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The hippocampus is involved in many cognitive domains which are difficult for autistic individuals. Our previous study using a Structural Learning task that has been shown to depend on hippocampal functioning found that structural learning is diminished in autistic adults (Ring et al., 2017). The aim of the present study was to examine whether those results can be replicated in and extended to a sample of autistic and non-autistic children. We tested 43 autistic children and 38 non-autistic children with a subsample of 25 autistic and 28 non-autistic children who were well-matched on IQ. The children took part in a Simple Discrimination task which a simpler form of compound learning, and a Structural Learning task. We expected both groups to perform similarly in Simple Discrimination but reduced performance by the autism group on the Structural Learning task, which is what we found in both the well-matched and the non-matched sample. However, contrary to our prediction and the findings from autistic adults in our previous study, autistic children demonstrated a capacity for Structural Learning and showed an overall better performance in the tasks than was seen in earlier studies. We discuss developmental differences in autism as well as the role of executive functions that may have contributed to better than predicted task performance in this study., (© 2024. The Author(s).)

Adolescent subcortical structural brain development might underlie psychopathological symptoms, which often emerge in adolescence. At the same time, sex differences exist in psychopathology, which might be mirrored in underlying sex differences in structural development. However, previous studies showed inconsistencies in subcortical trajectories and potential sex differences. Therefore, we aimed to investigate the subcortical structural trajectories and their sex differences across adolescence using for the first time a single cohort design, the same quality control procedure, software, and a general additive mixed modeling approach. We investigated two large European sites from ages 14 to 24 with 503 participants and 1408 total scans from France and Germany as part of the IMAGEN project including four waves of data acquisition. We found significantly larger volumes in males versus females in both sites and across all seven subcortical regions. Sex differences in age-related trajectories were observed across all regions in both sites. Our findings provide further evidence of sex differences in longitudinal adolescent brain development of subcortical regions and thus might eventually support the relationship of underlying brain development and different adolescent psychopathology in boys and girls., (© 2024 The Authors. Human Brain Mapping published by Wiley Periodicals LLC.)

Background: During the COVID 19 pandemic, there were social restrictions with severe mental stress for a long time. Most studies on mental health consequences of the pandemic focused primarily on the beginning of the pandemic. The present study on families of patients or study participants of a child and adolescent psychiatry aimed to examine long-term profiles of emotions and worries in adults with and without mental health condition (mhc) during the first 1.5 years of the COVID-19 pandemic., Methods: We surveyed emotions and worries of 128 adults with (n = 32) and without (n = 96) pre-pandemic mhc over a 1.5-year study period from spring 2020 until summer/autumn 2021. Emotions and worries were captured at four time points: [i] pre-pandemic, [ii] spring 2020 (first lockdown was implemented), [iii] December 2020 (hard lockdown at Christmas time) and [iv] summer/autumn 2021 (considerable ease of regulations); [i] pre-pandemic and [iii] December 2020 were measured retrospectively). First, we run non-parametric tests to compare emotions and worries between adults with and without pre-pandemic mhc at the four time points. Next, we conducted latent profile analysis to identify subgroups from the total sample who share similar trajectories of emotions and worries. Finally, a logistic regression analysis was run to examine whether socio-demographic and psycho-social factors were related to identified trajectories of emotions and worries., Results: Adults without pre-pandemic mhc reported a strong worsening of emotions and worries at the beginning of the pandemic and a lower worsening during the course, while adults with pre-pandemic mhc reported a constant worsening of emotions and worries. The latent profile analysis revealed three profiles of adults who show either i) an adaption, ii) no adaption or iii) a continuous high condition. With increasing age, higher perceived stress and pre-pandemic mhc, the likelihood of an adaption was increased., Conclusion: The results of the present study suggested that adults (both with and without pre-pandemic mhc) coped the crisis with different strategies and that most of them returned to their initial, pre-pandemic levels of emotions and worries when social restrictions were considerably eased or stopped., (© 2024. The Author(s).)

Background: Early negative life events (NLE) have long-lasting influences on neurodevelopment and psychopathology. Reduced orbitofrontal cortex (OFC) thickness was frequently associated with NLE and depressive symptoms. OFC thinning might mediate the effect of NLE on depressive symptoms, although few longitudinal studies exist. Using a complete longitudinal design with four time points, we examined whether NLE during childhood and early adolescence predict depressive symptoms in young adulthood through accelerated OFC thinning across adolescence., Methods: We acquired structural MRI from 321 participants at two sites across four time points from ages 14 to 22. We measured NLE with the Life Events Questionnaire at the first time point and depressive symptoms with the Center for Epidemiologic Studies Depression Scale at the fourth time point. Modeling latent growth curves, we tested whether OFC thinning mediates the effect of NLE on depressive symptoms., Results: A higher burden of NLE, a thicker OFC at the age of 14, and an accelerated OFC thinning across adolescence predicted young adults' depressive symptoms. We did not identify an effect of NLE on OFC thickness nor OFC thickness mediating effects of NLE on depressive symptoms., Conclusions: Using a complete longitudinal design with four waves, we show that NLE in childhood and early adolescence predict depressive symptoms in the long term. Results indicate that an accelerated OFC thinning may precede depressive symptoms. Assessment of early additionally to acute NLEs and neurodevelopment may be warranted in clinical settings to identify risk factors for depression., Competing Interests: Dr. Banaschewski served in an advisory or consultancy role for Lundbeck, Medice, Neurim Pharmaceuticals, Oberberg GmbH, Shire. He received conference support or speaker's fee by Lilly, Medice, Novartis and Shire. He has been involved in clinical trials conducted by Shire & Viforpharma. He received royalties from Hogrefe, Kohlhammer, CIP Medien, Oxford University Press. The present work is unrelated to the above grants and relationships. Dr. Poustka served in an advisory or consultancy role for Roche and Viforpharm and received speaker's fee by Shire. She received royalties from Hogrefe, Kohlhammer and Schattauer. The present work is unrelated to the above grants and relationships. The other authors report no biomedical financial interests or potential conflicts of interest., (© 2023 The Authors. JCPP Advances published by John Wiley & Sons Ltd on behalf of Association for Child and Adolescent Mental Health.)

