Search

The routine in-depth characterization of patients with methods of clinical and scale-based examination, neuropsychology, based on biomaterials, and sensor-based information opens up transformative possibilities on the way to personalized diagnostics, treatment and prevention in psychiatry, psychotherapy, and psychosomatics. Effective integration of the additional temporal and logistical effort into everyday care as well as the acceptance by patients are critical to the success of such an approach but there is little evidence on this to date. We report here on the establishment of the Diagnosis and Admission Center (DAZ) at the Central Institute of Mental Health (ZI) in Mannheim. The DAZ is an outpatient unit upstream of other care structures for clinical and scientific phenotyping across diagnoses as a starting point for data-driven, individualized pathways to further treatment, diagnostics or research. We describe the functions, goals, and implementation of the newly created clinical scientific translational structure, provide an overview of the patient populations it has reached, and provide data on its acceptance. In this context, the close integration with downstream clinical processes enables a better coordinated and demand-oriented allocation. In addition, DAZ enables a faster start of disorder-specific diagnostics and treatment. Since its launch in April 2021 up to the end of 2022, 1021 patients underwent psychiatric evaluation at DAZ during a pilot phase. The patient sample corresponded to a representative sample from standard care and the newly established processes were regarded as helpful by patients. In summary, the DAZ uniquely combines the interests and needs of patient with the collection of scientifically relevant data., (© 2024. The Author(s).)

Affective dysregulation (AD) is characterized by irritability, severe temper outbursts, anger, and unpredictable mood swings, and is typically classified as a transdiagnostic entity. A reliable and valid measure is needed to adequately identify children at risk of AD. This study sought to validate a parent-rated screening questionnaire, which is part of the comprehensive Diagnostic Tool for Affective Dysregulation in Children (DADYS-Screen), by analyzing relationships with comprehensive measures of AD and related mental disorders in a community sample of children with and without AD. The sample comprised 1114 children aged 8-12 years and their parents. We used clinical, parent, and child ratings for our analyses. Across all raters, the DADYS-Screen showed large correlations with comprehensive measures of AD. As expected, correlations were stronger for measures of externalizing symptoms than for measures of internalizing symptoms. Moreover, we found negative associations with emotion regulation strategies and health-related quality of life. In receiver operating characteristic (ROC) analyses, the DADYS-Screen adequately identified children with AD and provided an optimal cut-off. We conclude that the DADYS-Screen appears to be a reliable and valid measure to identify school-aged children at risk of AD., (© 2023. The Author(s).)

