Faculty Bibliography

IMPORTANCE/UNASSIGNED:Representation of race and ethnicity in randomized clinical trials (RCTs) is critical for understanding treatment efficacy across populations with different racial and ethnic backgrounds. OBJECTIVE/UNASSIGNED:To examine race and ethnicity representation and reporting across RCTs of pharmacotherapies for mental disorders. DATA SOURCES/UNASSIGNED:PubMed (Medline), Embase (Ovid), APA PsycInfo, and Web of Science were searched until March 1, 2024, to retrieve network meta-analyses including RCTs of pharmacotherapies for International Statistical Classification of Diseases and Related Health Problems, Tenth Revision mental disorders. STUDY SELECTION/UNASSIGNED:RCTs that recruited people of any age with a diagnosis of a mental disorder and that tested the efficacy of any pharmacologic intervention vs any control arm. DATA EXTRACTION AND SYNTHESIS/UNASSIGNED:Random-effects logit-transformed proportion meta-analyses were used to estimate prevalence rates of race and ethnicity groups and their temporal trends across RCTs and to compare US RCT prevalence rates with US Census data. The Preferred Reporting Items for Overviews of Reviews was used to report our review. MAIN OUTCOMES AND MEASURES/UNASSIGNED:Reporting of data and percentages of race and ethnicity. The year of publication, type of RCT, geographic location, age group, and sample size were also included. There were no deviations that occurred from the original protocol. RESULTS/UNASSIGNED:Data were obtained from 1683 RCTs (375 120 participants in total). Of these, 1363 (91.7% of participants) included participants aged 18 years or older; 680 RCTs (36.0% of participants) were from the US, 404 (17.1% of participants) were from Europe, and 293 (29.9% of participants) were from multiple geographic locations. Race and ethnicity were reported in 39.2% of RCTs; reporting was the highest in US-based RCTs (58.7%) and lowest in Central and South America (8.7%) and Asia and the Middle East (12.4%). Among participants, 2.7% (95% CI, 2.1%-3.5%) self-reported as Asian, 9.0% (95% CI, 8.1%-10.0%) as Black, 11.0% (95% CI, 9.1%-13.3%) as Hispanic among White, 80.2% (95% CI, 78.8%-81.5%) as White including Hispanic, and 5.8% (95% CI, 5.2%-6.4%) as other race or ethnicity, multiracial, or multiethnic. There was more frequent reporting of race and ethnicity in US RCTs (log odds increased by 0.066 each year) and less frequent reporting in non-US RCTs (log odds increased by 0.023 each year). Studies reporting race and ethnicity did not generally include larger sample sizes (mean sample size, 263.7 [95% CI, 15.0-860.3] participants) compared with those not reporting such data (mean sample size, 196.6 [95% CI, 12.0-601.3] participants), albeit not in all locations. In US RCTs, adults in the other or multiracial and multiethnic category were historically overrepresented, while adults in Asian, Black, Hispanic among White, and White including Hispanic categories were underrepresented; Asian, Black, and Hispanic among White children and adolescents are still currently underrepresented. CONCLUSIONS AND RELEVANCE/UNASSIGNED:The findings of this meta-analysis suggest that differences in reporting race and ethnicity across geographic locations and underrepresentation of certain racial and ethnic groups in US-based RCTs highlight the need for international guidelines to ensure equitable recruitment and reporting in clinical trials.

Although numerous studies have examined how child demographic characteristics may impact ratings of attention-deficit/hyperactivity disorder (ADHD) symptoms, there is limited research on how these factors are related to ratings of impairment. This study examined child characteristics (assigned sex, age, race, ethnicity) that may affect parent and teacher ratings of ADHD symptom-related impairments in relationships with family and/or teacher, peer relationships, behavior disruption, academic impairment, homework performance, and self-esteem. The study was conducted using independent U.S. national samples of parents (n = 2,075) and teachers (n = 1,070). Informants rated impairments related to inattention and hyperactivity-impulsivity using the ADHD Rating Scale-5. Rasch analyses were used to examine differential item functioning in relation to child characteristics. Separate analyses were conducted for inattention- and hyperactivity-impulsivity-related impairment for both the parent and teacher samples. For teacher ratings, only two items (behavior disruption, homework impairment) demonstrated differential item functioning with intermediate or large effect sizes (≥ .426 logits) in relation to any child characteristic; whereas for parent ratings, all six items displayed differential item functioning with at least intermediate effect sizes in relation to one or more child characteristics. The findings indicated several areas in which child characteristics may have an impact on ratings of ADHD-related impairment, particularly based on parent ratings, which have potential implications for the diagnostic assessment of ADHD and highlight the need for further research. (PsycInfo Database Record (c) 2025 APA, all rights reserved).

