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Health and Human Services Department

Thanks to President Trump's leadership, since 2017, the country has made significant progress in addressing mental health and substance use. However, President Trump and HHS Secretary Kennedy realize that the Department and country have more work to do. To facilitate this effort, HHS invites public comment in response to this RFI on the research, development, programs, and policies that have been most successful in improving availability of and access to effective prevention, treatment, and recovery interventions for addiction, mental illness, and co-occurring substance use and mental disorders. The purpose of this RFI is to identify research, programs, and policies that have been successful and recommend novel policy ideas and gaps in research that could be addressed and implemented to further the Great American Recovery using existing funding.

National Institutes of Health

-Purpose. This purpose of this Funding Opportunity Announcement (FOA) solicits Small Business Innovation Research (SBIR) grant applications from small business concerns (SBCs) that propose to develop and commercialize technologies for high throughput data acquisition and analysis that could aid the research fields of basic behavioral science, neuroscience or neuroAIDS relevant to the missions of the National Institute of Mental Health (NIMH) and National Institute of Neurological Disorders and Stroke (NINDS). -Mechanism of Support. This FOA will utilize the SBIR (R43/R44) grant mechanisms for Phase I, Phase II, and Fast-Track applications and runs in parallel with a FOA of identical scientific scope, PA-08-002, that solicits applications under the Small Business Technology Transfer (STTR) (R41/R42) grant mechanisms. -Funds Available and Anticipated Number of Awards. For this FOA, budgets up to $300,000 total costs per year and time periods up to 2 years for Phase I may be requested. Budgets up to $500,000 total costs per year and up to 3 years may be requested for Phase II. Awards issued under this FOA are contingent upon the availability of funds and the submission of a sufficient number of meritorious applications.

National Institutes of Health

-Purpose. This purpose of this Funding Opportunity Announcement (FOA) solicits Small Business Technology Transfer Program (STTR) grant applications from small business concerns (SBCs) that propose to develop and commercialize technologies for high throughput data acquisition and analysis that could aid the research fields of basic behavioral science, neuroscience or neuroAIDS, relevant to the missions of the National Institute of Mental Health (NIMH) and the National Institute of Neurological Disorders and Stroke (NINDS). -Mechanism of Support. This FOA will utilize the STTR (R41/R42) grant mechanisms for Phase I, Phase II, and Fast-Track applications and runs in parallel with a FOA of identical scientific scope, PA-08-001, that solicits applications under the Small Business Innovation Research (SBIR) (R43/R44) grant mechanisms. -Funds Available and Anticipated Number of Awards. For this FOA, budgets up to $300,000 total costs per year and time periods up to 2 years for Phase I may be requested. Budgets up to $500,000 total costs per year and up to 3 years may be requested for Phase II. Awards issued under this FOA are contingent upon the availability of funds and the submission of a sufficient number of meritorious applications.

NIMH - National Institute of Mental Health

PROJECT SUMMARY / ABSTRACT Monitoring neuronal activity modulation is pivotal for elucidating brain functionality and addressing neurological disorders. Despite the advancements brought by green fluorescent calcium indicators like GCaMP and neuromodulator sensors, a considerable gap persists in the development of red fluorescent sensors that match the properties of their green counterparts. This gap, characterized by limitations in dynamic range, photostability, and kinetics, restricts a more comprehensive exploration of neuronal interactions, especially in multiplexed, dual-imaging imaging scenarios. Additionally, the iterative engineering approach for new sensor development is notoriously slow and labor-intensive. Our central goal is to leverage our sensor screening platform, Opto-MASS, as well as our recent successes in using machine learning to expedite the optimization of fluorescent sensors. This project aims to engineer red fluorescent calcium and neuromodulator sensors that match the kinetics and dynamic range of green sensors and further enhance their properties. Our objectives include the rigorous benchmarking of these sensors against the best-in-class for properties such as dynamic range, kinetics, and photostability, followed by comprehensive in vivo validation across multiple laboratories and application scenarios using fiber photometry and two and 3-photon imaging. Our project is innovative because it utilizes a high-throughput screening assay capable of evaluating over 10,000 sensor variants from library collections in under an hour, a significant advancement over current methods. Coupled with pioneering machine learning models that identify key residues affecting sensor performance, we will significantly accelerate fluorescent sensor development, particularly for red calcium and GPCR-based sensors. Importantly, we aim to achieve these goals while reducing time and resource commitments. Our project directly addresses critical needs outlined in this FOA, including a broader range of reliable sensors in neuroscience research that facilitate nuanced, multidimensional studies of brain activity. By developing sensors with improved dynamic ranges, kinetics, and photostability, we aim to overcome existing barriers to multiplexed imaging of neuronal dynamics in vivo. Ultimately, the successful completion of this project would not only fill a vital gap in neuroscientific research tools but also align with the NIH BRAIN Initiative's objectives to advance neurotechnology and set new standards for molecular tool development and in vivo validation in neuroscience.

