Pharmacotherapy for ADHD in children and adolescents: A summary and overview of different European guidelines.

Attention deficit/hyperactivity disorder (ADHD) is a neurodevelopmental disorder characterized by a persistent pattern of inattention, hyperactivity, and impulsivity. It is the most common neurodevelopmental disorder presenting to pediatric services, and pediatricians are often involved in the early assessment, diagnosis, and treatment of children with ADHD. The treatment of ADHD typically involves a multimodal approach that encompasses a combination of psychoeducation, parent/teacher training, psychosocial/psychotherapeutic interventions, and pharmacotherapy. Concerning pharmacotherapy, guidelines vary in drug choice and sequencing, with psychostimulants, such as methylphenidate and (lis)dexamfetamine, generally being the favored initial treatment. Alternatives include atomoxetine and guanfacine. Pharmacotherapy has been proven effective, but close follow-up focusing on physical growth, cardiovascular monitoring, and the surveillance of potential side effects including tics, mood fluctuations, and psychotic symptoms, is essential. This paper presents an overview of current pharmacological treatment options for ADHD and explores disparities in treatment guidelines across different European countries.   Conclusion: Pharmacological treatment options for ADHD in children and adolescents are effective and generally well-tolerated. Pharmacotherapy for ADHD is always part of a multimodal approach. While there is a considerable consensus among European guidelines on pharmacotherapy for ADHD, notable differences exist, particularly concerning the selection and sequencing of various medications. What is Known: • There is a significant base of evidence for pharmacological treatment for ADHD in children and adolescents. • Pediatricians are often involved in assessment, diagnosis and management of children with ADHD. What is New: • Our overview of different European guidelines reveals significant agreement in the context of pharmacotherapy for ADHD in children and adolescents. • Discrepancies exist primarily in terms of selection and sequencing of different medications.

Screening for affective dysregulation in school-aged children: relationship with comprehensive measures of affective dysregulation and related mental disorders.

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.

Prevalences of mental distress and its associated factors in unaccompanied refugee minors in Germany.

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.

Impact of the COVID-19 pandemic on children with and without affective dysregulation and their families.

Analyzing COVID-19-related stress in children with affective dysregulation (AD) seems especially interesting, as these children typically show heightened reactivity to potential stressors and an increased use of maladaptive emotion regulation strategies. Children in out-of-home care often show similar characteristics to those with AD. Since COVID-19 has led to interruptions in psychotherapy for children with mental health problems and to potentially reduced resources to implement treatment strategies in daily life in families or in out-of-home care, these children might show a particularly strong increase in stress levels. In this study, 512 families of children without AD and 269 families of children with AD reported on COVID-19-related stress. The sample comprised screened community, clinical, and out-of-home care samples. Sociodemographic factors, characteristics of child and caregiver before the pandemic, and perceived change in external conditions due to the pandemic were examined as potential risk or protective factors. Interestingly, only small differences emerged between families of children with and without AD or between subsamples: families of children with AD and families in out-of-home care were affected slightly more, but in few domains. Improvements and deteriorations in treatment-related effects balanced each other out. Overall, the most stable and strongest risk factor for COVID-19-related stress was perceived negative change in external conditions-particularly family conditions and leisure options. Additionally, caregiver characteristics emerged as risk factors across most models. Actions to support families during the pandemic should, therefore, facilitate external conditions and focus on caregiver characteristic to reduce familial COVID-19-related stress. Trial registration: German Clinical Trials Register (DRKS), ADOPT Online: DRKS00014963 registered 27 June 2018, ADOPT Treatment: DRKS00013317 registered 27 September 2018, ADOPT Institution: DRKS00014581 registered 04 July 2018.

Remote assessment of ADHD in children and adolescents: recommendations from the European ADHD Guidelines Group following the clinical experience during the COVID-19 pandemic.

