CONTEXT: Studies aimed at identifying structural brain alterations associated with persistent violent behavior or psychopathy have not adequately accounted for a lifetime history of substance misuse. Thus, alterations in gray matter (GM) volume that have been reported to be correlates of violent behavior and/or psychopathy may instead be related to lifelong substance use disorders (SUDs). OBJECTIVE: To identify alterations in GM volume associated with violent behavior and those associated with lifelong SUDs. DESIGN: Cross-sectional study. SETTING: Participants were recruited from penitentiaries, forensic hospitals, psychiatric outpatient services, and communities in Germany. Structural magnetic resonance imaging was performed at a university hospital. PARTICIPANTS: Four groups of men were compared: 12 men with SUDs who exhibited violent behavior (hereafter referred to as violent offenders), 12 violent offenders without SUDs, 13 men with SUDs who did not exhibit violent behavior (hereafter referred to as nonoffenders), and 14 nonoffenders without SUDs. MAIN OUTCOME MEASURES: Voxel-based morphometry was used to analyze high-resolution magnetic resonance imaging scans. Assessments of mental disorders, psychopathy (using the Psychopathy Checklist-Screening Version), aggressive behavior, and impulsivity were conducted by trained clinicians. RESULTS: Compared with nonoffenders, violent offenders presented with a larger GM volume in the amygdala bilaterally, the left nucleus accumbens, and the right caudate head and with less GM volume in the left insula. Men with SUDs exhibited a smaller GM volume in the orbitofrontal cortex, ventromedial prefrontal cortex, and premotor cortex than did men without SUDs. Regression analyses indicated that the alterations in GM volume that distinguished the violent offenders from nonoffenders were associated with psychopathy scores and scores for lifelong aggressive behavior. The GM volumes of the orbitofrontal cortex and prefrontal cortex that distinguished the men with SUDs from the men without SUDs were correlated with scores for response inhibition. CONCLUSIONS: These findings suggest that a greater GM volume in the mesolimbic reward system may be associated with violent behavior and that reduced GM volumes in the prefrontal cortex, orbitofrontal cortex, and premotor area characterize men with SUDs.
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