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Background: Cannabis use is common, particularly during emerging adulthood when brain development is ongoing, and its use is associated with harmful outcomes for a subset of people. An improved understanding of the neural mechanisms underlying risk for problem-level use is critical to facilitate the development of more effective prevention and treatment approaches., Methods: The current study applied a whole-brain, data-driven, machine-learning approach to identify neural features predictive of problem-level cannabis use in a non-clinical sample of college students (n=191, 58% female) based on reward task functional connectivity data. We further examined whether the network identified would generalize to predict cannabis use in an independent sample of European adolescents/emerging adults (n=1320, 53% female), whether it would predict clinical characteristics among adults seeking treatment for cannabis use disorder (n=33, 9% female), and whether it was specific for predicting cannabis versus alcohol use outcomes across datasets., Results: Results demonstrated (i) identification of a problem cannabis risk network, which (ii) generalized to predict cannabis use in an independent sample of adolescents, and (iii) linked to increased addiction severity and poorer treatment outcome in a third sample of treatment-seeking adults; further, (iv) the identified network was specific for predicting cannabis versus alcohol use outcomes across all three datasets., Conclusions: Findings provide insight into neural mechanisms of risk for problem-level cannabis use among adolescents/emerging adults. Future work is needed to assess whether targeting this network can improve prevention and treatment outcomes., (Copyright © 2025. Published by Elsevier Inc.)

Laboratory studies show brain maturation involves synaptic pruning and cognitive development. Human studies suggest links between early cognitive performance and later mental health, but inconsistencies remain. It is unclear if specific brain regions mediate this relationship, and the molecular underpinnings are not well understood. Here, our longitudinal analyses in both the Adolescent Brain Cognitive Development and IMAGEN cohorts establish inverted U-shaped relationships between baseline executive function and subsequent symptom trajectories in the high-symptom individuals, whose externalizing (n = 963) or internalizing (n = 1762) symptoms exceed a clinical threshold at any point during the follow-up period, but not in the control group (n = 4291). Volumetric changes in the left lateral occipital cortex (LOC) mediated the relationship with externalizing symptoms (outwardly directed behaviors such as aggression), while changes in the right LOC and pars triangularis mediated the relationship with internalizing symptoms (inwardly directed emotional problems such as anxiety). Transcriptomic and genomic findings highlighted synaptic biology and particularly the gene ADCY1, which is implicated in synaptic pruning, as underlying both moderate executive function and its associated brain mediators. Notably, preadolescent cognitive performance predicts late-onset externalizing symptoms and remitting internalizing symptoms with high accuracies (area under the curve: 0.87 and 0.79). Our findings highlight the predictive value of cognitive performance for adolescent mental health trajectories, and indicate how this is mediated by specific brain regions, and underpinned by particular molecular pathways., Competing Interests: 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. Dr. Stein has received consultancy honoraria from Discovery Vitality, Johnson & Johnson, Kanna, L’Oreal, Lundbeck, Orion, Sanofi, Servier, Takeda and Vistagen. The other authors report no biomedical financial interests or potential competing interests. Ethics approval and consent to participate: Methods were carried out in accordance with the relevant guidelines and regulations. Ethical approval for the ABCD Study was granted by the institutional review boards of the University of California (San Diego) and each participating ABCD site, following their approved protocols, state regulations, and local guidelines. The IMAGEN project had obtained ethical approval by the local ethics committees, including King’s College London, University of Nottingham, Trinity College Dublin, University of Heidelberg, Technische Universität Dresden, Commissariat à l’Energie Atomique et aux Energies Alternatives, and University Medical Center, University of Hamburg, Hamburg, Germany. Informed consent was obtained from all participants., (© 2025. The Author(s), under exclusive licence to Springer Nature Limited.)

Alcohol Use Disorder (AUD), a prevalent and potentially severe psychiatric condition, is one of the leading causes of morbidity and mortality. This systematic review investigates the relationship between AUD and resting-state functional connectivity (rsFC) derived from functional magnetic resonance imaging data. Following the PRISMA guidelines, a comprehensive search yielded 248 papers, and a screening process identified 39 studies with 73 relevant analyses. Using the automated anatomical labeling atlas for whole-brain parcellation, relevance maps were generated to quantify associations between brain regions and their connections with AUD. These outcomes are based on the frequency with which significant findings are reported in the literature, to deal with the challenge of methodological diversity between analyses, including sample sizes, types of independent rsFC features, and AUD measures. The analysis focuses on whole-brain studies to mitigate selection biases associated with seed-based approaches. The most frequently reported regions include the middle and superior frontal gyri, the anterior cingulate cortex, and the insula. The generated relevance maps can serve as a valuable tool for formulating hypotheses and advancing our understanding of AUD's neural correlates in the future. This work also provides a template on how to quantitatively summarize a diverse literature, which could be applied to more specific aspects of AUD, including craving, relapse, binge drinking, or other diseases., (© 2025 The Author(s). Human Brain Mapping published by Wiley Periodicals LLC.)

