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Purpose Conduct problem behaviors are highly heterogeneous symptom clusters, creating many challenges in investigating etiology and planning treatment. The aim of this study was to first identify distinct subgroups of males and females with conduct problems using a data driven approach and, secondly, to investigate whether these subgroups differed in treatment outcome after an evidence-based crime prevention program. Methods We used a latent class analysis (LCA) in Mplus` to classify 517 males and 354 females (age 6–11) into classes based on the presence of conduct disorder or oppositional defiance disorder items from the Child Behavior Checklist. All children were then enlisted into the 13-week group core component (children and parent groups) of the program Stop Now And Plan (SNAP®), a cognitive-behavioral, trauma-informed, and gender-specific program that teaches children (and their caregivers) emotion-regulation, self-control, and problem-solving skills. Results The LCA revealed four classes for males, which separated into (1) “rule-breaking,” (2) “aggressive,” (3) “mild,” and (4) “severe” conduct problems. While all four groups showed a significant improvement following the SNAP program, they differed in the type and magnitude of their improvements. For females, we observed two classes of conduct problems that were largely distinguishable based on severity of conduct problems. Participants in both female groups significantly improved with treatment, but did not differ in the type or magnitude of improvement. Conclusion This study presents novel findings of sex differences in clustering of conduct problems and adds to the discussion of how to target treatment for individuals presenting with a variety of different problem behaviors.

As most research on conduct disorder (CD) has been conducted on male participants, it has been suggested that female-specific symptoms may be underestimated based on current DSM-5 criteria. In particular, relational aggression, i.e. the hurtful, often indirect, manipulation of relationships with the intention of damaging the other's social position, has been proposed as a characteristic of CD that is more common in females. In addition, sex-specific studies on correlates of relational aggressive behavior are lacking. Relational aggression may be strongly related to the correlates of proactive aggression, namely low affective empathy, and high levels of callous-unemotional (CU) traits and relational victimization. Thus, the present study investigated sex differences in relational aggression, and associations between relational aggression and correlates of proactive aggression in 662 adolescents with CD (403 females) and 849 typically-developing controls (568 females) aged 9-18 years (M = 14.74, SD = 2.34) from the European multi-site FemNAT-CD study. Females with CD showed significantly higher levels of relational aggression compared to males with CD, whereas no sex differences were seen in controls. Relational aggression was only partly related to correlates of proactive aggression in CD: Independent of sex, CU traits showed a positive association with relational aggression. In females only, cognitive, but not affective empathy, was negatively associated with relational aggression. Relational victimization was more strongly associated with relational aggression in males compared to females. Despite interesting sex specific correlates of relational aggression, effects are small and the potential clinical implications should be investigated in future studies.

Background: Stop, Now And Plan (SNAP) is a cognitive behavioral-based psychosocial intervention that has a strong evidence base for treating youth with high aggression and externalizing behaviors, many of whom have disruptive behavior disorders. In a pre-post design, we tested whether SNAP could improve externalizing behaviors, assessed by the parent-rated Child Behavior Checklist (CBCL) and also improve behavioral measures of impulsivity in children with high aggression and impulsivity. We then investigated whether any improvement in externalizing behavior or impulsivity was associated with gray matter volume (GMV) changes assessed using structural magnetic resonance imaging (sMRI). We also recruited typically developing youth who were assessed twice without undergoing the SNAP intervention.Methods: Ten children who were participating in SNAP treatment completed the entire study protocol. CBCL measures, behavioral measures of impulsivity, and sMRI scanning was conducted pre-SNAP and then 13 weeks later post-SNAP. Twelve healthy controls also completed the study; they were rated on the CBCL, performed the same behavioral measure of impulsivity, and underwent sMRI twice, separated by 13 weeks. They did not receive the SNAP intervention.Result: At baseline, SNAP participants had higher CBCL scores and performed worse on the impulsivity task compared with the healthy controls. At the second visit, SNAP participants still had higher scores on the CBCL compared with normally-developing controls, but their performance on the impulsivity task had improved to the point where their results were indistinguishable from the healthy controls. Structural magnetic resonance imaging in the SNAP participants further revealed that improvements in impulsivity were associated with GMV changes in the frontotemporal region.Conclusion: These results suggest that SNAP led to improvement in behavioral measures of impulsivity in a cohort of boys with high externalizing behavior. Improvement in impulsivity was also associated with increased GMV changes. The mechanism behind these brain changes is unknown but could relate to cognitive behavioral therapy and contingency management interventions, important components of SNAP, that target frontotemporal brain regions. Clinically, this study offers new evidence for the potential targeting of brain regions by non-invasive modalities, such as repetitive transcranial magnetic stimulation, to improve externalizing behavior and impulsivity.

