Faculty Bibliography

INTRODUCTION/BACKGROUND:The impact of maternal SARS-CoV-2 infection on fetal brain development during pregnancy remains unclear. Prior research has associated other antenatal infections with adverse neurodevelopmental outcomes in offspring. OBJECTIVE:To compare neurodevelopmental outcomes in infants born to mothers infected with SARS-CoV-2 during pregnancy (COVID+) to infants without congenital exposure (COVID-). METHODS:This study included 77 COVID+ infants and 157 COVID- infants assessed at 6 and/or 12 months. Outcomes were based on maternal self-report, observed infant behavior and brain fMRI. RESULTS:Overall, COVID+ and COVID- infant groups showed no significant differences across a range of neurobehavioral measures. However, analyses not adjusted for multiple comparisons revealed differences: fewer night awakenings at 6 (t(154) = 2.24, p < 0.03) and 12 months (t(107) = 1.94, p < 0.05), and reduced duration of orienting at 12 months (t(55.38) = 2.15, p < 0.04) in COVID+ infants. Neural differences were noted in posterior-anterior midline, insular-frontal, insular-posterior cingulate, and frontal-cingulate regions at an uncorrected threshold of p < 0.01. CONCLUSION/CONCLUSIONS:This study of multi-level infant development suggests that infants born to mothers infected with COVID during pregnancy are not experiencing harmful effects of that exposure. IMPACT/CONCLUSIONS:This study contributes comprehensive data on infant neurodevelopmental outcomes following prenatal SARS-CoV-2 exposure, evaluating a wide range of behavioral and neural measures to address gaps in previous research. Findings suggest that congenital exposure to SARS-CoV-2 does not result in significant neurodevelopmental impairments in infants, offering reassurance amidst concerns about potential long-term effects of maternal prenatal COVID-19 infection. Results indicate that any observed differences, such as fewer night awakenings and functional neural connectivity patterns, may reflect a more mature developmental profile in the exposed group. Continued longitudinal research is necessary to understand behaviorally relevant and lasting neurodevelopmental effects of prenatal SARS-CoV-2 exposure.

Autism and attention-deficit hyperactivity disorder (ADHD) are among the most common neurodivergent neurotypes worldwide. Epidemiological evidence shows that sleep and circadian disturbances, such as difficulty initiating and maintaining sleep, and delayed sleep-wake phase, are highly prevalent in autistic children, children with ADHD, and those with both neurotypes. Despite scientific advancements, a comprehensive framework integrating sleep and circadian mechanisms with targeted interventions for autism and ADHD remains underdeveloped. In this Review we examine sleep and circadian rhythm differences in autistic children and adolescents, and in those with ADHD or both neurotypes, focusing on the underlying biological mechanisms. We discuss recent advances in the genetic and molecular links between sleep, circadian rhythms, and neuroplasticity, alongside the influence of these systems on physiology and therapeutic strategies. Both pharmacological and non-pharmacological interventions are considered, with an emphasis on the need for an integrated support model that accounts for the dynamic interplay between sleep and circadian rhythms in these populations. We identify key gaps in the current evidence base, particularly in relation to non-pharmacological interventions, and outline future research directions. Although most randomised controlled trials in children and adolescents have focused on behavioural sleep interventions, we also discuss emerging findings from trials using alternative approaches, such as targeted light therapy in adults, with implications for paediatric populations. Finally, we emphasise the importance of incorporating the perspectives of autistic children and adolescents and those with ADHD, as well as their parents and caregivers, into research designs.

Stimulants such as methylphenidate (MPH) are the first-line pharmacological treatment for attention-deficit/hyperactivity disorder (ADHD). Although stimulants are effective at a group level, individual response varies, which advocates for tailored treatment approaches. Prior studies suggested that neurobiological measures following a single dose of stimulants are indicative of longer-term clinical response. To expand these findings, we tested whether an association between acute and longer-term treatment response can also be identified using measures commonly used in clinic. Sixty adults with ADHD completed clinico-neuropsychological measures, including the Barkley Adult ADHD Rating Scale-IV (BAARS-IV) and the Quantitative behavior (Qb) test, following a single dose of MPH (20 mg) and placebo. These measures were repeated after two-month MPH treatment to ascertain response. We tested associations between single-dose and longer-term response using univariate and multivariable (Lasso) regression approaches. We also ran correlations between predicted and true outcome measures. Univariate regressions showed significant associations between single-dose and two-month improvement in BAARS hyperactivity/impulsivity and Qb scores (all p < 0.001 but Qb activity, p = 0.006). Multivariable models including acute response and baseline clinicodemographic measures yielded significant correlations between predicted and actual values for all BAARS-IV and Qb scores at follow-up, except for BAARS inattention and Qb activity. Most had large/very large effect size (up to r = 0.69). These findings suggest that specific clinico-neuropsychological changes following a single dose of MPH may be indicative of longer-term treatment response, especially when combined with pre-treatment clinico-demographic characteristics. Once validated in larger and more heterogeneous samples, these results may support more informed and individualized treatment approaches for ADHD.