Current knowledge about functional connectivity in obsessive-compulsive disorder (OCD) is based on small-scale studies, limiting the generalizability of results. Moreover, the majority of studies have focused only on predefined regions or functional networks rather than connectivity throughout the entire brain. Here, we investigated differences in resting-state functional connectivity between OCD patients and healthy controls (HC) using mega-analysis of data from 1024 OCD patients and 1028 HC from 28 independent samples of the ENIGMA-OCD consortium. We assessed group differences in whole-brain functional connectivity at both the regional and network level, and investigated whether functional connectivity could serve as biomarker to identify patient status at the individual level using machine learning analysis. The mega-analyses revealed widespread abnormalities in functional connectivity in OCD, with global hypo-connectivity (Cohen's d: -0.27 to -0.13) and few hyper-connections, mainly with the thalamus (Cohen's d: 0.19 to 0.22). Most hypo-connections were located within the sensorimotor network and no fronto-striatal abnormalities were found. Overall, classification performances were poor, with area-under-the-receiver-operating-characteristic curve (AUC) scores ranging between 0.567 and 0.673, with better classification for medicated (AUC = 0.702) than unmedicated (AUC = 0.608) patients versus healthy controls. These findings provide partial support for existing pathophysiological models of OCD and highlight the important role of the sensorimotor network in OCD. However, resting-state connectivity does not so far provide an accurate biomarker for identifying patients at the individual level., (© 2023. The Author(s).)

(1) Background: 1-2% of children and adolescents are affected by Obsessive-Compulsive Disorder (OCD). The rigid, repetitive features of OCD and an assumed disability to inhibit recent mental representations are assumed to have led to a paradoxical advantage in that the Backward Inhibition (BI) effect was recently found to be lower in adolescents with OCD as compared to healthy controls. It was hypothesized that app-based mindfulness meditation training could reduce the disability to inhibit recent mental representations and thus increase the BI-effect by adapting cognitive flexibility and inhibition abilities according to healthy controls. (2) Methods: 58 adolescents (10-19 years) with OCD were included in the final sample of this interviewer-blind, randomized controlled study. Participants were allocated to an intervention group (app-based mindfulness meditation training) or an (active) control group (app-based audiobook) for eight weeks. Symptom (CY-BOCS), behavioral (reaction times and mean accuracy), and neurophysiological changes (in EEG) of the BI-effect were analyzed in a pre-post design. (3) Results: The intervention and the control group showed an intervention effect (Reliable Change Index: 67%) with a significant symptom reduction. Contrary to the hypothesis, the BI-effect did not differ between pre vs. post app-based mindfulness meditation training. In addition, as expected the audiobook application showed no effects. Thus, we observed no intervention-specific differences with respect to behavioral (reaction times and mean accuracy) or with respect to neurophysiological (perceptual [P1], attentional [N1], conflict monitoring [N2] or updating and response selection [P3]) processes. However, in an exploratory approach, we revealed that the BI-effect decreased in participants who did not benefit from using an app, regardless of group. (4) Conclusions: Both listening to an app-based mindfulness meditation training and to an audiobook reduce symptom severity in adolescent OCD as measured by the CY-BOCS; however, they have no specific effect on BI. The extent of the baseline BI-effect might be considered as an intra-individual component to predict the benefit of both mindfulness meditation training and listening to an audiobook.

Avoiding loss is a crucial, adaptive guide to human behavior. While previous developmental research has primarily focused on gaining rewards, less attention has been paid to loss processing and its avoidance. In daily life, it is often unknown how likely an action will result in a loss, making the role of uncertainty in loss processing particularly important. By using functional magnetic resonance imaging, we investigated the influence of varying outcome probabilities (12%, 34%, and 67%) on brain regions implicated in loss processing (ventral striatum (VS), anterior insula (AI)) by comparing 28 adolescents (10-18 years) and 24 adults (22-32 years) during the anticipation of potential monetary loss.Overall, results revealed slower RTs in adolescents compared to adults with both groups being faster in the experimental (monetary condition) vs. control trials (verbal condition). Fastest RTs were observed for the 67% outcome probability in both age groups. An age group × outcome probability interaction effect revealed the greatest differences between the groups for the 12% vs. the 67% outcome probability. Neurally, both age groups demonstrated a higher percent signal change in the VS and AI during the anticipation of potential monetary loss versus the verbal condition. However, adults demonstrated an even greater activation of VS and AI than adolescents during the anticipation of potential monetary loss, but not during the verbal condition. This may indicate that adolescents differ from adults regarding their experience of avoiding losing monetary rewards.

We investigated development from adolescence to young adulthood of neural bottom-up and top-down processes using a functional magnetic resonance imaging task on emotional attention. We followed 249 participants from age 14-22 in up to four waves resulting in 687 total scans of a matching task in which participants decided whether two pictures were the same including distracting emotional or neutral scenes. We applied generalized additive mixed models and a reliability approach for longitudinal analysis. Reaction times and error rates decreased longitudinally. For top-down processing, we found a longitudinal increase for the bilateral inferior frontal gyrus (IFG) for negative stimuli and in the left IFG also for positive and neutral stimuli. For bottom-up activation in the bilateral amygdala, we found a relative stability for negative and neutral stimuli. For positive stimuli, there was an increase starting in the twenties. Results show ongoing behavioral and top-down prefrontal development relatively independent from emotional valence. Amygdala bottom-up activation remained stable except for positive stimuli. Current findings add to the sparse literature on longitudinal top-down and bottom-up development into young adulthood and emphasize the role of reliability. These findings might help to characterize healthy in contrast to dysfunctional development of emotional attention., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Structural magnetic resonance imaging (sMRI) offers immense potential for increasing our understanding of how anatomical brain development relates to clinical symptoms and functioning in neurodevelopmental disorders. Clinical developmental sMRI may help identify neurobiological risk factors or markers that may ultimately assist in diagnosis and treatment. However, researchers and clinicians aiming to conduct sMRI studies of neurodevelopmental disorders face several methodological challenges. This review offers hands-on guidelines for clinical developmental sMRI. First, we present brain morphometry metrics and review evidence on typical developmental trajectories throughout adolescence, together with atypical trajectories in selected neurodevelopmental disorders. Next, we discuss challenges and good scientific practices in study design, image acquisition and analysis, and recent options to implement quality control. Finally, we discuss choices related to statistical analysis and interpretation of results. We call for greater completeness and transparency in the reporting of methods to advance understanding of structural brain alterations in neurodevelopmental disorders., (© 2021. The Author(s).)