Psychopharmacological treatment is an important component of the multimodal intervention approach to treating mental health conditions in children and adolescents. Currently, there are many unmet needs but also opportunities, alongside possible risks to consider, regarding the pharmacological treatment of mental health conditions in children and adolescents. In this Position Paper, we highlight and address these unmet needs and opportunities, including the perspectives of clinicians and researchers from the European College of Neuropsychopharmacology-Child and Adolescent Network, alongside those of experts by lived experience from national and international associations, via a survey involving 644 participants from 13 countries, and of regulators, through representation from the European Medicines Agency. We present and discuss the evidence base for medications currently used for mental disorders in children and adolescents, medications in the pipeline, opportunities in the development of novel medications, crucial priorities for the conduct of future clinical studies, challenges and opportunities in terms of the regulatory and legislative framework, and innovations in the way research is conducted, reported, and promoted., Competing Interests: Declaration of interests SCo declares honoraria and reimbursement for travel and accommodation expenses for lectures from the following non-profit associations: Association for Child and Adolescent Central Health, Canadian ADHD Alliance Resource, British Association of Pharmacology (BAP), honorarium from Medice, and grants from NIHR, European Research Executive Agency, and Solent NHS Trust. DPO declares honoraria from Medice; and support for attending meetings or travel form Medice, Boehringer Ingelsheim, and HAC pharma. CA declares grants from Stanley Foundation, Brystol-Myers Squibb, Caja Navarra, Comunidad de Madrid, Fundación Alicia Kplopwitz, Fundación Familia Alonso, Foundacion Mutua Madrileña, Instituto de Salud Carlos III, NARSAD, and Ministerio Educacion; consulting fees from Acadia, AMGEN, Angelini, Astra Zeneca, Bristol-Myers Squibb, Fundación Alicia Koplowitz, Gedeon Richter, Instituto de Salud Carlos III, Janssen-Cilag, Lundbeck, Otsuka, Roche, Sage, Schering Plough, Shire, Ministerio Educación, Stanley Foundation, Sumitomo Dainippon Pharma, Sunovion, Takeda, and Teva; and honoraria from AMGEN, AstraZeneca, Bristol-Myers, Squibb, Exeltis, Janssen-Cilag Lundbeck, Otsuka, Sanofi, Takeda, Roche, Sumitomo, and Dainippon Pharma. IB reports honoraria, participation on a Data Safety Monitoring Board or Advisory Board, and payment for expert testimony from Angelini; and support for attending meetings from Angelini and Lundbeck. TB reports royalties from Hogrefe, Kohlhammer, CIP Medie, and Oxford University Press; honoraria from Janssen Cilag, Medice, and Takeda; participation on data safety monitoring for eye level, Infectopharm, Medice, Neurim Pharmaceuticals, Oberberg, GmbH, and Takeda. JKB reports consulting fees from Boehringer-Ingelheim and Servier; honoraria from Takeda and Medice; and participation on a Data Safety Monitoring Board or Advisory Board for Angelini. DCoghill reports grants from National Health and Medical Research Council (Institution), and Medical Research and Futures Fund (Institution); royalties from Oxford University Press and Cambridge University Press; honoraria from Takeda, Medice, Servier, and Novartis; support for attending meetings from European College of Neuropsychopharmacology; and unpaid leadership roles for Director of Australian ADHD Professionals Association and Director of European Network for Hyperkinetic Disorders. DCohen reports support from Agence Régionale de Santé d'Ile de France; grants from Janssen; honoraria form Otsuka; participation on a Data Safety Monitoring Board or Advisory Board for Lundbeck; and stocks with School Rebounds. CUC reports grants from Janssen and Teva; royalties from UpToDate; consulting fees from AbbVie, Acadia, Alkermes, Allergan, Angelini, Aristo, Boehringer-Ingelheim, Cardio Diagnostics, Cerevel, CNX Therapeutics, Compass Pathways, Darnitsa, Gedeon Richter, Hikma, Holmusk, IntraCellular Therapies, Janssen/J&J, Karuna, LB Pharma, Lundbeck, MedAvanteProPhase, MedInCell, Merck, Mindpax, Mitsubishi Tanabe Pharma, Mylan, Neurocrine, Newron, Noven, Otsuka, Pharmabrain, PPD Biotech, Recordati, Relmada, Reviva, Rovi, Seqirus, SK Life Science, Sunovion, Sun Pharma, Supernus, Takeda, Teva, and Viatris; payment for expert testimony from Janssen and Otsuka; participation on a Data Safety Monitoring for Lundbeck, Relmada, Reviva, Rovi, Supernus, and Teva; stock options from Cardio Diagnostics, Mindpax, LB Pharma, and Quantic. EG received support for attending meetings from European College of Neuropsychopharmacology 2023, CINP 2023, and World ADHD Congress 2023. PJH reports payment for educational material from Takeda. MP reports support from Janssen Cilag, Servier, Roche, Exeltis, Otsuka, Instituto de Salud Carlos III (Spanish Ministry of Health, now Spanish Ministry of Economy and Competitiveness), Horizon2020, EMA, CIBERSAM, Fundación Alicia Koplowitz, and Fundación Mutua Madrileña. PS reports grants from Anavex Life Sciences Corp, NIHR Invention for Innovation (i4i) Programme, MRC Clinical Academic Research Partnerships, NIHR HTA, NIHR EME, NIHR PGfAR, British Heart Foundation, Reverse Rett, Newron Pharmaceuticals, HealthTracker, and Anavex Scientific Corporation; royalties from HealthTracker; consulting fees from Anavex Scientific Corporation; honoraria from Egyptian Psychiatry Association; and stocks from HealthTracker. AS reports the following leadership roles: President ISRCAP; Chief Scientific Officer Mazi Gia to Paidi; Scientific Advisory Board MRC Adolescent Brain Development; and royalties from Oxford University Press and Cambridge University Press. BV reports grants from CRT Foundation, Italian Ministry of Research and Fondazione Italina Autismo; consulting fees from Medice and Ethos-Angelini; honoraria from Angelini and Menarini; support for attending meetings from Medice; participation in data safety monitoring from NIH and Alkermes. SW reports grants from EU H2022, Swiss National Foundation, WASAD Congress 2023, Heuberg Foundation, University Medical Center Groningen, Uniscientia Foundation, Swiss State Secretariat for Education, Research and Innovation, UZH Foundation and Erika Schwarz Foundation, Ebnet Foundation: Oxford Brain @McGill – ZNZ Partnership in the Neurosciences, European Cooperation in Science and Technology, Gertrud Thalmann Fonds of UPK Basel, Swiss National Foundation, Federal institute for Drugs and Medical Devices, Olga Mayenfisch Foundation; royalties from Georg Thieme Verlag KG Stuttgart, Hogrefe Publishing Group, Kohlhammer Publishing, Springer Berlin, Beltz publishing group; honoraria from Education Weiterbildungsverein Deutschschweizer Kliniken; Takeda Pharmaceuticals International leadership roles: President of the IPKJ Psychotherapy Institute, Board Member Schweizerischer Gesellschaft für Kinder- und Jugendpsychiatrie und Psychotherapie, Chair of ICOCS, Board Member ZNZ, SGZ. ICKW reports grants from Amgen, Janssen, GSK, Novartis, Pfizer, Bayer, Bristol-Myers Squibb, and Takeda, along with funding from the Hong Kong RGC and the Hong Kong Health and Medical Research Fund in Hong Kong, National Institute for Health Research in England, European Commission, National Health and Medical Research Council in Australia, and The European Union's Seventh Framework Programme for research, technological development, and demonstration. Consulting fees from IQVIA and WHO, payment for expert testimony from Court in Hong Kong; leadership roles: Member of Pharmacy and Poisons Board, Member of the Expert Committee on Clinical Events Assessment Following COVID-19 Immunization, and Member of the Advisory Panel on COVID-19 Vaccines of the Hong Kong Government. SCa reports leadership roles: Secretary of the Psychiatric section of SINPIA and Participation as investigator in sponsored clinical trials by Lundbeck, Otsuka, Janssen, Angelini, and Acadia. MB reports honoraria from Medice, Takeda, Martinsclub Bremen e.V., Das frühgeborene Kind e.V., APK e.V., Dreiländerinstitut, Senatsverwaltung Berlin, Lehrerakademie Dillingen, and leadership roles: ADHS Deutschland e.V. and Gamian Europe. NH reports leadership roles: ADHD Europe. KG reports grants from Johnson & Johnson Foundation, Boehringer Ingelheim, Janssen, Institute of Translation and Interpreting; support to attend meetings from European College of Neuropsychopharmacology; and participation on a Data Safety Monitoring Board or Advisory Board for Janssen and Boehringer Ingelheim. CM reports consulting fees from Janssen, Angelini, and Compass; honoraria from Angelini, Neuraxpharm, Lundbeck, Esteve, Pfizer, Sunovion, and British Association of Psychopharmacology; support for attending meetings or travel from Exeltis, Janssen, and BAP, participation on a Data Safety Monitoring Board or Advisory Board for Otsuka, Servier, and Nuvelution. All other authors declare no competing interests., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Environmental adversities constitute potent risk factors for psychiatric disorders. Evidence suggests the brain adapts to adversity, possibly in an adversity-type and region-specific manner. However, the long-term effects of adversity on brain structure and the association of individual neurobiological heterogeneity with behavior have yet to be elucidated. Here we estimated normative models of structural brain development based on a lifespan adversity profile in a longitudinal at-risk cohort aged 25 years (n = 169). This revealed widespread morphometric changes in the brain, with partially adversity-specific features. This pattern was replicated at the age of 33 years (n = 114) and in an independent sample at 22 years (n = 115). At the individual level, greater volume contractions relative to the model were predictive of future anxiety. We show a stable neurobiological signature of adversity that persists into adulthood and emphasize the importance of considering individual-level rather than group-level predictions to explain emerging psychopathology., (© 2023. The Author(s).)

