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NIDA - National Institute on Drug Abuse

PROJECT SUMMARY/ABSTRACT Despite often being used legally, cannabis use is associated with several harmful outcomes (e.g., mental health problems). Moreover, cannabis use is disproportionately higher among sexual minorities (SM) relative to their heterosexual counterparts. SM who use cannabis are also more likely to develop cannabis use disorder (CUD) compared to heterosexuals. Our understanding of mechanisms that explain disparities in SM cannabis use outcomes is nascent. In line with NIDA’s funding priorities to identify mechanisms underlying differences in SM drug use outcomes, this K99/R00 application aims to evaluate mediators of associations between minority stressors, cannabis use, and use-related negative outcomes among young adult SM. The minority stress psychological mediation framework posits that minority stressors result in substance use outcomes through impaired coping, interpersonal, and cognitive processes. This model has support for SM alcohol use; however, only eight studies have tested putative mechanisms explaining how minority stressors relate to cannabis use. Among these studies, many are cross-sectional and most solely test coping motives mediation. Longitudinal research examining how minority stressors and these mechanisms relate to use and negative outcomes (e.g., CUD) is necessary to address these research gaps and advance understanding of SM health. Moreover, identifying how daily experiences relate to use will provide targets for prevention and intervention development, particularly when certain experiences (e.g., stigma) may be unavoidable. This K99/R00 study leverages ecological momentary assessment (EMA) to capture real-time measures in daily life of stressors, cannabis use, and related outcomes. Foundational work during the K99 phase will collect data to inform EMA item development (Aim 1), then conduct an EMA feasibility and acceptability study (Aim 2). Dr. Parnes’ training goals include (1) refine skills to independently design, develop, execute, and analyze EMA research, (2) build expertise in conducting substance use research with SM populations, (3) continue training in advanced statistical modeling of EMA data, and (4) promote a successful transition from postdoctoral fellow to independent faculty researcher. Dr. Parnes’ mentorship team, Drs. Miranda, Mereish, and Treloar Padovano, are experts in EMA, sexual minority research, and advanced statistical analysis. These training goals build on Dr. Parnes’ F32 (DA054718), which provided foundational training in identifying mechanisms of behavior change in adolescent cannabis treatment. Using the protocol finalized through the K00, the R00 study will conduct a 30-day EMA study among SM who use cannabis to test putative mechanisms relating daily minority stressors to use-related negative outcomes (Aim 3). Findings from the proposed study will inform whether and how SM minority stressors relate to harmful use-related outcomes. Evaluating mechanisms can also be used to identify intervention targets to complement or replace cannabis use, thus reducing liability for CUD or other negative outcomes, and reducing known health disparities in this population.

NIMH - National Institute of Mental Health

Grant Summary Neuromodulatory systems—comprising noradrenergic, serotonergic, cholinergic, and dopaminergic neurons—play a critical role in regulating mood, cognition, motor control, and physiological processes. These systems are central to understanding how the brain encodes reward, action selection, and memory, and they remain key therapeutic targets for neuropsychiatric and neurodegenerative disorders. Recent advances in high-throughput single-cell and spatial genomics have revealed a remarkable diversity among neuromodulatory cell types, with dozens to hundreds of distinct subpopulations. Despite this, tools capable of targeting these subpopulations with precision remain limited, hindering progress in both basic and translational neuroscience. This project seeks to address this gap by developing a comprehensive pipeline to nominate, validate, and disseminate cell-type-specific enhancers for neuromodulatory systems. Building upon prior successes in enhancer discovery for cortical interneurons and pyramidal neurons, we will employ advanced spatial multiomic profiling, computational prediction, and high-throughput AAV-based enhancer testing to generate a robust set of validated enhancers. Specifically, we will: 1) Nominate candidate enhancers by integrating publicly available data and performing spatial multiomic profiling on sorted cholinergic, dopaminergic, serotonergic, and noradrenergic cell types. 2) Quantitatively validate enhancer activity using cutting-edge techniques, including smFISH, Slide-Tag molecular profiling, and functional assays such as optogenetic and chemogenetic manipulation, neuronal activity monitoring, and CRISPR-based gene editing. 3) Disseminate validated tools through collaboration with the Allen Institute, Addgene, and other platforms, ensuring wide accessibility and standardization across the neuroscience community. The proposed research will produce at least 60 highly specific and validated enhancers targeting distinct neuromodulatory subpopulations, each characterized for their activity, specificity, and functional applications. These tools will be invaluable for studying neuromodulatory circuits in health and disease and for advancing therapeutic interventions targeting these systems. By providing the neuroscience community with these transformative tools, this project will facilitate unprecedented insights into the molecular and cellular underpinnings of brain function and dysfunction, addressing pressing challenges in the fields of psychiatry and neurology. The successful completion of this work will not only enable basic scientific discoveries but also lay the groundwork for the development of precision therapies for neuropsychiatric and neurodegenerative diseases.

