Search Grants — Free, No Account Required

National Institutes of Health

NIMH seeks applications for pilot research to adapt, optimize, and test behavioral interventions that address common sleep problems in adolescents and young adults with or at risk for a mental health disorder. This notice of funding opportunity (NOFO) supports pilot clinical trials designed to evaluate the feasibility, tolerability, acceptability, safety, and potential effectiveness of the approach in real world settings. Applications should aim to conduct a preliminary test of the intervention's impact on sleep and mental health outcomes, as well as an examination of the mechanisms that underlie the intervention's effectiveness, and to obtain preliminary data needed as a prerequisite for larger-scale effectiveness trials. In addition, interdisciplinary, collaborative teams of investigators from the fields of mental health, sleep medicine, developmental science, clinical trials research methods, behavioral economics, implementation science, data science, and human computer interaction are encouraged.

NIMH - National Institute of Mental Health

PROJECT SUMMARY Significance: Despite availability of modern antiretroviral therapy regimens in the United States, many people living with HIV (PWH) experience barriers to care, and targets to End the HIV Epidemic (EHE) have still not been achieved. Case management is an evidence-based intervention which can improve HIV outcomes; however, these programs require extensive human resources to deliver services to PWH who are hardest to reach, which can limit feasibility. To realize EHE targets, implementation innovations are needed to optimize delivery of these programs to facilitate viral suppression and retention in care. Setting: The HIV Enhanced Access to Treatment (HEAT) program at Massachusetts General Hospital is a Ryan-White supported intensive case management program for PWH who experience significant barriers to care, often due to mental health comorbidities, substance use, homelessness/unstable housing, and/or language/cultural barriers. Innovation: We propose to develop a novel multi-level case management implementation toolkit in conjunction with community partners, with components for both patients and care team members, that is designed specifically to optimize care for PWH with the greatest barriers to care who are often unreached. Investigators: Our multidisciplinary team of investigators with expertise in clinical epidemiology (Suzanne McCluskey), HIV program leadership (Jacqueline Chu), qualitative research (Christina Psaros), and implementation science (Ingrid Bassett) is well-suited to address these public health challenges through the following Specific Aims: Aim 1) We will conduct a mixed-methods study to assess the determinants of viral suppression achieved through participation in the HEAT program. We will analyze historical data from the HEAT program, followed by semi-structured in-depth interviews with HEAT program participants, HEAT program staff, and representatives of community-based organizations, guided by the Consolidated Framework for Implementation Research. Aim 2) We will employ a Delphi process to develop a toolkit to optimize the delivery of Ryan White-supported intensive case management programs. We will invite participation from multiple levels of stakeholders including HEAT program participants, HEAT program staff and leadership, representatives from partnering community- based organizations, Ryan White program administrators, and leaders of external Ryan White-supported programs. Aim 3) We will evaluate the pilot implementation of the toolkit within the HEAT program using the Proctor outcomes framework, assessing implementation outcomes of feasibility, acceptability, and appropriateness, as well as preliminary recipient-level outcomes of viral suppression and retention in care at six months. Impact: This study proposal responds directly to the NIH EHE priorities through development of an innovative strategy to expand engagement in HIV care with a focus on populations that are largely unreached. Results of this work will inform development of a future cluster randomized trial to evaluate deployment of the toolkit across Ryan White programs in priority areas where EHE targets have not been met.

NIMH - National Institute of Mental Health

PROJECT SUMMARY/ABSTRACT Across sub-Saharan Africa, approximately one-third of new HIV infections occur among men. Men in highly mobile occupations, such as fishing, are particularly vulnerable to poor HIV prevention engagement. Fisherfolk (men and women who work in the fishing industry) are the largest key/priority population in Kenya. Despite significant declines in HIV incidence in other populations in sub-Saharan Africa, fishermen have persistently high rates of HIV acquisition. Kenya has been a leader in scaling up biomedical HIV prevention, including oral tenofovir-based pre-exposure prophylaxis (PrEP), a daily pill that is highly effective with sufficient adherence. However, efforts to improve daily oral PrEP use have not been effectively deployed to address the unique barriers experienced by mobile fishermen, particularly as new HIV prevention technologies and regimens are introduced such as long-acting injectable PrEP (e.g., CAB-LA; injection every 2 months and lenacapavir; injection every 6 months), event- driven PrEP (oral PrEP taken before and after sexual contact), and post-exposure prophylaxis (oral PrEP taken after potential HIV exposure). Without tailored delivery strategies, these innovations risk reproducing the same access and adherence challenges that have limited the impact of existing prevention tools in this population. Evidence-based approaches tailored to the needs of mobile fishermen are urgently needed to optimize their engagement in biomedical HIV prevention. Evidence-based approaches such as differentiated and patient- centered service delivery for HIV prevention have been endorsed by the WHO, yet these service delivery models have not yet been effectively harnessed to improve mobile fishermen’s uptake and adherence to biomedical HIV prevention. Meaningful engagement of community members in tailoring evidence-based HIV interventions is recognized as an approach that may increase sustainability, ownership, and acceptance of interventions. However, established methods to effectively engage mobile populations, including fishermen, in research are limited. Community-led, participatory approaches in global HIV research have infrequently been utilized with priority populations such as mobile fishermen yet may be vital to addressing prevention gaps. The proposed research uses community-engaged and participatory approaches to identify factors influencing fishermen’s engagement in HIV prevention (Aim 1) and to co-design an evidence-based intervention in collaboration with fishermen (Aim 2). The co-designed intervention will then be piloted to evaluate its implementation and client outcomes (Aim 3). Completion of the proposed training and research plan will provide me with an expanded skillset in community-engaged research, intervention design, and implementation science approaches. I will be mentored by a team of experienced Kenyan and UCSF mentors. A future R01 will evaluate the co-designed intervention at scale.

