Epistatic interaction of BDNF and COMT on the frontostriatal system

C Wang; B Liu; H Long; L Fan; J Li; X Zhang; C Qiu; C Yu; T Jiang

doi:10.1016/j.neuroscience.2015.04.014

Epistatic interaction of BDNF and COMT on the frontostriatal system

Neuroscience. 2015 Jul 9:298:380-8. doi: 10.1016/j.neuroscience.2015.04.014. Epub 2015 Apr 18.

Authors

C Wang¹, B Liu², H Long², L Fan³, J Li³, X Zhang³, C Qiu³, C Yu⁴, T Jiang⁵

Affiliations

¹ Key Laboratory for NeuroInformation of Ministry of Education, School of Life Science and Technology, University of Electronic Science and Technology of China, Chengdu, China.
² 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.
³ Brainnetome Center, Institute of Automation, Chinese Academy of Sciences, Beijing, China.
⁴ Department of Radiology, Tianjin Medical University General Hospital, Tianjin, China. Electronic address: chunshuiyu@vip.163.com.
⁵ 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.

PMID: 25896799
DOI: 10.1016/j.neuroscience.2015.04.014

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.

Keywords: brain-derived neurotrophic factor (BDNF); catechol-O-methyltransferase (COMT); dopamine; frontostriatal system; functional connectivity.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adolescent
Adult
Brain Mapping
Brain-Derived Neurotrophic Factor / genetics*
Catechol O-Methyltransferase / genetics*
Corpus Striatum* / anatomy & histology
Corpus Striatum* / blood supply
Epistasis, Genetic*
Female
Frontal Lobe* / anatomy & histology
Frontal Lobe* / blood supply
Functional Laterality
Humans
Image Processing, Computer-Assisted
Magnetic Resonance Imaging
Male
Oxygen / blood
Polymorphism, Single Nucleotide / genetics
Statistics as Topic
Young Adult

Substances

Brain-Derived Neurotrophic Factor
COMT protein, human
Catechol O-Methyltransferase
Oxygen