Cortical structure and subcortical volumes in conduct disorder: a coordinated analysis of 15 international cohorts from the ENIGMA-Antisocial Behavior Working Group.

BACKGROUND: Conduct disorder is associated with the highest burden of any mental disorder in childhood, yet its neurobiology remains unclear. Inconsistent findings limit our understanding of the role of brain structure alterations in conduct disorder. This study aims to identify the most robust and replicable brain structural correlates of conduct disorder. METHODS: The ENIGMA-Antisocial Behavior Working Group performed a coordinated analysis of structural MRI data from 15 international cohorts. Eligibility criteria were a mean sample age of 18 years or less, with data available on sex, age, and diagnosis of conduct disorder, and at least ten participants with conduct disorder and ten typically developing participants. 3D T1-weighted MRI brain scans of all participants were pre-processed using ENIGMA-standardised protocols. We assessed group differences in cortical thickness, surface area, and subcortical volumes using general linear models, adjusting for age, sex, and total intracranial volume. Group-by-sex and group-by-age interactions, and DSM-subtype comparisons (childhood-onset vs adolescent-onset, and low vs high levels of callous-unemotional traits) were investigated. People with lived experience of conduct disorder were not involved in this study. FINDINGS: We collated individual participant data from 1185 young people with conduct disorder (339 [28·6%] female and 846 [71·4%] male) and 1253 typically developing young people (446 [35·6%] female and 807 [64·4%] male), with a mean age of 13·5 years (SD 3·0; range 7-21). Information on race and ethnicity was not available. Relative to typically developing young people, the conduct disorder group had lower surface area in 26 cortical regions and lower total surface area (Cohen's d 0·09-0·26). Cortical thickness differed in the caudal anterior cingulate cortex (d 0·16) and the banks of the superior temporal sulcus (d -0·13). The conduct disorder group also had smaller amygdala (d 0·13), nucleus accumbens (d 0·11), thalamus (d 0·14), and hippocampus (d 0·12) volumes. Most differences remained significant after adjusting for ADHD comorbidity or intelligence quotient. No group-by-sex or group-by-age interactions were detected. Few differences were found between DSM-defined conduct disorder subtypes. However, individuals with high callous-unemotional traits showed more widespread differences compared with controls than those with low callous-unemotional traits. INTERPRETATION: Our findings provide robust evidence of subtle yet widespread brain structural alterations in conduct disorder across subtypes and sexes, mostly in surface area. These findings provide further evidence that brain alterations might contribute to conduct disorder. Greater consideration of this under-recognised disorder is needed in research and clinical practice. FUNDING: Academy of Medical Sciences and Economic and Social Research Council.

Unique versus shared neural correlates of externalizing psychopathology in late childhood.

Childhood externalizing psychopathology is heterogeneous. Symptom variability in conduct disorder (CD), oppositional defiant disorder (ODD), attention-deficit/hyperactivity disorder (ADHD), and callous-unemotional (CU) traits designate different subgroups of children with externalizing problems who have specific treatment needs. However, CD, ODD, ADHD, and CU traits are highly comorbid. Studies need to generate insights into shared versus unique risk mechanisms, including through the use of functional magnetic resonance imaging (fMRI). In this study, we tested whether symptoms of CD, ODD, ADHD, and CU traits were best represented within a bifactor framework, simultaneously modeling shared (i.e., general externalizing problems) and unique (i.e., symptom-specific) variance, or through a four-correlated factor or second-order factor model. Participants (N = 11,878, age, M = 9 years) were from the Adolescent Brain and Cognitive Development Study. We used questionnaire and functional magnetic resonance imaging data (emotional N-back task) from the baseline assessment. A bifactor model specifying a general externalizing and specific CD, ODD, ADHD, and CU traits factors demonstrated the best fit. The four-correlated and second-order factor models both fit the data well and were retained for analyses. Across models, reduced right amygdala activity to fearful faces was associated with more general externalizing problems and reduced dorsolateral prefrontal cortex activity to fearful faces was associated with higher CU traits. ADHD scores were related to greater right nucleus accumbens activation to fearful and happy faces. Results give insights into risk mechanisms underlying comorbidity and heterogeneity within externalizing psychopathology. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Does the Relationship between Age and Brain Structure Differ in Youth with Conduct Disorder?