NHLBI - National Heart Lung and Blood Institute

Abstract (30 lines) Cystic fibrosis (CF) is a life-limiting genetic disease affecting multiple organ systems. Over the past several decades, novel therapies have driven improvements in lung function and survival. However, the burden of taking multiple treatments for people with CF (pwCF) have been substantial. The recent introduction of elexacaftor/tezacaftor/ivacaftor (ETI), a highly effective CF transmembrane conductance regulator (CFTR) modulator now used by approximately 80% of pwCF, has led to marked improvements in lung function and reductions in pulmonary exacerbations. This has prompted many pwCF and their healthcare providers to reconsider the necessity of conventional CF therapies, such as inhaled dornase alfa (DA) and hypertonic saline (HTS). While some studies have suggested that discontinuing these treatments may not immediately affect lung function, the longer-term consequences of reducing the conventional therapies remain unclear, particularly for individuals with more advanced lung disease. Additionally, ETIs have been linked to potential adverse effects including liver dysfunction and mental health issues. Robust real-world data studies are essential to understand the safety profile and variability in individual responses to guide clinical decision- making. To address these critical knowledge gaps in this rare but high-cost and -burden disease, we propose a comprehensive epidemiologic study leveraging patient registries and healthcare databases to evaluate the impact of reducing conventional CF therapies and the safety profile of ETI. We will link information in the Cystic Fibrosis Foundation Patient Registry to the healthcare database for pwCF insured by Medicaid or commercial insurances from Carelon Research to identify detailed information on genotype and phenotype, lung function, medication use, clinical outcomes, and adverse effects. The specific aims are to: (1) assess the effectiveness of adhering to conventional CF therapies among pwCF who initiated ETI; (2) identify and assess the effectiveness of an adaptive strategy, based on clinical course and pulmonary function test measures, to discontinue traditional CF medications compared to fixed strategies; and (3) assess non-pulmonary adverse events potentially associated with ETI treatment, like depression and liver disease. We have assembled an interdisciplinary team of methodological and clinical experts with prior collaboration and deep clinical and methodological experience relevant to the research questions, data sources, data linkage, and analytic methods, supported by extensive preliminary analyses demonstrating feasibility. This approach will allow us to examine the real-world outcomes of treatment discontinuation and identify optimal usage patterns of traditional CF medications based on lung function values and exacerbation history in the ETI era. Findings from this study will provide evidence-based guidance to optimize CF therapy, balancing the benefits of simplifying treatment regimens with the potential risks of medication discontinuation and drug-related complications.

NIMH - National Institute of Mental Health

PROJECT ABSTRACT Long-acting injectable (LAI) pre-exposure prophylaxis (PrEP) and antiretroviral therapy (ART) represent a promising but underutilized class of HIV medications that can significantly benefit patients who struggle with oral medication adherence. Despite their potential, LAIs face substantial implementation barriers due to their logistical complexity compared to traditional oral medications. While high-volume LAI delivery is currently rare across U.S. HIV clinics, clinical decision support (CDS) systems offer a potential solution for efficiently scaling LAI programs. This project addresses the critical need for infrastructural support in LAI delivery by developing and evaluating a comprehensive Resource Package to accelerate the adoption of LAI-specific CDS in HIV clinics nationwide. We hypothesize that providing clinics with a standardized Resource Package will lead to more efficient workflows, improved care coordination, enhanced patient outcomes, and sustainable LAI program growth. The Resource Package will include: (1) a compendium of LAI-specific CDS tool options with implementation guidance, (2) decision-making worksheets for CDS design, (3) low-fidelity prototypes with adaptable wireframes, (4) build checklists for tool development, and (5) evaluation metrics for assessing CDS tools. Our project has three specific aims. First, we will identify promising CDS tools and processes through synthesis of practices at 10 Clinical Partner Sites currently delivering LAIs at high volume. Second, we will co-create the Resource Package through five multi-disciplinary working groups, each including clinicians, CDS end-users, builders, and implementation scientists. Third, we will assess the Resource Package's impact on clinics' readiness to build LAI CDS tools and their progress in the build process through pre-post surveys and in-depth qualitative analysis. The project will be carried out by an interdisciplinary team including implementation scientists, clinicians, and CDS specialists, working collaboratively with 10 Clinical Partner Sites, two national dissemination partners, and a Community Advisory Board. This research directly responds to NIMH priorities (PAR-22-060 and NOT-MH-23-275) by developing a systematic intervention to promote organizational readiness and capacity for implementing LAIs with fidelity and effectiveness. By establishing a standardized approach to CDS development for LAIs, this project aims to overcome a significant barrier to widespread LAI implementation, ultimately expanding access to these valuable HIV prevention and treatment options for vulnerable populations currently underserved by conventional oral medication approaches.

National Institutes of Health

Purpose. This Funding Opportunity Announcement (FOA) issued by the National Institute of Dental and Craniofacial Research and the National Institute on Aging, National Institutes of Health, solicits grant applications from institutions/organizations that propose investigator-initiated clinical research focused on the oral health of special needs populations, including those with developmental or acquired physical or mental disabilities, people with mental retardation (MR), people living with HIV/AIDS, and frail or functionally dependent elders. Mechanism of Support. This FOA will utilize the 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. Eligible Institutions/Organizations. Public/State Controlled Institution of Higher Education; Private Institution of Higher Education; Nonprofit with 501(c)(3) IRS Status (Other than Institution of Higher Education); Nonprofit without 501(c)(3) IRS Status (Other than Institution of Higher Education); Small Business; For-Profit Organization (Other than Small Business); State Government; U.S. Territory or Possession; Indian/Native American Tribal Government (Federally Recognized); Indian/Native American Tribal Government (Other than Federally Recognized); Indian/Native American Tribally Designated Organization; Non-domestic (non-U.S.) Entity (Foreign Organization); Hispanic-serving Institution; Historically Black Colleges and Universities (HBCUs); Tribally Controlled Colleges and Universities (TCCUs); Alaska Native and Native Hawaiian Serving Institutions; Regional Organization; Other(s): Eligible agencies of the Federal government; Faith-based or community based organizations.

NIMH - National Institute of Mental Health

Project Summary/Abstract Depressive symptoms represent a serious challenge to youth mental health. There is therefore an urgent need for the identification of possible mechanisms underlying risk for youth depressive symptoms. This is especially crucial for certain high-risk populations, such as youth with a history of adversity exposure. Dysregulation of the oral microbiome, the community of microorganisms inhabiting the human oral cavity, may function as a mechanism underlying risk for depressive symptoms in youth. The oral microbiome is a compelling putative mechanism for youth depressive symptoms because it is manipulable via non-invasive interventions, such as probiotic supplementation, while, at the same time, remarkably resilient to insults once it has stabilized in early adulthood. Indeed, oral microbiome dysregulation has been linked to depressive symptoms, experimentally in animal models and observationally in human youth. However, in order for potential mechanisms underlying this link to be elucidated, there is a need for research that examines the oral microbiome and depressive symptoms longitudinally, that examines the microbiome at a functional level, and that incorporates neuroimaging to better understand depressive symptom etiology. The current project will address these gaps by leveraging a 3-year longitudinal study of youth, ages 6-16 at the first timepoint (N=152), with the first 2 timepoints completed and the 3rd underway. This project oversamples for adversity-exposed youth (N=66), a population at increased risk of both depressive symptoms and oral microbiome dysregulation. Oral microbiome composition and depressive symptoms will have been assessed at all three timepoints, and functional Magnetic Resonance Imaging (fMRI) conducted at the final timepoint. We will analyze the relationship between the oral microbiome and depressive symptoms, and the relationship between the oral microbiome and functional brain connectivity. We hypothesize that elevated pathogenic taxa, increased pro-inflammatory functions of the oral microbiome, and decreased aromatic amino acid precursor biosynthesis will be associated with increased depressive symptoms. We further hypothesize these same indicators of oral microbiome dysregulation will also be associated with altered functional brain connectivity, especially within the affective limbic network, reward network, default mode network, and cognitive control network. This project’s findings will yield critical understanding about potential peripheral mechanisms underlying depressive symptoms in both typically developing and high-risk youth.