The COVID-19 pandemic led ADHD services to modify the clinical practice to reduce in-person contact as much as possible to minimise viral spread. This had far-reaching effects on day-to-day clinical practice as remote assessments were widely adopted. Despite the attenuation of the acute threat from COVID, many clinical services are retaining some remote practices. The lack of clear evidence-based guidance about the most appropriate way to conduct remote assessments meant that these changes were typically implemented in a localised, ad hoc, and un-coordinated way. Here, the European ADHD Guidelines Group (EAGG) discusses the strengths and weaknesses of remote assessment methods of children and adolescents with ADHD in a narrative review based on available data and expert opinions to highlight key recommendations for future studies and clinical practice. We conclude that going forward, despite remote working in clinical services functioning adequately during the pandemic, all required components of ADHD assessment should still be completed following national/international guidelines; however, the process may need adaptation. Social restrictions, including changes in education provision, can either mask or exacerbate features associated with ADHD and therefore assessment should carefully chart symptom profile and impairment prior to, as well as during an ongoing pandemic. While remote assessments are valuable in allowing clinical services to continue despite restrictions and may have benefits for routine care in the post-pandemic world, particular attention must be paid to those who may be at high risk but not be able to use/access remote technologies and prioritize these groups for conventional face-to-face assessments.

Evaluation of data imputation strategies in complex, deeply-phenotyped data sets: the case of the EU-AIMS Longitudinal European Autism Project.

An increasing number of large-scale multi-modal research initiatives has been conducted in the typically developing population, e.g. Dev. Cogn. Neur. 32:43-54, 2018; PLoS Med. 12(3):e1001779, 2015; Elam and Van Essen, Enc. Comp. Neur., 2013, as well as in psychiatric cohorts, e.g. Trans. Psych. 10(1):100, 2020; Mol. Psych. 19:659-667, 2014; Mol. Aut. 8:24, 2017; Eur. Child and Adol. Psych. 24(3):265-281, 2015. Missing data is a common problem in such datasets due to the difficulty of assessing multiple measures on a large number of participants. The consequences of missing data accumulate when researchers aim to integrate relationships across multiple measures. Here we aim to evaluate different imputation strategies to fill in missing values in clinical data from a large (total N = 764) and deeply phenotyped (i.e. range of clinical and cognitive instruments administered) sample of N = 453 autistic individuals and N = 311 control individuals recruited as part of the EU-AIMS Longitudinal European Autism Project (LEAP) consortium. In particular, we consider a total of 160 clinical measures divided in 15 overlapping subsets of participants. We use two simple but common univariate strategies-mean and median imputation-as well as a Round Robin regression approach involving four independent multivariate regression models including Bayesian Ridge regression, as well as several non-linear models: Decision Trees (Extra Trees., and Nearest Neighbours regression. We evaluate the models using the traditional mean square error towards removed available data, and also consider the Kullback-Leibler divergence between the observed and the imputed distributions. We show that all of the multivariate approaches tested provide a substantial improvement compared to typical univariate approaches. Further, our analyses reveal that across all 15 data-subsets tested, an Extra Trees regression approach provided the best global results. This not only allows the selection of a unique model to impute missing data for the LEAP project and delivers a fixed set of imputed clinical data to be used by researchers working with the LEAP dataset in the future, but provides more general guidelines for data imputation in large scale epidemiological studies.

[Cohort studies in child and adolescent psychiatry]. / Kohortenstudien in der Kinder- und Jugendpsychiatrie.

BACKGROUND: Longitudinal cohort studies with early start and life span perspectives are increasingly recognized as being crucial to uncover developmental trajectories as well as risk and resilience factors of psychiatric disorders. OBJECTIVE: The importance of longitudinal studies is presented and the main findings of the Mannheim study of children at risk (MARS), the adolescent brain cognitive development (ABCD), the pediatric and adolescent health survey (Kinder- und Jugendgesundheitssurvey, KiGGS) and the AIMS longitudinal European autism project (LEAP) cohort studies are described. MATERIAL AND METHODS: A literature search was carried out in MEDLINE. RESULTS: The MARS followed participants with psychosocial and organic risks over more than 30 years starting from birth and showed the importance of early risk factors (prenatal period up to early childhood) for neuropsychosocial development. The ABCD cohort study (start 9-10 years old) underlined the developmental significance of early socioemotional and prenatal risks as well as toxin exposure. The KiGGS cohort followed children and adolescents from age 0-17 years up to the ages of 10-28 years. Main findings underline the importance of the socioeconomic status and gender-specific effects with respect to sensitive periods for the onset and trajectories of psychiatric disorders. The AIMS cohort followed patients with and without autism spectrum disorders aged between 6 and 30 years and first results revealed small effects regarding group differences. Further, cohort studies starting prenatally along with deep phenotyping are warranted to uncover the complex etiology of mental disorders. CONCLUSION: Existing cohort studies on early mental development have shown specific focal points. To identify general and specific risk and resilience factors for psychiatric disorders and to model trajectories, there is a need for multimodal integration of data sets.