Conduct disorder (CD) is characterised by persistent antisocial and aggressive behaviour and typically emerges in childhood or adolescence. Although several authors have proposed that CD is a neurodevelopmental disorder, very little evidence is available about brain development in this condition. Structural brain alterations have been observed in CD, and some indirect evidence for delayed brain maturation has been reported. However, no detailed analysis of age-related changes in brain structure in youth with CD has been conducted. Using cross-sectional MRI data, this study aimed to explore differences in brain maturation in youth with CD versus healthy controls to provide further understanding of the neurodevelopmental processes underlying CD. 291 CD cases (153 males) and 379 healthy controls (160 males) aged 9-18 years (Mage = 14.4) were selected from the European multisite FemNAT-CD study. Structural MRI scans were analysed using surface-based morphometry followed by application of the ENIGMA quality control protocols. An atlas-based approach was used to investigate group differences and test for group-by-age and group-by-age-by-sex interactions in cortical thickness, surface area and subcortical volumes. Relative to healthy controls, the CD group showed lower surface area across frontal, temporal and parietal regions as well as lower total surface area. No significant group-by-age or group-by-age-by-sex interactions were observed on any brain structure measure. These findings suggest that CD is associated with lower surface area across multiple cortical regions, but do not support the idea that CD is associated with delayed brain maturation, at least within the age bracket considered here.

Mapping potential pathways from polygenic liability through brain structure to psychological problems across the transition to adolescence.

BACKGROUND: We used a polygenic score for externalizing behavior (extPGS) and structural MRI to examine potential pathways from genetic liability to conduct problems via the brain across the adolescent transition. METHODS: Three annual assessments of child conduct problems, attention-deficit/hyperactivity problems, and internalizing problems were conducted across across 9-13 years of age among 4,475 children of European ancestry in the Adolescent Brain Cognitive DevelopmentSM Study (ABCD Study®). RESULTS: The extPGS predicted conduct problems in each wave (R2 = 2.0%-2.9%). Bifactor models revealed that the extPRS predicted variance specific to conduct problems (R2 = 1.7%-2.1%), but also variance that conduct problems shared with other measured problems (R2 = .8%-1.4%). Longitudinally, extPGS predicted levels of specific conduct problems (R2 = 2.0%), but not their slope of change across age. The extPGS was associated with total gray matter volume (TGMV; R2 = .4%) and lower TGMV predicted both specific conduct problems (R2 = 1.7%-2.1%) and the variance common to all problems in each wave (R2 = 1.6%-3.1%). A modest proportion of the polygenic liability specific to conduct problems in each wave was statistically mediated by TGMV. CONCLUSIONS: Across the adolescent transition, the extPGS predicted both variance specific to conduct problems and variance shared by all measured problems. The extPGS also was associated with TGMV, which robustly predicted conduct problems. Statistical mediation analyses suggested the hypothesis that polygenic variation influences individual differences in brain development that are related to the likelihood of conduct problems during the adolescent transition, justifying new research to test this causal hypothesis.

Functional Connectivity of the Nucleus Accumbens across Variants of Callous-Unemotional Traits: A Resting-State fMRI Study in Children and Adolescents.

A large body of literature suggests that the primary (high callousness-unemotional traits [CU] and low anxiety) and secondary (high CU traits and anxiety) variants of psychopathy significantly differ in terms of their clinical profiles. However, little is known about their neurobiological differences. While few studies showed that variants differ in brain activity during fear processing, it remains unknown whether they also show atypical functioning in motivational and reward system. Latent Profile Analysis (LPA) was conducted on a large sample of adolescents (n = 1416) to identify variants based on their levels of callousness and anxiety. Seed-to-voxel connectivity analysis was subsequently performed on resting-state fMRI data to compare connectivity patterns of the nucleus accumbens across subgroups. LPA failed to identify the primary variant when using total score of CU traits. Using a family-wise cluster correction, groups did not differ on functional connectivity. However, at an uncorrected threshold the secondary variant showed distinct functional connectivity between the nucleus accumbens and posterior insula, lateral orbitofrontal cortex, supplementary motor area, and parietal regions. Secondary LPA analysis using only the callousness subscale successfully distinguish both variants. Group differences replicated results of deficits in functional connectivity between the nucleus accumbens and posterior insula and supplementary motor area, but additionally showed effect in the superior temporal gyrus which was specific to the primary variant. The current study supports the importance of examining the neurobiological markers across subgroups of adolescents at risk for conduct problems to precise our understanding of this heterogeneous population.

