Faculty Bibliography

INTRODUCTION/BACKGROUND:Given the high prevalence of mental health disorders and their significant socioeconomic burden, there is a need to develop improved treatments, and to evaluate them through placebo-controlled trials. However, the magnitude of the placebo response in randomised controlled trials to test medications may be substantial, affecting their interpretation. Therefore, improved understanding of the patient, trial and mental disorder factors that influence placebo responses would inform clinical trial design to better detect active treatment effects. There is a growing literature exploring the placebo response within specific mental health disorders, but no overarching synthesis of this research has been produced to date. We present a protocol for an umbrella review of systematic reviews and/or meta-analyses in which we aim to understand the effect size and potential predictors of placebo response within, and across, mental health disorders. METHODS AND ANALYSIS/METHODS:We will systematically search databases (Medline, PsycINFO, EMBASE+EMBASE Classic, Web of Knowledge) for systematic reviews and/or meta-analyses that report placebo effect size in clinical trials in patients with mental health disorders (initial search date 23 October 2022). Screening of abstracts and full texts will be done in pairs. We will extract data to qualitatively examine how placebo effect size varies across mental health disorders. We also plan to qualitatively summarise predictors of increased placebo response identified either quantitatively (eg, through meta-regression) or qualitatively. Risk of bias will be assessed using the AMSTAR-2 tool. We aim to not only summarise the current literature but also to identify gaps in knowledge and generate further hypotheses. ETHICS AND DISSEMINATION/BACKGROUND:We do not believe there are any specific ethical considerations relevant to this study. We will publish the results in a peer-reviewed journal.

Autism spectrum disorder (ASD) is a type of neurodevelopmental disorder that has been diagnosed in an increasing number of children around the world. The existing data suggest that early diagnosis and intervention can improve ASD outcomes. The causes of ASD remain complex and unclear, and there are currently no clinical biomarkers for autism spectrum disorder. There is an increasing recognition that ASD might be associated with oxidative stress through several mechanisms including abnormal metabolism (lipid peroxidation) and the toxic buildup of reactive oxygen species (ROS). Glutathione acts as an antioxidant, a free radical scavenger and a detoxifying agent. This open-label pilot study investigates the tolerability and effectiveness of oral supplementation with Opitac^TM gluthathione as a treatment for patients with ASD. The various aspects of glutathione Opitac^TM glutathione bioavailability were examined when administered by oral routes. The absorption of glutathione from the gastrointestinal tract has been recently investigated. The results of this case series suggest that oral glutathione supplementation may improve oxidative markers, but this does not necessarily translate to the observed clinical improvement of subjects with ASD. The study reports a good safety profile of glutathione use, with stomach upset reported in four out of six subjects. This article discusses the role of the gut microbiome and redox balance in ASD and notes that a high baseline oxidative burden may make some patients poor responders to glutathione supplementation. In conclusion, an imbalance in redox reactions is only one of the many factors contributing to ASD, and further studies are necessary to investigate other factors, such as impaired neurotransmission, immune dysregulation in the brain, and mitochondrial dysfunction.

UNLABELLED:Interictal spikes (IIS) and seizures are well-documented in Alzheimer's disease (AD). IIS typically outnumber seizures, supporting their role as a prominent EEG biomarker in AD. In preclinical models, we showed that high frequency oscillations (HFOs>250Hz) also occur, but it is currently unknown how HFOs compare to IIS. Therefore, we asked whether the incidence of HFOs and IIS differed and if they are differentially affected by behavioral state. We used three mouse lines that simulate aspects of AD: Tg2576, presenilin 2 knockout, and Ts65Dn mice. We recorded and quantified HFOs and IIS in the hippocampus during wakefulness, slow-wave sleep, and rapid eye movement sleep. In all three mouse lines, HFOs were more frequent than IIS. High numbers of HFOs correlated with fewer IIS, suggesting for the first time possible competing dynamics among them in AD. Notably, HFOs occurred in more behavioral states than IIS. In summary, HFOs were the most abundant EEG abnormality when compared to IIS, and occurred in all behavioral states, suggesting they are a better biomarker than IIS. These findings pertained to three mouse lines, which is important because they simulate different aspects of AD. We also show that HFOs may inhibit IIS. SHORT SUMMARY/OBJECTIVE:Interictal spikes (IIS) and seizures are common in Alzheimer's disease (AD). IIS are more frequent than seizures and occur during earlier disease stages. In preclinical models, we showed that high frequency oscillations (HFOs>250Hz) occur, but a comparison between IIS and HFOs is lacking. Here we used 3 mouse lines with AD features and local field potential recordings to quantify IIS and HFOs. We found that HFOs outnumbered IIS and that their total numbers were inversely correlated with IIS. HFOs occurred during more behavioral states than IIS. Therefore, HFOs were the most abundant EEG abnormality, and this was generalizable across 3 types of preclinical AD.

