Faculty Bibliography

BACKGROUND/UNASSIGNED:Growing clinical interest in psychedelic-assisted therapies has led to a second wave of research involving psilocybin, lysergic acid diethylamide (LSD), 3,4-methylenedioxymethamphetamine (MDMA) and other substances. Data suggests that these compounds have the potential to treat mental health conditions that are especially prevalent in older adults such as depression, anxiety, existential distress, and posttraumatic stress disorder. AIMS/UNASSIGNED:The goal of this study was to quantify the prevalence of older adults enrolled in psychedelic clinical trials and explore safety data in this population. METHODS/UNASSIGNED:A systematic review was conducted following the 2020 PRISMA guidelines. Search criteria included all trials published in English using psychedelic substances to treat psychiatric conditions, including addiction as well as existential distress related to serious illness. Articles were identified from literature searches on PubMed, EBSCO, and EMBASE. RESULTS/UNASSIGNED:4376 manuscripts were identified, of which 505 qualified for further review, with 36 eventually meeting eligibility criteria. Of the 1400 patients enrolled in the 36 studies, only 19 were identified as 65 or older, representing less than 1.4% of all trial participants. For 10 of these 19 older adults, detailed safety data was obtained. No serious adverse events (AEs) occurred in any older adults and only transient mild-to-moderate AEs related to anxiety, gastrointestinal upset, and hypertension were reported during the psychedelic dosing sessions. CONCLUSIONS/UNASSIGNED:While existing data in older adults is limited, it suggests that psychedelic-assisted psychotherapy can be safe and well tolerated in older adults. Therefore, psychedelic-assisted psychotherapy should be more rigorously investigated for the treatment of psychiatric conditions in this population.

This study examines the effect of volunteering within a Professional Association of Therapeutic Horsemanship International (PATH Intl) premiere accredited center by exploring the experiences of volunteers leading horses in adaptive riding lessons. Adaptive Riding lessons are horseback riding lessons for individuals ages four through the lifespan, with special needs, varying from cognitive, physical, social-emotional, or other challenges. Volunteers directly impact the rider-horse bond by increasing accessibility to horseback riding for individuals with disabilities, fostering a meaningful bond between the rider and horse. The research questions were as follows: (1) do saliva measures of cortisol and alpha-amylase (stress), and oxytocin (affiliative bonding) change over time for volunteers; and (2) how satisfied are volunteers with volunteering for Equine Assisted Services (EAS)? Forty-one volunteers participated in Reining in Anxiety, an intervention combining adaptive riding and cognitive behavioral therapy. Physiological data (i.e., pooled saliva, saliva combined from various glands throughout the mouth, resting under the tongue prior to collection) were collected pre/post riding session at four time points during the 10-session intervention, measuring oxytocin, cortisol, and alpha-amylase. Post-intervention, volunteers completed a survey about their experiences as volunteers and as participants in the study. All saliva samples were collected successfully. There was a non-significant, positive trend in oxytocin and alpha-amylase, while cortisol remained level. The responses in the survey suggested that volunteers perceive their role positively, with nuanced experiences of a sense of responsibility to ensure safety, and enjoyment in assisting the riders. Volunteers are vital to the safety of the rider and horse. While their perceived and internalized responsibility is evidenced by an increase in stress (e.g., cortisol remaining level and an increase in alpha-amylase), it is not necessarily negative stress, as there is simultaneously affiliative bonding expressed (oxytocin). The complex emotions and experiences of volunteers are important to understand to create meaningful, sustainable volunteer engagement. This is particularly important in the EAS industry, which is reliant on volunteerism.

We conducted a prospective, single arm, multisite, multinational, open label trial assessing the safety and efficacy of a novel amygdala derived neurofeedback treatment, designated Amygdala-Derived-EFP, for chronic PTSD. Participants, including veterans and civilians, underwent screening, training, 15 neurofeedback sessions over 8 weeks and; baseline, termination (8 weeks) and 3 month post treatment assessments with validated measures. The primary endpoint was more than 50 % of the participants demonstrating a Minimally Clinically Important Difference (MCID) defined as a 6-point reduction, on the Clinician Administered PTSD Scale (CAPS-5) total score at 3 months. Secondary measures included the PCL-5, ERQ, PHQ-9, and CGI. Statistical analyses were performed using SAS®V9.4. The primary endpoint was met, with a CAPS-5 MCID response rate of 66.7 %. The average reduction in CAPS-5 total scores at 3 month follow up was 13.5 points, more than twice the MCID. Changes from baseline in CAPS-5, PCL-5, PHQ-9 scores at 8 weeks and the 3 month follow-up demonstrated statistically significant improvements in response and; demonstrated effect sizes ranging from 0.46 to 1.07. Adverse events were mild and resolved after treatment. This study builds on prior research demonstrating similar outcomes using amygdala-derived neurofeedback. Positive attributes of this therapy include monitoring by non-physician personnel, affordability, accessibility, and tolerability.