Newborn Brain Function and Early Emerging Callous-Unemotional Traits.

Importance: Children with high callous-unemotional traits are more likely to develop severe and persistent conduct problems; however, the newborn neurobiology underlying early callous-unemotional traits remains unknown. Understanding the neural mechanisms that precede the development of callous-unemotional traits could help identify at-risk children and encourage development of novel treatments. Objective: To determine whether newborn brain function is associated with early-emerging empathy, prosociality, and callous-unemotional traits. Design, Setting, and Participants: In this prospective, longitudinal cohort study, pregnant women were recruited from obstetric clinics in St Louis, Missouri, from September 1, 2017, to February 28, 2020, with longitudinal data collected until March 20, 2023. Mothers were recruited during pregnancy. Newborns underwent brain magnetic resonance imaging shortly after birth. Mothers completed longitudinal follow-up when the children were aged 1, 2, and 3 years. Exposures: The sample was enriched for exposure to socioeconomic disadvantage. Main Outcome and Measure: Functional connectivity between hypothesized brain regions was assessed using newborn-specific networks and voxel-based connectivity analyses. Children's callous-unemotional traits were measured using the Inventory of Callous-Unemotional Traits. Empathy and prosociality were assessed using the Infant and Toddler Socio-Emotional Assessment. Results: A total of 283 children (mean [SD] gestational age, 38 [2] weeks; 159 male [56.2%]; 2 Asian [0.7%], 171 Black [60%], 7 Hispanic or Latino [2.5%], 106 White [38%], 4 other racial or ethnic group [1.4%]) were included in the analysis. Stronger newborn functional connectivity between the cingulo-opercular network (CO) and medial prefrontal cortex (mPFC) was associated with higher callous-unemotional traits at age 3 years (ß = 0.31; 95% CI, 0.17-0.41; P < .001). Results persisted when accounting for parental callous-unemotional traits and child externalizing symptoms. Stronger newborn CO-mPFC connectivity was also associated with lower empathy and lower prosociality at ages 1, 2, and 3 years using multilevel models (ß = -0.12; 95% CI, -0.21 to -0.04; P = .004 and ß = -0.20; 95% CI, -0.30 to -0.10; P < .001, respectively). Conclusions and Relevance: Newborn functional connectivity was associated with early-emerging empathy, prosociality, and callous-unemotional traits, even when accounting for parental callous-unemotional traits and child externalizing symptoms. Understanding the neurobiological underpinnings of empathy, prosociality, and callous-unemotional traits at the earliest developmental point may help early risk stratification and novel intervention development.

Rapid white matter changes in children with conduct problems during a parenting intervention.

Studies report that the microstructural integrity of the uncinate fasciculus (UF; connecting the anterior temporal lobe to the orbitofrontal cortex) is abnormal in adults with psychopathy and children with conduct problems (CP), especially those with high callous-unemotional (CU) traits. However, it is unknown if these abnormalities are 'fixed' or 'reversible'. Therefore, we tested the hypothesis that a reduction in CP symptoms, following a parenting intervention, would be associated with altered microstructural integrity in the UF. Using diffusion tensor imaging tractography we studied microstructural differences (mean diffusivity (MD) and radial diffusivity (RD)) in the UF of 43 typically developing (TD) and 67 boys with CP before and after a 14-week parenting intervention. We also assessed whether clinical response in CP symptoms or CU traits explained changes in microstructure following the intervention. Prior to intervention, measures of MD and RD in the UF were increased in CP compared to TD boys. Following intervention, we found that the CP group had a significant reduction in RD and MD. Further, these microstructural changes were driven by the group of children whose CU traits improved (but not CP symptoms as hypothesized). No significant microstructural changes were observed in the TD group. Our findings suggest, for the first time, that microstructural abnormalities in the brains of children with CP may be reversible following parenting intervention.