Background: Advancing evidence-based, tailored interventions for substance use disorders (SUDs) requires understanding temporal directionality while upholding ecological validity. Previous studies identified loneliness and craving as pivotal factors associated with alcohol consumption, yet the precise directionality of these relationships remains ambiguous., Objective: This study aims to establish a smartphone-based real-life intervention platform that integrates momentary assessment and intervention into everyday life. The platform will explore the temporal directionality of contextual influences on alcohol use among individuals experiencing loneliness and craving., Methods: We will target 180 individuals aged 18 to 70 in Germany who report loneliness, alcohol cravings, and meet risk or binge drinking criteria (over 14 standard drinks per week or five drinks in a single day for males, and over seven drinks per week or four drinks in a single day for females). Using a Within-Person-Encouragement-Design and Just-In-Time-Adaptive-Interventions, we will manipulate the contexts of loneliness and alcohol craving with cognitive reappraisal and physical activity interventions against a control condition (working memory task)., Results: Recruitment started in June 2024, with data collection and processing expected by June 2027., Conclusion: Our real-life intervention platform endeavors to serve as a robust tool for discerning the directionality of the effects from time series data in everyday life influences on alcohol use for the future study. Ultimately, it will pave the way for low-threshold prevention, clinical treatment, and therapy to target diverse contexts of everyday life in SUD., Trial Registration: German Clinical Trials Register DRKS00033133., Competing Interests: The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2025.)

Brain glymphatic activity, as indicated by diffusion-tensor imaging analysis along the perivascular space (ALPS) index, is involved in developmental neuropsychiatric and neurodegenerative diseases, but its genetic architecture is poorly understood. Here, we identified 17 unique genome-wide significant loci and 161 candidate genes linked to the ALPS-indexes in a discovery sample of 31,021 individuals from the UK Biobank. Seven loci were replicated in two independent datasets. Genetic signals located at the 2p23.3 locus yielded significantly concordant effects in both young and aging cohorts. Genetic correlation and polygenic overlap analyses indicate a common underlying genetic mechanism between the ALPS-index, ventricular volumes, and cerebrospinal fluid tau levels, with GMNC (3q28) and C16orf95 (16q24.2) as the shared genetic basis. Our findings enhance the understanding of the genetics of the ALPS-index and provide insight for further research into the neurobiological mechanisms of glymphatic clearance activity across the lifespan and its relation to neuropsychiatric phenotypes., Competing Interests: Competing interests: The authors declare no competing interests., (© 2025. The Author(s).)

Unhealthy eating, a risk factor for eating disorders (EDs) and obesity, often coexists with emotional and behavioral problems; however, the underlying neurobiological mechanisms are poorly understood. Analyzing data from the longitudinal IMAGEN adolescent cohort, we investigated associations between eating behaviors, genetic predispositions for high body mass index (BMI) using polygenic scores (PGSs), and trajectories (ages 14-23 years) of ED-related psychopathology and brain maturation. Clustering analyses at age 23 years ( N  = 996) identified 3 eating groups: restrictive, emotional/uncontrolled and healthy eaters. BMI PGS, trajectories of ED symptoms, internalizing and externalizing problems, and brain maturation distinguished these groups. Decreasing volumes and thickness in several brain regions were less pronounced in restrictive and emotional/uncontrolled eaters. Smaller cerebellar volume reductions uniquely mediated the effects of BMI PGS on restrictive eating, whereas smaller volumetric reductions across multiple brain regions mediated the relationship between elevated externalizing problems and emotional/uncontrolled eating, independently of BMI. These findings shed light on distinct contributions of genetic risk, protracted brain maturation and behaviors in ED symptomatology., Competing Interests: Completing interestsT.B. served in an advisory or consultancy role for Eye Level, Infectopharm, Lundbeck, Medice, Neurim Pharmaceuticals, Oberberg, Roche and Takeda. He received conference support or speaker’s fees from Janssen, Medice and Takeda, and royalties from Hogrefe, Kohlhammer, CIP Medien and Oxford University Press; this work is unrelated to these relationships. G.J.B. received honoraria from General Electric Healthcare for teaching on scanner programming courses. L.P. served in an advisory or consultancy role for Roche and Viforpharm, and received speaker’s fees from Shire. She received royalties from Hogrefe, Kohlhammer and Schattauer. This work is unrelated to the above grants and relationships. All other authors declare no competing interests., (© The Author(s) 2025.)