NIMH - National Institute of Mental Health

PROJECT SUMMARY Major Depressive Disorder (MDD) and Generalized Anxiety Disorder (GAD) affect approximately 300 million people annually worldwide, with profound public health and economic consequences—lifetime prevalence in the U.S. approaches 1 in 3, healthcare costs exceed $40 billion per year, and existing treatments provide only modest relief. These disorders are characterized by persistent and recurrent negative emotional states, particularly during significant, personally meaningful events. However, most research in human affective neuroscience has relied on artificial affective stimuli that fail to evoke the intensity and relevance needed to capture real-world emotional dynamics, and moreover, prior studies have struggled to disentangle anticipatory processes (e.g., the emotional buildup before an event) from reactive processes (e.g., the emotional response to the event), especially within naturalistic conditions. This limitation has hindered progress in understanding the distinct yet interrelated mechanisms underlying emotion dysregulation in GAD and MDD. This study, building upon R21MH125311 (Heller, PI), addresses these critical gaps by leveraging a highly goal- relevant, emotionally impactful real-world event: undergraduate students receiving grades on challenging Chemistry ‘weed-out’ exams. Using fMRI to scan 144 participants (72 with GAD/MDD, 72 controls) across five sessions (four exam-related, one baseline), we will precisely delineate anticipatory and reactive neural processes over time. Advanced Hidden Markov Models will be applied to identify and differentiate negative affective brain states during anticipation, reaction, and recovery, providing insight into how these states emerge and persist. Preliminary findings suggest that hippocampal activity patterns may drive the recurrence of these states, offering novel clues to the neural circuit dynamics underlying emotion dysregulation in GAD and MDD. By using real-world, goal-relevant stimuli and cutting-edge computational tools, this will project uniquely disentangle anticipatory and reactive processes, capturing the full neural dynamics of naturalistic emotion. These insights into emotional brain states will inform the development of novel, brain-based interventions, directly targeting the mechanisms of emotional dysregulation and offering a path forward for improving mental health treatments.

NIMH - National Institute of Mental Health

PROJECT SUMMARY Disordered eating is a critical public health issue in the United States, due to the alarmingly high prevalence, and myriad of negative physical and psychosocial consequences. Adolescence is a critical developmental period for both the prevention and treatment of disordered eating. Many physical and social changes that occur in adolescence increase disordered eating risk, and early treatment intervention is imperative for treatment prognosis. However, social and environmental differences lead to high prevalence and worse clinical outcomes for disordered eating among rural adolescents. Rural adolescents face rates of disordered eating that are approximately double compared to nationally representative samples. Alarmingly high rates of disordered eating among rural adolescents are likely because they face unique social and structural influences that both increase the likelihood of developing disordered eating but also leads to lower likelihood of treatment. Factors that have been shown to be associated with increased risk of disordered eating in other populations are elevated in rural adolescents but also may be more iatrogenic in rural communities. For example, food insecurity is more common in rural populations, but harm may be further compounded by lack of access to healthful foods in rural communities. Additionally, rural adolescents may be more likely to delay or never receive care because of reduced treatment access and social stigma around mental health that is particularly pervasive in rural communities. It is also likely that factors such as social connectedness and body functionality appreciation may be uniquely protective for disordered eating in the rural context. However, there has never been a study designed to examine disordered eating risk factors, protective factors, or treatment obstacles specifically within rural adolescent populations. The proposed study would fill a critical gap in identifying the most salient risk factors, protective factors, and treatment obstacles as well as population-identified solutions within the context of rural adolescents. The study findings can be used to develop culturally relevant prevention and treatment interventions to reduce disordered eating rates among rural adolescents. We will use a concurrent triangulation mixed-methods approach including a cross-sectional survey (N=1,000) among rural high school students that will be analyzed using random forest algorithms, a machine learning technique, and semi-structured interviews (N=40) among rural high school students experiencing disordered eating, who both have and have not received treatment, to achieve the following specific aims: AIM 1: Determine the most salient risk/protective factors that predict disordered eating among rural emerging adults. AIM 2: Identify the most salient obstacles to disordered eating treatment that exist in rural communities and identify population- identified solutions to treatment obstacles.

NIMH - National Institute of Mental Health

PROJECT SUMMARY/ABSTRACT Despite advances in collecting large-scale behavioral datasets, our ability to gain insights into an individual’s learning and decision-making processes remains limited. This is particularly true for characterizing individual dif- ferences in task performance, or how behavior in psychological tasks relates to psychiatric symptoms. Progress towards this ambitious goal depends on computational models that formalize the relationships between behavioral observations, the underlying latent cognitive processes, and individual differences in behavior. Unfortunately, ex- isting modeling approaches are either too simple to handle the highly variable nature of behavior, or too complex to yield interpretable insights into the cognitive processes of interest. An approach combining flexibility and inter- pretability could transform our understanding of healthy decision-making and psychiatric conditions. This proposal addresses this critical need by developing a novel computational framework to model an individual’s learning and decision-making processes in a flexible and interpretable manner. The proposal focuses on reward learning due to its critical role in healthy and dysfunctional decision-making, as well as its prevalence in psychology. Critically, our approach captures behavioral idiosyncrasies in individual subjects, instead of focusing on group averages. To achieve this specificity without undue sacrifices in interpretability, our framework relies on two techniques: very small recurrent neural networks (RNNs) trained to imitate an individual’s behavior, and dynamical systems theory to interpret how the RNN converts observations into decisions. Our prior research shows these tiny RNNs predict individual choices more accurately than classical models while revealing complex, previously unobserved learning strategies. Preliminary analyses suggest this approach discovers relationships in strategy use across tasks and identifies distinct patterns of decision-making based on clinical diagnosis. The proposed work has two primary aims. First, we will validate the stability of individual differences across multiple decision-making tasks by relating subject-specific strategies across tasks. Second, we will relate cognitive processes to psychiatric symp- toms by examining how strategies vary with symptom severity. We will also predict psychiatric symptoms based on individual differences in strategies derived from the fitted RNN models. Both analyses will use a large dataset (N = 815) currently under acquisition in the research lab of co-investigator Dr. Catherine A. Hartley, which in- cludes data from three decision-making tasks and an array of psychiatric symptom assessments. Our approach is a novel integration of data-driven and theory-driven approaches for computational psychiatry, offering a frame- work that can benefit from large datasets while still providing theoretical insights. This ability to generate cognitive theories from data alone could accelerate the study of individual cognitive differences, and particularly benefit the study of mental health. Ultimately, this could lead to more precise diagnostic tools and targeted interventions for psychiatric conditions by providing deeper insights into the cognitive mechanisms underlying decision-making.