BACKGROUND/UNASSIGNED:Precision medicine has led to the development of targeted treatment strategies tailored to individual patients based on their characteristics and disease manifestations. Although precision medicine often focuses on a single health outcome for individualized treatment decision rules (ITRs), relying only on a single outcome rather than all available outcomes information leads to suboptimal data usage when developing optimal ITRs. METHODS/UNASSIGNED:To address this limitation, we propose a Bayesian multivariate hierarchical model that leverages the wealth of correlated health outcomes collected in clinical trials. The approach jointly models mixed types of correlated outcomes, facilitating the "borrowing of information" across the multivariate outcomes, and results in a more accurate estimation of heterogeneous treatment effects compared to using single regression models for each outcome. We develop a treatment benefit index, which quantifies the relative treatment benefit of the experimental treatment over the control treatment, based on the proposed multivariate outcome model. RESULTS/UNASSIGNED:We demonstrate the strengths of the proposed approach through extensive simulations and an application to an international Coronavirus Disease 2019 (COVID-19) treatment trial. Simulation results indicate that the proposed method reduces the occurrence of erroneous treatment decisions compared to a single regression model for a single health outcome. Additionally, the sensitivity analysis demonstrates the robustness of the model across various study scenarios. Application of the method to the COVID-19 trial exhibits improvements in estimating the individual-level treatment efficacy (indicated by narrower credible intervals for odds ratios) and optimal ITRs. CONCLUSION/UNASSIGNED:The study jointly models mixed types of outcomes in the context of developing ITRs. By considering multiple health outcomes, the proposed approach can advance the development of more effective and reliable personalized treatment.

The non-reporting of negative studies results in a scientific record that is incomplete, one-sided and misleading. The consequences of this range from inappropriate initiation of further studies that might put participants at unnecessary risk to treatment guidelines that may be in error, thus compromising day-to-day clinical practice.

IMPORTANCE/UNASSIGNED:Prenatal alcohol exposure (PAE) and prenatal tobacco exposure (PTE) are risk factors associated with adverse neurobehavioral and cognitive outcomes. OBJECTIVE/UNASSIGNED:To quantify long-term associations of PAE and PTE with brain activity in early and middle childhood via electroencephalography (EEG). DESIGN, SETTING, AND PARTICIPANTS/UNASSIGNED:This cohort study included participants enrolled in the Safe Passage Study (August 2007 to January 2015), from which a subset of 649 participants were followed up in the Environmental Influences on Child Health Outcomes Program. From September 2018 through November 2022, EEG recordings were obtained at ages 4, 5, 7, 9, or 11 years. Data were analyzed from November 2022 to November 2023. EXPOSURES/UNASSIGNED:Maternal self-reported consumptions of alcohol and tobacco during pregnancy were captured at the recruitment interview and at up to 3 visits during pregnancy (20-24, 28-32, and ≥34 weeks' gestation). Classifications of PAE (continuous drinking, quit-early drinking, and nondrinking) and PTE (continuous smoking, quit-early smoking, and nonsmoking) were previously obtained. MAIN OUTCOMES AND MEASURES/UNASSIGNED:EEG band powers (theta, alpha, beta, gamma) were extracted from the EEG recordings. Linear regression models were used to estimate the associations of PAE and PTE with EEG estimates. RESULTS/UNASSIGNED:The final sample included 649 participants (333 [51.3%] female) aged 4, 5, 7, 9, or 11 years. Children whose mothers were in the quit-early drinking cluster had increased alpha power (0.116 [95% CI, 0.023 to 0.209] μV2; P = .02) compared with individuals without PAE. The magnitude of this increase was approximately double for children exposed to continuous drinking (0.211 [95% CI, 0.005 to 0.417] μV2; P = .04). Children whose mothers were in the continuous smoking cluster had decreased beta power (-0.031 [95% CI, -0.059 to -0.003] μV2; P = .03) and gamma power (-0.020 [95% CI, -0.039 to -0.000] μV2; P = .04) compared with the nonsmoking cluster. In exploratory sex-stratified models, male participants in the quit-early PAE cluster had greater EEG power in the alpha band (0.159 [95% CI, 0.003 to 0.315] μV2; P = .04) compared with those with no PAE, and the difference was approximately double for male participants with continuous PAE (0.354 [95% CI, 0.041 to 0.667] μV2; P = .03). Male participants in the continuous PTE cluster had decreased beta (-0.048 [95% CI, -0.090 to - 0.007] μV2; P = .02) and gamma (-0.032 [95% CI, -0.061 - 0.002] μV2; P = .04) power compared with those with no PTE. CONCLUSIONS AND RELEVANCE/UNASSIGNED:These findings suggest that even low levels of PAE and PTE were associated with long-term alterations of brain activity.