The evidence supporting the presence of individual brain structure correlates of the externalizing spectrum (EXT) is sparse and mixed. To date, large-sample studies of brain-EXT relations have mainly found null to very small effects by focusing exclusively on either EXT-related personality traits (e.g., Hyatt et al., 2022) or EXT-related disorders/symptoms (e.g., Mewton et al., 2022). In this preregistered study using IMAGEN data ( N = 1,370), we investigated the structural brain correlates of EXT factors that comprise both personality (e.g., antagonism) and psychopathology constructs (e.g., conduct disorder) across levels of morphometric specificity. Brain morphometry was operationalized in terms of omnibus measures (e.g., total brain volume), subcortical volume, and Desikan atlas regions ( N = 161 structural magnetic resonance imaging metrics). We operationalized our integrated personality-psychopathology EXT through exploratory factor analyses of EXT-related measures, which identified two dimensions-nonsubstance use and substance use-and one overarching EXT domain. The results were consistent with previous large-sample neuroscientific investigations of EXT: The vast majority of relations were null, and all effect sizes were very small (largest marginal R² < .02). Preregistered supplementary analyses indicated that all significant relations found were driven by total intracranial volume and sex of the participant and became nonsignificant following the inclusion of these covariates. We conclude with suggestions regarding the importance of relevant covariates and large samples in clinical neuroscientific investigations. (PsycInfo Database Record (c) 2025 APA, all rights reserved).

Background: Early diagnosis and treatment of mental illnesses is hampered by the lack of reliable markers. This study used machine learning models to uncover diagnostic and risk prediction markers for eating disorders (EDs), major depressive disorder (MDD), and alcohol use disorder (AUD)., Methods: Case-control samples (aged 18-25 years), including participants with Anorexia Nervosa (AN), Bulimia Nervosa (BN), MDD, AUD, and matched controls, were used for diagnostic classification. For risk prediction, we used a longitudinal population-based sample (IMAGEN study), assessing adolescents at ages 14, 16 and 19. Regularized logistic regression models incorporated broad data domains spanning psychopathology, personality, cognition, substance use, and environment., Results: The classification of EDs was highly accurate, even when excluding body mass index from the analysis. The area under the receiver operating characteristic curves (AUC-ROC [95 % CI]) reached 0.92 [0.86-0.97] for AN and 0.91 [0.85-0.96] for BN. The classification accuracies for MDD (0.91 [0.88-0.94]) and AUD (0.80 [0.74-0.85]) were also high. The models demonstrated high transdiagnostic potential, as those trained for EDs were also accurate in classifying AUD and MDD from healthy controls, and vice versa (AUC-ROCs, 0.75-0.93). Shared predictors, such as neuroticism, hopelessness, and symptoms of attention-deficit/hyperactivity disorder, were identified as reliable classifiers. In the longitudinal population sample, the models exhibited moderate performance in predicting the development of future ED symptoms (0.71 [0.67-0.75]), depressive symptoms (0.64 [0.60-0.68]), and harmful drinking (0.67 [0.64-0.70])., Conclusions: Our findings demonstrate the potential of combining multi-domain data for precise diagnostic and risk prediction applications in psychiatry., Competing Interests: Declaration of competing interest 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. Dr. Barker has received honoraria from General Electric Healthcare for teaching on scanner programming courses. 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. M. John Broulidakis receives a salary from medical device manufacturer Emteq Labs for which he works as a research scientist. Emteq Labs had no role, financial or otherwise, in the STRATIFY or IMAGEN projects or this paper in particular. Views expressed in this paper do not necessarily reflect those of Emteq Labs. The present work is unrelated to the above grants and relationships. The other authors report no biomedical financial interests or potential conflicts of interest., (Copyright © 2024. Published by Elsevier B.V.)

