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NIMH - National Institute of Mental Health

PROJECT SUMMARY/ABSTRACT Autistic youth are far more likely to experience depression and suicidal thoughts and behaviors than their non- autistic peers, yet few autistic youth receive appropriate treatment. Untreated depression is associated with adverse short- (e.g., school refusal) and long-term outcomes (e.g., poor physical health) that impair quality of life. Families of autistic youth with depression encounter barriers to care including significant clinician shortages and high clinician uncertainty in treating this population. Clinicians frequently decline referrals due to limited autism training and few evidence-based treatments. Though Cognitive-Behavioral Therapy (CBT) is a leading intervention for depression in non-autistic youth, it has not been rigorously studied in autism. Given that autism- adapted CBT consistently outperforms standard CBT for anxiety and obsessive-compulsive disorder, it is likely that autism-adapted CBT for depression may be effective in treating symptoms; however, this remains largely underdeveloped and untested. To being to address this gap, we partnered with autistic stakeholders to develop Cognitive Behavioral Therapy for Depression in Autistic Youth (CBT-DAY) and tested the preliminary feasibility and acceptability of CBT-DAY in a pilot nonrandomized trial, with promising initial findings. CBT-DAY targets emotional reactivity, negative self-esteem, and autism self-knowledge in youth to improve depressive symptom severity. However, CBT-DAY has not been evaluated in a larger randomized controlled trial and when delivered by clinicians with limited autism training. Therefore, in this study, we seek to examine the feasibility, acceptability, and initial effectiveness of CBT-DAY and its associated clinician training model for verbally-fluent (Verbal IQ≥70) autistic youth with depression (11-17 years old) served in outpatient clinics. In the first phase of the study, we aim to develop a CBT-DAY clinician training model for clinicians with limited autism training based on feedback from 35 stakeholders including autistic youth with depression and their parents, clinicians, and clinic leaders. In the second phase, we will conduct a hybrid type 1 effectiveness-implementation trial with 60 autistic youth (11- 17 years old) with depression, 60 of their parents, and 20 clinicians with limited autism training in clinical settings, comparing CBT-DAY versus treatment-as-usual (TAU). We will test the initial feasibility, acceptability, and effectiveness of CBT-DAY in improving youth depressive symptom severity. In the final phase of the study, we will collect mixed methods data (i.e., interviews, surveys) on implementation outcomes (i.e., feasibility, acceptability, fidelity) and contextual factors influencing CBT-DAY implementation and sustainment from the recruited families, clinicians, and organizational leaders. Findings will inform future studies that scale up CBT- DAY and improve its implementation and sustainability in clinical settings. This R34 project has important clinical implications, as findings may support the testing and implementation of CBT-DAY and its associated clinician training model to improve outcomes for autistic youth with depression and increase the service workforce.

NIMH - National Institute of Mental Health

This project aims to develop federated multivariate harmonization and neuroimaging data analysis frameworks to investigate altered brain aging patterns in individuals with severe mental illness (SMI) and assess the modifying effects of metabolic syndrome (MetS). SMI, including schizophrenia spectrum disorders, bipolar disorder, and major depressive disorder, affects nearly 1 in 25 U.S. adults, is associated with reduced quality of life, and has been linked to accelerated brain aging and increased risk of early-onset dementia. Characterizing brain aging in SMI is critical for understanding its underlying neurobiological mechanisms and reducing excess morbidity and mortality in this population. Individuals with SMI face a 50% higher risk of developing MetS, a cluster of cardiometabolic risk factors associated with reduced brain health. However, how MetS modifies brain aging trajectories in SMI remains poorly understood. This project will address this knowledge gap by leveraging the ENIGMA (Enhancing NeuroImaging Genetics through Meta-Analysis) Consortium, which aggregates neuroimaging data from tens of thousands of participants across 47 countries. Despite ENIGMA’s unparalleled scope and population heterogeneity, key methodological challenges remain: (1) its distributed structure restricts data sharing to only summary-level information; (2) residual site-level heterogeneity from scanner and acquisition differences can bias results; and (3) high-dimensional, interdependent imaging features complicate statistical inference and reduce replicability of research findings. The overarching goal of this project is to develop novel, federated statistical methods that enable reliable and replicable neuroimaging analyses in large-scale, distributed collaborations, allowing participating sites to harmonize neuroimaging data and collaboratively build analytical models without sharing individual-level information. This project focuses on the following aims: Aim 1 will develop a network-aware multivariate harmonization strategy that identifies and leverages the covariance network structure among neuroimaging features to guide site-effect removal and design a summary-statistics-based federated learning method for distributed data. Aim 2 will develop a joint modeling framework that incorporates latent factor modeling to capture shared variations across neuroimaging outcomes and decorrelates the test statistic for robust multiple testing correction, and a federated learning method. In Aim 3, we will apply these methods to ENIGMA data from distributed sites to identify brain areas with abnormal aging patterns in SMI and further modified by MetS and releases user-friendly software to support scalable, distributed neuroimaging workflows. The proposed methods are broadly applicable beyond this study, enabling summary-statistics-based neuroimaging data integration, facilitating large-scale neuroscience collaborations and expanding opportunities for broader scientific partnerships.

