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Data aggregation in mental health is complicated by using different questionnaires, and little is known about the impact of item harmonization strategies on measurement precision. Therefore, we aimed to assess the impact of various item harmonization strategies for a target and proxy questionnaire using correlated and bifactor models. Data were obtained from the Brazilian High-Risk Study for Mental Conditions (BHRCS) and the Healthy Brain Network (HBN; N = 6,140, ages 5-22 years, 39.6% females). We tested six item-wise harmonization strategies and compared them based on several indices. The one-by-one (1:1) expert-based semantic item harmonization presented the best strategy as it was the only that resulted in scalar-invariant models for both samples and factor models. The between-questionnaires factor correlation, reliability, and factor score difference in using a proxy instead of a target measure improved little when all other harmonization strategies were compared with a completely at-random strategy. However, for bifactor models, between-questionnaire specific factor correlation increased from 0.05-0.19 (random item harmonization) to 0.43-0.60 (expert-based 1:1 semantic harmonization) in BHRCS and HBN samples, respectively. Therefore, item harmonization strategies are relevant for specific factors from bifactor models and had little impact on p -factors and first-order correlated factors when the child behavior checklist (CBCL) and strengths and difficulties questionnaire (SDQ) were harmonized., Competing Interests: Methodological DisclosureWe report our sample size presents enough power to detect differences in factor analysis, all data inclusions, all manipulations, and all measures in the study. Declaration of Conflicting InterestsThe author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: Luis Augusto Rohde has received grant or research support from, served as a consultant to, and served on the speakers’ bureau of Aché, Bial, Medice, Novartis/Sandoz, Pfizer/Upjohn, and Shire/Takeda in the last 3 years. The ADHD and Juvenile Bipolar Disorder Outpatient Programs chaired by Dr Rohde have received unrestricted educational and research support from the following pharmaceutical companies in the last 3 years: Novartis/Sandoz and Shire/Takeda. Dr Rohde has received authorship royalties from Oxford Press and ArtMed.Other author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Objective: To investigate the trajectory of positive attributes from childhood to early adulthood and how these trajectories might be modified by environmental factors., Methods: We enrolled 2,511 participants aged 6 to 14 years from a large prospective school-based community cohort of Brazilian children and adolescents, 45% of whom were girls. They were assessed and followed for up to 3 years (with 80% retention) or 6 years (with 71% retention). Positive attributes were assessed by using the Youth Strength Inventory (YSI). A composite measure using several indicators was used to assess childhood exposure to threats and deprivations., Results: The trajectories of YSI scores were nonlinear for male and female participants, being high in childhood, decreasing in adolescence, and being high again in early adulthood. Exposure to threat and deprivation presented a negative linear association with YSI over time. Furthermore, exposure to threat and deprivation early in life, but not later, presented an additional effect on decreasing positive attributes during the life course., Conclusion: Our findings provide new evidence on the trajectories of positive attributes in children and adolescents and show how early life adversity affects not only mental disorders but also positive aspects of mental health., Competing Interests: The authors report no conflicts of interest.

Objectives: Model configuration is important for mental health data harmonization. We provide a method to investigate the performance of different bifactor model configurations to harmonize different instruments., Methods: We used data from six samples from the Reproducible Brain Charts initiative (N = 8,606, ages 5-22 years, 41.0% females). We harmonized items from two psychopathology instruments, Child Behavior Checklist (CBCL) and GOASSESS, based on semantic content. We estimated bifactor models using confirmatory factor analysis, and calculated their model fit, factor reliability, between-instrument invariance, and authenticity (i.e., the correlation and factor score difference between the harmonized and original models)., Results: Five out of 12 model configurations presented acceptable fit and were instrument-invariant. Correlations between the harmonized factor scores and the original full-item models were high for the p-factor (>0.89) and small to moderate (0.12-0.81) for the specific factors. 6.3%-50.9% of participants presented factor score differences between harmonized and original models higher than 0.5 z-score., Conclusions: The CBCL-GOASSESS harmonization indicates that few models provide reliable specific factors and are instrument-invariant. Moreover, authenticity was high for the p-factor and moderate for specific factors. Future studies can use this framework to examine the impact of harmonizing instruments in psychiatric research., (© 2023 The Authors. International Journal of Methods in Psychiatric Research published by John Wiley & Sons Ltd.)