NIMH - National Institute of Mental Health

ABSTRACT HIV remains a major public health challenge in Kenya, with untreated depression complicating HIV care and impacting treatment adherence and viral suppression. Despite Kenya's success in meeting international HIV control targets to date, diagnosis and treatment of depression among people living with HIV (PLH) remains insufficiently addressed. Given the well-established adverse impacts of depression on HIV care outcomes, improving depression care is critically important to maintaining Kenya’s laudable progress in addressing their HIV epidemic. The 2022 Kenyan HIV Prevention and Treatment guidelines recommend at least annual use of the Patient Health Questionnaire-9 (PHQ-9) for depression screening in HIV care settings, but only 52% of PLH in care had been screened in the last year according to national administrative data. Our long-term goal is to improve rates of equitable screening, referral, and treatment for depression among PLH in Kenya, thereby improving HIV care outcomes. The objective of this R36 application is to leverage implementation science approaches to evaluate the current utilization of PHQ-9 screening in HIV clinics in Kenya. This project aims to evaluate the utilization of PHQ-9 screening in Kenyan HIV clinics using the Reach, Effectiveness, Adoption, Implementation, and Maintenance (RE-AIM) framework. This study will pursue three specific aims: (1) Estimate the prevalence of depression among PLH in Kenya and assess variations across key populations, clinic types, and geographic regions to inform targeted interventions. (2) Analyze the reach, effectiveness, and maintenance of PHQ-9 screening in government-funded HIV centers using electronic health record data, including evaluation of equity in screening based on demographic characteristics. (3) Conduct a qualitative evaluation of PHQ-9 implementation in three purposively selected HIV clinics in Kisumu, Kenya, exploring barriers and facilitators through in-depth interviews with purposively selected care providers. For aims 1 and 2, we will conduct quantitative analyses of nationally representative HIV program data. For aim 3, we will conduct qualitative, in-depth interviews with healthcare providers and staff at three selected HIV clinics in Kisumu, Kenya. This proposed research is highly significant because it aims to improve mental health integration into HIV care, enhance screening practices, and guide policy and program improvements, thereby advancing both mental health and HIV care outcomes in Kenya and potentially other African settings.

NIMH - National Institute of Mental Health

Project Summary Current methods for generating brain organoids are limited in their ability to mimic the spatial and structural complexity of the brain. Most organoid models lack reproducibility in cell-type patterning and tissue architecture, and they fail to capture the full cellular diversity seen in the brain. Brain organoids are typically generated by protocols that isotropically applying exogenous morphogens in the media, but they often produce oversimplified, poorly organized architectures and lack multi-regional interactions. A major limitation of these protocols is the lack of spatial control over morphogen signaling, which is a key driver of morphogenesis during natural development. Thus, there remains a critical need for scalable strategies that enable fine spatial and temporal control of morphogen signals to drive coordinated multi-axis and multi-regional patterning in brain organoids. We recently developed platform of engineered synthetic organizer cells – spatially self-assembling cells that produce morphogens from spatially defined positions. Here, we propose to use synthetic organizers to induce multi-axis patterning in 3D brain organoids. Our long-term goal of this exploratory project is to build platforms that produce reproducible, spatially organized brain tissues with greater complexity and functional relevance. Our specific aims are: Aim1: Construct synthetic organizers to control brain organoid axis formation. Engineer synthetic organizer cells (from cell lines) that produce morphogens involved in brain A–P and D–V differentiation (WNT3A, DKK1, FGF, CER, NOGGIN, BMP4 and SHH), providing a core toolkit. Aim2: Create synthetic gradients to shape A–P axis of brain organoids. Using tunable organizers at opposing poles that produce A–P morphogens (e.g. DKK1-Wnt), we can produce embryoids that cover selective ranges of the A–P axis body plan, including embryoids that primarily encompass the brain. We will optimize these organizer-driven brain organoids and use IHC, RNA scope and scRNA-seq to analyze the structures for neural subtypes and formation of key subregions (hind, mid and forebrain, as well as cortical layers). Aim3: Integrative multi-axis patterning in brain organoids. We will combine multiple synthetic organizers, arranged orthogonally to each other, to establish intersecting A–P and D–V axes. We will systematically and independently tune the following morphogen production organizers: WNT3A (posterior), DKK1/CER1/FGF8 (anterior), BMP4 (dorsal) and SHH (ventral). We will assess whether the resulting brain domains exhibit spatially organized A–P and D–V subregions and connections between subregions. Our central hypothesis is that synthetic organizers (programmable cellular morphogen sources) can be used to precisely and reproducible drive symmetry breaking and yield more complex and functional neural tissues. This work may provide a path toward more structured, reproducible, and physiologically relevant brain organoids, with applications in developmental biology, neuroscience, disease modeling, and neural engineering

National Institutes of Health

The purpose of this Notice of Funding Opportunity (NOFO) is to encourage applications to pursue invasive neural recording studies focused on mental health-relevant questions. Invasive neural recordings provide an unparalleled window into the human brain to explore the neural circuitry and neural dynamics underlying complex moods, emotions, cognitive functions, and behaviors with high spatial and temporal resolution. Additionally, the ability to stimulate, via the same electrodes, allows for direct causal tests by modulating network dynamics. This funding opportunity aims to target a gap in the scientific knowledge of neural circuit function related to mental health disorders. Researchers should target specific questions suited to invasive recording modalities that have high translational potential. Development of new technologies and therapies are outside the scope of this NOFO.