NIMH - National Institute of Mental Health

PROJECT SUMMARY G protein coupled receptor (GPCR) signaling pathways mediate actions of hormones and neurotransmitters. They are essential for the normal function of the nervous system, frequently disrupted in many neuropsychiatric and neurological conditions and/or exploited for therapeutic purposes. While we learned considerable information about molecular players involved in traditional GPCR signaling, many critical gaps remain. Among the biggest uncharted territories in the field is an issue of “orphan” GPCRs, receptors with unknown signaling mechanisms. It is generally recognized that orphan receptors have tremendous potential for uncovering novel biology of the nervous system and harnessing it for potential therapeutic benefits. Our long- term goal is to understand principles in organization and functional regulation of poorly explored GPCR pathways in the effort to develop better treatments for brain disorders. The focus of our attention is on the poorly understood orphan receptor- GPR158, that plays a pivotal role in stress-induced depression. During the previous award period we demonstrated that GPR158 serves as a receptor for major neurotransmitter glycine impacting synaptic transmission and neuronal excitability. We further delineated GPR158 signaling mechanism showing that it associates with a negative regulator of G protein signaling, RGS7 as well as extracellular synaptic proteins and controls production of the second messenger cAMP. We further solved a structure of GPR158 in complex with RGS7 revealing its organization at atomic level. These data led to an overarching hypothesis that glycine signals via GPR158 regulate activity of the associated RGS7 complex which in turn gates cAMP production to regulate neuronal activity that drives stress- induced behavioral changes. This hypothesis will be tested by pursuing three complementary Specific Aims that seek to: (1) establish molecular mechanisms of glycine action on GPR158, (2) delineate structural basis of glycine effects on GPR158 and interaction with binding partners and (3) dissect mechanics of GPR158 signal transduction in regulation of cAMP. The strategy proposed to address these Aims will entail a synergistic combination of biochemical, structural, and cell-biological approaches, exploiting the existence of a powerful array of technologies and animal models. We hope that accomplishment of these goals will provide critical new insights into the mood regulation in mammals and suggest novel targets for the development of therapeutic interventions.

NIMH - National Institute of Mental Health

Project Summary Social behavior in humans encompasses various close relationships, ranging from parental and romantic relationships to friendships, i.e. ‘peer relationships’. A common feature of these relationships is selectivity—the preference to spend time with a bonded individual over a stranger. These social bonds are integral to health and well-being, but the neural mechanisms underlying peer relationships remain poorly understood compared to reproductive attachments. This is a critical gap in knowledge, as difficulties in forming or maintaining peer relationships are associated with multiple psychiatric conditions. A mechanistic understanding of peer bond formation may therefore provide foundational insights for targeted therapeutic development. Foundational research in prairie voles—socially monogamous rodents that form stable, selective mate and peer relationships—has identified oxytocin and dopamine as key neuromodulators of social attachment. While much of this work has focused on mate bonds, the proposed project will leverage novel genetic tools and in vivo imaging approaches to dissect how oxytocin and dopamine signaling interact to reinforce selective peer attachment. The central hypothesis is that oxytocin signaling supports peer relationships by shaping dopamine- mediated reward signaling to reinforce partner affiliation and effectively encode peer social selectivity. This project will pursue two specific aims: (1) determine how a global oxytocin receptor null mutation influences real-time dopamine dynamics, and (2) identify the region-specific role of oxytocin receptors in the nucleus accumbens and ventral tegmental area in modulating reward circuitry and facilitating peer partner attachment. These experiments will provide a mechanistic framework for understanding how neuromodulatory interactions support peer bond formation in prairie voles. By focusing on a natural model of peer social attachment and integrating behavioral assays with neural imaging and site-specific viral manipulations, this project takes a novel approach to studying the neural basis of peer bonds. These research findings will broaden our understanding of social attachment beyond a reproductive context and inform models of social dysfunction in neuropsychiatric conditions. In parallel, the project will provide the applicant with rigorous training in neuroscience techniques—including genetic manipulation, and ex vivo and in vivo imaging coupled to complex behavioral phenotyping, establishing a strong foundation for an academic career investigating the neural basis of complex natural behaviors.

NIA - National Institute on Aging

Project Summary/Abstract Dementia spousal caregiving contributes to chronic diseases of aging that result from stress- associated increases in inflammation. Chronic stress in this population is characterized by negative emotions in response to disruptive behaviors, activities of daily life, and anticipatory grief associated with providing care for a person with dementia, among others. Negative emotions, however, are dynamic, altering over time in response to contextual change and internal emotion regulation processes. Negative emotions that resist change over time (i.e., negative emotional inertia) may pose additional threats to emotional and physical well-being. Indeed, research has shown that individuals reporting negative emotions that linger are at increased risk for poor emotional well-being and physiological dysregulation. Further, our team has shown that dementia spousal caregivers reporting traumatic childhoods show markedly increased pro-inflammatory cytokine production in response to a biological stressor relative to caregivers reporting less trauma in early life. As a result, the caregivers who experience negative emotional inertia and report relatively high levels of childhood trauma may exhibit the poorest self-rated health and immune dysregulation in pro- inflammatory cytokine production. Specific aims: (1) To evaluate the role of emotional inertia in caregiver self-reported health. (2) To assess the immune implications of emotional inertia in dementia spousal caregiving. (3) To assess whether childhood trauma is a risk factor for poor well-being experienced after high levels of emotional inertia. Study design: Within the funded RF1 parent grant, 140 dementia spousal caregivers will have a venous blood draw and report self-rated physical health at baseline and six months after baseline. Participants will also self-report affect throughout the day for two weeks with a smartphone via ecological momentary assessment. We will assess emotional inertia using dynamic structural equation modeling, defining emotional inertia as the within-person auto-regressive coefficient of negative emotion, as standard in the emotion dynamics literature. Blood assays will assess lipopolysaccharide (LPS)-induced cytokine (i.e., interleukin-1ß, interleukin-6, and tumor necrosis factor-α) production. This study will elucidate both the emotional dynamics and psychosocial risk factors that promote increased risk for poor emotional and physical well- being overall.