Mental Health

Fellowship Training Program in Child Psychiatry

Mental Health

Fellowship Training Program in Child Psychiatry

NIMH - National Institute of Mental Health

Financial Tools Access and Navigation (FinTAN) for Supported Financial Decision Making – Project Summary Financial hardship and mental illness intersect in ways that have devastating consequences for millions of Americans. People with serious mental illness (SMI) are more likely to run out of money, fall behind on rent and bills, be indebted, and experience financial stress, all of which impact mental health outcomes; people from low socioeconomic status backgrounds, particularly people of color, are more likely to experience financial hardship, given historical and ongoing structural discrimination. Financial hardship among people with SMI arises partly from meagre disability benefits and/or low wages but is exacerbated when people have difficulty managing money due to their illness. Currently, money management support is limited to ad hoc budgeting advice or, more commonly, removal of financial control through a representative payee or conservator; currently, 26% of people receiving disability benefits – mostly those with SMI - have a payee. Having a payee can reduce hospitalization, homelessness and substance use and increase likelihood of treatment adherence and paying essential bills. However, there is little evidence of positive impact on mental health outcomes, and some significant downsides; some people have their autonomy unnecessarily curtailed, the arrangement can damage important relationships and hinder recovery, and others do not get needed assistance due to the understandable reluctance of some people to relinquish financial control, and shortage of payees. This raises the risk of eviction, utility disconnection, hunger, and financial abuse among people with SMI. Work is underway to develop more person-centered models and to explore guidance that does not involve removal of financial control. An area that remains underexplored is the potential for financial tools and services such as bank accounts, payment cards, and digital apps to expand and improve money management support options for people with SMI; there is compelling evidence that these are crucial in shaping people’s financial management. This project will test an intervention that will guide people to use of financial tools and services that may allow people to more effectively manage their own finances, receive assistance from another person in a way that maximizes the autonomy of the owner of the funds, and that offer pathways towards greater autonomy over time, so improving mental health and quality of life. The specific aims of this study are to: i) collaboratively create a Financial Tools Access and Navigation (FinTAN) guide to assist persons and care providers to identify the potential utility of relevant financial products, and guide them in their use; ii) pilot test the feasibility and impact of using the FinTAN guide and the associated financial tools and services among 15 people with SMI and those who assist them with their money management; iii) prepare for a future full-scale clinical trial of the FinTAN guide and relevant financial tools and services. We will use a Community Based Participatory Research approach, deploying primarily qualitative methods to assess feasibility and impact of the intervention, as well as testing various quantitative measures to be used in a future larger clinical trial.

NIAAA - National Institute on Alcohol Abuse and Alcoholism

PROJECT SUMMARY Alcohol use and hazardous drinking are ubiquitous among firefighters in the United states and is associated with significant physical and mental health risks for this population. Due to the nature of their work, firefighters experience substantially higher rates of trauma exposure and are subsequently at greater risk of developing specific mental health conditions compared to the general population, particularly trauma-related psychopathology (e.g., posttraumatic stress). Hazardous drinking and posttraumatic stress frequently co-occur among firefighters, leading to poorer health outcomes compared to either condition alone. Despite this elevated risk, firefighters often lack access to tailored, empirically supported interventions, and no existing mental health interventions address hazardous drinking in a trauma-informed framework for this at-risk population. Personalized feedback interventions (PFIs) are a promising approach that could address this gap. By delivering brief, patient-centered feedback on drinking behaviors and perceptions within the context of trauma and occupational stress, PFIs aim to reduce problematic drinking behaviors and stigma related to coping-orientated drinking and improve stress management strategies. PFIs can be brief, cost-effective, and easily disseminated in a format accessible to large groups, making them a strong candidate for use with firefighters who face critical barriers to engaging in traditional mental health programs. This innovative study aims to develop a single-session, trauma-informed, online PFI tailored specifically for firefighters, using a comprehensive, three-phase approach to address three primary aims. The Development Phase involves developing, adapting, and enhancing a trauma-informed PFI by gathering qualitative feedback from firefighters (N = 45) and using an iterative, rapid user-centered design approach to ensure the intervention is engaging for firefighters as well as relevant and aligned with fire service culture. The Evaluation Phase will assess the feasibility, acceptability, and preliminary impact of the PFI in a mixed-methods longitudinal open trial with firefighters (N = 50), with a focus on the intervention's usability, delivery, and influence on drinking behaviors. The Implementation Planning Phase will involve qualitative and quantitative assessments with fire service leaders (N = 15) to identify implementation barriers and shape future research testing the implementation process for the intervention and inform future strategies for resource integration and fostering sustainable community partnerships. This proposal will equip Dr. Lebeaut with essential training for an independent research career, including training in (1) qualitative methodologies, (2) user-centered design, (3) developing, adapting, and enhancing trauma-informed alcohol interventions, and (4) developing collaborative relationships with community partners in the fire service. The proposed study will directly inform a future R01 to evaluate the intervention’s efficacy and scalability and support the development of a firefighter-focused research program.

Health and Human Services Department

This notice is to inform the public that the Substance Abuse and Mental Health Services Administration (SAMHSA) is supporting an administrative supplement in scope of the parent award for an eligible grant recipient funded under the FY 2022 Certified Community Behavioral Health Clinic (CCBHC) Planning, Development and Implementation Grants Notice of Funding Opportunity (NOFO) SM-22-002. The total available funding is $2,000,000. This supplemental funding will be used to expand CCBHC services to the Kensington area in Philadelphia, PA, which is currently experiencing one of the highest overdose mortality rates in the nation. The proliferation of new medetomidine-linked overdoses and associated medical complications, along with the emergence of a homeless encampment in April and May of 2024, meets the threshold of a novel, unanticipated public health event and provides a compelling rationale for targeted action through a non-competitive supplement to an existing CCBHC to provide comprehensive mental health and substance use services in Kensington.

Health and Human Services Department

This notice is to inform the public that the Substance Abuse and Mental Health Services Administration (SAMHSA) is supporting an administrative supplement in scope of the parent award for one eligible grant recipient funded in FY 2024 under the Prevention Technology Transfer Centers Cooperative Agreements, Notice of Funding Opportunity (NOFO) SP-24-002. The recipient may receive up to $1,198,000. The recipient has a project end date of September 29, 2029. The supplemental funding supports the implementation of a substance use prevention fellowship program. The program will be developed in collaboration with national-level state and community organizations and aims to develop and sustain a highly trained and knowledgeable workforce of prevention professionals drawn from communities that have faced challenges in maintaining sufficient prevention staffing to meet the full scope of community needs. Fellows will be equipped to understand, apply, and exemplify the core principles and evidence-based best practices of substance use prevention. This program will support a state level fellowship program and a community level program. This program will also prepare fellows to achieve certification from the International Certification and Reciprocity Consortium (IC&RC). The supplemental funding will support fellows in the following areas: hands-on experience working in state agencies and community organizations while supported by agency mentors; virtual and in-person training in professional development and prevention; acquiring proficiency in appropriate core competencies in preparation for the Certified Prevention Specialist exam; developing management and leadership skills; and preparing for potential employment opportunities within the prevention field.

