The influence of the COMT Val158Met polymorphism on prefrontal TDCS effects on aggression.
Carmen WeidlerLena HofhanselChristina RegenbogenDario MüllerBenjamin ClemensChristian MontagAndreas ReifUte HabelPublished in: Scientific reports (2024)
Increasing dorsolateral prefrontal cortex (DLPFC) activity by anodal transcranial direct current stimulation (tDCS) enhances cognitive control and might reduce aggression. The Val158Met polymorphism within the catechol-O-methyltransferase gene (rs4680) plays a pivotal role in prefrontal dopamine signaling, displaying associations with aggressive behavior, and potentially influencing the effects of tDCS. In a double-blind, sham-controlled study, we investigated the influence of rs4680 on tDCS effects on aggression. While undergoing functional magnetic resonance imaging, 89 healthy male participants performed the Taylor aggression paradigm before and immediately after tDCS. Actively stimulated participants (n = 45) received anodal tDCS (1.5 mA) for 20 min targeting the right DLPFC. Carriers of the val-allele (val+; n = 46; active tDCS n = 23) were compared to met-allele homozygotes (val-; n = 43; active tDCS n = 22). Analysis revealed decreased aggressive behavior in the val- group following active tDCS (p < 0.001). The val+ group showed increased aggression during the second session (p < 0.001) with an even higher increase following active as compared to sham tDCS (p < 0.001). No effects of stimulation or rs4680 on brain activation were found. Our study provides evidence for opposite tDCS effects on aggressive behavior in val-carriers and val-noncarriers. By shedding light on genetic factors predicting tDCS responsivity, the study will help to pave the way toward individualized-and thus more effective-tDCS treatment options.
Keyphrases
- transcranial direct current stimulation
- working memory
- magnetic resonance imaging
- prefrontal cortex
- gene expression
- metabolic syndrome
- drug delivery
- clinical trial
- dna methylation
- tyrosine kinase
- transcription factor
- functional connectivity
- brain injury
- transcranial magnetic stimulation
- resting state
- copy number
- magnetic resonance
- white matter
- uric acid
- blood brain barrier
- high speed
- atomic force microscopy