Early initiation of polysubstance use (PSU) is a strong predictor of subsequent addiction, however scarce individuals present resilience capacity. This neuroimaging study aimed to investigate structural correlates associated with cessation or reduction of PSU and determine the extent to which brain structural features accounted for this resilient outcome. Participants from a European community-based cohort self-reported their alcohol, tobacco and cannabis use frequency at ages 14, 16 and 19 and had neuroimaging sessions at ages 14 and 19. We included three groups in the study: the resilient-to-PSU participants showed PSU at 16 and/or 14 but no more at 19 (n = 18), the enduring polysubstance users at 19 displayed PSU continuation from 14 or 16 (n = 193) and the controls were abstinent or low drinking participants (n = 460). We conducted between-group comparisons of grey matter volumes on whole brain using voxel-based morphometry and regional fractional anisotropy using tract-based spatial statistics. Random-forests machine-learning approach generated individual-level PSU-behavior predictions based on personality and neuroimaging features. Adolescents resilient to PSU showed significant larger grey matter volumes in the bilateral cingulate gyrus compared with enduring polysubstance users and controls at ages 19 and 14 (p<0.05 corrected) but no difference in fractional anisotropy. The larger cingulate volumes and personality trait "openness to experience" were the best precursors of resilience to PSU. Early in adolescence, a larger cingulate gyrus differentiated adolescents resilient to PSU, and this feature was critical in predicting this outcome. This study encourages further research into the neurobiological bases of resilience to addictive behaviors., (Copyright © 2021. Published by Elsevier B.V.)

Adolescence has been linked to an enhanced tolerance of uncertainty and risky behavior and is possibly connected to an increased response toward rewards. However, previous research has produced inconsistent findings. To investigate whether these findings are due to different reward probabilities used in the experimental design, we extended a monetary incentive delay (MID) task by including three different reward probabilities. Using functional magnetic resonance imaging, 25 healthy adolescents and 22 adults were studied during anticipation of rewards in the VS. Differently colored cue stimuli indicated either a monetary or verbal trial and symbolized different reward probabilities, to which the participants were blinded. Results demonstrated faster reaction times for lower reward probabilities (33%) in both age groups. Adolescents were slower through all conditions and had less activation on a neural level. Imaging results showed a three-way interaction between age group x condition x reward probability with differences in percent signal change between adolescents and adults for the high reward probabilities (66%, 88%) while adolescents demonstrated differences for the lowest (33%). Therefore, previous inconsistent findings could be due to different reward probabilities, which makes examining these crucial for a better understanding of adolescent and adult behavior., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Bretzke, Wahl, Plichta, Wolff, Roessner, Vetter and Buse.)

There is an extensive body of literature linking ADHD to overweight and obesity. Research indicates that impulsivity features of ADHD account for a degree of this overlap. The neural and polygenic correlates of this association have not been thoroughly examined. In participants of the IMAGEN study, we found that impulsivity symptoms and body mass index (BMI) were associated (r = 0.10, n = 874, p = 0.014 FWE corrected), as were their respective polygenic risk scores (PRS) (r = 0.17, n = 874, p = 6.5 × 10 -6 FWE corrected). We then examined whether the phenotypes of impulsivity and BMI, and the PRS scores of ADHD and BMI, shared common associations with whole-brain grey matter and the Monetary Incentive Delay fMRI task, which associates with reward-related impulsivity. A sparse partial least squared analysis (sPLS) revealed a shared neural substrate that associated with both the phenotypes and PRS scores. In a last step, we conducted a bias corrected bootstrapped mediation analysis with the neural substrate score from the sPLS as the mediator. The ADHD PRS associated with impulsivity symptoms (b = 0.006, 90% CIs = 0.001, 0.019) and BMI (b = 0.009, 90% CIs = 0.001, 0.025) via the neuroimaging substrate. The BMI PRS associated with BMI (b = 0.014, 95% CIs = 0.003, 0.033) and impulsivity symptoms (b = 0.009, 90% CIs = 0.001, 0.025) via the neuroimaging substrate. A common neural substrate may (in part) underpin shared genetic liability for ADHD and BMI and the manifestation of their (observable) phenotypic association.

Attention-Deficit/Hyperactivity Disorder (ADHD) and conduct disorder (CD) exemplify top-down dysregulation conditions that show a large comorbidity and shared genetics. At the same time, they entail two different types of symptomology involving mainly non-emotional or emotional dysregulation. Few studies have tried to separate the specific biology underlying these two dimensions. It has also been suggested that both types of conditions consist of extreme cases in the general population where the symptoms are widely distributed. Here we test whether brain structure is specifically associated to ADHD or CD symptoms in a general population of adolescents (n = 1093) being part of the IMAGEN project. Both ADHD symptoms and CD symptoms were related to similar and overlapping MRI findings of a smaller structure in prefrontal and anterior cingulate cortex. However, our regions of interest (ROI) approach indicated that gray matter volume (GMV) and surface area (SA) in dorsolateral/dorsomedial prefrontal cortex and caudal anterior cingulate cortex were negatively associated to ADHD symptoms when controlling for CD symptoms while rostral anterior cingulate cortex GMV was negatively associated to CD symptoms when controlling for ADHD symptoms. The structural findings were mirrored in performance of neuropsychological tests dependent on prefrontal and anterior cingulate regions, showing that while performance on the Stop Signal test was specifically related to the ADHD trait, delayed discounting and working memory were related to both ADHD and CD traits. These results point towards a partially domain specific and dimensional capacity in different top-down regulatory systems associated with ADHD and CD symptoms.

