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NCCIH - National Center for Complementary and Integrative Health

Project Summary/Abstract Research: Fear activates the fight or flight stress-response, leading to rapid changes in behavior and physiological accommodations via the sympathetic nervous system. While the stress response facilitates survival from an acute threat, inappropriate activation or delayed termination after threats have passed can be maladaptive. Indeed, inappropriate sympathetic activation is a hallmark of psychiatric diseases such as post- traumatic stress disorder and major depressive disorder. Conversely, non-invasive brain modulation techniques such as transcranial direct current stimulation, which induces diverse physical and mental health benefits, may function in large part through its ability to mitigate the stress response. Together, this suggests that the neural circuits regulating the sympathetic nervous system could be an important therapeutic target. To map the central circuits regulating the adrenal gland, an essential effector of the fight-or-flight sympathetic response and the principal source of circulating epinephrine, I will use monosynaptic rabies. My preliminary data show that the adrenal medulla receives innervation not only from well-established hypothalamic nuclei, but also, surprisingly, from the motor cortex. The proposed project will expand upon this finding: In Aim 1) I will rigorously map the connections between the motor cortex and the adrenal gland and in Aim 2) I will investigate how these cortical neurons modulate epinephrine release and the physiological and behavioral response to stress. These aims will expand our understanding of this newly discovered neural circuit and its role underlying important mind-body interactions. Career development: This five-year research career development program will advance the career of a promising physician-scientist studying the neural circuits underlying mind-body connections as they relate to the physiological effects of stress. This proposal builds upon the candidate’s extensive background in molecular neuroscience and behavioral genetics, by promoting Dr. Greene’s acquisition of several necessary technical skills and extensive training to ensure that the candidate develops superb professional skills. The training goals are reflected in the expertise of the mentors (Dr. Andrés Bendesky and Dr. Rui Costa), tailored seminars and didactics, and the strong neuroscience training environment at Zuckerman Mind Brain and Behavior Institute. By completing the proposed studies and training plan, the candidate will acquire a unique and highly valued skill set that will support a successful transition to becoming an independent investigator.

NIMH - National Institute of Mental Health

PROJECT SUMMARY Top-down signals from the prefrontal cortex have long been postulated to regulate hippocampal function as part of numerous cognitive and emotional processes, but the specific pathways mediating top-down control have been unclear. We have found a novel long-range GABAergic pathway from prefrontal cortex to hippocampus that represents a potential substrate for top-down control. Notably, this pathway seems to operate in an unusual manner: by inhibiting disinhibitory circuits. Our initial studies found that these prefrontal- hippocampal GABAergic projections can promote object exploration by enhancing hippocampal representations of object locations and associated network oscillations. However, two major questions remain unresolved. First, prefrontal GABAergic neurons which project to the hippocampus are heterogeneous and the significance of this is unknown. Second, the detailed circuit mechanisms through which long-range GABAergic projections from prefrontal cortex alter hippocampal information processing remain unclear. The goal of this project is to first and foremost, elucidate mechanisms through which long-range prefrontal-hippocampal projections shape computation in downstream circuits, and second, relate these to the heterogeneity of long- range GABAergic neurons. This project will specifically test our hypothesis that long-range GABAergic projections exert top-down control over the hippocampus by targeting disinhibitory microcircuits, thereby regulating how competing input regions recruit and entrain feedforward inhibition in the hippocampus. This could explain how hippocampal circuits switch between different information processing modes, each characterized by rhythmic synchronization with a different upstream region. Furthermore, we may identify different subtypes of long-range GABAergic neurons that each promote synchrony with a unique input region, elucidating organizational principles and functional implications for the heterogeneity of long-range GABAergic neurons.

