Faculty Bibliography

A major challenge in designing large-scale, multi-site studies is developing a core, scalable protocol that retains the innovation of scientific advances while also lending itself to the variability in experience and resources across sites. In the development of a common Healthy Brain and Child Development (HBCD) protocol, one of the chief questions is "is fetal MRI ready for prime-time?" While there is agreement about the value of prenatal data obtained non-invasively through MRI, questions about practicality abound. There has been rapid progress over the past years in fetal and placental MRI methodology but there is uncertainty about whether the gains afforded outweigh the challenges in supporting fetal MRI protocols at scale. Here, we will define challenges inherent in building a common protocol across sites with variable expertise and will propose a tentative framework for evaluation of design decisions. We will compare and contrast various design considerations for both normative and high-risk populations, in the setting of the post-COVID era. We will conclude with articulation of the benefits of overcoming these challenges and would lend to the primary questions articulated in the HBCD initiative.

Local translation can provide a rapid, spatially targeted supply of new proteins in distal dendrites to support synaptic changes that underlie learning. Learning and memory are especially sensitive to manipulations of translational control mechanisms, particularly those that target the initiation step, and translation initiation at synapses could be a means of maintaining synapse specificity during plasticity. Initiation predominantly occurs via recruitment of ribosomes to the 5' mRNA cap by complexes of eukaryotic initiation factors (eIFs), and the interaction between eIF4E and eIF4G1 is a particularly important target of translational control pathways. Pharmacological inhibition of eIF4E-eIF4G1 binding impairs formation of memory for aversive Pavlovian conditioning as well as the accompanying increase in polyribosomes in the heads of dendritic spines in the lateral amygdala (LA). This is consistent with a role for initiation at synapses in memory formation, but whether eIFs are even present near synapses is unknown. To determine whether dendritic spines contain eIFs and whether eIF distribution is affected by learning, we combined immunolabeling with serial section transmission electron microscopy (ssTEM) volume reconstructions of LA dendrites after Pavlovian conditioning. Labeling for eIF4E, eIF4G1, and eIF2α - another key target of regulation - occurred in roughly half of dendritic spines, but learning effects were only found for eIF4E, which was upregulated in the heads of dendritic spines. Our results support the possibility of regulated translation initiation as a means of synapse-specific protein targeting during learning and are consistent with the model of eIF4E availability as a central point of control. This article is protected by copyright. All rights reserved.

Maternal care, including by non-biological parents, is important for offspring survival^1-8. Oxytocin^1,2,9-15, which is released by the hypothalamic paraventricular nucleus (PVN), is a critical maternal hormone. In mice, oxytocin enables neuroplasticity in the auditory cortex for maternal recognition of pup distress¹⁵. However, it is unclear how initial parental experience promotes hypothalamic signalling and cortical plasticity for reliable maternal care. Here we continuously monitored the behaviour of female virgin mice co-housed with an experienced mother and litter. This documentary approach was synchronized with neural recordings from the virgin PVN, including oxytocin neurons. These cells were activated as virgins were enlisted in maternal care by experienced mothers, who shepherded virgins into the nest and demonstrated pup retrieval. Virgins visually observed maternal retrieval, which activated PVN oxytocin neurons and promoted alloparenting. Thus rodents can acquire maternal behaviour by social transmission, providing a mechanism for adapting the brains of adult caregivers to infant needs via endogenous oxytocin.

BACKGROUND:The COVID-19 pandemic led to rapid changes in clinical service delivery across hospital systems nationally. Local realities and resources were key driving factors impacting workflow changes, including for pediatric consultation-liaison psychiatry service (PCLPS) providers. OBJECTIVE:This study aims to describe the early changes implemented by 22 PCLPSs from the United States and Canada during the COVID-19 pandemic. Understanding similarities and differences in adaptations made to PCLPS care delivery can inform best practices and future models of care. METHODS:A 20-point survey relating to PCLPS changes during the COVID-19 pandemic was sent to professional listservs. Baseline hospital demographics, hospital and PCLPS workflow changes, and PCLPS experience were collected from March 20 to April 28, 2020, and from August 18 to September 10, 2020. Qualitative data were collected from responding sites. An exploratory thematic analysis approach was used to analyze the qualitative data that were not dependent on predetermined coding themes. Descriptive statistics were calculated using Microsoft Excel. RESULTS:Twenty-two academic hospitals in the United States and Canada responded to the survey, with an average of 303 beds/hospital. Most respondents (18/22) were children's hospitals. Despite differences in regional impact of COVID-19 and resource availability, there was significant overlap in respondent experiences. Restricted visitation to one caregiver, use of virtual rounding, ongoing trainee involvement, and an overall low number of COVID-positive pediatric patients were common. While there was variability in PCLPS care delivery occurring virtually versus in person, all respondents maintained some level of on-site presence. Technological limitations and pediatric provider preference led to increased on-site presence. CONCLUSIONS:To our knowledge, this is the first multicenter study exploring pandemic-related PCLPS changes in North America. Findings of this study demonstrate that PCLPSs rapidly adapted to COVID-19 realities. Common themes emerged that may serve as a model for future practice. However, important gaps in understanding their effectiveness and acceptability need to be addressed. This multisite survey highlights the importance of establishing consensus through national professional organizations to inform provider and hospital practices.

