Journal of the American Academy of Child and Adolescent Psychiatry最新文献

Objective: Attention-deficit/hyperactivity disorder (ADHD) is a common neurodevelopmental disorder with high heritability. A total of 27 genome-wide significant loci for ADHD were previously identified through genome-wide association studies (GWASs), but the identification of risk genes that confer susceptibility to ADHD has remained largely unexplored.

Method: As ADHD is a neurodevelopmental disorder, we integrated human brain prenatal gene and transcript expression weight data (n = 120) and ADHD GWAS summary statistics (n = 225,534; 38,691 cases and 186,843 controls) to perform a transcriptome-wide association study (TWAS) by FUSION (an analytic suite).

Results: Our analysis identified 10 genes, including LSM6, HYAL3, METTL15, RPS26, LRRC37A15P, RP11-142I20.1, ABCB9, AP006621.5, AC000068.5, and PDXDC1, that are significantly associated with ADHD, along with 8 transcripts of 7 genes. We also conducted TWAS analysis using CommonMind Consortium (CMC) adult brain gene and gene-splicing expression weights (n = 452), which highlighted several risk genes that showed associations with ADHD in both prenatal and postnatal stages, such as LSM6 and HYAL3.

Conclusion: Overall, our TWAS of ADHD, by integrating human prenatal brain transcriptome and ADHD GWAS results, uncovered the cis-effects of gene/transcript regulation that are predicted to be associated with ADHD. By combining colocalization and FOCUS fine-mapping analysis, we further unraveled potential causal candidate risk genes. The risk genes/transcripts that we identified in this study can serve as a valuable resource for further investigation of the disease mechanisms underlying ADHD.

Objective: Attention-deficit/hyperactivity disorder (ADHD) is associated with lower birth weight, but also with obesity in childhood. Findings on the direction of this association are mixed. This study investigated the relationship between weight and ADHD from birth across development.

Method: We used data from the Millennium Cohort Study (MCS), collected at 7 time points between age 9 months and 17 years. ADHD diagnosis status and scores on the Strength and Difficulties Questionnaire (SDQ) were used to create an ADHD group and a control group. Random intercept cross-lagged panel models were conducted in female individuals (n = 4,051) and male individuals (n = 3,857) to examine bidirectional associations between body mass index (BMI) z scores and SDQ scores between ages 3 and 17 years. Analyses were adjusted for common risk factors for ADHD and obesity, such as sex assigned at birth, multiple births, and ADHD medication status.

Results: Children in the ADHD group were significantly lighter in weight at birth than the control group (t[5674] = 2.65, 95% CI = 0.02, 0.14, p = .008) and were significantly more likely to have obesity at age 5 years onward (odds ratio range = 1.57-2.46, relative risk range 0.98-2.29). Path analyses conducted separately for male and female individuals showed that higher ADHD symptoms in female individuals at ages 7, 11, and 14 years significantly predicted higher BMI z scores at ages 11, 14, and 17 years, respectively. In male individuals, this association was seen only between ages 11 and 14 years (β = 0.07; 95% CI = 0.04-0.10, p < .001).

Conclusion: Results suggest that interventions for children with ADHD, and their parents, should begin as soon as possible, ideally prenatally. Developmental sex differences should be considered.

Objective: To examine the magnitude of placebo response in randomized controlled trials (RCTs) of medications for Tourette's disorder.

Method: CENTRAL, Embase, PubMed, PsycInfo, Web of Science, WHO ICTRP, and ClinicalTrials.gov databases were searched to identify placebo-controlled RCTs assessing pharmacological interventions for Tourette's disorder. Standardized mean change and standardized mean difference were calculated for within-group (placebo, drug) and between-group (drug-placebo) change in tics. Data were pooled in random-effects meta-analysis. Meta-regressions were performed to identify study-level characteristics that could be differentially associated with placebo, drug, and drug-placebo response.

Results: Searchers identified 13,775 records, and 50 RCTs involving 1,566 participants were included in the placebo meta-analysis. Placebo response was medium to large (standardized mean change: -0.62; 95% CI: -0.75, -0.5; I² = 76%; τ² = 0.14). Several factors were associated with larger placebo responses (eg, non-US RCT, industry sponsorship, number of centers and participants). However, there was a moderate-to-high correlation between placebo and drug response (ρ = 0.66; 95% CI: 0.47, 0.79), and factors associated with larger placebo response were also generally associated with larger drug responses. There was not a significant correlation between placebo response and drug-placebo differences (ρ = -0.05; 95% CI: -0.32, 0.22), and factors associated with larger placebo response generally did not interfere in drug-placebo differences.