NIMH - National Institute of Mental Health

Advances in defining the genetic contributions to neuropsychiatric disorders (NPDs), such as autism spectrum disorder (ASD) and schizophrenia (SCZ), have led to the identification of over 200 risk genes harboring rare, protein-disrupting heterozygous mutations. Understanding how mutations in these genes alter brain development or function is essential for elucidating disease mechanisms. Here, we address the substantial challenges posed by genetic heterogeneity and pleiotropy in these two NPDs by studying approximately 50 risk genes in a highly parallel manner. This approach allows us to efficiently identify areas of overlap and convergence among mutations within and across disorders. We leverage our scalable human iPSC engineering platform alongside high-throughput, high-content phenotyping to conduct multi-layered analyses of molecular and cellular alterations caused by heterozygous mutations in these risk genes. Mutant and control lines will be differentiated into 2D neuronal cultures, where high-content imaging will assess proliferation and morphological features. RNA sequencing and high-sensitivity proteomics will be performed to measure gene expression and identify perturbed pathways. These data will be augmented by automated calcium imaging to assess spontaneous and evoked neuronal activity and network synchrony. To model early cortical development in vitro, complementing the 2D system, we will also generate 3D human cortical organoids (hCOs), enabling investigation of cell type specification, maturation, and tissue architecture. We will apply advanced platforms including the Phenocycler for multiplexed spatial proteomics and mononucleotide Repeat Frameshift (MORF) technology coupled with CLARITY imaging to examine cell and dendritic morphology in detail in maturing 3D hCOs. Proteomic and transcriptomic data will be integrated using weighted gene co-expression network analysis (WGCNA) to identify shared and distinct biological pathways affected by the various mutations and to relate these changes to alterations in cellular morphology and physiology in parallel across genes. Our work will clarify whether there are convergent molecular pathways disrupted within and across disorders, and how such disruptions propagate from the molecular to the physiological level, illuminating underlying disease mechanisms. In addition, the resulting ≈200 highly characterized iPSC lines representing ASD and SCZ risk genes will serve as a valuable resource for the field, supporting in-depth follow-up studies, replication, and data integration across platforms.

NIMH - National Institute of Mental Health

Project Summary Region-specific brain organoids derived from human induced pluripotent stem cells (hiPSCs) provide a tractable platform to study disease mechanisms in a human cellular context. Moreover, organoids have the capacity to generate a diversity of cell types that can be maintained in culture long-term and assembled in vitro to form physiologically relevant connections. However, despite this exciting potential, the high variability of organoid differentiation across and within hiPSC lines have halted their broad utility and significantly hindered biological and technical interrogations of human neural development reproducibly and at scale. To address these challenges, this MPI group has established the Brain Organoid Hub at Emory University. A primary goal for the hub, and for this proposal, is to understand the underlying biology of progenitor cells that contribute to variability in 3D neural cultures. Additionally, we hope to develop metrics of hiPSC biology (molecular and/or morphological) that accurately predict the likelihood of successful organoid differentiation, as well as attributes of young organoids that correlate with robust molecular and functional maturation at later stages of culture. Towards this goal, we have designed three specific aims to test the hypothesis that progenitor cell states contain information about future differentiation potential. First, we will use molecular profiling of hiPSCs prior to their 3D formation to ask whether cell state heterogeneity and/or specific gene programs correlate with successful cortical organoid differentiation. Second, we will use machine learning-based approaches to ask whether morphological features of hiPSC growth dynamics are correlated with organoid success. Finally, we will address questions of organoid maturation, and ask whether molecular readouts of young organoids can predict successful functional maturation in late-stage organoid cultures. Altogether, these complimentary aims will not only (1) help reveal fundamental principles that contribute to variation in neurodevelopmental patterning, and (2) provide new assays for improving brain organoid reproducibility while avoiding costly and uninformative differentiations, but also 3) uncover novel biological insights into the genetic programs underlying neural cell specification and maturation. This knowledge could circumvent wasteful studies and instead lead to inclusion of additional biological replicates (hiPSC lines) in experiments. Importantly, our questions are deliberately crafted to align with the core objectives of the Brain Organoid Hub, to ensure reproducibility, efficient resource management, accessibility, and effective dissemination in the field of brain organoid cultures.

National Institutes of Health

-Purpose. This funding opportunity announcement (FOA) issued by the National Institute of Mental Health and National Institute on Drug Abuse invites grant applications from applicant organizations to advance scientific research and intervention regarding HIV treatment adherence. -Mechanism of Support. This FOA will utilize the NIH Small Research Grant (R03) mechanism and runs in parallel with FOAs of similar scientific scope, PA-07-338, which solicits applications under the Research Project Grant (R01) mechanism; PA-07-340, which solicits applications under the Exploratory/Developmental (R21) mechanism; and PAR-07-341, which solicits applications under the Exploratory Grants for Mental Health Interventions and Services (R34) mechanism. Please note that the participating organizations vary across this set of FOAs. -The R03 grant mechanism supports different types of projects including pilot and feasibility studies; secondary analysis of existing data; small, self-contained research projects; development of research methodology; and development of new research technology.

