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Background Conduct disorder (CD) and oppositional defiant disorder (ODD) both convey a high risk for maladjustment later in life and are understudied in girls. Here, we aimed at confirming the efficacy of START NOW, a cognitive‐behavioral, dialectical behavior therapy‐oriented skills training program aiming to enhance emotion regulation skills, interpersonal and psychosocial adjustment, adapted for female adolescents with CD or ODD. Methods A total of 127 girls were included in this prospective, cluster randomized, multi‐center, parallel group, quasi‐randomized, controlled phase III trial, which tested the efficacy of START NOW (n = 72) compared with standard care (treatment as usual, TAU, n = 55). All female adolescents had a clinical diagnosis of CD or ODD, were 15.6 (±1.5) years on average (range: 12–20 years), and were institutionalized in youth welfare institutions. The two primary endpoints were the change in number of CD/ODD symptoms between (1) baseline (T1) and post‐treatment (T3), and (2) between T1 and 12‐week follow‐up (T4). Results Both treatment groups showed reduced CD/ODD symptoms at T3 compared with T1 (95% CI: START NOW = −4.87, −2.49; TAU = −4.94, −2.30). There was no significant mean difference in CD/ODD symptom reduction from T1 to T3 between START NOW and TAU (−0.056; 95% CI = −1.860, 1.749; Hedge's g = −0.011). However, the START NOW group showed greater mean symptom reduction from T1 to T4 (−2.326; 95% CI = −4.274, −0.378; Hedge's g = −0.563). Additionally, secondary endpoint results revealed a reduction in staff reported aggression and parent‐reported irritability at post assessment. Conclusions Although START NOW did not result in greater symptom reduction from baseline to post‐treatment compared with TAU, the START NOW group showed greater symptom reduction from baseline to follow‐up with a medium effect size, which indicates a clinically meaningful delayed treatment effect.

Conduct Disorder (CD) is an impairing psychiatric disorder of childhood and adolescence characterized by aggressive and dissocial behavior. Environmental factors such as maternal smoking during pregnancy, socio-economic status, trauma, or early life stress are associated with CD. Although the number of females with CD is rising in Western societies, CD is under-researched in female cohorts. We aimed at exploring the epigenetic signature of females with CD and its relation to psychosocial and environmental risk factors. We performed HpaII sensitive genome-wide methylation sequencing of 49 CD girls and 50 matched typically developing controls and linear regression models to identify differentially methylated CpG loci (tags) and regions. Significant tags and regions were mapped to the respective genes and tested for enrichment in pathways and brain developmental processes. Finally, epigenetic signatures were tested as mediators for CD-associated risk factors. We identified a 12% increased methylation 5’ of the neurite modulator SLITRK5 (FDR = 0.0046) in cases within a glucocorticoid receptor binding site. Functionally, methylation positively correlated with gene expression in lymphoblastoid cell lines. At systems-level, genes (uncorr. P < 0.01) were associated with development of neurons, neurite outgrowth or neuronal developmental processes. At gene expression level, the associated gene-networks are activated perinatally and during early childhood in neocortical regions, thalamus and striatum, and expressed in amygdala and hippocampus. Specifically, the epigenetic signatures of the gene network activated in the thalamus during early childhood correlated with the effect of parental education on CD status possibly mediating its protective effect. The differential methylation patterns identified in females with CD are likely to affect genes that are expressed in brain regions previously indicated in CD. We provide suggestive evidence that protective effects are likely me

Background: Conduct disorder (CD) rarely occurs alone but is typically accompanied by comorbid psychiatric disorders, which complicates the clinical presentation and treatment of affected youths. The aim of this study was to investigate sex differences in comorbidity pattern in CD and to systematically explore the ‘gender paradox’ and ‘delayed-onset pathway’ hypotheses of female CD. Methods: As part of the FemNAT-CD multisite study, semistructured clinical interviews and rating scales were used to perform a comprehensive phenotypic characterization of 454 girls and 295 boys with CD (9–18 years), compared to 864 sex- and age-matched typically developing controls. Results: Girls with CD exhibited higher rates of current major depression, anxiety disorders, post-traumatic stress disorder and borderline personality disorder, whereas boys with CD had higher rates of current attention-deficit/hyperactivity disorder. In line with the ‘gender paradox’ hypothesis, relative to boys, girls with CD showed significantly more lifetime psychiatric comorbidities (incl. Alcohol Use Disorder), which were accompanied by more severe CD symptoms. Female and male youths with CD also differed significantly in their CD symptom profiles and distribution of age-of-onset subtypes of CD (i.e. fewer girls with childhood-onset CD). In line with the ‘delayed-onset pathway’ hypothesis, girls with adolescent-onset CD showed similar levels of dimensional psychopathology like boys with childhood-onset CD, while boys with adolescent-onset CD had the lowest levels of internalizing psychopathology. Conclusions: Within the largest study of CD in girls performed to date, we found compelling evidence for sex differences in comorbidity patterns and clinical presentation of CD. Our findings further support aspects of the ‘gender paradox’ and ‘delayed-onset pathway’ hypotheses by showing that girls with CD had higher rates of comorbid lifetime mental disorders and functional impairments, and they usually deve

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.

