Epistatic interaction of BDNF and COMT on the frontostriatal system

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.