Background: The Summer Treatment Program (STP) for youth with attention-deficit/hyperactivity disorder (ADHD) includes a Daily Report Card (DRC) intervention administered by staff to provide feedback and contingencies for child behavior. The DRC has also been implemented by teachers in school settings, but less is known about parent implementation. Objective: Given the importance of supporting parenting efficacy and child behavior in the home setting, this study evaluated a parent-implemented DRC concurrent to STP participation to examine predictors and associated changes for parenting efficacy and child in home behavior. Method: Forty-three youth (and their caregivers) participated in dynamically adjusted home-based DRC during their participation in a traditional STP during the day. Results: Home DRC contingencies significantly predicted parenting efficacy scores, including when home goals were both emphasized and removed. Parenting efficacy also differed by targeted behavior problem. Conclusion: These findings replicate and extend previous work on leveraging DRCs to support generalization of skills in the STP to home.

The increasing administrative prevalence of Attention-Deficit Hyperactivity Disorder (ADHD) over recent years has correspondingly escalated the prescriptions of pharmacological treatments for ADHD, particularly methylphenidate (MPH), which remains the most extensively prescribed medication for this condition. In light of this trend, evaluating the long-term risks associated with using MPH is important. This article aims to present findings from studies concerning the long-term use of MPH, derived from a literature review of the past decade, primarily focusing on data sourced from PubMed to assess these risks. Our review has drawn on a diverse range of studies, including cohort studies, meta-analyses, and database reviews from various global regions, reflecting a comprehensive international perspective on the long-term safety of MPH. Our review highlights several key aspects. Initial worries about the adverse psychiatric effects of MPH did not find strong support in subsequent studies. Rather, the current body of literature suggests that MPH may have a protective effect against depression and substance use disorders. We found no significant increase in the likelihood of suicide or psychotic disorders among long-term users of MPH. In fact, studies indicate that MPH treatment might reduce the incidence of depression. Moreover, contrary to concerns that stimulant treatment might predispose individuals to SUDs, recent longitudinal studies have generally shown no increased risk of substance misuse. Some studies have even suggested a lower incidence of substance misuse among patients treated with MPH. The review also delved into cardiovascular risks, which have been a notable concern with long-term MPH usage. While short-term studies typically showed minimal cardiovascular risks, results on longer-term effects suggest potential increases in hypertension and other arterial diseases for a higher dosage, highlighting the necessity for careful cardiovascular monitoring in patients undergoing long-term treatment. No elevated risk was described concerning other cardiovascular diseases. Results regarding the impact on growth have been mixed. Some studies suggest a temporary reduction in growth velocity that normalizes over time. This pattern suggests a delayed, rather than permanently stunted, growth trajectory in children treated with MPH over the long term. Lastly, our review did not find any risk of testicular dysfunction in patients treated with MPH. The collective findings from the reviewed studies offer reassurance regarding several of the initial concerns about the long-term use of MPH. While there are concerns about potential hypertension and arterial disease risks and uncertainties regarding growth, it is important to regularly monitoring for patients using MPH. These findings should be communicated transparently to patients and their families, helping to inform shared decision-making about the initiation and continuation of MPH therapy for ADHD. As research continues to evolve, it is imperative to keep updating our understanding of the safety of MPH safety profile to optimize treatment strategies and ensure that patients receive the most effective and safe care possible.