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Neurobiological factors contributing to violence in humans remain poorly understood. One approach …


Biology Articles » Genetics » Behavioral Genetics » Neural mechanisms of genetic risk for impulsivity and violence in humans » Results

Results
- Neural mechanisms of genetic risk for impulsivity and violence in humans

All imaging results are derived from cross-sectional comparison of groups of genotyped healthy volunteers; therefore, reductions or increases are relative to the other genotype group(s) and do not imply that changes happen over time.

Genotype Effects on Brain Structure.

Analysis of brain structure revealed that allelic variation in MAOA was associated with pronounced regionally specific changes in gray matter volume (Fig. 1 A and Table 2, which is published as supporting information on the PNAS web site); compared with MAOA-H subjects, MAOA-L individuals showed a significant reduction in volume that encompassed virtually the entire cingulate gyrus and bilateral amygdalae, with a maximum in anterior cingulate cortex. In addition, we found significant reductions in insula and hypothalamus. Relative to the volume in MAOA-H subjects, reductions averaged around 8%. Examination of sex-by-genotype interaction maps revealed a sex-specific (males only) increase (of ≈14%) in bilateral lateral orbitofrontal cortex (OFC) [Brodmann’s area (BA) 47] volume in MAOA-L men, relative to MAOA-H men (Fig. 1 B), whereas no MAOA genotype-dependent structural changes were present in this region in women. The OFC was the only brain region where an interaction effect was found.

Genotype Effects on Brain Function.
 
Emotional arousal.Analysis of fMRI data during perceptual matching of angry and fearful faces showed significant activation of amygdala and task-related deactivation of limbic and paralimbic regions implicated in emotion processing, a pattern seen previously by our group (17) and others (21) (Fig. 2 and Table 2). Activity was strongly modulated by genotype: MAOA-L individuals showed significantly increased activity in left amygdala and decreased response of subgenual (BA 25) and supragenual (BA 32) ventral cingulate cortex, left lateral OFC, and left insular cortex, relative to MAOA-H subjects (P < 0.05, corrected for multiple comparisons) (Fig. 2 AD). These effects were present in both sexes (no significant sex-by-genotype interaction). Because both increased and decreased reactivity was seen in these various limbic regions that showed reduced structural volume in MAOA-L individuals, it is unlikely that the fMRI effects are related to smaller volume in these small structures.
 
Because OFC structure and function were affected by genotype and this prefrontal region has been implicated in amygdala regulation, we examined the effects of genotype and sex on amygdala–orbitofrontal connectivity (Fig. 5, which is published as supporting information on the PNAS web site). OFC was significantly less reactive in carriers of MAOA-L in both sexes, and overall connectivity with amygdala was significantly reduced in men when compared with women.
 
Emotional memory. We examined brain activation during emotional memory, i.e., the encoding and retrieval of aversively, compared with neutrally, valenced information. We found a pronounced effect of genotype and sex in left amygdala and hippocampal formation; men, but not women, carrying the low-expression MAOA genotype showed increased reactivity during retrieval of negatively valenced emotional material (Fig. 3 and Table 1). This effect was present for aversive, but not neutral, material and only during retrieval, as confirmed by a significant genotype-by-sex-by-task interaction in a post hoc ANOVA (F(3,258) = 3.0, P = 0.03). 
 
Inhibitory control.We probed the neural correlates of cognitive inhibitory control using a no-go “flanker task.” In men only, MAOA genotype had a pronounced effect on activation during response inhibition in dorsal anterior cingulate: MAOA-L hemizygotes showed deficient activation (Fig. 4 and Table 2). This finding is compatible with a previous observation in a small group of male subjects (16). Women had no significant effect of genotype, resulting in a significant sex-by-genotype interaction at this locus. Again, this functional change was located within the cingulate region of maximal structural change related to genotype. 
 
 

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