Aggression toward others is a socially destructive behavior repeatedly perpetrated by individuals of distinct genetic cognitive and affective characteristics. Aggressive behavior is also weaved into the symptom dimensions of multiple psychiatric disorders and is associated with poor social adjustment and prognosis. Therefore, understanding the basic genetic, neurochemical and neuroanatomical processes associated with aggression is an urgent public health concern. Functional MRI (fMRI) with select behavioral paradigms have revealed a neurofunctional pattern consistent with reduced prefrontal cortical control and increased subcortical response to emotionally challenging tasks in vulnerable individuals. Underlying this maladaptive pattern are genes and their products responsible for the regulation of monoamines. Specifically, monoamine oxidase A (MAO A), an enzyme regulating the neurotransmitters serotonin and norepinephrine, has been reliably implicated in aggression. The low activity alleles of the MAOA genotype and low brain MAO A activity have been independently identified as intermediate phenotypes of risk for aggressive behavior, poor cognitive control and dysregulated emotion. Other monoamine regulators, such as catechol-O-methyltransferase (COMT) and the serotonin transporter (5-HTT), together with MAO A, are also implicated as neurochemical markers in the study and treatment of highly aggressive behavior. However, the extent to which these genetic and brain function variables interact to contribute to human aggression is not known. Therefore we propose to preselect healthy men from the general population into aggressive versus non-aggressive groups and to compare in these groups (1) aggressive responses, anger reactivity and executive control (2) behavioral and neural circuitry response to emotional and cognitive conflict challenges using Stroop in fMRI (3) in-vivo brain MAO A catalytic activity using positron emission tomography (PET) and (4) susceptibility variants of the MAOA, 5-HTT and COMT genotypes. We hypothesize that aggressive participants will have sensitized functional neural pathways of emotional reactivity and reductions in the pathways underlying executive control. These effects will be associated with reduced brain MAO A and its interaction with the susceptibility genotype carriers. We therefore propose to conduct basic human studies using PET and fMRI, employing a multilevel investigation of intermediate phenotypes in a complex and understudied behavior. In particular, the integrated genes-brain-behavior approach in the same human subjects answers a critical need for bridging between disparate findings in the study of aggression, facilitating the uncovering of the complex interrelated mechanisms that underlie human aggressive behavior. Findings may provide a platform from which future studies can be developed to help understand, and control unremitting violent behavior in Axis I and II disorders.
Aggression toward others is a socially reactive behavior with genetic cognitive and affective characteristics. Aggressive behavior is also weaved into the symptom dimensions of multiple psychiatric disorders and contributes to assault and other damaging consequences. Therefore, understanding the basic genetic, neurochemical and neuroanatomical processes associated with aggression is a public health concern.
|Zilverstand, Anna; Huang, Anna S; Alia-Klein, Nelly et al. (2018) Neuroimaging Impaired Response Inhibition and Salience Attribution in Human Drug Addiction: A Systematic Review. Neuron 98:886-903|
|Alia-Klein, Nelly; Preston-Campbell, Rebecca N; Moeller, Scott J et al. (2018) Trait anger modulates neural activity in the fronto-parietal attention network. PLoS One 13:e0194444|
|Bachi, Keren; Sierra, Salvador; Volkow, Nora D et al. (2017) Is biological aging accelerated in drug addiction? Curr Opin Behav Sci 13:34-39|
|Parvaz, Muhammad A; Moeller, Scott J; d'Oleire Uquillas, Federico et al. (2017) Prefrontal gray matter volume recovery in treatment-seeking cocaine-addicted individuals: a longitudinal study. Addict Biol 22:1391-1401|
|Parvaz, Muhammad A; Moeller, Scott J; Malaker, Pias et al. (2017) Abstinence reverses EEG-indexed attention bias between drug-related and pleasant stimuli in cocaine-addicted individuals. J Psychiatry Neurosci 42:78-86|
|Gan, Gabriela; Preston-Campbell, Rebecca N; Moeller, Scott J et al. (2016) Reward vs. Retaliation-the Role of the Mesocorticolimbic Salience Network in Human Reactive Aggression. Front Behav Neurosci 10:179|
|Moeller, Scott J; Fleming, Stephen M; Gan, Gabriela et al. (2016) Metacognitive impairment in active cocaine use disorder is associated with individual differences in brain structure. Eur Neuropsychopharmacol 26:653-62|
|Parvaz, Muhammad A; Konova, Anna B; Proudfit, Greg H et al. (2015) Impaired neural response to negative prediction errors in cocaine addiction. J Neurosci 35:1872-9|
|Alia-Klein, Nelly; Wang, Gene-Jack; Preston-Campbell, Rebecca N et al. (2014) Reactions to media violence: it's in the brain of the beholder. PLoS One 9:e107260|
|Moeller, Scott J; Froböse, Monja I; Konova, Anna B et al. (2014) Common and distinct neural correlates of inhibitory dysregulation: stroop fMRI study of cocaine addiction and intermittent explosive disorder. J Psychiatr Res 58:55-62|
Showing the most recent 10 out of 11 publications