microstructural properties and regional brain activations, respectively. We confirmed that Parkinson's disease impairs response inhibition. Overall, drug effects on response inhibition varied substantially across patients at both behavioral and brain activity levels. We therefore built binary classifiers with leave-one-out cross-validation (LOOCV) to predict patients' responses in terms of improved stopping efficiency. We identified two optimal models: (1) a clinical model that predicted the response of an individual patient with 77-79% accuracy for atomoxetine and citalopram, using clinically available information including age, cognitive status, and levodopa equivalent dose, and a simple diffusion-weighted imaging scan; and (2) a mechanistic model that explained the behavioral response with 85% accuracy for each drug, using drug-induced changes of brain activations in the striatum and presupplementary motor area from functional imaging. These data support growing evidence for the role of noradrenaline and serotonin in inhibitory control. Although noradrenergic and serotonergic drugs have highly variable effects in patients with Parkinson's disease, the individual patient's response to each drug can be predicted using a pattern of clinical and neuroimaging features. Hum Brain Mapp 37:1026-1037, 2016. (c) 2016 Wiley Periodicals, Inc.
KeywordParkinson's disease impulsivity response inhibition stratification noradrenaline serotonin machine learning
DOI10.1002/hbm.23087
Indexed BySCI
Language英语
Funding OrganizationWellcome Trust(103838) ; Medical Research Council(MC_US_A060_0016 ; NIHR Cambridge Biomedical Research Centre ; Parkinson's UK ; RG62761)
WOS Research AreaNeurosciences & Neurology ; Radiology, Nuclear Medicine & Medical Imaging
WOS SubjectNeurosciences ; Neuroimaging ; Radiology, Nuclear Medicine & Medical Imaging
WOS IDWOS:000370243600014
WOS HeadingsScience & Technology ; Life Sciences & Biomedicine
WOS KeywordIMPULSE CONTROL DISORDERS ; STOP-SIGNAL ; NEUROCHEMICAL MODULATION ; EXTRACELLULAR LEVELS ; PREFRONTAL CORTEX ; WORKING-MEMORY ; DOPAMINE ; SEROTONIN ; BRAIN ; METHYLPHENIDATE
Citation statistics
Cited Times:24[WOS]   [WOS Record]     [Related Records in WOS]
Document Type期刊论文
Identifierhttp://ir.psych.ac.cn/handle/311026/19568
Collection健康与遗传心理学研究室
Affiliation1.Univ Cambridge, Dept Clin Neurosci, Herchel Smith Bldg,Forvie Site,Robinson Way,Cambr, Cambridge CB2 0SZ, England
2.Chinese Acad Sci, Inst Psychol, Key Lab Mental Hlth, Beijing 100101, Peoples R China
3.MRC, Cognit & Brain Sci Unit, Cambridge, England
4.Univ Leipzig, Rudolf Boehm Inst Pharmacol & Toxicol, Div Clin Pharmacol, D-04109 Leipzig, Germany
5.Univ Cambridge, Dept Psychol, Cambridge CB2 0SZ, England
6.Univ Cambridge, Dept Psychiat, Cambridge CB2 0SZ, England
7.Behav & Clin Neurosci Inst, Cambridge, England
First Author AffilicationKey Laboratory of Mental Health, CAS
Recommended Citation
GB/T 7714
Ye, Zheng,Rae, Charlotte L.,Nombela, Cristina,et al. Predicting beneficial effects of atomoxetine and citalopram on response inhibition in Parkinson's disease with clinical and neuroimaging measures[J]. HUMAN BRAIN MAPPING,2016,37(3):1026-1037.
APA Ye, Zheng.,Rae, Charlotte L..,Nombela, Cristina.,Ham, Timothy.,Rittman, Timothy.,...&Rowe, James B..(2016).Predicting beneficial effects of atomoxetine and citalopram on response inhibition in Parkinson's disease with clinical and neuroimaging measures.HUMAN BRAIN MAPPING,37(3),1026-1037.
MLA Ye, Zheng,et al."Predicting beneficial effects of atomoxetine and citalopram on response inhibition in Parkinson's disease with clinical and neuroimaging measures".HUMAN BRAIN MAPPING 37.3(2016):1026-1037.
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