Compassion-focused interventions represent a promising transdiagnostic approach, but the mechanisms involved in hybrid delivery combining face-to-face sessions and an ecological momentary intervention remain unexplored. The current study aimed at exploring associations of putative mechanisms with clinical outcomes at post-intervention/follow-up and mediation of outcome at follow-up by preceding pre-to post-intervention changes in putative mechanisms. The compassion-focused EMIcompass intervention was applied in an exploratory randomized controlled trial (treatment as usual (TAU) vs. TAU + EMIcompass) with youth with early mental health problems. Data was collected before randomization, at post-intervention and at four-week follow-up. We recruited N = 92 participants, N = 46 were allocated to the experimental condition. After control for baseline levels of the target outcomes, baseline-to post-intervention improvement in adaptive emotion regulation was associated with lower levels of clinical outcomes (e.g. psychological distress b = -1.15; 95%CI = -1.92 to -0.39) across time points. We could not detect indirect effects, but we observed associations of change in self-compassion and adaptive emotion regulation with outcomes at follow-up in the mediation analysis (e.g., β = -0.35, 95%CI = -0.52 to -0.16). If successfully targeted by interventions, self-compassion and emotion regulation may be promising putative therapeutic mechanisms of change., Competing Interests: Declaration of competing interest TB served in an advisory or consultancy role for eyelevel, Infectopharm, Lundbeck, Medice, Neurim Pharmaceuticals, Oberberg GmbH, Roche, and Takeda. He received conference support or speaker's fee by Medice and Takeda. He received royalities from Hogrefe, Kohlhammer, CIP Medien, Oxford University Press; the present work is unrelated to these relationships. The other authors declare that they have no competing interests., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Prevalences for mental disorders within minor refugees are comparatively high and heterogeneous. To reduce heterogeneity and identify high-risk subgroups, we compared unaccompanied refugee minors (URM) to accompanied refugee minors (ARM) regarding depressive symptoms and mental distress. Furthermore, we examined associative factors of mental distress in URM on a broad scale. We conducted a survey with a cross-sectional design in four German University hospitals. The sample consisted of n = 172 URM and n = 52 ARM aged 14-21. Depressive symptoms were assessed via the Patient Health Questionnaire (PHQ-9). Mental distress was assessed by the Refugee Health Screener (RHS-15). Mann-Whitney test was used to examine differences between URM and ARM. Associated factors of mental distress were evaluated via a stepwise multiple regression analysis. URM showed significantly higher mean scores for PHQ-9 (p < .001) and RHS-15 (p < .001) compared to ARM indicating medium effect sizes. Furthermore, URM were significantly more likely to surpass the cut-off for depression (61.6% vs. 30.8%) and overall mental distress (81.4% vs. 53.8%) compared to ARM. The factors Number of stressful life events (SLE), Female gender, and Fear of deportation were found to be associated with an increased mental distress in URM, whereas Weekly contact to a family member, School attendance, and German language skills were accompanied with lower distress scores. All six factors accounted for 32% of the variance of mental distress in URM (p < .001). Within minor refugees, URM are a highly vulnerable subgroup, which should receive particular attention and more targeted measures by health authorities. Our results indicate that these measures should comprise a rapid promotion of family contact, school attendance, language acquisition, and the fast processing of asylum applications. However, the cross-sectional design limits the interpretability of the results., (© 2021. The Author(s).)

Background/hypothesis: Digital interventions targeting transdiagnostic mechanisms in daily life may be a promising translational strategy for prevention and early intervention of psychotic and other severe mental disorders. We aimed to investigate the feasibility and initial signals of efficacy of a transdiagnostic, compassion-focused, hybrid ecological momentary intervention for improving resilience (ie, EMIcompass) in youth with early mental health problems., Study Design: In an exploratory, assessor-blind randomized controlled trial, youth aged 14-25 with current distress, broad at-risk mental state, or first episode of severe mental disorder were randomly allocated to experimental (EMIcompass+treatment as usual [TAU]) or control condition (TAU). Data on primary (stress reactivity) and secondary candidate mechanisms as well as candidate primary (psychological distress) and secondary outcomes were collected., Study Results: Criteria for the feasibility of trial methodology and intervention delivery were met (n = 92 randomized participants). No serious adverse events were observed. Initial outcome signals were evident for reduced momentary stress reactivity (stress×time×condition, B = -0.10 95%CI -0.16--0.03, d = -0.10), aberrant salience (condition, B = -0.38, 95%CI -0.57--0.18, d = -0.56) as well as enhanced momentary resilience (condition, B = 0.55, 95%CI 0.18-0.92, d = 0.33) and quality of life (condition, B = 0.82, 95%CI 0.10-1.55, d = 0.60) across post-intervention and 4-week follow-up. No outcome signals were observed for self-reported psychological distress (condition, B = 0.57, 95%CI -1.59-2.72, d = 0.09), but there was suggestive evidence of reduced observer-rated symptoms at the 4-week follow-up (B = -1.41, 95%CI -2.85-0.02, d = -0.41)., Conclusions: Our findings provide evidence of feasibility and initial signals that EMIcompass may reduce stress reactivity and improve quality of life. A definitive trial is now warranted., (© The Author(s) 2023. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Recent studies proposed a general psychopathology factor underlying common comorbidities among psychiatric disorders. However, its neurobiological mechanisms and generalizability remain elusive. In this study, we used a large longitudinal neuroimaging cohort from adolescence to young adulthood (IMAGEN) to define a neuropsychopathological (NP) factor across externalizing and internalizing symptoms using multitask connectomes. We demonstrate that this NP factor might represent a unified, genetically determined, delayed development of the prefrontal cortex that further leads to poor executive function. We also show this NP factor to be reproducible in multiple developmental periods, from preadolescence to early adulthood, and generalizable to the resting-state connectome and clinical samples (the ADHD-200 Sample and the Stratify Project). In conclusion, we identify a reproducible and general neural basis underlying symptoms of multiple mental health disorders, bridging multidimensional evidence from behavioral, neuroimaging and genetic substrates. These findings may help to develop new therapeutic interventions for psychiatric comorbidities., (© 2023. The Author(s).)

This study aimed to build on the relationship of well-established self-report and behavioral assessments to the latent constructs positive (PVS) and negative valence systems (NVS), cognitive systems (CS), and social processes (SP) of the Research Domain Criteria (RDoC) framework in a large transnosological population which cuts across DSM/ICD-10 disorder criteria categories. One thousand four hundred and thirty one participants (42.1% suffering from anxiety/fear-related, 18.2% from depressive, 7.9% from schizophrenia spectrum, 7.5% from bipolar, 3.4% from autism spectrum, 2.2% from other disorders, 18.4% healthy controls, and 0.2% with no diagnosis specified) recruited in studies within the German research network for mental disorders for the Phenotypic, Diagnostic and Clinical Domain Assessment Network Germany (PD-CAN) were examined with a Mini-RDoC-Assessment including behavioral and self-report measures. The respective data was analyzed with confirmatory factor analysis (CFA) to delineate the underlying latent RDoC-structure. A revised four-factor model reflecting the core domains positive and negative valence systems as well as cognitive systems and social processes showed a good fit across this sample and showed significantly better fit compared to a one factor solution. The connections between the domains PVS, NVS and SP could be substantiated, indicating a universal latent structure spanning across known nosological entities. This study is the first to give an impression on the latent structure and intercorrelations between four core Research Domain Criteria in a transnosological sample. We emphasize the possibility of using already existing and well validated self-report and behavioral measurements to capture aspects of the latent structure informed by the RDoC matrix., (© 2022. The Author(s).)

