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NIH

Significance to VA. Half of the 500,000 Veterans receiving cancer care in VA will encounter distress, a multifactorial psychological, social, spiritual, and/or physical experience that may interfere with one’s ability to cope effectively with cancer. Distress has major implications – decreased likelihood of completing cancer therapy, worse quality of life, more emergency room visits and hospitalizations, and higher mortality, including suicide. The collaborative care model (CoCM) is a proven delivery mechanism for evidence-based treatments that can reduce the negative impacts of distress. However, despite its evidence base, no VA medical centers (VAMCs) currently use CoCM to treat distress. Meanwhile, two out of three Veterans with distress do not receive care. To improve the quality of life and overall survival of Veterans living with cancer, the proposed research aims to understand why CoCM is not widely implemented and how CoCM could be successfully utilized in VA’s diverse care settings. This research directly addresses the major challenge facing VA of providing high-quality, highly-efficient mental health care for a rapidly growing population of Veterans facing life with cancer. It tackles top HSR and VA priorities – mental health & suicide prevention; access to high-quality, integrated health care; and use of foundational learning health systems methods in implementation science and engagement science. Innovation & Impact. This project will use innovative, patient- and clinician-centered implementation science techniques to create key constituent-informed, feasible, and acceptable implementation strategies for use of CoCM in VA cancer care. Specific Aims. Aim 1: Identify current distress care practices and potential determinants (i.e., barriers and facilitators) of CoCM in VA cancer care. Aim 2: Develop implementation strategies for use of CoCM in cancer care with key constituents. Aim 3: Assess the feasibility and acceptability of implementation protocols and materials at three VISN 10 sites. Methodology. Aim 1 uses a two-part study design: 1) semi-structured interviews with key constituents (patients (n=15), clinicians (n=18)) from three VAMCs currently participating in the VA Office of Mental Health’s Mental Health Integration in Oncology Clinics pilot project to understand acceptability and potential determinants of CoCM and 2) a national survey of VA medical oncologists to identify the workforce and workflows currently used to address distress across VA. Aim 2 uses a panel of key constituents (n=18 including two patients) to identify implementation outcomes, select implementation strategies, and produce implementation protocols and materials supporting CoCM use in VA cancer care. Aim 3 uses a mixed-methods, user-centered design approach to determine the feasibility and acceptability of the protocols and materials designed in Aim 2 through “think-aloud,” semi-structured interviews with and quantitative surveys of end-users (n=12, oncology and mental health clinicians) from three different VISN 10 sites. Path to Translation/Implementation. Future work will aim to 1) determine the quality of and preferences for distress care among women and young adult Veterans living with cancer – two quickly growing populations within VA who may have unique distress care needs that CoCM will need to meet (Year 3 IIR) and 2) conduct a multi-site, randomized, hybrid effectiveness-implementation trial in VISN 10 of the implementation strategies created in this proposal (Year 5 IIR). Understanding how to implement CoCM in cancer care will impact individuals with cancer broadly as non-VA health care settings also face gaps in distress care. The long-term goal of this research is widespread implementation of CoCM in VA cancer care to ultimately improve the quality and quantity of life of Veterans living with cancer. .

European Commission - HORIZON

Improve the Quality of Life of older cancer patients. Call: Supporting the implementation of the Cancer Mission. Programme: HORIZON. Keywords: Comparative effectiveness research, Homecare, Integrated care, Mechanisms of pain, Mental health, Patient care. Open call from the EU Funding & Tenders Portal.

NIA - National Institute on Aging

ABSTRACT An estimated 6.9 million Americans 65 years and older live with Alzheimer’s disease and related dementias (“dementia”). Advance Care Planning (ACP) conversations allow individuals to communicate their goals, values, and preferences to family members and healthcare providers. In the absence of these conversations, care partners must independently make difficult decisions to provide or to withhold treatments. Constructing an advance care plan requires individuals to predict their values, goals, and treatment preferences during future health states. Often, they use heuristics (i.e., mental shortcuts or intuitive judgments) to make these decisions. Unfortunately, several factors contribute to poor calibration of heuristics in advance care planning, with amplification in dementia. First, people inaccurately predict how they will feel in future health states (affective forecasting biases). Second, lack of knowledge of disease trajectory coupled with the insidious nature of dementia progression obscures recognition of terminal stages of the disease (representativeness biases). The objective of this application is to improve advance care planning by addressing these two sets of biases. We propose to develop a narrative video game that will provide insight into ways that people may adapt to the cognitive and functional limitations of dementia (mitigating affective forecasting biases) and into the trajectory of dementia (mitigating representativeness biases). We will test the feasibility of delivering the intervention in a pilot trial by recruiting a local sample of people at elevated risk of developing dementia and their care partners (N=60 dyads), randomizing them to receive the intervention or an active control, and then evaluating the fidelity of intervention delivery, acceptability, fidelity of intervention receipt, and fidelity of intervention enactment. This proposal advances the NIA's priorities to improve advance care planning among older adults with dementia and follows the NIH's goal of applying a mechanistic approach to the development of behavioral interventions.

