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General psychopathology and cognition are likely to have a bidirectional influence on each other. Yet, the relationship between brain structure, psychopathology, and cognition remains unclear. This brief report investigates the association between structural properties of the cerebral cortex [surface area, cortical thickness, intracortical myelination indexed by the T1w/T2w ratio, and neurite density assessed by restriction spectrum imaging (RSI)] with general psychopathology and cognition in a sample of children from the Adolescent Brain Cognitive Development (ABCD) study. Higher levels of psychopathology and lower levels of cognitive ability were associated with a smaller cortical surface area. Inter-regionally-across the cerebral cortex-the strength of association between an area and psychopathology is strongly correlated with the strength of association between an area and cognition. Taken together, structural deviations particularly observed in the cortical surface area influence both psychopathology and cognition., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Patel, Parker, Salum, Pausova and Paus.)

The ENIGMA group on Generalized Anxiety Disorder (ENIGMA-Anxiety/GAD) is part of a broader effort to investigate anxiety disorders using imaging and genetic data across multiple sites worldwide. The group is actively conducting a mega-analysis of a large number of brain structural scans. In this process, the group was confronted with many methodological challenges related to study planning and implementation, between-country transfer of subject-level data, quality control of a considerable amount of imaging data, and choices related to statistical methods and efficient use of resources. This report summarizes the background information and rationale for the various methodological decisions, as well as the approach taken to implement them. The goal is to document the approach and help guide other research groups working with large brain imaging data sets as they develop their own analytic pipelines for mega-analyses., (© 2020 The Authors. Human Brain Mapping published by Wiley Periodicals LLC.)

The goal of this study was to compare brain structure between individuals with generalized anxiety disorder (GAD) and healthy controls. Previous studies have generated inconsistent findings, possibly due to small sample sizes, or clinical/analytic heterogeneity. To address these concerns, we combined data from 28 research sites worldwide through the ENIGMA-Anxiety Working Group, using a single, pre-registered mega-analysis. Structural magnetic resonance imaging data from children and adults (5-90 years) were processed using FreeSurfer. The main analysis included the regional and vertex-wise cortical thickness, cortical surface area, and subcortical volume as dependent variables, and GAD, age, age-squared, sex, and their interactions as independent variables. Nuisance variables included IQ, years of education, medication use, comorbidities, and global brain measures. The main analysis (1020 individuals with GAD and 2999 healthy controls) included random slopes per site and random intercepts per scanner. A secondary analysis (1112 individuals with GAD and 3282 healthy controls) included fixed slopes and random intercepts per scanner with the same variables. The main analysis showed no effect of GAD on brain structure, nor interactions involving GAD, age, or sex. The secondary analysis showed increased volume in the right ventral diencephalon in male individuals with GAD compared to male healthy controls, whereas female individuals with GAD did not differ from female healthy controls. This mega-analysis combining worldwide data showed that differences in brain structure related to GAD are small, possibly reflecting heterogeneity or those structural alterations are not a major component of its pathophysiology., (© 2021. This is a U.S. government work and not under copyright protection in the U.S.; foreign copyright protection may apply.)

Objective: To determine whether psychiatric and gaming pattern variables are associated with gaming disorder in a school-based sample., Methods: We analyzed data from the Brazilian High-Risk Cohort for Psychiatric Disorders, a community sample aged 10 to 18, using questionnaires on gaming use patterns. We applied the Gaming Addiction Scale to diagnose gaming disorder and the Development and Well-Being Behavior Assessment for other diagnoses., Results: Out of 407 subjects, 83 (20.4%) fulfilled the criteria for gaming disorder. More role-playing game players were diagnosed with gaming disorder that any other genre. Gaming disorder rates increased proportionally to the number of genres played. Playing online, being diagnosed with a mental disorder, and more hours of non-stop gaming were associated with higher rates of gaming disorder. When all variables (including age and gender) were considered in a logistic regression model, the number of genres played, the number of non-stop hours, the proportion of online games, and having a diagnosed mental disorder emerged as significant predictors of gaming disorder., Conclusion: Each variable seems to add further risk of gaming disorder among children and adolescents. Monitoring the length of gaming sessions, the number and type of genres played, time spent gaming online, and behavior changes may help parents or guardians identify unhealthy patterns of gaming behavior.