Group preventative parent training programs (PPTPs) have been used successfully to improve outcomes for families living in poverty in settings such as Head Start. Nevertheless, such programs face significant enrollment and engagement challenges. Given that research on factors related to parent preferences for group PPTP participation is limited, the purpose of the current study is to examine what types of programs are most preferred by a combined sample of English and Spanish speaking Head Start parents, and to translate program modeling of parent preferences into feasible programming options. The current study relies on conjoint analysis, a technique derived from market research, to learn more about how Head Start parents leverage attributes of a parenting program when making hypothetical participation decisions. Based on a discrete choice experiment with 234 urban, Early Head Start and Head Start parents, findings indicate that parents prioritize program attributes that target strong improvements for their children on desired outcomes, such as academics and friendship skills, while also offering incentives for participation. Simulations indicated that 77.6% of parents preferred an Optimizing Outcomes Program, while 22.4% preferred a Foundational Needs Program. Finally, results indicate that child prosocial or difficult behavior and parent depression risk are associated with specific program preferences. Parents with fewer resources prefer programs that are more foundational and realistic to target more modest gains. Implications are discussed in terms of program modeling and offering programs tailored to preferences.

INTRODUCTION/BACKGROUND:Underlying causes of Alzheimer's disease (AD) remain unknown, making it imperative to identify molecular mechanisms driving the pathobiology of AD onset and progression. METHODS:Laser capture microdissection was used to isolate layer III pyramidal neurons from post mortem human prefrontal cortex (Brodmann area 9). Single population RNA sequencing was conducted using tissue from subjects with no cognitive impairment (NCI), mild cognitive impairment (MCI), and AD. Differentially expressed genes (DEGs) were compared across groups. RESULTS:DEGs increased from prodromal (MCI vs. NCI) to progression (AD vs. MCI) to frank AD (AD vs. NCI). The majority of DEGs and pathways shared between prodromal and progression exhibited a change in the direction of dysregulation unlike pathways between progression and frank AD. DISCUSSION/CONCLUSIONS:Candidate genes and pathways were identified that demarcate early-stage AD onset from AD progression, providing a roadmap to study cortical cellular vulnerability and key targets for intervention at early stages of AD. HIGHLIGHTS/CONCLUSIONS:Pyramidal neuron differentially expressed genes (DEGs) are directionally divergent between prodromal, progression, and frank Alzheimer's disease (AD). Pyramidal neuron DEGs are directionally convergent between progression and frank AD. Dysfunctional bioenergetic pathways increased dysregulation as the AD spectrum progressed. Immune response pathways were more dysregulated in frank AD than prodromal stages. DEGs, = biological pathways, and interactomes demarcate specific stages across the AD spectrum.

Assessment of psychiatric symptoms relies on subjective self-report, which can be unreliable. Digital phenotyping collects data from smartphones to provide near-continuous behavioral monitoring. It can be used to provide objective information about an individual's mental state to improve clinical decision-making for both diagnosis and prognostication. The goal of this study was to evaluate the feasibility and acceptability of smartphone-based digital phenotyping for long-term mental health monitoring in adolescents with bipolar disorder and typically developing peers. Participants (aged 14-19) with bipolar disorder (BD) or with no mental health diagnoses were recruited for an 18-month observational study. Participants installed the Beiwe digital phenotyping app on their phones to collect passive data from their smartphone sensors and thrice-weekly surveys. Participants and caregivers were interviewed monthly to assess changes in the participant's mental health. Analyses focused on 48 participants who had completed participation. Average age at baseline was 15.85 years old (SD = 1.37). Approximately half (54%) identified as female, and 54% identified with a minoritized racial/ethnic background. Completion rates across data types were high, with 99% (826/835) of clinical interviews completed, 89% of passive data collected (22,233/25,029), and 47% (4,945/10,448) of thrice-weekly surveys submitted. The proportion of days passive data were collected was consistent over time for both groups; the clinical interview and active survey completion decreased over the study course. Results of this study suggest digital phenotyping has significant potential as a method of long-term mental health monitoring in adolescents. In contrast to traditional methods, including interview and self-report, it is lower burden and provides more complete data over time. A necessary next step is to determine how well the digital data capture changes in mental health to determine the clinical utility of this approach.

