Faculty Bibliography

OBJECTIVE:To evaluate the association between attention-deficit/hyperactivity disorder (ADHD) and atypical sensory processing patterns. METHOD/METHODS:For this systematic review and meta-analysis, PubMed, Embase, and Web of Science were searched from their inception until June 30, 2024. Studies examining sensory processing patterns using questionnaires in participants with a diagnosis of ADHD compared with healthy controls were included. The study risk of bias was assessed using a modified Newcastle-Ottawa Scale. A random-effects meta-analysis was conducted using R Version 4.3.1 software, considering sensory modulation severity atypicities as the primary outcome. The risk of publication bias was explored, and sensitivity analyses were conducted to test the robustness of findings. RESULTS:= 97%). Heterogeneity was high in all analyses. Only 9 studies were deemed at overall low risk of bias. CONCLUSION/CONCLUSIONS:Even though available ADHD clinical guidelines do not specifically mention the need to assess sensory processing in ADHD, this meta-analysis suggests that this should be systematically explored in the evaluation of children and adults referred for ADHD. PLAIN LANGUAGE SUMMARY/CONCLUSIONS:This systematic review and meta-analysis examined 30 studies including over 5,000 participants to assess the link between attention-deficit/hyperactivity disorder (ADHD) and atypical sensory processing. Findings show that individuals with ADHD experience significantly higher sensory sensitivity, sensory avoidance, sensory seeking, and low sensory registration compared to controls. Given their impact on daily functioning, assessing sensory processing could improve clinical evaluations for both children and adults with ADHD. STUDY REGISTRATION INFORMATION/UNASSIGNED:Association between ADHD and sensory processing disorder: A systematic review and meta-analysis; https://www.crd.york.ac.uk/PROSPERO/view/CRD42022325271. DIVERSITY & INCLUSION STATEMENT/UNASSIGNED:We actively worked to promote sex and gender balance in our author group. 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.

Patients with hypoplastic left heart syndrome (HLHS) and its variants rely on the right ventricle (RV) to provide cardiac output. Diminished RV systolic function has been associated with poor clinical outcomes in this population. Echocardiographic strain has emerged as a useful method to quantify RV deformation. We aimed to describe fetal strain in the systemic RV and further investigate if there was any correlation with clinical outcomes. We conducted a retrospective, single center study evaluating strain in fetuses with systemic RV. We measured fetal RV global longitudinal strain (GLS) and segmental strain using Tomtec 2D speckle tracking software and compared these findings to controls. Fifty patients with systemic RV were included in the study group with controls matched one to one for each echocardiogram. Ten patients died after first-stage palliation. GLS was reproducible, with interobserver ICC 0.82. There was no statistically significant difference in GLS among different HLHS subtypes. Abnormal GLS did not correlate with worse clinical outcomes. GLS in systemic RVs in the 2nd and 3rd trimester did not vary significantly throughout gestation and did not correlate with clinical outcomes. Risk factors associated with poor outcome were mainly postnatal. Multi-centered studies are needed to determine if these findings hold true in a larger sample size.

Attention-deficit/hyperactivity disorder (ADHD) was once thought to be solely a childhood condition. Now it is well established that it can persist into adulthood, with an estimated worldwide prevalence of around 2.5%. Additionally, up to 70% of individuals with childhood-onset ADHD continue to experience impairing symptoms as adults, even if they no longer meet the criteria for a formal diagnosis. The validity of adult ADHD initially faced strong criticism. Today, empirical research supports its descriptive validity (identifying characteristic signs and symptoms), predictive validity (concerning specific outcomes, courses, and responses to treatment), and concurrent validity (evidence related to its underlying causes and biological mechanisms). Despite this progress, unresolved questions and ongoing debates about adult ADHD persist. This paper summarizes current empirical evidence, alongside uncertainties and controversies, regarding the definition, epidemiology, diagnosis, etiology, neurobiology, and management of ADHD in adults. Crucially, we also include perspectives from individuals with lived experience of this condition, highlighting their views on unmet needs and priorities for improving care. Key uncertainties and controversies on adult ADHD include: a) the possibility of late-onset ADHD; b) the significance of emotional dysregulation as a core symptom; c) the definition and characterization of functional impairment; d) the persistence of comorbid psychiatric and somatic conditions after accounting for confounders; e) the relevance of executive dysfunction in the definition of the condition; f) the use of objective diagnostic measures; g) the long-term effects of treatments; and h) the role of non-pharmacological interventions. Further research on adult ADHD is urgently needed. Funding for studies on this condition lags behind that for childhood ADHD and other mental disorders in adulthood. Hopefully, efforts by clinicians, researchers and other stakeholders will ultimately help ensure that adults with ADHD are better understood, supported, and empowered to thrive.

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/METHODS: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/CONCLUSIONS: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.