Health and Human Services Department

This notice is to inform the public that the Substance Abuse and Mental Health Services Administration (SAMHSA) is supporting an administrative supplement in scope of the parent award for one eligible grant recipient funded in FY 2024 under the Prevention Technology Transfer Centers Cooperative Agreements, Notice of Funding Opportunity (NOFO) SP-24-002. The recipient may receive up to $1,198,000. The recipient has a project end date of September 29, 2029. The supplemental funding supports the implementation of a substance use prevention fellowship program. The program will be developed in collaboration with national-level state and community organizations and aims to develop and sustain a highly trained and knowledgeable workforce of prevention professionals drawn from communities that have faced challenges in maintaining sufficient prevention staffing to meet the full scope of community needs. Fellows will be equipped to understand, apply, and exemplify the core principles and evidence-based best practices of substance use prevention. This program will support a state level fellowship program and a community level program. This program will also prepare fellows to achieve certification from the International Certification and Reciprocity Consortium (IC&RC). The supplemental funding will support fellows in the following areas: hands-on experience working in state agencies and community organizations while supported by agency mentors; virtual and in-person training in professional development and prevention; acquiring proficiency in appropriate core competencies in preparation for the Certified Prevention Specialist exam; developing management and leadership skills; and preparing for potential employment opportunities within the prevention field.

Health and Human Services Department

This notice is to inform the public that the Substance Abuse and Mental Health Services Administration (SAMHSA) is supporting an administrative supplement in scope of the parent award for one eligible grant recipient funded in FY 2024 under the Prevention Technology Transfer Centers Cooperative Agreements, Notice of Funding Opportunity (NOFO) SP-24-002. The recipient may receive up to $1,198,000. The recipient has a project end date of September 29, 2029. The supplemental funding supports the implementation of a substance use prevention fellowship program. The program will be developed in collaboration with national-level state and community organizations and aims to develop and sustain a highly trained and knowledgeable workforce of prevention professionals drawn from communities that have faced challenges in maintaining sufficient prevention staffing to meet the full scope of community needs. Fellows will be equipped to understand, apply, and exemplify the core principles and evidence-based best practices of substance use prevention. This program will support a state level fellowship program and a community level program. This program will also prepare fellows to achieve certification from the International Certification and Reciprocity Consortium (IC&RC). The supplemental funding will support fellows in the following areas: hands-on experience working in state agencies and community organizations while supported by agency mentors; virtual and in-person training in professional development and prevention; acquiring proficiency in appropriate core competencies in preparation for the Certified Prevention Specialist exam; developing management and leadership skills; and preparing for potential employment opportunities within the prevention field.

NIMH - National Institute of Mental Health

PROJECT SUMMARY Anorexia nervosa (AN) is a devastating eating disorder that has one of the highest mortality rates of any psychiatric illness. AN is characterized by persistent restriction of food intake below the body’s needs, which can be understood as a series of maladaptive food choices. Choices are guided by neural value signals that reflect an individual’s preference, encoded in the ventromedial prefrontal cortex (vmPFC). Individuals with AN assign low value to high-fat/calorie foods they consider to be unhealthy, and are consequently unwilling to eat these foods. The mechanisms underlying this disturbance in value assignment are unclear, though the significant eating-related distress experienced by individuals with AN suggests involvement of brain systems signaling aversive valence. This hypothesis has not been directly tested, which precludes targeting aversive valence systems in treatments for AN. This study will examine whether aversive valence is assigned to energy- dense foods in AN, and whether this is a mechanism of restrictive eating pathology. Patients with AN (n=50) and healthy controls (HC, n=50) will complete a food valuation task in which they rate their preference to eat a range of foods (including those typically highly disliked and liked by HC), while undergoing fMRI scanning and autonomous arousal (skin conductance response) assessment. After scanning participants will rate food items across 20 attributes, including aversive valence, healthiness, and nutritious and sensory features (e.g., fat content, texture). Using computational and multivariate fMRI analyses, we will examine 1) associations between ratings of aversive valence and food healthiness, 2) activation of aversive valence representations in the amygdala by foods considered unhealthy, 3) coupling of regions encoding aversive valence (amygdala) with those encoding healthiness (orbitofrontal cortex) and subjective preference (vmPFC). Comparing AN and HC groups will allow us to identify 1) whether assigning aversive valence to energy-dense foods is a mechanism of restrictive eating in AN; 2) regions encoding aversive valence of energy-dense foods in AN. Exploratory analyses will examine the mechanisms by which information about additional food attributes is integrated into value computations, to identify additional disturbances in food choice valuation processes in AN. Associations between the activation and coupling of brain regions encoding aversive valence, and clinical characteristics, will be explored among patients. In completing the planned research and training, the applicant will develop expertise in cognitive and computational neuroscience as applied to eating behavior. This expertise combined with study findings will 1) form the foundation of a unique research program examining disturbances in food choice valuation processes in eating disorders, and 2) support an R01 proposal to examine the malleability of aversive valence representations in AN, and mechanisms of/lack of change.