Different whole-brain functional connectivity correlates of reactive-proactive aggression and callous-unemotional traits in children and adolescents with disruptive behaviors.

BACKGROUND: Disruptive behavior in children and adolescents can manifest as reactive aggression and proactive aggression and is modulated by callous-unemotional traits and other comorbidities. Neural correlates of these aggression dimensions or subtypes and comorbid symptoms remain largely unknown. This multi-center study investigated the relationship between resting state functional connectivity (rsFC) and aggression subtypes considering comorbidities. METHODS: The large sample of children and adolescents aged 8-18 years (n = 207; mean age = 13.30±2.60 years, 150 males) included 118 cases with disruptive behavior (80 with Oppositional Defiant Disorder and/or Conduct Disorder) and 89 controls. Attention-deficit/hyperactivity disorder (ADHD) and anxiety symptom scores were analyzed as covariates when assessing group differences and dimensional aggression effects on hypothesis-free global and local voxel-to-voxel whole-brain rsFC based on functional magnetic resonance imaging at 3 Tesla. RESULTS: Compared to controls, the cases demonstrated altered rsFC in frontal areas, when anxiety but not ADHD symptoms were controlled for. For cases, reactive and proactive aggression scores were related to global and local rsFC in the central gyrus and precuneus, regions linked to aggression-related impairments. Callous-unemotional trait severity was correlated with ICC in the inferior and middle temporal regions implicated in empathy, emotion, and reward processing. Most observed aggression subtype-specific patterns could only be identified when ADHD and anxiety were controlled for. CONCLUSIONS: This study clarifies that hypothesis-free brain connectivity measures can disentangle distinct though overlapping dimensions of aggression in youths. Moreover, our results highlight the importance of considering comorbid symptoms to detect aggression-related rsFC alterations in youths.

Connectome-based predictive modeling of empathy in adolescents with and without the low-prosocial emotion specifier.

Empathy impairments are an important part of a broader affective impairments defining the youth antisocial phenotype callous-unemotional (CU) traits and the DSM-5 low prosocial emotion (LPE) specifier. While functional connectivity underlying empathy and CU traits have been well studied, less is known about what functional connections underly differences in empathy amongst adolescents qualifying for the LPE specifier. Such information can provide mechanistic distinctions for this clinically relevant specifier. The present study uses connectome-based predictive modeling that uses whole-brain resting-state functional connectivity data to predict cognitive and affective empathy for those meeting the LPE specifier (n = 29) and those that do not (n = 57). Additionally, we tested if models of empathy generalized between groups as well as density differences for each model of empathy between groups. Results indicate the LPE group had lower cognitive and affective empathy as well as higher CU traits and conduct problems. Negative and positive models were identified for affective empathy for both groups, but only the negative model for the LPE and positive model for the normative group reliably predicted cognitive empathy. Models predicting empathy did not generalize between groups. Density differences within the default mode, salience, executive control, limbic, and cerebellar networks were found as well as between the executive control, salience, and default mode networks. And, importantly, connections between the executive control and default mode networks characterized empathy differences the LPE group such that more positive connections characterized cognitive differences and less negative connections characterized affective differences. These findings indicate neural differences in empathy for those meeting LPE criteria that may explain decrements in empathy amongst these youth. These findings support theoretical accounts of empathy decrements in the LPE clinical specifier and extend them to identify specific circuits accounting for variation in empathy impairments. The identified negative models help understand what connections inhibit empathy whereas the positive models reveal what brain patterns are being used to support empathy in those with the LPE specifier. LPE differences from the normative group and could be an appropriate biomarker for predicting CU trait severity. Replication and validation using other large datasets are important next steps.

Altered functional connectivity of the amygdala across variants of callous-unemotional traits: A resting-state fMRI study in children and adolescents.