Maternal mental health during the perinatal period has been linked to the development of infant emotion regulation capacity, largely through its impact on caregiver-infant interactions during the first year of life. The majority of studies have focused on the effects of maternal depression, even though maternal anxiety is more prevalent and its effects on infant outcomes are less well understood. The current study aims to 1) explore differences in infant affect and regulatory behaviors across two commonly implemented infant stress-induction paradigms and 2) evaluate the differential effects of depression and anxiety on infant regulatory behaviors. Six-month-old infants and their mothers (N = 126) completed two tasks remotely in the home: the Arm Restraint task and the Still-Face Paradigm. Maternal depression and anxiety symptoms were measured using the Edinburgh Postnatal Depression Scale (EPDS) subscales. Within-person results indicated no significant associations among infant regulatory behaviors nor infant reactivity across the two paradigms. Additionally, no significant associations were found between maternal mental health and infant regulatory behaviors during the Still-Face Paradigm. However, higher EPDS composite scores were associated with fewer infant avoidance behaviors during the Arm Restraint task, and this result was driven by items on the anxiety subscale. These findings suggest that infant regulatory behaviors may differ depending on task used and may also be influenced by subclinical levels of maternal anxiety, but not maternal depression.

OBJECTIVE:This study aimed at identifying moderators of efficacy of stimulants against placebo to inform personalized recommendations for treatment in preschool children (< 6 years) with attention-deficit/hyperactivity disorder (ADHD). METHOD/METHODS:We acquired individual-level participant data from two randomized placebo-controlled trials (RCTs) of preschool ADHD: MAPPA (8-week methylphenidate, 102 participants, Brazil) and SPD489-347 (6-week lisdexamfetamine, 148 participants, US). We evaluated the moderator and predictor effects of baseline demographic (age, sex, race, ethnicity, maternal educational level) and baseline clinical (ADHD symptom severity, intelligence quotient, number of psychiatric comorbidities) characteristics, as available, on endpoint ADHD symptom severity scores. Data from each study were analyzed separately with linear mixed-effects model for repeated measures. For categorical variables, we also computed treatment effects (i.e., stimulants versus placebo) within subgroups and, when possible, pooled them alongside subgroup data from PATS (5-week methylphenidate, 165 participants, US) in random-effects meta-analyses. RESULTS:Stimulants had greater efficacy against placebo in White children compared to Black children considering data from US studies. Older age was not a moderator of greater efficacy of stimulants against placebo, nor was it associated with worse ADHD symptom severity at endpoint. Greater baseline ADHD symptom severity was associated with higher ADHD symptom severity at endpoint independently of the assigned treatment group. CONCLUSION/CONCLUSIONS:Race, but not older age or baseline ADHD symptom severity, may moderate the efficacy of stimulants for preschool ADHD. Given the post hoc nature of subgroup analyses, the findings should be interpreted as exploratory and viewed as hypothesis for confirmation in future studies.

BACKGROUND:Recent epidemiological evidence links early-life obesity and metabolic dysregulation to adult psychosis vulnerability, though a causal relationship remains unclear. Establishing causality in highly heritable psychotic disorders requires 1) demonstrating that early-life metabolic factors mediate between genetic vulnerability and psychosis trajectory, 2) dissecting mechanisms leading to early-life obesity in genetically vulnerable individuals, and 3) clarifying downstream neurodevelopmental pathways linking early-life obesity to psychosis symptoms. METHODS:Here we investigated bidirectional pathways linking behavioral, body mass index (BMI), and neurodevelopmental trajectories in a unique longitudinal cohort of 184 individuals at high genetic risk for psychosis, due to 22q11.2 deletion syndrome (22q11DS), and 182 neurotypical control individuals, followed-up since childhood. We combined repeated BMI measurements with clinical/neurocognitive phenotyping and neuroimaging. We investigated the relationship between BMI trajectories with risk of psychosis and tested whether altered cortical or cerebellar development could underlie this association. RESULTS:Childhood behavioral impulsivity predicted early and progressive deviations in BMI trajectories, mediating the effects of 22q11DS vulnerability to early-life obesity. Chronic BMI increases manifesting during childhood predicted the subsequent emergence of psychosis during late adolescence/early adulthood, mediating the effects of behavioral impulsivity. A dose-effect relationship linked duration of increased BMI status to worsening of motor and cognitive disorganization, a key schizophrenia symptom domain, which was mediated by progressive gray matter volume reductions in posterior-inferior cerebellum. CONCLUSIONS:These findings suggest that metabolic dysregulation associated with obesity may link childhood behavioral impulsivity to psychosis vulnerability in 22q11DS by influencing cerebellar maturation. These findings might support preventive interventions targeting early-life metabolic trajectories in individuals at risk of psychosis.