An explanatory, parallel mixed method design was used to examine trauma screening and behavioral health service rates in urban school-based health centers (SBHCs) and SBHC personnel's experiences providing culturally responsive, trauma-informed care. Logistic regressions were performed with electronic medical records from N = 4,794 patients ages 12-22 receiving care in a SBHC using trauma screening rates and service use as dependent variables. Quantitative analyses were supplemented with semistructured interviews with medical providers and behavioral health clinicians (N = 9) from eight SBHCs. The overall trauma screening rate across the SBHCs was 69.2%. Screening rates were higher for older and Spanish-speaking youth. The rate of behavioral health use was 32.9%, with higher rates among students screened for trauma at a prior medical visit, recent immigrant, and female youth. This suggests that trauma screening is feasible and facilitates access. Additionally, English-speaking youth were more likely to use behavioral health services than Spanish-speakers. Qualitative analyses suggested a strong sense of mission, collaboration, and beliefs that trauma screening facilitated access to care all facilitated trauma-focused screening. Barriers included staffing shortages and language translation challenges. Analysis also highlighted the importance of culturally responsive practices (e.g., interpreters, culture-specific assessment tools, knowledge of population needs). Mixed methods integrative analysis highlighted the ways in which barriers and facilitators aligned with the overall rates of access to screening and behavioral health care, and factors that helped the SBHCs tailor care to diverse youth. Limitations and implications for practice are discussed. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

BACKGROUND:The striatal-pallidal pathway plays an important role in cognitive control and modulation of behaviors. Globus pallidus interna (GPi), as a primary output structure, is crucial in modulating excitation and inhibition. Studies of GPi in psychiatric illnesses are lacking given the technical challenges of examining this small and functionally diverse subcortical structure. METHODS:71 medication-naïve first episode schizophrenia (FES) participants and 73 healthy controls (HC) were recruited at the Shanghai Mental Health Center. Clinical symptoms and imaging data were collected at baseline and, in a subset of patients, 8 weeks after initiating treatment. Resting-state functional connectivity of sub-regions of the GP were assessed using a novel mask that combines two atlases to create 8 ROIs in the GP. RESULTS: = 0.486, p < 0.001). CONCLUSIONS:Our results implicate striatal-pallidal-thalamic pathways in antipsychotic efficacy. If replicated, these findings may reflect failure of neurodevelopmental processes in adolescence and early adulthood that decrease functional connectivity as an index of failure of the limbic/associative GPi to appropriately inhibit irrelevant signals in psychosis.

OBJECTIVES/OBJECTIVE:Developmentally specified measures that identify clinically salient irritability are needed for early school-age youth to meaningfully capture this transdiagnostic risk factor for psychopathology. Thus, the current study modeled the normal:abnormal irritability spectrum and generated a clinically optimized screening tool for this population. METHODS:The irritability spectrum was modeled via the youth version of the Multidimensional Assessment Profile Scales-Temper Loss Scale (MAPS-TL-Youth) in children (n = 474; 6.0-8.9 years) using item response theory (IRT). Both cross-cutting core irritability items from the early childhood version and new developmentally specific items were included. Items uniquely associated with impairment were identified and used to derive a brief, clinically optimized irritability screener. Longitudinal data were then utilized to test the predictive utility of this clinically optimized screener in preadolescence (n = 348; 8.0-12.9 years). RESULTS:Most children exhibit irritability regularly, but daily occurrence was rare. Of the top 10 most severe items from the IRT analyses, 9 were from the developmentally specific items added for the MAPS-TL Youth version. Two items associated with concurrent impairment were identified for the clinically optimized irritability screener ("Become frustrated easily" and "Act irritable"). The MAPS-TL-Youth clinically optimized screener demonstrated good sensitivity (69%) and specificity (84%) in relation to concurrent DSM 5 irritability-related diagnoses. Youth with elevated scores on the screener at early school age (ESA) had more than 7x greater odds of irritability-related psychopathology at pre-adolescence. CONCLUSIONS:The MAPS-TL-Youth characterized the developmental spectrum of irritability at ESA and a clinically optimized screener showed promise at predicting psychopathology risk. Rigorous testing of clinical applications is a critical next step.

OBJECTIVE/UNASSIGNED:To document the experience of 14 academic child and adolescent psychiatry programs in transitioning to and managing telehealth services during the COVID-19 pandemic. The goal was to understand how programs adopted and sustained telehealth during the pandemic. Telehealth was defined as services delivered via videoconferencing and telephony. METHOD/UNASSIGNED:In this descriptive study, faculty from 14 programs completed online surveys about the use of both telehealth and in-person services from February 2020 to June 2021. Survey questions addressed telehealth practices (e.g., policies, support resources), monthly service utilization, telehealth modality (videoconferencing vs. telephony), and missed appointments. RESULTS/UNASSIGNED:Programs varied in the proportion of appointments delivered by telehealth prior to the pandemic (February 2020; 0-27%). By May 2020 all programs were providing a majority of visits via telehealth (64-100%). In June 2021, all programs continued to provide services via telehealth (41% to 100%) and reported that they would continue to do so moving forward. Programs addressed many challenges to telehealth provision during the study period, including adding interpreter services, technological support for providers and patients, and formalizing safety and training requirements. CONCLUSION/UNASSIGNED:Academic child and adolescent psychiatry programs provided outpatient services primarily via telehealth throughout the COVID-19 pandemic and reported that they planned to continue utilizing telehealth in combination with in-person services moving forward. Academic programs should therefore address logistical, technological, and financial barriers to the sustained use of telehealth.