Association of monoamine oxidase-A genetic variants and amygdala morphology in violent offenders with antisocial personality disorder and high psychopathic traits

Abstract

Violent offending is elevated among individuals with antisocial personality disorder (ASPD) and high psychopathic traits (PP). Morphological abnormalities of the amygdala and orbitofrontal cortex (OFC) are present in violent offenders, which may relate to the violence enacted by ASPD + PP. Among healthy males, monoamine oxidase-A (MAO-A) genetic variants linked to low in vitro transcription (MAOA-L) are associated with structural abnormalities of the amygdala and OFC. However, it is currently unknown whether amygdala and OFC morphology in ASPD relate to MAO-A genetic polymorphisms. We studied 18 ASPD males with a history of violent offending and 20 healthy male controls. Genomic DNA was extracted from peripheral leukocytes to determine MAO-A genetic polymorphisms. Subjects underwent a T1-weighted MRI anatomical brain scan that provided vertex-wise measures of amygdala shape and surface area and OFC cortical thickness. We found that ASPD + PP subjects with MAOA-L exhibited decreased surface area in the right basolateral amygdala nucleus and increased surface area in the right anterior cortical amygdaloid nucleus versus healthy MAOA-L carriers. This study is the first to describe genotype-related morphological differences of the amygdala in a population marked by high aggression. Deficits in emotional regulation that contribute to the violence of ASPD + PP may relate to morphological changes of the amygdala under genetic control.

Figure 1

Plot displays the main effect of monoamine oxidase-A (MAO-A) genotype on right amygdala volume, (F(1, 31) = 5.4, p = 0.027). Subjects with the low activity MAO-A (MAOA-L) genotype showed decreased right amygdala volume in comparison to subjects with the high activity MAO-A (MAOA-H) genotype (Tukey’s Honestly Significant Difference [HSD] post hoc result = 0.027).

Figure 2

Surface area differences in antisocial personality disorder with high psychopathic traits (ASPD + PP) and controls with MAOA-L genotype. Anterior, posterior, superior, and inferior views of the right amygdala and hippocampus (hippocampal surface provided for context only) are shown in the left and right panels, with significant surface area decreases in the right basolateral (BLA) nucleus (left panel) and significant increases in the right anterior cortical amygdaloid (ACo) nucleus on the right panel. Cortical representations in the center panel are provided for further context. Plots (A) and (B) display the surface area measurements at a peak vertex denoted by the yellow markers to demonstrate the nature of the effect. ASPD + PP offenders showed decreased surface area in the right BLA nucleus of the amygdala (posterior, inferior views, plot (A) as well as increased surface area in the right anterior ACo nucleus, (F(1, 13 = 6.82, 15% false discovery rate [FDR]) (anterior, inferior views, plot (B)).

Figure 3

Relationship between PCL-R scores and amygdala surface area among individuals with the MAOA-L genotype. Anterior, posterior, superior, and inferior views of the amygdala and hippocampus (provided for context) are shown in the left and right panels, with a significant negative correlation shown on the left. Cortical representations in the center panel are provided for further context. Plot (A) displays the surface area measurements at a peak vertex denoted by the yellow markers. PCL-R score showed a negative correlation with surface area in the right BLA nucleus of the amygdala, (F(1, 13) = 6.55, 15% FDR) (posterior, inferior views, Plot (A)).

Figure 4

Plot displays a main effect of group in cortical thickness in the left lateral orbitofrontal gyrus, (F(1, 31) = 5.13, p = 0.031). Cortical thickness for the region of interest (ROI) was computed on a per subject basis via application of the LPBA40 atlas to the cortical surface of each subject. Thickness measures across the ROI were then averaged to output a mean cortical thickness per ROI for each subject. In this comparison, ASPD + PP offenders showed decreased cortical thickness in the left lateral orbitofrontal gyrus (Tukey’s HSD post hoc test = 0.031).

Figure 5

Plots of standard deviation versus required sample size for power = 0.8 and α = 0.05. At each vertex, the sample size was calculated that would be required to obtain 80% power given α = 0.05 and a variety of standard deviations. These sample sizes are plotted in blue as simulated data. In red, the actual standard deviation was plotted at each vertex versus the sample size of each group (8), allowing a comparison of our sample size versus the sample size required to measure the effect. This procedure was performed for four separate vertices. Plots (A) and (B) show data from vertices where ASPD subjects showed significantly decreased surface area; plots (C) and (D) show vertices where significantly increased surface area was observed in ASPD. Plots (A) and (C) correspond to “strong vertices,” where the effect passed 15% FDR easily, while (B) and (D) correspond to “weak vertices,” where the effect barely passed 15% FDR. The goal of this experiment was to examine the full breadth of observed effects. In (A), (B), and (C), the actual sample size of 8 is at least sufficient for observing the effect given the standard deviation of surface area measurements at the corresponding vertex. In (D), the actual sample size of 8 would not have been sufficient to achieve 80% power given the observed standard deviation. Overall, plots (A–D) give confidence that the sample size of the study is sufficient to observe the reported effects.

Figure 6

Plots of standard deviation versus required sample size for power = 0.8 and α = 0.05. For the left lateral orbitofrontal gyrus, we calculated the sample size that would be required to obtain 80% power given α = 0.05 and a variety of standard deviations. These sample sizes are plotted in blue as simulated data. In red, the actual standard deviation of cortical thickness in each ROI versus the sample size of each group was plotted (8), allowing a comparison of our sample size versus the sample size required to measure the effect. Plot (A) depicts data from the left lateral orbitofrontal gyrus and plot (B) shows the corresponding plot of standard deviation versus required sample size. The actual sample size falls within a reasonable range of that required to observe the effect in a study with power = 0.8 and α = 0.05, giving confidence that the sample size of our study is sufficient to observe the reported effects.