title: Epistatic interaction of BDNF and COMT on the frontostriatal system.
abstract: The frontostriatal system plays a critical role in emotional and cognitive control. Brain-derived neurotrophic factor (BDNF) influences the release of dopamine (DA) in the ventral striatum (VST), while catechol-O-methyltransferase (COMT) impacts DA availability in the prefrontal cortex (PFC). Behavioral studies have already shown a genetic interaction of BDNF Val66Met and COMT Val158Met, but the interaction on the DA-related neural circuit has not been previously studied. Here we show, using functional magnetic resonance imaging in a sample of healthy human subjects, that BDNF and COMT epistatically interacted on the functional connectivity between the bilateral VST and the anterior cingulate cortex. Specifically, BDNF Val66Met impacted the VST-PFC functional connectivity in an inverted U-shaped in COMT Met carriers, while COMT Val homozygotes displayed a U-shaped. These data may be helpful elucidating the mechanism of the interaction between BDNF and COMT on the cognitive functions that are based in the frontostriatal system.
authors.affiliation: Key Laboratory for NeuroInformation of Ministry of Education, School of Life Science and Technology, University of Electronic Science and Technology of China, Chengdu, China.
authors.forename: C
authors.initials: C
authors.lastname: Wang
authors.affiliation: Brainnetome Center, Institute of Automation, Chinese Academy of Sciences, Beijing, China; National Laboratory of Pattern Recognition, Institute of Automation, Chinese Academy of Sciences, Beijing, China.
authors.forename: B
authors.initials: B
authors.lastname: Liu
authors.affiliation: Brainnetome Center, Institute of Automation, Chinese Academy of Sciences, Beijing, China; National Laboratory of Pattern Recognition, Institute of Automation, Chinese Academy of Sciences, Beijing, China.
authors.forename: H
authors.initials: H
authors.lastname: Long
authors.affiliation: Brainnetome Center, Institute of Automation, Chinese Academy of Sciences, Beijing, China.
authors.forename: L
authors.initials: L
authors.lastname: Fan
authors.affiliation: Brainnetome Center, Institute of Automation, Chinese Academy of Sciences, Beijing, China.
authors.forename: J
authors.initials: J
authors.lastname: Li
authors.affiliation: Brainnetome Center, Institute of Automation, Chinese Academy of Sciences, Beijing, China.
authors.forename: X
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Brainnetome Center, Institute of Automation, Chinese Academy of Sciences, Beijing, China.
authors.forename: C
authors.initials: C
authors.lastname: Qiu
authors.affiliation: Department of Radiology, Tianjin Medical University General Hospital, Tianjin, China. Electronic address: chunshuiyu@vip.163.com.
authors.forename: C
authors.initials: C
authors.lastname: Yu
authors.affiliation: Key Laboratory for NeuroInformation of Ministry of Education, School of Life Science and Technology, University of Electronic Science and Technology of China, Chengdu, China; Brainnetome Center, Institute of Automation, Chinese Academy of Sciences, Beijing, China; National Laboratory of Pattern Recognition, Institute of Automation, Chinese Academy of Sciences, Beijing, China; CAS Center for Excellence in Brain Science, Institute of Automation, Chinese Academy of Sciences, Beijing, China; The Queensland Brain Institute, University of Queensland, Brisbane, Australia. Electronic address: jiangtz@nlpr.ia.ac.cn.
authors.forename: T
authors.initials: T
authors.lastname: Jiang
mesh_terms: D000293:Adolescent; D000328:Adult; D001931:Brain Mapping; D019208:Brain-Derived Neurotrophic Factor / Q000235:genetics*; D002394:Catechol O-Methyltransferase / Q000235:genetics*; D003342:Corpus Striatum / Q000033:anatomy & histology / Q000098:blood supply; D004843:Epistasis, Genetic; D005260:Female; D005625:Frontal Lobe / Q000033:anatomy & histology / Q000098:blood supply; D007839:Functional Laterality; D006801:Humans; D007091:Image Processing, Computer-Assisted; D008279:Magnetic Resonance Imaging; D008297:Male; D010100:Oxygen / Q000097:blood; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D013223:Statistics as Topic; D055815:Young Adult
chemical_list: D019208:Brain-Derived Neurotrophic Factor; C588010:COMT protein, human; D002394:Catechol O-Methyltransferase; D010100:Oxygen
keywords: brain-derived neurotrophic factor (BDNF); catechol-O-methyltransferase (COMT); dopamine; frontostriatal system; functional connectivity