The Arf6 activator Efa6/PSD3 confers regional specificity and modulates ethanol consumption in Drosophila and humans.

Ubiquitously expressed genes have been implicated in a variety of specific behaviors, including responses to ethanol. However, the mechanisms that confer this behavioral specificity have remained elusive. Previously, we showed that the ubiquitously expressed small GTPase Arf6 is required for normal ethanol-induced sedation in adult Drosophila. Here, we show that this behavioral response also requires Efa6, one of (at least) three Drosophila Arf6 guanine exchange factors. Ethanol-naive Arf6 and Efa6 mutants were sensitive to ethanol-induced sedation and lacked rapid tolerance upon re-exposure to ethanol, when compared with wild-type flies. In contrast to wild-type flies, both Arf6 and Efa6 mutants preferred alcohol-containing food without prior ethanol experience. An analysis of the human ortholog of Arf6 and orthologs of Efa6 (PSD1-4) revealed that the minor G allele of single nucleotide polymorphism (SNP) rs13265422 in PSD3, as well as a haplotype containing rs13265422, was associated with an increased frequency of drinking and binge drinking episodes in adolescents. The same haplotype was also associated with increased alcohol dependence in an independent European cohort. Unlike the ubiquitously expressed human Arf6 GTPase, PSD3 localization is restricted to the brain, particularly the prefrontal cortex (PFC). Functional magnetic resonance imaging revealed that the same PSD3 haplotype was also associated with a differential functional magnetic resonance imaging signal in the PFC during a Go/No-Go task, which engages PFC-mediated executive control. Our translational analysis, therefore, suggests that PSD3 confers regional specificity to ubiquitous Arf6 in the PFC to modulate human alcohol-drinking behaviors.

Collaborative meta-analysis finds no evidence of a strong interaction between stress and 5-HTTLPR genotype contributing to the development of depression.

The hypothesis that the S allele of the 5-HTTLPR serotonin transporter promoter region is associated with increased risk of depression, but only in individuals exposed to stressful situations, has generated much interest, research and controversy since first proposed in 2003. Multiple meta-analyses combining results from heterogeneous analyses have not settled the issue. To determine the magnitude of the interaction and the conditions under which it might be observed, we performed new analyses on 31 data sets containing 38 802 European ancestry subjects genotyped for 5-HTTLPR and assessed for depression and childhood maltreatment or other stressful life events, and meta-analysed the results. Analyses targeted two stressors (narrow, broad) and two depression outcomes (current, lifetime). All groups that published on this topic prior to the initiation of our study and met the assessment and sample size criteria were invited to participate. Additional groups, identified by consortium members or self-identified in response to our protocol (published prior to the start of analysis) with qualifying unpublished data, were also invited to participate. A uniform data analysis script implementing the protocol was executed by each of the consortium members. Our findings do not support the interaction hypothesis. We found no subgroups or variable definitions for which an interaction between stress and 5-HTTLPR genotype was statistically significant. In contrast, our findings for the main effects of life stressors (strong risk factor) and 5-HTTLPR genotype (no impact on risk) are strikingly consistent across our contributing studies, the original study reporting the interaction and subsequent meta-analyses. Our conclusion is that if an interaction exists in which the S allele of 5-HTTLPR increases risk of depression only in stressed individuals, then it is not broadly generalisable, but must be of modest effect size and only observable in limited situations.

EFhd2/Swiprosin-1 is a common genetic determinator for sensation-seeking/low anxiety and alcohol addiction.