National Institutes of Health

The purpose of this Notice of Funding Opportunity (NOFO) is to encourage applications to pursue invasive neural recording studies focused on mental health-relevant questions. Invasive neural recordings provide an unparalleled window into the human brain to explore the neural circuitry and neural dynamics underlying complex moods, emotions, cognitive functions, and behaviors with high spatial and temporal resolution. Additionally, the ability to stimulate, via the same electrodes, allows for direct causal tests by modulating network dynamics. This funding opportunity aims to target a gap in the scientific knowledge of neural circuit function related to mental health disorders. Researchers should target specific questions suited to invasive recording modalities that have high translational potential. Development of new technologies and therapies are outside the scope of this NOFO.

National Institutes of Health

Reissue of RFA-20-351.The purpose of this Notice of Funding Opportunity (NOFO) is to encourage applications to pursue invasive neural recording studies focused on mental health-relevant questions. Invasive neural recordings provide an unparalleled window into the human brain to explore the neural circuitry and neural dynamics underlying complex moods, emotions, cognitive functions, and behaviors with high spatial and temporal resolution. Additionally, the ability to stimulate, via the same electrodes, allows for direct causal tests by modulating network dynamics. This funding opportunity aims to target a gap in the scientific knowledge of neural circuit function related to mental health disorders. Researchers should target specific questions suited to invasive recording modalities that have high translational potential. Development of new technologies and therapies are outside the scope of this NOFO.

National Institutes of Health

Reissue of RFA-20-351.The purpose of this Notice of Funding Opportunity (NOFO) is to encourage applications to pursue invasive neural recording studies focused on mental health-relevant questions. Invasive neural recordings provide an unparalleled window into the human brain to explore the neural circuitry and neural dynamics underlying complex moods, emotions, cognitive functions, and behaviors with high spatial and temporal resolution. Additionally, the ability to stimulate, via the same electrodes, allows for direct causal tests by modulating network dynamics. This funding opportunity aims to target a gap in the scientific knowledge of neural circuit function related to mental health disorders. Researchers should target specific questions suited to invasive recording modalities that have high translational potential. Development of new technologies and therapies are outside the scope of this NOFO.

NIMH - National Institute of Mental Health

BACKGROUND. Border identity groups—such as those who are bisexual/pansexual (bi+), Biracial/Multiracial, or gender nonbinary—challenge our nation's most basic group dichotomies (e.g., gay/straight, Black/White, man/woman) and are rapidly growing segments of the U.S. population. As NIH health disparity populations, it is unsurprising that border identity groups tend to demonstrate elevated HIV and mental health inequities as compared with the general U.S. population. However, more vexing are studies showing that bi+, Multiracial, and nonbinary people demonstrate greater sexual/mental health risk than their respective monosexual minority, monoracial minority, and binary gender minority counterparts. The potential drivers of these co-occurring health inequities are insufficiently theorized, poorly measured, and unevenly studied across groups. Yet, accumulating research supports an intriguing hypothesis—that bi+, Multiracial, and nonbinary populations demonstrate similar health risk profiles because, beyond traditional minority stressors, they are vulnerable to a distinct set of stigma-related stressors encountered by individuals holding identities that defy socially sanctioned dichotomies (i.e., border identity stressors). OBJECTIVE. In response to NIMH PAR-23-062 and NOT-MH-23-270, this R01 builds upon preliminary research to (a) develop a multigroup measure of border identity stress, (b) test a unified model of border identity stress, HIV risk, and mental health problems among bi+, Multiracial, and nonbinary adults, and (c) identify mutable mechanisms and protective factors concerning relations between border identity stress and co-occurring sexual and mental health risks. SPECIFIC AIMS. PI Jackson will work with Co-Is Bowleg, Esserman, Huynh, and Poteat to: develop a community-informed multigroup border identity stress scale—optimized for cross-sectional, longitudinal, and EMA HIV research (Aim 1); test longitudinally a conceptual model of border identity stress, HIV risk, and mental health—testing theorized mediators and moderators across bi+, Multiracial, and nonbinary adults (Aim 2); and detect relations between border identity stressors, daily HIV risk factors, and mental health symptoms among three higher-risk border identity subgroups via a 14-day microlongitudinal study—isolating daily mechanisms for intervention (Aim 3). SIGNIFICANCE. By highlighting how previously hidden forms of stigma drive health risk among bi+, Multiracial, and nonbinary adults, this model is poised to facilitate the development of much-needed interventions among three NIH health disparity groups disproportionately burdened by HIV—and is poised to shift how the field conceptualizes stigma, measures stigma-related stress, and combines stigmatized groups for study. DISSEMINATION. In addition to scholarly publications, we will produce and disseminate several scientific products (e.g., infographic summaries) for community members and health professionals, including: (1) bi+, Multiracial, and nonbinary research participants, (2) AIDS service organizations within Ending the HIV Epidemic priority jurisdictions, and (3) a national network of mental health providers serving stigmatized clients.

