From preparation to post-processing: Insights into evoked and induced cortical activity during pre-cued motor reactions in children and adolescents.

INTRODUCTION: The motor system undergoes significant development throughout childhood and adolescence. The contingent negative variation (CNV), a brain response reflecting preparation for upcoming actions, offers valuable insights into these changes. However, previous CNV studies of motor preparation have primarily focused on adults, leaving a gap in our understanding of how cortical activity related to motor planning and execution matures in children and adolescents. METHODS: The study addresses this gap by investigating the maturation of motor preparation, pre-activation, and post-processing in 46 healthy, right-handed children and adolescents aged 5-16 years. To overcome the resolution limitations of previous studies, we combined 64-electrode high-density Electroencephalography (EEG) and advanced analysis techniques, such as event-related potentials (ERPs), mu-rhythm desynchronization as well as source localization approaches. The combined analyses provided an in-depth understanding of cortical activity during motor control. RESULTS: Our data showed that children exhibited prolonged reaction times, increased errors, and a distinct pattern of cortical activation compared to adolescents. The findings suggest that the supplementary motor area (SMA) plays a progressively stronger role in motor planning and response evaluation as children age. Additionally, we observe a decrease in sensory processing and post-movement activity with development, potentially reflecting increased efficiency. Interestingly, adolescent subjects, unlike young adults in previous studies, did not yet show contralateral activation of motor areas during the motor preparation phase (late CNV). CONCLUSION: The progressive increase in SMA activation and distinct cortical activation patterns in younger participants suggest immature motor areas. These immature regions might be a primary cause underlying the age-related increase in motor action control efficiency. Additionally, the study demonstrates a prolonged maturation of cortical motor areas, extending well into early adulthood, challenging the assumption that motor control is fully developed by late adolescence. This research, extending fundamental knowledge of motor control development, offers valuable insights that lay the foundation for understanding and treating motor control difficulties.

Towards a youth mental health paradigm: a perspective and roadmap.

Most mental disorders have a typical onset between 12 and 25 years of age, highlighting the importance of this period for the pathogenesis, diagnosis, and treatment of mental ill-health. This perspective addresses interactions between risk and protective factors and brain development as key pillars accounting for the emergence of psychopathology in youth. Moreover, we propose that novel approaches towards early diagnosis and interventions are required that reflect the evolution of emerging psychopathology, the importance of novel service models, and knowledge exchange between science and practitioners. Taken together, we propose a transformative early intervention paradigm for research and clinical care that could significantly enhance mental health in young people and initiate a shift towards the prevention of severe mental disorders.

START NOW: a cognitive behavioral skills training for adolescent girls with conduct or oppositional defiant disorder - a randomized clinical trial.

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.

Intra-individual cortical networks in Anorexia Nervosa: Evidence from a longitudinal dataset.

OBJECTIVE: This work investigates cortical thickness (CT) and gyrification patterns in Anorexia Nervosa (AN) before and after short-term weight restoration using graph theory tools. METHODS: 38 female adolescents with AN underwent structural magnetic resonance imaging scans at baseline and after - on average - 3.5 months following short-term weight restoration while 53 age-matched healthy controls (HCs) were scanned once. Graph measures were compared between groups and longitudinally within the AN group. Associations with clinical measures such as age of onset, duration of illness, BMI standard deviation score (BMI-SDS), and longitudinal weight changes were tested via stepwise regression. RESULTS: Cortical thickness graphs of patients with acute AN displayed lower modularity and small-world index (SWI) than HCs. Modularity recovered after weight gain. Reduced global efficiency and SWI were observed in patients at baseline compared to HCs based on gyrification networks. Significant associations between local clustering of CT at admission and BMI-SDS, and clustering/global efficiency of gyrification and duration of illness emerged. CONCLUSIONS: Our results indicate a shift towards less organised CT networks in patients with acute AN. After weight recovery, the disarrangement seems to be partially reduced. However, longer-term follow-ups are needed to determine whether cortical organizational patterns fully return to normal.

Identifying structural brain markers of resilience to adversity in young people using voxel-based morphometry.

