Epistatic interaction of BDNF and COMT on the frontostriatal system. (9th July 2015)

• Record Type: Journal Article
• Authors: Wang, C.; Liu, B.; Long, H.; Fan, L.; Li, J.; Zhang, X.; Qiu, C.; Yu, C.; Jiang, T.
• Is Part Of: Neuroscience. Volume 298(2015)
• Page Start: 380
• Page End: 388
• Publication Date: 2015-07-09
• Subjects: ACC anterior cingulate -- ANOVA analysis of variance -- BDNF brain-derived neurotrophic factor -- COMT catechol-O-methyltransferase -- DA dopamine -- fMRI functional magnetic resonance imaging -- FWE family-wise-error -- MANCOVA multivariate analysis of covariance -- MNI Montreal Neurological Institute -- NAc nucleus accumbens -- PCR polymerase chain reaction -- PFC prefrontal cortex -- rs-FC resting-state functional connectivity -- SPM statistical parametric mapping -- SVC small-volume correction -- VST ventral striatum; brain-derived neurotrophic factor (BDNF) -- catechol-O-methyltransferase (COMT) -- dopamine -- frontostriatal system -- functional connectivity; Neurochemistry -- Periodicals; Neurophysiology -- Periodicals; Neurology -- Periodicals; Neurochimie -- Périodiques; Neurophysiologie -- Périodiques; Neurochemistry; Neurophysiology; Electronic journals; Periodicals; Electronic journals; 612.8
• DOI: 10.1016/j.neuroscience.2015.04.014
• Languages: English
• ISSNs: 0306-4522

Abstract

Highlights: We test the interaction effect of BDNF and COMT on the frontostriatal circuit. We use resting state functional connectivity as an index of the circuit. BDNF variants impact the functional circuit in an inverse U-shaped in COMT Met carrier. BDNF variants impact the functional circuit in a U-shaped in COMT Val/Val. We report an epistatic interaction of BDNF and COMT on the frontostriatal circuit. 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.