Less is known about the relationship between conduct disorder (CD), callous–unemotional (CU) traits, and positive and negative parenting in youth compared to early childhood. We combined traditional univariate analyses with a novel machine learning classifier (Angle-based Generalized Matrix Learning Vector Quantization) to classify youth (N = 756; 9–18 years) into typically developing (TD) or CD groups with or without elevated CU traits (CD/HCU, CD/LCU, respectively) using youth- and parent-reports of parenting behavior. At the group level, both CD/HCU and CD/LCU were associated with high negative and low positive parenting relative to TD. However, only positive parenting differed between the CD/HCU and CD/LCU groups. In classification analyses, performance was best when distinguishing CD/HCU from TD groups and poorest when distinguishing CD/HCU from CD/LCU groups. Positive and negative parenting were both relevant when distinguishing CD/HCU from TD, negative parenting was most relevant when distinguishing between CD/LCU and TD, and positive parenting was most relevant when distinguishing CD/HCU from CD/LCU groups. These findings suggest that while positive parenting distinguishes between CD/HCU and CD/LCU, negative parenting is associated with both CD subtypes. These results highlight the importance of considering multiple parenting behaviors in CD with varying levels of CU traits in late childhood/adolescence.

The journal of child psychology and psychiatry 63(2), 218-228 (2022). doi:10.1111/jcpp.13428, Published by Wiley-Blackwell, Oxford

As the main excitatory neurotransmitter in the central nervous system, glutamate, as measured in combination with glutamine (Glx), is implicated in several psychopathologies when levels are aberrant. One illness that shows heightened Glx levels is bipolar disorder (BD), an illness characterized by high impulsivity. In addition, although animal studies have reported elevated levels of Glx in aggressive and impulsive phenotypes, no study, to our knowledge, has reported Glx in the human cortex in relation to aggression. Here, we addressed the question of whether elevated levels of Glx would be present in patients with BD and antisocial personality disorder (ASPD), a condition associated with aggression and, like BD, also presents high impulsivity. We recruited individuals with ASPD (n = 18), individuals with BD (n = 16), and a healthy control group (n = 24). We used proton magnetic resonance spectroscopy to measure relative neurometabolite concentrations in the left dorsolateral prefrontal cortex (dlPFC) and supra-genual anterior cingulate cortex (ACC), two brain regions associated with impulsivity and behavior control. We found significantly elevated levels of Glx in the ASPD group relative to the BD and healthy control groups in the dlPFC (p = .014), and a positive correlation between Glx levels and aggression in the dlPFC in the ASPD group alone (r = .59, p = .026). These findings suggest a link between aggression in ASPD and Glx levels.

Journal of the American Heart Association 10(4), e017405 (2021). doi:10.1161/JAHA.120.017405, Published by American Heart Association, New York, NY

Translational Psychiatry 11(1), 492 (2021). doi:10.1038/s41398-021-01609-y, Published by Nature Publishing Group, London

Conduct disorder (CD) with high levels of callous-unemotional traits (CD/HCU) has been theoretically linked to specific difficulties with fear and sadness recognition, in contrast to CD with low levels of callous-unemotional traits (CD/LCU). However, experimental evidence for this distinction is mixed, and it is unclear whether these difficulties are a reliable marker of CD/HCU compared to CD/LCU. In a large sample (N = 1263, 9–18 years), we combined univariate analyses and machine learning classifiers to investigate whether CD/HCU is associated with disproportionate difficulties with fear and sadness recognition over other emotions, and whether such difficulties are a reliable individual-level marker of CD/HCU. We observed similar emotion recognition abilities in CD/HCU and CD/LCU. The CD/HCU group underperformed relative to typically developing (TD) youths, but difficulties were not specific to fear or sadness. Classifiers did not distinguish between youths with CD/HCU versus CD/LCU (52% accuracy), although youths with CD/HCU and CD/LCU were reliably distinguished from TD youths (64% and 60%, respectively). In the subset of classifiers that performed well for youths with CD/HCU, fear and sadness were the most relevant emotions for distinguishing them from youths with CD/LCU and TD youths, respectively. We conclude that non-specific emotion recognition difficulties are common in CD/HCU, but are not reliable individual-level markers of CD/HCU versus CD/LCU. These findings highlight that a reduced ability to recognise facial expressions of distress should not be assumed to be a core feature of CD/HCU.