NIMH - National Institute of Mental Health

Project Summary/Abstract The contribution of individual disease-relevant genes to brain development still remains unknown. The long-term goal of our laboratory is to elucidate the intersection of molecular signaling pathways that are disrupted in neurodevelopmental disorders with those pathways that are important for specific aspects of brain development. Two members of the FOXP family of transcription factors, FOXP1 and FOXP2, have been linked to monogenetic forms of intellectual disability, autism spectrum disorders, and specific speech and language deficits. Variants in FOXP1 or FOXP2 are among the most significant genes associated with autism spectrum disorders. We previously showed that Foxp1 and Foxp2 both have significant contributions to cortical and striatal development. We linked these developmental changes via studies of gene expression, electrophysiology, and behaviors. We further identified non-cell-autonomous changes in gene expression using newly available single-cell RNA- sequencing technology. Based on these data, the central hypothesis driving this proposal is that Foxp1 and Foxp2 are key orchestrators of transcriptional signaling cascades in a cell type-specific manner that are important for neuronal function and are at risk in neurodevelopmental disorders such as autism. We propose to identify these cell type-specific contributions in the developing cortex by using rodent models through three specific aims: 1) Determine the cell type-specific gene expression programs regulated by Foxp1 in the developing cortex; 2) Determine the cell type-specific gene expression programs regulated by Foxp2 in the developing cortex; and 3) Assess the role of Foxp1 and Foxp2 in cell type-specific activity-dependent neuronal function. Together, these aims will delineate the cell type contribution of both Foxp1 and Foxp2 to cortical development. The rodent models and cell-type specific genomic datasets will aprovide insight into the basic molecular mechanisms governing normal mammalian brain development.

National Institutes of Health

This Funding Opportunity Announcement (FOA) is intended to encourage research on 1) the development and/or pilot testing of new or adapted interventions; 2) pilot testing interventions with demonstrated efficacy in broader scale effectiveness trials; or 3) innovative services research directions that require preliminary testing or development. This FOA will utilize the R34 grant mechanism This FOA provides resources for evaluating the feasibility, tolerability, acceptability and safety of novel approaches to improving mental health and modifying health risk behavior, and for obtaining the preliminary data needed as a pre-requisite to a larger-scale (efficacy or effectiveness) intervention or services study. 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

Clinical Trials to Test the Effectiveness of Treatment, Preventive, and Services Interventions (R01 Clinical Trial Required). This NOFO is a key element of NIMHs set of NOFOs to support clinical trials research across the intervention development and testing pipeline. The NOFO supports (1) clinical trials to test the effectiveness of optimized therapeutic and preventive interventions for use in community and practice settings; and (2) clinical trials to evaluate the effectiveness of patient-, provider-, organizational-, or systems-level services interventions to improve access, continuity, quality, equity, and/or value of mental health services. This NOFO is intended to support trials that: address a significant problem, such that the findings have potential to inform practice; are adequately powered to definitively answer the primary research question(s), with well-justified hypotheses supported by pilot data; and are designed to examine questions regarding mediators and moderators of effects. Consistent with the NIMH experimental therapeutics approach, this NOFO is intended to support effectiveness trials that explicitly address whether the intervention engages the target(s)/mechanism(s) presumed to underlie the intervention effects (i.e., the mechanism(s) that accounts for changes in clinical/functional outcomes, changes in provider behavior, improved access or continuity of services, etc.). The collaborative R01 mechanism provides support for multisite trials when two or more sites are necessary for completion of the trial (e.g., to increase sample size, accelerate recruitment, or increase sample diversity and representation).

National Institutes of Health

Clinical Trials to Test the Effectiveness of Treatment, Preventive, and Services Interventions (R01 Clinical Trial Required). This NOFO is a key element of NIMHs set of NOFOs to support clinical trials research across the intervention development and testing pipeline. The NOFO supports (1) clinical trials to test the effectiveness of optimized therapeutic and preventive interventions for use in community and practice settings; and (2) clinical trials to evaluate the effectiveness of patient-, provider-, organizational-, or systems-level services interventions to improve access, continuity, quality, equity, and/or value of mental health services. This NOFO is intended to support trials that: address a significant problem, such that the findings have potential to inform practice; are adequately powered to definitively answer the primary research question(s), with well-justified hypotheses supported by pilot data; and are designed to examine questions regarding mediators and moderators of effects. Consistent with the NIMH experimental therapeutics approach, this NOFO is intended to support effectiveness trials that explicitly address whether the intervention engages the target(s)/mechanism(s) presumed to underlie the intervention effects (i.e., the mechanism(s) that accounts for changes in clinical/functional outcomes, changes in provider behavior, improved access or continuity of services, etc.). The collaborative R01 mechanism provides support for multisite trials when two or more sites are necessary for completion of the trial (e.g., to increase sample size, accelerate recruitment, or increase sample diversity and representation).

NIMH - National Institute of Mental Health

Summary: Astrocytes are active participants in synaptic function and impose their effect by mechanisms such as release of gliotransmitters and synaptogenic molecules involved in synapse formation, maturation and pruning. Astrocytes express a variety of channels and receptors which contribute to their function. Recent investigations using transgenic lines to selectively tag astrocytes and improved techniques for acute dissociation and in situ analysis have revealed robust expression of NMDA receptors in cortical astrocytes. Our recent studies and preliminary results utilizing genetic models, electrophysiology and pharmacological tools demonstrate that cortical and striatal astrocytes express non-canonical GluN2C-containing NMDA receptors. Importantly, these studies demonstrate a critical role of astrocytic NMDA receptors in behavioral control including fear extinction and maintenance of cocaine preference memory. However, there are still large gaps in our understanding of the properties and contribution of astrocytic NMDA receptors to physiology and drug responses. The proposed studies will advance the concept that astrocytic NMDA receptors regulate basal neurotransmission and have unique properties which contribute to NMDA receptor channel blocker effects. Further we hypothesize that astrocytic NMDA receptors regulate the levels of astrocyte-derived synaptogenic factors and their effect on synaptic organization and behavior. Proposed studies will focus on medial prefrontal cortex and dorsal striatum, regions relevant to pathophysiology of neuropsychiatric disorders. Specific Aim 1 will examine the properties and pharmacological characteristics and subunit composition of astrocytic NMDA receptors. In addition, sensitivity of astrocytic NMDA receptors to ketamine and their contribution to the antidepressant effects of ketamine will be tested. Specific Aim 2 will test the effect of modulation of astrocytic NMDA receptors on excitatory neurotransmission in medium spiny neurons. The underlying gliotransmitter mechanism in such effects and its behavioral consequence will be examined. Specific Aim 3 will test the role of astrocytic NMDA receptors in regulating the levels of astrocyte-derived synaptogenic factors and their effect on synaptic organization and cognitive flexibility. To accomplish these aims we will utilize a combination of brain slice electrophysiology, calcium imaging, novel pharmacological tools, in vivo fiber photometry, behavior and in vivo manipulation together with newly developed genetic models for selective manipulation of astrocytic NMDA receptors. The expected outcomes from the proposed studies will identify properties and novel functions of astrocytic NMDA receptors in neural circuits with important implications for neuropsychiatric disorders and NMDA receptor channel blocker effect. Moreover, given the unique subunit composition of astrocytic NMDA receptors, it may be possible to selectively target these receptors to achieve therapeutic effects. Scientific rigor of research design is established by the use of multiple methods and approaches, use of validated models and reagents, consideration of blinding, biological variables and sex in addition to other aspects of experimental design.

