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Voxel-based morphometry (VBM) studies of gray matter volume (GMV) in psychopathy have produced inconsistent results and few have been replicated. Therefore, to clarify GMV abnormalities associated with psychopathy as operationalized by Hare (2003), we conducted a meta-analysis of VBM studies using both categorical and dimensional analyses. We identified seven studies eligible for the categorical meta-analysis (136 men with psychopathy vs 150 male controls) and 11 studies (N = 519) eligible for dimensional metaregressions. First, we used seed-based d mapping with permutation of subject images for voxel-based meta-analyses. Statistical parametric maps of GMV were available for four (57%) of the studies included in the categorical meta-analysis and for five (45%) of the studies included in the dimensional metaregression analyses, with peak coordinates available for the remaining studies. Second, we used metadata of a large-scale neuroimaging database to provide an objective and quantitative account of psychological processes attributed to the brain regions we identified in our group meta-analysis and metaregressions. Men with psychopathy exhibited reliable GMV abnormalities circumscribed to the left hemisphere in the dorsolateral prefrontal cortex and the medial orbitofrontal cortex. Total psychopathy scores and Factors 1 and 2 scores were all related to decreased GMV within those two prefrontal regions, as well as decreased GMV in a wider set of regions encompassing midline, temporal, parietal, occipital, and subcortical structures. We discuss how decreased GMV in those regions likely account for the impairments in the emotion, cognition, action, and perception domains seen in the disorder. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

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.

Theory of mind (ToM), or the ability to infer and predict the intentions, thoughts and beliefs of others, involves cognitive perspective taking (cognitive ToM/cToM) and understanding emotions (affective ToM/aToM). While behavioral evidence indicates that ToM is influenced by sex and age, no study has examined the influence of these variables on the neural correlates of cToM and aToM in late childhood/adolescence. Using fMRI with 35 typically-developing youths (aged 9–18 years, 12 males), we investigated the influence of sex and age on the neural correlates of cToM and aToM. We also examined how callous-unemotional traits, indexing a lack of empathy, were related to brain responses during aToM. Across both conditions, we found convergent activity in ToM network regions, such as superior temporal sulcus/temporoparietal junction (TPJ) and precuneus across males and females, but males recruited the left TPJ significantly more than females during cToM. During aToM, age was negatively correlated with brain responses in frontal, temporal and posterior midline regions, while callous-unemotional traits were positively correlated with right anterior insula responses. These results provide the first evidence in youth that sex influences the neural correlates of cToM, while age and callous-unemotional traits are specifically related to brain responses during aToM.

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.

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

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.

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.

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.

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.]

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.

Speech perception and comprehension are often challenged by the need to recognize speech sounds that are degraded or ambiguous. Here, we explore the cognitive and neural mechanisms involved in resolving ambiguity in the identity of speech sounds using syllables that contain ambiguous phonetic segments (e.g., intermediate sounds between /b/ and /g/ as in “blade” and “glade”). We used an audio-morphing procedure to create a large set of natural sounding minimal pairs that contain phonetically ambiguous onset or offset consonants (differing in place, manner, or voicing). These ambiguous segments occurred in different lexical contexts (i.e., in words or pseudowords, such as blade–glade or blem–glem) and in different phonological environments (i.e., with neighboring syllables that differed in lexical status, such as blouse–glouse). These stimuli allowed us to explore the impact of phonetic ambiguity on the speed and accuracy of lexical decision responses (Experiment 1), semantic categorization responses (Experiment 2), and the magnitude of BOLD fMRI responses during attentive comprehension (Experiment 3). For both behavioral and neural measures, observed effects of phonetic ambiguity were influenced by lexical context leading to slower responses and increased activity in the left inferior frontal gyrus for high-ambiguity syllables that distinguish pairs of words, but not for equivalent pseudowords. These findings suggest lexical involvement in the resolution of phonetic ambiguity. Implications for speech perception and the role of inferior frontal regions are discussed.

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.]

Transcranial magnetic stimulation (TMS) has proven to be a useful tool in investigating the role of the articulatory motor cortex in speech perception. Researchers have used single-pulse and repetitive TMS to stimulate the lip representation in the motor cortex. The excitability of the lip motor representation can be investigated by applying single TMS pulses over this cortical area and recording TMS-induced motor evoked potentials (MEPs) via electrodes attached to the lip muscles (electromyography; EMG). Larger MEPs reflect increased cortical excitability. Studies have shown that excitability increases during listening to speech as well as during viewing speech-related movements. TMS can be used also to disrupt the lip motor representation. A 15-min train of low-frequency sub-threshold repetitive stimulation has been shown to suppress motor excitability for a further 15-20 min. This TMS-induced disruption of the motor lip representation impairs subsequent performance in demanding speech perception tasks and modulates auditory-cortex responses to speech sounds. These findings are consistent with the suggestion that the motor cortex contributes to speech perception. This article describes how to localize the lip representation in the motor cortex and how to define the appropriate stimulation intensity for carrying out both single-pulse and repetitive TMS experiments.