NIMH - National Institute of Mental Health

Project Summary/Abstract The rising incidence of youth hospitalized for self-injurious thoughts and behaviors (SITB) highlights the need to better understand underlying modifiable factors that could lead to targeted interventions during critical post-hospitalization periods. Nearly half of adolescents discharged after psychiatric hospitalization are readmitted, with the highest suicide risk occurring in the month following discharge. While prior research emphasizes the role of parenting as a protective factor, the specific, proximal parenting practices most effective during this period remain poorly understood. This study aims to address this gap by identifying modifiable parenting practices and their impact on SITB in the first month following discharge. Using a multi-method, prospective longitudinal design, we will investigate both general (e.g., warmth, communication, monitoring) and safety-specific (e.g., access to means, safety plan review) parenting practices. We will leverage real-time data through mobile diaries and behavioral assessments, and assess emotion regulation through fundamental frequency analysis during parent-adolescent interaction tasks. This innovative approach will allow us to capture day-to-day variations in parenting and their influence on adolescent SITB. The study will recruit 250 adolescents (ages 12-17) and their parents from a psychiatric inpatient unit. Participants will complete self-report measures at baseline and engage in interaction tasks. Over four weeks, daily mobile diaries will track fluctuations in parenting and adolescent mood, while follow-up assessments will be conducted at 1-, 3-, and 6-months post-discharge. The study will explore how general and safety-specific parenting practices relate to SITB, and how transactional dynamics between parents and adolescents influence long-term outcomes. This research will provide insights into how modifiable parenting practices can mitigate suicide risk in adolescents following psychiatric hospitalization, directly contributing to efforts to reduce suicide attempts in adolescents. The findings will inform the development of personalized interventions to support families during this vulnerable period, ultimately advancing public health objectives and improving clinical practices.

NIMH - National Institute of Mental Health

Project Summary and Abstract Suicide is a leading cause of death among females of reproductive age, with suicide attempts occurring most frequently around menses (perimenstrually), when estradiol (E2) and progesterone (P4) fall rapidly. Across three recent placebo-controlled crossover clinical trials with female outpatients experiencing suicidality (NCT03720847, NCT04112368, NCT03498313), we have documented that perimenstrual worsening of depression and suicidal ideation can be prevented by stabilizing perimenstrual estradiol (E2) and progesterone (P4) or E2 alone, relative to placebo. The proposed research combines expertise in clinical trials, pharmacologic fMRI acquisition/analysis, E2-related neural mechanisms, and group iterative multiple model estimation (GIMME), in order to advance understanding of the role of ovarian steroids in proximal suicide risk, with the long-term goal of developing diagnostics and treatments for hormonal contributions to suicide. The central aim of the current work is to identify behavioral and neural pathways underlying the anti-suicidality benefits of E2 observed in our prior trials. Design: The proposed study has two parts: a two-month longitudinal baseline with 200 recruited outpatients (150 completers), and a crossover placebo-controlled trial with 75 recruited participants (60 completers) examining E2 administration effects during perimenstrual weeks on symptom and neural networks. Specific Aims: Aim 1 is to identify idiographic hormone-symptom networks associated with proximal suicide risk, using GIMME. In subgroup analyses, we expect at least one group to show no hormonal effects, while other groups will demonstrate networks indicating E2-driven suicidality (linked with depressive symptoms), P4-driven suicidality (linked with irritability and social symptoms), or a combination of both. Aim 2 is to use GIMME to identify person-specific and subgroup-level effects of E2 stabilization on behavioral and neural networks that may explain the benefits of perimenstrual E2 treatment on suicidality. Relevance: By conducting a mechanistic experiment that probes the behavioral and neural mediators of a known cause of acute suicide risk, the research responds to public calls from the NIMH-sponsored Suicide Research Prioritization Agenda to identify modifiable causes of proximal suicide risk. Moreover, this project aligns with NIH’s recently stated interest in research focused on diseases and health conditions that predominantly affect women or are female-specific (NOT-OD-24-079).

NHLBI - National Heart Lung and Blood Institute

Sleep disturbances are highly prevalent during pregnancy, with 42–60% of individuals experiencing clinically significant insomnia. These disturbances are associated with impaired daytime functioning and serious maternal health risks such as gestational diabetes, preeclampsia, and depression, as well as adverse infant outcomes including low birth weight and sleep problems. Despite the substantial and well-documented consequences of poor prenatal sleep, these problems often go untreated in standard perinatal care. Cognitive Behavioral Therapy for Insomnia (CBT-I) is the first-line, evidence-based treatment for insomnia and poor sleep quality and has demonstrated efficacy during pregnancy. Yet access and engagement are limited. Approximately 40% of adults drop out of CBT-I prematurely, and it is typically delivered by clinical psychologists—only 6% of whom are trained in behavioral sleep medicine. This workforce limitation significantly constrains the scalability of CBT-I, particularly in communities that face challenges with health care access. Community-based delivery models offer a promising and innovative approach to expanding access to prenatal sleep care. Doulas—non-clinical, community-based perinatal support workers—are uniquely positioned to help address these gaps due to their sustained contact with families, shared community backgrounds, and growing integration into health systems, including via Medicaid. National surveys indicate strong interest among doulas in delivering mental health (81%) and sleep health (78%) interventions, and studies support their effectiveness in supporting maternal well-being. We aim to adapt and pilot a doula-delivered prenatal CBT-I intervention through a Human-Centered Design (HCD) implementation-focused process. We will first (HCD Discovery Phase; Aim 1) conduct a community sleep needs assessment to identify perinatal sleep-related strengths, assets, needs, challenges, and facilitators, engaging key stakeholders (patients, doulas, OBGYNs, sleep specialists) through focus groups and a Perinatal Sleep Day summit. Next (Aim 2), we will co-design a patient-centered adaptation of CBT-I for delivery by doulas. Using HCD design/build methods, we will engage an Implementation Workgroup in iterative co-creation sessions and assess usability, feasibility, appropriateness, and acceptability, followed by Theater Testing of the full intervention with target users. Lastly (Aim 3), we will conduct a pre-post feasibility and acceptability pilot trial of the adapted intervention, including recruitment and training of community doulas. We will use mixed methods to evaluate maternal sleep quality, insomnia symptoms, and mood, along with implementation outcomes guided by Proctor’s Framework and the Consolidated Framework for Implementation. Findings will inform the design of a subsequent hybrid type I effectiveness-implementation RCT study design, including feasibility of the study timeline, recruitment and training strategies, assessment processes, attrition and engagement, and estimates of effect size. This project will fill a critical gap in maternal health care by integrating evidence-based sleep interventions into community perinatal services, improving access and enhancing maternal and infant outcomes.