NIMH - National Institute of Mental Health

PROJECT SUMMARY/ABSTRACT The transition from adolescence to adulthood is a critical stage of development characterized by significant changes in social-emotional behavior. One of the central brain structures modulating this transition is the amygdala. The development of the amygdala continues through adolescence, undergoing an expansion in size and neuron number into early adulthood. These changes enable healthy social and emotional development, and perturbations in amygdala development and maturation are linked a host of mental health disorders, most notably autism spectrum disorders (ASD) and the long-term behavioral consequences as a result of early life stress (ELS). However, the amygdala neuronal and circuit substrates underlying changes coincident with this major life transition remain little understood. In our published studies in humans and mice, we identified and characterized a unique population of immature neurons in the paralaminar nucleus of the amygdala (PL). While these neurons are born embryonically, they interestingly delay their maturation until adolescence when they differentiate into excitatory neurons. Thus, our discovery and characterization of PL neurons that undergo maturation coincident with adolescence revealed a novel mechanism of brain plasticity during a critical stage of post-natal development. Using the mouse as a model, the goal of our proposed studies is to understand the function of amygdala late-maturing neurons from adolescence to early adulthood and what drives their maturation. To test this, we will examine how PL neuronal responses change over time (Aim 1), the necessity and sufficiency of PL neurons in this transition (Aim 2), and the role inhibitory neurotransmission plays in their maturation and later function (Aim 3). Our proposed studies are also an essential step to understanding the role late maturing PL neurons play in neuro-atypical brain function associated with disorders of social cognition to which the PL has previously been linked, such as ASD and the long-term consequences of ELS.

NIDCR - National Institute of Dental and Craniofacial Research

Project Summary Nonsyndromic orofacial cleft (OFC) is the most common craniofacial birth defect, affecting 1 in 700 individuals worldwide. OFCs cause significant psychosocial burden, increase risks for early life complications, cancer predisposition, and mental health disorders, while reducing quality of life and increasing mortality rates. OFC’s complex etiology involves multiple genetic and environmental factors, with over 60 identified risk loci accounting for only a minority of estimated risk. While family history exists in 23% of cases, monozygotic twins show only 50% concordance, suggesting factors beyond genetic risk. Epigenetic factors, such as differential DNA methylation (DNAm) are associated with increased OFC risk, can alter susceptibility to different cleft types and modify OFC penetrance; however, the overall role of epigenetics in OFC etiology remains understudied. DNAm is a covalent addition of a methyl (CH3) group to the nucleotide cytosine (CpG) that can lead to changes in expression of the target gene. DNAm can be affected by environmental influences and genetic variation via methylation quantitative loci (meQTLs). Our group recently showed evidence that differential methylation can contribute to phenotypic variability in patients with Van der Woude syndrome and nonsyndromic clefts, including monozygotic twins. Other studies have also shown that differentially methylated regions implicated in OFC etiology cluster near genes previously implicated in palatogenesis and some differential methylation is likely driven by genetic variation. These premises highlight the need for functional studies to test the role of the DNAm in OFC etiology. We hypothesize that aberrant DNAm and the resulting alterations in gene expression play a key role in the etiology of OFCs, and that certain common genetic variants that affect OFC risk do so by influencing DNAm. Based on our preliminary identification and replication of 9 meQTLs, we have implemented an in vitro CRISPR-based, gene- editing pipeline using relevant cell lines for functional meQTL validation. Our main goal is to leverage both our 9 confirmed meQTLs and our in vitro pipeline to investigate meQTL pathogenic mechanisms that lead to abnormal gene expression resulting in OFCs, via aims designed to (1) Functionally validate the impact of the meQTL (SNP) on the CpG methylation levels; and (2) Confirm CpG-target genes. Our pipeline has the potential to elucidate the biological mechanisms underlying statistical associations, particularly for non- coding SNPs with unclear functional relevance. The successful completion of these aims will lay the foundation for future R01 proposals designed to further investigate gene-epigenome networks in craniofacial development, including the functional impact of meQTLs on orofacial development using in vivo.