The ability to identify early risk factors for antisocial behavior in children is one of the most important and difficult challenges in the fields of developmental criminology and mental health. It is also a necessary first step in assigning suitable interventions to minimize risk for these children. The Early Risk Assessment List (EARL) was the first gender specific psychosocial assessment framework for identifying and monitoring risk and need for children with antisocial behavior under age 12. Since the first iteration in 1998, a broad range of scientific studies have been conducted on the validity and applicability of the EARL across settings and cultures. This chapter provides readers with a history of the EARL, the structure and content of the assessment, a review of its reliability and validity, and how the tool may be used to inform risk management plans to reduce disruptive behavior and the risk of criminal involvement in young children. A case example is provided.

Background: At the group level, youths with conduct disorder (CD) show deficient emotion processing across various tasks compared to typically developing controls (TDC). But little is known about neuropsychological subgroups within the CD population, the clinical correlates of emotion processing deficits [for instance, with regard to the presence or absence of the DSM-5 Limited Prosocial Emotions (LPE) specifier], and associated risk factors.Methods: 542 children and adolescents with CD (317 girls) and 710 TDCs (479 girls), aged 9–18 years, were included from the FemNAT-CD multisite study. All participants completed three neuropsychological tasks assessing emotion recognition, emotion learning, and emotion regulation. We used a self-report measure of callous-unemotional traits to create a proxy for the LPE specifier.Results: Relative to TDCs, youths with CD as a group performed worse in all three emotion domains. But using clinically based cut-off scores, we found poor emotion recognition skills in only 23% of the participants with CD, followed by emotion regulation deficits in 18%, and emotion learning deficits in 13% of the CD group. Critically, the majority of youths with CD (~56%) did not demonstrate any meaningful neuropsychological deficit, and only a very small proportion showed pervasive deficits across all three domains (~1%). Further analyses indicate that established DSM-5 subtypes of CD are not tightly linked to neurocognitive deficits in one particular emotion domain over another (i.e., emotion recognition deficits in CD+LPE vs. emotion regulation deficits in CD–LPE).Conclusions: Findings from this large-scale data set suggest substantial neuropsychological diversity in emotion processing in the CD population and, consequently, only a subgroup of youths with CD are likely to benefit from additional behavioral interventions specifically targeting emotion processing mechanisms.

Objective Conduct disorder (CD) is a serious neurodevelopmental disorder marked by notably higher prevalence rates for boys than girls. Converging evidence suggests that CD is associated with impairments in emotion recognition, learning, and regulation. However, it is not known whether there are sex differences in the relationship between CD and emotion dysfunction. Prior studies on emotion functioning in CD have so far been underpowered for investigating sex differences. Therefore, our primary aim was to characterize emotion processing skills in a large sample of girls and boys with CD compared to typically developing controls (TDCs) using a comprehensive neuropsychological test battery. Method We included 542 youths with CD (317 girls) and 710 TDCs (479 girls), 9 to 18 years of age, from a European multisite study (FemNAT-CD). Participants completed three experimental tasks assessing emotion recognition, learning, and regulation, respectively. Data were analyzed to test for effects of group and sex, and group-by-sex interactions, while controlling for potentially confounding factors. Results Relative to TDCs, youths with CD showed impaired emotion recognition (that was related to more physical and proactive aggression, and higher CU traits), emotional learning (specifically from punishment), and emotion regulation. Boys and girls with CD, however, displayed similar impairments in emotion processing. Conclusion This study provides compelling evidence for a relationship between CD and deficient neurocognitive functioning across three emotional domains that have previously been linked to CD etiology. However, there was no support for sex-specific profiles of emotion dysfunction, suggesting that current neurocognitive models of CD apply equally to both sexes.