NIMH - National Institute of Mental Health

Project Summary Parvalbumin interneurons (PVIs) are essential for regulating cortical network activity, playing key roles in both the primary visual cortex (V1) and in the prefrontal cortex (PFC). PVIs have been implicated in schizophrenia, bipolar disorder, autism, and major depression, with transcriptomic alterations more pronounced than in other neuron types. However, the relationship between these changes in PVIs and corresponding physiological or morphological alterations remains unclear. Assessing these relations is the primary goal of this application. This exploratory R21 proposal investigates, using patch-seq, the properties of PVI subtypes and the effects of social isolation (SI), which induces PVI transcriptome changes in a manner relevant to psychiatric disorders. We will test whether region-specific PVI properties in mouse PFC and V1 contribute to the changes produced by SI. Our pilot studies revealed distinct electrophysiological subtypes of PVIs (continuous firing [cFS] and delayed fast-spiking [dFS]), in PFC and V1, as well as differences in axonal morphology. These baseline differences may contribute to region-specific PVI vulnerability to psychiatric disease or related manipulations. Aim 1 will establish the baseline transcriptomic signatures of PVI subtypes in PFC and V1 under standard group-housed conditions. Using patch-seq, we will integrate single-cell RNA sequencing, electrophysiology, and morphology to define the transcriptional markers distinguishing cFS and dFS subtypes in each region. Aim 2 will determine how SI alters PVI subtypes in PFC and V1 using patch-seq to assess changes in gene expression, excitability, and morphology. By correlating transcriptional changes with cellular phenotypes in the same neurons, this aim will reveal whether region-specific PVI properties shape differential responses to SI. This study is innovative in applying patch-seq to link transcriptional changes to multimodal cellular phenotypes in PVIs. It represents the first investigation of how experimental manipulations affect PVI subtypes across cortical regions. Our findings will provide crucial insights into region-specific PVI dysfunction and generate testable hypotheses on how molecular alterations contribute to disease-relevant cortical circuit changes.

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

PROJECT SUMMARY Caregiver-mediated interventions are considered an evidence-based intervention for autistic children. However, caregivers of autistic children often experience chronic stress which can blunt the benefits of early parent- mediated interventions. A critical barrier to improving family support is the lack of a home-ready tool that can simultaneously capture branch-specific autonomic signals from both caregiver and child and link those signals to what the dyad is actually doing in the moment. PATCHES fills this gap with a 15-g, skin-soft chest patch that streams high-fidelity electrocardiogram (ECG) and seismocardiogram (SCG) to a smartphone app that also records synchronized video clips of family routines and delivers brief ecological-momentary surveys. Aim 1 will finalize the hardware, firmware, and HIPAA-compliant app-to-cloud pipeline, then validate physiological specificity in ten healthy adults by comparing patch-derived pre-ejection period (sympathetic) and respiratory sinus arrhythmia (parasympathetic) against laboratory gold standards during a battery of controlled autonomic challenges. Aim 2 will deploy PATCHES for one week in 25 caregiver–child dyads (ages 3–8 years) during both high-stress (mealtime) and low-stress (preferred play) routines, assessing feasibility, usability, and data yield while using cross-correlations, wavelet coherence analysis, and mixed effects models to map second- by-second physiological synchrony to video-coded behavioral observations and in-app stress ratings. Data travels over TLS 1.3 directly from phones to Mount Sinai’s HIPAA-compliant servers, where automated pipelines de-identify files, compute autonomic metrics, and archive outputs in a role-restricted repository. Innovation lies in integrating dual-branch cardiac sensing, auto-synchronized video, and real-time surveys into a single, caregiver-operated platform that quantifies dyadic autonomic regulation in natural settings. Expected outcomes include validated algorithms, feasibility benchmarks, and preliminary effect sizes that will underpin a multi-site efficacy trial. This novel platform will lay the foundation for future studies aiming to personalize parent- mediated interventions, ultimately improving both caregiver mental health and child developmental trajectories.

National Institutes of Health

-Purpose. The purpose of this Funding Opportunity Announcement (FOA) is to invite grant applications for research on the pathophysiological aspects of late-life mood and anxiety disorders and on the utility of findings in this research area for developing new treatments or predicting older adults response to existing mental health treatments, and to attract new investigators into interdisciplinary studies of these issues. -Mechanism of Support. This FOA will use the NIH Research Project Grant (R01), but applications under the NIH Small Research Grant Program (R03); the NIH Exploratory/Developmental Research Grant Program (R21); and the NIMH Clinical Exploratory Grant Program (R34) are also sought. Applicants for the R03 should respond to PA-06-180, applicants for the R21 should respond to PA-06-181, and applicants for the NIMH R34 should respond to PA-06-248. -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.

FDA - Food and Drug Administration

Effective engagement with the public is essential to expand the impact of the U.S. Food and Drug Administration, and for the efficient transfer of information and insights among the Agency, patients, academia, consumers, healthcare, and regulated industry. Through PRISM: Pathways for Regulatory Innovation and Strategic Modernization, the Reagan-Udall Foundation for the FDA proposes a multi-year effort to support the FDA's mission to protect and promote the public's health. As a Congressionally chartered, independent nonprofit, the Foundation serves as a neutral bridge between FDA and diverse stakeholders, delivering applied regulatory science, real-world insights, and transparent engagement. The Foundation does not participate in regulatory decision-making. Building on more than 70 collaborative projects completed between 2020 and 2025, the PRISM project portfolio advances FDA priorities through three Specific Aims: 1) Support the Development and Use of Regulatory Science Tools, 2) Support Programs and Research to Enhance Development of and Access to FDA-Regulated Products, and 3) Engagements, Convenings, and Operational Evaluations to Support the Work of FDA. Aim 1 strengthens regulatory science tools, with emphasis on modern use of real-world data and artificial intelligence, evaluation of data transparency, trust, and governance, and assessment of the predictive utility of animal studies to support efforts to reduce animal testing. Aim 2 focuses on improving development of and access to FDA-regulated products by expanding patient- and consumer-centered initiatives, enabling access to investigational new drugs, studying appropriate use of controlled substances, supporting gold-standard food and nutrition research, incentivizing drug development for animals, and assisting rapid response collaboration during cross-sectoral outbreaks. Aim 3 leverages the Foundation's expertise in convenings—roundtables, expert panels, and public meetings—to support FDA implementation across complex policy areas, including drug development, cosmetics oversight, rare diseases, food safety, mental health, and counterfeit products. Projects are jointly designed with FDA staff, delivered on defined timelines and budgets, and culminate in public outputs to promote learning, transparency, trust, and impact. Collectively, through PRISM, the Foundation provides FDA with timely evidence, stakeholder insight, and practical tools to modernize regulatory science and address emerging public health challenges efficiently, transparently, and in a trustworthy manner.