The neurobiological bases of the association between development and psychopathology remain poorly understood. Here, we identify a shared spatial pattern of cortical thickness (CT) in normative development and several psychiatric and neurological disorders. Principal component analysis (PCA) was applied to CT of 68 regions in the Desikan-Killiany atlas derived from three large-scale datasets comprising a total of 41,075 neurotypical participants. PCA produced a spatially broad first principal component (PC1) that was reproducible across datasets. Then PC1 derived from healthy adult participants was compared to the pattern of CT differences associated with psychiatric and neurological disorders comprising a total of 14,886 cases and 20,962 controls from seven ENIGMA disease-related working groups, normative maturation and aging comprising a total of 17,697 scans from the ABCD Study® and the IMAGEN developmental study, and 17,075 participants from the ENIGMA Lifespan working group, as well as gene expression maps from the Allen Human Brain Atlas. Results revealed substantial spatial correspondences between PC1 and widespread lower CT observed in numerous psychiatric disorders. Moreover, the PC1 pattern was also correlated with the spatial pattern of normative maturation and aging. The transcriptional analysis identified a set of genes including KCNA2, KCNS1 and KCNS2 with expression patterns closely related to the spatial pattern of PC1. The gene category enrichment analysis indicated that the transcriptional correlations of PC1 were enriched to multiple gene ontology categories and were specifically over-represented starting at late childhood, coinciding with the onset of significant cortical maturation and emergence of psychopathology during the prepubertal-to-pubertal transition. Collectively, the present study reports a reproducible latent pattern of CT that captures interregional profiles of cortical changes in both normative brain maturation and a spectrum of psychiatric disorders. The pubertal timing of the expression of PC1-related genes implicates disrupted neurodevelopment in the pathogenesis of the spectrum of psychiatric diseases emerging during adolescence., (© 2022. The Author(s), under exclusive licence to Springer Nature Limited.)

Precision psychiatry stands to benefit from the latest digital technologies for assessment and analyses to tailor treatment towards individuals. Insights into dynamic psychological processes as they unfold in humans' everyday life can critically add value in understanding symptomatology and environmental stressors to provide individualized treatment where and when needed. Towards this goal, ambulatory assessment encompasses methodological approaches to investigate behavioral, physiological, and biological processes in humans' everyday life. It combines repeated assessments of symptomatology over time, e.g., via Ecological Momentary Assessment (e.g., smartphone-diaries), with monitoring of physical behavior, environmental characteristics (such as geolocations, social interactions) and physiological function via sensors, e.g., mobile accelerometers, global-positioning-systems, and electrocardiography. In this review, we expand on promises of ambulatory assessment in the investigation of mental states (e.g., real-life, dynamical and contextual perspective), on chances for precision psychiatry such as the prediction of courses of psychiatric disorders, detection of tipping points and critical windows of relapse, and treatment effects as exemplified by ongoing projects, and on future avenues of how ambulatory interventions can benefit personalized care for psychiatric patients (e.g., through real-time feedback in everyday life). Ambulatory assessment is a key contributor to precision psychiatry, opening up promising avenues in research, diagnoses, prevention and treatment., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Importance: Eating disorders are serious mental disorders with increasing prevalence. Without early identification and treatment, eating disorders may run a long-term course., Objective: To characterize any associations among disordered eating behaviors (DEBs) and other mental health disorders and to identify early associations with the development of symptoms over time., Design, Setting, and Participants: This multicenter, population-based, longitudinal cohort study used data from baseline (collected in 2010), follow-up 1 (collected in 2012), and follow-up 2 (collected in 2015) of the IMAGEN Study, which included adolescents recruited from 8 European sites. The present study assessed data from 1623 healthy adolescents, aged 14 years at baseline, recruited from high schools. Data analyses were performed from January 2018 to September 2019., Main Outcomes and Measures: Body mass index (BMI), mental health symptoms, substance use behaviors, and personality variables were investigated as time-varying associations of DEBs (dieting, binge eating, and purging) or change in BMI over time. Polygenic risk scores were calculated to investigate genetic contributions associated with BMI, attention-deficit/hyperactivity disorder (ADHD) and neuroticism to DEBs., Results: In this cohort study of 1623 adolescents (829 girls [51.1%]) recruited at a mean (SD) age of 14.5 (0.4) years and followed up at ages 16 and 19 years, 278 adolescents (17.1%) reported binge eating, 334 adolescents (20.6%) reported purging, and 356 adolescents (21.9%) reported dieting at 14, 16, or 19 years. Among the precursors of DEBs, high BMI was associated with future dieting (OR, 3.44; 95% CI, 2.09-5.65). High levels of neuroticism (OR, 1.04; 95% CI, 1.01-1.06), conduct problems (OR, 1.41; 95% CI, 1.17-1.69), and deliberate self-harm (OR, 2.18; 95% CI, 1.37-3.45) were associated with future binge eating. Low agreeableness (OR, 0.95; 95% CI, 0.92-0.97), deliberate self-harm (OR, 2.59; 95% CI, 1.69-3.95), conduct problems (OR, 1.42; 95% CI, 1.20-1.68), alcohol misuse (OR, 1.31; 95% CI, 1.10-1.54), and drug abuse (OR, 2.91; 95% CI, 1.78-4.74) were associated with future purging. Polygenetic risk scores for BMI were associated with dieting (at 14 years: OR, 1.27; lower bound 95% CI, 1.08; at 16 years: OR, 1.38; lower bound 95% CI, 1.17); ADHD, with purging (at 16 years: OR, 1.25; lower bound 95% CI, 1.08; at 19 years, OR, 1.23; lower bound 95% CI, 1.06); and neuroticism, with binge eating (at 14 years: OR, 1.32; lower bound 95% CI, 1.11; at 16 years: OR, 1.24; lower bound 95% CI, 1.06), highlighting distinct etiologic overlaps between these traits. The DEBs predated other mental health problems, with dieting at 14 years associated with future symptoms of depression (OR, 2.53; 95% CI, 1.56-4.10), generalized anxiety (OR, 2.27; 95% CI, 1.14-4.51), deliberate self-harm (OR, 2.10; 95% CI, 1.51-4.24), emotional problems (OR, 1.24; 95% CI, 1.08-1.43), and smoking (OR, 2.16; 95% CI, 1.36-3.48). Purging at 14 years was also associated with future depression (OR, 2.87; 95% CI, 1.69-5.01) and anxiety (OR, 2.48; 95% CI, 1.49-4.12) symptoms., Conclusions and Relevance: The findings of this study delineate temporal associations and shared etiologies among DEBs and other mental health disorders and emphasize the potential of genetic and phenotypical assessments of obesity, behavioral disorders, and neuroticism to improve early and differential diagnosis of eating disorders.

