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Objective: Conduct disorder (CD) involves aggressive and antisocial behavior and is associated with blunted cortisol stress response in male youths. Far less is known about cortisol stress responsivity in female youths with CD or other neuroendocrine responses in both sexes. Although CD is linked to early adversity, the possibility that neuroendocrine alterations may mediate the relationship between early adversity and CD has not been systematically investigated.Method: Within the European FemNAT-CD multi-site study, salivary cortisol, testosterone, the testosterone/cortisol ratio, oxytocin, and psychological stress response to a standardized psychosocial stress test (the Trier Social Stress Test [TSST]), together with common pre- and postnatal environmental risk factors, were investigated in 130 pubertal youths with CD (63% female, 9-18 years of age) and 160 sex-, age-, and puberty-matched healthy controls (HCs).Results: The TSST induced psychological stress in both CD and HCs. In contrast, female and male youths with CD showed blunted cortisol, testosterone, oxytocin, and testosterone/cortisol stress responses compared to HCs. These blunted stress responses partly mediated the relationship between environmental risk factors and CD.Conclusion: Findings from this unique sample, including many female youths with CD, provide evidence for a widespread attenuated stress responsivity of not only stress hormones, but also sex hormones and neuropeptides in CD and its subgroups (eg, with limited prosocial emotions). Results are the first to demonstrate blunted neuroendocrine stress responses in both female and male youths with CD. Early adversity may alter neuroendocrine stress responsivity. Biological mechanisms should be investigated further to pave the way for personalized intervention, thereby improving treatments for CD. [ABSTRACT FROM AUTHOR]

Background: This article reports reliability, validity, and norms for the German version of the multi-informant questionnaire Inventory of Callous–Unemotional Traits (ICU). Method: The ICU was filled in by nonreferred children aged 13 to 18 years old (n = 645), parents of children aged 6 to 18 years old (n = 1,005), and their teachers (n = 955). Results: Confirmatory factor analysis resulted in a two-factor solution giving the best fit. Still none of the models showed an adequate model-fit applying the chi-square exact fit test. The internal consistency of the parent's, teacher's, and self-report version were α =.830, α =.877 and α =.769, respectively. Interrater reliability was moderate. Convergent validity with the Youth Psychopathic Traits Inventory, the externalizing scores of the Youth Self-Report/Child Behavior Checklist, and with the German oppositional Defiant Disorder/Conduct Disorder Rating Scale "FBB-SSV" were good. German norms were calculated. Conclusions: The ICU is a reliable and valid dimensional measure to describe callous–unemotional traits. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Youth with disruptive behavior disorders (DBD; Oppositional defiant disorder and/or conduct disorder) are known to show impaired social relationships. Little is known about positive (PFQ) and negative best friendship quality (NFQ) in youth with DBD, and their relations with DBD specific symptoms such as aggression subtypes, empathic abilities, and callous unemotional (CU)-traits. The current study includes N = 115 youth with and N = 146 without DBD (Mage = 13.98, SD = 2.2). A diagnostic interview and self-rating questionnaires assessed ODD/CD diagnosis, friendship quality, aggression, empathy, and CU-traits. When examined on a categorical level, youth with and without DBD did not differ in friendship quality. On a dimensional level across groups, perspective taking was positively associated with PFQ. Proactive aggression was positively associated with NFQ. CU-traits in females were positively, while CU-traits in males were negatively, associated with NFQ. Results highlight that behavioral and cognitive symptoms, rather than clinical categories, are important to consider when discussing friendship qualities. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Evidence of alterations in emotion processing in maltreated youth has been hypothesized to reflect latent vulnerability for psychopathology. However, previous studies have not systematically examined the influence of psychopathology on the results. Here, we examined emotion recognition and learning in youth who differed in terms of presence vs. absence of maltreatment and psychopathology and tested for potential sex effects. Maltreatment and psychopathology were assessed in 828 youth (514 females) aged 9–18 years using diagnostic interviews and self- and parent-report questionnaires. Emotion recognition was assessed via identification of morphed facial expressions of six universal emotions. For emotion learning, reward and punishment values were assigned to novel stimuli and participants had to learn to correctly respond/withhold response to stimuli to maximize points. A three-way interaction of maltreatment by psychopathology by emotion indicated that when psychopathology was low, maltreated youth were less accurate than non-maltreated youth for happy, fear and disgust. A three-way interaction of sex, maltreatment and emotion indicated that maltreated girls and boys were impaired for fear, but girls showed an impairment for happy, while boys for disgust. There were no effects of maltreatment, psychopathology, or sex on reward learning. However, a two-way interaction between sex and maltreatment showed that maltreated girls were worse at learning from punishment relative to non-maltreated girls, while maltreated boys were better than non-maltreated boys. The study provides the first clear evidence of latent-vulnerability in emotion recognition in maltreated youth and suggests that girls and boys might be characterized by distinct profiles of emotion recognition and learning following maltreatment. [ABSTRACT FROM AUTHOR]