NIMH - National Institute of Mental Health

PROJECT SUMMARY/ABSTRACT Suicide is the second leading cause of death among young adults ages 15-241, with rates continuing to rise2. While research has identified some broad predictive factors3, our ability to predict who will experience suicidal thoughts and behaviors (STB) and when these crises will occur remains limited4. This challenge stems from the fact that suicide risk fluctuates dramatically in response to emotional and interpersonal distress5,6, with social threats often acting as precipitating events7,8. The tendency to respond impulsively to negative emotions (e.g., negative urgency9) may help explain why some individuals engage in STB as a maladaptive attempt to escape emotional pain following social threat or rejection. Evidence from neuroscience indicates that social- affective circuitry reflects subjective affective sensitivity to social threat10,11, and overlaps with putative neural correlates of negative urgency12,13, suggesting a potential neural profile that may drive associations between social threat and STB. To test this, I will utilize data from an ongoing R01 including 6 months of ecological momentary assessment (EMA), a personalized peer social feedback fMRI task, and self-report questionnaires from 150 young adults (ages 18-30) with chronic STB to examine how function in social-affective systems and real-world experiences of social threat interact to predict STB. The Specific Aims of this study are to: (1) test associations between negative urgency and STB using both baseline and prospective EMA assessments; (2) investigate associations between functional connectivity of social-affective systems during social threat and trait-level negative urgency; and (3) examine whether individual differences in neural response to social threat moderate same-day relationships between social rejection-generated negative affect and suicidal thoughts. This project, and the associated F31 fellowship at the University of Pittsburgh, will provide critical training for the applicant to become an independent researcher investigating how neural and behavioral responses to social contexts influence suicide risk during key developmental periods. To accomplish the proposed research, this application includes a comprehensive training and mentorship plan that builds on the applicant’s prior clinical psychology and developmental neuroscience training. These Training Goals will focus on expanding the applicant’s knowledge and/or skills in: (1) neurodevelopmental pathways to suicide; (2) negative urgency as a mechanism of suicidal thoughts; (3) task-based fMRI methods, with an emphasis on functional connectivity analyses; and (4) implementing mixed-effects modeling for intensive longitudinal data. These goals will be accomplished through mentorship meetings, workshops, conferences, and coursework with a committed interdisciplinary team. Complemented by support from a dedicated research environment at the University of Pittsburgh, this fellowship will accelerate the applicant’s trajectory toward becoming an independent researcher focused on using multimodal research to identify how individual neurobiology interacts with one’s social environment to create enduring risk for STB.

U.S. Mission to Poland

Purpose of Grants: PD Poland invites proposals for programs that strengthen ties between the United States and Poland through activities that highlight shared values, promote bilateral cooperation, and forge enduring connections between the United States and emerging Polish leaders (high school students, university students, and young professionals ages 16 to 35), as well as established community leaders in the public, private, and nonprofit sectors. All proposals are required to have a clear connection to the United States, either through U.S. organizations, experts, and/or best practices in order to increase the awareness and understanding of U.S. perspectives, policies, and society. Proposals without significant U.S. content will not be considered for funding. Examples of possible public diplomacy grant activities include, but are not limited to: Youth engagement programs. Participatory and/or problem-solving workshops like tech camps. Soft skills and leadership-building workshops, seminars, and trainings that develop human capital and social or economic innovation. Workshops, seminars, trainings, master classes, and exhibitions on themes or topics that advance shared democracy, economic, and security goals. Programs that reinforce and amplify lessons learned by Polish alumni of U.S. Government-funded and private sector exchange programs. Priority Program Areas: ECONOMIC PROSPERITY Addressing barriers to the advancement of women in STEM fields and business. Strengthening the business skills of young entrepreneurs. Sharing best practices of U.S. businesses operating in Poland. Promoting the development of trade and investment with the United States, including entrepreneurship, small- and medium-sized businesses, and innovation as the basis for strong, sustainable, inclusive economic growth that creates quality employment and incorporates diverse and excluded groups. Promoting joint Polish-U.S. science, space, and innovation initiatives carried out by research organizations, nongovernmental organizations, universities, and private companies. ENSURING SECURITY Demonstrating the benefits of the of the Polish-U.S. security partnership and NATO Alliance for Polish emerging leaders (high school and university students ages 15-25 and/or young professionals ages 25-34). Promoting a deeper understanding of the impact of Polish and U.S. political, military, and humanitarian support for Ukraine and for Ukrainians in Poland. Strengthen cyber security awareness. STRENGTHENING DEMOCRACY Leadership training fostering innovation and critical thinking among young people (ages 16 to 24). Strengthening media practitioners and media consumers media literacy and ability to detect and combat mis/disinformation. Promoting Holocaust education and/or human rights education. Participants and Audiences: Proposals should describe both the primary and secondary audiences for the program, including anticipated numbers to be reached. Primary audiences are those who will participate directly in the program, while secondary audiences are those who will be reached by the project s primary audiences as a result of their participation. Priority target audiences in Poland for this funding opportunity are youth and young professionals (aged 16 to 35) who have demonstrated strong leadership potential, established professionals engaged in fields relevant to the U.S.-Polish partnership, and community leaders. The following types of programs are not eligible for funding: Programs relating to partisan political activity; Charitable, clinical (including mental health services), or development activities; Construction programs; Programs that support specific religious activities; Fund-raising campaigns; Lobbying for specific legislation or programs; Academic or scientific research; Programs intended primarily for the growth or institutional development of the organization; and Individual travel to attend a conference and/or courses at any educational institution. This funding opportunity aims to support specific projects with objectives that can be achieved within a set timeframe. We will not accept applications that are aimed more broadly at supporting your organization s usual or typical daily activities and operations. Those will be deemed technically ineligible and will not be considered for funding by the review committee.