Over the past years, research has shown that primary (high callousness and low anxiety) and secondary (high callousness and anxiety) variants of CU traits may be associated with opposite amygdala activity (hypo- and hyper-reactivity, respectively). However, their differences in amygdala functional connectivity remains largely unexplored. We conducted a Latent Profile Analysis on a large sample of adolescents (n = 1416) to identify homogeneous subgroups with different levels of callousness and anxiety. We then performed a seed-to-voxel connectivity analysis on resting-state fMRI data to compare subgroups on connectivity patterns of the amygdala. We examined the results in relation to conduct problems to identify potential neural risk factors. The Latent Profile Analysis revealed four subgroups, including the primary and secondary variants, anxious, and typically developing adolescents. The seed-to-voxel analyses showed that the primary variant was mainly characterized by increased connectivity between the left amygdala and left thalamus. The secondary variant exhibited deficient connectivity between the amygdala and the dorsomedial prefrontal cortex, temporo-parietal junction, premotor, and postcentral gyrus. Both variants showed increased connectivity between the left amygdala and the right thalamus but exhibited opposite functional connectivity between the left amygdala and the parahippocampal gyrus. Dimensional analyses indicated that conduct problems may play a mediating role between callousness and amygdala-dmPFC functional connectivity across youths with already high levels of callousness. Our study highlights that both variants differ in the functional connectivity of the amygdala. Our results support the importance of disentangling the heterogeneity of adolescents at risk for conduct problems in neuroimaging.

Disrupted functional networks within white-matter served as neural features in adolescent patients with conduct disorder.

BACKGROUND: Conduct disorder (CD) has been conceptualized as a psychiatric disorder associated with white-matter (WM) structural abnormalities. Although diffusion tensor imaging could identify WM structural architecture changes, it cannot characterize functional connectivity (FC) within WM. Few studies have focused on disentangling the WM dysfunctions in CD patients by using functional magnetic resonance imaging (fMRI). METHODS: The resting-state fMRI data were first obtained from both adolescent CD and typically developing (TD) controls. A voxel-based clustering analysis was utilized to identify the large-scale WM FC networks. Then, we examined the disrupted WM network features in CD, and further investigated whether these features could predict the impulsive symptoms in CD using support vector regression prediction model. RESULTS: We identified 11 WM functional networks. Compared with TDs, CD patients showed increased FCs between occipital network (ON) and superior temporal network (STN), between orbitofrontal network (OFN) and corona radiate network (CRN), as well as between deep network and CRN. Further, the disrupted FCs between ON and STN and between OFN and CRN were significantly negatively associated with non-planning impulsivity scores in CD. Moreover, the disrupted WM networks could be served as features to predict the motor impulsivity scores in CD. CONCLUSIONS: Our results provided further support on the existence of WM functional networks and could extended our knowledge about the WM functional abnormalities related with emotional and perception processing in CD patients from the view of WM dysfunction.

Emotion processing in youths with conduct problems: an fMRI meta-analysis.

Functional magnetic resonance imaging (fMRI) studies consistently indicate differences in emotion processing in youth with conduct problems. However, no prior meta-analysis has investigated emotion-specific responses associated with conduct problems. This meta-analysis aimed to generate an up-to-date assessment of socio-affective neural responding among youths with conduct problems. A systematic literature search was conducted in youths (ages 10-21) with conduct problems. Task-specific seed-based d mapping analyses examined responses to threatening images, fearful and angry facial expressions, and empathic pain stimuli from 23 fMRI studies, which included 606 youths with conduct problems and 459 comparison youths. Whole-brain analyses revealed youths with conduct problems relative to typically developing youths, when viewing angry facial expressions, had reduced activity in left supplementary motor area and superior frontal gyrus. Additional region of interest analyses of responses to negative images and fearful facial expressions showed reduced activation in right amygdala across youths with conduct problems. Youths with callous-unemotional traits also exhibited reduced activation in left fusiform gyrus, superior parietal gyrus, and middle temporal gyrus when viewing fearful facial expressions. Consistent with the behavioral profile of conduct problems, these findings suggest the most consistent dysfunction is found in regions associated with empathic responding and social learning, including the amygdala and temporal cortex. Youth with callous-unemotional traits also show reduced activation in the fusiform gyrus, consistent with reduced attention or facial processing. These findings highlight the potential role of empathic responding, social learning, and facial processing along with the associated brain regions as potential targets for interventions.