Perseverative negative thoughts, known as rumination, might arise from emotional challenges and preclude mental health when transitioning into adulthood. Due to its multifaceted nature, rumination can take several ruminative response styles, that diverge in manifestations, severity, and mental health outcomes. Still, prospective ruminative phenotypes remain elusive insofar. Longitudinal study designs are ideal for stratifying ruminative response styles, especially with resting-state functional MRI whose setup naturally elicits people's ruminative traits. Here, we considered self-rated questionnaires on rumination and psychopathology, along with resting-state functional MRI data in 595 individuals assessed at age 18 and 22 from the IMAGEN cohort. We conducted independent component analysis to characterize eight single static resting-state functional networks in each subject and session and furthermore conducted a dynamic analysis, tackling the time variations of functional networks during the entire scanning time. We then investigated their longitudinal mediation role between changes in three ruminative response styles (reflective pondering, brooding, and depressive rumination) and changes in internalizing and co-morbid externalizing symptoms. Four static and two dynamic networks longitudinally differentiated these ruminative styles and showed complemental sensitivity to internalizing and co-morbid externalizing symptoms. Among these networks, the right frontoparietal network covaried with all ruminative styles but did not play any mediation role towards psychopathology. The default mode, the salience, and the limbic networks prospectively stratified these ruminative styles, suggesting that maladaptive ruminative styles are associated with altered corticolimbic function. For static measures, only the salience network played a longitudinal causal role between brooding rumination and internalizing symptoms. Dynamic measures highlighted the default-mode mediation role between the other ruminative styles and co-morbid externalizing symptoms. In conclusion, we identified the ruminative styles' psychometric and neural outcome specificities, supporting their translation into applied research on young adult mental healthcare., Competing Interests: Competing interests: TB served in an advisory or consultancy role for ADHS Digital, Infectopharm, Lundbeck, Medice, Neurim Pharmaceuticals, Oberberg GmbH, Roche, and Takeda. He received conference support or speaker’s fee by Medice and Takeda. He has been involved in clinical trials conducted by Shire & Viforpharma. He received royalties from Hogrefe, Kohlhammer, CIP Medien, and Oxford University Press. He has been involved in clinical trials conducted by Shire & Viforpharma. GB has received honoraria from General Electric Healthcare for teaching on scanner programming courses. LP 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 commercial relationships or conflicts of interest., (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)

Background: Neurobiological understanding of eating disorders (EDs) is limited. This study presents the first comparative multimodal magnetic resonance imaging assessments of anorexia nervosa and bulimia nervosa and uncovers neurobiological differences associated with these disorders., Methods: This case-control study included 57 healthy female control participants and 130 female participants with EDs (bulimia nervosa and anorexia nervosa subtypes). Structural and functional magnetic resonance imaging assessed gray matter volume (GMV), cortical thickness, and task-based activities related to reward processing, socioemotional functioning, and response inhibition. Whole-brain group differences were correlated with ED psychopathology., Results: Significant structural differences were observed in the ED group compared with healthy control participants, including reduced GMV in the left lateral orbitofrontal cortex and lower cortical thickness in the left rostral middle frontal gyrus and precuneus after adjusting for body mass index. Specific structural alterations were only evident in anorexia nervosa subgroups. GMV reductions in the orbitofrontal cortex were linked to impulsivity, while lower cortical thickness in the frontal gyrus correlated with cognitive restraint in eating, suggesting that these regions may play key roles in ED psychopathology. Functional magnetic resonance imaging also revealed notable differences. During reward anticipation, participants with EDs exhibited deactivations in the cerebellum and right superior frontal gyrus together with reduced activation in the left lingual gyrus. These functional changes were associated with heightened neuroticism. Mediation analyses suggested that starvation-related GMV reductions in EDs disrupt reward-related brain function, increase neuroticism, and reinforce cognitive restraint, likely contributing to the persistence of ED symptoms., Conclusions: These findings illuminate key neurobehavioral mechanisms that underlie EDs and point to potential brain-based targets for developing specialized treatment., (Copyright © 2024 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.)

Maternal education was strongly correlated with adolescent brain morphology, cognitive performances, and mental health. However, the molecular basis for the effects of maternal education on the structural neurodevelopment remains unknown. Here, we conducted gene-environment-wide interaction study using the Adolescent Brain Cognitive Development cohort. Seven genomic loci with significant gene-environment interactions (G×E) on regional gray matter volumes were identified, with enriched biological functions related to metabolic process, inflammatory process, and synaptic plasticity. Additionally, genetic overlapping results with behavioral and disease-related phenotypes indicated shared biological mechanism between maternal education modified neurodevelopment and related behavioral traits. Finally, by decomposing the multidimensional components of maternal education, we found that socioeconomic status, rather than family environment, played a more important role in modifying the genetic effects on neurodevelopment. In summary, our study provided analytical evidence for G×E effects regarding adolescent neurodevelopment and explored potential biological mechanisms as well as social mechanisms through which maternal education could modify the genetic effects on regional brain development.