BACKGROUND: Conduct disorder (CD), which is characterized by severe aggressive and antisocial behavior, is linked to emotion processing and regulation deficits. However, the neural correlates of emotion regulation are yet to be investigated in adolescents with CD. Furthermore, it remains unclear whether CD is associated with deficits in emotional reactivity, emotion regulation, or both. METHODS: We used functional magnetic resonance imaging to study effortful emotion regulation by cognitive reappraisal in 59 female adolescents 15 to 18 years of age (30 with a CD diagnosis and 29 typically developing (TD) control adolescents). RESULTS: Behaviorally, in-scanner self-report ratings confirmed successful emotion regulation within each group individually but significant group differences in emotional reactivity and reappraisal success when comparing the groups (CD < TD). Functional magnetic resonance imaging results revealed significantly lower activation in left dorsolateral prefrontal cortex and angular gyrus in CD compared with TD adolescents during emotion regulation, but no group differences for emotional reactivity. Furthermore, connectivity between left dorsolateral prefrontal cortex and the bilateral putamen, right prefrontal cortex, and amygdala was reduced in CD compared with TD adolescents during reappraisal. Callous-unemotional traits were unrelated to neural activation, but these traits correlated negatively with behavioral reports of emotional reactivity. CONCLUSIONS: Our results demonstrate reduced prefrontal brain activity and functional connectivity during effortful emotion regulation in female adolescents with CD. This sheds light on the neural basis of the behavioral deficits that have been reported previously. Future studies should investigate whether cognitive interventions are effective in enhancing emotion-regulation abilities and/or normalizing prefrontal and temporoparietal activity in female adolescents with CD.

The aim of the present study was to test if a cognitive strategy improves older adults' prospective memory performance in a naturalistic health task. Moreover, it was tested if a possible strategy effect is moderated by individual differences. Therefore, a group of older adults was asked to perform a task taken from the medication adherence literature (i.e., blood pressure monitoring). Half of them were asked to form implementation intentions. Additionally, crystallized pragmatics and fluid mechanics, conscientiousness, self-efficacy, and lifestyle factors were assessed as possible moderators. Results showed a strong positive strategy effect on prospective memory. Moreover, the effect was qualified by a significant interaction and only emerged for participants with low levels in fluid mechanics. No other moderator showed an effect. In conclusion, an enhancing effect of implementation intentions on prospective memory seems to be dependent on individual differences in cognitive capacity and less related to key motivational or personality variables.

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 ( = 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 cal

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 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.

Objective: Previous studies have reported reduced cortical thickness and surface area and altered gyrification in frontal and temporal regions in adolescents with conduct disorder (CD). Although there is evidence that the clinical phenotype of CD differs between males and females, no studies have examined whether such sex differences extend to cortical and subcortical structure. Method: As part of a European multisite study (FemNAT-CD), structural magnetic resonance imaging (MRI) data were collected from 48 female and 48 male participants with CD and from 104 sex-, age-, and pubertal-status−matched controls (14–18 years of age). Data were analyzed using surface-based morphometry, testing for effects of sex, diagnosis, and sex-by-diagnosis interactions, while controlling for age, IQ, scan site, and total gray matter volume. Results: CD was associated with cortical thinning and higher gyrification in ventromedial prefrontal cortex in both sexes. Males with CD showed lower, and females with CD showed higher, supramarginal gyrus cortical thickness compared with controls. Relative to controls, males with CD showed higher gyrification and surface area in superior frontal gyrus, whereas the opposite pattern was seen in females. There were no effects of diagnosis or sex-by-diagnosis interactions on subcortical volumes. Results are discussed with regard to attention-deficit/hyperactivity disorder, depression, and substance abuse comorbidity, medication use, handedness, and CD age of onset. Conclusion: We found both similarities and differences between males and females in CD–cortical structure associations. This initial evidence that the pathophysiological basis of CD may be partly sex-specific highlights the need to consider sex in future neuroimaging studies and suggests that males and females may require different treatments.

The aim of the present study was to test if a cognitive strategy improves older adults' prospective memory performance in a naturalistic health task. Moreover, it was tested if a possible strategy effect is moderated by individual differences. Therefore, a group of older adults was asked to perform a task taken from the medication adherence literature (i.e., blood pressure monitoring). Half of them were asked to form implementation intentions. Additionally, crystallized pragmatics and fluid mechanics, conscientiousness, self-efficacy, and lifestyle factors were assessed as possible moderators. Results showed a strong positive strategy effect on prospective memory. Moreover, the effect was qualified by a significant interaction and only emerged for participants with low levels in fluid mechanics. No other moderator showed an effect. In conclusion, an enhancing effect of implementation intentions on prospective memory seems to be dependent on individual differences in cognitive capacity and less related to key motivational or personality variables.