Losing control: Prefrontal emotion regulation relates to symptom severity and predicts treatment-related symptom change in adolescent girls with conduct disorder.

BACKGROUND: Emotion regulation skills are linked to corticolimbic brain activity (e.g., dorsolateral prefrontal cortex (dlPFC) and limbic regions) and enable an individual to control their emotional experiences thus allowing healthy social functioning. Disruptions in emotion regulation skills are reported in neuropsychiatric disorders, including conduct disorder or oppositional defiant disorder (CD/ODD). Clinically recognized means to ameliorate emotion regulation deficits observed in CD/ODD include cognitive or dialectical behavioral skills therapy as implemented in the START-NOW program. However, the role of emotion regulation and its neural substrates in symptom severity and prognosis following treatment of adolescent CD/ODD has yet to be investigated. METHODS: Cross-sectional data including fMRI responses during emotion regulation (N=114; average age=15years), repeated-measures assessments of symptom severity (pre-, post-treatment, long-term follow-up), and fMRI data collected prior to and following the START-NOW randomized controlled trial (n=44) for female adolescents with CD/ODD were analyzed using group comparisons and multiple regression. RESULTS: First, behavioral and neural correlates of emotion regulation are disrupted in female adolescents with CD/ODD. Second, ODD symptom severity is negatively associated with dlPFC/precentral gyrus activity during regulation. Third, treatment-related symptom changes are predicted by pre-treatment ODD symptom severity and regulatory dlPFC/precentral activity. Additionally, pre-treatment dlPFC/precentral activity and ODD symptom severity predict long-term reductions in symptom severity following treatment for those participants that received the START NOW treatment. CONCLUSION: Our findings demonstrate the important role that emotion regulation skills play in the characteristics of CD/ODD and show that regulatory dlPFC/precentral activity is positively associated with treatment response in female adolescents with CD/ODD.

Synergy of the mirror neuron system and the mentalizing system in a single brain and between brains during joint actions.

Cooperative action involves the simulation of actions and their co-representation by two or more people. This requires the involvement of two complex brain systems: the mirror neuron system (MNS) and the mentalizing system (MENT), both of critical importance for successful social interaction. However, their internal organization and the potential synergy of both systems during joint actions (JA) are yet to be determined. The aim of this study was to examine the role and interaction of these two fundamental systems-MENT and MNS-during continuous interaction. To this hand, we conducted a multiple-brain connectivity analysis in the source domain during a motor cooperation task using high-density EEG dual-recordings providing relevant insights into the roles of MNS and MENT at the intra- and interbrain levels. In particular, the intra-brain analysis demonstrated the essential function of both systems during JA, as well as the crucial role played by single brain regions of both neural mechanisms during cooperative activities. Specifically, our intra-brain analysis revealed that both neural mechanisms are essential during Joint Action (JA), showing a solid connection between MNS and MENT and a central role of the single brain regions of both mechanisms during cooperative actions. Additionally, our inter-brain study revealed increased inter-subject connections involving the motor system, MENT and MNS. Thus, our findings show a mutual influence between two interacting agents, based on synchronization of MNS and MENT systems. Our results actually encourage more research into the still-largely unknown realm of inter-brain dynamics and contribute to expand the body of knowledge in social neuroscience.

[The S3 Guideline on the Treatment of Language Development Disorders: Summary of Recommendations]. / Die S3-Leitlinie zur Therapie von Sprachentwicklungsstörungen.

The S3 Guideline on the Treatment of Language Development Disorders: Summary of Recommendations Abstract: The German S3 Guidelines on the Treatment of Developmental Speech and Language Disorders (AWMF: No. 049-015) were published on the AWMF homepage at the end of 2022. The German Society for Phoniatrics and Paedaudiologie coordinated the work and developed the guideline text together with linguists and speech and language therapists. Many scientific medical societies consented to the respective recommendations. For the first time in the German-speaking area, the guideline group reviewed international research results on the treatment of various speech and language disorders and formulated evidence- or consensus-based recommendations for clinical care. The present article summarizes these recommendations and evaluates the guidelines from the perspective of child and adolescent psychiatry and psychotherapy.

