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Neuroimaging studies point to neurostructural abnormalities in youth with anxiety disorders. Yet, findings are based on small-scale studies, often with small effect sizes, and have limited generalizability and clinical relevance. These issues have prompted a paradigm shift in the field towards highly powered (i.e., big data) individual-level inferences, which are data-driven, transdiagnostic, and neurobiologically informed. Here, we built and validated neurostructural machine learning (ML) models for individual-level inferences based on the largest-ever multi-site neuroimaging sample of youth with anxiety disorders (age: 10-25 years, N=3,343 individuals from 32 global sites), as compiled by three ENIGMA Anxiety Working Groups: Panic Disorder (PD), Generalized Anxiety Disorder (GAD), and Social Anxiety Disorder (SAD). ML classifiers were trained on MRI-derived regional measures of cortical thickness, surface area, and subcortical volumes to classify patients and healthy controls (HC) for each anxiety disorder separately and across disorders (transdiagnostic classification). Modest, yet robust, classification performance was achieved for PD vs. HC (AUC=0.62), but other disorder-specific and transdiagnostic classifications were not significantly different from chance. However, above chance-level transdiagnostic classifications were obtained in exploratory subgroup analyses of male patients vs. male HC, unmedicated patients vs. HC, and patients with low anxiety severity vs. HC (AUC 0.59-0.63). The above chance-level classifications were based on plausible and specific neuroanatomical features in fronto-striato-limbic and temporo-parietal regions. This study provides a realistic estimate of classification performance in a large, ecologically valid, multi-site sample of youth with anxiety disorders, and may as such serve as a benchmark.

Individual differences in cognitive abilities emerge early during development, and children with poorer cognition are at increased risk for adverse outcomes as they enter adolescence. Caregiving plays an important role in supporting cognitive development, yet it remains unclear how specific types of caregiving behaviors may shape cognition, highlighting the need for large-scale studies. In the present study, we characterized replicable yet specific associations between caregiving behaviors and cognition in two large sub-samples of children ages 9-10 years old from the Adolescent Brain and Cognitive Development (ABCD) study. Across both discovery and replication sub-samples, we found that child reports of caregiver monitoring (supervision or regular knowledge of the child’s whereabouts) were positively associated with general cognition abilities, after covarying for age, sex, household income, neighborhood deprivation, and parental education. This association was specific to the type of caregiving behavior (caregiver monitoring, but not caregiver warmth), and was most strongly associated with a broad domain of general cognition (but not executive function or learning/memory). Additionally, we found that caregiver monitoring partially mediated the association between household income and cognition, furthering our understanding of how socioeconomic disparities may contribute to disadvantages in cognitive development. Together, these findings underscore the influence of subtle differences in caregiving behavior in shaping youth cognition.

Background: Schools have adapted to the online environment during the COVID-19 pandemic, but the factors influencing access to online resources and the impact of these changes on youth mental health are largely unknown. The current study has two aims (1) to investigate if mental health problems previous to COVID-19 pandemic are associated with access to online learning; (2) to investigate whether those accessing online learning have lower levels of mental health problems during the COVID-19 pandemic. Methods: The sample consisted of 672 young people (16 - 24 years of age) from the Brazilian High-Risk Cohort that were enrolled in an educational institution and had access to the internet. Participants were evaluated during the COVID-19 pandemic and in a previous time point. A total of 511 students were enrolled in online classes, while 161 were not enrolled. Psychopathology was measured using the Strengths and Difficulties Questionnaire (SDQ) in both time points. Attendance to online classes during COVID-19 was obtained by self-report. Data were analyzed using multiple regression models.Results: Prospective analysis revealed that every one-point increase in the total SDQ score before the COVID-19 pandemic was associated with an increase of 6% in the chance of a participant not accessing online classes, above and beyond previous negative school events, such as suspensions and grade repetition and other confounders (adjusted OR 0.94; 95%CI 0.91-0.98; p=0.0009). Cross-sectional analysis revealed that participants that accessed online classes had a slightly lower number of inattention/hyperactivity problems if compared to those without online classes (Cohen's d=0.25; β=-0.63, p=0.006); however, those results were fully explained by previous symptoms of inattention/hyperactivity.Conclusion: Children with pre-pandemic mental health problems have disproportionately lower access to educational resources during the pandemic if compared with the general population, which might widen the gap of opportunities for this underserved population to thrive.

QuestionRandomised controlled trials assessing treatments for anxiety, obsessive-compulsive and stress-related disorders often present high placebo response rates in placebo groups. Understanding the placebo response is essential in accurately estimating the benefits of pharmacological agents; nevertheless, no studies have evaluated the placebo response across these disorders using a lifespan approach.Study selection and analysisWe searched MEDLINE, PsycINFO, Embase, Cochrane, websites of regulatory agencies and international registers from inception to 9 September 2022. The primary outcome was the aggregate measure of internalising symptoms of participants in the placebo arms of randomised controlled trials designed to assess the efficacy of selective serotonin reuptake inhibitors (SSRIs) and serotonin and norepinephrine reuptake inhibitors (SNRIs) in individuals diagnosed with anxiety, obsessive-compulsive or stress-related disorders. The secondary outcomes were placebo response and remission rates. Data were analysed through a three-level meta-analysis.FindingsWe analysed 366 outcome measures from 135 studies (n=12 583). We found a large overall placebo response (standardised mean difference (SMD)=−1.11, 95% CI −1.22 to −1.00). The average response and remission rates in placebo groups were 37% and 24%, respectively. Larger placebo response was associated with a diagnosis of generalised anxiety disorder and post-traumatic stress disorder, when compared with panic, social anxiety and obsessive-compulsive disorder (SMD range, 0.40–0.49), and with absence of a placebo lead-in period (SMD=0.44, 95% CI 0.10 to 0.78). No significant differences were found in placebo response across age groups. We found substantial heterogeneity and moderate risk of bias.ConclusionsPlacebo response is substantial in SSRI and SNRI trials for anxiety, obsessive-compulsive and stress-related disorders. Clinicians and researchers should accurately interpret the benefits of pharmacological agents in contrast to placebo response.PROSPERO registration numberCRD42017069090.

