Faculty Bibliography

BACKGROUND:Children born very preterm (VPT) are at high risk for attention problems. This study's purpose was to describe the Conners Kiddie Continuous Performance Test (K-CPT) assessment in children born VPT, including rates of clinically elevated scores, change over time, and associations between K-CPT scores and parent reported attention problems. METHODS:We studied 305 children from a multi-site study of children born VPT who completed at least one K-CPT assessment at age 5, 6, and/or 7 years. Parent-reported ADHD symptoms and diagnosis were also collected. We calculated K-CPT completion rates, mean scores, and rates of clinically elevated scores at each timepoint. Linear mixed models examined change over time in K-CPT scores. Correlations and generalized linear models investigated associations between K-CPT scores and ADHD symptoms and diagnoses. RESULTS:K-CPT scores showed expected age-related improvements from age 5-7, with significant intra- and inter-individual variability. Up to 1/3 of children had clinically elevated attention problems and another 1/3 had subclinical elevations. K-CPT scores were modestly correlated with parent-rated ADHD symptoms and children with a parent-reported ADHD diagnosis performed worse on nearly all K-CPT metrics. CONCLUSION/CONCLUSIONS:Performance-based measures like the K-CPT can be useful for research and clinical practice in VPT populations. IMPACT/CONCLUSIONS:Attention problems are a specific area of weakness for children born very preterm. Performance-based tests of attention have benefits and drawbacks compared to parent report measures yet are understudied in this population. We examined one performance-based measure (the Conners Kiddie Continuous Performance Test [K-CPT]) in 305 children born very preterm. We observed improving task scores from age 5-7 years with significant intra- and inter-individual variability, a sizable proportion of children with clinically and subclinically elevated scores, and modest associations between K-CPT scores and parent reported attention problems. The K-CPT could be a useful clinical and research tool in this population.

Children presenting comorbid attention-deficit/hyperactivity disorder (ADHD) and depression symptoms have higher risks of later suicidal ideation and attempt. However, it is unclear to what extent this risk stems from individual differences in the genetic predisposition for ADHD and/or depression. We investigated the unique and combined contribution of genetic predisposition to ADHD and depression to suicidal ideation and attempt by early adulthood. Data were from two longitudinal population-based birth cohorts, the Quebec Longitudinal Study of Child Development and the Quebec Newborn Twin Study (total N = 1207). Genetic predisposition for ADHD and depression were measured using polygenic scores. Suicidal ideation and attempt by age 20 years were self-reported via questionnaires. Across the two cohorts, suicidal ideation and attempt were reported by 99 (8.2%) and 75 (6.1%) individuals, respectively. A higher polygenic score for depression was associated with significantly higher risk of suicidal ideation and attempt, while no significant associations were found for ADHD polygenic score. However, we found an interaction between polygenic scores for depression and ADHD in the association with suicide attempt (P = 0.012), but not suicidal ideation (P = 0.897). The association between polygenic score for depression and suicide attempt was significantly stronger for individuals with a higher polygenic score for ADHD. Individuals scoring ≥ 1-SD above the mean for both polygenic scores were at increased risk for suicide attempt compared to individuals with lower scores (OR 4.03, CI 1.64-9.90), as well as compared to individuals scoring ≥ 1-SD above the mean in only depression (OR 2.92, CI 1.01-8.50) or only ADHD (OR 4.88, CI 1.56-15.26) polygenic scores. Our findings suggest that genetic predisposition for ADHD and depression contributes to increase the risk of suicide attempt in a multiplicative, rather that additive, way. Our results contribute to our understanding of the etiology of suicide risk and may inform screening and risk stratification.