Introduction: A growing literature has shown that exposure to adverse life events during childhood or adolescence is associated with the presence of psychotic-like experiences (PLEs), which is in turn associated with the risk of psychotic outcomes. Ruminative thinking, i.e., the tendency to dwell on particular issues or ideas, may affect the perceived aversiveness and ability to cope with adverse life events. However, the role that rumination plays in the relationship between adverse life events and the presence of PLEs remains unclear. The purpose of this study is to assess the association between adverse life events and PLEs in a longitudinal sample of young adults and adolescents, and to investigate whether this relationship is mediated by ruminative thinking., Methods: We used a longitudinal naturalistic sample of 706 volunteers assessed at ages 18 and 22 years, within the Imagen consortium. Lifetime occurrence of adverse life events (i.e., events perceived as strongly negative by participants) was investigated using the Life Events Questionnaire. The Community Assessment of Psychic Experience (CAPE-42) served to assess the presence of PLEs, while ruminative thinking was investigated through the Ruminative Response Scale., Results: Results showed that both frequency of PLEs and their persistence over time were associated with greater adverse life events exposure ( r = 0.32, p < 0.001 and F 1 = 9.8; p < 0.001, respectively) and greater ruminative response ( r = 0.66, p < 0.001 and F 1 = 94.9; p < 0.001, respectively). Mediation analyses showed that relationship between adverse life events and PLEs frequency was partially mediated by rumination (direct effect Z: 5.4, p < 0.001; indirect effect Z: 6.9, p < 0.001; total effect Z: 5.9, p < 0.001). Considering changes between the two assessment timepoints, relationship between PLEs variation between 18 and 22 years and adverse life events occurred during the same period was partially mediated by changes in rumination (direct effect Z: 2.8, p < 0.005; indirect effect Z: 4.3, p < 0.001; total effect Z: 4.3; p < 0.001)., Discussion: Overall, our findings confirm that the presence of adverse life events may increase the risk of experiencing PLEs in healthy individuals and suggest that dysfunctional coping strategies, such as ruminative thinking, may be related to psychosis proneness. Results do not disentangle whether individuals with greater risk for psychosis tend to ruminate more or whether rumination exacerbates psychosis risk., Competing Interests: GP received lecture fees from Lundbeck and MEGIN. AB received consulting fees from Biogen and lecture fees from Otsuka, Janssen, and Lundbeck. TB served in an advisory or consultancy role for eye level, Infectopharm, Medice, Neurim Pharmaceuticals, Oberberg GmbH, and Takeda, received conference support or speaker's fee by Janssen, Medice, and Takeda, and received royalties from Hogrefe Kohlhammer CIP Medien Oxford University Press. LP served in an advisory or consultancy role for Roche and Viforpharm and received speaker's fee by Shire and received royalties from Hogrefe Kohlhammer and Schattauer. The present work is unrelated to the above grants and relationships. The remaining 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. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision. The reviewer GS declared a shared affiliation, with no collaboration, with the authors AR, AB, GP, and LA to the handling editor at the time of the review., (Copyright © 2024 Fazio, Raio, Banaschewski, Bokde, Desrivières, Flor, Garavan, Gowland, Grigis, Heinz, Martinot, Paillère Martinot, Artiges, Nees, Papadopoulos Orfanos, Paus, Poustka, Smolka, Hohmann, Holz, Vaidya, Walter, Whelan, Schumann, Bertolino, Pergola, Antonucci and the IMAGEN Consortium.)

Background: Psychotic symptoms in adolescence are associated with social adversity and genetic risk for schizophrenia. This gene-environment interplay may be mediated by personality, which also develops during adolescence. We hypothesized that (i) personality development predicts later Psychosis Proneness Signs (PPS), and (ii) personality traits mediate the association between genetic risk for schizophrenia, social adversities, and psychosis., Methods: A total of 784 individuals were selected within the IMAGEN cohort (Discovery Sample-DS: 526; Validation Sample-VS: 258); personality was assessed at baseline (13-15 years), follow-up-1 (FU1, 16-17 years), and FU2 (18-20 years). Latent growth curve models served to compute coefficients of individual change across 14 personality variables. A support vector machine algorithm employed these coefficients to predict PPS at FU3 (21-24 years). We computed mediation analyses, including personality-based predictions and self-reported bullying victimization as serial mediators along the pathway between polygenic risk score (PRS) for schizophrenia and FU3 PPS. We replicated the main findings also on 1132 adolescents recruited within the TRAILS cohort., Results: Growth scores in neuroticism and openness predicted PPS with 65.6% balanced accuracy in the DS, and 69.5% in the VS Mediations revealed a significant positive direct effect of PRS on PPS (confidence interval [CI] 0.01-0.15), and an indirect effect, serially mediated by personality-based predictions and victimization (CI 0.006-0.01), replicated in the TRAILS cohort (CI 0.0004-0.004)., Conclusions: Adolescent personality changes may predate future experiences associated with psychosis susceptibility. PPS personality-based predictions mediate the relationship between PRS and victimization toward adult PPS, suggesting that gene-environment correlations proposed for psychosis are partly mediated by personality.