There is increasing evidence that resilience in youth may have a neurobiological basis. However, the existing literature lacks a consistent way of operationalizing resilience, often relying on arbitrary judgments or narrow definitions (e.g., not developing PTSD) to classify individuals as resilient. Therefore, this study used data-driven, continuous resilience scores based on adversity and psychopathology to investigate associations between resilience and brain structure in youth. Structural MRI data from 298 youth aged 9-18 years (Mage = 13.51; 51% female) who participated in the European multisite FemNAT-CD study were preprocessed using SPM12 and analyzed using voxel-based morphometry. Resilience scores were derived by regressing data on adversity exposure against current/lifetime psychopathology and quantifying each individual's distance from the regression line. General linear models tested for associations between resilience and gray matter volume (GMV) and examined whether associations between resilience and GMV differed by sex. Resilience was positively correlated with GMV in the right inferior frontal and medial frontal gyri. Sex-by-resilience interactions were observed in the middle temporal and middle frontal gyri. These findings demonstrate that resilience in youth is associated with volume in brain regions implicated in executive functioning, emotion regulation, and attention. Our results also provide evidence for sex differences in the neurobiology of resilience.

The Development and Validation of the First German Open Scale of Social Information Processing.

INTRODUCTION: This study introduces the first German Open Scale of Social Information Processing (GOSSIP) and evaluates its psychometric properties. Even though social information processing (SIP) and its important role in developmental psychopathology is a rising field of interest, model-based standardized assessment tools are still scarce. METHODS: GOSSIP was developed to assess SI processes in boys and girls aged eight to 21 years. First, 61 vignettes (combinations of pictures and short written descriptions of the situation depicted) were evaluated by an expert group and piloted with 48 healthy participants (aged 8-21). The best-rated vignettes were then implemented in a Web-based application. 191 participants completed GOSSIP. Of those, 76 answered additional questionnaires to assess their social skills and psychopathology. Internal consistencies for the emotional and cognitive GOSSIP scales were determined. Latent profile analysis (LPA) was used to identify subgroups of children and adolescents characterized by specific SIP profiles (i.e., patterns of emotional, cognitive, and behavioral responses to the GOSSIP). Furthermore, the external validity of the participants' attribution tendencies in GOSSIP was evaluated in real life by smartphone-based Ecological Momentary Assessments (EMA). RESULTS: The internal consistencies for the emotional and cognitive scales (angry, ashamed, physical aggression, pro-social response, revenge, and outcome expectancy) were good to excellent. The scales of hostile interpretation, relation aggression, sadness, and exclusion showed borderline/acceptable internal consistency. Correlation analysis confirmed convergent validity with self-reported social skills and external validity with ratings of aggressive and pro-social behaviors. The LPA revealed three profiles as the best fit of the data. The first group is named "aggressors," the second "social-emotional group," and a third named "ashamed-internalizing group." However, no significant association was found between the attribution tendencies derived from GOSSIP and EMA data. DISCUSSION/CONCLUSION: GOSSIP is the first model-based German Web-based assessment for several SIP mechanisms that showed overall adequate psychometric properties. GOSSIP can be used to classify individuals into SIP profiles that differ in terms of their cognitive and emotional response tendencies and therefore could contribute to the development of targeted interventions. Integrating assessments of emotional responses into GOSSIP revealed an important role of "shame" in SIP and the development of psychopathology. Furthermore, the lack of external validity between GOSSIP and EMA calls into question how attribution tendencies are best assessed in future studies.

Challenging the Sensitive Window Hypothesis: Timing Effects of Maternal Depressive Symptoms on the Intergenerational Transmission of Maltreatment and Psychopathology in the Next Generation.