Due to modern technological innovations, aggressive behaviors have expanded into the cyberspace, creating a new matter of public concern: cyberbullying. Antisocial and aggressive behaviors, including bullying are characteristic for children and adolescents diagnosed with conduct disorder (CD), raising the question whether these youths are highly involved in cyberbullying experiences, too. 206 participants with CD versus typically developing controls (TDCs) aged 9–19 years (57% girls) were included in the study. Individuals completed several self-report measures investigating cyber- and traditional bullying experiences, and hierarchical multiple regression analyses were conducted to explain the relationship between cyberbullying victimization and perpetration with demographic and clinical variables. Experiences of cyberbullying victimization and perpetration were significantly higher among youth with CD compared to TDCs, and this was accompanied by significantly higher scores on a measure of traditional bullying in CD versus TDCs. CD diagnosis, female sex and higher levels of callous-unemotional (CU) traits were each uniquely associated with increased experiences of cyberbullying victimization, whereas CD diagnosis, higher levels of CU traits and older age were each uniquely associated with increased experiences of cyberbullying perpetration. Individuals with CD, compared to TDCs are at higher risk of becoming cyberbully victims and perpetrators, hence representing an important novel aspect in the assessment and treatment of these youths. [ABSTRACT FROM AUTHOR]

Abstract Oxytocin (OXT) shows anxiolytic and stress-reducing effects, but salivary OXT response to laboratory-induced stress has only been assessed in one study in healthy adults. The present study aimed at extending these findings by assessing salivary OXT stress reactivity in healthy adolescents (aged 11–18) compared to a control condition. A higher salivary OXT response to stress compared to the control condition was expected. In addition, the association between OXT, cortisol (CORT) and psychological reactivity patterns was explored. Psychosocial stress was induced using the Trier Social Stress Test (TSST; 13 males, 15 females), while the Control-TSST (14 males, 15 females) served as a non-stress control condition. Salivary OXT increased in response to the TSST with a peak at +1 and decline at +10 min after stress. Baseline OXT correlated negatively with experienced anxiety and insecurity, while both correlated positively with OXT reactivity. OXT and CORT increase as well as OXT increase and CORT recovery were positively correlated. Results indicate that salivary OXT in response to the TSST is a valid method to assess biological effects of laboratory-induced stress also in adolescents. Due to a rapid increase and decline, salivary OXT needs to be assessed directly after stress exposure. Given the interplay of OXT with affective symptoms and CORT response, the combined measure of salivary OXT and CORT reactivity adds to studying stress reactivity in typically developing and clinical samples. Highlights • Salivary oxytocin (OXT) is responsive to stress in healthy adolescents. • Salivary OXT needs to be assessed soon after the stress task due to fast increase. • Salivary OXT peaked and returned to baseline levels earlier than salivary cortisol. • OXT and cortisol appear to be co-activated in response to stress. • High baseline OXT levels were related to low anxiety and insecurity feelings. [ABSTRACT FROM AUTHOR]