NIMH - National Institute of Mental Health

Project Summary Schizophrenia (SCZ) is a severe psychiatric disorder with a complex genetic component. Genetic studies have identified a strong link between genetic risk and the neurodevelopmental processes of the brain, contributing to SCZ etiology. Notably, neurogenesis is especially vulnerable to disruption by SCZ genetic factors. However, which SCZ-associated risk genes and variants affect neurogenesis and how non-coding risk variants influence risk gene expression remains largely unknown. The overarching goal of this K99/R00 project is to systematically delineate the direct connection among SCZ-associated variants, risk genes, and neurogenesis by developing and applying advanced functional genomic screening platforms in cerebral organoids. During the K99 phase, I will elucidate the roles of SCZ risk genes in neurogenesis by conducting pooled high throughput CRISPR interference screens in key neurogenic cell types derived from cerebral organoids. During the K99/R00 phase, I will employ prime editing screens in cerebral organoids to assess the effects of individual SCZ-associated variants on neurogenesis. Finally, during the R00 phase, I will investigate the regulatory impact of non-coding SCZ variants on gene expression using single-cell prime editing screens in cerebral organoids. The successful completion of these aims will provide novel insights into which and how SCZ-associated genes and variants disrupt neurogenesis, advancing our understanding of the neurodevelopmental basis of SCZ and aiding in identifying novel therapeutic targets. Additionally, this research will enhance our ability to interpret the broader role of genetic factors in neurogenesis and will generate essential training data for machine learning models focused on neurogenesis, with potential implications for other neurodevelopmental disorders. During the K99 phase, I will further improve my expertise in functional genomics, organoid models, statistical analysis, machine learning, and neurobiology of SCZ, as well as other essential professional skills, including leadership, mentoring, writing, and presentation. To achieve my training and research objectives, I have assembled an exceptional and interdisciplinary team of mentors and collaborators including Dr. Yin Shen (primary mentor, functional genomics and gene regulation), Dr. Arnold Kriegstein (co-mentor, brain organoid), Dr. Katherine Pollard (co-mentor, statistics and machine learning), Dr. Hongjun Song (co-mentor, SCZ neurobiology), and Dr. Xin Jin (collaborator, complex in vivo screening methodologies). This comprehensive mentorship and collaborative research environment will foster my transition to an independent research career, with a long-term goal of elucidating the genomic mechanisms underpinning neurological disorders, ultimately enabling the identification of novel therapeutic targets for prevention and treatment.

NIMH - National Institute of Mental Health

PROJECT SUMMARY Somatic mosaicism, the genomic differences among the billions of cells in the human brain, may explain the incomplete penetrance and variable expressivity in highly heritable neurodevelopmental disorders. Thousands of clonal somatic mosaic variants (SMVs) in subpopulations of neurons have been discovered in brains of schizophrenia and autism patients, necessitating an urgent, unmet demand to determine if these diverse somatic mutations have a causal role in disease. Major challenges include (1) the inability of using conventional statistical methods for common variants to associate disease status with risk variant, (2) the vast space of non-coding candidates with unknown function, and (3) the unresolved relevant cell types and developmental stages linking mutations to phenotypes. Just as integrating high-throughput genomic-, CRISPR, and stem cell-based technologies resulted in significant progress in understanding germline risk variants, they represent a novel approach to uniquely address the major challenges in the field of somatic mosaicism. As a co-mentored computational and experimental biologist, I will leverage state-of-the-art functional genomic technologies and bioinformatic pipelines to systematically characterize all brain non-coding SMVs discovered to date, resolving their causal roles in neurodevelopmental disorders. From all SMVs identified in case and control brains, I will first create a functional catalog of expression-modulated SMVs in a developmental- and cell-type-specific manner by applying massively parallel reporter assays in human induced pluripotent stem cells (hiPSCs)-derived neural progenitor cells (NPCs) and post-mitotic neurons. By doing so, I will be able to interrogate whether differences in patterns of expression-modulated SMVs exist between cases and controls. Second, I will compare the somatic and germline genetic architectures across neurodevelopmental disorders, determining whether somatic mutations act via the same pathways as germline mutations, or affect genes relevant to diseases, indicating a causal role. By simultaneously uncovering the downstream transcriptomic profiles of hundreds of regulatory elements harboring SMVs with CRISPR screen, I will be able to pinpoint putative disease-causal SMVs. Finally, I will validate the phenotypic impact of putative causal SMVs in physiologically complex and relevant models including 3D brain organoids and “mosaicism-in-a-dish”, testing both cell-autonomous and non-autonomous mechanisms of SMVs. Overall, this work, representing a novel application of scalable functional genomic technologies to SMVs, provides a framework to identify SMVs with putative causal effects in neurodevelopmental diseases, advancing our understanding of a poorly understood disease mechanism. This fellowship will provide me with training encompassing computational genomics, stem cell models and broadly applicable phenotyping techniques, setting a foundation for me to launch an independent research program distinct from my mentors', querying somatic mosaicism's impact into novel cell types, contexts and diseases towards discovering novel therapeutic targets.

Office of National Drug Control Policy

<p><span style="color: rgb(34, 34, 34);">ONDCP’s Drug Court Training and Technical Assistance Cooperative Agreement supports training and technical assistance (TTA) to ensure access to evidence-based addiction treatment through drug courts, including when substance use disorder co-occurs with other mental healthconditions. ONDCP seeks to reduce drug use and its consequences through evidence-based treatment that leads to long-term recovery, and this cooperative agreement will support the President’s priorities by applying this to the criminal justice system.&nbsp;The purpose of this cooperative agreement is to: (1) educate, train, and produce materials to improve the implementation of evidence-based treatment to individuals with addiction, including when substance use disorder co-occurs with other mental health conditions; (2)decrease criminal justice costs and recidivism rates; and (3) improve access to evidence-based addiction treatment that includes medications for opioid use disorder through drug courts. The cooperative agreement recipient shall:• Use expert practitioners in the science of addiction and evidence-based addiction treatment, as well as integration of treatment into the criminal justice system.• Use licensed behavioral health practitioners.• Provide in-person training, online training, and jurisdiction-specific technical assistanceto a wide range of geographically distributed areas—including rural locations—at thestate, local, and tribal levels.• Ensure close alignment of all TTA materials with the Trump Administration’s policy priorities, including the 2026 National Drug Control Strategy; an evidence-based approach to treating addiction--to include FDA-approved medications for opioid use disorder--contingency management, and other evidence-based behavioral health modalities for other substance use disorders; naloxone distribution and naloxone training.• Designate and fund a research or academic organization to conduct an independent assessment of the effectiveness and impact of training and technical assistance conducted under this cooperative agreement. The independent study should involve data collectionfrom state, local, and tribal jurisdictions engaged in cooperative agreement recipient programming.</span></p>