National Institutes of Health

-Purpose. This funding opportunity announcement (FOA) issued by the National Institute of Mental Health, National Institute on Drug Abuse, and National Institute of Nursing Research invites grant applications from applicant organizations to advance scientific research and intervention regarding HIV treatment adherence. -Mechanism of Support. This FOA will utilize the NIH Exploratory/Developmental (R21) grant mechanism and runs in parallel with FOAs of similar scientific scope, PA-07-338, which solicits applications under the Research Project Grant (R01) mechanism; PA-07-339, which solicits applications under the under the Small Research Grant (R03) mechanism; and PAR-07-341, which solicits applications under the Exploratory Grants for Mental Health Interventions and Services (R34) mechanism. Please note that the participating organizations vary across this set of FOAs. -The R21 grant mechanism is intended to encourage exploratory and developmental research projects by providing support for the early and conceptual stages of these projects. These studies may involve considerable risk but may lead to a breakthrough in a particular area, or to the development of novel techniques, agents, methodologies, models, or applications that could have a major impact on a field of biomedical, behavioral, or clinical research.

National Institutes of Health

-Purpose. This funding opportunity announcement (FOA) issued by the National Institute of Mental Health invites applications for Exploratory Grants for Mental Health Interventions and Services (R34) from applicant organizations to advance scientific research and intervention regarding HIV treatment adherence. -Mechanism of Support. This FOA will utilize the NIMH Exploratory Grants for Mental Health Interventions and Services (R34) grant mechanism and runs in parallel with FOAs of similar scientific scope, PA-07-338, which solicits applications under the Research Project Grant (R01) mechanism; PA-07-339, which solicits applications under the under the Small Research Grant (R03) mechanism; and PA-07-340, which solicits applications under the Exploratory/Developmental (R21) mechanism. Please note that the participating organizations vary across this set of FOAs. -Funds Available and Anticipated Number of Awards. Awards issued under this FOA are contingent upon the availability of funds and the submission of a sufficient number of meritorious applications.

NIMH - National Institute of Mental Health

Despite the widespread use of antiretroviral therapy (ART), it is estimated that up to 50% of people living with HIV (PLWH) experience HIV-associated neurocognitive disorders (HAND). HAND decreases quality of life but critically, progression to more severe forms like HIV-associated dementia (HAD) often occurs, especially with increasing age. Associations between neuroinflammation and HAND are known to exist, but the molecular mechanisms driving this are poorly understood. Recently, it has been established that previous inflammatory insults can alter the response of innate immune cells to subsequent inflammatory stimuli, a concept termed innate immune memory (IIM). Trained immunity (TI) is an IIM phenotype classified by hyperresponsiveness to secondary stimulation and is established through epigenetic and metabolic reprogramming. TI is protective in the context of repeated acute insults, but maladaptive in chronic disease. Multiple published studies have suggested that TI occurs in peripheral myeloid cells of PLWH, but whether this occurs in microglia remains unexplored. Preliminary data in the C20 microglial cell line has suggested exposure to HIV-1 induces TI. In addition, multiple reported microglia gene expression signatures in the context of HIV-1 align with trained microglia signatures in other contexts. If TI is established in microglia of PLWH, the characteristic hyperresponsiveness to inflammatory insult could exacerbate neuroinflammation, driving establishment or progression of HAND. Further, TI-like epigenetic reprogramming is known to persist despite cure from other diseases of viral etiology such as hepatitis C virus (HCV), where “epigenetic scarring” drives persistent chronic inflammation and increased liver cancer risk despite virus eradication. Similarly, chronic neuroinflammation and HAND could persist despite HIV cure due to long-lived microglia remaining in the trained state. This possibility, along with the implications of TI in HAND pathogenesis, warrants scientific inquiry into the mechanisms and functional outcomes of HIV-1-induced TI in microglia. In Aim 1, a novel in vitro TI model will be established in human monocyte-derived microglia (MDMi), solving the long- standing issue of lacking physiologically relevant models in the broader microglia TI field. Using this model, HIV- derived molecular inducers of TI will be identified, and epigenetic and metabolic mechanisms of HIV-induced TI will be elucidated utilizing chromatin immunoprecipitation (ChIP) and Seahorse metabolic assays. In Aim 2, the functional outcomes of HIV-1 induced TI will be explored through investigation of perturbations in phagocytic capacity, ROS production, iNOS activity, and microglia morphology. Further, RNA-sequencing will generate transcriptomic signatures of HIV-trained microglia, aiding in elucidation of therapeutic targets and identification of biomarkers for HIV-trained microglia. The proposed fellowship training plan integrates advanced technical training with professional development, leadership, and career preparation. Research will be conducted in an environment that offers extensive expertise in neuroHIV, access to state-of-the-art core facilities, and a collaborative, interdisciplinary culture that supports both rigorous science and trainee development.