Effectiveness of a positive psychology and mindfulness-based app on mental health for parents of children with a neurodevelopmental disorder: study protocol of a pragmatic international randomized controlled trial.

INTRODUCTION: Parents of children with a neurodevelopmental disorder (NDD) experience more stress than parents of typically developing children. In a cocreation process with experts and parents, a low-threshold application that uses exercises based on the principles of positive psychology and mindfulness was developed. This application, called "Adappt," aims at enhancing the ability to adapt of the parents and caregivers of children with NDDs and at supporting their mental health. This protocol describes the evaluation study of the effectiveness of Adappt, its core working mechanisms and user experiences. METHOD: A pragmatic international multicenter randomized controlled trial will compare the effectiveness of Adappt with a (delayed) waitlist control condition. At least 212 parents or primary caregivers of children younger than 18 years diagnosed with or suspected of a NDD will be randomly assigned to the intervention or waitlist control condition. Participants are excluded if they have severe anxiety or depression levels or are in treatment for mental health issues. Measures will be collected online at baseline, post-intervention (1 month after baseline), and 4 and 7 months after baseline. The primary outcome is the improvement in generic sense of ability to adapt as measured with the Generic Sense of Ability to Adapt Scale (GSAAS; (Front Psychol 14:985408, 2023)) at 4-month follow-up. Secondary outcomes are mental well-being, (parental) distress, and client satisfaction with "Adappt." DISCUSSION: Results of this study will contribute to knowledge on the effectiveness of a low-threshold application for parents of children with a NDD in multiple countries. If the application is found to be effective in improving mental health, recommendations will be made for implementation in health care. TRIAL REGISTRATION: This study is registered on clinicaltrials.gov (NCT06248762) on February 8, 2024, and the Open Science Framework ( https://osf.io/5znqv ).

Does the Relationship between Age and Brain Structure Differ in Youth with Conduct Disorder?

Conduct disorder (CD) is characterised by persistent antisocial and aggressive behaviour and typically emerges in childhood or adolescence. Although several authors have proposed that CD is a neurodevelopmental disorder, very little evidence is available about brain development in this condition. Structural brain alterations have been observed in CD, and some indirect evidence for delayed brain maturation has been reported. However, no detailed analysis of age-related changes in brain structure in youth with CD has been conducted. Using cross-sectional MRI data, this study aimed to explore differences in brain maturation in youth with CD versus healthy controls to provide further understanding of the neurodevelopmental processes underlying CD. 291 CD cases (153 males) and 379 healthy controls (160 males) aged 9-18 years (Mage = 14.4) were selected from the European multisite FemNAT-CD study. Structural MRI scans were analysed using surface-based morphometry followed by application of the ENIGMA quality control protocols. An atlas-based approach was used to investigate group differences and test for group-by-age and group-by-age-by-sex interactions in cortical thickness, surface area and subcortical volumes. Relative to healthy controls, the CD group showed lower surface area across frontal, temporal and parietal regions as well as lower total surface area. No significant group-by-age or group-by-age-by-sex interactions were observed on any brain structure measure. These findings suggest that CD is associated with lower surface area across multiple cortical regions, but do not support the idea that CD is associated with delayed brain maturation, at least within the age bracket considered here.

Temporal progression of pupil dilation and gaze behavior to emotion expressions in preschoolers with autism spectrum disorder.

Previous work has shown divergent pupil dilation (PD) and gaze behavior in individuals with autism spectrum disorder (ASD), which may relate to the development of social difficulties in early life. Here, we investigated temporal dynamics of both phenotypes during naturalistic videos of a person displaying facial emotion expressions in 61 autistic and 61 non-autistic preschoolers. PD was segmented into three serial time components derived from a principal component analysis. Growth curve analysis was applied to analyze changes in looking time on eye and mouth regions over time. Groups did not differ in PD time components. Growth curve analysis revealed initially shorter looking times on the eyes and longer looking times on the mouth in autistic versus non-autistic preschoolers. However, a reversion of this pattern was observed over time, suggesting a delayed compensatory increase in eye attention during prolonged viewing periods in autistic children. Positive and negative associations of PD components and gaze behavior over time indicated a dynamic temporal relationship during emotion viewing. Our findings emphasize the need to apply time-sensitive measures in ecologically valid research, which may index etiological mechanisms of social difficulties in ASD.