NIMH - National Institute of Mental Health

PROJECT SUMMARY Working memory allows past events to be transiently maintained in the brain so that it can be compared with ongoing experiences to drive behavior. This cognitive process has been shown to be severely impacted by the progression of many neuropsychiatric diseases and disorders. Thus, it is critical to understand the components of working memory to determine how normal mental function can be restored. Working memory must be selective to relevant stimuli and resistant to noise or irrelevant stimuli. It has been proposed that information is maintained through persistent activity at the single-cell or population level, either among local recurrently connected neurons or through long-range loops across multiple brain areas. Alternatively, it has been proposed that information could be maintained through activity-silent intracellular processes which are defined by specific genes and molecules. These theories are not necessarily mutually exclusive and may both be implemented in the nervous system. To achieve a comprehensive understanding of these mechanisms, it is necessary to investigate working memory across multiple biological scales spanning genes, cell types, local circuit dynamics, brain-wide communication, and behavior. Using a combination of multi-area two-photon calcium imaging, long-range anatomical tracing, cell-resolution optogenetic manipulation, and comprehensive spatial transcriptomic analysis, we will dissect working memory circuits as animals perform sensory-guided working memory tasks. In Aim 1, we will determine how specific stimuli are maintained in working memory by monitoring and perturbing local and long-range cortical activity to distinguish working memory maintenance from sensory-to-working-memory transformations. In Aim 2, we will determine the cellular and molecular mechanisms supporting local working memory by combining functional connectivity and gene expression measurements to distinguish their contributions to persistent activity and activity silent properties. Through this, we will determine the precise local and long-range dynamics that underlie working memory and the cellular and molecular properties that support these computations.

National Institutes of Health

-Purpose. The purpose of this Funding Opportunity Announcement (FOA) issued by the National Institute on Drug Abuse and the National Institute of Mental Health, National Institutes of Health, is to solicit Research Project Grant (R01) applications from institutions/organizations that propose to identify chromosomal loci and/or genetic variation in genes and haplotypes that are associated with either increased or decreased vulnerability to, dependence on, and/or treatment response for addiction to stimulants (e.g., cocaine, amphetamine, caffeine), narcotics (e.g. opiates), nicotine, benzodiazepines, barbiturates, cannabis, hallucinogens, and/or multiple drugs of abuse and/or their associated mental co-morbidities (e.g., major depression, schizophrenia, bipolar disorder) in human beings or animal models. Similarly, there is interest in chromosomal loci and/or genetic variation in genes and haplotypes that are associated with differences in responses to treatment for addiction to drugs of abuse, and treatments for co-morbid disorders -Mechanism of Support. This FOA will utilize the NIH Research Project Grant R01 award mechanism. -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

How networks of molecules persistently modify neuronal ensembles to store long-term memory is a fundamental question in neuroscience, relevant for disorders characterized by memory-like dysfunction of brain circuits. Whereas transient second messengers activate many kinases to briefly modify synaptic strength, the second messenger-independent, atypical PKC isoform, PKMz, is persistently active. Strong stimulation of synapses increases cellular PKMz through new synthesis; however, the kinase’s action maintains potentiation only at activated synapses. Our initial work on how PKMz selectively targets active synapses reveals PKMz does not act alone, but interacts continually with other molecules to maintain potentiation of specific synaptic connections. The postsynaptic scaffolding protein, KIBRA, genetically linked to human memory, forms persistent complexes with PKMz in LTP. Blocking their interaction reverses established LTP, without affecting unstimulated synaptic strength. The antagonists disrupt 1-month-old spatial memory, during which PKMz has been degraded and resynthesized. Thus, KIBRA acts as a persistent synaptic tag, anchoring PKMz to maintain LTP and memory despite protein turnover. PKCi/l compensates for PKMz loss in z-knockout mice and is also anchored at active synapses. Understanding this persistent synaptic tagging requires elucidating molecular networks that form and maintain potentiation at active synapses, and how this tagging modifies neuronal ensembles to store memory. Thus, Aim 1 is to identify the molecules establishing KIBRA-PKMz coupling at activated synapses. Multiple proteins interact with KIBRA, including the actin-associated protein dendrin and protein interacting with C-kinase (PICK1) that also binds both PKMz and AMPARs. Actin filaments and postsynaptic AMPARs increase in early-LTP. We will test whether dendrin and PICK1, together with other molecules identified by proteomic screening, accumulate KIBRA in early-LTP, which then anchors PKMz in establishing late-LTP. Aim 2 examines molecular networks maintaining KIBRA-PKMz complexes in LTP and memory. KIBRA stabilizes PKMz, and we will test if this stabilization and the persistent action of PKMz to strengthen synapses act in feedback pathways to perpetuate KIBRA-tagging in maintenance. We will use dual-eGRASP that persistently labels with fluorescent markers synapses activated in learning to examine KIBRA-PKMz coupling in activated synapses during spatial memory. Aim 3 investigates how KIBRA-PKMz persistent synaptic tagging expresses memory through modifications of place cell ensembles. Standard measures of place cell fields change only modestly as animals learn spatial information. Our recent optical recordings of hundreds of place cells reveal subpopulations of cells that form and maintain new cofiring relationships during spatial memory. Initial data show decoupling KIBRA-PKMz erases memory, and we will test if memory-related place cell ensembles and the spatial information they encode are also disrupted. Our 3 Aims will elucidate the molecular networks crucial for persistent synaptic tagging and so establish a basis for understanding disorders of memory.

