Faculty Bibliography

IMPORTANCE/UNASSIGNED:There are concerns about the safety of medications for treatment of attention-deficit/hyperactivity disorder (ADHD), with mixed evidence on possible cardiovascular risk. OBJECTIVE/UNASSIGNED:To assess whether short-term methylphenidate use is associated with risk of cardiovascular events. DESIGN, SETTING, AND PARTICIPANTS/UNASSIGNED:This retrospective, population-based cohort study was based on national Swedish registry data. Participants were individuals with ADHD aged 12 to 60 years with dispensed prescriptions of methylphenidate between January 1, 2007, and June 30, 2012. Each person receiving methylphenidate (n = 26 710) was matched on birth date, sex, and county to up to 10 nonusers without ADHD (n = 225 672). Statistical analyses were performed from September 13, 2022, to May 16, 2023. MAIN OUTCOMES AND MEASURES/UNASSIGNED:Rates of cardiovascular events, including ischemic heart disease, venous thromboembolism, heart failure, or tachyarrhythmias, 1 year before methylphenidate treatment and 6 months after treatment initiation were compared between individuals receiving methylphenidate and matched controls using a bayesian within-individual design. Analyses were stratified by history of cardiovascular events. RESULTS/UNASSIGNED:The cohort included 252 382 individuals (15 442 [57.8% men]; median age, 20 (IQR, 15-31) years). The overall incidence of cardiovascular events was 1.51 per 10 000 person-weeks (95% highest density interval [HDI], 1.35-1.69) for individuals receiving methylphenidate and 0.77 (95% HDI, 0.73-0.82) for the matched controls. Individuals treated with methylphenidate had an 87% posterior probability of having a higher rate of cardiovascular events after treatment initiation (incidence rate ratio [IRR], 1.41; 95% HDI, 1.09-1.88) compared with matched controls (IRR, 1.18; 95% HDI, 1.02-1.37). The posterior probabilities were 70% for at least a 10% increased risk of cardiovascular events in individuals receiving methylphenidate vs 49% in matched controls. No difference was found in this risk between individuals with and without a history of cardiovascular disease (IRR, 1.11; 95% HDI, 0.58-2.13). CONCLUSIONS AND RELEVANCE/UNASSIGNED:In this cohort study, individuals receiving methylphenidate had a small increased cardiovascular risk vs matched controls in the 6 months after treatment initiation. However, there was little evidence for an increased risk of 20% or higher and for differences in risk increase between people with and without a history of cardiovascular disease. Therefore, before treatment initiation, careful consideration of the risk-benefit trade-off of methylphenidate would be useful, regardless of cardiovascular history.

Major attention-deficit/hyperactivity disorder (ADHD) treatment advances have occurred in addressing functional impairments associated with the con-dition. Work to understand how the core symptoms of inattention and hy-peractivity/impulsivity hinder family, school, and social functioning has been conducted. This work has created approaches with proven or promising efficacy in altering the life course of young persons afflicted with this chronic condition. This review describes well-established methods and newly emerging treatments for reducing the impact of ADHD on the home, school, social, and emotional lives of ADHD youth.

Taken together, anxiety disorders are the most common mental health disorders, and typically onset in childhood or early adolescence. Left untreated, anxiety disorders in youth can lead to additional psychopathology and decreased overall functioning in adulthood. This article provides a review of recent findings regarding best practices in the psychosocial treatment of anxiety disorders in children and adolescents. Special topics, such as obsessive-compulsive disorder, parenting, technological advances, and psychopharmacology are also covered.

The coronavirus disease 2019 (COVID-19) pandemic has caused significant medical, social, and economic impacts globally, both in the short and long term. Although most individuals recover within a few days or weeks from an acute infection, some experience longer lasting effects. Data regarding the postacute sequelae of severe acute respiratory syndrome coronavirus 2 infection (PASC) in children, or long COVID, are only just emerging in the literature. These symptoms and conditions may reflect persistent symptoms from acute infection (eg, cough, headaches, fatigue, and loss of taste and smell), new symptoms like dizziness, or exacerbation of underlying conditions. Children may develop conditions de novo, including postural orthostatic tachycardia syndrome, myalgic encephalomyelitis/chronic fatigue syndrome, autoimmune conditions and multisystem inflammatory syndrome in children. This state-of-the-art narrative review provides a summary of our current knowledge about PASC in children, including prevalence, epidemiology, risk factors, clinical characteristics, underlying mechanisms, and functional outcomes, as well as a conceptual framework for PASC based on the current National Institutes of Health definition. We highlight the pediatric components of the National Institutes of Health-funded Researching COVID to Enhance Recovery Initiative, which seeks to characterize the natural history, mechanisms, and long-term health effects of PASC in children and young adults to inform future treatment and prevention efforts. These initiatives include electronic health record cohorts, which offer rapid assessments at scale with geographical and demographic diversity, as well as longitudinal prospective observational cohorts, to estimate disease burden, illness trajectory, pathobiology, and clinical manifestations and outcomes.