OBJECTIVE: The current study explored the role of maternal depressive symptoms in the intergenerational transmission of childhood maltreatment and developmental psychopathology. Based on the sensitive window hypothesis, the effects of earlier versus later maternal depression symptoms on child development were analysed. METHOD: Ninety-nine mother-child dyads, 65% of which had high-risk teenage mothers, participated in a longitudinal study with three assessments in the first 18 months of the child's life (T1-T3) and a 4th reassessment (T4) at the child's preschool age. Using serial mediation analyses, we tested whether the relationship between the mother's own maltreatment history (Childhood Experience of Care and Abuse Questionnaire) and the child's psychopathological outcome at preschool age was mediated in a causal effect chain by maternal depression in the first 2 years of life, by current maternal depression (Beck Depression Inventory-II) and by current maternal child abuse potential (Child Abuse Potential Inventory). The children's emotional problems and externalizing symptoms were assessed at preschool age by parent or teacher Strengths and Difficulties Questionnaire ratings. RESULTS: The results indicated that especially later maternal depression mediated the relationship between maternal childhood maltreatment and negative developmental outcomes in the next generation. The effects of maltreatment type on maternal depression were rather nonspecific. However, mental abuse affected existing risk factors more directly over time compared to physical and sexual abuse. Additionally, the impact of early life maltreatment and maternal depression on child psychopathology varied by rater. The pathway to externalizing symptoms was significant only in teacher ratings and for the pathway to emotional problems only in maternal ratings. CONCLUSIONS: The present findings suggest that early maternal depression followed by ongoing maternal depression plays a mediating role in the intergenerational cycle of maltreatment. Therefore, in the future, interventions should be offered at an early stage, but also extend well beyond the first 2 years of a child's life, addressing maternal depression and trauma.

Perpetrators and victims of cyberbullying among youth with conduct disorder.

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.

Emotion processing in maltreated boys and girls: Evidence for latent vulnerability.

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.

Machine learning classification of conduct disorder with high versus low levels of callous-unemotional traits based on facial emotion recognition abilities.

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.

Longitudinal Associations Between Parenting and Child Behaviour Problems and the Moderating Effect of Child Callous Unemotional Traits in Foster and Biological Families.

The goals of the current study were to examine (i) differences in parenting between foster and biological parents, (ii) the longitudinal associations with children's internalising and externalising problems and iii) the potential moderation of these by children's callous-unemotional traits (CU traits). Data from 86 foster children (M = 4.44 years, male = 48%) and 148 biological children (M = 3.69 years, male = 49%) with their families were analysed in a longitudinal study with three measurement times. Parenting behaviour did not significantly differ between the foster and biological family groups. Significant longitudinal cross-lagged effects were found for parental warmth and support and children's externalising problems. CU traits moderated the relationship between warmth and support and externalising problems of children. Findings suggest that parenting behaviours and child psychopathology do influence each other over time reciprocally and to a similar extent in both groups. However, there was also evidence for greater temporal stability of psychopathological symptoms and reduced responsivity to parental warmth in children with higher CU traits.

Sex-dependent clinical presentation, body image, and endocrine status in long-term remitted anorexia nervosa.

OBJECTIVE: Although anorexia nervosa (AN) in males has recently gained attention, knowledge of its psychological and physiological outcomes is still scarce. We explore sex-specific characteristics of long-term remitted AN with respect to residual eating disorder (ED) psychopathology, body image, and endocrinology. METHOD: We recruited 33 patients with AN in remission for at least 18 months (24 women, 9 men) and 36 matched healthy controls (HCs). Eating disorder psychopathology and body image ideals were assessed via clinical interviews, questionnaires, and an interactive 3D body morphing tool. Plasma levels of leptin, free triiodothyronine, cortisol, and sex hormones were quantified. Univariate models controlled for age and weight were used to test for the effects of diagnosis and sex. RESULTS: Both patient groups showed residual ED psychopathology but normal weight and hormone levels relative to HCs. Male remitted patients demonstrated significantly stronger muscularity-focused body image ideals, evident in interviews, self-reports, and behavioural data, than both female patients and HCs. CONCLUSIONS: Sex-specific body image characteristics in patients with remitted AN point towards the need to adjust test instruments and diagnostic criteria to male-specific psychopathology. In the future, sufficiently powered studies should evaluate the risk of men with AN developing muscle dysmorphia in the long term.