NIMH - National Institute of Mental Health

Project Summary/Abstract Dopamine neurons in the ventral tegmental area (VTA) fire action potentials in complex patterns of tonic and phasic activity in response to environmental stimuli and during behavioral tasks. Transcriptomic, anatomical, and functional studies have established that VTA dopamine neurons can be divided into multiple subpopulations with variable gene expression, projection patterns, and response profiles. We recently completed a transcriptomic study that identified genetic markers for three distinct subpopulations of VTA dopamine neurons, and also found evidence for variability in ion channel gene expression between populations that correlated with differences in activity-dependent gene expression. However, much remains unknown regarding how specific genes encoding ion channels, receptors, transcription factors, or other signaling components contribute to the variability in baseline physiological properties observed across the VTA. Here we propose to combine slice electrophysiology recordings of VTA dopamine neurons with post-hoc single-cell sequencing analysis (i.e. patch-seq), which will allow us to directly correlate gene expression and physiological properties in order to identify candidate genes that may be key drivers of the variability between subpopulations. We also propose to validate and utilize a novel dual-recombinase CRISPR/Cas9 system for targeted gene mutagenesis in intersectional neuronal populations, which will provide a mechanism for testing gene function with unprecedented precision. We will use this approach to test the function of two candidate ion channel genes, the potassium channels Kcnh5 and Kcnh7, previously identified in our transcriptomic study as potential contributors to dopamine neuron action potential firing properties. We hypothesize that these genes are important for enabling rapid action potential firing in highly excitable dopamine neurons found in specific subpopulations. As a whole, with this proposal we aim to generate a valuable dataset linking gene expression in VTA dopamine neurons with physiology and subpopulation identification, as well as develop an intersectional gene mutagenesis strategy that can be used throughout the brain to precisely target neuronal subpopulations to test gene function. With this approach, we hope to facilitate future precision targeting of the dopamine system and dopamine-dependent behaviors.