Resting-state connectivity underlying cognitive control's association with perspective taking in callous-unemotional traits.

Callous-Unemotional (CU) traits are often associated with impairments in perspective taking and cognitive control (regulating goal directed behavior); and adolescents with CU traits demonstrate aberrant brain activation/connectivity in areas underlying these processes. Together cognitive control and perspective taking are thought to link mechanistically to explain CU traits. Because increased cognitive control demands modulate perspective taking ability among both typically developing samples and individuals with elevated CU traits, understanding the neurophysiological substrates of these constructs could inform efforts to alleviate societal costs of antisocial behavior. The present study uses GIMME to examine the heterogenous functional brain properties (i.e., connection density, node centrality) underlying cognitive control's influence on perspective taking among adolescents on a CU trait continuum. Results reveal that cognitive control had a negative indirect association with CU traits via perspective taking; and brain connectivity indirectly associated with lower CU traits - specifically the social network via perspective taking and conflict network via cognitive control. Additionally, less negative connection density between the social and conflict networks was directly associated with higher CU traits. Our results support the growing literature on cognitive control's influence on socio-cognitive functioning in CU traits and extends that work by identifying underlying functional brain properties.

Selective Amygdala Hypoactivity to Fear in Boys With Persistent Conduct Problems After Parent Training.

BACKGROUND: Parenting interventions reduce antisocial behavior (ASB) in some children with conduct problems (CPs), but not others. Understanding the neural basis for this disparity is important because persistent ASB is associated with lifelong morbidity and places a huge burden on our health and criminal justice systems. One of the most highly replicated neural correlates of ASB is amygdala hypoactivity to another person's fear. We aimed to assess whether amygdala hypoactivity to fear in children with CPs is remediated following reduction in ASB after successful treatment and/or if it is a marker for persistent ASB. METHODS: We conducted a prospective, case-control study of boys with CPs and typically developing (TD) boys. Both groups (ages 5-10 years) completed 2 magnetic resonance imaging sessions (18 ± 5.8 weeks apart) with ASB assessed at each visit. Participants included boys with CPs following referral to a parenting intervention group and TD boys recruited from the same schools and geographical regions. Final functional magnetic resonance imaging data were available for 36 TD boys and 57 boys with CPs. Boys with CPs were divided into those whose ASB improved (n = 27) or persisted (n = 30) following the intervention. Functional magnetic resonance imaging data assessing fear reactivity were then analyzed using a longitudinal group (TD/improving CPs/persistent CPs) × time point (pre/post) design. RESULTS: Amygdala hypoactivity to fear was observed only in boys with CPs who had persistent ASB and was absent in those whose ASB improved following intervention. CONCLUSIONS: Our findings suggest that amygdala hypoactivity to fear is a marker for ASB that is resistant to change following a parenting intervention and a putative target for future treatments.

Neuroanatomical markers of familial risk in adolescents with conduct disorder and their unaffected relatives.

BACKGROUND: Previous studies have reported brain structure abnormalities in conduct disorder (CD), but it is unclear whether these neuroanatomical alterations mediate the effects of familial (genetic and environmental) risk for CD. We investigated brain structure in adolescents with CD and their unaffected relatives (URs) to identify neuroanatomical markers of familial risk for CD. METHODS: Forty-one adolescents with CD, 24 URs of CD probands, and 38 healthy controls (aged 12-18), underwent structural magnetic resonance imaging. We performed surface-based morphometry analyses, testing for group differences in cortical volume, thickness, surface area, and folding. We also assessed the volume of key subcortical structures. RESULTS: The CD and UR groups both displayed structural alterations (lower surface area and folding) in left inferior parietal cortex compared with controls. In contrast, CD participants showed lower insula and pars opercularis volume than controls, and lower surface area and folding in these regions than controls and URs. The URs showed greater folding in rostral anterior cingulate and inferior temporal cortex than controls and greater medial orbitofrontal folding than CD participants. The surface area and volume differences were not significant when controlling for attention-deficit/hyperactivity disorder comorbidity. There were no group differences in subcortical volumes. CONCLUSIONS: These findings suggest that alterations in inferior parietal cortical structure partly mediate the effects of familial risk for CD. These structural changes merit investigation as candidate endophenotypes for CD. Neuroanatomical changes in medial orbitofrontal and anterior cingulate cortex differentiated between URs and the other groups, potentially reflecting neural mechanisms of resilience to CD.