Bright light therapy versus physical exercise to prevent co-occurring depression in adolescents and young adults with attention-deficit/hyperactivity disorder: a multicentre, three-arm, randomised controlled, pilot phase-IIa trial.

Depression is common in attention-deficit/hyperactivity disorder (ADHD), but preventive behavioural interventions are lacking. This randomised controlled, pilot phase-IIa trial aimed to study a physical exercise intervention (EI) and bright light therapy (BLT)-both implemented and monitored in an individual, naturalistic setting via a mobile health (m-health) system-for feasibility of trial design and interventions, and to estimate their effects on depressive symptoms in young people with ADHD. Two hundred seven participants aged 14-45 years were randomised to 10-week add-on intervention of either BLT (10,000 lx; daily 30-min sessions) (n = 70), EI (aerobic and muscle-strengthening activities 3 days/ week) (n = 69), or treatment-as-usual (TAU) (n = 68), of whom 165 (80%) were retained (BLT: n = 54; EI: n = 52; TAU: n = 59). Intervention adherence (i.e. ≥ 80% completed sessions) was very low for both BLT (n = 13, 22%) and EI (n = 4, 7%). Usability of the m-health system to conduct interventions was limited as indicated by objective and subjective data. Safety was high and comparable between groups. Changes in depressive symptoms (assessed via observer-blind ratings, Inventory of Depressive Symptomatology) between baseline and end of intervention were small (BLT: -0.124 [95% CI: -2.219, 1.971], EI: -2.646 [95% CI: -4.777, -0.515], TAU: -1.428 [95% CI: -3.381, 0.526]) with no group differences [F(2,153) = 1.45, p = 0.2384]. These findings suggest that the m-health approach did not achieve feasibility of EI and BLT in young people with ADHD. Prior to designing efficacy studies, strategies how to achieve high intervention adherence should be specifically investigated in this patient group. TRIAL REGISTRATION: ClinicalTrials.gov, NCT03371810, 13 December 2017.

Neuroanatomical Predictors of Transcranial Direct Current Stimulation (tDCS)-Induced Modifications in Neurocognitive Task Performance in Typically Developing Individuals.

Transcranial direct current stimulation (tDCS) is a noninvasive neuromodulation technique gaining more attention in neurodevelopmental disorders (NDDs). Due to the phenotypic heterogeneity of NDDs, tDCS is unlikely to be equally effective in all individuals. The present study aimed to establish neuroanatomical markers in typically developing (TD) individuals that may be used for the prediction of individual responses to tDCS. Fifty-seven male and female children received 2 mA anodal and sham tDCS, targeting the left dorsolateral prefrontal cortex (DLPFCleft), right inferior frontal gyrus, and bilateral temporoparietal junction. Response to tDCS was assessed based on task performance differences between anodal and sham tDCS in different neurocognitive tasks (N-back, flanker, Mooney faces detection, attentional emotional recognition task). Measures of cortical thickness (CT) and surface area (SA) were derived from 3 Tesla structural MRI scans. Associations between neuroanatomy and task performance were assessed using general linear models (GLM). Machine learning (ML) algorithms were employed to predict responses to tDCS. Vertex-wise estimates of SA were more closely linked to differences in task performance than measures of CT. Across ML algorithms, highest accuracies were observed for the prediction of N-back task performance differences following stimulation of the DLPFCleft, where 65% of behavioral variance was explained by variability in SA. Lower accuracies were observed for all other tasks and stimulated regions. This suggests that it may be possible to predict individual responses to tDCS for some behavioral measures and target regions. In the future, these models might be extended to predict treatment outcome in individuals with NDDs.

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.

The Course of Anxiety-Specific Cognitive Bias Following Daycare/Inpatient Treatment in Youths with Social Phobia and School Absenteeism.