In many societies, the majority of adults regularly consume alcohol. However, only a small proportion develops alcohol addiction. Individuals at risk often show a high sensation-seeking/low-anxiety behavioural phenotype. Here we asked which role EF hand domain containing 2 (EFhd2; Swiprosin-1) plays in the control of alcohol addiction-associated behaviours. EFhd2 knockout (KO) mice drink more alcohol than controls and spontaneously escalate their consumption. This coincided with a sensation-seeking and low-anxiety phenotype. A reversal of the behavioural phenotype with ß-carboline, an anxiogenic inverse benzodiazepine receptor agonist, normalized alcohol preference in EFhd2 KO mice, demonstrating an EFhd2-driven relationship between personality traits and alcohol preference. These findings were confirmed in a human sample where we observed a positive association of the EFhd2 single-nucleotide polymorphism rs112146896 with lifetime drinking and a negative association with anxiety in healthy adolescents. The lack of EFhd2 reduced extracellular dopamine levels in the brain, but enhanced responses to alcohol. In confirmation, gene expression analysis revealed reduced tyrosine hydroxylase expression and the regulation of genes involved in cortex development, Eomes and Pax6, in EFhd2 KO cortices. These findings were corroborated in Xenopus tadpoles by EFhd2 knockdown. Magnetic resonance imaging (MRI) in mice showed that a lack of EFhd2 reduces cortical volume in adults. Moreover, human MRI confirmed the negative association between lifetime alcohol drinking and superior frontal gyrus volume. We propose that EFhd2 is a conserved resilience factor against alcohol consumption and its escalation, working through Pax6/Eomes. Reduced EFhd2 function induces high-risk personality traits of sensation-seeking/low anxiety associated with enhanced alcohol consumption, which may be related to cortex function.

Slow cortical potentials neurofeedback in children with ADHD: comorbidity, self-regulation and clinical outcomes 6 months after treatment in a multicenter randomized controlled trial.

Despite sizeable short-term effects of neurofeedback (NF) therapy on attention-deficit and hyperactivity disorder (ADHD), longer-term clinical, comorbidity and self-regulation outcomes are less systematically studied. The aim of this largest NF follow-up to date was to evaluate these outcomes 6 months after NF compared to a semi-active control to disentangle specific from unspecific sustained effects. We performed a multicenter, randomized, parallel, controlled, clinical, superiority trial in five German university outpatient departments. Participants were eligible if they fulfilled DSM-IV-TR criteria for ADHD and were aged from 7 to 9 years. Participants were randomly assigned (1:1-ratio) to 25 sessions of slow cortical potential (SCP)-NF or electromyogram biofeedback (EMG-BF). Participants were not blinded, since they received instructions according to each treatment setting. Primary outcomes were parent ratings of ADHD. The trial was registered, number ISRCTN761871859. Both groups showed improvement of ADHD symptoms compared to baseline at 6-months follow-up with large effect sizes for SCP-NF (d = 1.04) and EMG-BF (d = 0.85), but without group differences. When analyzing all assessments (pre-test, post-test-1, post-test-2 and follow-up), a group-by-time interaction emerged (p = 0.0062), with SCP-NF showing stable improvement following treatment but EMG-BF showing a relapse from post-test-1 to post-test-2, and subsequent remission at follow-up. Six months after the end of treatment, improvement after SCP-NF remained large and stable. However, the lack of group differences at follow-up suggests shared specific and unspecific effects contributing to this clinical outcome. Our correlational results indicate specificity of SCP-NF for selected subscales after training, but not at follow-up.

Association of preterm birth with ADHD-like cognitive impairments and additional subtle impairments in attention and arousal malleability.