Structural abnormalities in adolescents with conduct disorder and high versus low callous unemotional traits.

There may be distinct conduct disorder (CD) etiologies and neural morphologies in adolescents with high callous unemotional (CU) traits versus low CU traits. Here, we employed surface-based morphometry methods to investigate morphological differences in adolescents diagnosed with CD [42 with high CU traits (CD-HCU) and 40 with low CU traits (CD-LCU)] and healthy controls (HCs, N = 115) in China. Whole-brain analyses revealed significantly increased cortical surface area (SA) in the left inferior temporal cortex and the right precuneus, but decreased SA in the left superior temporal cortex in the CD-LCU group, compared with the HC group. There were no significant cortical SA differences between the CD-HCU and the HC groups. Compared to the CD-HCU group, the CD-LCU group had a greater cortical thickness (CT) in the left rostral middle frontal cortex. Region-of-interest analyses revealed significant group differences in the right hippocampus, with CD-HCU group having lower right hippocampal volumes than HCs. We did not detect significant group differences in the amygdalar volume, however, the right amygdalar volume was found to be a significant moderator of the correlation between CU traits and the proactive aggression in CD patients. The present results suggested that the manifestations of CD differ between those with high CU traits versus low CU traits, and underscore the importance of sample characteristics in understanding the neural substrates of CD.

Antisocial behavior is associated with reduced frontoparietal activity to loss in a population-based sample of adolescents.

BACKGROUND: Adolescent antisocial behavior (AB) is a public health concern due to the high financial and social costs of AB on victims and perpetrators. Neural systems involved in reward and loss processing are thought to contribute to AB. However, investigations into these processes are limited: few have considered anticipatory and consummatory components of reward, response to loss, nor whether associations with AB may vary by level of callous-unemotional (CU) traits. METHODS: A population-based community sample of 128 predominantly low-income youth (mean age = 15.9 years; 42% male) completed a monetary incentive delay task during fMRI. A multi-informant, multi-method latent variable approach was used to test associations between AB and neural response to reward and loss anticipation and outcome and whether CU traits moderated these associations. RESULTS: AB was not associated with neural response to reward but was associated with reduced frontoparietal activity during loss outcomes. This association was moderated by CU traits such that individuals with higher levels of AB and CU traits had the largest reductions in frontoparietal activity. Co-occurring AB and CU traits were also associated with increased precuneus response during loss anticipation. CONCLUSIONS: Findings indicate that AB is associated with reduced activity in brain regions involved in cognitive control, attention, and behavior modification during negative outcomes. Moreover, these reductions are most pronounced in youth with co-occurring CU traits. These findings have implications for understanding why adolescents involved in AB continue these behaviors despite severe negative consequences (e.g. incarceration).

Associated functional network connectivity between callous-unemotionality and cognitive and affective empathy.