Reduced responsiveness to emotions is hypothesized to contribute to the development of conduct disorder (CD) in children and adolescents. Accordingly, blunted psychophysiological responses to emotions have been observed in boys with CD, but this has never been tested in girls. Therefore, this study compared psychophysiological responses to sadness in girls and boys with and without CD, and different clinical phenotypes of CD: with versus without limited prosocial emotions (LPE), and with versus without comorbid internalizing disorders (INT). Nine-hundred and 27 girls (427 CD, 500 controls) and 519 boys (266 CD, 253 controls) aged 9-18 years participated. Psychophysiological responses were measured while participants watched two validated sad film clips, specifically: heart rate (HR), respiratory sinus arrhythmia (RSA; indexing parasympathetic activity), preejection period (PEP; indexing sympathetic activity). Girls and boys with CD showed larger HR responses to sadness than controls. This effect was rendered nonsignificant, however, after controlling for covariates. We observed aberrant RSA responses to sadness in CD compared with controls. Similarly, we found a significant positive association between RSA responsivity and antisocial behavior when assessed dimensionally. The effects were very small, though. Results were similar for boys and girls. We found no evidence for emotional underresponsiveness in CD in the largest psychophysiological study to date in this field. More research is needed to explore whether this is specific to sadness or generalizes to other emotions. Furthermore, we recommend that studies on emotion processing in CD assess different physiological measures to help disentangle CD-related effects on sympathetic and parasympathetic activity. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

BackgroundPrevious studies of conduct disorder (CD) have reported structural and functional alterations in the limbic system. However, the white matter tracts that connect limbic regions have not been comprehensively studied. The uncinate fasciculus (UF), a tract connecting limbic to prefrontal regions, has been implicated in CD. However, CD-related alterations in other limbic tracts, such as the cingulum and the fornix, have not been investigated. Furthermore, few studies have examined the influence of sex and none have been adequately powered to test whether the relationship between CD and structural connectivity differs by sex. We examined whether adolescent males and females with CD exhibit differences in structural connectivity compared with typically developing controls.MethodsWe acquired diffusion-weighted magnetic resonance imaging data from 101 adolescents with CD (52 females) and 99 controls (50 females). Data were processed for deterministic spherical deconvolution tractography. Virtual dissections of the UF, the three subdivisions of the cingulum [retrosplenial cingulum (RSC), parahippocampal and subgenual cingulum], and the fornix were performed and measures of fractional anisotropy (FA) and hindrance-modulated orientational anisotropy (HMOA) were analysed.ResultsThe CD group had lower FA and HMOA in the right RSC tract relative to controls. Importantly, these effects were moderated by sex – males with CD significantly lower FA compared to male controls, whereas CD and control females did not differ.ConclusionsOur results highlight the importance of considering sex when studying the neurobiological basis of CD. Sex differences in RSC connectivity may contribute to sex differences in the clinical presentation of CD.

This chapter reviews the neuroscience of antisocial and offending behavior in child and adolescent populations. It explores the role of neurobiological factors in driving the age-crime curve in offending behavior and the neurobiological bases of sex differences in aggression and antisocial behavior. The chapter discusses what neurobiological and neuroimaging evidence has to say about the validity and utility of different subtyping approaches such as those based on age-of-onset of antisocial behavior or the presence or absence of callous-unemotional personality traits. It expresses that some subtyping approaches, such as those based on assessing callous-unemotional traits, have been tested quite extensively using neurobiological or neuroimaging methods, whereas others, such as the behavioral subtype approach have received relatively little attention in the neuroimaging literature. The chapter considers potential of neuroscience methods to contribute to clinical practice in forensic psychology and psychiatry, evaluation of treatment or rehabilitation approaches, and the prediction of future risk for violence or criminal behavior.