Adding context information has been shown to attenuate the age-related decline of emotion recognition. Specifically, older adults might benefit from emotional congruent context information due to their greater social knowledge. Contrary, emotional neutral context information might impair older adults' performance more due to their decline of inhibitory abilities. Our aim was to examine the age-related decline of complex emotion recognition across three context conditions (emotional congruent, emotional neutral and no context). We hypothesized that emotional congruent context will help older adults to perform at the same level as younger adults and expected worse performance of older adults in the emotional neutral and no context conditions. Twenty-eight older and 28 younger adults watched film clips with complex emotions preceded by a fixation cross (no context), emotional congruent context or emotional neutral context. Emotional neutral context affected older adults' performance more negatively than young adults', whereas emotional congruent improved performance of both young and older adults to a similar extent. Results suggest that emotional congruent context does not eliminate the overall age-related deficit in complex emotion recognition. In contrast, this deficit might be intensified by emotional neutral context.

Objective: Cannabis consumption during adolescence has been reported as a risk factor for psychotic-like experiences (PLEs) and schizophrenia. However, brain developmental processes associated with cannabis-related PLEs are still poorly described., Method: A total of 706 adolescents from the general population who were recruited by the IMAGEN consortium had structural magnetic resonance imaging scans at both 14 and 19 years of age. We used deformation-based morphometry to map voxelwise brain changes between the two time points, using the pairwise algorithm in SPM12b. We used an a priori region-of-interest approach focusing on the hippocampus/parahippocampus to perform voxelwise linear regressions. Lifetime cannabis consumption was assessed using the European School Survey Project on Alcohol and other Drugs (ESPAD), and PLEs were assessed with the Comprehensive Assessment Psychotic-like experiences (CAPE) tool. We first tested whether hippocampus/parahippocampus development was associated with PLEs. Then we formulated and tested an a priori simple mediation model in which uncus development mediates the association between lifetime cannabis consumption and PLEs., Results: We found that PLEs were associated with reduced expansion within a specific region of the right hippocampus/parahippocampus formation, the uncus (p = .002 at the cluster level, p = .018 at the peak level). The partial simple mediation model revealed a significant total effect from lifetime cannabis consumption to PLEs (b = 0.069, 95% CI = 0.04-0.1, p =2 × 10 -16 ), as well as a small yet significant, indirect effect of right uncus development (0.004; 95% CI = 0.0004-0.01, p = .026)., Conclusion: We show here that the uncus development is involved in the cerebral basis of PLEs in a population-based sample of healthy adolescents., (Copyright © 2019 American Academy of Child and Adolescent Psychiatry. Published by Elsevier Inc. All rights reserved.)

Though adolescence is a time of emerging sex differences in emotions, sex-related differences in the anatomy of the maturing brain has been under-explored over this period. The aim of this study was to investigate whether puberty and sexual differentiation in brain maturation could explain emotional differences between girls and boys during adolescence. We adapted a dedicated longitudinal pipeline to process structural and diffusion images from 335 typically developing adolescents between 14 and 16 years. We used voxel-based and Regions of Interest approaches to explore sex and puberty effects on brain and behavioral changes during adolescence. Sexual differences in brain maturation were characterized by amygdala and hippocampal volume increase in boys and decrease in girls. These changes were mediating the sexual differences in positive emotional regulation as illustrated by positive attributes increase in boys and decrease in girls. Moreover, the differential maturation rates between the limbic system and the prefrontal cortex highlighted the delayed maturation in boys compared to girls. This is the first study to show the sex effects on the differential cortico/subcortical maturation rates and the interaction between sex and puberty in the limbic system maturation related to positive attributes, reported as being protective from emotional disorders., (Copyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved.)

Importance: Alcohol abuse correlates with gray matter development in adolescents, but the directionality of this association remains unknown., Objective: To investigate the directionality of the association between gray matter development and increase in frequency of drunkenness among adolescents., Design, Setting, and Participants: This cohort study analyzed participants of IMAGEN, a multicenter brain imaging study of healthy adolescents in 8 European sites in Germany (Mannheim, Dresden, Berlin, and Hamburg), the United Kingdom (London and Nottingham), Ireland (Dublin), and France (Paris). Data from the second follow-up used in the present study were acquired from January 1, 2013, to December 31, 2016, and these data were analyzed from January 1, 2016, to March 31, 2018. Analyses were controlled for sex, site, socioeconomic status, family history of alcohol dependency, puberty score, negative life events, personality, cognition, and polygenic risk scores. Personality and frequency of drunkenness were assessed at age 14 years (baseline), 16 years (first follow-up), and 19 years (second follow-up). Structural brain imaging scans were acquired at baseline and second follow-up time points., Main Outcomes and Measures: Increases in drunkenness frequency were measured by latent growth modeling, a voxelwise hierarchical linear model was used to observe gray matter volume, and tensor-based morphometry was used for gray matter development. The hypotheses were formulated before the data analyses., Results: A total of 726 adolescents (mean [SD] age at baseline, 14.4 [0.38] years; 418 [58%] female) were included. The increase in drunkenness frequency was associated with accelerated gray matter atrophy in the left posterior temporal cortex (peak: t1,710 = -5.8; familywise error (FWE)-corrected P = 7.2 × 10-5; cluster: 6297 voxels; P = 2.7 × 10-5), right posterior temporal cortex (cluster: 2070 voxels; FWE-corrected P = .01), and left prefrontal cortex (peak: t1,710 = -5.2; FWE-corrected P = 2 × 10-3; cluster: 10 624 voxels; P = 1.9 × 10-7). According to causal bayesian network analyses, 73% of the networks showed directionality from gray matter development to drunkenness increase as confirmed by accelerated gray matter atrophy in late bingers compared with sober controls (n = 20 vs 60; β = 1.25; 95% CI, -2.15 to -0.46; t1,70 = 0.3; P = .004), the association of drunkenness increase with gray matter volume at age 14 years (β = 0.23; 95% CI, 0.01-0.46; t1,584 = 2; P = .04), the association between gray matter atrophy and alcohol drinking units (β = -0.0033; 95% CI, -6 × 10-3 to -5 × 10-4; t1,509 = -2.4; P = .02) and drunkenness frequency at age 23 years (β = -0.16; 95% CI, -0.28 to -0.03; t1,533 = -2.5; P = .01), and the linear exposure-response curve stratified by gray matter atrophy and not by increase in frequency of drunkenness., Conclusions and Relevance: This study found that gray matter development and impulsivity were associated with increased frequency of drunkenness by sex. These results suggest that neurotoxicity-related gray matter atrophy should be interpreted with caution.

