Faculty Bibliography

INTRODUCTION/BACKGROUND:Cannabis use and cannabis use disorder (CUD) are associated with adverse psychosocial outcomes, but their impact on workplace absenteeism remains poorly understood. Moreover, few studies have examined the role of CUD severity. This study aims to address these gaps by examining the associations between cannabis use recency, frequency, CUD severity, and workplace absenteeism. METHODS:Cross-sectional data from a U.S. representative sample of full-time employed adults aged ≥18 from the 2021 to 2022 National Survey on Drug Use and Health (N=46,499) were analyzed. The associations between cannabis use recency, past-month cannabis use frequency, CUD severity, and workplace absenteeism (measured by self-reported number of missed days due to illness/injury and skipped work in the last 30 days) were evaluated using negative binomial regression, adjusting for sociodemographic characteristics and other substance use. Data were analyzed in 2023-2024. RESULTS:An estimated 15.9% of full-time employed adults used cannabis in the past month, with 6.5% meeting CUD criteria. Past-month cannabis use (compared to no lifetime use), more frequent past-month cannabis use (compared to no use in the past month), and each level of CUD (compared to no CUD) were associated with increased incidence of both missing work due to illness/injury and skipping work, with a dose-response relationship observed between CUD severity and skipping work (mild: adjusted incident rate ratio [aIRR]=1.60 [95% confidence interval [CI]=1.24, 2.08]; moderate: aIRR=1.98 [95% CI=1.50, 2.61]); severe (aIRR=2.87 [95% CI=2.12, 3.88]). CONCLUSIONS:Individuals with recent and frequent cannabis use and CUD are disproportionately prone to workplace absenteeism. Results support the enforcement of workplace drug prevention and treatment policies.

This review summarizes recent findings on stress-related programming of brain development in utero, with an emphasis on situating findings within the mothers' broader psychosocial experiences. Meta-analyses of observational studies on prenatal stress exposure indicate the direction and size of effects on child neurodevelopment are heterogeneous across studies. Inspired by lifespan and topological frameworks of adversity, we conceptualize individual variation in mothers' lived experience during and prior to pregnancy as a key determinant of these heterogeneous effects across populations. We structure our review to discuss experiential categories that may uniquely shape the psychological and biological influence of stress on pregnant mothers and their developing children, including current socioeconomic resources, exposure to chronic and traumatic stressors, culture and historical trauma, and the contours of prenatal stress itself. We conclude by identifying next steps that hold potential to meaningfully advance the field of fetal programming.

Children's mental health problems are pressing social, economic, and public health concerns in the U.S. While pediatric primary care offers important venues to integrate mental health services for children and their families, new challenges, including widening educational, economic, and health disparities in the context of structural racism and COVID-related social isolation, underscore the need for innovative approaches. The authors reviewed 6 innovative methods in pediatric care that have helped address these issues and amplify intervention efforts focused on children's mental health. Limitations and future directions for research and clinical practice in pediatric mental health services are also discussed.

Anxiety is highly prevalent in Alzheimer's disease (AD), correlating with cerebrospinal fluid/positron emission tomography biomarkers and disease progression. Relationships to plasma biomarkers are unclear. Herein, we compare levels of plasma biomarkers in research participants with and without anxiety at cognitively normal, mild cognitive impairment, and AD dementia stages. We observed significantly higher plasma tau/amyloid-β₄₂ ratio in AD participants with anxiety versus those without, but did not observe differences at other stages or plasma biomarkers. No such relationships were evident with depression. These results support a unique pathophysiological relationship between anxiety and AD that can be reflected in plasma biomarkers, suggestive of heightened neurodegeneration.

Fetal inflammation, typically measured indirectly through prenatal maternal cytokine markers, has been shown to impact early childhood executive functions (EFs), which are central to later cognitive and life outcomes. Here, we assessed the impact of prenatal inflammation on EF developmental trajectories using direct placenta histopathology measures in 131 mothers who predominantly self-identified as Black (90.8% Black; 0.8% Asian American, 1.5% biracial, 0.8% Latinx, 3.1% White, 3.1% Missing). We found that placental measures of inflammation were associated with limited gain in EF development from 3 to 5 years old. In follow up analyses, we addressed whether screening questionnaires in infancy might aid in classification of infants as higher risk for subsequent EF problems. We found that parent responses to the Ages & Stages Questionnaire and the Infant/Toddler Sensory Profile at 12 months predict the development of EF abilities in children exposed to chronic inflammation. These findings open promising opportunities for early screening of children at risk for poor executive functioning in children exposed to prenatal inflammation.

BACKGROUND:The randomized, phase 2 RENEW trial (NCT01721161) evaluated efficacy/safety of opicinumab (anti-LINGO-1) versus placebo in patients with first-episode unilateral acute optic neuritis (AON). Although no significant differences in the latency recovery of visual evoked potential (VEP) were observed between opicinumab and placebo groups in the intention to treat (ITT) population, the prespecified per-protocol (PP) population showed better recovery with opicinumab than with placebo. RENEWED (NCT02657915) was a one-visit, follow-up study 2 years after the last RENEW study visit (Week 32) designed to assess the long-term electrophysiological and clinical outcomes for participants previously enrolled and having received study treatment in RENEW. METHODS:In the original study (RENEW), participants (aged 18-55 years) with a first unilateral AON episode were enrolled ≤28 days from first symptom onset and after treatment with methylprednisolone 1 g/day intravenously for 3-5 days; these participants were randomized to receive opicinumab 100 mg/kg or placebo intravenously once every 4 weeks from baseline to Week 20, assessed up to Week 32. Participants who received ≥1 dose of opicinumab 100 mg/kg or placebo in RENEW were eligible for the RENEWED follow-up study. Participants enrolled in RENEWED at 2 years (with an additional up to 12-month window) after the last RENEW study visit (Week 32) in both ITT and PP populations. The primary endpoint was change in full-field VEP (FF-VEP) latency of the affected eye at RENEWED study visit versus baseline of the fellow eye in RENEW, comparing between participants who received opicinumab and placebo in RENEW. Clinical progression and severity of multiple sclerosis (MS) were assessed. A substudy evaluated latency recovery using multifocal VEP (mfVEP) as an exploratory endpoint. RESULTS:Of 82 RENEW participants, 52 (63.4 %; opicinumab n = 28, placebo n = 24) enrolled in and completed RENEWED. The adjusted mean (95 % CI) difference in FF-VEP latency delay between opicinumab and placebo groups was -6.0 (-14.6, 2.6) msec (p = 0.165) for the PP population and -4.5 (-12.6, 3.7) msec (p = 0.274) for the ITT population at the RENEWED study visit. Nominally significant improvement on mfVEP latency in the opicinumab group versus placebo was observed in participants of the mfVEP substudy (p = 0.009). In participants from the PP population without clinically definite MS (CDMS) at RENEW baseline,12 (55 %) in the opicinumab group and 12 (67 %) in the placebo group developed CDMS from enrollment in the RENEW study up to RENEWED Day 1; the estimated proportion of participants with CDMS at 2 years after the last study visit assessment in RENEW was lower when treated with opicinumab (0.50) than when treated with placebo (0.61) (hazard ratio p-value = 0.23). No benefit on visual acuity or other neurological functions was observed in the opicinumab group vs placebo in RENEWED. CONCLUSION/CONCLUSIONS:The numerically increased VEP latency recovery with opicinumab treatment in RENEWED was consistent with those observed in the parent study RENEW. However, the VEP latency and clinical data in RENEWED should be interpreted with caution, given the nature of the follow-up study, the small sample size and the limitation in study design.