National Institutes of Health

-Purpose. This Funding Opportunity Announcement (FOA) issued by the National Institute of Mental Health (NIMH), the National Institute on Drug Abuse (NIDA), and the National Institute on Alcohol Abuse and Alcoholism (NIAAA), National Institutes of Health (NIH), invites research grant applications focused on persons with severe mental illness (SMI), either before or after HIV infection, and the expansion of HIV-related research to include homeless persons. The FOA solicits studies on the development, implementation, evaluation, and dissemination of effective HIV-prevention interventions, and studies related to the epidemiology of HIV infection in the target populations. Multidisciplinary research teams and collaborative alliances are encouraged. -Mechanism of Support. This FOA will utilize the NIH Research Project Grant (R01) grant mechanism, Applications of related or identical scientific scope are also solicited under the NIH Small Research Grant (R03), the NIH Exploratory/Developmental Grant (R21), and the NIMH Clinical Exploratory Research Grant (R34) grant mechanisms, responding to FOAs PA-06-180, PA-06-181, and PAR-06-248, respectively. -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.

Hogg Foundation for Mental Health

Funds mental health programs and policy in Texas communities.

Centers for Disease Control - NCHHSTP

STIs represent a serious public health and economic burden in the United States (U.S.), with approximately 2.2 million new infections occurring each year. As the nation's lead public health agency, the Centers for Disease Control and Prevention (CDC) has a unique responsibility to provide national leadership in STI prevention and control. To meet this challenge, CDC supports a comprehensive and integrated approach to STI prevention that goes beyond simply addressing the absence of disease. It empowers individuals to make healthy choices and build healthy relationships, as an approach to reducing STIs in the U.S. This whole-person approach focuses not just on physical health, but also considers the emotional, mental, and social well-being of the individual. A key component of this approach is supporting a national coalition of sexual health and wellness expertise that allows for the strategic use of limited resources for STI prevention. The coalition brings together a range of organizations, clinical experts, and individuals committed to comprehensive and holistic sexual health and wellness frameworks for STI prevention. The goal is for them to work together to share clear, accurate information, promote quality sexual health care, and empower individuals and communities to make choices that improve health and reduce STI risk with a particular focus on priority groups most affected by STIs. This funding strengthens STI prevention efforts by supporting coalition management and the development, promotion, and dissemination of high-quality, evidence-based sexual health-related materials, resources, and tools to their partners, health care providers, and the public. Together, these efforts complement and supplement traditional STI prevention strategies, accelerating progress toward increasing timely diagnoses and treatment and reducing the STI morbidity in the U.S.

Centers for Disease Control - NCHHSTP

<p>STIs represent a serious public health and economic burden in the United States (U.S.), with approximately 2.2 million new infections occurring each year. As the nation's lead public health agency, the Centers for Disease Control and Prevention (CDC) has a unique responsibility to provide national leadership in STI prevention and control. To meet this challenge, CDC supports a comprehensive and integrated approach to STI prevention that goes beyond simply addressing the absence of disease. It empowers individuals to make healthy choices and build healthy relationships, as an approach to reducing STIs in the U.S. This whole-person approach focuses not just on physical health, but also considers the emotional, mental, and social well-being of the individual.&nbsp;</p><p>A key component of this approach is supporting a national coalition of sexual health and wellness expertise that allows for the strategic use of limited resources for STI prevention. The coalition brings together a range of organizations, clinical experts, and individuals committed to comprehensive and holistic sexual health and wellness frameworks for STI prevention.&nbsp; The goal is for them to work together to share clear, accurate information, promote quality sexual health care, and empower individuals and communities to make choices that improve health and reduce STI risk – with a particular focus on priority groups most affected by STIs.&nbsp;</p><p>This funding strengthens STI prevention efforts by supporting coalition management and the development, promotion, and dissemination of high-quality, evidence-based sexual health-related materials, resources, and tools to their partners, health care providers, and the public. Together, these efforts complement and supplement traditional STI prevention strategies, accelerating progress toward increasing timely diagnoses and treatment and reducing the STI morbidity in the U.S.</p>