NIMH - National Institute of Mental Health

PROJECT SUMMARY People experiencing major depression often decline their approach to rewards, to instead avoid threats (including irrelevant ones). Despite the prevalence of these costly behaviors featuring decision-making impairments, their underlying neurobiology is poorly defined. Here, I combine powerful mouse models to provide a multilevel characterization of approach and avoidance decisions linked to depression. Previous studies highlight specific areas within the corticostriatal-limbic system as signaling approach and avoidance expression. However, I propose to go beyond this limited approach by unbiasedly profiling neuronal activity in the whole brain of mice showing approach and avoidance decisional biases linked to depression-related phenotypes. Further, I propose to unbiasedly profile transcriptional patterns in key areas and to chemogenetically test the role of key cell types. I hypothesize that, in addition to proven areas, our results will reveal overlooked areas and cell types whose activity might be crucial in driving approach and avoidance biases linked to depression. Moreover, our transcriptional analyses will identify proven (i.e., ∆FOSB & CREB) and novel transcriptional regulators driving these biases. In Aim 1, I adapted a platform-mediated avoidance task, to profile approach and avoidance biases in mice exposed to chronic social defeat stress (CSDS), a model used to study depression-related pathology. I first demonstrated that mice susceptible to the CSDS, similar to depressed patients, show persistent avoidance to a cue previously announcing a shock threat, at the cost of missing rewards. In contrast, mice resilient to the CSDS quickly decrease their avoidance to maximize gaining rewards. To further characterize these behavioral biases, in Experiment 1.1, I use brain-wide immunostaining of cFOS as a proxy for correlated neuronal activity. Next, to leverage neuronal activity and gene expression patterns, in Experiment 1.2, I will use RNA-sequencing to transcriptionally profile areas whose activity most strongly correlated with approach and avoidance biases. Simultaneously, I will profile the nucleus accumbens, amygdala, and prefrontal cortex within the corticostriatal- limbic system, which have been proven to signal approach and avoidance and to be sensitive to the adverse consequences of stress. Next, in Experiment 1.3, I will perform chemogenetics, to test the causal role of key areas and cell types in biasing approach or avoidance decisions after CSDS. Capitalizing on this training, in the K00 phase, I will study in vivo temporospatial dynamics of decision-making circuits sensitive to stress, by combining behavior with calcium-imaging and computational modeling. The overall training and research plans outlined here will reveal novel insights into decision-making processes impacted by stress, and will greatly support my successful transition to a postdoctoral fellowship and subsequent scientific independence.

NIMH - National Institute of Mental Health

Abstract/Summary Advances in antiretroviral therapy (ART) have reduced the incidence of severe clinical neurocognitive complications associated with chronic HIV infection, such as HIV-associated dementia (HAD). Nevertheless, nearly half of people with HIV (PWH) still experience asymptomatic neurocognitive disorder (ANI) and mild neurocognitive disorder (MND). Opportunities for using novel, data-driven approaches, such as Artificial Intelligence (AI) in making predictions, real-time monitoring, or improving clinical decision-making to address HIV-related neurocognitive disorders (HAND) proliferate but have yet been fully realized. Recent studies have employed machine learning (ML) and/or deep learning (DL) techniques to either cluster neurocognitive phenotypes or identify key predictors of neurocognitive impairment in PWH. Data from these studies, however, are typically “siloed” and unimodal (e.g., only electronic health records [EHR] data or imaging data). Given the broad spectrum of modalities of neurocognitive disorder, multimodal approach (i.e., integration of different data modalities) provides opportunities to increase robustness and accuracy of diagnostic and prognostic models by utilizing complementary and supplementary information in modalities. However, such multimodal approach is limited often due to the lack of multimodal data and advanced methodologies such as multimodal AI. One novel and ambitious initiative funded by the NIH to advance precision medicine is the All of Us (AoU) Research Program, a centralized data repository, offering secure access to de-identified multimodal data (e.g., EHR data, genomic data, survey data, and imaging data) from almost one million program participants. In our preliminary study, we have developed a computational phenotyping that identified 6,664 confirmed PWH among 633,000+ participants as of October 2023. In response to RFA-MH- 26-105, we propose to apply multimodal AI with a series of longitudinal EHR data (laboratory and medication), genomic data, self-reported survey data (e.g., lifestyle, physical measurement, healthcare access), and imaging data in AoU to 1) identify different biotypes of neurocognitive disorders in PWH (e.g., ANI, MND, HAND) and employ ML/DL approaches to cluster neurocognitive phenotypes; 2) develop, evaluate, and validate multimodal AI models to predict neurocognitive disorders in PWH accounting for comprehensive information and enhance the model interpretability through synergistic integration of a domain-specific knowledge graph; and 3) develop a multimodal AI based decision-making prototype to assist with the identification of PWH with risk of neurocognitive disorders and pilot test its feasibility, usability, and implementation strategies in clinical settings. Personalized risk prediction through multimodal AI could improve the predictive accuracy and early detection of neurocognitive decline in PWH and inform tailored intervention and treatment for PWH. The insights gleaned from our project could also be a demonstration of the power of cutting-edge multimodal AI models to expand our capacity to accelerate HIV care and address the dynamic, complex, and evolving HIV epidemic.