NIMH - National Institute of Mental Health

Project Summary / Abstract Chronic stress is a well-established contributor to neurobiological changes that influence behavioral responses to threat and uncertainty. The hippocampus plays a central role in stress-related plasticity, yet the specific circuits and molecular mechanisms through which stress alters hippocampal output remain incompletely defined. One pathway of interest is the projection from the ventral hippocampus to the medial prefrontal cortex (vHipp–mPFC), which has been implicated in modulating behavioral reactivity to aversive stimuli. My preliminary data indicate that chronic unpredictable stress (CUS) enhances activity in this circuit, coinciding with increased defensive behavioral responses. The current project aims to uncover the transcriptional mechanisms driving stress-induced hyperactivity in the vHipp–mPFC circuit and assess its causal role in stress-related behavioral adaptations. In Specific Aim 1, I will use circuit-specific labeling combined with single-nucleus RNA sequencing (snRNAseq) to identify stress-induced transcriptional changes in the vHipp–mPFC pathway following CUS. Then, I will assess the relevance of these changes to human pathology by comparing differentially expressed genes to single-nucleus data collected from individuals with post-traumatic stress disorder (PTSD) using the PsychENCODE human hippocampal PTSD dataset. In Specific Aim 2, I will use chemogenetic tools to bidirectionally manipulate vHipp–mPFC pathway activity in mice exposed to CUS to determine whether hyperactivity in this pathway is necessary and/or sufficient to drive changes in defensive behavior. The proposed research will advance our understanding of how chronic stress alters hippocampal-prefrontal circuits to influence behavior, potentially identifying new biomarkers or molecular targets for therapeutic development. The project integrates transcriptomic profiling, circuit-level manipulation, and behavioral analysis, providing me with comprehensive and rigorous training in both bioinformatics and systems neuroscience and preparing me for a career that integrates these fields to elucidate the neurobiology of stress-related disorders.

NIA - National Institute on Aging

PROJECT SUMMARY Aging is characterized by the gradual loss of physiological integrity, and this process may be accelerated in the presence of obesity, increasing susceptibility to disease, frailty, and death. Although the shared molecular pathways involved have not been fully elucidated, adipose tissue dysfunction is likely a key contributor to multisystem functional decline in aging and obesity. Despite growing evidence that β3 adrenergic receptor {β3AR) mediated activation of brown adipose tissue {BAT) may alter pathophysiological pathways implicated in various aging-related diseases including metabolic, cardiovascular, and neurodegenerative diseases, BAT has been largely ignored in aging research. In this highly innovative study, we propose to conduct a randomized, double-blind, placebo-controlled trial to investigate whether treatment with a β3AR agonist (vibegron) can improve energy metabolism, cardiometabolic risk factors, and physical and cognitive function. Vibegron {Gemtesa) was FDA-approved in 2020 for the treatment of overactive bladder and has greater selectivity, potency, and activity at the β3AR than other agonists studied to date. This presents a timely opportunity to explore pharmacological activation of β3ARs as a way to improve multiple health outcomes relevant in aging and obesity. To test our hypothesis, 40 middle-aged and older adults {45-75 yrs) with obesity will be randomized to vibegron {75 mg/day) or placebo for 12 weeks to compare their effects on various bioenergetic, cardiometabolic, physical function, and cognitive outcomes. Specifically, in Aim 1 we will assess the effects of vibegron vs. placebo on energy expenditure, core body temperature, mitochondrial bioenergetics, and thermogenic protein expression. In Aim 2 we will assess the effects of vibegron vs. placebo on glucose and insulin indices, lipid levels, body composition, and body fat distribution. In Aim 3 we will assess the effects of vibegron vs. placebo on self-report and objective measures of lower extremity function, muscle strength and pOY1er, global cognition, memory, executive function, quality of life, and depression. Notable innovations include blood-based bioenergetic profiling to assess systemic mitochondrial function, isolation and characterization of adipose tissue-derived small extracellular vesicles to assess target engagement, and continuous monitoring of core body temperature to assess circadian thermoregulation. In exploratory analyses we will compare the effects of vibegron vs. placebo on the accumulation of health deficits {i.e., frailty) and the preservation of physical and mental abilities {i.e., intrinsic capacity), two integrated measures of phenotypic aging that will provide estimates of the potential for vibegron to impact multisystem functional decline. This unique study will be the first clinical trial to explore the potential to repurpose vibegron for the treatment of aging-related obesity and associated comorbidities. If successful, the results of this study will be used to inform the design of a larger, longer trial to confirm the efficacy of vibegron as a novel treatment to IOY1er risk for multisystem functional decline in both aging and obesity.

