Benefits managers' attitudes toward obesity treatment coverage.

Despite the existence of effective treatments, obesity continues to present a severe public health crisis. Limited access to treatments works against efforts to reduce obesity prevalence. A major barrier to treatment access is a lack of insurance coverage. This study focused on an important population of stakeholders: benefits managers. The purpose of this study was to explore the relationships between attitudes about insurance coverage of obesity treatments and obesity stigma. Benefits managers have the ability to advocate for insurance coverage of medical interventions. We assessed whether attitudes toward covering obesity benefits for employees could be modified by receiving targeted information or were associated with particular factors. We recruited participants from Dun & Bradstreet's employer database using emails. Participants were randomized to one of three conditions that provided written information about: (1) prevalence of obesity (control), (2) prevalence + financial implications of obesity, and (3) prevalence + physiology of obesity. Questionnaires were self-administered online. The response rate was 4.8%, with 404 participants meeting eligibility criteria. While attitudes toward coverage of obesity interventions did not differ significantly based on condition (p > 0.05), gender, history of previous obesity treatment, and an individual's likelihood to attribute obesity to biological and environmental factors showed significant associations with supporting coverage of obesity treatment (p < 0.05). Findings suggest that understanding obesity as a condition caused by biological factors as opposed to personal responsibility and behavior is associated with greater support for coverage of all its treatments.

A Suicide Prevention Intervention for Emerging Adult Sexual and Gender Minority Groups: Protocol for a Pilot Hybrid Effectiveness Randomized Controlled Trial.

BACKGROUND: Suicide attempts and suicide death disproportionately affect sexual and gender minority emerging adults (age 18-24 years). However, suicide prevention strategies tailored for emerging adult sexual and gender minority (EA-SGM) groups are not widely available. The Safety Planning Intervention (SPI) has strong evidence for reducing the risk for suicide in the general population, but it is unclear how best to support EA-SGM groups in their use of a safety plan. Our intervention (Supporting Transitions to Adulthood and Reducing Suicide [STARS]) builds on content from an existing life skills mobile app for adolescent men who have sex with men (iREACH) and seeks to target core risk factors for suicide among EA-SGM groups, namely, positive affect, discrimination, and social disconnection. The mobile app is delivered to participants randomized to STARS alongside 6 peer mentoring sessions to support the use of the safety plan and other life skills from the app to ultimately reduce suicide risk. OBJECTIVE: We will pilot-test the combination of peer mentoring alongside an app-based intervention (STARS) designed to reduce suicidal ideation and behaviors. STARS will include suicide prevention content and will target positive affect, discrimination, and social support. After an in-person SPI with a clinician, STARS users can access content and activities to increase their intention to use SPI and overcome obstacles to its use. EA-SGM groups will be randomized to receive either SPI alone or STARS and will be assessed for 6 months. METHODS: Guided by the RE-AIM (reach, efficacy, adoption, implementation, and maintenance) framework, we will recruit and enroll a racially and ethnically diverse sample of 60 EA-SGM individuals reporting past-month suicidal ideation. Using a type-1 effectiveness-implementation hybrid design, participants will be randomized to receive SPI (control arm) or to receive SPI alongside STARS (intervention arm). We will follow the participants for 6 months, with evaluations at 2, 4, and 6 months. Preliminary effectiveness outcomes (suicidal ideation and behavior) and hypothesized mechanisms of change (positive affect, coping with discrimination, and social support) will serve as our primary outcomes. Secondary outcomes include key implementation indicators, including participants' willingness and adoption of SPI and STARS and staff's experiences with delivering the program. RESULTS: Study activities began in September 2021 and are ongoing. The study was approved by the institutional review board of the University of Pennsylvania (protocol number 849500). Study recruitment began on October 14, 2022. CONCLUSIONS: This project will be among the first tailored, mobile-based interventions for EA-SGM groups at risk for suicide. This project is responsive to the documented gaps for this population: approaches that address chosen family, focus on a life-course perspective, web approaches, and focus on health equity and provision of additional services relevant to sexual and gender minority youth. TRIAL REGISTRATION: ClinicalTrials.gov NCT05018143; https://classic.clinicaltrials.gov/ct2/show/NCT05018143. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/48177.

Calcitonin receptor signaling in nucleus accumbens D1R- and D2R-expressing medium spiny neurons bidirectionally alters opioid taking in male rats.