© 2017, The Author(s). Altered decision making processes and excessive risk-seeking behaviours are key features of conduct disorder (CD). Previous studies have provided compelling evidence of abnormally increased preference for risky options, higher sensitivity to rewards, as well as blunted responsiveness to aversive outcomes in adolescents with CD. However, most studies published to date have focused on males only; thus, it is not known whether females with CD show similar alterations in decision making. The current study investigated potential sex differences in decision making and risk-seeking behaviours in adolescents with CD. Forty-nine adolescents with CD (23 females) and 51 control subjects (27 females), aged 11-18 years, performed a computerised task assessing decision making under risk—the Risky Choice Task. Participants made a series of decisions between two gamble options that varied in terms of their expected values and probability of gains and losses. This enabled the participants’ risk preferences to be determined. Taking the sample as a whole, adolescents with CD exhibited increased risk-seeking behaviours compared to healthy controls. However, we found a trend towards a sex-by-group interaction, suggesting that these effects may vary by sex. Follow-up analyses showed that males with CD made significantly more risky choices than their typically developing counterparts, while females with CD did not differ from typically developing females in their risk-seeking behaviours. Our results provide preliminary evidence that sex may moderate the relationship between CD and alterations in risk attitudes and reward processing, indicating that there may be sex differences in the developmental pathways and neuropsychological deficits that lead to CD. European Commission’s Seventh Framework Programme for research, technological development and demonstration (FP7/2007-2013) under Grant Agreement no. 602407 (FemNAT-CD).

Purpose: Autonomic nervous system (ANS) functioning has been widely studied in relation to antisocial behavior, such as Conduct Disorder (CD). However, research in females is scarce and findings are inconsistent. This study investigated baseline ANS activity in CD children and adolescents and tested for sex differences. Furthermore, subgroups of CD were investigated: +/‐ Limited Prosocial Emotions (LPE), +/‐ comorbid internalizing disorders (INT). Methods: Baseline ANS activity was measured by Heart Rate (HR), Heart Rate Variability (HRV; parasympathetic activity), Pre-Ejection Period (PEP; sympathetic activity), and Respiration Rate (RR). 659 females (296 CD, 363 controls) and 351 males (187 CD, 164 controls), aged 9–18 years participated. Results: Baseline HR, HRV and PEP did not differ between CD subjects and controls in both sexes. RR was higher in CD participants than controls amongst females, but not males. LPE was unrelated to ANS activity, whereas females with CD + INT presented lower HRV. Conclusions: These results suggest that baseline ANS activity is not a robust indicator for CD. However, deviant ANS activity – especially parasympathetic activity - was observed in CD females with internalizing comorbidity. The psychophysiological abnormalities observed in this subgroup are indicative of emotion regulation problems. Accordingly, this subgroup may require specific interventions.

Journal of the American Academy of Child and Adolescent Psychiatry : JAACAP 58(12), 1184-1196 (2019). doi:10.1016/j.jaac.2019.02.019, Published by Elsevier, Kidlington [u.a.]

Journal of criminal justice 65, 101536 (2019). doi:10.1016/j.jcrimjus.2018.01.004 special issue: "Practical implications of neuroscience in the field of criminal justice / Edited by Liza Cornet, Katy de Kogel, Florian Bootsman", Published by Pergamon Press, New York, NY [u.a.]

Human communication relies on the ability to process linguistic structure and to map words and utterances onto our environment. Furthermore, as what we communicate is often not directly encoded in our language (e.g. in the case of irony, jokes or indirect requests), we need to extract additional cues to infer the beliefs and desires of our conversational partners. Although the functional interplay between language and the ability to mentalise has been discussed in theoretical accounts in the past, the neurobiological underpinnings of these dynamics are currently not well understood. Here, we address this issue using functional imaging (fMRI). Participants listened to question-reply dialogues. In these dialogues, a reply is interpreted as a direct reply, an indirect reply or a request for action, depending on the question. We show that inferring meaning from indirect replies engages parts of the mentalising network (mPFC) while requests for action also activate the cortical motor system (IPL). Subsequent connectivity analysis using Dynamic Causal Modelling (DCM) revealed that this pattern of activation is best explained by an increase in effective connectivity from the mentalising network (mPFC) to the action system (IPL). These results are an important step towards a more integrative understanding of the neurobiological basis of indirect speech processing.