NICHD - Eunice Kennedy Shriver National Institute of Child Health and Human Development

PROJECT SUMMARY / ABSTRACT This project will improve best practice care delivery and psychosocial outcomes for families of critically ill children hospitalized in the pediatric intensive care unit (PICU). The focus of this proposal is family-centered rounds (FCR), which is recognized as a best practice for hospitalized children. FCR enhances family-centered communication, engagement, understanding of the care plan, and trust in providers. Importantly, these benefits are also strategies to mitigate PICU-related psychosocial harms to family members of the critically ill child. However, FCR is only possible when parents or guardians (“parents” hereafter) can be physically at bedside during rounds. Yet circumstances that prevent physical presence (e.g., work, travel) hinder some families. PICUs lack evidence-based strategies to promote parents’ access to and attendance at FCR. We address this critical gap by testing a telehealth intervention to expand access to and attendance at FCR. We propose a dual cluster randomized trial, which is two simultaneous randomized trials: one testing the intervention of inviting families to use virtual FCR and one testing implementation strategies. Families will be randomized to one of three arms: (1) virtual FCR plus digital navigators (active implementation strategy), (2) virtual FCR plus informative handouts/videos (control implementation strategy), and (3) usual care. In this proposal, we pursue three Specific Aims: Evaluate and compare the impact of providing parents the option of virtual FCR versus usual care on parent FCR attendance, utilization, and psychosocial outcomes (Aim 1). Evaluate and compare two implementation strategies for virtual FCR (Aim 2). Conduct a mixed methods implementation evaluation of the virtual FCR intervention (Aim 3). Aims 1 and 2 will measure heterogeneity of intervention effects and implementation effects, respectively, by pre-specified subgroups. Our team’s preliminary research found that the option to use telehealth to conduct virtual FCR improved parent FCR attendance. All groups benefited from the intervention except for those with the lowest digital literacy and those without a smartphone. We thus build on our prior work to now propose a type 2 hybrid study utilizing the rigorous but underused dual randomized trial design. Our team’s expertise encompasses hospital care delivery interventions, clinical trials, implementation science, community engagement, linguistically appropriate care, mixed methods, and advanced statistics. Our team also includes two patient/provider advisory groups. This application is responsive to NICHD priorities in that it focuses on psychosocial issues related to the care of critically ill children and their families by transforming the delivery of PICU care to be more family- centered and accessible. In summary, this project will advance an innovative FCR solution in the PICU to address families’ unmet needs; and improve parent FCR attendance, healthcare utilization, parent mental health, and sibling well-being.

NIMH - National Institute of Mental Health

Project Summary/Abstract To curb the rising rates of suicide, interventions that directly target the causal mechanisms for suicidal behaviors (SB; i.e., suicide capability) are needed. Virtual reality (VR) suicidal decision scenarios are a valid and safe proxy for SB among at-risk individuals and have enabled causal examinations of suicide capability mechanisms. Intriguingly, these studies, including our preliminary data (N = 63), show that exposure to VR suicidal decision scenarios may evoke clinically meaningful reductions in suicide risk via suicide capability mechanisms. These findings converge with mounting evidence for the effectiveness of VR-based exposure in treating numerous psychiatric disorders. We consider a putative suicide capability mechanism that can be safely therapeutically targeted using VR suicidal decision exposure: motivational relevance of the suicidal decision process that facilitates the development of non-threat associations (i.e., inhibitory learning) with suicide ideation (SI) and the reintegration of suicidal deterrents (i.e., negative consequences of SB; reasons for living). This aligns with recent electroencephalography (EEG) findings that suicide attempters, but not ideators, show decreased sustained reactivity to threat/violence, reflecting an ability to volitionally dampen fear-inducing aspects of SI (i.e., suicidal deterrents), temporarily increasing their ability to approach SB. Our pilot EEG data (N = 28 suicidal adults) show VR suicidal decision scenarios engage the target mechanism of motivational relevance. This K23 proposal will evaluate VR suicidal decision exposure as a mechanistic intervention for SB and is designed to make the next critical steps in intervention development: (1) provide preclinical evidence for the feasibility, acceptability, and safety of the intervention in a transdiagnostic sample of 100 adults with recent SI and 50% with a suicide attempt history; (2) test whether the intervention, relative to treatment as usual, effectively engages the proposed mechanistic targets (neural; increases in late-LPP to suicide-related images and fronto-central gamma during the VR decision scenarios) and behavioral indicators (subjective accessibility of suicidal deterrents; behavioral orientation toward death/life) both in lab and in daily life; and (3) test whether change in the mechanistic targets and behavioral indicators account for intervention-associated change in clinical outcomes related to SB. We will use a multi-method approach involving EEG, subjective and behavioral responses, ecological momentary assessment (EMA), and self-reports/interviews to assess changes pre-post the intervention. This K-award addresses crucial gaps in the candidate’s training and will prepare them to be a leader in suicide intervention science employing an experimental therapeutics approach. The candidate will receive advanced training from an expert mentorship team, including mentors Drs. Joiner, Siegle, and Scott and consultants Drs. Patrick and Krafty. Findings will inform future R-level studies focused on 1) intervention refinement and clinical translation and 2) integrative multi-method (neurophysiology, subjective, behavioral, EMA) approaches to further clarify suicide capability mechanisms and develop effective, mechanistically targeted, and scalable SB interventions.

Wellcome Trust

Funds research to understand the science of mental health and develop new interventions. Focus on anxiety, depression, and psychosis across the lifespan.

National Institutes of Health

-Purpose. This Funding Opportunity Announcement (FOA) solicits research project grant applications on the topic of women's mental health in relation to pregnancy and the postpartum period. The FOA encourages research on perinatal mood and other mental disorders in four areas: (1) clinical course, epidemiology and risk factors; (2) basic and clinical neuroscience; (3) interventions; and (4) services. Research is encouraged both on perinatal non-psychotic mood disorders and on psychotic disorders. Studies exploring the effects of current or lifetime drug abuse, including treatment status and comorbid conditions, on onset and course of mental disorders during the perinatal period are also encouraged. -Mechanism of Support. This FOA will utilize the NIH Research Project Grant (R01) award mechanism and runs in parallel with an FOA of identical scientific scope, PA-06-377, that solicits applications under the Exploratory/Developmental (R21) grant mechanism. -Funds Available and Anticipated Number of Awards. Because the nature and scope of the proposed research will vary from application to application, it is anticipated that the size and duration of each award will also vary. The total amount awarded and the number of awards will depend upon the mechanism numbers, quality, duration, and costs of the applications received.