Social phobia (SP) is a common mental disorder in youth often accompanied by absence from school, which may require daycare or inpatient intervention (DC/IN). Objective: The present explorative study investigates changes in anxiety-specific implicit assumptions and interpretation bias following DC/IN. Methods: The study included 16 youths with SP (M age = 15.8 [SD = 1.24], females: 62.5 %) participating in DC/IN. We assessed the main outcomes using the Implicit Association Test and Affective Misattribution Procedure. Results: A large effect was shown for reducing implicit assumptions of feeling anxious (p = .142; η2p = .171) and for reducing the implicit interpretation bias (p = .137; η2p = .162). No change was indicated by effect size in implicit assumptions of feeling socially rejected (p = .649; η2p = .016). Social phobia symptoms initially correlated with changes in implicit assumptions of feeling anxious (r = .45). Conclusion: Effect sizes indicate that implicit anxiety-specific assumptions and interpretation bias descriptively improved following DC/IN. Thus, DC/IN may lead to meaningful improvements of anxiety-specific cognition in some individuals with high SP symptoms, emphasizing the relevance of cognitive behavioral approaches in the treatment of SP. Several limitations are discussed.

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.

Impaired Punishment Learning in Conduct Disorder.

OBJECTIVE: Conduct disorder (CD) has been associated with deficits in the use of punishment to guide reinforcement learning (RL) and decision making. This may explain the poorly planned and often impulsive antisocial and aggressive behavior in affected youths. Here, we used a computational modeling approach to examine differences in RL abilities between CD youths and typically developing controls (TDCs). Specifically, we tested 2 competing hypotheses that RL deficits in CD reflect either reward dominance (also known as reward hypersensitivity) or punishment insensitivity (also known as punishment hyposensitivity). METHOD: The study included 92 CD youths and 130 TDCs (aged 9-18 years, 48% girls) who completed a probabilistic RL task with reward, punishment, and neutral contingencies. Using computational modeling, we investigated the extent to which the 2 groups differed in their learning abilities to obtain reward and/or to avoid punishment. RESULTS: RL model comparisons showed that a model with separate learning rates per contingency explained behavioral performance best. Importantly, CD youths showed lower learning rates than TDCs specifically for punishment, whereas learning rates for reward and neutral contingencies did not differ. Moreover, callous-unemotional (CU) traits did not correlate with learning rates in CD. CONCLUSION: CD youths have a highly selective impairment in probabilistic punishment learning, regardless of their CU traits, whereas reward learning appears to be intact. In summary, our data suggest punishment insensitivity rather than reward dominance in CD. Clinically, the use of punishment-based intervention techniques to achieve effective discipline in patients with CD may be a less helpful strategy than reward-based techniques.

Admission rates and clinical profiles of children and youth with eating disorders treated as inpatients before and during the COVID-19 pandemic in a German university hospital.

Introduction: Children and youth at risk for mental health disorders, such as eating disorders (ED), were particularly affected by the COVID-19 pandemic, yet evidence for the most seriously affected and thus hospitalized youth in Germany is scarce. Methods: This crosssectional study investigated anonymized routine hospital data (demographic information, diagnoses, treatment modalities) of patients admitted (n = 2,849) to the Department of Child and Adolescence Psychiatry, Psychosomatics and Psychotherapy (DCAPPP) of a German University Hospital between 01/2016 and 02/2022. Absolute and relative number of inpatients with or without ED prior to (01/2016-02/2020) and during the COVID-19 pandemic (03/2020-02/2022) were compared. The effect of school closures as part of social lockdown measures for COVID-19 mitigation on inpatient admission rate was explored as it has been discussed as a potential risk factor for mental health problems in youth. Results: During the COVID-19 pandemic, ED inpatient admission rate increased from 10.5 to 16.7%, primarily driven by Anorexia Nervosa (AN). In contrast to previous reports, we found no change in somatic and mental disorder comorbidity, age or sexratio for hospitalized youth with ED. However, we did observe a shortened length of hospital stay (LOS) for hospitalized youth with and without ED. In addition, non-ED admissions presented with an increased number of mental disorder comorbidities. In contrast to our hypothesis, school closures were not related to the observed increase in ED. Discussion: In summary, the COVID-19 pandemic was associated with an increased rate of inpatient treatment for youth suffering from AN, and of youth affected by multiple mental disorders. Accordingly, we assume that inpatient admission was prioritized for individuals with a higher burden of disease during the COVID-19 pandemic. Our findings pinpoint the need for adequate inpatient mental health treatment capacities during environmental crises, and a further strengthening of child and adolescence psychiatry services in Germany.

