Epistatic interaction of BDNF and COMT on the frontostriatal system

Interaction Effects of BDNF and COMT Genes on Resting-State Brain Activity and Working Memory

“…Indeed, previous research has reported mixed findings, with some studies linking the Val allele to better performance on learning (Soliman et al, 2010), episodic memory (Egan et al, 2003), and WM tasks (Echeverria et al, 2005; Rybakowski et al, 2006), whereas others showed conflicting findings (Hansell et al, 2007; Schofield et al, 2009). Some of these conflicting results may well have been due to potential interactions between BDNF and COMT as found in our study on WM and ReHo, as well as in previous studies on paired-associates learning, stimulation-induced cortical plasticity (Witte et al, 2012), gray matter volumes (Mortby et al, 2014), and functional connectivity (Wang et al, 2015; Li et al's, 2016). …”

“…In contrast, the other two combinations ( COMT- VV and BDNF- VV; COMT- M+ and BDNF- M+) are expected to show moderate levels of dopamine. Li et al (2016) finding that the latter two groups (with presumed medium levels of dopamine signaling) showed higher global functional connectivity density than the other two groups (either low or high levels of dopamine signaling) fits the commonly accepted inverted U-shaped association between dopamine level and outcomes (see Wang et al, 2015; Li et al's, 2016 for detailed discussions).…”

“…Other studies suggested such an effect indirectly by demonstrating similar interaction effects on the anatomy of the hippocampus (Hajek et al, 2012) and PFC (Gothelf et al, 2005; Ho et al, 2007; Takahashi et al, 2008), brain cortical plasticity and frontostriatal circuit brain activities (Wang et al, 2015), all of which could affect memory performance. Interactions between COMT and BDNF polymorphisms exist for WM likely because both genes are widely expressed in the cortex and white matter (in humans and mice, see The Human Protein Atlas, http://www.proteinatlas.org/, and Allen Brain Atlas, http://www.brainatlas.org) (Su et al, 2004).…”

Interaction ofCOMTrs4680 andBDNFrs6265 polymorphisms on functional connectivity density of the left frontal eye field in healthy young adults

“…For each subject, the COMT rs4680 and BDNF rs6265 were genotyped using the polymerase chain reaction and ligation detection reaction [Thomas et al, ; Yi et al, ] with technical support from the Shanghai Biowing Applied Biotechnology Company. The detailed procedures for genotyping have been previously described [Wang et al, ].…”

“…Indeed, significant COMT × BDNF interactions have been reported on boredom susceptibility of sensation seeking traits [Kang et al, ], implicit grammar learning [Witte et al, ], resilience [Kang et al, ], and cognitive performance [Das et al, ] in healthy subjects, and on symptoms and cognition in schizophrenia [Han et al, ], dysfunctional beliefs in obsessive‐compulsive disorder [Alonso et al, ], and anxiety sensitivity in panic disorder [Konishi et al, ]. To investigate the neural mechanisms underlying the COMT × BDNF interaction on these external phenotypes, a COMT × BDNF interaction has been found in paired associative stimulation‐induced plasticity in the motor cortex [Witte et al, ] and resting‐state functional connectivity (rsFC) between the ventral striatum and the anterior cingulate cortex [Wang et al, ]. However, these hypothesis‐driven analyses cannot provide us a full picture of the COMT × BDNF interaction on brain properties.…”