About 50% of attention deficit hyperactivity disorder (ADHD) patients suffer from comorbidity with oppositional defiant disorder/conduct disorder (ODD/CD). Most previous studies on structural morphology did not differentiate between pure (ADHD-only) and comorbid ADHD (ADHD+ODD/CD). Therefore, we aimed to investigate the structural profile of ADHD-only versus ADHD+ODD/CD spanning the indices subcortical and cortical volume, cortical thickness, and surface area. We predicted a reduced total gray matter, striatal, and cerebellar volume in both patient groups and a reduced amygdalar and hippocampal volume for ADHD+ODD/CD. We also explored alterations in prefrontal volume, thickness, and surface area. We acquired structural images from an adolescent sample ranging from 11 to 17 years, matched with regard to age, pubertal status, and IQ-including 36 boys with ADHD-only, 26 boys with ADHD+ODD/CD, and 30 typically developing (TD) boys. We analyzed structural data with FreeSurfer. We found reductions in total gray matter and total surface area for both patient groups. Boys with ADHD+ODD/CD had a thicker cortex than the other groups in a right rostral middle frontal cluster, which was related to stronger ODD/CD symptoms, even when controlling for ADHD symptoms. No group differences in local cortical volume or surface area emerged. We demonstrate the necessity to carefully differentiate between ADHD and ADHD+ODD/CD. The increased rostral middle frontal thickness might hint at a delayed adolescent cortical thinning in ADHD+ODD/CD. Patients with the double burden ADHD and ODD or CD seem to be even more affected than patients with pure ADHD., (© 2019 The Authors. Human Brain Mapping published by Wiley Periodicals, Inc.)

Great advances have been made in functional Magnetic Resonance Imaging (fMRI) studies, including the use of longitudinal design to more accurately identify changes in brain development across childhood and adolescence. While longitudinal fMRI studies are necessary for our understanding of typical and atypical patterns of brain development, the variability observed in fMRI blood-oxygen-level dependent (BOLD) signal and its test-retest reliability in developing populations remain a concern. Here we review the current state of test-retest reliability for child and adolescent fMRI studies (ages 5-18 years) as indexed by intraclass correlation coefficients (ICC). In addition to highlighting ways to improve fMRI test-retest reliability in developmental cognitive neuroscience research, we hope to open a platform for dialogue regarding longitudinal fMRI study designs, analyses, and reporting of results., (Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Patients with attention deficit hyperactivity disorder (ADHD) suffer from poor emotion regulation that might arise from problems in the distribution of attentional resources when confronted with emotional distractors. Previous studies investigating the neurocognitive basis of these problems remain inconclusive. Moreover, most of these studies did not exclude participants with comorbidity, particularly of conduct or oppositional defiant disorder. The aim of this study was to assess alterations in fronto-limbic activation in ADHD adolescents specifically during negative distractors in an emotional attention task. For this purpose, we used functional magnetic resonance imaging to assess 25 boys with noncomorbid ADHD and 25 typically developing (TD) boys while they performed an emotional attention task with positive, negative, and neutral emotional distractors. Boys with ADHD had increased activation relative to TD boys specifically during the negative valenced stimuli in an emotional processing network comprising left anterior insula reaching into the inferior frontal gyrus. The findings suggest altered salience processing in ADHD of negative valenced emotional stimuli that may lead to higher distractibility in ADHD specifically when faced with negative emotional distractors., (© 2018 Wiley Periodicals, Inc.)

Basic facial emotion recognition is suggested to be negatively affected by puberty onset reflected in a "pubertal dip" in performance compared to pre- or post-puberty. However, findings remain inconclusive. Further, research points to an own-age bias, i.e., a superior emotion recognition for peer faces. We explored adolescents' ability to recognize specific emotions. Ninety-five children and adolescents, aged 8-17 years, judged whether the emotions displayed by adolescent or adult faces were angry, sad, neutral, or happy. We assessed participants a priori by pubertal status while controlling for age. Results indicated no "pubertal dip", but decreasing reaction times across adolescence. No own-age bias was found. Taken together, basic facial emotion recognition does not seem to be disrupted during puberty as compared to pre- and post-puberty.

Background: Nociceptin is a key regulator linking environmental stress and alcohol drinking. In a genome-wide methylation analysis, we recently identified an association of a methylated region in the OPRL1 gene with alcohol-use disorders., Methods: Here, we investigate the biological basis of this observation by analysing psychosocial stressors, methylation of the OPRL1 gene, brain response during reward anticipation and alcohol drinking in 660 fourteen-year-old adolescents of the IMAGEN study. We validate our findings in marchigian sardinian (msP) alcohol-preferring rats that are genetically selected for increased alcohol drinking and stress sensitivity., Results: We found that low methylation levels in intron 1 of OPRL1 are associated with higher psychosocial stress and higher frequency of binge drinking, an effect mediated by OPRL1 methylation. In individuals with low methylation of OPRL1, frequency of binge drinking is associated with stronger BOLD response in the ventral striatum during reward anticipation. In msP rats, we found that stress results in increased alcohol intake and decreased methylation of OPRL1 in the nucleus accumbens., Conclusions: Our findings describe an epigenetic mechanism that helps to explain how psychosocial stress influences risky alcohol consumption and reward processing, thus contributing to the elucidation of biological mechanisms underlying risk for substance abuse., (© 2017 Association for Child and Adolescent Mental Health.)

