Neural mechanisms of anger regulation as a function of genetic risk for violence

Abstract

Genetic risk may predispose individuals to compromised anger regulation, potentially through modulation of brain responses to emotionally evocative stimuli. Emphatically expressed, the emotional word No can prohibit behavior through conditioning. In a recent functional magnetic resonance imaging study, the authors showed that healthy males attribute negative valence to No while showing a lateral orbitofrontal response that correlated with their self-reported anger control. Here, the authors examined the influence of the monoamine oxidase A (MAOA) gene (low vs. high transcription variants) on brain response to No and in relationship to trait anger reactivity and control. The orbitofrontal response did not differ as a function of the genotype. Instead, carriers of the low-MAOA genotype had reduced left middle frontal gyrus activation to No compared with the high variant. Furthermore, only for carriers of the up low-MAOA genotype, left amygdala and posterior thalamic activation to No increased with anger reactivity. Thus, vulnerability to aggression in carriers of the low-MAOA genotype is supported by decreased middle frontal response to No and the unique amygdala/thalamus association pattern in this group with anger reactivity but not anger control.

Figure 1

Gene-brain response to No. Left panel: Image of response to No as a function of the monoamine oxidase A (MAOA) genotype with corresponding standard error of the mean (SEM) bars on the right showing that low-MAOA participants had reduced percent blood-oxygen level dependent (BOLD) signal change (y axis) in left lateral middle frontal gyrus (BA 9), compared with high-MAOA participants (independent samples t = -4.1, p = .0001). This figure was derived from the No-Up contrast and validated through comparison of brain responses, derived from regions of interest, to No fixation and Up fixation see Figure S5 in the Supplementary Online Results).

Figure 2

Gene-brain-behavior model in anger reactivity. Left panels: Images of the clusters in positive correlation with self-reported anger reactivity and blood-oxygen-level-dependent (BOLD) response to No in the left amygdala and thalamus. Right panels: Scatterplots of percent BOLD signal change to No and scores on trait anger reactivity in the left amygdala (in upper right panel: low MAOA, R² = 0.61, p = .002; vs. high, R² = 0.16, p = .157) and left thalamus (pulvinar: low, R² = 0.48, p = .009; versus high, R² = 0.43, p = .011). This figure was derived from the No-Up contrast and validated through comparison of brain responses, derived from regions of interest, to No fixation and Up fixation (see Table S4 in the Supplementary Online Results). Squares and solid regression line indicate low (L) MAOA; circles and dotted line indicate high (H) MAOA.

Figure 3

Gene-brain-behavior model in anger control. Left panel: Image of the voxel clusters in positive correlation with self-reported anger control and blood-oxygen-level-dependent (BOLD) response to No in left insula and right amygdala hippocampus formation (AHF). Right panels: Scatterplots of percent BOLD signal change from the left insula (top right panel: low MAOA, R² = 0.08, p = .344; vs. high MAOA, R² = 0.48, p = .007) and right AHF (bottom panel: low MAOA, R² = 0.006, p = .897; vs. high MAOA, R² = 0.45, p = .009). This figure was derived from the No-Up contrast and validated through comparison of the brain responses, derived from regions of interest, to No fixation and Up fixation (see Table S5 in the Supplementary Online Results). Squares and solid regression line indicate low (L) MAOA; circles and dotted line indicate high (H) MAOA.

Figure 4

Gene-brain-behavior model in anger control. Top left panel: Image of the voxel clusters in negative correlation with self-reported anger control and blood-oxygen-level-dependent (BOLD) response to No in bilateral thalamus and left amygdala-hippocampal formation (AHF). The corresponding scatterplots represent of percent BOLD signal change in left AHF (low MAOA, R² = 0.30, p = .053; vs. high MAOA, R² = 0.48, p = .009), left anterior thalamus (low MAOA, R² = 0.09, p = .326; vs. high MAOA, R² = 0.58, p = .001), and right anterior thalamus (low MAOA, R² = 0.00, p = .782; vs. high MAOA, R² = 0.46, p = .008). This figure was derived from the No-Up contrast and validated through comparison of brain responses, derived from regions of interest, to No fixation and Up fixation (see Table S5 in the Supplementary Online Results). Squares and solid regression line indicate low (L) MAOA; circles and dotted line indicate high (H) MAOA.