Structural brain aging has demonstrated strong inter-individual heterogeneity and mirroring patterns with brain development. However, due to the lack of large-scale longitudinal neuroimaging studies, most of the existing research focused on the cross-sectional changes of brain aging. In this investigation, we present a data-driven approach that incorporate both cross-sectional changes and longitudinal trajectories of structural brain aging and identified two brain aging patterns among 37,013 healthy participants from UK Biobank. Participants with accelerated brain aging also demonstrated accelerated biological aging, cognitive decline and increased genetic susceptibilities to major neuropsychiatric disorders. Further, by integrating longitudinal neuroimaging studies from a multi-center adolescent cohort, we validated the 'last in, first out' mirroring hypothesis and identified brain regions with manifested mirroring patterns between brain aging and brain development. Genomic analyses revealed risk loci and genes contributing to accelerated brain aging and delayed brain development, providing molecular basis for elucidating the biological mechanisms underlying brain aging and related disorders., Competing Interests: HD, RS, JK, AB, SD, HF, AG, HG, PG, AH, RB, JM, MM, EA, FN, DP, SH, NN, JF, MS, NV, HW, RW, GS, XL, JF No competing interests declared, TB Dr Banaschewski served in an advisory or consultancy role for eye level, Infectopharm, Lundbeck, Medice, Neurim Pharmaceuticals, Oberberg GmbH, Roche, and Takeda. He received conference support or speaker's fee by Janssen, Medice and Takeda. He received royalities from Hogrefe, Kohlhammer, CIP Medien, Oxford University Press; the presentwork is unrelated to these relationships, CB Reviewing editor, eLife, LP 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, (© 2024, Duan et al.)

Resilience to emotional disorders is critical for adolescent mental health, especially following childhood abuse. Yet, brain signatures of resilience remain undetermined due to the differential susceptibility of the brain's emotion processing system to environmental stresses. Analyzing brain's responses to angry faces in a longitudinally large-scale adolescent cohort (IMAGEN), we identified two functional networks related to the orbitofrontal and occipital regions as candidate brain signatures of resilience. In girls, but not boys, higher activation in the orbitofrontal-related network was associated with fewer emotional symptoms following childhood abuse, but only when the polygenic burden for depression was high. This finding defined a genetic-dependent brain (GDB) signature of resilience. Notably, this GDB signature predicted subsequent emotional disorders in late adolescence, extending into early adulthood and generalizable to another independent prospective cohort (ABCD). Our findings underscore the genetic modulation of resilience-brain connections, laying the foundation for enhancing adolescent mental health through resilience promotion., Competing Interests: Declaration of interest Dr Banaschewski served in an advisory or consultancy role for eye level, Infectopharm, Lundbeck, Medice, Neurim Pharmaceuticals, Oberberg GmbH, Roche, and Takeda. He received conference support or speaker’s fee by Janssen, Medice and Takeda. He received royalities from Hogrefe, Kohlhammer, CIP Medien, Oxford University Press; the present work is unrelated to these 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.

Human brain morphology undergoes complex changes over the lifespan. Despite recent progress in tracking brain development via normative models, current knowledge of underlying biological mechanisms is highly limited. We demonstrate that human cortical thickness development and aging trajectories unfold along patterns of molecular and cellular brain organization, traceable from population-level to individual developmental trajectories. During childhood and adolescence, cortex-wide spatial distributions of dopaminergic receptors, inhibitory neurons, glial cell populations, and brain-metabolic features explain up to 50% of the variance associated with a lifespan model of regional cortical thickness trajectories. In contrast, modeled cortical thickness change patterns during adulthood are best explained by cholinergic and glutamatergic neurotransmitter receptor and transporter distributions. These relationships are supported by developmental gene expression trajectories and translate to individual longitudinal data from over 8000 adolescents, explaining up to 59% of developmental change at cohort- and 18% at single-subject level. Integrating neurobiological brain atlases with normative modeling and population neuroimaging provides a biologically meaningful path to understand brain development and aging in living humans., (© 2024. The Author(s).)