We examined the association between childhood poverty and mental health disorders (MHD) in childhood and early adulthood. We also investigated whether the association between poverty in childhood and MHD is mediated by exposure to stressful life events (SLE).We used data from a prospective community cohort of young people assessed at baseline (M = 9.7 years, SD = 1.9), first (M = 13.5 years, SD = 1.9), and second (M = 18.2 years, SD = 2.0) follow-ups (N = 1,590) in Brazil. Poverty was assessed using a standardized classification. Exposure to 20 different SLE was measured using the Life History instrument. Psychiatric diagnoses were evaluated using the Development and Well-Being Assessment. Latent growth models investigated the association between poverty at baseline and the growth of any MHD, externalizing, and internalizing disorders. Mediation models evaluated whether the association between childhood poverty and MHD in early adulthood was mediated by exposure to SLE.Poverty affected 11.4% of the sample at baseline and was associated with an increased propensity for presenting externalizing disorders in adolescence or early adulthood (standardized estimate = 0.27, p = 0.016). This association was not significant for any disorder or internalizing disorders. Childhood poverty increased the likelihood of externalizing disorders in early adulthood through higher exposure to SLE (OR = 1.07, 95 CI% 1.01-1.14). Results were only replicated among females in stratified analyses.Childhood poverty had detrimental consequences on externalizing MHD in adolescence, especially among females. Poverty and SLE are preventable risk factors that need to be tackled to reduce the burden of externalizing disorders in young people.

The psychosis phenotype is generally associated with altered experience of salience associated with internal or external events, giving rise to experiences such as hallucinations or delusional ideation. Psychotic experiences (PEs) and traits vary in severity, frequencyand functional impairment, and compose a wide behavioral range for the trait. Here, we examine how methodological expansions in psychometrics provide unique information about the internal structure and chronological transformations of PEs. We present the procedures of this paper in three steps: (1) validation of constructs using classical factor analysis; (2) evaluation derived from the data’s topological structure;(3) assessment of longitudinal changes in magnitudes of PEs. A discussion follows, exposing methodological limitations and highlighting how this framework may benefit psychometrics and impact clinical practice.

Background The prevalence of Psychotic Experiences (PE) in the general population is approximately 7%. Several studies report on the association of PE with non-psychotic mental disorders and dimensional psychopathology. However, few have addressed this relationship during adolescence using longitudinal data. Here, we aim to explore bidirectional associations of PE and common mental disorder in youth in a 3-year follow-up community-based study. We hypothesized that there is a link between PE and depression, corroborating findings from adult studies, and that mental disorders comorbidity significantly correlates to PE, showing a nonspecific effect of PE as a risk for a broad “psychiatric load/liability”. Methods We analyzed data from the Brazilian High Risk Cohort (HRC), a large multi-site school-based study. At baseline, we evaluated 2,244 subjects (6–12 years old) using the Community Assessment of Psychotic Experiences (CAPE) and an adapted version of the Comprehensive Assessment of At-risk Mental States (CAARMS) by self-report and clinician ratings, respectively. Mental disorders in youth were assessed by the Development and Well-Being Assessment (DAWBA). We grouped mental disorders into 4 DSM-based categories: any depressive disorder, any anxiety disorder, any Attention Deficit Hyperactivity Disorder (ADHD), and any Oppositional Defiant Disorder or Conduct Disorder (ODD/CD). Subjects were reassessed after 3 years, with a retention rate of 75%. We used regression analyses to explore predictors of PE and mental disorders at follow-up. Finally, we investigated the bidirectional effect of PE as a nonspecific psychiatric “load/liability” by creating count variables for the number of comorbid psychiatric disorders for each participant. Poisson regression models tested the effect of PE (as a predictor) in the count variable (the outcome) controlling for potential confounders. Results We found bidirectional associations between PE and mental disorders in youth. Baseline PE increased the risk of any depressive disorder at follow-up, and baseline ADHD was associated with PE at 3-year follow-up. Comorbidity analyses showed significant relationships in both directions, with an increased risk of PE according to the number of comorbid psychiatric disorders. Discussion We showed that subthreshold psychotic symptoms predict subsequent depressive disorder, and nonspecifically relate to psychiatric comorbidity. These findings are concordant with the notion that psychotic experiences are part of the same psychiatric vulnerability conferred to common mental disorders, such as depression and ADHD. Our results may inform future research on testing subclinical psychotic symptoms to further our understating on identifying high-risk groups for early intervention.