NIMH - National Institute of Mental Health

Penn CFAR Scholars Program: Preparing the Next Generation of HIV Scientists through Early Engagement in Mentored Research Abstract The Penn Center for AIDS Research (CFAR) provides dynamic scientific leadership, organizational structure, resources, & infrastructure to advance HIV/AIDS research across the integrated campus of the University of Pennsylvania, Children’s Hospital of Philadelphia (CHOP) & the Wistar Institute. The Center is comprised of >150 members from our 3 institutions, including 9 of the 12 Penn schools & 21 of 29 departments within the School of Medicine. The success of the Penn CFAR is reflected by key discoveries in HIV/AIDS priority areas including HIV reservoirs/cure, immune function, prevention, implementation science, behavioral and mental health, management of comorbidities & other areas. The Penn CFAR Scholars (PCS) program is a CFAR-wide initiative that leverages expertise and engagement across CFAR scientific domains and Cores for education and mentorship for learners across a wide academic spectrum (undergraduate to graduate students). The program was created in 2022 with a CFAR supplement and was led by 2 senior leaders with complementary clinical/implementation (Momplaisir) and basic/laboratory (Jordan-Sciutto) expertise. Our short-term goal is to provide early exposure to HIV research and clinical opportunities to early-stage trainees, provide professional skill building, and widen the Scholars’ social/professional networks. Our long-term goal is to increase the pool of interested and academically prepared students for careers in biomedical research or academic medicine and enrich the HIV/AIDS field that critically requires differing perspectives to develop innovative solutions to the HIV epidemic. Over the past 3 years, the PCS program has been remarkably successful with accelerating momentum, energy and significant outcomes. Since its inception, we have mentored 49 Scholars, including 14 Scholars this summer and collected outcomes longitudinally on 35 Scholars (through summer 2024). To date, 14/35 (40%) matriculated into graduate or medical school. Many of our Scholars present their work at scientific meetings and publish their research findings. In addition, based on results of qualitative interviews and subsequent program evaluations, ~20% of our Scholars are newly interested in pursuing a career in HIV medicine or research. With sunsetting of the CFAR supplement program in 2023, this R25 application will provide support to continue and expand the PCS program which will focus on HIV mentored research opportunities for undergraduate, post-baccalaureate and graduate students. Looking ahead, Drs. Momplaisir and Jordan-Sciutto will continue to lead the PSC program, and early-stage investigator (ESI) Dr. Edward Kreider (basic science) will serve as multiple principal investigator. ESI Dr. Arianne Morrison (HIV clinical/prevention) will join the team to serve as PCS Associate Program Director and spearhead professional development skills & clinical shadowing experiences. Dr. Favor will continue his role as program evaluation lead and a key link to Lincoln University. We will continue to engage in robust program evaluation using innovative methods from the Penn Mixed Methods Research Laboratory, track program outcomes and make iterative improvement to increase our impact.

NIMH - National Institute of Mental Health

PROJECT SUMMARY The proposed fellowship aims to prepare the applicant, Ananya Bhaktaram, for a career as a leading mixed methods researcher who examines the influence of social and spatial factors on social relationships and health. To develop the skillset necessary to become a leading expert, Ms. Bhaktaram proposes to investigate social and spatial factors that influence social connectedness and mental health, substance use, and HIV- related behaviors and outcomes in people living with HIV (PLWH) and populations highly affected by HIV (PHAH). Ms. Bhaktaram will conduct the proposed research while engaging in individualized mentorship, by a team of complementary experts to target the following training objectives: 1) Build competence in qualitative methodologies, and mixed methods approaches; 2) Enhance expertise in theory-driven geospatial analysis; 3) Advance expertise in advanced quantitative methods; 4) Cultivate a strong foundation in research ethics; 5) Engage in professional development opportunities to ensure success as an independent researcher. The proposed research is highly relevant for addressing mental health, substance use, and HIV comorbidities among PLWH/PHAH. Loneliness and social isolation have comparable levels of risk to health and premature death as smoking and obesity. Social connectedness is an important comorbid risk factor for poor/worse HIV- related outcomes, as social connections can serve as protective factors by acting as sources of resource and instrumental support. PLWH/PHAH report higher levels of loneliness and social isolation. Gaining insight into the social and spatial factors that influence social connectedness will allow for better assessment of future intervention points to improve mental health, substance use, and HIV-related comorbidities. To address these gaps, the proposed research will use data collected by Dr. Carl Latkin’s (Sponsor) research team at the Lighthouse to 1) Assess associations between social connection, mental health, substance use, and HIV-related behaviors and outcomes in PLWH/PHAH; 2) Explore social and spatial dynamics that characterize, facilitate, and hinder social connectedness among PLWH/PHAH; 3) Examine the relationship between spatial factors, social connectedness, HIV, and mental health related outcomes. Findings from this study will provide insight into the social and geographic factors that influence loneliness and social isolation to inform measurement and targeted strategies for preventive interventions, while offering conceptual insight that can improve the understanding of the distinct pathways of loneliness and social isolation. The proposed research aligns with Goals 2 and 3 of the NIMH’s Strategic Plan by providing conceptual and contextual evidence to understand mental illness trajectories and enhance prevention strategies to improve mental health, substance use, and HIV comorbidities in PLWH/PHAH.