BACKGROUND: Whilst preterm-born individuals have an increased risk of developing attention-deficit/hyperactivity disorder (ADHD), and are reported to have ADHD-like attention and arousal impairments, direct group comparisons are scarce. METHODS: We directly compared preterm-born adolescents (n = 186) to term-born adolescents with ADHD (n = 69), and term-born controls (n = 135), aged 11-23, on cognitive-performance, event-related potential and skin conductance level (SCL) measures associated with attention and arousal. The measures are from baseline and fast-incentive conditions of a four-choice reaction time task, previously shown to discriminate between the individuals with ADHD and controls. We aimed to establish whether preterm-born adolescents show: (a) identical cognitive-neurophysiological impairments to term-born adolescents with ADHD (b) possible additional impairments, and whether (c) the observed impairments correlate with ADHD symptom scores. RESULTS: The preterm group, like the term-born ADHD group, showed increased mean reaction time (MRT) and reaction time variability (RTV) in the baseline condition, and attenuated contingent negative variation (CNV) amplitude (response preparation) in the fast-incentive condition. The preterm group, only, did not show significant within-group adjustments in P3 amplitude (attention allocation) and SCL (peripheral arousal). Dimensional analyses showed that ADHD symptoms scores correlated significantly with MRT, RTV and CNV amplitude only. CONCLUSIONS: We find impairments in cognition and brain function in preterm-born adolescents that are linked to increased ADHD symptoms, as well as further impairments, in lack of malleability in neurophysiological processes. Our findings indicate that such impairments extend at least to adolescence. Future studies should extend these investigations into adulthood.

EEG Source Imaging Indices of Cognitive Control Show Associations with Dopamine System Genes.

Cognitive or executive control is a critical mental ability, an important marker of mental illness, and among the most heritable of neurocognitive traits. Two candidate genes, catechol-O-methyltransferase (COMT) and DRD4, which both have a roles in the regulation of cortical dopamine, have been consistently associated with cognitive control. Here, we predicted that individuals with the COMT Met/Met allele would show improved response execution and inhibition as indexed by event-related potentials in a Go/NoGo task, while individuals with the DRD4 7-repeat allele would show impaired brain activity. We used independent component analysis (ICA) to separate brain source processes contributing to high-density EEG scalp signals recorded during the task. As expected, individuals with the DRD4 7-repeat polymorphism had reduced parietal P3 source and scalp responses to response (Go) compared to those without the 7-repeat. Contrary to our expectation, the COMT homozygous Met allele was associated with a smaller frontal P3 source and scalp response to response-inhibition (NoGo) stimuli, suggesting that while more dopamine in frontal cortical areas has advantages in some tasks, it may also compromise response inhibition function. An interaction effect emerged for P3 source responses to Go stimuli. These were reduced in those with both the 7-repeat DRD4 allele and either the COMT Val/Val or the Met/Met homozygous polymorphisms but not in those with the heterozygous Val/Met polymorphism. This epistatic interaction between DRD4 and COMT replicates findings that too little or too much dopamine impairs cognitive control. The anatomic and functional separated maximally independent cortical EEG sources proved more informative than scalp channel measures for genetic studies of brain function and thus better elucidate the complex mechanisms in psychiatric illness.

[Diagnostics and initial estimation of refugee minors]. / Diagnostik und Ersteinschätzung bei minderjährigen Flüchtlingen.

The number of underage refugees arriving in Germany has rapidly increased since 2015. Many of these children and adolescents have been and still are, exposed to a large number of stressful circumstances. The group of those helping refugee minors is heterogeneous with both volunteers and professional workers from the fields of child welfare and healthcare services. Easily applicable instruments to assess both burdens and resources are needed in order to plan appropriate interventions. This paper focuses on instruments for assessing the circumstances of refugee minors and includes pilot data of an online-based screening instrument to assess burdens and resources (providing online resource and trauma assessment for refugees, PORTA). Field application was tested by the staff of a clearing and preclearing institution with 33 cases and good practical feasibility was reported. Applying a simple to use screening instrument for refugee minors and their helpers, which is available in several languages creates the possibility of a shared definition of problems and solutions and is beneficial to helpers (e.g. volunteers, youth welfare services and medical doctors) as well as refugee minors.

Genomic architecture of human neuroanatomical diversity.

Human brain anatomy is strikingly diverse and highly inheritable: genetic factors may explain up to 80% of its variability. Prior studies have tried to detect genetic variants with a large effect on neuroanatomical diversity, but those currently identified account for <5% of the variance. Here, based on our analyses of neuroimaging and whole-genome genotyping data from 1765 subjects, we show that up to 54% of this heritability is captured by large numbers of single-nucleotide polymorphisms of small-effect spread throughout the genome, especially within genes and close regulatory regions. The genetic bases of neuroanatomical diversity appear to be relatively independent of those of body size (height), but shared with those of verbal intelligence scores. The study of this genomic architecture should help us better understand brain evolution and disease.

