Faculty Bibliography

INTRODUCTION/UNASSIGNED:Poor dental health is linked to poor physical and mental health. This study was aimed to examine the characteristics of U.S. adults that are associated with having seen a dentist in the past year. METHODS/UNASSIGNED:A cross-section of adults aged 18-64 years (N=19,975) from the 2023 National Health Interview Survey was examined. Bivariate analyses examined the associations of sociodemographic and financial variables with recent dental visits in the last 12 months. Multinomial modeling was used to assess these variables to predict 3 outcomes of time since the last dental visit: in the last 12 months; over a year but <10 years; and over 10 years or never, which was the reference category. RESULTS/UNASSIGNED:In young and middle-aged adults, 4.8% of Americans, representing over 9 million people, had either never seen a dentist or not seen a dentist in 10 years or more. The likelihood of a dental visit in the last 12 months increased with education level (no high-school degree versus a graduate or professional degree [AOR=0.21, 95% CI=0.09, 0.50]) and income (income below the federal poverty line versus income in the highest quartile [AOR=0.20, 95% CI=0.11, 0.35]). Having dental coverage in a private plan or Medicaid, compared with having no coverage, predicted having a dental visit within the last 12 months in both multinomial and bivariate analyses. CONCLUSIONS/UNASSIGNED:Access to dental care in young and middle-aged adults is determined by financial ability. Increasing access to dental care could happen once the financial barriers to dental care are reduced, including increasing the age at which a young adult can be covered by a parent's plan and making dental coverage comparable with physical health coverage. Given the current data about the links between dental, mental, and physical health, parity for all care is warranted.

BACKGROUND:Autism spectrum disorder (ASD) has a complex inheritance pattern and is more common in males. Etiological models suggest that majority of ASD risk is transmitted through common and rare de-novo genetic variation. It has been hypothesized that rare variation could be inherited and therefore contribute to the overall risk-burden in subsequent generations, especially through female lineage in disorders with male-skewed sex-ratios. Here we test this hypothesis using multigeneration information on paternal age, because burden of de-novo mutations has been linked to paternal age, and there is a well-established association between older age of fathers and ASD. METHODS:We analyzed combined data from Sweden's, Denmark's and Finland's national registers totaling 12.6 million family-members, including information about parental ages at the time of birth of offspring in two generations, and ASD diagnosis in the third generation. RESULTS:Among the 1,808,892 children in the third generation, 23,397 (1.29%) were diagnosed with ASD. Increased paternal age at the time of birth of a daughter was associated with increased risk of ASD in the daughter's own offspring. Increased paternal age at the time of birth of a son was not associated with increased ASD risk in the son's offspring, nor was older maternal age in the first or second generations. We observed that young maternal age at birth of a son or a daughter was associated with ASD risk in their offspring. CONCLUSIONS:Collectively, our results suggest that etiologic risk-factors for ASD could extend over multiple generations through different underlying mechanisms, suggesting new directions for research on genetic and non-genetic risk-factors.

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:Anxiety disorders may partly stem from altered neurodevelopment of attention-related networks. Neonatal alterations in resting-state functional connectivity (rsFC) among the dorsal attention (DAN); frontal parietal (FPN); salience (SN); and default mode networks (DMN)) relate to fearful temperament, a risk marker for anxiety. Nevertheless, little research examines development of these networks beyond the first months of life, particularly in fearful infants. This study examines how changes in these networks in the first two years of life relate to fearful temperament. METHODS:Using data from the Baby Connectome Project (from 180 infants across 396 sessions), we conducted independent components analysis to extract rsFC among the DMN, SN, DAN, and FPN. Longitudinal modeling characterized 1) age-related changes (slope) in rsFC through age two; 2) relations between rsFC change (slope) and fearfulness at age 2; 3) relations between rsFC and fearfulness trajectories (slope and intercept) over the first two years of life. RESULTS:Age-related decreases occurred in rsFC in DAN - FPN and DMN - SN. Smaller decreases in DAN - FPN rsFC over time related to greater fear at age 2, and to increases in fearfulness over time. High initial DAN-FPN rsFC and low initial DAN - SN rsFC also related to increasing fearfulness over time. CONCLUSION/CONCLUSIONS:This study provides the first evidence that changes in attention-related brain networks are related to early-life fearfulness, a robust early-life risk marker of anxiety.