IMPORTANCE/UNASSIGNED:Studies suggest developmental concerns for infants born during the COVID-19 pandemic, but evidence on its impact on toddler behavioral and emotional well-being remains limited. OBJECTIVE/UNASSIGNED:To assess whether birth timing relative to the COVID-19 pandemic is associated with toddler internalizing and externalizing problems. DESIGN, SETTING, AND PARTICIPANTS/UNASSIGNED:This retrospective cohort study utilized Environmental Influences on Child Health Outcomes (ECHO) cohort data collected between September 27, 2009, and July 21, 2023. Children were divided into 3 groups: the prepandemic group, who were born and assessed before March 13, 2020; the pandemic-assessed group, who were born before March 13, 2020, but assessed after that date; and the pandemic-born group, who were born and assessed on or after March 13, 2020. Data were collected from 9 ECHO cohort sites across the United States and Puerto Rico. EXPOSURE/UNASSIGNED:The COVID-19 pandemic, designated as starting on March 13, 2020. MAIN OUTCOME AND MEASURE/UNASSIGNED:Parent-reported internalizing and externalizing symptoms on the Preschool Child Behavior Checklist (CBCL 1½-5) at age 18 to 39 months. RESULTS/UNASSIGNED:The 3438 children (mean [SD] age, 2.33 years [5.38 months]; 1770 [51.5%] male; 537 [16.2%] Black, 1722 [50.1%] Hispanic; and 1538 [44.7%] White) were divided into 3 groups: 1323 in the prepandemic group (mean [SD] age, 2.41 years [5.66 months]); 1690 in the pandemic-assessed group (mean [SD] age, 2.32 years [5.16 months]); and 425 in the pandemic-born group (mean [SD] age, 2.14 years [4.47 months]). Both the pandemic-assessed group (unadjusted β = -1.51; 95% CI, -2.27 to -0.75; adjusted β = -1.73; 95% CI, -2.48 to -0.99) and the pandemic-born group (unadjusted β = -2.03; 95% CI, -3.13 to -0.93; adjusted β = -1.90; 95% CI, -2.99 to -0.80) had lower levels of internalizing problems compared with the prepandemic (ie, historical) group. Similarly, both the pandemic-assessed (unadjusted β = -1.74; 95% CI, -2.46 to -1.02; adjusted β = -1.81; 95% CI, -2.53 to -1.09) and the pandemic-born group (unadjusted β = -3.16; 95% CI, -4.20 to -2.12; adjusted β = -3.17; 95% CI, -4.22 to -2.12) each had lower levels of externalizing problems compared with the prepandemic group. CONCLUSIONS AND RELEVANCE/UNASSIGNED:In this study, toddlers with prenatal and postnatal as well as those with only postnatal COVID-19 pandemic exposure showed fewer internalizing and externalizing problems than those born and assessed prior to the onset of the pandemic. These findings underscore the need for further research to identify protective factors that may buffer the impact of the pandemic on child behavior.

OBJECTIVE:Rates of suicide, anxiety, and depression have soared in US youth, and professional organizations strongly urge earlier identification, particularly in pediatric emergency departments (PEDs). However, there are few commonly used suicide screeners that also identify other mental health (MH) problems. A new, electronically administered instrument, the K-CAT, screens for suicide and multiple MH problems. We hypothesized that the K-CAT would enhance suicide identification compared with routine screening and identify significant anxiety and depression in youth presenting with non-MH chief complaints. METHODS:This observational study was conducted in 2 PEDs. Eligible youth were 7 to 17 accompanied by a caregiver without: severe medical concerns, difficult behaviors, limited verbal language, or only a psychiatric complaint. Of the 341 eligible, 241 (70.7%) were screened, and 228 both presented with a non-MH problem and had complete K-CAT data. A Fisher exact test determined whether suicidal behaviors/ideation rates differed between the K-CAT and retrospective chart review data. RESULTS:Seventy-four or 32.46% of youth scored positive for suicide, anxiety, and/or depression on the K-CAT. Females were more likely to screen positive (P<0.001). Compared with the retrospective data, more youth were identified with suicide risk by the K-CAT (3.95% vs. 0%; P=0.004). Youth identified by the K-CAT were 62.5% female and 33.3% 7 to 11 years. CONCLUSIONS:The K-CAT increases the identification of suicidal ideation and behaviors overall and in younger children. It identifies significant rates of depression and anxiety in youth and could be an important first step in identifying MH problems in youth.

Chronic motor or vocal tic disorder (CMVTD) is a distressing neuropsychiatric condition. A subset of patients remains refractory to currently approved therapies. The present report describes a pediatric patient with CMVTD who had previously failed multiple pharmacological treatments, including two Food and Drug Administration (FDA)-approved agents (pimozide, aripiprazole), guanfacine, psychotherapy, and novel compounds (lumateperone, cariprazine). The patient was initiated on valbenazine, titrated to 80 mg daily. Clinical improvement was noted within 24-48 hours, with sustained benefit and good tolerability. Tic severity, measured by the Yale Global Tic Severity Scale-Revised (YGTSS-R), improved from 65 at baseline to five following treatment (net reduction of 60 points). This case illustrates a marked therapeutic response to valbenazine in a patient with CMVTD refractory to conventional and novel therapies. These observations highlight the potential role of vesicular monoamine transporter 2 (VMAT2) inhibition in tic disorders and also the need for further clinical study.