Insomnia is the most common sleep disorder among all ages; unfortunately, however, child and adolescent insomnia is infrequently addressed. Given the importance of adequate sleep for proper brain development, pediatric populations are particularly vulnerable to the negative effects of insomnia. Therefore, proper clinical assessment and treatment of pediatric insomnia is crucial. This article is the result of a comprehensive literature review and serves as a guide to the disorder and how it presents differently across child development.

Although a considerable literature documents associations between early mother-infant interaction and cognitive outcomes in the first years of life, few studies examine the contributions of contingently coordinated mother-infant interaction to infant cognitive development. This study examined associations between the temporal dynamics of the contingent coordination of mother-infant face-to-face interaction at 4 months and cognitive performance on the Bayley Scales of Infant Development at age one year in a sample of (N = 100) Latina mother-infant pairs. Split-screen videotaped interactions were coded on a one second time base for the communication modalities of infant and mother gaze and facial affect, infant vocal affect, and mother touch. Multi-level time-series models evaluated self- and interactive contingent processes in these modalities and revealed 4-month patterns of interaction associated with higher one-year cognitive performance, not identified in prior studies. Infant and mother self-contingency, the moment-to-moment probability that the individual's prior behavior predicts the individual's future behavior, was the most robust measure associated with infant cognitive performance. Self-contingency findings showed that more varying infant behavior was optimal for higher infant cognitive performance, namely, greater modulation of negative affect; more stable maternal behavior was optimal for higher infant cognitive performance, namely, greater likelihood of sustaining positive facial affect. Although interactive contingency findings were sparse, they showed that, when mothers looked away, or dampened their faces to interest or mild negative facial affect, infants with higher 12-month cognitive performance were less likely to show negative vocal affect. We suggest that infant ability to modulate negative affect, and maternal ability to sustain positive affect, may be mutually reinforcing, together creating a dyadic climate that is associated with more optimal infant cognitive development.

Sleep disturbances have been linked to suicidal ideation and behaviors in adolescents. Specifically, insomnia and nightmares are associated with current suicide risk and predict future ideation. Associations between hypersomnia, sleep apnea, and suicide remain inconclusive. Potential biological mechanisms underlying these relationships include executive functioning deficits and hyperarousal. Related psychological factors may include thwarted belongingness, perceived burdensomeness, and negative appraisals. Assessing suicide risk in patients with sleep disturbances, and vice versa, is needed. Therapeutic interventions such as cognitive behavior therapy for insomnia and imagery rehearsal treatment, as well as pharmacologic treatments, show promise in treating sleep disorders and suicidal behavior.

Traumatic experiences and sleep disturbances are both common in children and adolescents. Because of the reciprocal relationship between sleep complaints and trauma, a mental health evaluation should include not only an assessment of posttraumatic stress disorder and other trauma symptoms but also a specific evaluation of sleep-related complaints. Similarly, if a history of both trauma and sleep complaints is identified, an effective trauma-informed intervention, whether psychological, psychopharmacologic, or a combination of the two, should directly address sleep issues.

Brain-derived neurotrophic factor (BDNF) is important in the development and maintenance of neurons and their plasticity. Hippocampal BDNF has been implicated in Alzheimer's disease (AD) because hippocampal levels in AD patients and AD animal models are often downregulated, suggesting that reduced BDNF contributes to AD. However, the location where hippocampal BDNF protein is most highly expressed, the mossy fiber (MF) axons of dentate gyrus granule cells (GCs), has been understudied, and not in controlled conditions. Therefore, we evaluated MF BDNF protein in the Tg2576 mouse model of AD. Tg2576 and wild-type (WT) mice of both sexes were examined at 2-3 months of age, when amyloid-β (Aβ) is present in neurons but plaques are absent, and 11-20 months of age, after plaque accumulation. As shown previously, WT mice exhibited high levels of MF BDNF protein. Interestingly, there was no significant decline with age in either the genotype or sex. Notably, MF BDNF protein was correlated with GC ΔFosB, a transcription factor that increases after 1-2 weeks of elevated neuronal activity. We also report the novel finding that Aβ in GCs or the GC layer was minimal even at old ages. The results indicate that MF BDNF is stable in the Tg2576 mouse, and MF BDNF may remain unchanged due to increased GC neuronal activity, since BDNF expression is well known to be activity dependent. The resistance of GCs to long-term Aβ accumulation provides an opportunity to understand how to protect vulnerable neurons from increased Aβ levels and therefore has translational implications.