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

Project Summary Sustained attention (SA)—the ability to maintain engagement with people or objects over time—is a foundational skill that supports early learning across domains, including language, cognitive development, and social interaction. Disruptions in early SA have been linked to later difficulties in academic achievement, emotion regulation, and mental health. Yet, little is known about how SA naturally emerges, stabilizes, and becomes self-directed in infancy, particularly in everyday social contexts. This project investigates how SA develops through dynamic coordination among behavioral, neural, and autonomic systems, captured in real time during naturalistic parent–infant interactions. We will conduct a longitudinal study of typically developing infants between 6 and 30 months, integrating head-mounted eye tracking (ET), electroencephalography (EEG), and heart rate monitoring (ECG). This multimodal design enables precise identification of SA episodes and their physiological signatures as they unfold in the real world. We hypothesize that caregiver scaffolding—such as holding—shapes the salience and structure of infants’ attention, triggering coordinated multisystem engagement that supports the emergence of self-directed SA. We will characterize age-related changes in SA, examine its variation across social contexts, and assess whether early multisystem patterns predict later individual differences in attention control, language development, and neural function. This project is innovative in its longitudinal, ecologically grounded approach to studying attention, combining first-person ET with neural and autonomic measures during live interaction. Findings will advance theories of developmental attention and clarify how early multisystem dynamics contribute to variation in cognitive and social outcomes.

NIMH - National Institute of Mental Health

Psychotic disorders are a leading contributor to the global disease burden, causing high levels of disability and increased mortality. To improve outcomes, it is essential to identify and treat patients in the early stages of psychotic disorders, especially before overt symptoms appear. Yet, despite decades of research, we are unable to accurately identify early on individuals who will progress to develop a psychotic disorder, even those who are clinically high risk for psychosis, due in part to small sample sizes and extant approaches that do not capture the multifactorial etiology of psychotic disorders. There is therefore an urgent need to substantially improve prognostic precision. Critically, accurate and robust prognostic markers are needed to understand the origins and progression of psychosis and to identify precise neurobiological targets for early treatment. Newly available large-scale multimodal data—clinical, cognitive, and neurobiological—as well as exciting recent advances in artificial intelligence models and methods that overcome limitations of extant approaches offer an unprecedented opportunity for developing accurate and robust prognostic markers for psychosis. The overarching goal of our proposal is to identify accurate and robust multimodal prognostic markers for psychosis using a novel data-driven AI-based computational framework. Building on our highly encouraging preliminary results, we will use an innovative approach combining our recent work on AI models and explainable AI methods as well as integrative theoretical models of psychosis with a wealth of newly available large-scale multimodal data from multiple consortia. The specific objectives of our proposed work are threefold. In Aim 1, we will identify prognostic markers using clinical, cognitive, and neurobiological data to predict future psychosis transition, particularly in youths at clinical high risk. In Aim 2, we will evaluate the generalizability and the temporal (longitudinal) stability of the identified prognostic markers. In Aim 3, we will determine whether the identified prognostic markers predictive of future psychosis transition in youths at clinical high risk are a characteristic trait of psychosis. Through the successful completion of the work described here, our multidisciplinary team is uniquely positioned to transform our understanding of the mechanisms associated with the risk for and development of psychotic disorders, as well as identify neurobiological targets. Ultimately, these advances will lead to the development of individualized prognostic tools and early targeted treatments for psychosis and, more broadly, advance precision psychiatry.