NIMHD - National Institute on Minority Health and Health Disparities

Project Summary / Abstract Persons experiencing homelessness are far sicker, age faster, and die younger than their housed neighbors. Homelessness, a federally recognized social driver of health, is caused by multi-level, intersecting factors. Cross-sectional studies have repeatedly shown that persons experiencing homelessness have poorer health than their housed counterparts. For example, chronic conditions such as diabetes and kidney disease are increasingly common conditions among the aging homeless population, but their management is made harder by lack of stable housing. Further, the progression, morbidity, and mortality of these conditions is accelerated for persons experiencing homelessness due to reduced access to care and suboptimal treatment of risk factors including hypertension, chronic viral diseases, mental health conditions and substance abuse. While the detrimental impact of housing loss and improvement from gaining housing is conceptually clear, the evidence of the impact of these housing transitions remains sparse. Systematic reviews, consensus, and federal reports highlight gaps in research where little evidence exists to support that becoming housed improves health outcomes. Most research has focused on single-source data that represent only a snapshot of health – a substantial limitation given the reduced surveillance and access to regular care for persons experiencing homelessness – or come from pilot programs rather than real-world data. Thus, there remains a limited understanding of the longitudinal relationship between housing and health and a resultant lack of adequate targeted health care interventions. We will create a first-of-its-kind integrated dataset by harmonizing data from national, state, and local data sources and then use this dataset coupled with a novel qualitative approach to investigate housing status and health outcomes for persons experiencing homelessness. Our unique longitudinal data, transdisciplinary Housing and Health Advisory Board, and expertise of the study team will enable novel investigations of the health care needs of persons experiencing homelessness during times of housing transitions. Our study aims to (1) Develop a comprehensive and integrated housing and health dataset using real-world data from national, state, and local data sources, (2) Examine the impact of housing status changes, housing program participation, and social service support on health outcomes among persons experiencing homelessness with diabetes and kidney disease, and (3) Identify pathways, facilitators, and barriers that contribute to health care and outcomes for persons experiencing homelessness. This study will yield actionable information to guide clinics and providers in care for persons experiencing homelessness, isolate leverage points and propose interventions, and guide federal-, state-, and local policymakers and program administrators in ways to improve the health for persons experiencing homelessness.

Black Child Development Institute

To honor Black Childcare providers and offer them resources that support their own care and their status as essential care givers, educators and business owners. This event is free and will include self-care advocates, nutrition support, dialogue with mental health professionals, business and finance consultants, and local funders. The event will be held from 10am until 3pm on October 22, 2022 at Rainier Beach Community Center.

NIMH - National Institute of Mental Health

PROJECT SUMMARY To retain new memories over long periods of time, the brain must be able to change in response to learning and then stabilize those changes to store long-term memories. However, the cellular mechanisms that enable long-term memory recall remain incompletely understood. Intriguingly, recent evidence suggests that myelin, the lipid-rich substance produced by glial cells known as oligodendrocytes, is critical for long- term memory recall. Myelin, previously thought to be static and stable after development, is critical for nervous system function; its primary role is to increase the conduction velocity of electrical signaling by neurons. In the adult brain, learning can induce the formation of new myelinating oligodendrocytes, known as oligodendrogenesis. The new myelin sheaths created by oligodendrogenesis are critical for the recall of long-term memories. However, how myelin is precisely modulated to regulate the neural activity underlying long- term memory storage remains an open question. To address this, I use an active avoidance paradigm in which mice learn to associate a light cue with a mild footshock and escape by shuttling to avoid footshock. The trial-based structure, the ability to compare correct and incorrect trials, and the greater diversity of behavioral readouts enable precise correlation between neural features and behavior. Furthermore, the specificity of these readouts can help uncover the precise circuits that are impacted by new myelin formation. Using the active avoidance, I will 1) identify which neurons become myelinated in the medial prefrontal cortex after avoidance learning using two-photon microscopy and 2) determine how oligodendrogenesis influences synchronization in the cortical-hippocampal-amygdala network during avoidance memory recall. Together, I will uncover how learning shapes myelination and how this myelin plasticity influences neural dynamics during long-term memory. These studies will shed light on underexplored, non-neuronal plasticity mechanisms that shape neural dynamics and have broad implications for our understanding of how the brain changes after learning. I will be conducting these experiments in Dr. Mazen Kheirbek’s laboratory, where all the techniques necessary for my project have been set up. The Kheirbek laboratory is located at the University of California, San Francisco, a world-renowned biomedical research facility. With the support of Dr. Kheirbek, co-sponsor Dr. Vikaas Sohal, and additional support from Dr. Jonah Chan, I am perfectly positioned to complete the described project. My postdoctoral work will enable me to achieve my ultimate career goal of running an independent academic laboratory studying how neuron-glia interactions influence neural circuit dynamics and behavior.

NIMH - National Institute of Mental Health

ABSTRACT The dynamics of HIV infection in the brain is poorly understood. Infected cells that transport HIV across the blood brain barrier and into the brain causes inflammation and subsequent damage to resident brain cells. This manifests as a group of symptoms collectively referred to as HIV associated neurocognitive deficits (HAND). Today, in the post ART era, HAND consists of mild to moderate symptoms. This research is significant because it uses an in vivo model to assess the unique interactions among brain cells and peripheral immune cells in vivo in an HIV infected ASRT treated model. Results from these studies will give a better understanding of the events that define neuroHIV in the ART era.