The two hemispheres of the human brain differ functionally and structurally. Despite over a century of research, the extent to which brain asymmetry is influenced by sex, handedness, age, and genetic factors is still controversial. Here we present the largest ever analysis of subcortical brain asymmetries, in a harmonized multi-site study using meta-analysis methods. Volumetric asymmetry of seven subcortical structures was assessed in 15,847 MRI scans from 52 datasets worldwide. There were sex differences in the asymmetry of the globus pallidus and putamen. Heritability estimates, derived from 1170 subjects belonging to 71 extended pedigrees, revealed that additive genetic factors influenced the asymmetry of these two structures and that of the hippocampus and thalamus. Handedness had no detectable effect on subcortical asymmetries, even in this unprecedented sample size, but the asymmetry of the putamen varied with age. Genetic drivers of asymmetry in the hippocampus, thalamus and basal ganglia may affect variability in human cognition, including susceptibility to psychiatric disorders.

Objective: The authors sought to explore how conduct, hyperactivity/inattention, and emotional symptoms are associated with neural reactivity to social-emotional stimuli, and the extent to which psychosocial stress modulates these relationships., Method: Participants were community adolescents recruited as part of the European IMAGEN study. Bilateral amygdala regions of interest were used to assess the relationship between the three symptom domains and functional MRI neural reactivity during passive viewing of dynamic angry and neutral facial expressions. Exploratory functional connectivity and whole brain multiple regression approaches were used to analyze how the symptoms and psychosocial stress relate to other brain regions., Results: In response to the social-emotional stimuli, adolescents with high levels of conduct or hyperactivity/inattention symptoms who had also experienced a greater number of stressful life events showed hyperactivity of the amygdala and several regions across the brain. This effect was not observed with emotional symptoms. A cluster in the midcingulate was found to be common to both conduct problems and hyperactivity symptoms. Exploratory functional connectivity analyses suggested that amygdala-precuneus connectivity is associated with hyperactivity/inattention symptoms., Conclusions: The results link hyperactive amygdala responses and regions critical for top-down emotional processing with high levels of psychosocial stress in individuals with greater conduct and hyperactivity/inattention symptoms. This work highlights the importance of studying how psychosocial stress affects functional brain responses to social-emotional stimuli, particularly in adolescents with externalizing symptoms.

Objective: This study investigated the neural correlates of psychotic-like experiences in youths during tasks involving inhibitory control, reward anticipation, and emotion processing. A secondary aim was to test whether these neurofunctional correlates of risk were predictive of psychotic symptoms 2 years later., Method: Functional imaging responses to three paradigms-the stop-signal, monetary incentive delay, and faces tasks-were collected in youths at age 14, as part of the IMAGEN study. At baseline, youths from London and Dublin sites were assessed on psychotic-like experiences, and those reporting significant experiences were compared with matched control subjects. Significant brain activity differences between the groups were used to predict, with cross-validation, the presence of psychotic symptoms in the context of mood fluctuation at age 16, assessed in the full sample. These prediction analyses were conducted with the London-Dublin subsample (N=246) and the full sample (N=1,196)., Results: Relative to control subjects, youths reporting psychotic-like experiences showed increased hippocampus/amygdala activity during processing of neutral faces and reduced dorsolateral prefrontal activity during failed inhibition. The most prominent regional difference for classifying 16-year-olds with mood fluctuation and psychotic symptoms relative to the control groups (those with mood fluctuations but no psychotic symptoms and those with no mood symptoms) was hyperactivation of the hippocampus/amygdala, when controlling for baseline psychotic-like experiences and cannabis use., Conclusions: The results stress the importance of the limbic network's increased response to neutral facial stimuli as a marker of the extended psychosis phenotype. These findings might help to guide early intervention strategies for at-risk youths.

Longitudinal developmental fMRI studies just recently began to focus on within-subject reliability using the intraclass coefficient (ICC). It remains largely unclear which degree of reliability can be achieved in developmental studies and whether this depends on the type of task used. Therefore, we aimed to systematically investigate the reliability of three well-classified tasks: an emotional attention, a cognitive control, and an intertemporal choice paradigm. We hypothesized to find higher reliability in the cognitive task than in the emotional or reward-related task. 104 healthy mid-adolescents were scanned at age 14 and again at age 16 within M = 1.8 years using the same paradigms, scanner, and scanning protocols. Overall, we found both variability and stability (i.e. poor to excellent ICCs) depending largely on the region of interest (ROI) and task. Contrary to our hypothesis, whole brain reliability was fair for the cognitive control task but good for the emotional attention and intertemporal choice task. Subcortical ROIs (ventral striatum, amygdala) resulted in lower ICCs than visual ROIs. Current results add to the yet sparse overall ICC literature in both developing samples and adults. This study shows that analyses of stability, i.e. reliability, are helpful benchmarks for longitudinal studies and their implications for adolescent development.

In structural magnetic resonance imaging motion artifacts are common, especially when not scanning healthy young adults. It has been shown that motion affects the analysis with automated image-processing techniques (e.g., FreeSurfer). This can bias results. Several developmental and adult studies have found reduced volume and thickness of gray matter due to motion artifacts. Thus, quality control is necessary in order to ensure an acceptable level of quality and to define exclusion criteria of images (i.e., determine participants with most severe artifacts). However, information about the quality control workflow and image exclusion procedure is largely lacking in the current literature and the existing rating systems differ. Here, we propose a stringent workflow of quality control steps during and after acquisition of T1-weighted images, which enables researchers dealing with populations that are typically affected by motion artifacts to enhance data quality and maximize sample sizes. As an underlying aim we established a thorough quality control rating system for T1-weighted images and applied it to the analysis of developmental clinical data using the automated processing pipeline FreeSurfer. This hands-on workflow and quality control rating system will aid researchers in minimizing motion artifacts in the final data set, and therefore enhance the quality of structural magnetic resonance imaging studies.

