Faculty Bibliography

BACKGROUND:The COVID-19 pandemic exacerbated challenges faced by pregnant women, introducing new risks and intensifying existing disparities, particularly among those routinely experiencing race- and ethnicity-based discrimination. It remains unclear how the pandemic affected perceptions of perinatal quality of care (QoC). OBJECTIVES/OBJECTIVE:To explore mothers' experiences of pregnancy, birth, and the early postpartum period during the early COVID-19 pandemic, attending to both health care encounters and to the broader structural and social forces shaping those experiences. DESIGN/METHODS:The COVID-19 Mother Baby Outcomes (COMBO) Initiative is a longitudinal, prospective cohort study investigating maternal-child outcomes among women from a predominantly low socioeconomic status, Latinx community in New York City who delivered during the pandemic. This qualitative substudy analyzed a subset of participants using modified grounded theory. METHODS:Semi-structured interviews explored perinatal and pandemic experiences, perceptions of inequitable or poor treatment, and protective factors among 64 participants purposively sampled from the parent cohort. Analysis focused on 48 transcripts highlighting discrimination-related themes, which were transcribed and systematically coded using both inductive and deductive approaches. RESULTS:phenomenon. CONCLUSION/CONCLUSIONS:Giving birth during the pandemic worsened perceptions of perinatal QoC, with discrimination compounding negative experiences. Findings underscore the link between care quality and trust in medical institutions, highlighting the need for evidence-based crisis protocols that both reduce unnecessary risk while preserving patient agency, particularly for marginalized populations. The pandemic exposed longstanding structural inequities, presenting an opportunity to address these patient-level manifestations and strengthen support for populations facing systemic barriers.

BackgroundRates of psychiatric disorders and related hospitalizations among youth in the United States have risen substantially over recent decades. Despite evidence supporting outpatient care, fewer than half of youth receive treatment. When outpatient management is insufficient, inpatient psychiatric hospitalization is required, though it is costly, disruptive, and limited in availability. Prior research on predictors of inpatient length of stay has been dated and heterogenous, highlighting the need to identify current clinical and non-clinical factors associated with prolonged stays among youth populations.MethodThis IRB-approved retrospective study reviewed the medical records of 1,101 child and adolescent patients admitted to an inpatient psychiatric unit between June 1, 2018, and November 30, 2021. Baseline sociodemographic and clinical data were collected, and LOS was categorized into three groups: below-average (0-6 days), average (7-14 days), and above-average (15+ days). Comparative statistics were performed, and linear regression was used to identify independent predictors of LOS.ResultsThe average LOS was 10.5 days. Significant predictors of prolonged LOS included public insurance, admission for psychosis or suicide attempt, involvement of child protective services, number of prior hospitalizations, and number of medications prior to admission.ConclusionProlonged LOS in psychiatrically hospitalized youth is associated with specific clinical and non-clinical factors. Identifying these predictors at admission can guide treatment planning and set realistic expectations for families. Further research is required to validate these findings and explore the impact of LOS on treatment outcomes.

Autism spectrum disorder (ASD) is a neurodevelopmental condition, with ex vivo studies suggesting its neurobiological origin as early as the first and second trimester of pregnancy. Functional MRI studies using graph-theoretical approaches have isolated features in the global connectome architecture that distinguish toddlers with ASD from their typically developing peers. Additionally, functional connectivity patterns in the infant brain have shown to be predictive of later ASD diagnosis. An important yet unexplored question in the literature is whether graph-theoretical differences are evident prior to infancy, in the brain of fetuses who will later exhibit ASD traits in early childhood. In this study, we address this question using a sample of 88 children with both quality-assured fetal brain resting-state functional MRI data and standardized parent assessment of ASD traits including social-emotional and social communication skills and repetitive and restricted behaviors at age 3. Multiple regression analyses revealed no significant associations between fetal global graph features (e.g., network segregation, integration, and small-world architecture) and ASD traits at age 3 (p's > 0.1). Therefore, our findings do not provide support for prenatal emergence of global topographical differences of brain functional organization in fetuses who later develop ASD traits. However, this does not rule out the possibility of other neural signatures in the fetal functional connectome that may predict autistic traits and future ASD diagnosis.

Maternal psychological distress during pregnancy and the early postpartum period is a risk factor for dysregulated affective and regulatory function in young infants. Animal models suggest that perinatal stress may alter offspring development via allopregnanolone (ALLO) exposure. For example, variations in placentally derived ALLO in preterm infants have been linked with altered fetal neurodevelopment. However, no studies have investigated naturalistic variations in ALLO concentrations in maternal milk as a potential moderator of associations between maternal distress and infant temperament during the postnatal period. The current study assesses associations among ALLO concentrations in human milk, maternal psychological distress, and infant temperament in 81 mother-infant dyads (31 females) measured at approximately 6.5 months postpartum (M = 6.55 months, range = 5.5-8 months). Results indicated that human milk ALLO concentration moderated effects of maternal psychological distress on infant regulatory capacity. Specifically, there was a negative association between maternal psychological distress and regulatory capacity in infants of mothers with below-mean ALLO concentrations, but not in infants of mothers with above-mean ALLO concentrations. However, there were no effects of ALLO on infant negative affect or surgency/positive affect. This study provides some of the first preliminary evidence that ALLO concentrations in human milk may moderate associations between maternal psychological distress and infant regulatory capacity.