[The biopsychosocial understanding of health disorders and impairments in children with a focus on developmental neurological relationships]. / Das biopsychosoziale Verständnis von Gesundheitsstörungen und Beeinträchtigungen bei Kindern mit Fokus auf entwicklungsneurologische Zusammenhänge.

The distinction between mental (spiritual and psychological) and physical health disorders is particularly difficult due to the special features of neurobiological development in children and adolescents. In this review article, the basics of developmental neurology are briefly described. On the basis of some congenital or early acquired neurological diseases, it is then shown to what extent mental processes can be impaired in interactions with the social context. Taking these aspects into account plays an important role in child and family-oriented counseling and support. The common occurrence of physical, mental, and psychological development disorders, which is also very variable between individuals and fluctuates over the course of a person's life, requires good interdisciplinary cooperation between conservative and surgical child and adolescent medicine and child and adolescent psychiatry.

[Developing Knowledge Together: Participatory Methods in Psychological and Neuroscientific Research with Children and Adolescents]. / Wissen gemeinsam erarbeiten: Partizipative Methoden in der psychologischen und neurowissenschaftlichen Forschung mit Kindern und Jugendlichen.

Developing Knowledge Together: Participatory Methods in Psychological and Neuroscientific Research with Children and Adolescents Abstract: Participatory action research understands the implementation of research as a cooperation or coproduction of researchers with nonscientific individuals. However, the general knowledge about the participatory approach as well as participatory methods and their implementation is still limited. Especially the active involvement and empowerment of children and adolescents require special measures and a creative and flexible application of various methods. In addition, the use of participatory methods in neurodevelopmental research first demands prior explanation of complex techniques to successfully implement the cooperation and coproduction between researchers and children and adolescents. In this contribution, we emphasize the relevance of the participatory approach for scientific work, present different methods that allow an introduction of complex techniques in neurodevelopmental research, and illustrate how to systematically apply this approach to research in children and adolescents.

Multimodal hyperscanning reveals that synchrony of body and mind are distinct in mother-child dyads.

Hyperscanning studies have begun to unravel the brain mechanisms underlying social interaction, indicating a functional role for interpersonal neural synchronization (INS), yet the mechanisms that drive INS are poorly understood. The current study, thus, addresses whether INS is functionally-distinct from synchrony in other systems - specifically the autonomic nervous system and motor behavior. To test this, we used concurrent functional near-infrared spectroscopy - electrocardiography recordings, while N = 34 mother-child and stranger-child dyads engaged in cooperative and competitive tasks. Only in the neural domain was a higher synchrony for mother-child compared to stranger-child dyads observed. Further, autonomic nervous system and neural synchrony were positively related during competition but not during cooperation. These results suggest that synchrony in different behavioral and biological systems may reflect distinct processes. Furthermore, they show that increased mother-child INS is unlikely to be explained solely by shared arousal and behavioral similarities, supporting recent theories that postulate that INS is higher in close relationships.

Interacting brains revisited: A cross-brain network neuroscience perspective.

Elucidating the neural basis of social behavior is a long-standing challenge in neuroscience. Such endeavors are driven by attempts to extend the isolated perspective on the human brain by considering interacting persons' brain activities, but a theoretical and computational framework for this purpose is still in its infancy. Here, we posit a comprehensive framework based on bipartite graphs for interbrain networks and address whether they provide meaningful insights into the neural underpinnings of social interactions. First, we show that the nodal density of such graphs exhibits nonrandom properties. While the current hyperscanning analyses mostly rely on global metrics, we encode the regions' roles via matrix decomposition to obtain an interpretable network representation yielding both global and local insights. With Bayesian modeling, we reveal how synchrony patterns seeded in specific brain regions contribute to global effects. Beyond inferential inquiries, we demonstrate that graph representations can be used to predict individual social characteristics, outperforming functional connectivity estimators for this purpose. In the future, this may provide a means of characterizing individual variations in social behavior or identifying biomarkers for social interaction and disorders.

Consortium neuroscience of attention deficit/hyperactivity disorder and autism spectrum disorder: The ENIGMA adventure.