The high rates of relapse associated with current medications used to treat opioid use disorder (OUD) necessitate research that expands our understanding of the neural mechanisms regulating opioid taking to identify molecular substrates that could be targeted by novel pharmacotherapies to treat OUD. Recent studies show that activation of calcitonin receptors (CTRs) is sufficient to reduce the rewarding effects of addictive drugs in rodents. However, the role of central CTR signaling in opioid-mediated behaviors has not been studied. Here, we used single nuclei RNA sequencing (snRNA-seq), fluorescent in situ hybridization (FISH), and immunohistochemistry (IHC) to characterize cell type-specific patterns of CTR expression in the nucleus accumbens (NAc), a brain region that plays a critical role in voluntary drug taking. Using these approaches, we identified CTRs expressed on D1R- and D2R-expressing medium spiny neurons (MSNs) in the medial shell subregion of the NAc. Interestingly, Calcr transcripts were expressed at higher levels in D2R- versus D1R-expressing MSNs. Cre-dependent viral-mediated miRNA knockdown of CTRs in transgenic male rats was then used to determine the functional significance of endogenous CTR signaling in opioid taking. We discovered that reduced CTR expression specifically in D1R-expressing MSNs potentiated/augmented opioid self-administration. In contrast, reduced CTR expression specifically in D2R-expressing MSNs attenuated opioid self-administration. These findings highlight a novel cell type-specific mechanism by which CTR signaling in the ventral striatum bidirectionally modulates voluntary opioid taking and support future studies aimed at targeting central CTR-expressing circuits to treat OUD.

Single nucleus transcriptomic analysis of rat nucleus accumbens reveals cell type-specific patterns of gene expression associated with volitional morphine intake.

Opioid exposure is known to cause transcriptomic changes in the nucleus accumbens (NAc). However, no studies to date have investigated cell type-specific transcriptomic changes associated with volitional opioid taking. Here, we use single nucleus RNA sequencing (snRNAseq) to comprehensively characterize cell type-specific alterations of the NAc transcriptome in rats self-administering morphine. One cohort of male Brown Norway rats was injected with acute morphine (10 mg/kg, i.p.) or saline. A second cohort of rats was allowed to self-administer intravenous morphine (1.0 mg/kg/infusion) for 10 consecutive days. Each morphine-experienced rat was paired with a yoked saline control rat. snRNAseq libraries were generated from NAc punches and used to identify cell type-specific gene expression changes associated with volitional morphine taking. We identified 1106 differentially expressed genes (DEGs) in the acute morphine group, compared to 2453 DEGs in the morphine self-administration group, across 27 distinct cell clusters. Importantly, we identified 1329 DEGs that were specific to morphine self-administration. DEGs were identified in novel clusters of astrocytes, oligodendrocytes, and D1R- and D2R-expressing medium spiny neurons in the NAc. Cell type-specific DEGs included Rgs9, Celf5, Oprm1, and Pde10a. Upregulation of Rgs9 and Celf5 in D2R-expressing neurons was validated by RNAscope. Approximately 85% of all oligodendrocyte DEGs, nearly all of which were associated with morphine taking, were identified in two subtypes. Bioinformatic analyses identified cell type-specific upstream regulatory mechanisms of the observed transcriptome alterations and downstream signaling pathways, including both novel and previously identified molecular pathways. These findings show that volitional morphine taking is associated with distinct cell type-specific transcriptomic changes in the rat NAc and highlight specific striatal cell populations and novel molecular substrates that could be targeted to reduce compulsive opioid taking.

A novel approach to treating opioid use disorders: Dual agonists of glucagon-like peptide-1 receptors and neuropeptide Y2 receptors.

The widespread misuse of opioids and opioid use disorder (OUD) together constitute a major public health crisis in the United States. The greatest challenge for successfully treating OUD is preventing relapse. Unfortunately, there are few FDA-approved medications to treat OUD and, while effective, these pharmacotherapies are limited by high relapse rates. Thus, there is a critical need for conceptually new approaches to developing novel medications to treat OUD. Here, we review an emerging preclinical literature that suggests that glucagon-like peptide-1 receptor (GLP-1R) agonists could be re-purposed for treating OUD. Potential limitations of this approach are also discussed along with an alternative strategy that involves simultaneously targeting and activating GLP-1Rs and neuropeptide Y2 receptors (Y2Rs) in the brain using a novel monomeric dual agonist peptide. Recent studies indicate that this combinatorial pharmacotherapy approach attenuates voluntary fentanyl taking and seeking in rats without producing adverse effects associated with GLP-1R agonist monotherapy alone. While future studies are required to comprehensively determine the behavioral effects of GLP-1R agonists and dual agonists of GLP-1Rs and Y2Rs in rodent models of OUD, these provocative preclinical findings highlight a potential new GLP-1R-based approach to preventing relapse in humans with OUD.