Active avoidance responses (ARs) are instrumental behaviors that prevent harm. Adaptive ARs may contribute to active coping, whereas maladaptive avoidance habits are implicated in anxiety and obsessive-compulsive disorders. The AR learning mechanism has remained elusive, as successful avoidance trials produce no obvious reinforcer. We used a novel outcome-devaluation procedure in rats to show that ARs are positively reinforced by response-produced feedback cues that develop into safety signals during training. Males were sensitive to feedback devaluation after moderate training, but not overtraining, consistent with a transition from goal-directed to habitual avoidance. Using chemogenetics and feedback devaluation, we also show that goal-directed vs. habitual ARs depend on dorsomedial vs. dorsolateral striatum, suggesting a significant overlap between the mechanisms of avoidance and rewarded instrumental behavior. Females were insensitive to feedbackdevaluation due to a remarkable context-dependence of counterconditioning. However, degrading the contingency between avoidance and feedback suggests that both sexes rely on safety signals to perform goal-directed ARs.

Osteoarthritis, especially knee osteoarthritis, is a leading cause of disability and reduced quality of life. The etiology of pain in osteoarthritis is multifactorial, and one promising potential treatment approach involves targeting chemokine systems. The present study was a phase 2, multisite, multiperiod randomized crossover trial of CNTX-6970, a small molecule and selective oral cytokine chemokine receptor type 2 (CCR2) and CCR5 antagonist, in patients with painful knee osteoarthritis (OA). It represents the first trial performed within the National Institutes of Health's Early Phase Pain Investigation Clinical Network. The primary objectives were to evaluate the safety and efficacy of CNTX-6970, relative to placebo, for the treatment of moderate to severe pain related to knee OA. A total of 55 participants were randomized in this multiperiod crossover trial. Linear mixed effects models revealed no significant pain-related benefits of active medication; indeed, trial participants reported slightly higher knee pain intensity when taking the novel chemokine antagonist CNTX-6970 than when taking placebo. In addition, biomarker analysis revealed notably higher level of serum monocyte chemoattractant protein 1 levels when patients were on CNTX-6970 compared to placebo. Overall, although CNTX-6970 was safe and relatively well-tolerated, pharmacologic blockade of specific chemokine receptors with this compound was not effective in reducing moderate-to-severe knee osteoarthritis pain.

BACKGROUND AND OBJECTIVE/OBJECTIVE:Individuals with attention-deficit/hyperactivity disorder, their families and clinicians may report worsening symptoms despite compliant use of medication, suggesting potential tolerance, but evidence remains conflicting. Some studies have also suggested tachyphylaxis, or acute tolerance, though research is limited. We conducted the first systematic review of empirical studies focussing on tolerance/tachyphylaxis to attention-deficit/hyperactivity disorder medication to clarify their potential clinical relevance. METHODS:As registered on PROSPERO (CRD42024594759), we searched PubMed, OVID (including PsychInfo and MEDLINE) and Web of Knowledge up to 1 September, 2024, and assessed the risk of bias using National Institutes of Health quality assessment tools. RESULTS:The identified 17 studies were either interventional or observational, and varied greatly in design and duration. Four investigated tachyphylaxis, nine tolerance to the subjective and behavioural effects, and four tolerance to cardiovascular effects. We found preliminary evidence of tachyphylaxis to the affective or behavioural effects of stimulants, as well as tolerance to the subjective effects of d-amphetamine, such as drug liking and excitation, in neurotypical volunteers in the short term. Conversely, there was little or no evidence for tolerance to the therapeutic or cardiovascular effects of attention-deficit/hyperactivity disorder medication in clinical settings in the longer term. Quality was rated as low in most studies because of small sample sizes and methodological limitations. CONCLUSIONS:Overall, these results do not support the hypothesis that tolerance commonly develops to the therapeutic effects of attention-deficit/hyperactivity disorder medication, although robustly designed longitudinal studies are needed to provide more conclusive evidence. Clinicians may consider other potential explanations for reduced therapeutic effects over time, including natural fluctuations of symptoms, limited compliance, life events and co-occurrent mental health conditions.

Socioeconomic disadvantage has been established as a key risk factor for adverse child behavioral outcomes. Understanding how individual components of socioeconomic status (SES) interact with each other can elucidate protective factors and inform interventions and policies to promote positive developmental outcomes. This study examined the interactive effects of prenatal household income and neighborhood deprivation on child externalizing and internalizing problems (N = 793; M