Abstract
CONTEXT: Methamphetamine abuse is associated with high rates of aggression but few studies have addressed the contributing neurobiological factors. OBJECTIVE: To quantify aggression, investigate function in the amygdala and prefrontal cortex, and assess relationships between brain function and behavior in methamphetamine-dependent individuals. DESIGN: In a case-control study, aggression and brain activation were compared between methamphetamine-dependent and control participants. SETTING: Participants were recruited from the general community to an academic research center. PARTICIPANTS: Thirty-nine methamphetamine-dependent volunteers (16 women) who were abstinent for 7 to 10 days and 37 drug-free control volunteers (18 women) participated in the study; subsets completed self-report and behavioral measures. Functional magnetic resonance imaging (fMRI) was performed on 25 methamphetamine-dependent and 23 control participants. MAIN OUTCOME MEASURES: We measured self-reported and perpetrated aggression and self-reported alexithymia. Brain activation was assessed using fMRI during visual processing of facial affect (affect matching) and symbolic processing (affect labeling), the latter representing an incidental form of emotion regulation. RESULTS: Methamphetamine-dependent participants self-reported more aggression and alexithymia than control participants and escalated perpetrated aggression more following provocation. Alexithymia scores correlated with measures of aggression. During affect matching, fMRI showed no differences between groups in amygdala activation but found lower activation in methamphetamine-dependent than control participants in the bilateral ventral inferior frontal gyrus. During affect labeling, participants recruited the dorsal inferior frontal gyrus and exhibited decreased amygdala activity, consistent with successful emotion regulation; there was no group difference in this effect. The magnitude of decrease in amygdala activity during affect labeling correlated inversely with self-reported aggression in control participants and perpetrated aggression in all participants. Ventral inferior frontal gyrus activation correlated inversely with alexithymia in control participants. CONCLUSIONS: Contrary to the hypotheses, methamphetamine-dependent individuals may successfully regulate emotions through incidental means (affect labeling). Instead, low ventral inferior frontal gyrus activity may contribute to heightened aggression by limiting emotional insight.