Neural Mechanisms of Genetic Risk for Impulsivity and Violence in Humans

Abstract

Neurobiological factors contributing to violence in humans remain poorly understood. One approach to this question is examining allelic variation in the X-linked monoamine oxidase A (MAOA) gene, previously associated with impulsive aggression in animals and humans. Here, we have studied the impact of a common functional polymorphism in MAOA on brain structure and function assessed with MRI in a large sample of healthy human volunteers. We show that the low expression variant, associated with increased risk of violent behavior, predicted pronounced limbic volume reductions and hyperresponsive amygdala during emotional arousal, with diminished reactivity of regulatory prefrontal regions, compared with the high expression allele. In men, the low expression allele is also associated with changes in orbitofrontal volume, amygdala and hippocampus hyperreactivity during aversive recall, and impaired cingulate activation during cognitive inhibition. Our data identify differences in limbic circuitry for emotion regulation and cognitive control that may be involved in the association of MAOA with impulsive aggression, suggest neural systems-level effects of X-inactivation in human brain, and point toward potential targets for a biological approach toward violence.aggression ͉ antisocial ͉ functional MRI ͉ monoamine oxidase A ͉ serotonin

Structural brain abnormalities in psychopaths—a review

“…Moreover, there was a gender-specific (only males) increase in the lateral orbitofrontal cortex (BA 47) volume bilaterally in the low expression variant of the MAO-A as compared with the high expression variant (Figure 3(B)). Meyer-Lindenberg et al (2006) reported the most robust structural changes in the cingulate cortex. The cingulate cortex is involved in the regulation of emotions and social behavior, a region with a very high serotonin transporter density (Mantere et al, 2002).…”

“…It has been suggested that the two dimensions of aggression are genetically dissociable (Meyer-Lindenberg et al, 2006). A recent neuroimaging study by Meyer-Lindenberg and colleagues (2006) reports a link between the X-linked monoaminoxidase A (MAO-A) gene and structural brain abnormalities.…”

“…A first clear link between genetic predisposition and impulsive aggression has been provided for the monoaminoxidase A (MAO-A) gene (Meyer-Lindenberg et al, 2006). This link does not hold true, unfortunately, for instrumental aggression, primarily seen in psychopaths.…”

A Possible Solution to the Etiological Paradox that Ties Anti-Social Personality Disorder to Major Depression

“…It is believed that it leads to higher intolerance to adverse interactions, in the context of past victimization [21]. The nature-nurture relation that is established seems to take place through impairments in the neurodevelopment of the limbic system (which is rendered increased in size) and amygdala hyper-responsivity [22], which affect inhibitory capacities and general affective stability.…”

Long-term citalopram maintenance in mice: selective reduction of alcohol-heightened aggression

“…Preclinical research shows a similar population trend, with a small proportion of rodents (between 15 and 30%) consistently exhibiting escalated attack behavior after alcohol intake Miczek et al 1992Miczek et al , 1998van Erp and Miczek 1997). It has been hypothesized that a preexisting genetic vulnerability predisposes an individual to drink and to engage in violence as a function of certain environmental influences (Higley and Bennett 1999;Higley et al 1996;Meyer-Lindenberg et al 2006).…”