Objective: Mental disorders can have a major impact on brain development. Peripheral blood concentrations of brain-derived neurotrophic factor (BDNF) are lower in adult psychiatric disorders. Serum BDNF concentrations and BDNF genotype have been associated with cortical maturation in children and adolescents. In 2 large independent samples, this study tests associations between serum BDNF concentrations, brain structure, and psychopathology, and the effects of BDNF genotype on BDNF serum concentrations in late childhood and early adolescence., Methods: Children and adolescents (7-14 years old) from 2 cities (n = 267 in Porto Alegre; n = 273 in São Paulo) were evaluated as part of the Brazilian high-risk cohort (HRC) study. Serum BDNF concentrations were quantified by sandwich ELISA. Genotyping was conducted from blood or saliva samples using the SNParray Infinium HumanCore Array BeadChip. Subcortical volumes and cortical thickness were quantified using FreeSurfer. The Development and Well-Being Behavior Assessment was used to identify the presence of a psychiatric disorder., Results: Serum BDNF concentrations were not associated with subcortical volumes or with cortical thickness. Serum BDNF concentration did not differ between participants with and without mental disorders, or between Val homozygotes and Met carriers., Conclusions: No evidence was found to support serum BDNF concentrations as a useful marker of developmental differences in brain and behavior in early life. Negative findings were replicated in 2 of the largest independent samples investigated to date.

Current first-line treatments for major depressive disorder (MDD) include pharmacotherapy and cognitive-behavioral therapy. However, one-third of depressed patients do not achieve remission after multiple medication trials, and psychotherapy can be costly and time-consuming. Although non-implantable neuromodulation (NIN) techniques such as transcranial magnetic stimulation, transcranial direct current stimulation, electroconvulsive therapy, and magnetic seizure therapy are gaining momentum for treating MDD, the efficacy of non-convulsive techniques is still modest, whereas use of convulsive modalities is limited by their cognitive side effects. In this context, we propose that NIN techniques could benefit from a precision-oriented approach. In this review, we discuss the challenges and opportunities in implementing such a framework, focusing on enhancing NIN effects via a combination of individualized cognitive interventions, using closed-loop approaches, identifying multimodal biomarkers, using computer electric field modeling to guide targeting and quantify dosage, and using machine learning algorithms to integrate data collected at multiple biological levels and identify clinical responders. Though promising, this framework is currently limited, as previous studies have employed small samples and did not sufficiently explore pathophysiological mechanisms associated with NIN response and side effects. Moreover, cost-effectiveness analyses have not been performed. Nevertheless, further advancements in clinical trials of NIN could shift the field toward a more "precision-oriented" practice.

Background: Although low-grade inflammation is associated with onset and persistence of depression, most biomarkers display modest predictive effects. GlycA (glycoprotein acetylation) is a unique metabolomic composite of pro-inflammatory acute-phase glycoproteins. We hypothesized that GlycA levels would predict depression incidence, remission and persistence, with higher accuracy than high-sensitivity c-reactive protein (hsCRP). We also explored the additive predictive value of GlycA above and beyond hsCRP., Methods: Cohort design using the sample of the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil)'s São Paulo site. Baseline GlycA and hsCRP levels were measured in blood plasma. Depression incidence, remission, and persistence were assessed using the Clinical Interview Scheduled Revised (CIS-R) at two time points separated by a mean of 3.8 years. Multivariable Poisson, logistic and linear regression models were used for prediction. Models were adjusted for sociodemographic and clinical confounders, including age, gender, ethnicity, education, cardiovascular assessments, antidepressant and anti-inflammatory drug use, anxiety disorders, alcohol use, and body mass index., Results: We included 4,364 participants (53.2% females, mean age 51.4 ± 8.9 years) with no autoimmune disorders. GlycA robustly predicted depression persistence (relative risk of 7.28, 95% confidence interval 1.33-45.57, p = 0.023 in the fully-adjusted model), but not depression onset. Although hsCRP also predicted depression persistence, its effects were fully explained by confounders and by GlycA levels. GlycA also predicted worsening of depressive symptoms in depressed patients and depression persistence vs. remission in fully-adjusted models., Limitations: Brief depressive episodes could not be measured by our assessments., Conclusions: GlycA might be a new inflammatory prognosis biomarker for depression., Competing Interests: Declaration of Competing Interest None, (Copyright © 2020 Elsevier B.V. All rights reserved.)

