Faculty Bibliography

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.

The transition from pediatric to adult healthcare is a critical stage for young individuals with chronic neurological disorders, particularly those with rare and complex epilepsies. This paper aims to explore the practice of transition by healthcare providers within EpiCARE. Through a comprehensive questionnaire, developed in collaboration with European Patient Advocacy Groups, this study investigates the current management of transition and identifies key barriers hindering stakeholders' needs. The questionnaire was completed by 60 EpiCARE members. Half of the respondents reported existing written transition procedures in their centers. Findings reveal significant hurdles in dedicated transition services, with nearly half of the respondents indicating their centers lack such pipelines. A critical gap exists in multidisciplinary team involvement, with inconsistent participation from key specialists like psychiatrists and social workers. The transition process typically begins at 16-18 years according to 70% of respondents; though 61% believe it should occur prior to the age of 17, highlighting the need for early planning to prevent gaps in care continuity. Furthermore, routinely used informal communication methods for clinical coordination underscore the need for standardized protocols and structured processes. This survey highlights the urgent need for tailored transition protocols that address the unique challenges of managing patients with rare and complex epilepsies, emphasizing the importance of integrating psychosocial support, optimizing comorbidity management, and ensuring coordination by experts in transitional care for these conditions. Fostering collaboration among healthcare providers, patients, and families is essential for refining transition strategies and ensuring comprehensive care for individuals with rare and complex epilepsies. Further initiatives are required to bridge the gaps between pediatric and adult healthcare systems, enhancing the overall quality of life for this vulnerable population. PLAIN LANGUAGE SUMMARY: Moving from child to adult healthcare is a key step for young people with rare and complex epilepsies. This study surveyed EpiCARE centers to understand how transitions are managed. Only half have written procedures, and many lack dedicated services or full specialist teams. Most start the transition at ages 16-18, but many believe it should begin earlier. Communication is often informal, without clear protocols. The results highlight the urgent need for structured, personalized transition plans that include psychological support and expert coordination to ensure continuous, high-quality care into adulthood.

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.

The objective of this study was to explore the buffering effect of support on the association between stress and postpartum depression (PPD) among immigrant women. We surveyed 223 Chinese pregnant or postpartum (within one year post-delivery) immigrant women in New York City. Surveys were conducted in English, Simplified Chinese or Mandarin, March-June 2021. PPD was measured with the Edinburgh PPD scale (EPDS); scores of 13 or higher indicate probable depression. Perceived stress was measured with one question, "How often did you feel stressed in the past week?"; responses were collapsed into a binary measure: Never/Rarely and Sometimes/Often/Always. Support was assessed with a general question about perception of receiving needed support and the Patient-Reported Outcomes Measurement Information System (PROMIS) V2.0 Short Form Informational, Instrumental, and Emotional Support measures. Bivariate and multivariable general linear regression models assessed the relationship among stress, support, and PPD. The EPDS mean score was 11.9 (95%CI:11.1-12.7) and 50% (95%CI: 42-57%) had EPDS scores ≥ 13, indicative of serious symptoms; 56% felt stressed in the past week and 37% reported getting needed support. Among women without perceived needed support, mean EPDS scores were higher among women who were stressed compared with women who were not (adjusted mean difference (aMD) 5.4; 95%CI:3.3-7.5); the association between stress and EPDS score was attenuated among women with needed support (aMD 1.1; 95%CI:-1.0, 3.1). Similar patterns held for emotional and instrumental support. Perceived and social support attenuated the association between perceived stress and depression symptoms among Chinese immigrant women. Enhancing support may be effective in countering the impact of stressors on PPD.

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.

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.

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.

The use of Attention-Deficit/Hyperactivity Disorder (ADHD) medications during pregnancy is increasing, raising concerns about potential long-term effects on offspring. This study investigates in utero exposure to methylphenidate, amphetamines and atomoxetine and risk of offspring neurodevelopmental disorders (NDDs). The population-based cohort study identified from Swedish registers included 861,650 children born by 572,731 mothers from 2008-2017. We categorized exposure based on redeemed medication during pregnancy and compared exposed children to those whose mothers discontinued medication before conception. Main outcomes were any NDD, including ADHD and autism spectrum disorder (ASD). Cox proportional hazards regression estimated hazard ratios (HRs), adjusting for maternal psychiatric and sociodemographic factors. Sensitivity analyses included stratifications by medication type, timing, and duration of exposure, and sibling comparisons. We also performed a meta-analysis combining data from the present study with those from a previous Danish study. Results showed no increased risk for any NDD (HR_adjusted 0.95, 95% CI 0.82-1.11), ADHD (HR_adjusted 0.92, 95% CI 0.78-1.08), or ASD (HR_adjusted 0.86, 95% CI 0.63-1.18). Sensitivity analyses showed consistent patterns of no increased risks across different exposure durations, medication types and between siblings. Meta-analyses further supported the findings (pooled HR for any NDD 1.00, 95% CI 0.83;1.20). Our study provides evidence that in utero exposure to ADHD medications does not increase the risk of long-term NDDs in offspring. This study replicates safety data for methylphenidate and extends it with new safety data on amphetamines and atomoxetine. These findings are crucial for informing clinical guidelines and helping healthcare providers and expectant mothers make informed decisions.