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Original Investigation |

Mediation of the Relationship Between Callous-Unemotional Traits and Proactive Aggression by Amygdala Response to Fear Among Children With Conduct Problems

Leah M. Lozier, BS1; Elise M. Cardinale, BA2; John W. VanMeter, PhD1; Abigail A. Marsh, PhD2
[+] Author Affiliations
1Department of Neurology, Georgetown University, Washington, DC
2Department of Psychology, Georgetown University, Washington, DC
JAMA Psychiatry. 2014;71(6):627-636. doi:10.1001/jamapsychiatry.2013.4540.
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Importance  Among youths with conduct problems, callous-unemotional (CU) traits are known to be an important determinant of symptom severity, prognosis, and treatment responsiveness. But positive correlations between conduct problems and CU traits result in suppressor effects that may mask important neurobiological distinctions among subgroups of children with conduct problems.

Objective  To assess the unique neurobiological covariates of CU traits and externalizing behaviors in youths with conduct problems and determine whether neural dysfunction linked to CU traits mediates the link between callousness and proactive aggression.

Design, Setting, and Participants  This cross-sectional case-control study involved behavioral testing and neuroimaging that were conducted at a university research institution. Neuroimaging was conducted using a 3-T Siemens magnetic resonance imaging scanner. It included 46 community-recruited male and female juveniles aged 10 to 17 years, including 16 healthy control participants and 30 youths with conduct problems with both low and high levels of CU traits.

Main Outcomes and Measures  Blood oxygenation level–dependent signal as measured via functional magnetic resonance imaging during an implicit face-emotion processing task and analyzed using whole-brain and region of interest–based analysis of variance and multiple-regression analyses.

Results  Analysis of variance revealed no group differences in the amygdala. By contrast, consistent with the existence of suppressor effects, multiple-regression analysis found amygdala responses to fearful expressions to be negatively associated with CU traits (x = 26, y = 0, z = −12; k = 1) and positively associated with externalizing behavior (x = 24, y = 0, z = −14; k = 8) when both variables were modeled simultaneously. Reduced amygdala responses mediated the relationship between CU traits and proactive aggression.

Conclusions and Relevance  The results linked proactive aggression in youths with CU traits to hypoactive amygdala responses to emotional distress cues, consistent with theories that externalizing behaviors, particularly proactive aggression, in youths with these traits stem from deficient empathic responses to distress. Amygdala hypoactivity may represent an intermediate phenotype, offering new insights into effective treatment strategies for conduct problems.

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Figure 1.
Results of a Regression Analysis in the Right Amygdala Region of Interest (ROI)

Right amygdala responses to full-intensity fearful expressions were contrasted over implicit baseline. The leverage plots show the unique association between mean beta values extracted from the entire amygdala ROI and externalizing behaviors (A) and callous-unemotional traits (B) after accounting for the variance of the other. C, Results of a multiple-regression analysis including 30 participants with conduct problems found activation restricted to the 6-mm spherical ROI was positively associated with externalizing behaviors (red voxels) and negatively associated with callous-unemotional traits (blue voxels), with overlapping areas in yellow (P < .05, familywise error).

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Figure 2.
Amygdala Response Mediates the Relationship Between Callous-Unemotional Traits and Proactive Aggression

Unstandardized regression coefficients and bias-corrected 95% CI for the indirect effect from a bootstrap-mediation analysis that found that right amygdala responses to fearful expressions mediated the relationship between callous-unemotional traits and proactive aggression among 30 youths with conduct problems.

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