Abstract
ObjectivePrevious research suggested that structural and functional abnormalities within the amygdala and orbitofrontal cortex contribute to the pathophysiology of Conduct Disorder (CD). Here, we investigated whether the integrity of the white-matter pathways connecting these regions is abnormal and thus may represent a putative neurobiological marker for CD.MethodsDiffusion Tensor Imaging (DTI) was used to investigate white-matter microstructural integrity in male adolescents with childhood-onset CD, compared with healthy controls matched in age, sex, intelligence, and socioeconomic status. Two approaches were employed to analyze DTI data: voxel-based morphometry of fractional anisotropy (FA), an index of white-matter integrity, and virtual dissection of white-matter pathways using tractography.ResultsAdolescents with CD displayed higher FA within the right external capsule relative to controls (T = 6.08, P<0.05, Family-Wise Error, whole-brain correction). Tractography analyses showed that FA values within the uncinate fascicle (connecting the amygdala and orbitofrontal cortex) were abnormally increased in individuals with CD relative to controls. This was in contrast with the inferior frontal-occipital fascicle, which showed no significant group differences in FA. The finding of increased FA in the uncinate fascicle remained significant when factoring out the contribution of attention-deficit/hyperactivity disorder symptoms. There were no group differences in the number of streamlines in either of these anatomical tracts.ConclusionsThese results provide evidence that CD is associated with white-matter microstructural abnormalities in the anatomical tract that connects the amygdala and orbitofrontal cortex, the uncinate fascicle. These results implicate abnormal maturation of white-matter pathways which are fundamental in the regulation of emotional behavior in CD.
Highlights
Conduct Disorder (CD) is a psychiatric condition characterized by a pervasive pattern of aggressive and antisocial behavior [1]
Consistent with this, individuals with CD show impaired fear conditioning and recognition of facial expressions, and reduced startle magnitudes [8,9]. Since these functions have been linked to the amygdala and prefrontal cortex [10,11,12,13,14], it is of note that functional magnetic resonance imaging studies have shown that, relative to healthy controls, male adolescents with CD display dysfunctional neural responses in these regions when viewing emotional facial expressions [6] or emotional images [15,16]
Since whole-brain Diffusion Tensor Imaging (DTI) analyses (see voxel-based diffusion tensor imaging (VB-DTI) section below) identified increased fractional anisotropy (FA) values between individuals with CD and controls within the external capsule, and given prior findings in adult psychopaths [23], we focused our tractography analyses on the two major anatomical tracts that pass through this white-matter area – the uncinate fascicle (UF) and the inferior frontal-occipital fascicle (IFOF)
Summary
Conduct Disorder (CD) is a psychiatric condition characterized by a pervasive pattern of aggressive and antisocial behavior [1]. Studies of children with high levels of callousunemotional (CU) traits, a constellation of personality traits proposed as a risk factor for CD and psychopathy, showed reduced amygdala activity to fearful faces and decreased functional connectivity between the amygdala and ventromedial prefrontal cortex [17,18]. In accord with these findings, structural MRI studies have revealed reduced gray matter volumes within the amygdala, anterior insula, and orbitofrontal cortex (OFC) in adolescents with CD relative to healthy controls [7,19,20]. We investigate whether adolescents with CD show abnormalities in the white-matter pathways that connect these two regions
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