Mental disorders represent an increasing personal and financial burden and yet treatment development has stagnated in recent decades. Current disease classifications do not reflect psychobiological mechanisms of psychopathology, nor the complex interplay of genetic and environmental factors, likely contributing to this stagnation. Ten years ago, the longitudinal IMAGEN study was designed to comprehensively incorporate neuroimaging, genetics, and environmental factors to investigate the neural basis of reinforcement-related behavior in normal adolescent development and psychopathology. In this article, we describe how insights into the psychobiological mechanisms of clinically relevant symptoms obtained by innovative integrative methodologies applied in IMAGEN have informed our current and future research aims. These aims include the identification of symptom groups that are based on shared psychobiological mechanisms and the development of markers that predict disease course and treatment response in clinical groups. These improvements in precision medicine will be achieved, in part, by employing novel methodological tools that refine the biological systems we target. We will also implement our approach in low- and medium-income countries to understand how distinct environmental, socioeconomic, and cultural conditions influence the development of psychopathology. Together, IMAGEN and related initiatives strive to reduce the burden of mental disorders by developing precision medicine approaches globally.

Disruptions in psychiatric care delivery during the transition from adolescence to adulthood frequently lead - particularly in the case of severe mental illness - to a considerable treatment delay and an especially high rate of treatment dropout with a high risk of early chronification. The joint Task Force Transition, of the German Society of Child and Adolescent Psychiatry, Psychosomatics and Psychotherapy (DGKJP) and the German Association for Psychiatry, Psychotherapy and Psychosomatics (DGPPN), therefore analyzed general, sector-specific and disorder-specific gaps in the German psychiatric care system which obstruct a successful transition to the adult psychiatric care system. The article summarizes the results of the Task Force, outlines the aims and challenges of transition-psychiatric treatment models, and addresses their structural and professional prerequisites. The requirements and recommendations derived from this are transferred to psychiatric planning, health and research policy as well as education, training and professional development in order to optimally shape the transition from adolescent-centered to adult-oriented psychiatric care in the future., Competing Interests: T. Banaschewski war innerhalb der letzten drei Jahre als Berater für die Firmen Lundbeck, Medice, Neurim Pharmaceuticals, Oberberg-GmbH, Shire und Infectopharm tätig und hat Vortragshonorare von den Firmen Lilly, Medice und Shire erhalten. J.M. Fegert erhielt in den letzten fünf Jahren Förderungen von der EU, der Deutschen Forschungsgemeinschaft (DFG), dem Bundesministerium für Bildung und Forschung (BMBF), dem Bundesministerium für Gesundheit (BMG), dem Bundesministerium für Familie, Senioren, Frauen und Jugend (BMFSFJ), dem Bundesministerium für Verteidigung (BMVg), mehrerer Landessozialministerien, der Landesstiftung Baden-Württemberg, der UBS Optimus Stiftung, der Päpstlichen Universität Gregoriana CJD, Caritas und der Diözese Rottenburg-Stuttgart. Darüber hinaus erhielt er in den letzten 5 Jahren von der DFG, AACAP, NIMH/NIH, EU, Pro Helvetia, Janssen-Cilag (J&J), Shire, verschiedenen Universitäten und Wissenschaftskollegs, Berufsverbänden, politischen Stiftungen sowie Bundes- und Landesministerien Reiseaufwandsentschädigungen, Vortragshonorare und Sponsoring für Konferenzen und medizinische Bildungszwecke. Jede Zuwendung wird beim Universitätsklinikum Ulm angemeldet. Prof. Karow has been consultant and/or advisor to or has received honoraria from: AstraZeneca, Bristol-Myers Squibb, Lilly Deutschland GmbH, Janssen Cilag GmbH, Lundbeck GmbH, Otsuka Pharma GmbH, Roche Deutschland Holding GmbH. A. Reif war innerhalb der letzten drei Jahre als Berater tätig für folgende Firmen oder hat Vortragshonorare erhalten von folgenden Firmen: Medice, Shire, Janssen-Cilag, neuraxpharm, Servier. Außerdem hat A. Reif Forschungsgelder von der Firma Medice erhalten. M. Driessen, C. Schaff und U. Voderholzer haben keine Interessenskonflikte., (© Georg Thieme Verlag KG Stuttgart · New York.)

Introduction: The aim of the study was to examine adolescence-specific treatment models throughout Germany, to describe the implementation process of transition psychiatric care and to identify relevant health care problem areas for adolescents with mental disorders., Methodology: A questionnaire-based cross-sectional survey (N = 26) of hospital-based adolescent psychiatric treatment models was conducted. Service structures, treatment groups and interventions were investigated by the 28-item questionnaire., Results: There is an increase in adolescence-specific hospital-based services in Germany. These are characterized by multi-professional team work in diagnosis and adolescence-specific therapy approaches. Most of the treatment available is for young adults only (>18 years). Some of the services are organized in interdisciplinary cooperation models. Structural deficits in acute and crisis treatment, cross-sectoral cooperation and systematic transition are reported. Conclusions There is growing interest throughout Germany in the development of adolescent psychiatric treatment. Close interdisciplinary cooperation between child and adolescent psychiatry and adult psychiatry is necessary to overcome interface problems with the aim of a successful transition, but has not yet been implemented. Structural problems should be reduced in order to facilitate further development in transition psychiatry., Competing Interests: P. Abzieher: Es bestehen keine Interessenskonflikte für diese PublikationM. Lipp: Es bestehen keine Interessenskonflikte für diese Publikation T. Banaschewski war innerhalb der letzten drei Jahre als Berater für die Firmen Lundbeck, Medice, Neurim Pharmaceuticals, Oberberg-GmbH, Shire und Infectopharm tätig und hat Vortragshonorare von den Firmen Lilly, Medice und Shire erhalten. Die vorliegende Publikation steht damit nicht im Zusammenhang.M. Driessen: Berater/Gutachtertätigkeit: KBO München 2016, Beratung zur Suchttherapie. FNK Düsseldorf 2017, BerufungskomiteeIndirekte Interessen:Mitgliedschaft/Funktion in Interessensverbänden: DGPPN, BDK, DeGT, APK, Zeitraum durchgehendSchwerpunkte wissenschaftlicher Tätigkeiten, Publikationen: Auch traumaassoziierte Themen, Zeitraum durchgehendSchwerpunkte klinischer Tätigkeiten: Gesamtgebiet psychiatrischer Störungen, Zeitraum durchgehendH. Staats: Es bestehen keine Interessenskonflikte für diese PublikationA. Karow has been consultant and/or advisor to or has received honoraria from: AstraZeneca, Bristol-Myers Squibb, Lilly Deutschland GmbH, Janssen Cilag GmbH, Lundbeck GmbH, Otsuka Pharma GmbH, Roche Deutschland Holding GmbH., (© Georg Thieme Verlag KG Stuttgart · New York.)