Reaction times (RTs) are a valuable measure for assessing cognitive processes. However, RTs are susceptible to confounds and therefore variable. Exposure to threat, for example, speeds up or slows down responses. Distinct task types to some extent account for differential effects of threat on RTs. But also do inter-individual differences like trait anxiety. In this functional magnetic resonance imaging (fMRI) study, we investigated whether activation within the amygdala, a brain region closely linked to the processing of threat, may also function as a predictor of RTs, similar to trait anxiety scores. After threat conditioning by means of aversive electric shocks, 45 participants performed a choice RT task during alternating 30 s blocks in the presence of the threat conditioned stimulus [CS+] or of the safe control stimulus [CS-]. Trait anxiety was assessed with the State-Trait Anxiety Inventory and participants were median split into a high- and a low-anxiety subgroup. We tested three hypotheses: (1) RTs will be faster during the exposure to threat compared to the safe condition in individuals with high trait anxiety. (2) The amygdala fMRI signal will be higher in the threat condition compared to the safe condition. (3) Amygdala fMRI signal prior to a RT trial will be correlated with the corresponding RT. We found that, the high-anxious subgroup showed faster responses in the threat condition compared to the safe condition, while the low-anxious subgroup showed no significant difference in RTs in the threat condition compared to the safe condition. Though the fMRI analysis did not reveal an effect of condition on amygdala activity, we found a trial-by-trial correlation between blood-oxygen-level-dependent signal within the right amygdala prior to the CRT task and the subsequent RT. Taken together, the results of this study showed that exposure to threat modulates task performance. This modulation is influenced by personality trait. Additionally and most importantly, activation in the amygdala predicts behavior in a simple task that is performed during the exposure to threat. This finding is in line with "attentional capture by threat"-a model that includes the amygdala as a key brain region for the process that causes the response slowing.

Importance: Psychotic disorders are characterized by attenuated activity in the brain's valuation system in key reward processing areas, such as the ventral striatum (VS), as measured with functional magnetic resonance imaging., Objective: To examine whether common risk variants for psychosis are associated with individual variation in the VS., Design, Setting, and Participants: A cross-sectional study of a large cohort of adolescents from the IMAGEN study (a European multicenter study of reinforcement sensitivity in adolescents) was performed from March 1, 2008, through December 31, 2011. Data analysis was conducted from October 1, 2015, to January 9, 2016. Polygenic risk profile scores (RPSs) for psychosis were generated for 1841 healthy adolescents. Sample size and characteristics varied across regression analyses, depending on mutual information available (N = 1524-1836)., Main Outcomes and Measures: Reward-related brain function was assessed with blood oxygen level dependency (BOLD) in the VS using the monetary incentive delay (MID) task, distinguishing reward anticipation and receipt. Behavioral impulsivity, IQ, MID task performance, and VS BOLD were regressed against psychosis RPS at 4 progressive P thresholds (P < .01, P < .05, P < .10, and P < .50 for RPS models 1-4, respectively)., Results: In a sample of 1841 healthy adolescents (mean age, 14.5 years; 906 boys and 935 girls), we replicated an association between increasing psychosis RPS and reduced IQ (matrix reasoning: corrected P = .003 for RPS model 2, 0.4% variance explained), supporting the validity of the psychosis RPS models. We also found a nominally significant association between increased psychosis RPS and reduced MID task performance (uncorrected P = .03 for RPS model 4, 0.2% variance explained). Our main finding was a positive association between psychosis RPS and VS BOLD during reward anticipation at all 4 psychosis RPS models and for 2 P thresholds for reward receipt (RPS models 1 and 3), correcting for the familywise error rate (0.8%-1.9% variance explained)., Conclusions and Relevance: These findings support an association between psychosis RPS and VS BOLD in adolescents. Genetic risk for psychosis may shape an individual's response to rewarding stimuli.

The processing of emotional faces is an important prerequisite for adequate social interactions in daily life, and might thus specifically be altered in adolescence, a period marked by significant changes in social emotional processing. Previous research has shown that the cannabinoid receptor CB1R is associated with longer gaze duration and increased brain responses in the striatum to happy faces in adults, yet, for adolescents, it is not clear whether an association between CBR1 and face processing exists. In the present study we investigated genetic effects of the two CB1R polymorphisms, rs1049353 and rs806377, on the processing of emotional faces in healthy adolescents. They participated in functional magnetic resonance imaging during a Faces Task, watching blocks of video clips with angry and neutral facial expressions, and completed a Morphed Faces Task in the laboratory where they looked at different facial expressions that switched from anger to fear or sadness or from happiness to fear or sadness, and labelled them according to these four emotional expressions. A-allele versus GG-carriers in rs1049353 displayed earlier recognition of facial expressions changing from anger to sadness or fear, but not for expressions changing from happiness to sadness or fear, and higher brain responses to angry, but not neutral, faces in the amygdala and insula. For rs806377 no significant effects emerged. This suggests that rs1049353 is involved in the processing of negative facial expressions with relation to anger in adolescence. These findings add to our understanding of social emotion-related mechanisms in this life period., (© 2015 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.)

The main purpose of the present study was to analyse the internal structure and to test the measurement invariance of the Strengths and Difficulties Questionnaire (SDQ), self-reported version, in five European countries. The sample consisted of 3012 adolescents aged between 12 and 17 years (M = 14.20; SD = 0.83). The five-factor model (with correlated errors added), and the five-factor model (with correlated errors added) with the reverse-worded items allowed to cross-load on the Prosocial subscale, displayed adequate goodness of-fit indices. Multi-group confirmatory factor analysis showed that the five-factor model (with correlated errors added) had partial strong measurement invariance by countries. A total of 11 of the 25 items were non-invariant across samples. The level of internal consistency of the Total difficulties score was 0.84, ranging between 0.69 and 0.78 for the SDQ subscales. The findings indicate that the SDQ's subscales need to be modified in various ways for screening emotional and behavioural problems in the five European countries that were analysed.

