Epistatic interaction of BDNF and COMT on the frontostriatal system
Chao Wang, Bing Liu, Haixia Long, Linzhong Fan, Jin Li, Xiaolong Zhang, Chengxiang Qiu, Chunshui Yu, Tianzi Jiang
- 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 line in COMT Met carrier.
- BDNF variants impact the functional circuit in a U line in COMT Val/Val.
- We report an epistatic interaction of BDNF and COMT on the frontostriatal circuit.
The frontostriatal system plays a critical role in emotional and cognitive control. Brain-derived neurotrophic factor (BDNF) influences the release of dopamine in the ventral striatum, while catechol-O-methyltransferase (COMT) impacts dopamine 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 dopamine-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 ventral striatum (VST) and the anterior cingulate cortex. Specifically, BDNF Val66Met impacted the VST-PFC functional connectivity in an inverted U-relationship in COMT Met carriers, while COMT Val homozygotes displayed a U-relationship. 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.