Background: Understanding deviations from typical brain development is a promising approach to comprehend pathophysiology in childhood and adolescence. We investigated if cerebellar volumes different than expected for age and sex could predict psychopathology, executive functions and academic achievement., Methods: Children and adolescents aged 6-17 years from the Brazilian High-Risk Cohort Study for Mental Conditions had their cerebellar volume estimated using Multiple Automatically Generated Templates from T1-weighted images at baseline ( n = 677) and at 3-year follow-up ( n = 447). Outcomes were assessed using the Child Behavior Checklist and standardized measures of executive functions and school achievement. Models of typically developing cerebellum were based on a subsample not exposed to risk factors and without mental-health conditions ( n = 216). Deviations from this model were constructed for the remaining individuals ( n = 461) and standardized variation from age and sex trajectory model was used to predict outcomes in cross-sectional, longitudinal and mediation analyses., Results: Cerebellar volumes higher than expected for age and sex were associated with lower externalizing specific factor and higher executive functions. In a longitudinal analysis, deviations from typical development at baseline predicted inhibitory control at follow-up, and cerebellar deviation changes from baseline to follow-up predicted changes in reading and writing abilities. The association between deviations in cerebellar volume and academic achievement was mediated by inhibitory control., Conclusions: Deviations in the cerebellar typical development are associated with outcomes in youth that have long-lasting consequences. This study highlights both the potential of typical developing models and the important role of the cerebellum in mental health, cognition and education.

Background: Specific pathways of intergenerational transmission of behavioral traits remain unclear. Here, we aim to investigate how parental genetics influence offspring cognition, educational attainment, and psychopathology in youth., Methods: Participants for the discovery sample were 2,189 offspring (aged 6-14 years), 1898 mothers and 1,017 fathers who underwent genotyping, psychiatric, and cognitive assessments. We calculated polygenic scores (PGS) for cognition, educational attainment, attention-deficit hyperactivity disorder (ADHD), and schizophrenia for the trios. Phenotypes studied included educational and cognitive measures, ADHD and psychotic symptoms. We used a stepwise approach and multiple mediation models to analyze the effect of parental PGS on offspring traits via offspring PGS and parental phenotype. Significant results were replicated in a sample of 1,029 adolescents, 363 mothers, and 307 fathers., Results: Maternal and paternal PGS for cognition influenced offspring general intelligence and executive function via offspring PGS (genetic pathway) and parental education (phenotypic pathway). Similar results were found for parental PGS for educational attainment and offspring reading and writing skills. These pathways fully explained associations between parental PGS and offspring phenotypes, without residual direct association. Associations with maternal, but not paternal, PGS were replicated. No associations were found between parental PGS for psychopathology and offspring specific symptoms., Conclusions: Our findings indicate that parental genetics influences offspring cognition and educational attainment by genetic and phenotypic pathways, suggesting the expression of parental phenotypes partially explain the association between parental genetic risk and offspring outcomes. Multiple mediations might represent an effective approach to disentangle distinct pathways for intergenerational transmission of behavioral traits., (© 2022 Association for Child and Adolescent Mental Health.)

In genetics, aggregation of many loci with small effect sizes into a single score improved prediction. Nevertheless, studies applying easily replicable weighted scores to neuroimaging data are lacking. Our aim was to assess the reliability and validity of the Neuroimaging Association Score (NAS), which combines information from structural brain features previously linked to mental disorders. Participants were 726 youth (aged 6-14) from two cities in Brazil who underwent MRI and psychopathology assessment at baseline and 387 at 3-year follow-up. Results were replicated in two samples: IMAGEN (n = 1627) and the Healthy Brain Network (n = 843). NAS were derived by summing the product of each standardized brain feature by the effect size of the association of that brain feature with seven psychiatric disorders documented by previous meta-analyses. NAS were calculated for surface area, cortical thickness and subcortical volumes using T1-weighted scans. NAS reliability, temporal stability and psychopathology and cognition prediction were analyzed. NAS for surface area showed high internal consistency and 3-year stability and predicted general psychopathology and cognition with higher replicability than specific symptomatic domains for all samples. They also predicted general psychopathology with higher replicability than single structures alone, accounting for 1-3% of the variance, but without directionality. The NAS for cortical thickness and subcortical volumes showed lower internal consistency and less replicable associations with behavioural phenotypes. These findings indicate the NAS based on surface area might be replicable markers of general psychopathology, but these links are unlikely to be causal or clinically useful yet., (© 2020. Springer-Verlag GmbH Germany, part of Springer Nature.)

Objective: Population neuroscience is an emerging field that combines epidemiology and neuroscience to study how genes and the environment shape typical and atypical brain functioning. The objective of this study was to review key studies on population neuroscience from low- and middle-income countries (LMICs) and to identify potential gaps vis-à-vis studies conducted in high-income countries., Methods: We conducted a systematic review to search for longitudinal cohort studies investigating the development of psychiatric disorders in children and adolescents in LMICs. We performed an electronic search in the EMBASE and MEDLINE databases from inception to July 5th, 2019., Results: We found six cohorts from four countries that met our search criteria: three cohorts from Brazil, one from China, one from South Africa, and one from Mauritius. Relevant examples of findings from these studies are reported., Conclusion: Our results demonstrate the impact of the valuable science output these cohort designs promote, allowing LMICs to have a share in frontline global psychiatry research. National and international funding agencies should invest in LMIC population neuroscience in order to promote replication and generalization of research from high-income countries.