Neural variability, or variation in brain signals, facilitates dynamic brain responses to ongoing demands. This flexibility is important during development from childhood to young adulthood, a period characterized by rapid changes in experience. However, little is known about how variability in the engagement of recurring brain states changes during development. Such investigations would require the continuous assessment of multiple brain states concurrently. Here, we leverage a new computational framework to study state engagement variability (SEV) during development. A consistent pattern of SEV changing with age was identified across cross-sectional and longitudinal datasets (N>3000). SEV developmental trajectories stabilize around mid-adolescence, with timing varying by sex and brain state. SEV successfully predicts executive function (EF) in youths from an independent dataset. Worse EF is further linked to alterations in SEV development. These converging findings suggest SEV changes over development, allowing individuals to flexibly recruit various brain states to meet evolving needs.

Substance use, including cigarettes and cannabis, is associated with poorer sustained attention in late adolescence and early adulthood. Previous studies were predominantly cross-sectional or under-powered and could not indicate if impairment in sustained attention was a predictor of substance use or a marker of the inclination to engage in such behavior. This study explored the relationship between sustained attention and substance use across a longitudinal span from ages 14 to 23 in over 1000 participants. Behaviors and brain connectivity associated with diminished sustained attention at age 14 predicted subsequent increases in cannabis and cigarette smoking, establishing sustained attention as a robust biomarker for vulnerability to substance use. Individual differences in network strength relevant to sustained attention were preserved across developmental stages and sustained attention networks generalized to participants in an external dataset. In summary, brain networks of sustained attention are robust, consistent, and able to predict aspects of later substance use., Competing Interests: YW, JK, LR, KR, RB, LF, ES, TN, JH, AS, TF, AB, SD, HF, AG, HG, PG, AH, RB, JM, MM, EA, JM, FN, DP, TP, LP, NH, JF, MS, NV, GS, RW No competing interests declared, TB Served in an advisory or consultancy role for Actelion, Hexal Pharma, Lilly, Lundbeck, Medice, Novartis, Shire. He received conference support or speaker's fee by Lilly, Medice Novartis and Shire. Has been involved in clinical trials conducted by Shire & Viforpharma. Received royalities from Hogrefe, Kohlhammer, CIP Medien, Oxford University Press. The present work is unrelated to the above grants and relationships, HW Received a speaker honorarium from Servier (2014), (© 2024, Weng et al.)

Background: Personality traits have been associated with eating disorders (EDs) and comorbidities. However, it is unclear which personality profiles are premorbid risk rather than diagnostic markers., Methods: We explored associations between personality and ED-related mental health symptoms using canonical correlation analyses. We investigated personality risk profiles in a longitudinal sample, associating personality at age 14 with onset of mental health symptoms at ages 16 or 19. Diagnostic markers were identified in a sample of young adults with anorexia nervosa (AN, n = 58) or bulimia nervosa (BN, n = 63) and healthy controls (n = 47)., Results: Two significant premorbid risk profiles were identified, successively explaining 7.93 % and 5.60 % of shared variance (R c 2 ). The first combined neuroticism (canonical loading, r s  = 0.68), openness (r s  = 0.32), impulsivity (r s  = 0.29), and conscientiousness (r s  = 0.27), with future onset of anxiety symptoms (r s  = 0.87) and dieting (r s  = 0.58). The other, combined lower agreeableness (r s  = -0.60) and lower anxiety sensitivity (r s  = -0.47), with future deliberate self-harm (r s  = 0.76) and purging (r s  = 0.55). Personality profiles associated with "core psychopathology" in both AN (R c 2  = 80.56 %) and BN diagnoses (R c 2  = 64.38 %) comprised hopelessness (r s  = 0.95, 0.87) and neuroticism (r s  = 0.93, 0.94). For BN, this profile also included impulsivity (r s  = 0.60). Additionally, extraversion (r s  = 0.41) was associated with lower depressive risk in BN., Limitations: The samples were not ethnically diverse. The clinical cohort included only females. There was non-random attrition in the longitudinal sample., Conclusions: The results suggest neuroticism and impulsivity as risk and diagnostic markers for EDs, with neuroticism and hopelessness as shared diagnostic markers. They may inform the design of more personalised prevention and intervention strategies., Competing Interests: Declaration of competing interest Dr. Banaschewski served in an advisory or consultancy role for ADHS digital, Infectopharm, Lundbeck, Medice, Neurim Pharmaceuticals, Oberberg GmbH, Roche, and Takeda. He received conference support or speaker's fee by Medice and Takeda. He received royalties from Hogrefe, Kohlhammer, CIP Medien, Oxford University Press. 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 these relationships. The other authors report no biomedical financial interests or potential conflicts of interest., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: Depressive symptoms are highly prevalent, present in heterogeneous symptom patterns, and share diverse neurobiological underpinnings. Understanding the links between psychopathological symptoms and biological factors is critical in elucidating its etiology and persistence. We aimed to evaluate the utility of using symptom-brain network models to parse the heterogeneity of depressive complaints in a large adolescent sample., Methods: We used data from the third wave of the IMAGEN study, a multi-center panel cohort study involving 1317 adolescents (52.49 % female, mean ± SD age = 18.5 ± 0.7). Two network models were estimated: one including an overall depressive symptom severity sum score based on the Adolescent Depression Rating Scale (ADRS), and one incorporating individual ADRS item scores. Both networks included measures of cortical thickness in several regions (insula, cingulate, mOFC, fusiform gyrus) and hippocampal volume derived from neuroimaging., Results: The network based on individual item scores revealed associations between cortical thickness measures and specific depressive complaints, obscured when using an aggregate depression severity score. Notably, the insula's cortical thickness showed negative associations with cognitive dysfunction (partial cor. = -0.15); the cingulate's cortical thickness showed negative associations with feelings of worthlessness (partial cor. = -0.10), and mOFC was negatively associated with anhedonia (partial cor. = -0.05)., Limitations: This cross-sectional study relied on the self-reported assessment of depression complaints and used a non-clinical sample with predominantly healthy participants (19 % with depression or sub-threshold depression)., Conclusions: This study showcases the utility of network models in parsing heterogeneity in depressive complaints, linking individual complaints to specific neural substrates. We outline the next steps to integrate neurobiological and cognitive markers to unravel MDD's phenotypic heterogeneity., Competing Interests: Declaration of competing interest 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. Barker has received honoraria from General Electric Healthcare for teaching on scanner programming courses. 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 conflicts of interest. All authors have approved the final article., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

