Faculty Bibliography

Adverse childhood experiences (ACE) are common risk factors for many psychiatric disorders. Their underlying biological mechanisms may involve oxidative stress (OS), which has deleterious effects on cells through its own actions and through its interactions with inflammation and the stress axes, particularly in the brain. In order to assess the role of OS in the association between ACE and psychopathology, we performed a systematic review of animal and human research (PROSPERO CRD42023378418 and CRD42022378376), funded by the Swiss National Science Foundation (grant number 204033). PubMed, Web of Science, PsycInfo, Scopus and Embase were searched from inception until 31 October 2024. We included 130 studies involving animal models exposed to stressor-paradigms recognized as ACE analogs before they reached adulthood, or human participants with a history of ACE and assessment of psychopathology, and reporting outcomes on OS-related markers. Animal studies overall show increased OS and psychopathology after stress, thus supporting the hypothesis that OS mediates the relationship between ACE and psychopathology. Human studies are heterogeneous and less conclusive. Although the association between ACE exposure and OS, in animals and humans, was likely affected by the nature, the timing, and the intensity of the exposure, these parameters were only evaluated in a small fraction of studies. Similarly, though some studies hinted at sex differences in the OS response to ACE in animals, the majority of studies did not address this issue. Further research, using longitudinal designs and more thorough examination of ACE history in participants, is therefore needed.

Providing care to pediatric oncology patients involves delivering sensitive information to families, addressing diverse psychosocial needs, and navigating patient and family emotions. Psychosocial providers embedded within pediatric oncology clinics are uniquely qualified to address communication gaps between patients and providers, provide support to patients, and facilitate collaborative discussions between patients and the medical team. This quality improvement project aimed to describe the impact of including psychosocial providers in critical conversations between medical teams and families. Through conversation tracking, members of the psychosocial team recorded their involvement in thirty-six critical conversations. The psychosocial team offered various interventions including therapeutic processing, emotional assessment, medical translation, psychosocial support, child-focused support, and facilitation of discussions between families and medical providers. While challenges were identified including time and availability, physicians noted several benefits of psychosocial involvement, particularly in addressing emotional needs and enhancing communication with families. Psychosocial providers also noted benefits including demonstrating alignment with the medical team and enhancing the support that they are able to provide the family following the conversation. By integrating psychosocial support into critical conversations, medical providers can foster a patient-centered approach to care and optimize care delivery to effectively support families facing childhood cancer diagnoses.

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.

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.

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.

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.