Cortical and Subcortical Abnormalities in Youths With Conduct Disorder and Elevated Callous-Unemotional Traits

doi:10.1016/j.jaac.2013.12.008

Journal of the American Academy of Child & Adolescent Psychiatry

Volume 53, Issue 4, April 2014, Pages 456-465.e1

https://doi.org/10.1016/j.jaac.2013.12.008 Get rights and content

Objective

Although there is growing evidence of brain abnormalities among individuals with conduct disorder (CD), the structural neuroimaging literature is mixed and frequently aggregates cortical volume rather than differentiating cortical thickness from surface area. The current study assesses CD-related differences in cortical thickness, surface area, and gyrification as well as volume differences in subcortical structures critical to neurodevelopmental models of CD (amygdala; striatum) in a carefully characterized sample. We also examined whether group structural differences were related to severity of callous-unemotional (CU) traits in the CD sample.

Method

Participants were 49 community adolescents aged 10 to 18 years, 22 with CD and 27 healthy comparison youth. Structural MRI was collected and the FreeSurfer image analysis suite was used to provide measures of cortical thickness, surface area, and local gyrification as well as subcortical (amygdala and striatum) volumes.

Results

Youths with CD showed reduced cortical thickness in the superior temporal cortex. There were also indications of reduced gyrification in the ventromedial frontal cortex, particularly for youths with CD without comorbid attention-deficit/hyperactivity disorder. There were no group differences in cortical surface area. However, youths with CD also showed reduced amygdala and striatum (putamen and pallidum) volumes. Right temporal cortical thickness was significantly inversely related to severity of CU traits.

Conclusions

Youths with CD show reduced cortical thickness within superior temporal regions, some indication of reduced gyrification within ventromedial frontal cortex and reduced amygdala and striatum (putamen and pallidum) volumes. These results are discussed with reference to neurobiological models of CD.

Section snippets

Participants

A total of 49 youths participated: 22 youths with CD and 27 healthy comparison youths (Table 1). Youths were recruited from the community through newspaper ads, fliers, and referrals from area mental health practitioners. Statements of informed assent and consent were obtained from participating children and parents. This study was approved by the National Institute of Mental Health Institutional Review Board.

All youths and parents completed Kiddie Schedule for Affective Disorders and

Results

Initially, the potential influence of sex differences was tested; however, no significant interactions with sex were found; hence, the main results below include comparisons of groups composed of both males and females. Furthermore, re-running the analyses including males only (given the small number of females) provides the same pattern of results as reported below.

Discussion

The current study examined cortical thickness, surface area, local gyrification, and volumes of several critical subcortical structures in a sample of youths with CD. This study found reduced cortical thickness within extensive regions of infero-parietal cortex (extending into the temporal–parietal junction, superior temporal cortex, and precuneus/posterior cingulate cortex in the right hemisphere), in the youths with CD relative to the typically developing group, after applying a cluster