Incomplete Hippocampal Inversion (IHI), sometimes called hippocampal malrotation, is an atypical anatomical pattern of the hippocampus found in about 20% of the general population. IHI can be visually assessed on coronal slices of T1 weighted MR images, using a composite score that combines four anatomical criteria. IHI has been associated with several brain disorders (epilepsy, schizophrenia). However, these studies were based on small samples. Furthermore, the factors (genetic or environmental) that contribute to the genesis of IHI are largely unknown. Large-scale studies are thus needed to further understand IHI and their potential relationships to neurological and psychiatric disorders. However, visual evaluation is long and tedious, justifying the need for an automatic method. In this paper, we propose, for the first time, to automatically rate IHI. We proceed by predicting four anatomical criteria, which are then summed up to form the IHI score, providing the advantage of an interpretable score. We provided an extensive experimental investigation of different machine learning methods and training strategies. We performed automatic rating using a variety of deep learning models ("conv5-FC3", ResNet and "SECNN") as well as a ridge regression. We studied the generalization of our models using different cohorts and performed multi-cohort learning. We relied on a large population of 2,008 participants from the IMAGEN study, 993 and 403 participants from the QTIM and QTAB studies as well as 985 subjects from the UKBiobank. We showed that deep learning models outperformed a ridge regression. We demonstrated that the performances of the "conv5-FC3" network were at least as good as more complex networks while maintaining a low complexity and computation time. We showed that training on a single cohort may lack in variability while training on several cohorts improves generalization (acceptable performances on all tested cohorts including some that are not included in training). The trained models will be made publicly available should the manuscript be accepted., Competing Interests: 6.3.1Disclosure statement Competing financial interests related to the present article: none to disclose for all authors. Competing financial interests unrelated to the present article: OC reports having received consulting fees from AskBio (2020) and Therapanacea (2022–2024), and that his laboratory has received grants (paid to the institution) from Qynapse (2017–2022). Members from his laboratory have co-supervised a PhD thesis with Qynapse (2017–2022). OC’s spouse was an employee of myBrainTechnologies and is an employee of DiamPark. OC holds a patent registered at the International Bureau of the World Intellectual Property Organization (PCT/IB2016/0526993, Schiratti J-B, Allassonniere S, Colliot O, Durrleman S, A method for determining the temporal progression of a biological phenomenon and associated methods and devices) (2017). Tobias Banaschewski served in an advisory or consultancy role for eye level, Infectopharm, Lundbeck, Medice, Neurim Pharmaceuticals, Oberberg GmbH, Roche, and Takeda. He received conference support or speaker’s fee by Janssen, Medice and Takeda. He received royalities from Hogrefe, Kohlhammer, CIP Medien, Oxford University Press; the present work is unrelated to these relationships. Dr. Barker has received honoraria from General Electric Healthcare for teaching on scanner programming courses. 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.