Purpose of Review: Mental health and substance use problems are among the most prevalent and challenging problems faced by both high-income and low-income countries worldwide. This review will focus on summarizing scattered evidence of school-based interventions to promote well-being and prevent mental health problems and substance use disorders in children and adolescents., Recent Findings: We focus on two main areas of research: promotion of healthy school climate and prevention of bullying. Choosing among available interventions might be challenging, both because of the difficulties in assessing their efficacy and tailoring interventions to specific needs, but also because of the scarcity of intervention in low-resource settings. We provide some guidance on principles encompassed by the available evidence that can be used for policymakers and local communities aiming to integrate mental health promotion and prevention into their schools., Summary: Developing, implementing, scaling and sustaining school-based interventions is a necessity of our field if we want to move closer to sustainable development goals.

Objectives: To investigate the 5-year prevalence of patients admitted to public inpatient care units due to a mental disorder, stratifying them by age group and diagnosis, and to assess trends of admissions over this time period in Porto Alegre., Methods: All admissions to the public mental health care system regulated by the city-owned electronic system Administração Geral dos Hospitais (AGHOS) were included in the analysis. The total population size was obtained by estimations of Fundação de Economia e Estatística (FEE). General information about 5-year prevalence of inpatient admissions, time-series trends e prevalence by age groups and diagnosis were presented., Results: There were 32,608 admissions over the 5-year period analyzed. The overall prevalence of patients was 1.62% among the total population, 0.01% among children, 1.12% among adolescents, 2.28% among adults and 0.93% among the elderly. The most common diagnosis was drug-related, followed by mood, alcohol-related and psychotic disorders. There was a linear trend showing an increase in the number of admissions from 2013 to the midst of 2014, which dropped in 2015., Conclusions: Admissions due to mental disorders are relatively common, mainly among adults and related to drug use and mood disorders. Time trends varied slightly over the 5 years. Prevalence rates in real-world settings might be useful for policymakers interested in planning the public mental health system in large Brazilian cities.

Background: The Extended Strengths and Weaknesses Assessment of Normal Behavior (E-SWAN) reconceptualizes each diagnostic criterion for selected DSM-5 disorders as a behavior, which can range from high (strengths) to low (weaknesses). Initial development focused on Panic Disorder, Social Anxiety, Major Depression, and Disruptive Mood Dysregulation Disorder., Methods: Data were collected from 523 participants (ages 6-17). Parents completed each of the four E-SWAN scales and traditional unidirectional scales addressing the same disorders. Distributional properties, Item Response Theory Analysis (IRT), and Receiver Operating Characteristic (ROC) curves were used to assess and compare the performance of E-SWAN and traditional scales., Results: In contrast to the traditional scales, which exhibited truncated distributions, all four E-SWAN scales had symmetric distributions. IRT analyses indicate the E-SWAN subscales provided reliable information about respondents throughout the population distribution; traditional scales only provided reliable information about respondents at the high end of the distribution. Predictive value for DSM-5 diagnoses was comparable to prior scales., Conclusions: E-SWAN bidirectional scales can capture the full spectrum of the population distribution of behavior underlying DSM disorders. The additional information provided can better inform examination of inter-individual variation in population studies, as well as facilitate the identification of factors related to resiliency in clinical samples., (© 2019 The Authors. Journal of Child Psychology and Psychiatry published by John Wiley & Sons Ltd on behalf of Association for Child and Adolescent Mental Health.)

Objective: The aim of this study is to investigate measurement invariance (MI) for an ADHD latent trait across different sociodemographic groups (sex, age, and maternal education), IQs, and co-occurring psychiatric diagnoses., Method: Participants were 2,299 children aged 6 to 14 years. ADHD symptoms were assessed by parent report using the Development and Well-Being Assessment (DAWBA). MI was tested through multigroup confirmatory factor analysis and multiple indicators multiple causes models., Results: In a bifactor model including a general ADHD factor and three specific factors (hyperactivity, inattention, and impulsivity), invariance properties were demonstrated and no individual items showed differential functioning. The ADHD general factor was higher in boys and in those with psychiatric disorders. Younger age predicted hyperactivity. Lower IQ and higher level of education of the mother predicted inattention., Conclusion: The ADHD trait, as measured by the DAWBA, functions in the same way, and with equivalent scale, revealing true differences in ADHD symptoms based on those.