Neuroimaging has been extensively used to study brain structure and function in individuals with attention deficit/hyperactivity disorder (ADHD) and autism spectrum disorder (ASD) over the past decades. Two of the main shortcomings of the neuroimaging literature of these disorders are the small sample sizes employed and the heterogeneity of methods used. In 2013 and 2014, the ENIGMA-ADHD and ENIGMA-ASD working groups were respectively, founded with a common goal to address these limitations. Here, we provide a narrative review of the thus far completed and still ongoing projects of these working groups. Due to an implicitly hierarchical psychiatric diagnostic classification system, the fields of ADHD and ASD have developed largely in isolation, despite the considerable overlap in the occurrence of the disorders. The collaboration between the ENIGMA-ADHD and -ASD working groups seeks to bring the neuroimaging efforts of the two disorders closer together. The outcomes of case-control studies of subcortical and cortical structures showed that subcortical volumes are similarly affected in ASD and ADHD, albeit with small effect sizes. Cortical analyses identified unique differences in each disorder, but also considerable overlap between the two, specifically in cortical thickness. Ongoing work is examining alternative research questions, such as brain laterality, prediction of case-control status, and anatomical heterogeneity. In brief, great strides have been made toward fulfilling the aims of the ENIGMA collaborations, while new ideas and follow-up analyses continue that include more imaging modalities (diffusion MRI and resting-state functional MRI), collaborations with other large databases, and samples with dual diagnoses.

Childhood adversity and approach/avoidance-related behaviour in boys.

Childhood adversity has been suggested to affect the vulnerability for developmental psychopathology, including both externalizing and internalizing symptoms. This study examines spontaneous attention biases for negative and positive emotional facial expressions as potential intermediate phenotypes. In detail, typically developing boys (6-13 years) underwent an eye-tracking paradigm displaying happy, angry, sad and fearful faces. An approach bias towards positive emotional facial expressions with increasing childhood adversity levels was found. In addition, an attention bias away from negative facial expressions was observed with increasing childhood adversity levels, especially for sad facial expressions. The results might be interpreted in terms of emotional regulation strategies in boys at risk for reactive aggression and depressive behaviour.

Caregiving quality modulates neuroendocrine and immunological markers in young children in foster care who have experienced early adversity.

BACKGROUND: Early adversity is believed to alter the body's stress-response systems, putting children at increased risk for somatic and mental health problems. However, it remains unclear whether such alterations normalize under improved caregiving experiences. Thus, the goal of the present study was to investigate (a) whether children in foster care show endocrine and immunological alterations relative to children living with their biological families, (b) whether these alterations change over time spent with the foster family, and (c) whether the alterations are modulated by current caregiving experiences. METHODS: A total of 94 children in foster care and 157 biological children, aged two to seven years, took part in a longitudinal study with three assessments conducted over a 12-month study period. At the initial assessment, children lived for an average of 18 months with their current foster families. Children's cortisol, dehydroepiandrosterone (DHEA) and progesterone concentrations and cortisol/DHEA ratios were measured in scalp hair and children's secretory immunoglobulin A (sIgA) levels in saliva. Caregiving quality was assessed based on caregiver-reports and observational measures of caregiver-child interactions. RESULTS: Children in foster care had lower cortisol/DHEA ratios and higher progesterone concentrations than biological children, while no group differences were found for cortisol, DHEA or sIgA. Time spent with the current foster family did not significantly influence the child's endocrine or immunological markers. Importantly, caregiving quality modulated cortisol/DHEA ratios and sIgA concentrations: children in foster care of lower caregiving quality had lower cortisol/DHEA ratios than children in foster care of higher caregiving quality and showed decreasing, rather than increasing, sIgA concentrations across the study period. CONCLUSIONS: Our results indicate that caregiving quality in the foster family may have an important modulating effect on selected indicators of the child's stress response and could thereby mitigate the possible consequences of early childhood adversity.

Sex differences in psychiatric comorbidity and clinical presentation in youths with conduct disorder.

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.