Identifying cortical structure markers of resilience to adversity in young people using surface-based morphometry

Previous research on the neurobiological bases of resilience in youth has largely used categorical definitions of resilience and voxel-based morphometry methods that assess gray matter volume. However, it is important to consider brain structure more broadly as different cortical properties have distinct developmental trajectories. To address these limitations, we used surface-based morphometry and data-driven, continuous resilience scores to examine associations between resilience and cortical structure. Structural MRI data from 286 youths (Mage = 13.6 years, 51% female) who took part in the European multi-site FemNAT-CD study were pre-processed and analyzed using surface-based morphometry. Continuous resilience scores were derived for each participant based on adversity exposure and levels of psychopathology using the residual regression method. Vertex-wise analyses assessed for correlations between resilience scores and cortical thickness, surface area, gyrification and volume. Resilience scores were positively associated with right lateral occipital surface area and right superior frontal gyrification and negatively correlated with left inferior temporal surface area. Moreover, sex-by-resilience interactions were observed for gyrification in frontal and temporal regions. Our findings extend previous research by revealing that resilience is related to surface area and gyrification in frontal, occipital and temporal regions that are implicated in emotion regulation and face or object recognition

Sex-specific associations of basal steroid hormones and neuropeptides with Conduct Disorder and neuroendocrine mediation of environmental risk

Conduct Disorder (CD) is characterized by severe aggressive and antisocial behavior. The stress hormone system has frequently been investigated as a neurobiological correlate of CD, while other interacting neuroendocrine biomarkers of sex hormone or neuropeptide systems have rarely been studied, especially in females. We examined multiple basal neuroendocrine biomarkers in female and male adolescents with CD compared to healthy controls (HCs), and explored whether they mediate effects of environmental risk factors on CD. Within the FemNAT-CD study, salivary cortisol, alpha-amylase, testosterone, dehydroepiandrosterone-sulfate (DHEA-S), estradiol, progesterone, oxytocin, and arginine-vasopressin were measured under basal conditions in 166 pubertal adolescents with CD, and 194 sex-, age-, and puberty-matched HCs (60% females, 9-18 years). Further, environmental risk factors were assessed. Single hormone analyses showed higher DHEA-S, and lower estradiol and progesterone levels in both females and males with CD relative to HCs. When accounting for interactions between neuroendocrine systems, a male-specific sex hormone factor (testosterone/DHEA-S) predicted male CD, while estradiol and a stress-system factor (cortisol/alpha-amylase) interacting with oxytocin predicted female CD. Estradiol, progesterone, and oxytocin partly explained associations between early environmental risk and CD. Findings provide evidence for sex-specific associations between basal neuroendocrine measures and CD. Especially altered sex hormones (androgen increases in males, estrogen reductions in females) robustly related to CD, while basal stress-system measures did not. Early environmental risk factors for CD may act partly through their effects on the neuroendocrine system, especially in females. Limitations (e.g., basal neuroendocrine assessment, different sample sizes per sex, pubertal participants, exploratory mediation analyses) are discussed

Relational aggression in adolescents with conduct disorder:sex differences and behavioral correlates

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

Investigating Sex Differences in Emotion Recognition, Learning, and Regulation among Youths with Conduct Disorder

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.</p

Positive and Negative Parenting in Conduct Disorder with High versus Low Levels of Callous-Unemotional Traits

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- A nd 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

Community Violence Exposure and Conduct Problems in Children and Adolescents with Conduct Disorder and Healthy Controls

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

Community Violence Exposure and Conduct Problems in Children and Adolescents with Conduct Disorder and Healthy Controls

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

Resting autonomic nervous system activity is unrelated to antisocial behaviour dimensions in adolescents: Cross-sectional findings from a European multi-centre study

Purpose: Autonomic nervous system (ANS) functioning has long been studied in relation to antisocial behaviour, but relevant measures (heart rate, heart rate variability, pre-ejection period, respiration rate) have rarely been considered together. This study investigated the relationship between these measures and antisocial behaviour. Methods: Using a sample of 1010 youths with (47.8%) and without conduct disorder (52.2%) aged between 9 and 18. years (659 females, 351 males, mean age = 14.2. years, SD = 2.4), principal component analysis (PCA) was applied to various measures of psychopathology and antisocial behavior. Structural equation modelling was performed in order to test whether the ANS measures predicted PCA-dimensions. Cluster analysis was used in order to classify patterns of ANS activity. Analyses were performed separately for males/females and controlled for body-mass-index, age, caffeine use, cigarette smoking, sports, socioeconomic status, medication, cardiac problems. Results: The PCA yielded three components: antisocial behaviour/comorbid psychopathology, narcissistic traits, and callous-unemotional traits. ANS measures were only weakly correlated with these components. Cluster analysis yielded high and low arousal clusters in both sexes. When controlling for covariates, all associations disappeared. Conclusion: Our findings suggest that resting ANS measures are only weakly related to antisocial behaviour and indicate that smoking should be considered as an important covariate in future psychophysiological studies

Sex differences in risk-based decision-making in adolescents with conduct disorder

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