A Functional Polymorphism of the MAOA Gene Is Associated with Neural Responses to Induced Anger Control

Abstract

Abstract■ Aggressiveness is highly heritable. Recent experimental work has linked individual differences in a functional polymorphism of the monoamine oxidase-A gene (MAOA) to anger-driven aggression. Other work has implicated the dorsal ACC (dACC) in cognitive-emotional control and the amygdala in emotional arousal. The present imaging genetics study investigated dACC and amygdala reactivity to induced anger control as a function of MAOA genotype. A research assistant asked 38 healthy male undergraduates to control their anger in response to an insult by a rude experimenter. Men with the low-expression allele showed increased dACC and amygdala activation after the insult, but men with the high-expression allele did not. Both dACC and amygdala activation independently mediated the relationship between MAOA genotype and self-reported anger control. Moreover, following the insult, men with the high-functioning allele showed functional decoupling between the amygdala and dACC, but men with the low-functioning allele did not. These results suggest that heightened dACC and amygdala activation and their connectivity are neuroaffective mechanisms underlying anger control in participants with the low-functioning allele of the MAOA gene. ■

Prefrontal recruitment during social rejection predicts greater subsequent self-regulatory imbalance and impairment: neural and longitudinal evidence

“…To do so, we extracted the time-series of the cue reactivity task for each participant from the bilateral NAcc and rVLPFC, using the ROI masks described previously. After segregating the time-series by condition (i.e., alcohol, marijuana, polydrug, appetitive, neutral), we correlated the rVLPFC and NAcc time-series yielding a Pearson’s r coefficient for each participant and for each condition (as in Denson, Dobson-Stone, Ronay, von Hippel, & Schira, in press). We then used multiple linear regression to correlate these r values with rVLPFC signal change units from the rejection > acceptance contrast, separately for each cue reactivity condition.…”

Monoamine oxidase A (MAOA) genotype predicts greater aggression through impulsive reactivity to negative affect

“…This association between low functioning MAOA genotype and hyper reactivity of the amygdala to negatively valenced affective stimuli was recently replicated, using an ecologically valid provocation paradigm, and shown to predict greater subsequent effort required to control anger (Denson, Dobson-Stone, Ronay, von Hippel, & Schira, 2014). This effect of MAOA genotype on anger control also held for the dorsal anterior cingulate cortex (dACC), a neural region implicated in responding to events characterized by negative affect (Denson et al, 2014). Further, the association between low functioning MAOA genotype and aggression was mediated by greater reactivity of the dACC during an instance of social rejection (Eisenberger, Way, Taylor, Welch, & Lieberman, 2007).…”

The role of monoamine oxidase A in aggression: Current translational developments and future challenges

“…Specifically, these subjects exhibit elevated and reduced volumes of the orbitofrontal cortex and amygdala, respectively; these morphological changes are accompanied by diminished prefrontal activity during tasks of inhibitory control as well as heightened limbic responsiveness to emotional arousal (Meyer-Lindenberg et al, 2006; Buckholtz et al, 2008; Nymberg et al, 2013). Furthermore, these individuals showed a significant enhancement of neural activity in the PFC, in correspondence of their high responsiveness to social rejection, insults and facial affect (Eisenberger et al, 2007; Denson et al, 2014). These data support the possibility that MAOA in the PFC modulates both the ability to properly assess the emotional salience of contextual cues (towards a less severe hostile attribution bias), and the selection of appropriate adaptive responses; early disruptions of this system may enhance the sensitivity to adverse-life experience and result in a negative socio-cognitive bias (Buckholtz and Meyer-Lindenberg, 2008; Dorfman et al, 2014).…”