The aim of this article is to review findings from the neurobiological, neuroimaging, and neuropsychological literature that have contributed to our understanding of the etiology and development of disruptive behavior disorders, with particular reference to conduct disorder. This review focuses on neurobiological systems such as the hypothalamic–pituitary–adrenal axis and neuroimaging evidence linking disruptive behavior disorders to changes in brain functioning or structure. Overall, this research suggests that brain areas involved in emotional processing and regulation are particularly compromised in children and adolescents with disruptive behavior disorder, which fits with evidence obtained from neuropsychological studies. This review highlights the importance of neuroscientific research in characterizing reliable brain-based functional and structural biomarkers that may contribute to an increased understanding of, and the development of new treatments for, antisocial and aggressive behavior in children and adolescents.

Callous-unemotional traits are characterized by a lack of empathy, a disregard for others' feelings and shallow or deficient affect, such as a lack of remorse or guilt. Neuroanatomical correlates of callous-unemotional traits have been demonstrated in clinical samples (i.e., adolescents with disruptive behavior disorders). However, it is unknown whether callous-unemotional traits are associated with neuroanatomical correlates within normative populations without clinical levels of aggression or antisocial behavior. Here we investigated the relationship between callous-unemotional traits and gray matter volume using voxel-based morphometry in a large sample of typically-developing boys and girls (N = 189). Whole-brain multiple regression analyses controlling for site, total intracranial volume, and age were conducted in the whole sample and in boys and girls individually. Results revealed that sex and callous-unemotional traits interacted to predict gray matter volume when considering the whole sample. This interaction was driven by a significant positive correlation between callous-unemotional traits and bilateral anterior insula volume in boys, but not girls. Insula gray matter volume explained 19% of the variance in callous-unemotional traits for boys. Our results demonstrate that callous-unemotional traits are related to variations in brain structure beyond psychiatric samples. This association was observed for boys only, underlining the importance of considering sex as a factor in future research designs. Future longitudinal studies should determine whether these findings hold over childhood and adolescence, and whether the neuroanatomical correlates of callous-unemotional traits are predictive of future psychiatric vulnerability. General scientific summary This study suggests that callous-unemotional traits have a neuroanatomical correlate within typically developing boys, but not girls. Bilateral anterior insula volume explains up to 19% of the variance in callous-unemotional traits in boys., Highlights • Sex-specific correlations between callous-unemotional (CU) traits and insula volume. • CU-traits are positively linked to anterior insula in typically-developing boys. • Variations in insula volume explained 19% of the variance in CU-traits in boys. • Accounting for sex in neuroanatomical studies of individual differences is important.

Exposure to community violence through witnessing or being directly victimized has been associated with conduct problems in a range of studies. However, the relationship between community violence exposure (CVE) and conduct problems has never been studied separately in healthy individuals and individuals with conduct disorder (CD). Therefore, it is not clear whether the association between CVE and conduct problems is due to confounding factors, because those with high conduct problems also tend to live in more violent neighborhoods, i.e., an ecological fallacy. Hence, the aim of the present study was: (1) to investigate whether the association between recent CVE and current conduct problems holds true for healthy controls as well as adolescents with a diagnosis of CD; (2) to examine whether the association is stable in both groups when including effects of aggression subtypes (proactive/reactive aggression), age, gender, site and socioeconomic status (SES); and (3) to test whether proactive or reactive aggression mediate the link between CVE and conduct problems. Data from 1178 children and adolescents (62% female; 44% CD) aged between 9 years and 18 years from seven European countries were analyzed. Conduct problems were assessed using the Kiddie-Schedule of Affective Disorders and Schizophrenia diagnostic interview. Information about CVE and aggression subtypes was obtained using self-report questionnaires (Social and Health Assessment and Reactive-Proactive aggression Questionnaire (RPQ), respectively). The association between witnessing community violence and conduct problems was significant in both groups (adolescents with CD and healthy controls). The association was also stable after examining the mediating effects of aggression subtypes while including moderating effects of age, gender and SES and controlling for effects of site in both groups. There were no clear differences between the groups in the strength of the association between witnessing violence and conduct problems. However, we found evidence for a ceiling effect, i.e., individuals with very high levels of conduct problems could not show a further increase if exposed to CVE and vice versa. Results indicate that there was no evidence for an ecological fallacy being the primary cause of the association, i.e., CVE must be considered a valid risk factor in the etiology of CD.

Journal of the American Academy of Child and Adolescent Psychiatry 56(8), 703-712 (2017). doi:10.1016/j.jaac.2017.05.015, Published by Elsevier, Kidlington [u.a.]