BACKGROUND: Low empathy is one component of affective impairments defining the antisocial youth phenotype callous-unemotional (CU) traits. Research suggests CU traits may be negatively associated with neural networks that are positively associated with cognitive and affective empathy - specifically the default mode (DMN), frontoparietal (FPN), and salience (SAL) networks. Determining which functional network connections are shared between CU traits and empathy could elucidate the extent to which CU traits shares neural substrates with cognitive versus affective empathy. The present study tested whether CU traits and both cognitive and affective empathy share network connections within and between the DMN, FPN, and SAL. METHODS: Participants (n = 112, aged 13-17, 43 % female) completed resting-state functional magnetic resonance imaging and self-reports for CU traits and empathy as part of a Nathan-Kline Institute study. RESULTS: Analyses revealed inverse associations with shared network connections between CU traits and both cognitive and affective empathy. Specifically, within-DMN connectivity negatively associated with CU traits, but positively associated with cognitive empathy; and between DMN-SAL connectivity positively associated with CU traits, but negatively associated with both cognitive and affective empathy. However, joint models revealed little variance explained by CU traits and empathy overlapped. LIMITATIONS: The sample was cross-sectional collection with limited participants (n = 112) from the community that may not generalize to incarcerated adolescents. CONCLUSIONS: Results demonstrate CU traits inversely associated with similar connectivity patterns as cognitive and affective empathy though prediction among constructs did not significantly overlap. Further investigation of these connections can inform a mechanistic understanding of empathy impairments in CU traits.

Neuroanatomical changes associated with conduct disorder in boys: influence of childhood maltreatment.

Childhood maltreatment (CM) poses a serious risk to the physical, emotional and psychological well-being of children, and can advance the development of maladaptive behaviors, including conduct disorder (CD). CD involves repetitive, persistent violations of others' basic rights and societal norms. Little is known about whether and how CM influences the neural mechanisms underlying CD, and CD-characteristic neuroanatomical changes have not yet been defined in a structural magnetic resonance imaging (sMRI) study. Here, we used voxel-based morphometry (VBM) and surface-based morphometry (SBM) to investigate the influence of the CD diagnosis and CM on the brain in 96 boys diagnosed with CD (62 with CM) and 86 typically developing (TD) boys (46 with CM). The participants were 12-17 years of age. Compared to the CM- CD group, the CM+ CD group had structural gray matter (GM) alterations in the fronto-limbic regions, including the left amygdala, right posterior cingulate cortex (PCC), right putamen, right dorsolateral prefrontal cortex (dlPFC) and right anterior cingulate cortex (ACC). We also found boys with CD exhibited increased GM volume in bilateral dorsomedial prefrontal cortex (dmPFC), as well as decreased GM volume and decreased gyrification in the left superior temporal gyrus (STG) relative to TD boys. Regional GM volume correlated with aggression and conduct problem severity in the CD group, suggesting that the GM changes may contribute to increased aggression and conduct problems in boys with CD who have suffered CM. In conclusion, these results demonstrate previously unreported CM-associated distinct brain structural changes among CD-diagnosed boys.

Conduct disorder symptomatology is associated with an altered functional connectome in a large national youth sample.

Conduct disorder (CD), characterized by youth antisocial behavior, is associated with a variety of neurocognitive impairments. However, questions remain regarding the neural underpinnings of these impairments. To investigate novel neural mechanisms that may support these neurocognitive abnormalities, the present study applied a graph analysis to resting-state functional magnetic resonance imaging (fMRI) data collected from a national sample of 4,781 youth, ages 9-10, who participated in the baseline session of the Adolescent Brain Cognitive DevelopmentSM Study (ABCD Study®). Analyses were then conducted to examine the relationships among levels of CD symptomatology, metrics of global topology, node-level metrics for subcortical structures, and performance on neurocognitive assessments. Youth higher on CD displayed higher global clustering (ß = .039, 95% CIcorrected [.0027 .0771]), but lower Degreesubcortical (ß = -.052, 95% CIcorrected [-.0916 -.0152]). Youth higher on CD had worse performance on a general neurocognitive assessment (ß = -.104, 95% CI [-.1328 -.0763]) and an emotion recognition memory assessment (ß = -.061, 95% CI [-.0919 -.0290]). Finally, global clustering mediated the relationship between CD and general neurocognitive functioning (indirect ß = -.002, 95% CI [-.0044 -.0002]), and Degreesubcortical mediated the relationship between CD and emotion recognition memory performance (indirect ß = -.002, 95% CI [-.0046 -.0005]). CD appears associated with neuro-topological abnormalities and these abnormalities may represent neural mechanisms supporting CD-related neurocognitive disruptions.