National Institutes of Health

- This funding opportunity announcement (FOA) solicits exploratory/developmental (R21) research grant applications on women's mental health and sex/gender differences in mental health across the lifespan. The epidemiology and disability burden of mental disorders provide clear evidence of the value of a focus on sex differences research. There are differences in both the prevalence and clinical course of mental disorders between men and women. Starting in childhood, girls have higher rates of anxiety disorders than boys. Boys have higher rates of autism and attention deficit disorder. After puberty, women have higher rates than men of depression, eating disorders, and anxiety disorders, including post-traumatic stress disorder. Men are more likely to suffer from substance abuse disorders. For other serious mental disorders, such as schizophrenia and bipolar disorder, gender disparities in incidence are not found. However, significant differences in clinical course have been demonstrated across the lifespan. This pattern of disparities in the epidemiology of mental disorders in males and females provides indirect evidence of genetic, hormonal, biological, social, cultural and developmental factors in etiology and course. An increasing body of basic and clinical research also provides evidence of neurobiological sex differences that may predispose to clinical differences in mental disorders. The finding of sex/gender differences in epidemiological, basic, and clinical studies has also increased interest in the application of that knowledge to improving interventions and services for males and females. In recognition of the importance of studying sex/gender differences in health outcomes, NIH has provided guidelines to researchers for inclusion of women and men in clinical research and for gender analysis of clinical trials outcomes. Through research such as that called for in this FOA, NIMH seeks to increase the understanding of the significance of sex/gender differences in mental health outcomes and to assess their significance for mental health prevention, treatment and services.-This funding opportunity will utilize the R21 mechanism, but will be run in parallel with a program announcement of identical scientific scope that will utilize the traditional research project grant (R01) (PA-06-333).-Because the nature and scope of the proposed research will vary from application to application, it is anticipated that the size and duration of each award will also vary. The total amount awarded and the number of awards will depend upon the mechanism numbers, quality, duration, and costs of the applications received.-The total project period for an application submitted in response to this funding opportunity may not exceed two years. Direct costs are limited to $275,000 over an R21 two-year period, with no more than $200,000 in direct costs allowed in any single year.-Eligible organizations: For profit organizations; Non-profit organizations; Public or private institutions, such as universities, colleges, hospitals and laboratories; Units of State government; Units of local government; Eligible institutions of the Federal government; Domestic institutions; Foreign institutions; Faith-based or community-based organizations; Units of State Tribal government; and Units of Local Tribal government. -Eligible Project Directors/Principal Investigators (PD/PIs): Any individual with the skills, knowledge, and resources necessary to carry out the proposed research is invited to work with their institution to develop an application for support. Individuals from underrepresented racial and ethnic groups as well as individuals with disabilities are always encouraged to apply for NIH programs.-Applicants may submit more than one application, provided each application is scientifically distinct.

Centers for Disease Control and Prevention - ERA

The National Institute for Occupational Safety and Health (NIOSH) World Trade Center (WTC) Health Program K01 Award supports early-career investigators in developing independent research careers focused on improving the health and well-being of populations affected by the September 11, 2001, terrorist attacks (9/11). This award provides up to three years of mentored research and career development support, including at least 75 percent protected time. The program supports research that improves understanding of physical and mental health effects associated with 9/11 exposures, addresses diagnostic or treatment uncertainty, identifies emerging health concerns, examines aging among exposed populations, and informs improvements in clinical care, public health practice, and long-term health outcomes. Research that helps translate scientific findings into improved care and public health practice is encouraged. Responsive research may include epidemiologic, clinical, translational, preclinical, health services, health outcomes, diagnostic, treatment, prevention, quality-of-life, and implementation research. Generalizability to other populations is not required. The award also supports the development of the next generation of investigators needed to address health needs related to 9/11 exposure. More information, including the WTC Health Program Research Agenda and previously funded projects, is available at: https://www.cdc.gov/wtc/researchagenda.html and https://www.cdc.gov/wtc/fundingdashboard.html.

Centers for Disease Control and Prevention - ERA

<p>The National Institute for Occupational Safety and Health (NIOSH) World Trade Center (WTC) Health Program K01 Award supports early-career investigators in developing independent research careers focused on improving the health and well-being of populations affected by the September 11, 2001, terrorist attacks (9/11). This award provides up to three years of mentored research and career development support, including at least 75 percent protected time. The program supports research that improves understanding of physical and mental health effects associated with 9/11 exposures, addresses diagnostic or treatment uncertainty, identifies emerging health concerns, examines aging among exposed populations, and informs improvements in clinical care, public health practice, and long-term health outcomes. Research that helps translate scientific findings into improved care and public health practice is encouraged. Responsive research may include epidemiologic, clinical, translational, preclinical, health services, health outcomes, diagnostic, treatment, prevention, quality-of-life, and implementation research. Generalizability to other populations is not required. The award also supports the development of the next generation of investigators needed to address health needs related to 9/11 exposure. More information, including the WTC Health Program Research Agenda and previously funded projects, is available at: <a href="https://www.cdc.gov/wtc/researchagenda.html">https://www.cdc.gov/wtc/researchagenda.html</a> and <a href="https://www.cdc.gov/wtc/fundingdashboard.html">https://www.cdc.gov/wtc/fundingdashboard.html</a>.</p>

Wounded Warrior Project

Grants for mental health treatment programs for post-9/11 veterans with PTSD, TBI, and combat-related injuries.