Appropriate reactions toward emotional stimuli depend on the distribution of prefrontal attentional resources. In mid-adolescence, prefrontal top-down control systems are less engaged, while subcortical bottom-up emotional systems are more engaged. We used functional magnetic resonance imaging to follow the neural development of attentional distribution, i.e. attending versus ignoring emotional stimuli, in adolescence. 144 healthy adolescents were studied longitudinally at age 14 and 16 while performing a perceptual discrimination task. Participants viewed two pairs of stimuli--one emotional, one abstract--and reported on one pair whether the items were the same or different, while ignoring the other pair. Hence, two experimental conditions were created: "attending emotion/ignoring abstract" and "ignoring emotion/attending abstract". Emotional valence varied between negative, positive, and neutral. Across conditions, reaction times and error rates decreased and activation in the anterior cingulate and inferior frontal gyrus increased from age 14 to 16. In contrast, subcortical regions showed no developmental effect. Activation of the anterior insula increased across ages for attending positive and ignoring negative emotions. Results suggest an ongoing development of prefrontal top-down resources elicited by emotional attention from age 14 to 16 while activity of subcortical regions representing bottom-up processing remains stable., (Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Research indicates ongoing development of prospective memory as well as theory of mind and executive functions across late childhood and adolescence. However, so far the interplay of these processes has not been investigated. Therefore, the purpose of the current study was to investigate whether theory of mind and executive control processes (specifically updating, switching, and inhibition) predict prospective memory development across adolescence. In total, 42 adolescents and 41 young adults participated in this study. Young adults outperformed adolescents on tasks of prospective memory, theory of mind, and executive functions. Switching and theory of mind predicted prospective memory performance in adolescents., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Affective Theory of Mind (ToM), an important aspect of ToM, involves the understanding of affective mental states. This ability is critical in the developmental phase of adolescence, which is often related with socio-emotional problems. Using a developmentally sensitive behavioral task in combination with functional magnetic resonance imaging, the present study investigated the neural development of affective ToM throughout adolescence. Eighteen adolescent (ages 12-14 years) and 18 young adult women (aged 19-25 years) were scanned while evaluating complex affective mental states depicted by actors in video clips. The ventromedial prefrontal cortex (vmPFC) showed significantly stronger activation in adolescents in comparison to adults in the affective ToM condition. Current results indicate that the vmPFC might be involved in the development of affective ToM processing in adolescence., (© The Author (2013). Published by Oxford University Press. For Permissions, please email: journals.permissions@oup.com.)

Objective: Functional magnetic resonance imaging (fMRI) studies have identified increased amygdala responses to negative stimuli as a risk marker of depression in adults, and as a state marker of depression in adults and adolescents. Hyperreactivity of the amygdala has been linked to negatively biased emotional processing in depression. However, no study has elucidated whether similar amygdala perturbations can be found in healthy mid-adolescents with familial liability for depression. We hypothesized that healthy 14-year-olds with relatives with depression would demonstrate increased amygdala responses to negative stimuli, as compared with their peers with no family history of mental disorders., Method: We investigated a community-based sample of 164 typically developing 14-year-olds without record of past or current mental disorders. Of these individuals, 28 fulfilled criteria for family history of depression, and 136 served as controls. Groups did not differ with regard to cognitive ability, depressive symptomatology, and anxiety. During fMRI they performed a perceptual discrimination task in which visual target and distractor stimuli varied systematically with regard to emotional valence., Results: Both a hypothesis-driven region-of-interest analysis and a whole-brain analysis of variance revealed that negative distractors elicited greater amygdala activation in adolescents with a family history of depression compared to controls. Amygdala responses also differed during the processing of negative target stimuli, but effects were reversed., Conclusion: Our study demonstrates that familial liability for depression is associated with correlates of negatively biased emotional processing in healthy adolescents. Amygdala perturbations during the processing of negative stimuli might reflect an early and subtle risk marker for depression., (Copyright © 2014 American Academy of Child and Adolescent Psychiatry. Published by Elsevier Inc. All rights reserved.)

The primary aim of this study was to examine the impact of an inhibition manipulation on the effect of age on theory of mind (ToM) in an ecologically valid, affective ToM task. Participants were 30 young and 30 old adults. The Cambridge Mindreading Face-Voice Battery was used to measure ToM; in addition, measures of fluid and crystallized intelligence were taken. Participants were subjected to three levels of inhibitory demand during ToM reasoning: emotional inhibition, non-emotional inhibition, and no inhibition. Old adults performed worse than young adults. The emotional and non-emotional inhibition conditions resulted in worse ToM performance compared to the no inhibition condition. There were no differences in the impact of the inhibition conditions on old and young adults. Regression analyses suggested that old adults' crystallized intelligence was a significant predictor of ToM performance, whereas it did not predict young adults' ToM performance. Results are discussed in terms of verbal ability as a possible compensatory mechanism in coping with verbal inhibitory load in ToM reasoning.

Theory of mind, the ability to understand mental states, involves inferences about others' cognitive (cognitive theory of mind) and emotional (affective theory of mind) mental states. The current study explored the role of executive functions in developing affective theory of mind across adolescence. Affective theory of mind and three subcomponents of executive functions (inhibition, updating, and shifting) were measured. Affective theory of mind was positively related to age, and all three executive functions. Specifically, inhibition explained the largest amount of variance in age-related differences in affective theory of mind.

Age differences in social cognition between adolescents and young adults were investigated. Two large groups of adolescents and young adults were given tasks of theory of mind and emotion recognition. In addition, to control for possibly related basic cognitive development, working memory, speed of processing, and verbal ability were assessed. A strong age effect was revealed across both measures of social cognition. Adolescents performed with a lower accuracy than adults. Further analyses indicated that those age differences remained significant even after controlling for basic cognitive abilities. Exploratory analyses indicated no influence of pubertal phase on social cognition. Results suggest ongoing development of social cognition across adolescence, independent of individual differences in more basic cognitive abilities.