BACKGROUND:Concerns about the cardiovascular safety of medications used for the treatment of attention-deficit hyperactivity disorder (ADHD) remain. We aimed to compare the effects of pharmacological treatments for ADHD on haemodynamic values and electrocardiogram (ECG) parameters in children, adolescents, and adults. METHODS:For this systematic review and network meta-analysis, we searched 12 electronic databases, including Cochrane CENTRAL, Embase, PubMed, and the WHO International Clinical Trials Registry Platform, from database inception to Jan 18, 2024, for published and unpublished randomised controlled trials comparing amphetamines, atomoxetine, bupropion, clonidine, guanfacine, lisdexamfetamine, methylphenidate, modafinil, or viloxazine against each other or placebo. Primary outcomes were change in systolic blood pressure (SBP) and diastolic blood pressure (DBP), measured in mm Hg, and pulse, measured in beats per minute, at timepoints closest to 12 weeks, 26 weeks, and 52 weeks. Summary data were extracted and pooled in random-effects network meta-analyses. Certainty of evidence was assessed with the Confidence in Network Meta-Analysis (CINeMA) framework. This study was registered with PROSPERO, CRD42021295352. Before study initiation, we contacted representatives of a UK-based charity of people with lived experience of ADHD-the ADHD Foundation-regarding the relevance of the topic and the appropriateness of the outcomes chosen. FINDINGS/RESULTS:102 randomised controlled trials with short-term follow-up (median 7 weeks [IQR 5-9]) were included, encompassing 13 315 children and adolescents (aged ≥5 years and <18 years; mean age 11 years [SD 3]; of available data, 9635 [73%] were male and 3646 [27%] were female; of available data, 289 [2%] were Asian, 1719 [15%] were Black, and 8303 [71%] were White) and 9387 adults (≥18 years, mean age 35 years [11]; of available data, 5064 [57%] were male and 3809 [43%] were female; of available data, 488 [6%] were Asian, 457 [6%] were Black, and 6372 [79%] were White). Amphetamines, atomoxetine, lisdexamfetamine, methylphenidate, and viloxazine led to increments in haemodynamic values in children and adolescents, adults, or both. In children and adolescents, mean increase against placebo ranged from 1·07 (95% CI 0·36-1·79; moderate CINeMA confidence) with atomoxetine to 1·81 (1·05-2·57; moderate) with methylphenidate for SBP; from 1·93 (0·74-3·11; high) with amphetamines to 2·42 (1·69-3·15; low) with methylphenidate for DBP; and from 2·79 (1·05-4·53; moderate) with viloxazine to 5·58 (4·67-6·49; high) with atomoxetine for pulse. In adults, mean increase against placebo ranged from 1·66 (95% CI 0·38-2·93; very low) with methylphenidate to 2·3 (0·66-3·94; very low) with amphetamines for SBP; from 1·60 (0·29-2·91; very low) with methylphenidate to 3·07 (0·69-5·45; very low) with lisdexamfetamine for DBP; and from 4·37 (3·16-5·59; very low) with methylphenidate to 5·8 (2·3-9·3; very low) with viloxazine for pulse. Amphetamines, lisdexamfetamine, or methylphenidate were not associated with larger increments in haemodynamic values compared with atomoxetine or viloxazine in either children and adolescents or adults. Guanfacine was associated with decrements in haemodynamic values in children and adolescents (mean decrease against placebo of -2·83 [95% CI -3·8 to -1·85; low CINeMA confidence] in SBP, -2·08 [-3 to -1·17; low] in DBP, and -4·06 [-5·45 -2·68; moderate] in pulse) and adults (mean decrease against placebo of -10·1 [-13·76 to -6·44; very low] in SBP, -7·73 [-11·88 to -3·58; very low] in DBP, and -6·83 [-10·85 to -2·81; very low] in pulse). Only four RCTs informed on effects in the medium term and none on the long term. INTERPRETATION/CONCLUSIONS:Practitioners should monitor blood pressure and pulse in patients with ADHD treated with any pharmacological intervention, and not stimulants only. Given the short duration of available randomised controlled trials, new research providing insights on the causal effects of ADHD medications on cardiovascular parameters in the longer term should be funded. FUNDING/BACKGROUND:National Institute for Health and Care Research.

INTRODUCTION/BACKGROUND:Foundational preacademic skills are crucial for academic success and serve as predictors of socioeconomic status, income and access to healthcare. However, there is a gap in our understanding of neurodevelopmental patterns underlying preacademic skills in children across low-income and middle-income countries (LMICs). It is essential to identify primary global and regional factors that drive children's neurodevelopment in LMICs. This study aims to characterise the typical development of healthy children and factors that influence child development in Bahir Dar, Ethiopia. METHODS AND ANALYSIS/METHODS:The Bahir Dar Child Development Study is a cross-sectional study implemented in two health centres, Shimbit and Abaymado and in Felege Hiwot Comprehensive Specialized Hospital (FHCSH) in Bahir Dar, Amhara, Ethiopia. Healthy children between 6 and 60 months of age will be recruited from the health centres during vaccination visits or via community outreach. Young children aged 6-36 months will complete the Global Scale for Early Development. A battery of paper and tablet-based assessments of neurocognitive outcomes including visual and verbal reasoning, executive functions and school readiness will be completed for children aged 48-60 months. Caregivers will respond to surveys covering sociodemographic information, the child's medical history and nutrition, and psychosocial experiences including parental stress and mental health. During a second visit, participants will undergo a low-field MRI scan using the ultra-low-field point-of-care Hyperfine MRI machine at FHCSH. Analyses will examine relationships between risk and protective factors, brain volumes and neurocognitive/developmental outcomes. ETHICS AND DISSEMINATION/BACKGROUND:The study is approved by the Institutional Review Boards of Addis Continental Institute of Public Health (ACIPH/lRERC/004/2023/Al/05-2024), Mass General Brigham Hospital (2022P002539) and Brown University (STUDY00000474). Findings will be disseminated via local dissemination events, international conferences and publications. TRIAL REGISTERATION NUMBER/BACKGROUND:NCT06648863.