Individual differences in how the brain responds to novelty are present from infancy. A common method of studying novelty processing is through event-related potentials (ERPs). While ERPs possess millisecond precision, spatial resolution remains poor, especially in infancy. This study aimed to balance spatial and temporal precision by combining ERP data with functional magnetic resonance imaging (fMRI) data. Twenty-nine infants (15 female) underwent resting-state fMRI (M

Fetal iron status has long-lasting effects on neurodevelopmental outcomes and risk of psychopathology. Although prenatal exposure to maternal psychological stress has been linked to offspring peripheral iron status at birth, it is unknown whether maternal prenatal stress is related to fetal brain iron during gestation. We utilized 86 multi-echo functional magnetic resonance imaging (fMRI) scans from 52 fetuses (23 females; gestational age [GA] 24-38 weeks) to estimate R2* relaxometry as a proxy for fetal brain iron levels. Our results showed that greater maternal anxiety symptoms were associated with higher estimated fetal iron levels in the left cerebellar vermis after controlling for fetal sex and GA. Our finding suggests that fetal brain iron levels may be sensitive to exposure to maternal stress in utero. In a subset of participants with available infant outcome data (n = 31), no significant associations were found between fetal brain iron levels and later cognitive, language, and motor development during infancy. Overall, this study presents the first evidence of associations between maternal prenatal stress and fetal brain iron, which lays the groundwork for future investigations of biological embedding of prenatal maternal stress on the fetal brain and later neurodevelopment through prenatal iron accumulation as a potential mechanism.

Altered fetal brain function is proposed as a mechanism underlying the relationship between prenatal maternal depression (PMD) and neurodevelopmental outcomes in offspring. This study investigated the association between PMD symptoms and fetal brain functional connectivity (FC) using graph theory. A total of 123 pregnant women participated in the study, completed the Center for Epidemiologic Studies Depression Scale (CES-D), and underwent fetal MRI scans. Results revealed a significant relationship between elevated PMD symptoms and reduced global efficiency in the right insular region of the fetal brain. However, because fetal age was not associated with local or global efficiency in the insular brain region, we cannot determine if the PMD-related reduction in insula global efficiency is indicative of an accelerated or delayed developmental pattern. This study is one of the few to examine fetal brain connectivity in relation to prenatal maternal depression, providing valuable insights into early neurodevelopmental risks and potential targets for early intervention.

BACKGROUND/OBJECTIVES/OBJECTIVE:Malignant peripheral nerve sheath tumors (MPNSTs) are aggressive malignancies with a challenging prognosis, especially for patients with Neurofibromatosis type 1 (NF1). Their low incidence necessitates comprehensive studies to investigate the survival outcome. METHODS:We conducted a systematic review and meta-analysis, including data from 16 studies and 4265 patients, to explore surgical outcomes and survival rates, focusing on time-related outcomes, including overall survival (OS), progression-free survival (PFS), and recurrence rate. RESULTS:The analysis revealed that the OS rate was 86% [95% CI: 75-97%] at 1 year, decreasing to 60% [95% CI: 45-75%] at 3 years, and further declining to 47% [95% CI: 35-58%] by 5 years. For PFS, the 1-year rate was 61% [95% CI: 25-98%], which remained similar at 62% [95% CI: 35-89%] for 3 and 5 years. In NF1-associated MPNSTs, the 1-year OS was relatively high at 93% [95% CI: 83-100%], but it dropped to 68% [95% CI: 53-84%] at 3 years and further to 50% [95% CI: 31-68%] at 5 years. Additionally, the hazard ratio indicated a 38% lower survival rate in NF1 patients than those with sporadic MPNSTs when data were presented in the same study. Recurrence rates were high, with 56% of patients experiencing a relapse, primarily as local recurrences (70.6%). Mortality was significant, with over 50% of patients dying within an average follow-up period of 33.45 months. CONCLUSIONS:MPNSTs, particularly in NF1 patients, are associated with poor prognosis and high recurrence rates. These results underline the necessity of targeted therapeutic strategies and improved programs for screening, mainly through a multidisciplinary approach to optimize management.

Sleep disturbances are prominent across neurodevelopmental disorders (NDDs) and may reflect specific abnormalities in brain development and function. Overnight polysomnography (PSG) allows for detailed investigation of sleep architecture, offering a unique window into neurocircuit function. Analysis of existing pediatric PSGs from clinical studies could enhance the availability of sleep studies in pediatric patients with NDDs towards a better understanding of mechanisms underlying abnormal development in NDDs. Here, we introduce and characterize a retrospective collection of 1527 clinical pediatric overnight PSGs across five different sites. We first developed an automated stager trained on independent pediatric sleep data, which yielded better performance compared to a generic stager trained primarily on adults. Using consistent staging across cohorts, we derived a panel of EEG micro-architectural features. This unbiased approach replicated broad trajectories previously described in typically developing sleep architecture. Further, we found sleep architecture disruptions in children with Down's Syndrome (DS) that were consistent across independent cohorts. Finally, we built and evaluated a model to predict age from sleep EEG metrics, which recapitulated our previous findings of younger predicted brain age in children with DS. Altogether, by creating a resource pooled from existing clinical data we expanded the available datasets and computational resources to study sleep in pediatric populations, specifically towards a better understanding of sleep in NDDs. This Retrospective Analysis of Sleep in Pediatric (RASP) cohorts dataset, including staging annotation derived from our automated stager, is deposited at https://sleepdata.org/datasets/rasp.