NIMH - National Institute of Mental Health

PROJECT SUMMARY/ABSTRACT Externalizing behavior disorders (EBDs) occur at high rates and have long term negative consequences for children, their families, and for society as a whole. There is robust empirical support for the efficacy of Behavioral Parent Training interventions (BPTs) such as Parent-Child Interaction Therapy (PCIT) for EBDs in children. However, BPT outcomes, including for PCIT, vary widely between controlled efficacy trials and community-based effectiveness trials, and there are variable rates of engagement across families, with dropout rates as high as 82%. Understanding mechanisms that affect parent engagement and treatment outcomes in BPTs is particularly important for services received in community mental health settings (CMHS), where families are most likely to access care. In addition, developing tools to increase engagement and outcome may have strong application in light of large-scale implementations of PCIT in CMHS. A personalized version of PCIT (called MY PCIT) has been developed, addressing key risk factors for low treatment engagement and poor outcomes in BPT that relate to differences between parent and treatment explanatory models. MY PCIT begins with a pre-treatment assessment of parent explanatory models, then provides therapists with a report with personalization guidance and a suite of personalization tools that may be deployed based on the pre-treatment assessment. While pilot data supports the successful development of MY PCIT and its potential to reduce targeted risk factors, more research is needed to prepare it for self-sustaining implementability in CMHS, and to compare engagement and outcomes to standard PCIT. This study is a pilot hybrid type 1 effectiveness-implementation trial designed to gather preliminary data to evaluate the effectiveness and the self-sustaining implementability of MY PCIT in CMHS through the following aims: 1) Engage representative CMHS therapists in mixed methods user testing sessions to identify barriers to/facilitators of implementing MY PCIT and inform areas for modifications to make it more feasible, usable, and appropriate in CMHS. 2) Conduct a randomized controlled trial in CMHS comparing PCIT as usual to MY PCIT to obtain pilot data on engagement, clinical outcomes and targeted mechanism change. 3) Gather therapist-level implementation outcomes data on MY PCIT from the clinical trial. Findings from this pilot study will inform and support a future R01 proposal for a fully powered trial of MY PCIT. This project directly supports the mission of NIMH by advancing research to improve how effective treatments are adapted and sustained in real-world care. It also advances several NIMH Strategic Plan objectives, including: tailoring interventions to increase effectiveness (3.2), testing interventions in real-world settings (3.3), developing innovative service models to improve outcomes (4.3), and promoting sustained implementation of evidence-based treatments (4.2).

NIDA - National Institute on Drug Abuse

SUMMARY/ABSTRACT Adolescent nicotine vaping remains prevalent alongside increases in cannabis vaping, nicotine-cannabis co-vaping, and daily/near-daily nicotine and cannabis vaping rates since 2019. Nicotine and cannabis vaping are associated with nicotine and cannabis dependence, carcinogen exposure, and pulmonary, cognitive, and mental health symptoms, with co-vaping posing additive health risk. Despite the critical role of parents in preventing adolescents’ tobacco and cannabis smoking, adolescents’ vaping poses difficulties for parents in their ability to engage in vaping prevention parenting behaviors (VPPBs), as vape devices may be disguised as other products and modified to vape cannabis and higher levels of nicotine. Less than half of parents report knowledge of vape device characteristics, vaping health consequences, adolescent vaping norms, and youth-targeted vaping marketing. Social media messages about vaping and VPPBs are ideal prevention tools, as 90% of US parents use social media regularly including for health information and parenting advice. This proposal is informed by social cognitive theory and the health belief model and builds on our team’s expertise in longitudinal studies of parenting and adolescent substance use and experimental studies testing youth vaping messaging. The overall goal of this work is to understand how to empower parents to prevent adolescent nicotine and cannabis vaping. We will conduct a 6-wave longitudinal survey study among 1,000 US parent-adolescent (ages 12-17) dyads recruited via social media and a 5-week online experimental study among a subset of 300 parents with low parent vaping knowledge (PVK) to test messages designed to improve PVK and VPPBs. Parents will be randomly assigned to view Facebook posts in a 4 (within-persons) X 3 (between-persons) mixed design. Each parent will view: 1) 4 sets of messages aimed at promoting PVK (device characteristics, harms, norms, youth-targeted marketing) in a randomized order; and 2) one of 3 sets of messages aimed at promoting VPPBs (rules, monitoring, communication). Experimental outcomes include PVK (i.e., device characteristics, health consequences, vaping norms, youth-targeted marketing), use of VPPBs (i.e., rules, monitoring, communication), and adolescents’ vaping outcomes (i.e., any current nicotine/cannabis vaping, frequency of nicotine/cannabis vaping, co-vaping vs. nicotine-/cannabis-only vaping, susceptibility to future nicotine/cannabis vaping). We will address 2 specific aims: Aim 1 (longitudinal surveys) - Examine 1a) direct associations of PVK and VPPBs with adolescents’ nicotine and cannabis vaping trajectories; and 1b) indirect associations of PVK with adolescents’ nicotine and cannabis vaping trajectories via VPPBs as mediators; and Aim 2 (experimental study) - Examine: 2a) within-persons effects of PVK messaging themes on PVK outcomes and between-persons effects of VPPB messaging themes on VPPB outcomes; and 2b) within-persons effects of PVK messaging themes on adolescents’ vaping outcomes via increases in PVK and between-persons effects of VPPB messaging themes on adolescents’ vaping outcomes via increases in VPPB use. This proposal is responsive to NIDA’s NOT-DA-22-004: Epidemiology of Drug Abuse and will inform large-scale social media messaging campaigns empowering parents to prevent adolescent nicotine and cannabis vaping initiation and progression.