Single nucleotide polymorphism in the neuroplastin locus associates with cortical thickness and intellectual ability in adolescents.

Despite the recognition that cortical thickness is heritable and correlates with intellectual ability in children and adolescents, the genes contributing to individual differences in these traits remain unknown. We conducted a large-scale association study in 1583 adolescents to identify genes affecting cortical thickness. Single-nucleotide polymorphisms (SNPs; n=54,837) within genes whose expression changed between stages of growth and differentiation of a human neural stem cell line were selected for association analyses with average cortical thickness. We identified a variant, rs7171755, associating with thinner cortex in the left hemisphere (P=1.12 × 10(-)(7)), particularly in the frontal and temporal lobes. Localized effects of this SNP on cortical thickness differently affected verbal and nonverbal intellectual abilities. The rs7171755 polymorphism acted in cis to affect expression in the human brain of the synaptic cell adhesion glycoprotein-encoding gene NPTN. We also found that cortical thickness and NPTN expression were on average higher in the right hemisphere, suggesting that asymmetric NPTN expression may render the left hemisphere more sensitive to the effects of NPTN mutations, accounting for the lateralized effect of rs7171755 found in our study. Altogether, our findings support a potential role for regional synaptic dysfunctions in forms of intellectual deficits.

[The German research network for mental disorders]. / Das deutsche Forschungsnetz zu psychischen Erkrankungen.

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.

Trust, but verify. The errors and misinterpretations in the Cochrane analysis by O. J. Storebo and colleagues on the efficacy and safety of methylphenidate for the treatment of children and adolescents with ADHD.

Objective: A recent Cochrane review published by O. J. Storebo and colleagues (2015) raised substantial doubts about the benefit from stimulant medication with methylphenidate in the treatment of childhood ADHD due to the overall poor quality of studies. The systematic review thus contradicts all previous reviews and meta-analyses. Method: We here detail various examples of errors, inconsistencies, and misinterpretations in the review which led to false results and inadequate conclusions. Results: We demonstrate that the study selection is flawed and undertaken without sufficient scientific justification resulting in an underestimation of effect sizes, which, furthermore, are inadmissibly clinically interpreted. The methodology of the assessment of bias and quality is not objective and cannot be substantiated by the data. Conclusions: Cochrane reviews lay claim to a high scientific quality and substantial relevance for evidence-based clinical decisions. The systematic review by Storebo and colleagues (2015) illustrates that, despite adhering to strict standards and high-quality protocols, even Cochrane works should be critically read and verified, sometimes with surprising results.

Resilience and corpus callosum microstructure in adolescence.

BACKGROUND: Resilience is the capacity of individuals to resist mental disorders despite exposure to stress. Little is known about its neural underpinnings. The putative variation of white-matter microstructure with resilience in adolescence, a critical period for brain maturation and onset of high-prevalence mental disorders, has not been assessed by diffusion tensor imaging (DTI). Lower fractional anisotropy (FA) though, has been reported in the corpus callosum (CC), the brain's largest white-matter structure, in psychiatric and stress-related conditions. We hypothesized that higher FA in the CC would characterize stress-resilient adolescents. METHOD: Three groups of adolescents recruited from the community were compared: resilient with low risk of mental disorder despite high exposure to lifetime stress (n = 55), at-risk of mental disorder exposed to the same level of stress (n = 68), and controls (n = 123). Personality was assessed by the NEO-Five Factor Inventory (NEO-FFI). Voxelwise statistics of DTI values in CC were obtained using tract-based spatial statistics. Regional projections were identified by probabilistic tractography. RESULTS: Higher FA values were detected in the anterior CC of resilient compared to both non-resilient and control adolescents. FA values varied according to resilience capacity. Seed regional changes in anterior CC projected onto anterior cingulate and frontal cortex. Neuroticism and three other NEO-FFI factor scores differentiated non-resilient participants from the other two groups. CONCLUSION: High FA was detected in resilient adolescents in an anterior CC region projecting to frontal areas subserving cognitive resources. Psychiatric risk was associated with personality characteristics. Resilience in adolescence may be related to white-matter microstructure.