Increased reaction time variability (RTV) is one of the most replicable behavioral correlates of attention-deficit/hyperactivity disorder (ADHD). However, this may not be specific to ADHD but a more general marker of psychopathology. Here we compare RT variability in individuals with ADHD and those with other childhood internalizing and externalizing conditions both in terms of standard (i.e., the standard deviation of reaction time) and alternative indices that capture low-frequency oscillatory patterns in RT variations over time thought to mark periodic lapses of attention in ADHD. A total of 667 participants (6-12 years old) were classified into non-overlapping diagnostic groups consisting of children with fear disorders (n = 91), distress disorders (n = 56), ADHD (n = 103), oppositional defiant or conduct disorder (ODD/CD; n = 40) and typically developing controls (TDC; n = 377). We used a simple two-choice reaction time task to measure reaction time. The strength of oscillations in RTs across the session was extracted using spectral analyses. Higher RTV was present in ADHD compared to all other disorder groups, effects that were equally strong across all frequency bands. Interestingly, we found that lower RTV to characterize ODD/CD relative to TDC, a finding that was more pronounced at lower frequencies. In general, our data support RTV as a specific marker of ADHD. RT variation across time in ADHD did not show periodicity in a specific frequency band, not supporting that ADHD RTV is the product of spontaneous periodic lapses of attention. Low-frequency oscillations may be particularly useful to differentiate ODD/CD from TDC.

Background: The objective of this study is to assess group differences in symptom reduction between individuals receiving group cognitive behavioral therapy (G-CBT) and attention bias modification (ABM) compared to their respective control interventions, control therapy (CT), and attention control training (ACT), in a 2 × 2 factorial design., Methods: A total of 310 treatment-naive children (7-11 years of age) were assessed for eligibility and 79 children with generalized, separation or social anxiety disorder were randomized and received G-CBT (n = 42) or CT (n = 37). Within each psychotherapy group, participants were again randomized to ABM (n = 38) or ACT (n = 41) in a 2 × 2 factorial design resulting in four groups: G-CBT + ABM (n = 21), G-CBT + ACT (n = 21), CT + ABM (n = 17), and CT + ACT (n = 20). Primary outcomes were responder designation as defined by Clinical Global Impression-Improvement (CGI-I) scale (≤2) and change on the Pediatric Anxiety Rating Scale (PARS)., Results: There were significant improvements of symptoms in all groups. No differences in response rates or mean differences in PARS scores were found among groups: G-CBT + ABM group (23.8% response; 3.9 points, 95% confidence interval [CI] -0.3 to 8.1), G-CBT + ACT (42.9% response; 5.6 points, 95% CI 2.2-9.0), CT + ABM (47.1% response; 4.8 points 95% CI 1.08-8.57), and CT + ACT (30% response; 0.8 points, 95% CI -3.0 to 4.7). No evidence or synergic or antagonistic effects were found, but the combination of G-CBT and ABM was found to increase dropout rate., Conclusions: We found no effect of G-CBT or ABM beyond the effects of comparison groups. Results reveal no benefit from combining G-CBT and ABM for anxiety disorders in children and suggest potential deleterious effects of the combination on treatment acceptability.

Background: Integration of positive psychology into clinical research and treatment has been slow. This integration can be facilitated by the conceptualisation of mental disorders as the high, symptomatic extreme of continuous normal variation. This assumes that there is also a low, positive extreme, which is, however, unchartered territory. This study aims to examine how well current measures capture the low extreme of mental disorder continua, using attention-deficit hyperactivity disorder (ADHD) as an example., Methods: The ability of three validated scales to capture ADHD as a continuous trait was examined using Item Response Theory in a sample of 9,882 adolescents from the UK population-representative Twins Early Development Study. These scales were: the Strengths and Weakness of ADHD Symptoms and Normal behaviour scale (SWAN), Strength and Difficulties Questionnaire (SDQ - hyperactivity subscale), and Conners' Parent Rating Scale (Conners)., Results: Only the SWAN reliably differentiated interindividual differences between participants lying at any level of the continuous ADHD latent trait, including the extreme low, positive end (z-scores from -3 to +3). The SDQ showed low reliability across the ADHD latent trait. In contrast, the Conners performed best at differentiating individuals scoring at or above the mean to the high symptomatic range (z-scores from 0 to +3). The SWAN was the only measure to provide indicators of 'positive mental health', endorsed in the presence of particularly good attentive abilities., Conclusions: Scales such as the SWAN that reliably capture ADHD as a continuous trait, including the positive end, are important for not missing meaningful variation in population-based studies. Indicators of positive mental health may be helpful in clinical practice, as positive attributes have been shown to directly influence as well as buffer negative effects of psychiatric symptoms., (© 2017 Association for Child and Adolescent Mental Health.)