NIMH - National Institute of Mental Health

Project Summary Despite widespread prevention efforts, suicide remains a major public health concern. Most extant research has focused on suicide in adolescents and adults; yet suicide risk among children is understudied. Suicide is now the 3rd leading cause of death among 8-12-year-olds, reflecting a clear public health crisis. The pediatric emergency department (ED) is often the primary point of clinical contact to manage suicidal thoughts and behaviors (STB) for children and the months post-ED discharge are a high-risk period for STB to reoccur. Improving identification and prediction of suicide risk for children in the ED is a critical gap. This R21 will leverage rich electronic health records (EHR) from 5 pediatric EDs across the United States that have been harmonized within the Pediatric Emergency Care Applied Research Network (PECARN). We anticipate ~7,000 EHR from 8-12-years-old patients yielding sufficient power for nuanced analytics. Preliminary data highlight that STB are unfortunately common among children receiving psychiatric evaluation in the ED; ~20% of children in our ED reported a history of suicide behaviors or attempts and another ~40% expressed lifetime suicide ideation. To improve understandings of STB in children, the following aims will be addressed. First, to identify sociodemographic and clinical factors related to STB risk, we will directly compare children in the ED for suicide-related concerns with patients admitted for non-suicide-related psychiatric concerns (e.g., depression). Second, we will examine predictors of return ED visits for STBs within 1-year of discharge. Our preliminary data suggest that ~15% of children will return to the ED within 1-year. Risk factors for return ED visits will be ascertained from both structured EHR data (e.g., insurance status) as well as clinician free-text notes. In preliminary data, we developed lexicon-based approaches to parse clinician notes and extracted novel risk factors for analysis. Preliminary results show that clinician notes can be used to identify key factors of interest, including a history of prior psychiatric hospitalization, and impulsivity. Third, we will apply natural language processing using large language models trained on independent EHR to identity severity and frequency of domains of risk, including negative affect and sleep disturbance, which will further improve prediction of return visits to the ED for STBs. Finally, these aims will be integrated into a practical risk calculator to aid in screening and triaging potential suicide risk for children in the ED. Together, this work will lead to a future multi-center, prospective project designed to improve screening and intervention for high-risk, suicidal children.

NIMH - National Institute of Mental Health

PROJECT SUMMARY/ABSTRACT. The overall objective of the proposed K23 is to support Dr. Rachel Siciliano in acquiring the skills necessary to become an independent investigator focused on elucidating mechanisms underlying treatment and individual differences corresponding to treatment response in trauma- exposed youth. Trauma-related mental health problems are a major public health problem. Over four million adolescents meet criteria for posttraumatic stress disorder (PTSD) in the U.S., and while evidence-based treatments (EBTs) are effective, up to a quarter of youth do not respond. EBT mechanisms and predictors of EBT components remain largely unknown. EBTs for PTSD include repeated imaginal exposure to trauma- related content, hypothesized to impact distress and PTSD symptoms via shifts in biological reactivity. Further, baseline threat reactivity and emotion regulation characteristics may influence EBT response. The proposed K23 directly addresses critical gaps in understanding how and for whom repeated imaginal exposure is effective in adolescents with trauma-exposure and PTSD symptoms. The goals of the proposed project are to: (1) examine the biobehavioral effects of repeated imaginal exposure and assess psychophysiological change as a potential mechanism of anxiety change; (2) assess baseline threat reactivity and emotion regulation as predictors of exposure task response; and (3) determine if baseline characteristics and exposure task responses relate to PTSD symptoms longitudinally. Dr. Siciliano is a promising candidate with a strong foundation in biobehavioral assessment and trauma-focused treatment but requires additional training. The proposed training plan closely aligns with the research goals and includes: (1) clinical and randomized controlled trials for adolescent PTSD; (2) EEG and EMG acquisition and analysis with data integration techniques; (3) experimental therapeutics, treatment mechanisms, causal inference, and longitudinal statistics; (4) precision medicine approaches and subgroup analyses; and (5) professional development. The rich academic environment at the Medical University of South Carolina and collective expertise of the mentorship team (Drs. Danielson, McTeague, Cisler, Whitfield-Gabrieli, Hayat) are uniquely suited to provide this training. The mentorship team, coursework, seminars, workshops, and conference attendance afforded by the K23 are essential for launching the candidate's independent career as a high impact translational scientist focused on EBT mechanisms and precision medicine advances for trauma-exposed youth. Findings have wide-ranging implications, as imaginal exposure is a central component in multiple interventions, and identifying distinct combinations of baseline characteristics matching onto exposure may improve treatment response predictions, thus advancing more precise interventions. Results from the proposed research will inform the development of future R01 grants targeting specific mechanisms of EBT components and testing if response to those components varies as a function of baseline characteristics or profiles.