With increasing frequency, clinical and laboratory-based mycologists are consulted on invasive fungal diseases caused by rare fungal species. This review aims to give an overview of the management of invasive aspergillosis (IA) caused by non-fumigatus Aspergillus spp.—namely A. flavus, A. terreus, A. niger and A. nidulans—including diagnostic and therapeutic differences and similarities to A. fumigatus. A. flavus is the second most common Aspergillus spp. isolated in patients with IA and the predominant species in subtropical regions. Treatment is complicated by its intrinsic resistance against amphotericin B (AmB) and high minimum inhibitory concentrations (MIC) for voriconazole. A. nidulans has been frequently isolated in patients with long-term immunosuppression, mostly in patients with primary immunodeficiencies such as chronic granulomatous disease. It has been reported to disseminate more often than other Aspergillus spp. Innate resistance against AmB has been suggested but not yet proven, while MICs seem to be elevated. A. niger is more frequently reported in less severe infections such as otomycosis. Triazoles exhibit varying MICs and are therefore not strictly recommended as first-line treatment for IA caused by A. niger, while patient outcome seems to be more favorable when compared to IA due to other Aspergillus species. A. terreus-related infections have been reported increasingly as the cause of acute and chronic aspergillosis. A recent prospective international multicenter surveillance study showed Spain, Austria, and Israel to be the countries with the highest density of A. terreus species complex isolates collected. This species complex seems to cause dissemination more often and is intrinsically resistant to AmB. Non-fumigatus aspergillosis is difficult to manage due to complex patient histories, varying infection sites and potential intrinsic resistances to antifungals. Future investigational efforts should aim at amplifying the knowledge on specific diagnostic measures and their on-site availability, as well as defining optimal treatment strategies and outcomes of non-fumigatus aspergillosis. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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 developed CD during adolescence. These novel data on sex‐specific clinical profiles of CD will be critical in informing intervention and prevention programmes. [ABSTRACT FROM AUTHOR]

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 mediated by epigenetic mechanisms impairing specific brain developmental networks and therefore exerting a long-term effect on neural functions in CD. Our results are exploratory and thus, further replication is needed. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

The aim of this study was to assess a recently established 3D model of congenital ichthyosis, representing severe epidermal barrier function defects, for skin penetration and permeation. We have generated disease models by knock-down of either TGM1 or ALOXE3 in primary human keratinocytes, and using keratinocytes and fibroblasts from patients with congenital ichthyosis. The results indicate disturbed barrier function as demonstrated by increased permeation of testosterone and caffeine particularly in TGM1 knock-down models compared to control models. In addition, enhanced penetration of the model dye nile red incorporated into solid lipid nanoparticles and core-multishell nanotransporters, respectively, was evident in disease models. Thus, in vitro skin disease models reproduce differences in barrier permeability and function seen in congenital ichthyosis and pave the way to personalised disease models. Furthermore, our findings indicate that nanocarriers may be useful in new, topical therapeutic approaches for the currently very limited treatment of congenital ichthyosis. [ABSTRACT FROM AUTHOR]

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). 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. 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. 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. • First large psychophysiological study on females with Conduct Disorder (CD). • Autonomic Nervous System (ANS) activity did not distinguish CD from controls. • CD females with internalizing comorbidity (INT) have lower parasympathetic activity. • CD subgroups with callous-unemotional traits did not show deviant ANS activity. • No overall relation between CD and ANS, but CD + INT show deviant ANS activity. [ABSTRACT FROM AUTHOR]