Introduction: Social anxiety disorder (SAD) is the most common anxiety disorder, usually with no remission, and is commonly associated with significant functional and psychosocial impairment. The Brazilian Medical Association (BMA), with the project named Diretrizes (Guidelines, in English), seeks to develop consensus for the diagnosis and treatment of common diseases. The aim of this article is to present the most important findings of the guidelines on the treatment of SAD, serving as a reference for the general practitioner and specialist., Method: The method used was proposed by the BMA. The search was conducted in the databases of MEDLINE (PubMed), Scopus, Web of Science and LILACS, between 1980 and 2010. The strategy used was based on structured questions as PICO (acronym formed by the initials of "patient or population", "intervention, display or exhibition", "control or comparison" and "outcome")., Results: Studies show that the first-line pharmacological treatment for adults and children are serotonin selective reuptake inhibitors and serotonin and norepinephrine reuptake inhibitors, whereas cognitive-behavioral therapy is considered the best psychotherapeutic treatment. Moreover, some psychiatric comorbidities were associated with a worse outcome of SAD., Conclusions: Despite its high prevalence, SAD does not receive adequate attention and treatment. The best choice for the treatment of adults is a combination of cognitive-behavioral psychotherapy with serotonin selective reuptake inhibitors and serotonin and norepinephrine reuptake inhibitors. Other options as benzodiazepines or monoamine oxidase inhibitors must be used as second and third choices, respectively.

Objective: To investigate predictors of relapse two years after a brief cognitive-behavior group therapy in patients with panic disorder who had failed to respond to pharmacologic treatment., Method: A total of 56 patients with panic disorder were followed who had met remission criteria at 1 year evaluation after 12 sessions of cognitive-behavior group therapy. Demographic and clinical features and life stressors were investigated as predictors of relapse., Results: At the 2 year assessment, 39 (70%) patients maintained remission status and use of medication was reduced significantly, such that 36 (64%) patients were not undergoing any psychiatric treatment. Among all independent variables investigated, only "conflict" as a stressful life event, RR = 3.20 (CI95% 1.60; 7.20 - p = 0.001), and the severity or residual anxiety symptoms, RR = 3.60 for each scale point (CI95% 1.02; 1.08 - p < 0.001), emerged as nonredundant predictors., Conclusion: In spite of the high treatment gains across two years of follow-up, clinicians should pay attention to stress management and to the role of residual symptoms during this period. Results were discussed in the context of treatment cost-efficacy and potential strategies to prolong treatment gains from cognitive-behavior group therapy.

Objective: Social anxiety disorder is the most common anxiety disorder. The condition has a chronic course usually with no remission and is frequently associated with significant functional and psychosocial impairment. The Brazilian Medical Association, with the project named Diretrizes ('Guidelines', in English), endeavors to develop diagnostic and treatment protocols for the most common disorders. This work presents the most relevant findings regarding the guidelines of the Brazilian Medical Association concerning the diagnosis and differential diagnosis of social anxiety disorder., Method: We used the methodology proposed by the Brazilian Medical Association for the Diretrizes project. The search was performed on the online databases Medline (PubMed), Scopus, Web of Science, and Lilacs, with no time restraints. Searchable questions were structured using PICO format (acronym for "patient or population"; "intervention, indicator or exposition"; "control or comparison" and; "outcome or ending")., Results: We present data regarding the clinical manifestations of social anxiety disorder, impairments and implications related to the condition, differences between the generalized and specific subtypes, and the relationship with depression, drug dependence and abuse, and other anxiety disorders. Additionally, the main differential diagnoses are discussed., Conclusion: The guidelines are intended to serve as references to the general practitioner and the specialist as well, facilitating the diagnosis of social anxiety disorder.