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Testing the Ecophenotype Model: Cortical Structure Alterations in Conduct Disorder With Versus Without Childhood Maltreatment
2023, Biological Psychiatry: Cognitive Neuroscience and Neuroimaging
Childhood maltreatment is common in youths with conduct disorder (CD), and both CD and maltreatment have been linked to neuroanatomical alterations. Nonetheless, our understanding of the contribution of maltreatment to the neuroanatomical alterations observed in CD remains limited. We tested the applicability of the ecophenotype model to CD, which holds that maltreatment-related psychopathology is (neurobiologically) distinct from psychopathology without maltreatment.
Surface-based morphometry was used to investigate cortical volume, thickness, surface area, and gyrification in a mixed-sex sample of participants with CD (n = 114) and healthy control subjects (HCs) (n = 146), ages 9 to 18 years. Using vertexwise general linear models adjusted for sex, age, total intracranial volume, and site, the control group was compared with the overall CD group and the CD subgroups with (n = 49) versus without (n = 65) maltreatment (assessed by the Children’s Bad Experiences interview). These subgroups were also directly compared.
The overall CD group showed lower cortical thickness in the right inferior frontal gyrus. CD youths with a history of maltreatment showed more widespread structural alterations relative to HCs, comprising lower thickness, volume, and gyrification in inferior and middle frontal regions. Conversely, CD youths with no history of maltreatment only showed greater left superior temporal gyrus folding relative to HCs. When contrasting the CD subgroups, those with maltreatment displayed lower right superior temporal gyrus volume, right precentral gyrus surface area, and gyrification in frontal, temporal, and parietal regions.
Consistent with the ecophenotype model, findings indicated that CD youths with versus without maltreatment differ neurobiologically. This highlights the importance of considering maltreatment history in neuroimaging studies of CD and other disorders.
How reliable are amygdala findings in psychopathy? A systematic review of MRI studies
2022, Neuroscience and Biobehavioral Reviews
The amygdala is a key component in predominant neural circuitry models of psychopathy. Yet, after two decades of neuroimaging research on psychopathy, the reproducibility of amygdala findings is questionable. We systematically reviewed MRI studies (81 of adults, 53 of juveniles) to determine the consistency of amygdala findings across studies, as well as within specific types of experimental tasks, community versus forensic populations, and the lowest- versus highest-powered studies. Three primary findings emerged. First, the majority of studies found null relationships between psychopathy and amygdala structure and function, even in the context of theoretically relevant tasks. Second, findings of reduced amygdala activity were more common in studies with low compared to high statistical power. Third, the majority of peak coordinates of reduced amygdala activity did not fall primarily within the anatomical bounds of the amygdala. Collectively, these findings demonstrate significant gaps in the empirical support for the theorized role of the amygdala in psychopathy and indicate the need for novel research perspectives and approaches in this field.
The implications of frontotemporal dementia for brain dysfunction in psychopathy
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Understanding how psychopathy compares with brain disease can help clarify its underlying mechanisms. This literature review is a broad overview of the neurobiology of psychopathic traits in comparison to behavioral variant frontotemporal dementia (bvFTD), a disorder uniquely associated with criminal behavior. In addition to violation of social norms, both psychopathy and bvFTD result in impaired socioemotional perception and empathy, impulsivity, and altered moral judgment. Despite wide areas of decreased function in psychopathy, structural changes are primarily evident in amygdala and, to a lesser extent, anterior insula, whereas in bvFTD neuropathology involves a wider paralimbic region. In psychopathy, relatively intact medial prefrontal and anterior cingulate cortices facilitate theory of mind and psychopathic traits such as deceitfulness and manipulation, bold fearlessness, and risk-taking behavior. In conclusion, many frontotemporal areas are hypoactive in psychopathy and bvFTD, but differences in dysfunctional connectivity in psychopathy vs. direct involvement in bvFTD potentially explain similarities and differences between these two conditions.
Structural Brain Correlates of the Externalizing Spectrum in Young Adults
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The externalizing spectrum, including traits and behaviors such as aggression, reduced inhibitiory control and substance abuse, is associated with altered prefrontal brain morphology. However, the degree to which different manifestations of the externalizing spectrum are associated with distinct or overlapping variations in individual brain morphology is unclear. Here, we therefore used structural magnetic resonance imaging, self-report assessment, and a response inhibition task in a sample of 59 young adults to examine how cortical thickness in the anterior cingulate cortex (ACC), orbitofrontal cortex (OFC), and dorsolateral prefrontal cortex (DLPFC) relate to four different manifestations of the externalizing spectrum: disinhibition, callous aggression, substance abuse, and behavioral inhibitory control. Using Bayesian linear regression models controlling for age, gender, and years of education, we found that the different manifestations of the externalizing spectrum were associated with both distinct and overlapping morphology variations. Specifically, both callous aggression and inhibitory control was associated with increased cortical thickness of the OFC, a region involved in reward processing, decision-making, and regulation of anxiety and fear. Both disinhibition and substance abuse were associated with DLPFC thickness, although with opposite association patterns, possibly reflecting processes related to inhibitory control, working memory and attention. Moreover, disinhibition, but not callous aggression or substance abuse, was associated with behavioral inhibitory control. Our results provide further support for the link between externalizing behaviors and prefrontal brain morphology, while identifying distinct prefrontal areas associated with different clinically relevant manifestations. These findings may help guide further research aimed at developing novel treatment and intervention strategies for externalizing behaviors and disorders.
Sex differences in medial prefrontal and parietal cortex structure in children with disruptive behavior
2021, Developmental Cognitive Neuroscience
Citation Excerpt :
Lastly, disruptive behavior tends to appear during preschool years and Oppositional Defiant Disorder has the onset between 6 and 8 years of age (Ezpeleta et al., 2019). However, to our knowledge, all studies of brain morphology of DBD were conducted with adolescents (with the exception of the study by Wallace et al. (2014) that included an age range from 10 to 18 years). Our study addresses this limitation by investigating sex differences in cortical thickness and gray matter volume in 8- to 16-year-old children with disruptive behavior disorders.
Sex differences in brain structure in children with disruptive behavior disorders (DBD) remain poorly understood. This study examined sex differences in gray matter volume in children with DBD in a priori regions-of-interest implicated in the pathophysiology of disruptive behavior. We then conducted a whole-brain analysis of cortical thickness to examine sex differences in regions not included in our hypothesis. Exploratory analyses investigated unique associations between structure, and dimensional measures of severity of disruptive behavior and callous-unemotional traits. This cross-sectional study included 88 children with DBD (30 females) aged 8–16 years and 50 healthy controls (20 females). Structural MRI data were analyzed using surface-based morphometry to test for interactions between sex and group. Multiple-regression analyses tested for sex-specific associations between structure, callous-unemotional traits, and disruptive behavior severity. Boys with DBD showed reduced gray matter volume in the left ventromedial prefrontal cortex (vmPFC) and reduced cortical thickness in the supramarginal gyrus, but not girls compared to respective controls. Dimensional analyses revealed associations between sex, callous-unemotional traits, and disruptive behavior for amygdala and vmPFC volume, and ventrolateral prefrontal cortex cortical thickness. Sex-specific differences in prefrontal structures involved in emotion regulation may support identification of neural biomarkers of disruptive behavior to inform target-based treatments.
Resting-state network topology characterizing callous-unemotional traits in adolescence
2021, NeuroImage: Clinical
Callous-unemotional (CU) traits, a youth antisocial phenotype, are hypothesized to associate with aberrant connectivity (dis-integration) across the salience (SAL), default mode (DMN), and frontoparietal (FPN) networks. However, CU traits have a heterogeneous presentation and previous research has not modeled individual heterogeneity in resting-state connectivity amongst adolescents with CU traits. The present study models individual-specific network maps and examines topological features of individual and subgroup maps in relation to CU traits.
Participants aged 13–17 (n = 84, male = 55%, female = 45%) completed resting-state functional connectivity and the inventory of callous-unemotional traits as part of the Nathan Klein Rockland study. A sparse network approach (GIMME) was used to derive individual-level and subgroup maps of all participants. We then examined heterogeneous network features, including positive and negative connection density, associated with CU traits.
Higher rates of CU traits increased probability of inclusion in one subgroup, which had the highest mean level of CU traits. Analysis of network features reveals less density (positive and negative) within the FPN and greater density between DMN-FPN associated with CU traits.
Findings indicate heterogeneous person-specific connections and some subgroup connections amongst adolescents associate with CU traits. Higher CU traits associate with lower density in the FPN, which has been associated with attention and inhibition, and higher density between the DMN-FPN, which have been linked with cognitive control, social working memory, and empathy. Our findings suggest less efficiency in FPN function which, when considered mechanistically, could result in difficulty suppressing DMN when task positive networks are engaged. This is an area for further exploration but could explain cognitive and socio-affective impairments in CU traits.