NIMH - National Institute of Mental Health

PROJECT SUMMARY Major depressive disorder (MDD) has long been theorized to reflect an overly broad disorder class that collapses across heterogenous risk pathways. A rate limiting factor to examining the divergent validity of MDD subtypes using genomic methods is a lack of sufficiently powered data. As part of the proposed project, we will utilize Co-I Dr. Lewis’ role as a leader in depression genetics and co-chair of the PGC MDD working group to put together the largest genome-wide association study (GWAS) yet performed for various MDD subtypes, including sex-stratified, atypical, postpartum, and severe MDD. In addition, we will employ Genomic LOSEM, a novel method introduced in the grant for examining non-linear changes in genetic signal that we will use to examine how different ages at onset and socioeconomic status shift MDD genetic architecture. The subtype GWAS and Genomic LOSEM package will be made available as public resources. Standard univariate approaches that focus strictly on either meta-analyzing across MDD in all its forms or analysis of a particular subtype are unable to parse genetic risk pathways that are broadly relevant to MDD from those that are unique to a specific subtype. In addition, family-based approaches are pragmatically limited to examining a handful of subtypes at a time and cannot describe underlying biology. Genomic Structural Equation Modeling (Genomic SEM) is an innovative, multivariate framework developed by the grant PI Dr. Grotzinger for modeling genetic overlap derived from GWAS data. The well-powered GWAS of MDD subtypes will be used as input to Genomic SEM models that will formally disambiguate shared and subtype-specific genetic signal. A unique advantage of Genomic SEM is that even mutually exclusive subtypes can be included in the same statistical model. The remaining analyses will characterize subtype-specific genetic signal at varying levels of biological granularity, including estimating genetic overlap with clinically relevant external correlates (e.g., cognition, other psychiatric disorders). By applying Stratified Genomic SEM, a novel extension for estimating multivariate functional enrichment, we will characterize biological pathways involved in subtype specific risk. These biological pathways can include, for example, genes expressed early in development, in certain brain regions, or in specific types of neurons. At the gene expression level, Transcriptome-wide SEM will be used to identify the lists of genes uniquely associated with an MDD subtypes. These results will be cross-referenced with the Connectivity Map drug repurposing dataset to identify existing pharmacological interventions that may have therapeutic benefit. By utilizing sex-stratified GWAS summary statistics we will explicitly consider biological sex as a moderator of relevant genetic pathways. In addition, expanding African, East Asian, and LatinX ancestry GWAS datasets, LD-scores, functional annotations, gene expression weights and cross-ancestry methods will allow us to extend the grant aims across diverse samples. Our analyses will collectively provide the most comprehensive evaluation to-date of subtype-specific etiology within MDD.

NIMH - National Institute of Mental Health

PROJECT SUMMARY/ABSTRACT People with HIV (PWH) who experience challenges with antiretroviral therapy (ART) adherence are at increased risk for suboptimal treatment outcomes, including viral non-suppression and disengagement from care. Despite advancements in ART delivery options, personalized treatment approaches that integrate patient preferences remain underutilized, particularly among PWH facing psychosocial and documented barriers. Clinical decision support (CDS) tools offer a promising avenue to address this gap by tailoring treatment recommendations based on patient-specific needs and barriers. However, current CDS tools often fail to incorporate rich patient insights available from unstructured electronic health record (EHR) notes or systematically integrate directly reported preferences, limiting their potential to enhance adherence and outcomes. The proposed training and research plan for this K23 will enable José I. Gutierrez, Jr., PhD, FNP- BC, to acquire the expertise necessary to become an NIH-funded independent investigator who designs patient-informed CDS interventions that optimize HIV treatment delivery. Under the mentorship of an experienced multidisciplinary team, Dr. Gutierrez will use a mixed-methods approach to develop foundational components of a CDS prototype that integrates natural language processing (NLP)–derived EHR information with patient-reported preference data. Building on prior work in HIV treatment delivery and preference evaluation, he will pursue the following specific aims: (1) explore HIV treatment delivery preferences, barriers, and facilitators within EHR notes using NLP; (2) identify and quantify patient preferences, barriers, and facilitators using qualitative interviews and MaxDiff; and (3) develop the key features of a CDS prototype that generates tailored suggested actions informed by EHR and patient-preference data, and evaluate its acceptability, feasibility, usability, and intended adoption in a 9-month, cross-sectional, non-clinical user-testing study using standardized vignettes and de-identified/fictionalized cases (no live EHR). This research plan aligns with Dr. Gutierrez's career development goal to gain advanced skills in clinical informatics and NLP, qualitative and mixed-methods research, and patient-informed intervention design. Findings will provide the foundation for a subsequent NIH R01 to rigorously evaluate effectiveness in clinical settings, with the overarching goal of improving ART adherence and treatment outcomes among PWH. 1