The collection of electroencephalography (EEG) data in neonates typically occurs during sleep. EEG activity is highly sleep-state dependent, therefore differentiating between states during data processing can provide important insights into neurodevelopment. Despite this, there have been a paucity of studies directly comparing how infant EEG data, especially event-related potentials, differ between these sleep states. Here, we adapted the Maryland Analysis of Developmental EEG pipeline (MADE) to integrate sleep-state coding into its automated preprocessing pipeline. We recorded EEG in 102 sleeping one month old infants and evaluated their responses during a resting state and during a three-stimuli auditory oddball paradigm. Examination of resting-state power revealed significant differences between two sleep states, namely active (AS) and quiet (QS) sleep across all frequency bands in both absolute and relative power. For the auditory oddball paradigm, we computed responses to both standard and deviant tones and then created a difference score reflecting the Mismatch Response (MMR). For the novel tones we examined the evoked response (P300). Results revealed for the MMR, a significant electrode cluster by sleep-state interaction (F = 5.36, p = .01), indicating that the MMR was present at all three electrode clusters during AS (p-values <.05), but only at the frontal cluster during QS (t = 2.05, p = .04). There were no differences in the amplitude of the P300 to the novel sound as a function of sleep state.

Individuals with Down syndrome (DS) are at risk for early-onset Alzheimer's disease (AD), marked by neurodegeneration in hippocampal and basal forebrain circuits. Early-life interventions offer therapeutic potential, including maternal choline supplementation (MCS). MCS improves cognitive outcomes and neuroplasticity in rodent models of neurodevelopmental and neurodegenerative disorders, yet cell-type specific molecular effects remain unknown. We investigated the effect of MCS upon the onset of septohippocampal degeneration at 6 months of age in the Ts65Dn mouse model of DS/AD. Using laser capture microdissection and single population RNA-sequencing, transcriptomic changes were profiled within hippocampal CA1 and CA3 pyramidal neurons and dentate gyrus granule cells comparing trisomic and disomic offspring. Bioinformatic analysis revealed MCS-mediated downregulation of apoptotic pathways and upregulation of cognition-related functions across all populations, alongside cell-specific responses. These findings highlight MCS as a promising strategy for modulating disease-relevant pathways in a hippocampal cell-type-specific manner during early neurodegeneration in DS/AD.

Youth are presenting to Emergency Departments (EDs) following a suicide-related crisis at higher rates and younger ages. Clinicians lack tools to effectively discern suicide risk in younger patients. The present investigation examines how ED-based, suicidal pre-adolescents and adolescents conceptualize death. One hundred and sixty-seven suicidal pre-adolescents and adolescents (10-17 years; M = 12, SD = 1.4) presenting to a psychiatric ED with a suicide-related chief complaint completed assessments of suicidal ideation (SI; passive and active thoughts), suicide attempt (SA), depressive symptoms, and death conceptualizations (Death Avoidance, Escape Acceptance, Neutral Acceptance). Post-discharge SI and SA were assessed via survey emailed to participants 6 months later and via electronic medical record. At baseline, lower levels of Death Avoidance and higher levels of Escape Acceptance were most robustly associated with active SI. Pre-adolescents reported higher levels of Death Avoidance and lower levels of Escape Acceptance than adolescents at baseline. Death conceptualizations did not predict follow-up SI and SA. Youth who have recently experienced a suicide-related crisis are more likely to accept death as an escape from painand spend less time avoiding thoughts about death. This profile appears to be more representative of adolescents, relativeto pre-adolescents who display the opposite pattern.