title: Circadian modulation of dopamine levels and dopaminergic neuron development contributes to attention deficiency and hyperactive behavior.
abstract: Attention-deficit/hyperactivity disorder (ADHD) is one of the most prevalent psychiatric disorders in children and adults. While ADHD patients often display circadian abnormalities, the underlying mechanisms are unclear. Here we found that the zebrafish mutant for the circadian gene period1b (per1b) displays hyperactive, impulsive-like, and attention deficit-like behaviors and low levels of dopamine, reminiscent of human ADHD patients. We found that the circadian clock directly regulates dopamine-related genes monoamine oxidase and dopamine β hydroxylase, and acts via genes important for the development or maintenance of dopaminergic neurons to regulate their number and organization in the ventral diencephalic posterior tuberculum. We then found that Per1 knock-out mice also display ADHD-like symptoms and reduced levels of dopamine, thereby showing highly conserved roles of the circadian clock in ADHD. Our studies demonstrate that disruption of a circadian clock gene elicits ADHD-like syndrome. The circadian model for attention deficiency and hyperactive behavior sheds light on ADHD pathogenesis and opens avenues for exploring novel targets for diagnosis and therapy for this common psychiatric disorder.
authors: Center for Circadian Clocks, School of Biology & Basic Medical Sciences, Medical College.
authors: Jian
authors: J
authors: Huang
authors: Center for Circadian Clocks, School of Biology & Basic Medical Sciences, Medical College.
authors: Zhaomin
authors: Z
authors: Zhong
authors: Center for Circadian Clocks, School of Biology & Basic Medical Sciences, Medical College.
authors: Mingyong
authors: M
authors: Wang
authors: Center for Circadian Clocks, School of Biology & Basic Medical Sciences, Medical College.
authors: Xifeng
authors: X
authors: Chen
authors: Center for Circadian Clocks, School of Biology & Basic Medical Sciences, Medical College.
authors: Yicheng
authors: Y
authors: Tan
authors: Center for Circadian Clocks, School of Biology & Basic Medical Sciences, Medical College.
authors: Shuqing
authors: S
authors: Zhang
authors: Center for Circadian Clocks, School of Biology & Basic Medical Sciences, Medical College.
authors: Wei
authors: W
authors: He
authors: Center for Circadian Clocks, School of Biology & Basic Medical Sciences, Medical College.
authors: Xiong
authors: X
authors: He
authors: Center for Circadian Clocks, School of Biology & Basic Medical Sciences, Medical College.
authors: Guodong
authors: G
authors: Huang
authors: Department of Pediatrics and Child Health, Affiliated Children's Hospital, Soochow University, Suzhou 215003, Jiangsu, China.
authors: Haiping
authors: H
authors: Lu
authors: School of Biology & Basic Medical Sciences, Medical College.
authors: Ping
authors: P
authors: Wu
authors: School of Biology & Basic Medical Sciences, Medical College.
authors: Yi
authors: Y
authors: Che
authors: Center for Circadian Clocks, Institute of Neuroscience, University of Oregon, Eugene, Oregon 97403, and.
authors: Yi-Lin
authors: YL
authors: Yan
authors: Institute of Neuroscience, University of Oregon, Eugene, Oregon 97403, and.
authors: John H
authors: http://orcid.org/0000-0002-5476-2137
authors: JH
authors: Postlethwait
authors: Center for Circadian Clocks, Department of Molecular Physiology and Biophysics, Vanderbilt University School of Medicine, Nashville, Tennessee 37232.
authors: Wenbiao
authors: W
authors: Chen
authors: Center for Circadian Clocks, School of Biology & Basic Medical Sciences, Medical College, han.wang88@gmail.com wanghan@suda.edu.cn.
authors: Han
authors: http://orcid.org/0000-0003-2420-3147
authors: H
authors: Wang
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified; D001289:Attention Deficit Disorder with Hyperactivity / Q000188:drug therapy / Q000378:metabolism* / Q000523:psychology*; D001362:Avoidance Learning / Q000502:physiology; D001522:Behavior, Animal; D002940:Circadian Rhythm; D004298:Dopamine / Q000378:metabolism*; D059290:Dopaminergic Neurons; D007175:Impulsive Behavior; D007814:Larva; D051379:Mice; D009043:Motor Activity; D041681:NIH 3T3 Cells; D056950:Period Circadian Proteins / Q000235:genetics / Q000378:metabolism; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism; D015027:Zebrafish / Q000502:physiology*; D029961:Zebrafish Proteins / Q000235:genetics / Q000378:metabolism
chemical_list: D056950:Period Circadian Proteins; D029961:Zebrafish Proteins; C539027:per1b protein, zebrafish; D014446:Tyrosine 3-Monooxygenase; D004298:Dopamine
keywords: attention deficiency; circadian clock; dopamine; hyperactivity; per1b; zebrafish