INTRODUCTION:COVID-19 affects multiple organ systems causing substantial long-term morbidity. The implications of the Post-Acute Sequelae of SARS-CoV-2 infection, particularly for primary care, remain unknown. This cross-sectional study examines new symptoms reported at primary care encounters during three post-acute follow-up intervals after initial SARS-CoV-2 infection. METHODS:Electronic health record data from the NYU Langone COVID Deidentified Dataset were queried for adults with a positive SARS-CoV-2 PCR test, and then restricted to those with a new ICD-10-CM code documented at a post-acute COVID-related primary care follow-up >14 days after testing positive. New diagnoses and the corresponding Clinical Classifications Software Refined categories were assessed at the following intervals: 0.5-3 months ("subacute"), 3-6 months ("prolonged"), and 6-9 months ("persistent"). RESULTS:Out of 3,154 patients, a new ICD-10-CM code was documented among 499 patients (∼16%). Respiratory complaints, including cough, shortness of breath, dyspnea, and hypoxemia, were most common. Malaise and fatigue were reported consistently among 10-13% of patients at all three time-intervals. Musculoskeletal pain, circulatory symptoms, and sleep-wake disorders were also observed at primary care follow-up. CONCLUSION:This cross-sectional study provides support of a post-acute COVID syndrome, demonstrating that patients continue to experience symptoms after the acute infection period. Extensive follow-up data allowed for examining new symptoms up to 9 months after initial SARS-CoV-2 infection. Understanding of the course of multi-organ post-acute sequelae is restricted by cross-sectional study design limitations. Standardized, sequelae-related ICD-10-CM codes to specify the type and duration of post-acute COVID-related symptoms would enable better monitoring of the growing number of SARS-CoV-2 infection survivors.

OBJECTIVE:Risk calculators (RC) to predict clinical outcomes are gaining interest. An RC to estimate risk of bipolar spectrum disorders (BPSD) could help reduce the duration of undiagnosed BPSD and improve outcomes. Our objective was to adapt an RC previously validated in the Pittsburgh Bipolar Offspring Study (BIOS) sample to achieve adequate predictive ability in both familial high-risk and clinical high-risk youths. METHOD/METHODS:Participants (aged 6-12 years at baseline) from the Longitudinal Assessment of Manic Symptoms (LAMS) study (N = 473) were evaluated semi-annually. Evaluations included a Kiddie Schedule for Affective Disorders (K-SADS) interview. After testing an RC that closely approximated the original, we made modifications to improve model prediction. Models were trained in the BIOS data, which included biennial K-SADS assessments, and tested in LAMS. The final model was then trained in LAMS participants, including family history of BPSD as a predictor, and tested in the familial high-risk sample. RESULTS:Over follow-up, 65 youths newly met criteria for BPSD. The original RC identified youths who developed BPSD only moderately well (area under the curve [AUC] = 0.67). Eliminating predictors other than the K-SADS screening items for mania and depression improved accuracy (AUC = 0.73) and generalizability. The model trained in LAMS, including family history as a predictor, performed well in the BIOS sample (AUC = 0.74). CONCLUSION/CONCLUSIONS:The clinical circumstances under which the assessment of symptoms occurs affects RC accuracy; focusing on symptoms related to the onset of BPSD improved generalizability. Validation of the RC under clinically realistic circumstances will be an important next step.

The purpose of this study was to develop a greater understanding of the factors influencing the adoption of evidence-based interventions in outpatient mental health clinics serving youth. An improved understanding of these factors can potentially improve efforts to ensure effective adoption, implementation, and sustainment of evidence-based interventions, and thus improve treatment for youth in mental health settings. This explanatory cross-sectional study involves secondary data analysis of a longitudinal randomized control intervention trial. The SEM- based model that was tested supported the primary hypothesis that a more supportive organizational climate with greater readiness for change is more likely to improve the chances for the adoption of evidence-based interventions in outpatient mental health clinics serving youths.

OBJECTIVE:To determine whether there are racial/ethnic differences in depression treatment for caregivers investigated by the US child welfare system. METHODS:This cross-sectional study used baseline data from the Second National Survey of Child and Adolescent Well-being, a nationally representative sample of children and caregivers investigated by US child welfare agencies (February 2008-April 2009). We included permanent caregivers who met criteria for major depression and had available covariate data (n = 908). In multivariable logistic regression models, we estimated the associations between caregiver race/ethnicity and past-year receipt of: any depression treatment, minimally adequate depression treatment, and depression treatment from 4 sectors (general medical, psychiatry, nonpsychiatry mental health, and human services). We controlled for clinical need and access variables according to the Institute of Medicine's definition of health care disparities. RESULTS:Black caregivers had the lowest rates of treatment receipt of any racial/ethnic group, with 42.2% receiving any depression treatment and 17.2% receiving minimally adequate depression treatment in the past year. In multivariable analyses controlling for clinical need and access variables, Black caregivers were less likely than White caregivers to receive any depression treatment (odds ratio [OR] = 0.49 [95% CI: 0.24-0.97]), minimally adequate depression treatment (OR = 0.37 [95% CI: 0.16-0.85]), and depression treatment from the general medical sector (OR = 0.40 [95% CI: 0.18-0.89]) in the past year (all P< .05). CONCLUSIONS:Future research should examine the underlying mechanisms of Black-White disparities in depression treatment for caregivers involved with the US child welfare system and develop targeted interventions to promote equitable mental health care for this highly vulnerable population.