NIMH - National Institute of Mental Health

ABSTRACT A major challenge in clinical genomics is the interpretation of variants of uncertain significance (VUS), which comprise the majority of disease-associated mutations cataloged in human genetic databases. This limitation is especially acute in neuropsychiatric and neurodevelopmental disorders, where cellular context and gene function are tightly intertwined. CACNA1C, which encodes the L-type calcium channel Cav1.2, exemplifies this challenge: common variants are strongly associated with psychiatric disorders such as schizophrenia and bipolar disorder, while rare mutations cause severe developmental syndromes like Timothy Syndrome. To address the need for scalable, physiologically relevant functional annotation, we propose to develop a next-generation neural multiplexed assay of variant effect (MAVE) platform that combines prime editing with a calcium-activity–based phenotyping system in human neurons. Using ~2,000 CACNA1C variants as a test case, we will integrate precision genome editing with a novel biochemical calcium recorder (CaST) in hiPSC-derived neurons to assess variant impact on calcium signaling. This approach enables classification of variants into gain-, loss-, or benign- function categories in a scalable and context-specific manner. By overcoming limitations of existing MAVEs in fidelity, scalability, and neuronal relevance, this platform will accelerate variant interpretation, enable therapeutic prioritization, and be broadly extensible to other calcium channel genes and functional modalities.

NIMH - National Institute of Mental Health

ABSTRACT Studying multi-animal interactions is crucial for understanding cognitive mechanisms underlying social behaviors and decision-making processes. Observing collective behaviors can reveal the neural basis of social bonding, aggression, and cooperation. However, current methods for automating multi-animal behavior analysis are often too simplistic and may neglect interactions, context, and the complexity of multi-animal behavior. Here we argue that understanding complex animal behaviors requires breaking them down into fundamental units, and then forming an understanding of how these units combine to form more complex natural behaviors. Our approach is inspired by linguistic concepts, where basic elements (syllables) combine according to gram- matical rules (syntax) to convey meaning (intent). We aim to dissect multi-animal behaviors by identifying these fundamental units and their combinations to gain deeper insights into social interactions. To achieve our goals, we will organize the effort along three main aims, progressing from behavioral syllables (Aim 1), to syntax (Aim 2), and finally to intent (Aim 3). In Aim 1, we will develop methods for learning latent representations from multi-animal behavioral time se- ries and segment them into behavioral syllables—brief movements or actions efficiently describing behavioral features. The syllables from multi-animal data are mainly social syllables representing exchanges between indi- viduals that best capture or generate natural behaviors. In Aim 2, we will extract motifs, i.e., longer sequences of interactions, to comprehend complex social behaviors. To solve such a long sequence learning problem, we propose transformers for their ability to capture long-term and intricate patterns in sequential data. We will craft a compositional model that combines behavior syllables to form motifs, effectively revealing behavior syntax. In Aim 3, we will develop a novel framework for understanding intent and rewards in multi-animal behaviors, extending inverse reinforcement learning to include multiple animals. Each animal will be treated as a decision- maker whose state space will be expanded to include others' states and actions. We aim to reveal underlying intents driving social behaviors. The project will produce innovative tools for modeling multi-animal behavior, transforming raw data into frame-level behavioral syllables and constructing abstract representations of behavioral rules, patterns, and in- tent. We will provide accessible software and demos for the research community. The project's impact will be substantial, offering advanced computational tools to deepen insights into the cognitive mechanisms of social in- teractions, cooperative behaviors, and decision-making processes. This framework will enhance the analysis and prediction of complex social behaviors across species, benefit the fields of behavioral and social neuroscience, and contribute to long-term advancements in human health research.

National Alliance on Mental Illness

Grants for mental health programs specifically designed for veterans and military families experiencing mental illness.

National Institutes of Health

Reissue of PAR-20-118. This Notice of Funding Opportunity (NOFO) encourages applications to advance the discovery, preclinical development, and proof of concept (PoC) testing of new, rationally based candidate agents and neurostimulation approaches to treat mental disorders, substance use disorders (SUDs) or alcohol use disorder (AUD), and to develop novel ligands and circuit-engagement devices as tools to further characterize existing or to validate new drug/device targets. Partnerships between academia and industry are strongly encouraged. This NOFO using the U01 mechanism supports a discrete, specified, circumscribed project to be performed by the named investigator(s) in an area representing his or her specific interest and competencies Projects seeking support for a research program of multiple projects directed toward a specific major objective, basic theme or program goal, requiring a broadly based, multidisciplinary and often long-term approach should consider the companion U19 FOA.

