| 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
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| 摘要 | Recent 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. |
| 关键词 | Parkinson's disease impulsivity response inhibition stratification noradrenaline serotonin machine learning |
| 2016-03-01 | |
| 语种 | 英语 |
| DOI | 10.1002/hbm.23087 |
| 发表期刊 | HUMAN BRAIN MAPPING
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| ISSN | 1065-9471 |
| 卷号 | 37期号:3页码:1026-1037 |
| 期刊论文类型 | Article |
| 收录类别 | SCI |
| WOS关键词 | IMPULSE CONTROL DISORDERS ; STOP-SIGNAL ; NEUROCHEMICAL MODULATION ; EXTRACELLULAR LEVELS ; PREFRONTAL CORTEX ; WORKING-MEMORY ; DOPAMINE ; SEROTONIN ; BRAIN ; METHYLPHENIDATE |
| WOS标题词 | Science & Technology ; Life Sciences & Biomedicine |
| WOS研究方向 | Neurosciences & Neurology ; Radiology, Nuclear Medicine & Medical Imaging |
| WOS类目 | Neurosciences ; Neuroimaging ; Radiology, Nuclear Medicine & Medical Imaging |
| WOS记录号 | WOS:000370243600014 |
| 资助机构 | Wellcome Trust(103838) ; Medical Research Council(MC_US_A060_0016 ; NIHR Cambridge Biomedical Research Centre ; Parkinson's UK ; RG62761) |
| 引用统计 | |
| 文献类型 | 期刊论文 |
| 条目标识符 | http://ir.psych.ac.cn/handle/311026/19568 |
| 专题 | 健康与遗传心理学研究室 |
| 作者单位 | 1.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 |
| 第一作者单位 | 中国科学院心理健康重点实验室 |
| 推荐引用方式 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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