Research suggested accumulation of tau proteins might lead to the degeneration of functional networks. Studies investigating the impact of genetic risk for Alzheimer's disease (AD) on early brain connections might shed light on mechanisms leading to AD development later in life. Here, we aim to investigate whether the polygenic risk score for Alzheimer's disease (AD-PRS) influences the connectivity among regions susceptible to tau pathology during childhood and adolescence. Participants were youth, aged 6-14 years, and recruited in Porto Alegre (discovery sample, n = 332) and São Paulo (replication sample, n = 304), Brazil. Subjects underwent genotyping and 6-min resting state funcional magnetic resonance imaging. Connections between the local maxima of tau pathology networks were used as dependent variables. The AD-PRS was associated with the connectivity between the right precuneus and the right superior temporal gyrus (discovery sample: β = 0.180, p adjusted  = 0.036; replication sample: β = 0.202, p = 0.031). This connectivity was also associated with inhibitory control (β = 0.157, p adjusted  = 0.035) and moderated the association between the AD-PRS and both immediate and delayed recall. These findings suggest the AD-PRS may affect brain connectivity in youth, which might impact memory performance and inhibitory control in early life., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Objective: Alzheimer's disease is a heritable neurodegenerative disorder in which early-life precursors may manifest in cognition and brain structure. The authors evaluate this possibility by examining, in youths, associations among polygenic risk score for Alzheimer's disease, cognitive abilities, and hippocampal volume., Method: Participants were children 6-14 years of age in two Brazilian cities, constituting the discovery (N=364) and replication samples (N=352). As an additional replication, data from a Canadian sample (N=1,029), with distinct tasks, MRI protocol, and genetic risk, were included. Cognitive tests quantified memory and executive function. Reading and writing abilities were assessed by standardized tests. Hippocampal volumes were derived from the Multiple Automatically Generated Templates (MAGeT) multi-atlas segmentation brain algorithm. Genetic risk for Alzheimer's disease was quantified using summary statistics from the International Genomics of Alzheimer's Project., Results: Analyses showed that for the Brazilian discovery sample, each one-unit increase in z-score for Alzheimer's polygenic risk score significantly predicted a 0.185 decrement in z-score for immediate recall and a 0.282 decrement for delayed recall. Findings were similar for the Brazilian replication sample (immediate and delayed recall, β=-0.259 and β=-0.232, both significant). Quantile regressions showed lower hippocampal volumes bilaterally for individuals with high polygenic risk scores. Associations fell short of significance for the Canadian sample., Conclusions: Genetic risk for Alzheimer's disease may affect early-life cognition and hippocampal volumes, as shown in two independent samples. These data support previous evidence that some forms of late-life dementia may represent developmental conditions with roots in childhood. This result may vary depending on a sample's genetic risk and may be specific to some types of memory tasks.

Objective To describe the cross-cultural adaptation of the Anger Rumination Scale (ARS) for use in Brazil. Methods The cross-cultural adaptation followed a four-step process, based on specialized literature: 1) investigation of conceptual and item equivalence; 2) translation and back-translation; 3) pretest; and 4) investigation of operational equivalence. Results A final Brazilian version of the instrument (ARS-Brazil) was defined and is presented. Pretest results revealed that the instrument was generally well understood by adults as well as indicated a few modifications that were included in the final version presented here. Conclusion The Brazilian Portuguese version of the ARS seems to be very similar to the original ARS in terms of conceptual and item equivalence, semantics, and operational equivalence, suggesting that future cross-cultural studies may benefit from this early version. As a result, a new instrument is now available for the assessment of rumination symptoms of anger and irritability for adults in community, clinical, and research settings.

Purpose: Dimensional approaches are likely to advance understanding of human behaviors and emotions. Nevertheless, it is unclear whether instruments in psychiatry capture variability at the full spectrum of these dimensions. We aimed to investigate this issue for two scales assessing distinct aspects of social functioning: the Social Aptitudes Scale (SAS), a "bidirectional" scale constructed to investigate both "ends" of social functioning; and the social Child Behavior Checklist (CBCL-social), a "unidirectional" scale constructed to assess social problems., Methods: We investigated 2512 children and adolescents aged 6-14. Item response theory was used to investigate on which range of the trait each scale captures information. We performed quantile regressions to investigate if correlations between SAS and CBCL-social vary within different levels of social aptitudes dimension and multiple logistic regressions to investigate associations with negative and positive clinical outcomes., Results: SAS was able to provide information on the full range of social aptitudes, whereas CBCL-social provided information on subjects with high levels of social problems. Quantile regressions showed SAS and CBCL-social have higher correlations for subjects with low social aptitudes and non-significant correlations for subjects with high social aptitudes. Multiple logistic regressions showed that SAS was able to provide independent clinical predictions even after adjusting for CBCL-social scores., Conclusions: Our results provide further validity to SAS and exemplify the potential of "bidirectional" scales to dimensional assessment, allowing a better understanding of variations that occur in the population and providing information for children with typical and atypical development.