National Institutes of Health

Reissue of PAR-20-118. This Notice of Funding Opportunity (NOFO) encourages applications to advance the discovery, preclinical development, and proof of concept (PoC) testing of new, rationally based candidate agents and neurostimulation approaches to treat mental disorders, substance use disorders (SUDs) or alcohol use disorder (AUD), and to develop novel ligands and circuit-engagement devices as tools to further characterize existing or to validate new drug/device targets. Partnerships between academia and industry are strongly encouraged. This NOFO using the U01 mechanism supports a discrete, specified, circumscribed project to be performed by the named investigator(s) in an area representing his or her specific interest and competencies Projects seeking support for a research program of multiple projects directed toward a specific major objective, basic theme or program goal, requiring a broadly based, multidisciplinary and often long-term approach should consider the companion U19 FOA.

National Institutes of Health

Reissue of PAR-20-119. This FOA encourages applications to advance the discovery, preclinical development, and proof of concept (PoC) testing of new, rationally based candidate agents and neurostimulation approaches to treat mental disorders, substance use disorders (SUDs) or alcohol use disorder (AUD), and to develop novel ligands and circuit-engagement devices as tools to further characterize existing or to validate new drug/device targets. Partnerships between academia and industry are strongly encouraged. This FOA supports a research program of multiple projects directed toward a specific major objective, basic theme or program goal, requiring a broadly based, multidisciplinary and often long-term approach. Projects seeking support for a discrete, specified, circumscribed project to be performed by the named investigator(s) in an area representing his or her specific interest and competencies should consider the companion U01 FOA.

National Institutes of Health

Reissue of PAR-20-119. This FOA encourages applications to advance the discovery, preclinical development, and proof of concept (PoC) testing of new, rationally based candidate agents and neurostimulation approaches to treat mental disorders, substance use disorders (SUDs) or alcohol use disorder (AUD), and to develop novel ligands and circuit-engagement devices as tools to further characterize existing or to validate new drug/device targets. Partnerships between academia and industry are strongly encouraged. This FOA supports a research program of multiple projects directed toward a specific major objective, basic theme or program goal, requiring a broadly based, multidisciplinary and often long-term approach. Projects seeking support for a discrete, specified, circumscribed project to be performed by the named investigator(s) in an area representing his or her specific interest and competencies should consider the companion U01 FOA.

Administration for Children and Families - OFVPS

The Resource Centers support efforts to prevent and respond to family, domestic, and dating violence by providing information, training, and technical assistance to individuals, organizations, government agencies, and communities.The National Resource Centers on Domestic Violence focus on strengthening services and knowledge in the field. One center provides training and technical assistance on domestic violence programs, research, and services for victims and their children. Another maintains a national resource library to collect, analyze, and share information on domestic violence, prevention strategies, and services for adult and youth victims.The National Indian Resource Center works with tribes and tribal organizations to improve responses to domestic violence and increase safety for Indian women. It also coordinates with federal partners that serve Native communities.Special Issue Resource Centers address key systems that impact victims of domestic violence. These centers provide training and technical assistance on responses within the justice system, child protective services, health care, and mental health systems. Additional centers focus on improving services and prevention efforts for racial and ethnic minority communities.Native-focused resource centers, including those serving Native Hawaiian and Alaska Native communities, build capacity among tribes, organizations, and service providers. They coordinate with the National Indian Resource Center and deliver culturally relevant prevention and education efforts.The National Resource Center to Expand Services for Children, Youth, and Abused Parents strengthens support for non-abusing parents and their children, including efforts to prevent or reduce foster care involvement.Sexual Assault Technical Assistance Centers support grantees in improving sexual assault prevention and response through specialized expertise and training.