Conclusion: The magnitude of placebo response in Tourette's disorder may be large, but similar to that in other child and adolescent psychiatric conditions. Clinical researchers may manipulate study-level factors to diminish placebo response (eg, carefully selecting study sites and keeping them at the minimum feasibility). However, drug-placebo differences may not increase as drug response will likely diminish as well.

Study preregistration information: Comparative Efficacy, Tolerability, and Acceptability of Pharmacological Interventions for Chronic Tic Disorders Including Tourette's Syndrome in Children, Adolescents, and Adults: Protocol for a Systematic Review and Network Meta-analysis; https://www.crd.york.ac.uk; CRD42022296975.

Diversity & inclusion statement: One or more of the authors of this paper self-identifies as a member of one or more historically underrepresented sexual and/or gender groups in science. One or more of the authors of this paper self-identifies as a member of one or more historically underrepresented racial and/or ethnic groups in science.

Objective: Youth criminal justice systems are under growing pressure to reduce re-offending behavior and to support young people's health and developmental needs. This systematic review and meta-analysis sought to synthesise evidence for 2 prominent community-based interventions for delinquent and antisocial behavior, namely, multisystemic therapy (MST) and functional family therapy (FFT).

Method: We searched Medline, PsycInfo, Scopus, Web of Science, and Social Services Abstracts for randomized controlled trials (RCTs) and quasi-experimental studies evaluating MST/FFT. Included studies involved participants aged under 18 years; included interventions targeted delinquent/antisocial behavior, but not maltreatment. We estimated effect sizes for 6 primary outcomes, synthesising RCTs comparing MST/FFT to usual care using correlated hierarchical effects meta-analysis. We assessed risk of bias and evidence strength using best-practice tools. Given the additional resources needed to implement MST/FFT, we rated evidence strength against a minimum clinically important difference rather than a null effect. This study is registered with PROSPERO, CRD42021279736.

Results: We included 35 studies for MST (16 RCTs meta-analyzed comprising 4,095 participants, 26% female) and 19 studies for FFT (7 RCTs meta-analyzed comprising 1,471 participants, 22% female). MST had a likely clinically important effect on time in out-of-home care, but no clinically important effects on other primary outcomes (delinquency, new offenses/convictions, placement in out-of-home care, substance use), with low-to-moderate evidence strength. FFT demonstrated possible clinically important effects for the number of new offenses/convictions, time in out-of-home care, and substance use, but evidence strength was low.

Conclusion: Contrary to reports in some evidence clearinghouses indicating that MST/FFT are supported by the highest level of evidence strength, there is limited evidence that these interventions are superior to usual care in reducing delinquent and antisocial behavior in adolescence. These findings should be viewed in the context of important methodological differences with prior reviews, including the rating of evidence strength against a minimum clinically important difference.

Study preregistration information: The effect of Multi-Systemic Therapy and Functional Family Therapy in addressing child and adolescent delinquent and/or antisocial behavior and childhood maltreatment; https://www.crd.york.ac.uk/; 279736.

Objective: We tested whether the implementation of standardized, high-fidelity screening for autism during routine well-child check-ups results in the following: increasing the number of children with suspected autism referred to diagnostic evaluation; lowering the age at which they are referred; and facilitating autism diagnosis for children across a more diverse range of demographic backgrounds and clinical presentations, including those with subtle manifestations.

Method: As part of a multi-site cluster randomized trial, pediatric practices were randomly assigned to an experimental condition involving training and supervision in the universal, standardized, high-fidelity implementation of the Modified Checklist for Autism in Toddlers, Revised with Follow-Up (M-CHAT-R/F), or a usual care condition. Children in both conditions identified as having a high likelihood of autism during well-child visits were referred to a diagnostic evaluation conducted by clinicians naive to referral source.

Results: Children referred to the diagnostic evaluation from the practices in the experimental condition were more numerous (n = 186) and younger (mean age = 20.65 months) than those referred from the practices in the usual care condition (n = 39; mean age = 23.58 months). Children referred by experimental practices who received an autism diagnosis had milder clinical presentations across measures of cognitive, language, adaptive, and social-communication functioning, compared to those referred from usual care practices. Demographic characteristics were similar across groups.

Conclusion: Standardized, high-fidelity implementation of autism screening during pediatric well-child visits facilitates the identification of children with high autism likelihood at a younger age, including those presenting with more subtle clinical manifestations.

Clinical trial registration information: Promoting Positive Outcomes for Individuals With ASD: Linking Early Detection, Treatment, and Long-term Outcomes; https://clinicaltrials.gov/; NCT03333629.