NIDA - National Institute on Drug Abuse

PROJECT SUMMARY Opioid use has reached epidemic proportions and is a significant public health concern particularly among pregnant women. Notably, the prevalence of opioid use disorder (OUD) has increased four-fold within the past two decades and steadily continues to rise with maternal opioid related diagnoses increasing by 131% from 2010-2017. OUD during pregnancy has been associated with maternal-infant bonding impairments and deficits in perinatally exposed children (i.e. low birth weight, neonatal withdrawal syndrome, etc.). To mitigate these effects, opioid-dependent women are often prescribed medications for OUD (MOUD), such as buprenorphine (BUP), as BUP produces more favorable infant outcomes compared to other MOUDs or continued illicit use. Of additional concern, psychiatric comorbidities are common among pregnant women taking MOUDs, so polysubstance exposure is reported in most clinical cases. Accumulating evidence indicates that infants exposed to both MOUDs and selective serotonin reuptake inhibitors (SSRIs) exhibit more severe neonatal withdrawal symptoms and have longer hospital stays compared to infants exposed to only one of these medications. Although MOUDs and SSRIs, like sertraline, are deemed relatively safe for use during pregnancy, there remains a significant gap in our understanding of their unique and combined effects on the maternal brain, behavior, physiology and offspring outcomes that stems from insufficient or inconsistent research findings. Maternal neural circuitry is comprised of various systems, including the endogenous opioid system, neurotransmitter systems, and peptide and steroid hormones, that contribute significantly to facilitating physiological changes that underlie successful maternal neural and behavioral adaptations. It remains unclear how exogenous opioids and SSRIs may interact to modulate these systems that are necessary for matrescence and regulation of maternal care following parturition. In our proposed study, female rats (n=48) will be exposed to vehicle, BUP (1.0mg/kg), sertraline (20mg/kg), or both medications in a translationally relevant paradigm starting before conception and continued throughout postpartum. The specific aims of this project are to 1.) Assess the effects of BUP and sertraline exposure on the initiation and maintenance of maternal behavior; 2.) Investigate the neurochemical and behavioral effects of BUP and sertraline exposure on offspring development; 3.) Evaluate the impact of BUP and sertraline exposure on the maternal brain and physiology. The overall hypothesis is that perinatal exposure to BUP will result in decreased activation of important areas of the MBN and the presence of additional serotonin through sertraline exposure will exacerbate this decreased activation and thus hinder the initiation of maternal care and motivation. This in turn will lead to poorer offspring outcomes. This training project will provide me with the critical skills and research training to subsequently expand on this work as a postdoctoral research fellow, ultimately leading to a fruitful career as an independent neuroscientist committed to identifying effective clinical management strategies for pregnant women with substance use and mental health comorbidities.

NIDA - National Institute on Drug Abuse

PROJECT SUMMARY The United States faces a maternal health crisis driven by an ongoing opioid epidemic. As a result, mental health and substance use problems are the leading drivers of pregnancy-associated deaths in the United States. While opioid use disorder (OUD) treatment during pregnancy has been shown to reduce risk of death, improve health outcomes for mother and child, and reduce foster care entries, few pregnant women with OUD receive it. As the largest funder of pregnancy-related OUD services, Medicaid serves as an important policy lever to improve pregnancy-associated overdose mortality by improving coverage of OUD treatment — particularly within Medicaid managed care organization (MCO) as the majority of pregnant and postpartum Medicaid beneficiaries are enrolled in a MCO plan. Prior research on the general Medicaid population have demonstrated considerable discretion in MCO plan coverage and utilization management strategies offered for OUD treatment; however, no research has focused on MCO benefit variation in OUD treatment for pregnant and postpartum women. Examining variation in benefit design for this population in particular is important as they not only experience differences in coverage and utilization management strategies from the traditional adult population, but also require treatment that is safe and recommended for use during pregnancy and breastfeeding. To address this, the proposed study leverages a unique and highly integrated dataset in a state with automatic, random assignment into MCO plans so that we can link MCO benefit comprehensiveness to mother-infant dyads to examine the causal effect of such benefit design on perinatal OUD treatment utilization and OUD-related maternal health and child protective services outcomes. Aim 1 will examine how MCO plan perinatal OUD benefit design effects perinatal OUD treatment utilization— both psychosocial services and medication treatment for OUD. Aim 2 will examine how MCO plan perinatal OUD benefit design effects OUD- related maternal health outcomes (e.g. pregnancy-associated overdose mortality, opioid-related emergency department visits, and opioid-related hospitalizations) and child protective services outcomes (e.g. number of child welfare investigations, foster care entries and outcomes, time for reunification). As the first study to assess whether MCO plan benefit design impacts perinatal OUD treatment utilization and related maternal and child outcomes, findings from the proposed study will provide guidance to health policymakers on mandated benefit design coverage and utilization management strategies. As an NIH F31 predoctoral trainee, I will obtain skills using large-scale administrative claims and encounter data, using advanced statistical econometric methods, deepening my understanding of the intersection of substance use and maternal and child health, and disseminating research findings in peer-reviewed publications and scientific conference presentations.

NIMH - National Institute of Mental Health

Antenatal depression affects 7–20% of pregnant females and is linked to obstetric, fetal, and infant complications1. Treatment options during pregnancy are limited, with many avoiding medication due to concerns about fetal exposure. There is an urgent need for safe, scalable, non-pharmacologic alternatives. This R61/R33 project evaluates a novel, personalized brain stimulation intervention, ‘Personalized Antenatal Depression Aperiodic transcranial alternating current stimulation (PandA-tACS)’, which uses EEG-derived waveforms to normalize neural excitation/inhibition (E/I) balance, a core mechanism of depression. The current leading tACS approach for depression, individual alpha frequency (IAF)-tACS, targets pathologically elevated alpha rhythms2,3. However, recent evidence suggests that depression involves broader shifts in E/I imbalance across multiple frequency bands (not just alpha), particularly in the pregnant brain4. Specifically, depression relates to increased cortical inhibition, indexed by a steeper aperiodic slope (1/f decay) in the EEG power spectrum, particularly in the left dorsolateral prefrontal cortex (dlPFC)5. Flattening of this slope has been linked to clinical response to antidepressants, including esketamine, suggesting it is a mechanistic target of therapeutic change6. PandA-tACS represents a paradigm shift from narrowband, rhythm-based stimulation to broadband, aperiodic modulation. It delivers naturalistic waveforms derived from each participant’s EEG, modified to flatten the left dlPFC aperiodic slope, a region implicated in depression and anhedonia 5–8. In the R61 Phase, 60 pregnant females with moderate-to-severe depression will be randomized to receive a single session of PandA-tACS, IAF-tACS, or sham. High-density EEG (HD-EEG) will measure slope flattening in the left dlPFC as the primary target engagement outcome. Safety, feasibility, and tolerability will also be assessed. These Go/No-Go criteria will determine progression to the R33 Phase. In the R33 Phase, a new cohort of 60 females with antenatal depression will receive five daily sessions of PandA-tACS or sham. EEG and clinical outcomes (e.g., HDRS-17) will be measured at baseline, post-intervention, and two-week follow-up. Primary outcomes are replicated target engagement and associated symptom improvement, alongside safety, feasibility and tolerability. This project is the first brain stimulation trial to directly target the aperiodic slope and to personalize stimulation using EEG-derived waveforms. By shifting from alpha-specific to broadband E/I-targeted modulation, it addresses the unique neurobiology of antenatal depression. This work will lay the foundation for safe, accessible brain-based treatments in pregnancy and advance transdiagnostic neuromodulation research aligned with NIMH priorities.