BACKGROUND:Numerous studies support the association of exercise training, physical activity (PA) and sedentary behaviour (SB) with both mortality and morbidity outcomes. The results across studies have been inconsistent, and no umbrella reviews have yet been conducted on this topic. METHODS:We conducted an umbrella review of meta-analyses of observational studies by screening articles in PubMed/MEDLINE, EMBASE and Web of Science databases from inception to 30 April 2024. Quality appraisal of each included meta-analysis was done using the AMSTAR 2 tool, with evidence certainty evaluated based on statistical significance, study size, heterogeneity, small-study effects, prediction intervals (PI) and potential biases. RESULTS:Frothy-eight meta-analyses were included (AMSTAR 2 ratings: high 25, moderate 10, low 2 and critically low 11). No evidence was highly suggestive or convincing. Suggestive evidence linked any PA and SB to lower and higher risks of all-cause, cardiovascular and cancer mortality. Suggestive evidence indicated a significant association between self-reported and device-measured total PA (equivalent odds ratio [eOR] 0.78 [0.70-0.86] and eHR = 0.50 [0.38-0.65], respectively), self-reported leisure time PA (eHR = 0.73 [0.66-0.80]), device-measured daily steps (eHR = 0.44 [0.35-0.56]) and aerobic plus resistance training (eHR = 0.60 [0.56-0.64]) with lower all-cause mortality. Weak evidence supported links between self-reported and device-measured SB and higher mortality (eHR = 1.3 [1.22-1.38] and eHR = 2.16 [1.09-4.28], respectively). Suggestive evidence was noted for the association between self-reported leisure time PA (eHR = 0.74 [0.69-0.80]) and resistance training (eHR = 0.82 [0.81-0.84]) with cardiovascular mortality. Suggestive evidence was also found for the association between self-reported leisure time PA (eHR = 0.87 [0.83-0.91]) with cancer mortality. Associations between self-reported running time and mortality from all causes, cardiovascular diseases (CVD) and cancer did not reach statistical significance nor did the association between low skeletal muscle mass and all-cause mortality. Meta-regression analyses showed that physical activity reduces mortality risk, with age reducing the protective effects against all-cause, CVD and cancer mortality. We also found that combined exercise training (aerobic plus resistance) most effectively reduces all-cause and CVD mortality. CONCLUSIONS:Converging evidence supports that physical activity and sedentary behaviour are associated with lower and higher rates of all-cause, cardiovascular and cancer mortality. More high-quality prospective studies are needed for a better understanding of the associations between running time and also TV-viewing time and health-related outcomes.

Mass univariate testing on functional connectivity MRI (fcMRI) data is limited by difficulties achieving experiment-wide significance. Recent work addressing this problem has used enrichment analysis, which aggregates univariate screening statistics for a set of variables into a single enrichment statistic. There have been promising results using this method to explore fcMRI-behavior associations. However, there has not yet been a rigorous examination of the statistical properties of enrichment analysis when applied to fcMRI data. Establishing power for fcMRI enrichment analysis will be important for future neuropsychiatric and cognitive neuroscience study designs that plan to include this method. Here, we use realistic simulation methods, which mimic the covariance structure of fcMRI data, to examine the false positive rate and statistical power of one technique for enrichment analysis, over-representation analysis. We find it can attain high power even for moderate effects and sample sizes, and it strongly outperforms univariate analysis. The false positive rate associated with permutation testing is robust.

Trauma-focused psychotherapies for infants, toddlers, and preschoolers comprise a unique subset of child trauma interventions. Given the developmental age range in question, certain characteristics of these therapies differ significantly from those for older children. This study reviews evidence-based, trauma-focused treatments for young children and their caregivers, followed by evidence-based treatments for trauma-vulnerable families with very young children that do not target trauma directly but rather reinforce attachment-related protective factors such as parental sensitivity and reflective functioning. Directions for further research are discussed.

Dyadic assessment is an essential component of understanding a young child's mental health, providing critical information about the contexts within which they live and develop. This article describes how to observe the behaviors of a child and caregiver together, either by systematically reviewing key domains of the dyadic interaction or by using a formal observation procedure. Though challenged by issues of training and time to complete them, cultural responsiveness, and the balance of making them both naturalistic and feasible, dyadic assessments are indispensable. They can provide a foundation and jumping-off point for therapy and healing.

The current study investigates the conjoint effect of prenatal Superstorm Sandy stress (SS) and postnatal parenting, as measured by affectionless control (AC), in determining the risk of early childhood psychopathology. The study included 154 children (45.5% males) longitudinally tracked from ages 2-5 years. Maternal AC was assessed using the Parental Bonding Instrument. The prevalence of child diagnostic outcomes (DSM-IV anxiety disorders, phobias, and disruptive behavior disorders) was ascertained by trained clinical interviewers using maternal responses to the Preschool Age Psychiatric Assessment. Children were stratified into four groups by SS and AC status to identify synergistic effects on psychopathology exceeding the risks expected in an additive model. Children exposed to both SS and AC had over 5-fold increased risk of any anxiety disorder, a 12-fold increased risk for disruptive behavior disorders, and a nearly 5-fold increased risk of any disorder relative to the reference group of children with neither exposure. The risks of anxiety, disruptive behavior, and any disorders were synergistically greater than the sum of independent effects of the two stressors, as evident in the synergy index. Evaluation of synergistically increased risks for childhood disorders will help to identify high-risk children, which in turn could inform design of multi-level interventions to mitigate child psychopathology.