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GIT1 is associated with ADHD in humans and ADHD-like behaviors in mice

Cited 67 time in Web of Science Cited 71 time in Scopus
Authors
Won, Hyejung; Mah, Won; Kim, Eunjin; Kim, Jae-Won; Kim, Myoung-Hwan; Kim, Jeongjin; Cho, Soo-Churl; Shin, Min-Sup; Jeong, Jaeseung; Kim, Eunjoon; Kang, Changwon; Kim, Daesoo; Choi, Se-Young; Seo, Jinsoo; Kim, Boong-Nyun; Jang, Hyeran; Cho, Sukhee; Hahm, Eun-Kyoung
Issue Date
2011-05
Publisher
NATURE PUBLISHING GROUP
Citation
NATURE MEDICINE, Vol.17, No.5; pp.566-U83
Abstract
Attention deficit hyperactivity disorder (ADHD) is a psychiatric disorder that affects similar to 5% of school-aged children; however, the mechanisms underlying ADHD remain largely unclear. Here we report a previously unidentified association between G protein-coupled receptor kinase-interacting protein-1 (GIT1) and ADHD in humans. An intronic single-nucleotide polymorphism in GIT1, the minor allele of which causes reduced GIT1 expression, shows a strong association with ADHD susceptibility in humans. Git1-deficient mice show ADHD-like phenotypes, with traits including hyperactivity, enhanced electroencephalogram theta rhythms and impaired learning and memory. Hyperactivity in Git1(-/-) mice is reversed by amphetamine and methylphenidate, psychostimulants commonly used to treat ADHD. In addition, amphetamine normalizes enhanced theta rhythms and impaired memory. GIT1 deficiency in mice leads to decreases in ras-related C3 botulinum toxin substrate-1 (RAC1) signaling and inhibitory presynaptic input; furthermore, it shifts the neuronal excitation-inhibition balance in postsynaptic neurons toward excitation. Our study identifies a previously unknown involvement of GIT1 in human ADHD and shows that GIT1 deficiency in mice causes psychostimulant-responsive ADHD-like phenotypes.
ISSN
1078-8956
Language
English
URI
http://hdl.handle.net/10371/80444
DOI
https://doi.org/10.1038/nm.2330
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College of Dentistry/School of Dentistry (치과대학/치의학대학원)Dept. of Dentistry (치의학과)Journal Papers (저널논문_치의학과)
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