Action initiation and punishment learning differ from childhood to adolescence while reward learning remains stable.

Theoretical and empirical accounts suggest that adolescence is associated with heightened reward learning and impulsivity. Experimental tasks and computational models that can dissociate reward learning from the tendency to initiate actions impulsively (action initiation bias) are thus critical to characterise the mechanisms that drive developmental differences. However, existing work has rarely quantified both learning ability and action initiation, or it has relied on small samples. Here, using computational modelling of a learning task collected from a large sample (N = 742, 9-18 years, 11 countries), we test differences in reward and punishment learning and action initiation from childhood to adolescence. Computational modelling reveals that whilst punishment learning rates increase with age, reward learning remains stable. In parallel, action initiation biases decrease with age. Results are similar when considering pubertal stage instead of chronological age. We conclude that heightened reward responsivity in adolescence can reflect differences in action initiation rather than enhanced reward learning.

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.

Linking heart rate variability to psychological health and brain structure in adolescents with and without conduct disorder.

Aims: Heart rate variability (HRV) measures have been suggested in healthy individuals as a potential index of self-regulation skills, which include both cognitive and emotion regulation aspects. Studies in patients with a range of psychiatric disorders have however mostly focused on the potential association between abnormally low HRV at rest and specifically emotion regulation difficulties. Emotion regulation deficits have been reported in patients with Conduct Disorder (CD) however, the association between these emotion regulation deficits and HRV measures has yet to be fully understood. This study investigates (i) the specificity of the association between HRV and emotion regulation skills in adolescents with and without CD and (ii) the association between HRV and grey matter brain volumes in key areas of the central autonomic network which are involved in self-regulation processes, such as insula, lateral/medial prefrontal cortices or amygdala. Methods: Respiratory sinus arrhythmia (RSA) measures of HRV were collected from adolescents aged between 9-18 years (693 CD (427F)/753 typically developing youth (TD) (500F)), as part of a European multi-site project (FemNAT-CD). The Inverse Efficiency Score, a speed-accuracy trade-off measure, was calculated to assess emotion and cognitive regulation abilities during an Emotional Go/NoGo task. The association between RSA and task performance was tested using multilevel regression models. T1-weighted structural MRI data were included for a subset of 577 participants (257 CD (125F); 320 TD (186F)). The CerebroMatic toolbox was used to create customised Tissue Probability Maps and DARTEL templates, and CAT12 to segment brain images, followed by a 2 × 2 (sex × group) full factorial ANOVA with RSA as regressor of interest. Results: There were no significant associations between RSA and task performance, neither during emotion regulation nor during cognitive regulation trials. RSA was however positively correlated with regional grey matter volume in the left insula (pFWE = 0.011) across all subjects. Conclusion: RSA was related to increased grey matter volume in the left insula across all subjects. Our results thus suggest that low RSA at rest might be a contributing or predisposing factor for potential self-regulation difficulties. Given the insula's role in both emotional and cognitive regulation processes, these brain structural differences might impact either of those.

Reward processing in adolescents with social phobia and depression.

OBJECTIVE: Impaired reward processing has been found in individuals with anxiety, but also major depressive disorder (MDD). Here, we studied neural correlates of reward anticipation and processing in a sample of youth with severe social phobia and comorbid depression (SP/MDD) and investigated the specific contribution of SP and MDD symptoms. METHODS: 15 affected, unmedicated and 25 typically developing (TD) youth completed a monetary gambling task, which included a positive, negative and ambiguous reward condition. Event-related potentials representing cue processing (cue P300), reward anticipation (stimulus preceding negativity, SPN), reward sensitivity (feedback related negativity, FRN) and reward processing (reward P300) were analysed. RESULTS: Reduced amplitudes of the right hemispheric (r)SPN and reward P300 were observed in SP/MDD compared to TD. Within the SP/MDD group SP symptoms correlated with larger rSPN, and FRN amplitudes. MDD symptoms correlated with smaller rSPN and smaller FRN positive-negative difference wave. CONCLUSIONS: Reward anticipation and feedback processing are reduced in SP/MDD. Higher SP symptoms are associated with stronger neural activation during reward anticipation and reward sensitivity. Depressive symptoms are associated with decreased reward anticipation and sensitivity. Findings are in line with the theory of heightened vigilance in anxiety and blunted reward processing due to anhedonia in MDD. SIGNIFICANCE: The study results can inform behavioural interventions for SP and MDD.