Reward processing is altered in various psychopathologies and has been shown to be susceptible to genetic and environmental influences. Here, we examined whether maternal care may buffer familial risk for psychiatric disorders in terms of reward processing. Functional magnetic resonance imaging during a monetary incentive delay task was acquired in participants of an epidemiological cohort study followed since birth (N = 172, 25 years). Early maternal stimulation was assessed during a standardized nursing/playing setting at the age of 3 months. Parental psychiatric disorders (familial risk) during childhood and the participants' previous psychopathology were assessed by diagnostic interview. With high familial risk, higher maternal stimulation was related to increasing activation in the caudate head, the supplementary motor area, the cingulum and the middle frontal gyrus during reward anticipation, with the opposite pattern found in individuals with no familial risk. In contrast, higher maternal stimulation was associated with decreasing caudate head activity during reward delivery and reduced levels of attention deficit hyperactivity disorder (ADHD) in the high-risk group. Decreased caudate head activity during reward anticipation and increased activity during delivery were linked to ADHD. These findings provide evidence of a long-term association of early maternal stimulation on both adult neurobiological systems of reward underlying externalizing behavior and ADHD during development.

Disorders of the brain can exhibit considerable epidemiological comorbidity and often share symptoms, provoking debate about their etiologic overlap. We quantified the genetic sharing of 25 brain disorders from genome-wide association studies of 265,218 patients and 784,643 control participants and assessed their relationship to 17 phenotypes from 1,191,588 individuals. Psychiatric disorders share common variant risk, whereas neurological disorders appear more distinct from one another and from the psychiatric disorders. We also identified significant sharing between disorders and a number of brain phenotypes, including cognitive measures. Further, we conducted simulations to explore how statistical power, diagnostic misclassification, and phenotypic heterogeneity affect genetic correlations. These results highlight the importance of common genetic variation as a risk factor for brain disorders and the value of heritability-based methods in understanding their etiology., (Copyright © 2018 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.)

Youth- and parent-rated screening measures derived from the Strengths and Difficulties Questionnaire (SDQ) and Development and Well-Being Assessment (DAWBA) were compared on their psychometric properties as predictors of caseness in adolescence (mean age 14). Successful screening was judged firstly against the likelihood of having an ICD-10 psychiatric diagnosis and secondly by the ability to discriminate between community (N = 252) and clinical (N = 86) samples (sample status). Both, SDQ and DAWBA measures adequately predicted the presence of an ICD-10 disorder as well as sample status. The hypothesis that there was an informant gradient was confirmed: youth self-reports were less discriminating than parent reports, whereas combined parent and youth reports were more discriminating-a finding replicated across a diversity of measures. When practical constraints only permit screening for caseness using either a parent or an adolescent informant, parents are the better source of information.

The traditional view that mental disorders are distinct, categorical disorders has been challenged by evidence that disorders are highly comorbid and exist on a continuum (e.g., Caspi et al., 2014; Tackett et al., 2013). The first objective of this study was to use structural equation modeling to model the structure of psychopathology in an adolescent community-based sample (N = 2,144) including conduct disorder, attention-deficit/hyperactivity disorder (ADHD), oppositional-defiant disorder (ODD), obsessive-compulsive disorder, eating disorders, substance use, anxiety, depression, phobias, and other emotional symptoms, assessed at 16 years. The second objective was to identify common personality and cognitive correlates of psychopathology, assessed at 14 years. Results showed that psychopathology at 16 years fit 2 bifactor models equally well: (a) a bifactor model, reflecting a general psychopathology factor, as well as specific externalizing (representing mainly substance misuse and low ADHD) and internalizing factors; and (b) a bifactor model with a general psychopathology factor and 3 specific externalizing (representing mainly ADHD and ODD), substance use and internalizing factors. The general psychopathology factor was related to high disinhibition/impulsivity, low agreeableness, high neuroticism and hopelessness, high delay-discounting, poor response inhibition and low performance IQ. Substance use was specifically related to high novelty-seeking, sensation-seeking, extraversion, high verbal IQ, and risk-taking. Internalizing psychopathology was specifically related to high neuroticism, hopelessness and anxiety-sensitivity, low novelty-seeking and extraversion, and an attentional bias toward negatively valenced verbal stimuli. Findings reveal several nonspecific or transdiagnostic personality and cognitive factors that may be targeted in new interventions to potentially prevent the development of multiple psychopathologies. (PsycINFO Database Record, ((c) 2016 APA, all rights reserved).)

Mental disorders are among the greatest medical and social challenges facing us. They can occur at all stages of life and are among the most important commonly occurring diseases. In Germany 28 % of the population suffer from a mental disorder every year, while the lifetime risk of suffering from a mental disorder is almost 50 %. Mental disorders cause great suffering for those affected and their social network. Quantitatively speaking, they can be considered to be among those diseases creating the greatest burden for society due to reduced productivity, absence from work and premature retirement. The Federal Ministry of Education and Research is funding a new research network from 2015 to 2019 with up to 35 million euros to investigate mental disorders in order to devise and develop better therapeutic measures and strategies for this population by means of basic and translational clinical research. This is the result of a competitive call for research proposals entitled research network for mental diseases. It is a nationwide network of nine consortia with up to ten psychiatric and clinical psychology partner institutions from largely university-based research facilities for adults and/or children and adolescents. Furthermore, three cross-consortia platform projects will seek to identify shared causes of diseases and new diagnostic modalities for anxiety disorders, attention deficit hyperactivity disorders (ADHS), autism, bipolar disorders, depression, schizophrenia and psychotic disorders as well as substance-related and addictive disorders. The spectrum of therapeutic approaches to be examined ranges from innovative pharmacological and psychotherapeutic treatment to novel brain stimulation procedures. In light of the enormous burden such diseases represent for society as a whole, a sustainable improvement in the financial support for those researching mental disorders seems essential. This network aims to become a nucleus for long overdue and sustained support for a German center for mental disorders.