Introduction Drug-induced liver injury (DILI) is the 4th most common cause of liver damage in Western countries and can be caused by antidepressants. Methods Against the background of increasing antidepressant prescriptions and increasing use of polypharmacy, we analyzed administered antidepressants and other pharmacological substances, liver toxicity, comorbid somatic secondary diseases together with the occurrence of DILI in a patient population of 6 centers throughout Germany. Results The majority of the enrolled 329 patients received polypharmacological treatment in an inpatient setting. During antidepressant treatment 5.1% of the patients had elevated serum transaminase levels, whereby exactly and not more than 1 criterion proposed to be indicative for DILI, was fulfilled by 3 patients (0.9%). Discussion During patient characterization it becomes clear that a sensitization for relevant risk constellations causing liver injury in MDD patients is relevant to prevent further serious adverse events. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background: In Europe, the number of females exhibiting oppositional defiant disorder (ODD) and conduct disorder (CD) is growing. Many of these females live in youth welfare institutions. Consequently, there is a great need for evidence-based interventions within youth welfare settings. A recently developed approach targeting the specific needs of girls with ODD and CD in residential care is START NOW. The aim of this group-based behavioural skills training programme is to specifically enhance emotional regulation capacities to enable females with CD or ODD to appropriately deal with daily-life demands. It is intended to enhance psychosocial adjustment and well-being as well as reduce oppositional and aggressive behaviour. We present the study protocol (version 4.1; 10 February 2016) of the FemNAT-CD intervention trial titled 'Group-Based Treatment of Adolescent Female Conduct Disorders: The Central Role of Emotion Regulation'. Methods/design: The study is a prospective, confirmatory, cluster-randomised, parallel-group, multi-centre, randomised controlled trial with 128 institutionalised female adolescents who fulfil the diagnostic criteria of ODD and/or CD. Institutions/wards will be randomised either to provide the 12-week skills training as an add-on intervention or to provide treatment as usual. Once the first cycle is completed, each institution will run a second cycle with the opposite condition. Primary endpoints are the pre-post change in number of CD/ODD symptoms as assessed by a standardised, semi-structured psychiatric interview (Kiddie Schedule for Affective Disorders and Schizophrenia for School-Age Children-Present and Lifetime, CD/ODD section) between baseline and the end of intervention, as well as between baseline and a 3-month follow-up point. Secondary objectives include pre-post change in CD/ODD-related outcome measures, most notably emotional regulation on a behavioural and neurobiological level after completion of START NOW compared with treatment as usual. Discussion: To our knowledge, this study is the first to date to systematically investigate the effectiveness of an adapted integrative psychosocial intervention designed for female adolescents with ODD and CD in youth welfare settings. [ABSTRACT FROM AUTHOR]

Generalized peeling skin disease is an autosomal-recessive ichthyosiform erythroderma characterized by lifelong patchy peeling of the skin. After genome-wide linkage analysis, we have identified a homozygous nonsense mutation in CDSN in a large consanguineous family with generalized peeling skin, pruritus, and food allergies, which leads to a complete loss of corneodesmosin. In contrast to hypotrichosis simplex, which can be associated with specific dominant CDSN mutations, peeling skin disease is characterized by a complete loss of CDSN expression. The skin phenotype is consistent with a recent murine Cdsn knockout model. Using three-dimensional human skin models, we demonstrate that lack of corneodesmosin causes an epidermal barrier defect supposed to account for the predisposition to atopic diseases, and we confirm the role of corneodesmosin as a decisive epidermal adhesion molecule. Therefore, peeling skin disease will represent a new model disorder for atopic diseases, similarly to Netherton syndrome and ichthyosis vulgaris in the recent past. [ABSTRACT FROM AUTHOR]

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. 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. 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. 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. • Respiration rate and antisocial behaviour were positively associated in females. • Covariates rendered links between the ANS and antisocial behaviour non-significant. • For both sexes, a low and a high arousal cluster arose. • Smoking was strongly related to antisocial behaviour and comorbid psychopathology. [ABSTRACT FROM AUTHOR]

Highlights from the article: B Abstract: b Conduct Disorder (CD) is an impairing psychiatric disorder of childhood and adolescence characterized by aggressive and dissocial behavior. We have now explored the genome wide methylation signature of 50 girls with CD and 50 matched controls and translated findings from differential methylation analysis to gene expression signatures of human brain development. The environmental risk factors associated with CD may exert their consequences by differentially altering epigenetic patterns of specific gene networks regulating brain development.

A correction to the article "START NOW - a comprehensive skills training programme for female adolescents with oppositional defiant and conduct disorders: study protocol for a cluster randomised controlled trial" which was published online on March 2, 2017 is presented.