NIDA - National Institute on Drug Abuse

PROJECT SUMMARY Hemp-derived intoxicating cannabis products (DICPs), such as Delta-8 THC, THC-A, and THC-P, have rapidly expanded in the U.S. market following the 2018 Farm Bill. Unlike traditional cannabis, DICPs are often sold in unregulated retail settings, making them widely accessible to youth. Despite their recent introduction, DICPs like Delta-8 THC have already achieved substantial levels of youth use. DICP use can pose significant health risks to youth, including intoxication-related accidents, mental health concerns, and cannabis dependence. The growing concern over accidental ingestion and overdose among minors also highlights the urgent need for actions to reduce youth use. While the public health risks of DICP use among youth are increasingly evident, the marketing practices of DICP brands remain largely unexamined. Historically, youth have been highly vulnerable to targeted marketing by tobacco and alcohol industries, which has played a critical role in generating their positive attitudes and intentions toward using these products. DICP brand marketing on social media may further amplify youth’s DICP use interest by leveraging highly engaging visual and interactive features and youth- oriented cultural references. As part of our ongoing research, we identified extensive DICP marketing on youth- popular social media platforms (Instagram, TikTok, and YouTube), characterized by frequent use of vibrant colors, dessert and fruit imagery, cartoon and anime characters, and pop culture references—marketing features well-documented to attract youth and increase product appeal. No research, however, has systematically examined the youth appeal of DICP social media marketing from leading DICP brands. In the absence of concrete evidence on the extent and tactics by which the DICP industry employs youth-appealing marketing on social media, and its behavioral influence among youth, protective policies will remain reactive and vulnerable to legal challenges. Generating this evidence is therefore critical not only to inform and strengthen policy development but also to support and defend existing regulations against industry opposition. To address this, the proposed project will systematically identify and assess youth-appealing marketing features in social media by leading DICP brands over two years (Aim 1) and examine the associations between the presence of youth- appealing marketing features and DICP use intentions and positive marketing engagement among youth (Aim 2). Our multidisciplinary team of accomplished investigators, with demonstrated expertise in relevant domains, is well-positioned to implement the proposed research, ensuring a high degree of scientific rigor and feasibility. Findings from this project will inform actionable, policy-focused strategies to curb youth-appealing social media marketing by leading DICP brands, enhance regulatory oversight of the industry’s marketing practices, and guide social media platforms in limiting youth exposure to DICP marketing content. The proposed project will establish a foundation for ongoing surveillance of DICP marketing on social media and support a sustained research program examining its behavioral impacts on youth.

NICHD - Eunice Kennedy Shriver National Institute of Child Health and Human Development

Emotional and behavioral health (EBH) during the transition from adolescence to young adulthood is critical to long-term health and wellbeing. When EBH is compromised, it places young people at risk for mental health and substance use disorders and other chronic health conditions into adulthood. Adults in the community, including police officers, play an influential role in youth development and EBH. In urban areas of the United States (US), interactions between police and community members are commonplace, and a large portion involve youth and young adults. Young people may have varied responses to these interactions depending on their type and situational features (e.g., whether the interaction is direct or vicarious). Recent data suggests youth-police interactions and their features are tied to adolescents’ psychosocial functioning (e.g., executive functioning, self-regulation). Moreover, psychosocial functioning has been linked to EBH during the transition from adolescence to young adulthood. Yet how youth-police interactions and their features relate to young adult EBH — and the role of psychosocial functioning as a developmental pathway — remains unclear. Informed by the biopsychosocial framework and developmental psychopathology, the proposed R01 will use a convergent parallel mixed methods design to examine associations between youth-police interactions and young adult EBH, focusing on a viable developmental pathway via psychosocial functioning and the role of external protective factors. We will employ data from the Future of Families and Child Wellbeing Study (FFCWS), a longitudinal birth cohort study of young people across 20 urban US areas (N=2,990). In Aim 1, we will examine associations between youth-police interactions and young adult EBH outcomes (emotional wellness, mental and behavioral health problems, substance use; Aim 1a), and test psychosocial functioning as a mediating developmental pathway (Aim 1b), assessing situational features of youth-police interactions as moderators throughout. In Aim 2, we will evaluate how external protective factors (e.g., teacher support, caregiver-child relationships, neighborhood collective efficacy) moderate associations between youth-police interactions and EBH. In Aim 3, we will conduct life history interviews with 120 young adults (ages 18-24) in urban areas across three states reporting direct or vicarious police interactions to explore how these experiences, their situational features, psychosocial functioning, and protective factors relate to EBH (Aim 3a), and integrate quantitative and qualitative findings to generate data-informed recommendation for improving young adult EBH (Aim 3b). EBH is foundational to health across the lifespan. The EBH of young adults in urban areas who report youth-police interactions remains understudied despite widespread police presence in these settings. Study goals reflect NICHD's scientific priorities of improving adolescent health during the transition to adulthood, elucidating developmental mechanisms tied to health outcomes, and identifying protective factors that promote resilience and EBH across the life course.