Attention-deficit/hyperactivity disorder (ADHD) is a persistent neurodevelopmental disorder that affects 5% of children and adolescents and 2.5% of adults worldwide. Throughout an individual's lifetime, ADHD can increase the risk of other psychiatric disorders, educational and occupational failure, accidents, criminality, social disability and addictions. No single risk factor is necessary or sufficient to cause ADHD. In most cases ADHD arises from several genetic and environmental risk factors that each have a small individual effect and act together to increase susceptibility. The multifactorial causation of ADHD is consistent with the heterogeneity of the disorder, which is shown by its extensive psychiatric co-morbidity, its multiple domains of neurocognitive impairment and the wide range of structural and functional brain anomalies associated with it. The diagnosis of ADHD is reliable and valid when evaluated with standard criteria for psychiatric disorders. Rating scales and clinical interviews facilitate diagnosis and aid screening. The expression of symptoms varies as a function of patient developmental stage and social and academic contexts. Although there are no curative treatments for ADHD, evidenced-based treatments can markedly reduce its symptoms and associated impairments. For example, medications are efficacious and normally well tolerated, and various non-pharmacological approaches are also valuable. Ongoing clinical and neurobiological research holds the promise of advancing diagnostic and therapeutic approaches to ADHD. For an illustrated summary of this Primer, visit: http://go.nature.com/J6jiwl.

Objective: To investigate the role of personality factors and attentional biases towards emotional faces, in establishing concurrent and prospective risk for mental disorder diagnosis in adolescence., Method: Data were obtained as part of the IMAGEN study, conducted across 8 European sites, with a community sample of 2257 adolescents. At 14 years, participants completed an emotional variant of the dot-probe task, as well two personality measures, namely the Substance Use Risk Profile Scale and the revised NEO Personality Inventory. At 14 and 16 years, participants and their parents were interviewed to determine symptoms of mental disorders., Results: Personality traits were general and specific risk indicators for mental disorders at 14 years. Increased specificity was obtained when investigating the likelihood of mental disorders over a 2-year period, with the Substance Use Risk Profile Scale showing incremental validity over the NEO Personality Inventory. Attentional biases to emotional faces did not characterise or predict mental disorders examined in the current sample., Discussion: Personality traits can indicate concurrent and prospective risk for mental disorders in a community youth sample, and identify at-risk youth beyond the impact of baseline symptoms. This study does not support the hypothesis that attentional biases mediate the relationship between personality and psychopathology in a community sample. Task and sample characteristics that contribute to differing results among studies are discussed.

Discovering the genetic basis of early-onset psychiatric disorders has been the aim of intensive research during the last decade. We will first selectively summarize results of genetic research in child and adolescent psychiatry by using examples from different disorders and discuss methodological issues, emerging questions and future directions. In the second part of this review, we will focus on how to link genetic causes of disorders with physiological pathways, discuss the impact of genetic findings on diagnostic systems, prevention and therapeutic interventions. Finally we will highlight some ethical aspects connected to genetic research in child and adolescent psychiatry. Advances in molecular genetic methods have led to insights into the genetic architecture of psychiatric disorders, but not yet provided definite pathways to pathophysiology. If replicated, promising findings from genetic studies might in some cases lead to personalized treatments. On the one hand, knowledge of the genetic basis of disorders may influence diagnostic categories. On the other hand, models also suggest studying the genetic architecture of psychiatric disorders across diagnoses and clinical groups.

Objective: The genetic component of alcohol use disorder is substantial, but monozygotic twin discordance indicates a role for nonheritable differences that could be mediated by epigenetics. Despite growing evidence associating epigenetics and psychiatric disorders, it is unclear how epigenetics, particularly DNA methylation, relate to brain function and behavior, including drinking behavior., Method: The authors carried out a genome-wide analysis of DNA methylation of 18 monozygotic twin pairs discordant for alcohol use disorder and validated differentially methylated regions. After validation, the authors characterized these differentially methylated regions using personality trait assessment and functional MRI in a sample of 499 adolescents., Results: Hypermethylation in the 3'-protein-phosphatase-1G (PPM1G) gene locus was associated with alcohol use disorder. The authors found association of PPM1G hypermethylation with early escalation of alcohol use and increased impulsiveness. They also observed association of PPM1G hypermethylation with increased blood-oxygen-level-dependent response in the right subthalamic nucleus during an impulsiveness task., Conclusions: Overall, the authors provide first evidence for an epigenetic marker associated with alcohol consumption and its underlying neurobehavioral phenotype.

Most psychiatric disorders are moderately to highly heritable. The degree to which genetic variation is unique to individual disorders or shared across disorders is unclear. To examine shared genetic etiology, we use genome-wide genotype data from the Psychiatric Genomics Consortium (PGC) for cases and controls in schizophrenia, bipolar disorder, major depressive disorder, autism spectrum disorders (ASD) and attention-deficit/hyperactivity disorder (ADHD). We apply univariate and bivariate methods for the estimation of genetic variation within and covariation between disorders. SNPs explained 17-29% of the variance in liability. The genetic correlation calculated using common SNPs was high between schizophrenia and bipolar disorder (0.68 ± 0.04 s.e.), moderate between schizophrenia and major depressive disorder (0.43 ± 0.06 s.e.), bipolar disorder and major depressive disorder (0.47 ± 0.06 s.e.), and ADHD and major depressive disorder (0.32 ± 0.07 s.e.), low between schizophrenia and ASD (0.16 ± 0.06 s.e.) and non-significant for other pairs of disorders as well as between psychiatric disorders and the negative control of Crohn's disease. This empirical evidence of shared genetic etiology for psychiatric disorders can inform nosology and encourages the investigation of common pathophysiologies for related disorders.

Background: In many severely mentally disordered children, the clinical presentation is complicated by comorbid affective and behavioral dysregulation. Recently, a highly heritable behavioral phenotype of simultaneous deviance on the anxious/depressed, attention problems, and aggressive behavior syndrome scales has been identified on the Child Behavior Checklist Dysregulation Profile (CBCL-DP). The aim of the present pilot study was to determine an equivalent to the CBCL-DP using the Strengths and Difficulties Questionnaire (SDQ)., Sampling and Methods: We applied stepwise linear discriminant analyses and receiver operating characteristic (ROC) analysis to data from 543 consecutively referred children and adolescents, aged 5-17 years. The CBCL and the SDQ were completed by parents as part of the diagnostic routine. ICD-10 discharge diagnoses were established in consensus conferences., Results: A combination of five SDQ items (SDQ-Dysregulation Profile, SDQ-DP) yielded the best discrimination of children with and without CBCL-DP and classified 81.0% of the subjects correctly leading to an area under the curve of 0.93. The content of the five SDQ-DP items mirrors well the mixed behavioral phenotype of anxious-depressive, aggressive and attention problems captured by the CBCL-DP. SDQ-DP status was highly correlated with CBCL-DP status and was best defined by a SDQ-DP score ≥5., Conclusions: The psychometric properties of the SDQ-DP have been robustly tested and validated. Based on these results, clinicians may use the SDQ-DP as a useful and economical screening measure to improve the assessment, prevention, and treatment of severe dysregulation in childhood and adolescence. Future investigations should study the longitudinal stability, heritability, and genetic associations of this behavioral phenotype., (Copyright © 2010 S. Karger AG, Basel.)

