Faculty Bibliography

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.

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.

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.

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.

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

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.

BACKGROUND:Maternal infections are linked to neurodevelopmental impairments, highlighting the need to investigate SARS-CoV-2-induced immune activation. OBJECTIVE:This study aimed to evaluate the impact of maternal infection on neurodevelopment and investigate whether cytokine and chemokine profiles predict delays at 24 months. METHODS:Conducted in Brazil (January 2021-March 2022), this follow-up study included 18 SARS-CoV-2 positive pregnant women at 35-37 weeks' gestation, 15 umbilical cord blood samples, and blood samples from 15 children at 6 months and 14 at 24 months. Developmental delay was defined using the Bayley Scales of Infant and Toddler Development, Third Edition, with scores below 90 in cognitive, communication, or motor domains. RESULTS:At 6 months, 33.3% of infants exhibited cognitive delays, 20% communication delays, and 40% motor delays, increasing to 35.71%, 64.29%, and 57.14% at 24 months, respectively. Elevated interferon-gamma and tumor necrosis factor-alpha in cord blood correlated with cognitive delays, while interleukin (IL)-6, IL-8, IL-17, and IL-1β were associated with motor delays. Increased C-X-C motif chemokine ligand 10 and other cytokines were associated with communication delays. CONCLUSION/CONCLUSIONS:Maternal SARS-CoV-2 may impact infant neurodevelopment, as early cytokine elevations correlate with delays, highlighting the importance of early monitoring and interventions to reduce long-term effects. IMPACT/CONCLUSIONS:Prenatal SARS-COV-2 infection in pregnant women is linked to developmental delays in toddlers, with cytokine and chemokine changes associated with neurodevelopmental outcomes at 24 months. This study shows the long-term impact of maternal SARS-COV-2 infection on child development, highlighting inflammatory markers like IFN-γ, TNFα, IL-6, IL-8, IL-17, IL-1β, and CXCL10. Identifying specific cytokines correlating with cognitive, communication, and motor delays suggests potential biomarkers for early intervention. Conducted in Fortaleza, Brazil, the study emphasizes understanding local epidemiological impacts on child development, especially in regions with high infection rates. Graphical depiction of the SARS-CoV-2-induced maternal immune activation and its impact on the child's neurological development. Maternal immune activation from SARS-CoV-2 infection can affect a baby's neurological development, leading to motor, communication, and cognitive delays, assessed at 6 and 24 months old. Alterations in cytokine and chemokine levels in cord blood at six months may help predict these adverse outcomes observed at 24 months.

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.

Recent changes to US research funding are having far-reaching consequences that imperil the integrity of science and the provision of care to vulnerable populations. Resisting these changes, the BJPsych Portfolio reaffirms its commitment to publishing mental science and advancing psychiatric knowledge that improves the mental health of one and all.