Office of National Drug Control Policy

ONDCP s Drug Court Training and Technical Assistance Cooperative Agreement supports training and technical assistance (TTA) to ensure access to evidence-based addiction treatment through drug courts, including when substance use disorder co-occurs with other mental healthconditions. ONDCP seeks to reduce drug use and its consequences through evidence-based treatment that leads to long-term recovery, and this cooperative agreement will support the President s priorities by applying this to the criminal justice system. The purpose of this cooperative agreement is to: (1) educate, train, and produce materials to improve the implementation of evidence-based treatment to individuals with addiction, including when substance use disorder co-occurs with other mental health conditions; (2)decrease criminal justice costs and recidivism rates; and (3) improve access to evidence-based addiction treatment that includes medications for opioid use disorder through drug courts. The cooperative agreement recipient shall: Use expert practitioners in the science of addiction and evidence-based addiction treatment, as well as integration of treatment into the criminal justice system. Use licensed behavioral health practitioners. Provide in-person training, online training, and jurisdiction-specific technical assistanceto a wide range of geographically distributed areas including rural locations at thestate, local, and tribal levels. Ensure close alignment of all TTA materials with the Trump Administration s policy priorities, including the 2026 National Drug Control Strategy; an evidence-based approach to treating addiction--to include FDA-approved medications for opioid use disorder--contingency management, and other evidence-based behavioral health modalities for other substance use disorders; naloxone distribution and naloxone training. Designate and fund a research or academic organization to conduct an independent assessment of the effectiveness and impact of training and technical assistance conducted under this cooperative agreement. The independent study should involve data collectionfrom state, local, and tribal jurisdictions engaged in cooperative agreement recipient programming.

Community Oriented Policing Services

The Office of Community Oriented Policing Services (COPS) is the component of the U.S. Department of Justice responsible for advancing the practice of community policing and the Administration’s priority of Making America Safe Again by supporting the nation’s state, local, territorial and Tribal law enforcement agencies through information and grant resources. This is a notice of funding opportunity (NOFO) for the FY26 Safer Outcomes: Enhancing Crisis Response Training for Law Enforcement Program. This opportunity seeks to promote safe outcomes during police encounters through relevant training. Awards will be made to entities seeking to implement training and related supports. Training is supported for law enforcement officers, support personnel employed by law enforcement agencies, and associated mental health professionals working on crisis intervention teams as employees of a law enforcement agency or under a legal agreement with a law enforcement agency. Training programs and related funding requests must address one of more of the areas of focus listed below: 1. De-escalation tactics and alternatives to use of force. For purposes of this funding opportunity, the term “de-escalation” means taking action or communicating verbally or nonverbally during a potential force encounter in an attempt to stabilize the situation and reduce the immediacy of the threat so that more time, options, and resources can be called upon to resolve the situation without the use of force or with a reduction in the force necessary. 2. Safely responding to an individual experiencing a mental or behavioral health or suicidal crisis. Such a crisis is one in which the behavior of a person puts the person at risk of hurting himself or herself or others or impairs or prevents the person from being able to care for himself or herself or function effectively in the community. This also includes situations in which a person is under the influence of a drug or alcohol, is suicidal, or experiences symptoms of a mental illness; or may exhibit symptoms, including emotional reactions (such as fear or anger), psychological impairments (such as inability to focus, confusion, or psychosis), and behavioral reactions (such as the activation of a freeze, fight, or flight response). Under this focus area, applicants can request funds for co-responding clinicians. 3. Safe encounters with individuals with disabilities. The term “disability” has the meaning given that term in section 3 of the Americans with Disabilities Act of 1990 (42 U.S.C. 12102). 4. Successfully participating on a crisis intervention team. The term “crisis intervention team” means a collaborative, interdisciplinary team that brings together specially trained law enforcement officers, mental health providers, and other community stakeholders to respond to mental health–related calls, use appropriate de-escalation techniques, and assess if referral to services or transport for mental health evaluation is appropriate. 5. Making referrals to community-based services and support. This may include mental and behavioral health services and support, housing assistance programs, public benefits programs, the National Suicide Prevention Lifeline, and other services. Important Notice – Upcoming LEDTA National Standards. Please visit https://ledtatraining.org/. If applicable, the COPS Office will notify your organization of any award requirements to align with LEDTA national standards The COPS Office seeks to promote safe outcomes during police encounters through relevant training through this NOFO in the following three funding categories: Category 1: FY26 Safer Outcomes: Support for Law Enforcement Agencies Proposed projects for this category must address one or more of the areas of focus listed in the Purpose section of this funding opportunity. Category 2: FY26 Safer Outcomes: Continuation of Regional De-Escalation Training Centers Awards under this category will be made through two funding paths: Path 1: The Continuation of Regional De-escalation Training Centers path will provide continuation funding for the provision of training and programming to state, local, tribal, and territorial law enforcement agencies in a multistate region. Path 2: The Continuation and Coordination of Regional De-escalation Training Centers path will support the coordination of the Regional De-escalation Training Centers, as well as the provision of training and programming to state, local, tribal, and territorial law enforcement agencies in a multistate region. Regardless of the path selected, proposed projects for this category must address one or more of the areas of focus in the Purpose area of this funding opportunity. Category 3: FY26 Safer Outcomes: Curriculum Integration for Law Enforcement Academies and State-Level Training Centers This program promotes safe outcomes during police encounters through the integration of de-escalation and crisis response training into the curriculum of law enforcement academies and state-level training commissions. Partnerships with experts in adult learning concepts and curriculum development are highly encouraged. Awards under this funding opportunity will be made through two funding paths: Funding Paths Path 1: The Academy Path Traditional academy curricula provide separate blocks of instruction on prescribed material, whereas a curriculum that integrates one or more concepts will revisit these concepts throughout the entire training program within the context of new material. De-escalation and crisis response concepts are ideal for integration because they are relevant in the contexts of many traditional law enforcement training domains, including use of force, criminal law, communication, and procedural justice. These awards are intended to provide resources for academies seeking to update, revise, and supplement basic training curricula in a way that includes integration of training on de-escalation and crisis response as described in the five areas of focus. Path 2: The Commission Path Many state POSTs enforce training standards or mandate various training curricula that have developed over time to reflect changes to legislation, technological advancements, and evolving responsibilities of the police profession. This can sometimes result in a set of standards or a program of training that is not clearly defined or synthesized. These awards are intended to provide resources for commissions seeking to update, revise, and supplement law enforcement training standards or mandated curricula in a way that includes integration of training on de-escalation and crisis response as described in the five focus areas.