A fundamental function of the brain is to evaluate the emotional and motivational significance of stimuli and to adapt behaviour accordingly. The IMAGEN study is the first multicentre genetic-neuroimaging study aimed at identifying the genetic and neurobiological basis of individual variability in impulsivity, reinforcer sensitivity and emotional reactivity, and determining their predictive value for the development of frequent psychiatric disorders. Comprehensive behavioural and neuropsychological characterization, functional and structural neuroimaging and genome-wide association analyses of 2000 14-year-old adolescents are combined with functional genetics in animal and human models. Results will be validated in 1000 adolescents from the Canadian Saguenay Youth Study. The sample will be followed up longitudinally at the age of 16 years to investigate the predictive value of genetics and intermediate phenotypes for the development of frequent psychiatric disorders. This review describes the strategies the IMAGEN consortium used to meet the challenges posed by large-scale multicentre imaging-genomics investigations. We provide detailed methods and Standard Operating Procedures that we hope will be helpful for the design of future studies. These include standardization of the clinical, psychometric and neuroimaging-acquisition protocols, development of a central database for efficient analyses of large multimodal data sets and new analytic approaches to large-scale genetic neuroimaging analyses.

Psychophysiological research focusing on child development and on child and adolescent psychiatric disorders has provided many important insights. The use of cognitive neuroscience methods along with the assessment of peripheral psychophysiological measures - particularly functional magnetic resonance imaging and electroencephalography reflecting brain activity - have advanced our understanding of the physiological basis of many cognitive processes such as attention, memory, learning, and language in the context of child development and psychiatric disorders. These insights are proving increasingly helpful when evaluating and advancing treatment. The following review introduces the reader to psychophysiological and particularly electrophysiological methods widely used in child and adolescent psychiatry research.

It is now generally accepted that complex mental disorders are the results of interplay between genetic and environmental factors. This holds out the prospect that by studying G x E interplay we can explain individual variation in vulnerability and resilience to environmental hazards in the development of mental disorders. Furthermore studying G x E findings may give insights in neurobiological mechanisms of psychiatric disorder and so improve individualized treatment and potentially prevention. In this paper, we provide an overview of the state of field with regard to G x E in mental disorders. Strategies for G x E research are introduced. G x E findings from selected mental disorders with onset in childhood or adolescence are reviewed [such as depressive disorders, attention-deficit/hyperactivity disorder (ADHD), obesity, schizophrenia and substance use disorders]. Early seminal studies provided evidence for G x E in the pathogenesis of depression implicating 5-HTTLPR, and conduct problems implicating MAOA. Since then G x E effects have been seen across a wide range of mental disorders (e.g., ADHD, anxiety, schizophrenia, substance abuse disorder) implicating a wide range of measured genes and measured environments (e.g., pre-, peri- and postnatal influences of both a physical and a social nature). To date few of these G x E effects have been sufficiently replicated. Indeed meta-analyses have raised doubts about the robustness of even the most well studied findings. In future we need larger, sufficiently powered studies that include a detailed and sophisticated characterization of both phenotype and the environmental risk.

The present study aimed to clarify the functional role of genes in the dopamine and serotonin systems by examining whether polymorphisms in these genes are related to adolescent externalizing behavior either alone or in interaction with each other. Participants were selected from an ongoing prospective study of the outcome of early risk factors. At age 15 years, 298 adolescents (144 males, 154 females) completed the Youth Self Report, 296 primary caregivers the Child Behavior Checklist and 253 teachers the Teacher Report Form. DNA was genotyped for the DRD4 exon III VNTR and the 5-HTTLPR polymorphisms. Results revealed that individuals with the DRD4 7r allele reported significantly more externalizing behavior than carriers of other variants. In addition, a significant interaction emerged, indicating that adolescents carrying two copies of the 5-HTTLPR short allele and the DRD4 7r variant scored highest on aggressive and/or delinquent behavior compared to other genotypes. This result suggests an effect of 5-HTTLPR on externalizing behavior in the presence of DRD4 7r but no effect in its absence.

Background: In Tourette syndrome (TS) as a neurodevelopmental disorder not only the tics but also the comorbid conditions change with increasing age. ADHD is highly comorbid with TS and usually impairs psychosocial functioning more than the tics. Its impact on further comorbidity during development is important for clinical practice and still a matter of debate., Method: Aspects of developmental psychopathology considering the impact of ADHD were examined by logistic regression (year wisely) in a cross-sectional sample of children and adolescents (n = 5060) from the TIC database., Results: In TS+ADHD (compared to TS-ADHD) higher rates of comorbid conditions like OCD, anxiety disorders, CD/ODD and mood disorders were found in children (5-10 years). In adolescents (11-17 years) higher comorbidity rates in TS+ADHD remained only for CD/ODD and mood disorders. Accordingly, for OCD and anxiety disorders there was a steeper year wise increase of these comorbidities in TS-ADHD while it was a similar for CD/ODD and mood disorders in TS-ADHD as well as TS+ADHD., Conclusion: Children with TS+ADHD have more comorbidities than the TS-ADHD group, whereas in both adolescent groups this did no longer hold for OCD and anxiety disorders. These findings indicate that in TS comorbid ADHD is associated with high rates of externalizing and internalizing problems, whereas TS without ADHD is associated only with internalizing problems in adolescence.

Background: Monitoring brain processes in real time requires genuine subsecond resolution to follow the typical timing and frequency of neural events. Non-invasive recordings of electric (EEG/ERP) and magnetic (MEG) fields provide this time resolution. They directly measure neural activations associated with a wide variety of brain states and processes, even during sleep or in infants. Mapping and source estimation can localise these time-varying activation patterns inside the brain., Methods: Recent EEG/ERP research on brain functions in the domains of attention and executive functioning, perception, memory, language, emotion and motor processing in ADHD, autism, childhood-onset schizophrenia, Tourette syndrome, specific language disorder and developmental dyslexia, anxiety, obsessive-compulsive disorder, and depression is reviewed., Results: Over the past two decades, electrophysiology has substantially contributed to the understanding of brain functions during normal development, and psychiatric conditions of children and adolescents. Its time resolution has been important to measure covert processes, and to distinguish cause and effect., Conclusions: In the future, EEG/ERP parameters will increasingly characterise the interplay of neural states and information processing. They are particularly promising tools for multilevel investigations of etiological pathways and potential predictors of clinical treatment response.