In youth, lithium is an effective medication for mood disorders, particularly for mixed and manic episodes of bipolar disorder, and is generally well-tolerated. In some clinical contexts, lithium is used off-label to manage other conditions. We conducted a scoping review of studies on the efficacy/effectiveness and safety/tolerability of lithium for treating youths with psychiatric conditions other than mood disorders or neurological disorders. We searched EMBASE, MEDLINE, PsycINFO, PubMed, and ClinicalTrials.gov up to March 31, 2025, with no restrictions on language or document type. We included studies of any design involving children and adolescents (mean age up to 18) treated with lithium, either as monotherapy or in combination with other psychotropic agents. We assessed study quality using the appropriate NHLBI tools and visually summarized the results with a heat map displaying sample size by study design and conditions, as well as the timeline of included studies' publication years. From 2687 records initially identified, after de-duplication removal and screening, 367 full-text reports were assessed, and 41 studies were included in the review, grouped by type of psychiatric or neurological disorder, most of which had a small sample. Among the assessed studies, 60 % of were considered of "fair" quality and 40 % of "poor" quality. Overall, although the clinical use of lithium beyond bipolar disorder in youth is increasing, the underlying evidence base remains limited. More rigorous research based on RCTs and observational studies with designs aimed at reducing confounding are needed to guide clinical practice.

Improving meaningful outcomes is the main goal of clinical care for mental disorders. Traditionally, the focus in clinical research and practice has been on outcome domains that refer to symptom severity or service use (e.g., hospitalization), relate to categorical diagnoses, and favour clinician-rated measures. More recently, self-rated and dimensional as well as transdiagnostic outcome domains have gained traction, and functioning, quality of life and well-being/life satisfaction, along with the construct of personal recovery, have become a stronger focus. These key multidimensional outcome domains need to be properly defined and assessed. Further, the concepts of "functional" and "personal" recovery need to be differentiated. "Functional recovery" is defined by observed functioning across the domains of self-care, social interactions, leisure time activities, and educational or vocational activities. "Personal recovery" involves the subjective sense of living a personally meaningful life, irrespective of whether symptoms continue, or ongoing/intermittent support is needed. Despite the multi-stakeholder relevance of these outcome domains, no comprehensive account of how to measure them is available. To fill this gap, we provide here an overview of the main tools to assess functioning, quality of life/well-being/life satisfaction, and personal recovery outcomes across mental disorders in adults, aiming to also identify additional needs that should be addressed. We identified tools that can be used in clinical and research practice to assess people with the following mental health conditions: anxiety disorders, bipolar disorder, dementias, eating disorders, major depressive disorder, obsessive-compulsive and related disorders, personality disorders, post-traumatic stress disorder, schizophrenia, and substance use disorders. Both transdiagnostic and disorder-specific measures are described. Suggested tools were selected keeping feasibility and scalability needs in mind. The incorporation of these measures in both research and clinical care will enrich patient assessment as well as treatment planning and evaluation, increasing the likelihood of enhanced outcomes in people living with mental disorders.

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.

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:The comparative effectiveness of 2 transitions of care programs for improving health status and reducing readmissions among patients hospitalized with heart failure is unknown. OBJECTIVE/UNASSIGNED:To compare the effectiveness adding mobile integrated health (MIH) to a transitions of care coordinator for improving health status and reducing 30-day all-cause readmissions among patients discharged after heart failure. DESIGN, SETTINGS, AND PARTICIPANTS/UNASSIGNED:The Mighty-Heart randomized clinical trial included Medicare- or Medicaid-enrolled adult (≥18 years) patients hospitalized with heart failure in 11 New York City (New York) hospitals between January 2021 and September 2024. Participants were randomized 1:1 to MIH or TOCC. TOCC provided a follow-up call by a nurse 48 to 72 hours after discharge. MIH included the same TOCC postdischarge call, and added ongoing nurse care coordination, community paramedic home visits, and facilitated synchronous telehealth with emergency medicine physicians. Data analysis occurred between September 2024 and June 2025. INTERVENTIONS/UNASSIGNED:Receiving MIH plus TOCC or TOCC alone during the first 30 days after hospital discharge. MAIN OUTCOMES AND MEASURES/UNASSIGNED:Coprimary outcomes were health status at 30 days measured with the Kansas City Cardiomyopathy Questionnaire Overall Summary score, and 30-day all-cause hospital readmission, with heart failure-specific readmissions as a secondary outcome. RESULTS/UNASSIGNED:Among 2003 participants (median [IQR] age, 67 [58-78] years; 1040 female [52%]), no adjusted differences were observed in the Kansas City Cardiomyopathy Questionnaire Overall Summary score at 30 days between MIH and TOCC groups (mean difference, 1.83; 95% CI, -0.75 to 4.40; P = .16). Exploratory analysis showed a significant age-by-treatment interaction effect, with younger participants who received MIH having larger improvement in health status (β: 4.40; 95% CI, 1.01 to 7.79). There were no significant differences in overall 30-day readmissions between study groups (20.3% vs 20.4%; odds ratio, 0.99; 95% CI, 0.83 to 1.19; P = .95). CONCLUSIONS AND RELEVANCE/UNASSIGNED:This randomized clinical trial found that MIH conferred no additional benefit on health status or 30-day readmissions for postacute patients with heart failure compared to TOCC alone. Preliminary subgroup analyses suggest potential variations in MIH effects by age and sex; therefore, further research is warranted. TRIAL REGISTRATION/UNASSIGNED:ClinicalTrials.gov Identifier: NCT04662541.

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.