Cross-sectional and longitudinal neuroanatomical profiles of distinct clinical (adaptive) outcomes in autism.

Individuals with autism spectrum disorder (henceforth referred to as autism) display significant variation in clinical outcome. For instance, across age, some individuals' adaptive skills naturally improve or remain stable, while others' decrease. To pave the way for 'precision-medicine' approaches, it is crucial to identify the cross-sectional and, given the developmental nature of autism, longitudinal neurobiological (including neuroanatomical and linked genetic) correlates of this variation. We conducted a longitudinal follow-up study of 333 individuals (161 autistic and 172 neurotypical individuals, aged 6-30 years), with two assessment time points separated by ~12-24 months. We collected behavioural (Vineland Adaptive Behaviour Scale-II, VABS-II) and neuroanatomical (structural magnetic resonance imaging) data. Autistic participants were grouped into clinically meaningful "Increasers", "No-changers", and "Decreasers" in adaptive behaviour (based on VABS-II scores). We compared each clinical subgroup's neuroanatomy (surface area and cortical thickness at T1, ∆T (intra-individual change) and T2) to that of the neurotypicals. Next, we explored the neuroanatomical differences' potential genomic associates using the Allen Human Brain Atlas. Clinical subgroups had distinct neuroanatomical profiles in surface area and cortical thickness at baseline, neuroanatomical development, and follow-up. These profiles were enriched for genes previously associated with autism and for genes previously linked to neurobiological pathways implicated in autism (e.g. excitation-inhibition systems). Our findings suggest that distinct clinical outcomes (i.e. intra-individual change in clinical profiles) linked to autism core symptoms are associated with atypical cross-sectional and longitudinal, i.e. developmental, neurobiological profiles. If validated, our findings may advance the development of interventions, e.g. targeting mechanisms linked to relatively poorer outcomes.

Testing the Ecophenotype Model: Cortical Structure Alterations in Conduct Disorder With Versus Without Childhood Maltreatment.

BACKGROUND: Childhood maltreatment is common in youths with conduct disorder (CD), and both CD and maltreatment have been linked to neuroanatomical alterations. Nonetheless, our understanding of the contribution of maltreatment to the neuroanatomical alterations observed in CD remains limited. We tested the applicability of the ecophenotype model to CD, which holds that maltreatment-related psychopathology is (neurobiologically) distinct from psychopathology without maltreatment. METHODS: Surface-based morphometry was used to investigate cortical volume, thickness, surface area, and gyrification in a mixed-sex sample of participants with CD (n = 114) and healthy control subjects (HCs) (n = 146), ages 9 to 18 years. Using vertexwise general linear models adjusted for sex, age, total intracranial volume, and site, the control group was compared with the overall CD group and the CD subgroups with (n = 49) versus without (n = 65) maltreatment (assessed by the Children's Bad Experiences interview). These subgroups were also directly compared. RESULTS: The overall CD group showed lower cortical thickness in the right inferior frontal gyrus. CD youths with a history of maltreatment showed more widespread structural alterations relative to HCs, comprising lower thickness, volume, and gyrification in inferior and middle frontal regions. Conversely, CD youths with no history of maltreatment only showed greater left superior temporal gyrus folding relative to HCs. When contrasting the CD subgroups, those with maltreatment displayed lower right superior temporal gyrus volume, right precentral gyrus surface area, and gyrification in frontal, temporal, and parietal regions. CONCLUSIONS: Consistent with the ecophenotype model, findings indicated that CD youths with versus without maltreatment differ neurobiologically. This highlights the importance of considering maltreatment history in neuroimaging studies of CD and other disorders.