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: This work was supported by the Intramural Research Program at NIMH, NIH under grant number 1-ZIA-MH002860-08. Ethics approval for this study was granted by the NIH Combined Neuroscience Institutional Review Board under protocol number 05-M-0105.

: Disclosure: Drs. Wallace, White, Sinclair, Hwang, Martin, and Blair, and Ms. Robustelli report no biomedical financial interests or potential conflicts of interest.

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New researchCortical and Subcortical Abnormalities in Youths With Conduct Disorder and Elevated Callous-Unemotional Traits

Objective

Method

Results

Conclusions

Section snippets

Participants

Results

Discussion

Trends Cogn Sci

Trends Cogn Sci

Neuroimage

Drug Alcohol Depend

Biol Psychiatry

Neuroimage

Psychiatry Res

J Am Acad Child Adolesc Psychiatry

Int J Law Psychiatry

Neuroimage

Neuroimage

Neuroimage

Neuron

Neuroimage

Neuroimage

Psychiatry Res

Psychiatry Res

Biol Psychiatry

Biol Psychiatry

Neuroimage

Callous-unemotional traits in predicting the severity and stability of conduct problems and delinquency

J Abnorm Child Psychol

Classification of behavior disorders in adolescence: scaling methods, predictive validity, and gender differences

J Abnorm Psychol

Deviant Children Grow Up

Disrupted expected value and prediction error signaling in youths with disruptive behavior disorders during a passive avoidance task

Am J Psychiatry

A theory of Pavlovian conditioning: variations in the effectiveness of reinforcement and nonreinforcement

Contributions of the ventromedial prefrontal cortex to goal-directed action selection

Ann N Y Acad Sci

Reduced amygdala response in youths with disruptive behavior disorders and psychopathic traits: decreased emotional response versus increased top-down attention to nonemotional features

Am J Psychiatry

Reduced amygdala response to fearful expressions in children and adolescents with callous-unemotional traits and disruptive behavior disorders

Am J Psychiatry

Neural abnormalities in early-onset and adolescence-onset conduct disorder

Arch Gen Psychiatry

New research
Cortical and Subcortical Abnormalities in Youths With Conduct Disorder and Elevated Callous-Unemotional Traits