NIMH - National Institute of Mental Health

PROJECT SUMMARY P HIV Pre-Exposure Prophylaxis (PrEP)harmacist autonomous-prescribing of is an HIV prevention strategy that is rapidly rising in the US – the number of states with pharmacist-prescribed PrEP has over quintupled in the past five years andPrEP prescribing by pharmacists increased doubled within four years of the first state policy. Yet, studies of this HIV prevention strategy have been concentrated in a few cities and the impact of these policies have not been evaluated. Thus, we lack rigorous national data about when, where or to whom pharmacists are prescribing PrEP, whether it is happening in areas where PrEP is most needed, or the public health impact it might be having on PrEP adherence, persistence, or subsequent HIV rates. This study’s primary purpose is to evaluate, on a national level, where pharmacist-prescribed HIV PrEP is happening or not happening within states that allow it, who it reaches, and what population-level impacts it is having on HIV. Our team was the first to identify a novel population-based surveillance metric of PrEP adherence using national pharmacy claims data, finding that nearly 1 in 5 patients with an insurance-approved, new, oral PrEP script who did not pick up PrEP from their pharmacy, of which, over 70% still did not pick up PrEP within 365 days, conferring up to 5 times higher HIV risk than those who picked up PrEP consistently. We then assessed non-adherence for by the specialty of prescribing provider, but we could not assess pharmacists as a group of providers, as legislation for pharmacist-prescribed PrEP was too new for that earlier 2019 data capture. We now embark on a timely investigation of pharmacist-prescribed PrEP, to better understand where it is happening or not happening, what populations are best reached by pharmacists, and HIV rates of patients prescribed PrEP by pharmacists compared with other prescribers. We use a nationally representative claims dataset (IQVIA) that captures ~85% of all PrEP prescriptions in the US, including public, private and individual payers, along with patient demographics and National Provider Identifier, linked to prescriber data from the National Plan and Provider Enumeration System to: compare trends and timing of pharmacist-prescribed PrEP to other prescribers, mapping to where PrEP need is high (i.e., high HIV incidence) but allowed pharmacist- prescribing is not happening (Aim 1); identify the profile of patients most reached by pharmacist-prescribed PrEP (Aim 2); and compare PrEP adherence, persistence, and HIV incidence at one year, among those prescribed by pharmacists versus other prescribers (Aim 3) as an indicator of whether patients remain engaged in PrEP care after initiation at pharmacies. Our team includes expertise in epidemiology, pharmacy, biostatistics, GIS, and HIV prevention. The study has policy implications for how pharmacists are engaged in care, and where care needs to be expanded based on populations being underserved, with the expected outcome of fully integrating pharmacists into HIV prevention.

National Institutes of Health

The purpose of this NOFO is to build research about the effectiveness, implementation, and optimization of family navigation ED diversion models for non-urgent mental health problems. Models of interest are designed to (a) utilize triage tools to identify mental health acuity, (b) facilitate engagement in mental health services and needed resources, and (c) provide support, knowledge about the mental health condition, and facilitate linkages/address barriers to help-seeking among families.

National Institutes of Health

The purpose of this NOFO is to build research about the effectiveness, implementation, and optimization of family navigation ED diversion models for non-urgent mental health problems. Models of interest are designed to (a) utilize triage tools to identify mental health acuity, (b) facilitate engagement in mental health services and needed resources, and (c) provide support, knowledge about the mental health condition, and facilitate linkages/address barriers to help-seeking among families.

National Institutes of Health

The purpose of this NOFO is to build research about the effectiveness, implementation, and optimization of family navigation ED diversion models for non-urgent mental health problems. Models of interest are designed to (a) utilize triage tools to identify mental health acuity, (b) facilitate engagement in mental health services and needed resources, and (c) provide support, knowledge about the mental health condition, and facilitate linkages/address barriers to help-seeking among families.

National Institutes of Health

The purpose of this NOFO is to build research about the effectiveness, implementation, and optimization of family navigation ED diversion models for non-urgent mental health problems. Models of interest are designed to (a) utilize triage tools to identify mental health acuity, (b) facilitate engagement in mental health services and needed resources, and (c) provide support, knowledge about the mental health condition, and facilitate linkages/address barriers to help-seeking among families.

NC Department of Health and Human Services

NCDHHS funds nonprofits, health organizations, and community agencies providing mental health, substance abuse, developmental disability, public health, and social services to vulnerable North Carolinians.