Community Oriented Policing Services

The Office of Community Oriented Policing Services (COPS) is the component of the U.S. Department of Justice responsible for advancing the practice of community policing and the Administration s priority of Making America Safe Again by supporting the nation s state, local, territorial and Tribal law enforcement agencies through information and grant resources. This is a notice of funding opportunity (NOFO) for the FY26 Safer Outcomes: Enhancing Crisis Response Training for Law Enforcement Program. This opportunity seeks to promote safe outcomes during police encounters through relevant training. Awards will be made to entities seeking to implement training and related supports. Training is supported for law enforcement officers, support personnel employed by law enforcement agencies, and associated mental health professionals working on crisis intervention teams as employees of a law enforcement agency or under a legal agreement with a law enforcement agency. Training programs and related funding requests must address one of more of the areas of focus listed below: 1. De-escalation tactics and alternatives to use of force. For purposes of this funding opportunity, the term de-escalation means taking action or communicating verbally or nonverbally during a potential force encounter in an attempt to stabilize the situation and reduce the immediacy of the threat so that more time, options, and resources can be called upon to resolve the situation without the use of force or with a reduction in the force necessary. 2. Safely responding to an individual experiencing a mental or behavioral health or suicidal crisis. Such a crisis is one in which the behavior of a person puts the person at risk of hurting himself or herself or others or impairs or prevents the person from being able to care for himself or herself or function effectively in the community. This also includes situations in which a person is under the influence of a drug or alcohol, is suicidal, or experiences symptoms of a mental illness; or may exhibit symptoms, including emotional reactions (such as fear or anger), psychological impairments (such as inability to focus, confusion, or psychosis), and behavioral reactions (such as the activation of a freeze, fight, or flight response). Under this focus area, applicants can request funds for co-responding clinicians. 3. Safe encounters with individuals with disabilities. The term disability has the meaning given that term in section 3 of the Americans with Disabilities Act of 1990 (42 U.S.C. 12102). 4. Successfully participating on a crisis intervention team. The term crisis intervention team means a collaborative, interdisciplinary team that brings together specially trained law enforcement officers, mental health providers, and other community stakeholders to respond to mental health related calls, use appropriate de-escalation techniques, and assess if referral to services or transport for mental health evaluation is appropriate. 5. Making referrals to community-based services and support. This may include mental and behavioral health services and support, housing assistance programs, public benefits programs, the National Suicide Prevention Lifeline, and other services. Important Notice Upcoming LEDTA National Standards. Please visit https://ledtatraining.org/. If applicable, the COPS Office will notify your organization of any award requirements to align with LEDTA national standards The COPS Office seeks to promote safe outcomes during police encounters through relevant training through this NOFO in the following three funding categories: Category 1: FY26 Safer Outcomes: Support for Law Enforcement Agencies Proposed projects for this category must address one or more of the areas of focus listed in the Purpose section of this funding opportunity. Category 2: FY26 Safer Outcomes: Continuation of Regional De-Escalation Training Centers Awards under this category will be made through two funding paths: Path 1: The Continuation of Regional De-escalation Training Centers path will provide continuation funding for the provision of training and programming to state, local, tribal, and territorial law enforcement agencies in a multistate region. Path 2: The Continuation and Coordination of Regional De-escalation Training Centers path will support the coordination of the Regional De-escalation Training Centers, as well as the provision of training and programming to state, local, tribal, and territorial law enforcement agencies in a multistate region. Regardless of the path selected, proposed projects for this category must address one or more of the areas of focus in the Purpose area of this funding opportunity. Category 3: FY26 Safer Outcomes: Curriculum Integration for Law Enforcement Academies and State-Level Training Centers This program promotes safe outcomes during police encounters through the integration of de-escalation and crisis response training into the curriculum of law enforcement academies and state-level training commissions. Partnerships with experts in adult learning concepts and curriculum development are highly encouraged. Awards under this funding opportunity will be made through two funding paths: Funding Paths Path 1: The Academy Path Traditional academy curricula provide separate blocks of instruction on prescribed material, whereas a curriculum that integrates one or more concepts will revisit these concepts throughout the entire training program within the context of new material. De-escalation and crisis response concepts are ideal for integration because they are relevant in the contexts of many traditional law enforcement training domains, including use of force, criminal law, communication, and procedural justice. These awards are intended to provide resources for academies seeking to update, revise, and supplement basic training curricula in a way that includes integration of training on de-escalation and crisis response as described in the five areas of focus. Path 2: The Commission Path Many state POSTs enforce training standards or mandate various training curricula that have developed over time to reflect changes to legislation, technological advancements, and evolving responsibilities of the police profession. This can sometimes result in a set of standards or a program of training that is not clearly defined or synthesized. These awards are intended to provide resources for commissions seeking to update, revise, and supplement law enforcement training standards or mandated curricula in a way that includes integration of training on de-escalation and crisis response as described in the five focus areas.