NIMH - National Institute of Mental Health

PROJECT SUMMARY For the 20 million individuals with serious mental illness (SMI), limited access to evidence-based and coordinated treatments is associated with poor medical outcomes, higher costs, and devastating societal impacts, including suicide. Outpatient treatment plays an important role during the high-risk period following hospital discharge. However, only about 50% of discharged patients receive any outpatient follow-up within 30 days with lack of pre-crisis engagement with mental health care being the most important predictor of follow-up treatment. Outpatient mental health specialty clinics are a frequent source of treatment for patients who use hospital-based services, but many clinics do not offer the full continuum of evidence-based specialty mental health services, nor do they have the ability to share electronic medical records with other providers. More generally, little is known about existing patterns in hospitals’ formal and informal relationships with these clinics. New payment and delivery models that target specialty mental health clinics, such as the Certified Community Behavioral Health Clinic (CCBHC) program, have the potential to improve clinical capacity to deliver integrated and coordinated care for patients with SMI. Our proposal is designed to better understand these relationships and their effects on follow-up care for patients to inform future care coordination strategies between hospitals and specialty behavioral health clinics. Specifically, we propose to use Medicaid administrative claims from multiple states and a quasi-experimental approach to (1) assess whether CCBHC implementation was associated with changes in follow-up care after hospital-based treatment and (2) whether patterns of follow up care after hospital-based treatment improved for patients with no prior mental health treatment engagement. This will be supplemented by a mixed methods study in Texas, an early CCBHC adopter state with 44 CCBHCs, to assess organizational strategies that mediate the relationship between CCBHC and follow-up care. This grant is responsive to NOT-MH-24-270, “Notice of Special Interest: Impact of Financing and Payment Mechanisms to Improve Behavioral Health Access, Utilization and Outcomes,” and will provide information on outcomes targeted by federal and state agencies, and help to bridge the gap between those who need treatment and those who receive treatment. The significance of this study lies in its focus on how to optimize delivery systems to improve mental health treatment and outcomes for those with SMI.

NIH

SUMMARY/ABSTRACT Significance to VA: Improving rehabilitation outcomes for Veterans with comorbid posttraumatic stress disorder (PTSD) and history of mild traumatic brain injury (mTBI) is an urgent need. These conditions frequently co-occur and are associated with worse cognitive performance, mental health, everyday functioning, community integration, quality of life, and response to evidence-based psychotherapies than in PTSD or mTBI alone. Additional comorbidities, such as depression and sleep disturbance, are common and further contribute to poor outcomes. Innovation and Impact: Our proposed study addresses the significant gap in services and evidence-based treatments for Veterans with mTBI+PTSD. Cognitive rehabilitation treatments emphasizing cognitive strategy training, such as Compensatory Cognitive Training (CCT), are associated with improvements in cognitive functioning, functional capacity, and quality of life in Veterans with mTBI and mTBI+PTSD. However, CCT is an intensive cognitive intervention requiring highly motivated, fully engaged participants. Concomitant depression and sleep disturbance, in addition to contributing directly to cognitive impairment, may reduce the ability of participants to engage in the treatment and learn and practice the strategies taught. Thus, novel intervention combinations directly targeting depression and sleep disturbance may improve treatment effects. Morning bright light therapy (MBLT) has well documented effects on both mood and sleep. We thus propose to enhance CCT by adding MBLT to target depression and sleep disturbance in Veterans with mTBI+PTSD. Our combined expertise in VA behavioral trials, cognitive rehabilitation, TBI, PTSD, neurology, sleep medicine, and biostatistics has led to the development of this proposal and this comprehensive, Whole Health-congruent approach. Our pilot data demonstrate the feasibility and acceptability of CCT+MBLT, as well as the efficacy of CCT and MBLT for Veterans with mTBI, PTSD, and mTBI+PTSD. Specific Aims: We aim to determine (1) whether CCT+MBLT is more efficacious than CCT+sham for improving cognition, functioning, and secondary outcomes such as PTSD and postconcussive symptom severity and quality of life; (2) whether improved rehabilitation outcomes are mediated by improvements in mood and sleep; and (3) whether there are factors that moderate outcomes. Methodology: Our proposed randomized controlled trial will compare CCT+MBLT with CCT+sham in a representative sample of 144 post- 9/11 Veterans with mTBI+PTSD at two VA sites (San Diego and Portland). Assessments will be conducted at baseline, mid-treatment (5 weeks), post-treatment (10 weeks), and three-month follow-up. Path to Translation/Implementation: Our study has the potential to yield a manualized, empirically validated, pragmatic, Veteran-centered intervention that meets the needs of Veterans with mTBI+PTSD across the United States. Thus, the project is a low-risk/high-reward proposal with clear relevance to the mission of VA Rehabilitation Research, Development and Translation. If found to be efficacious, our study team will work with VA Central Office leaders toward national dissemination and scale-up of CCT+MBLT for Veterans with mTBI+PTSD.

National Institutes of Health

-Purpose. Diet and physical activity are lifestyle and behavioral factors that play a role in the etiology and prevention of many chronic diseases such as cancer and coronary heart disease. Both also play roles in preventing overweight/obesity and in maintaining weight loss. Therefore, diet and physical activity are assessed for both surveillance and epidemiologic/clinical research purposes. The measurement of usual dietary intake or physical activity over varying time periods or in the past, by necessity, has relied on self-report instruments. Such subjective reporting instruments are cognitively difficult for respondents, and are prone to considerable measurement errors that may vary among population subgroups and depend on the time frame considered and the characteristics of the respondents. -The National Cancer Institute (NCI), the National Heart, Lung, and Blood Institute (NHLBI), the National Institute on Aging (NIA), the National Institute of Child Health and Human Development (NICHD), the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), the National Institute of Mental Health (NIMH), the National Institute of Nursing Research (NINR), and the National Institutes of Health (NIH) Office of the Director (OD) Office of Dietary Supplements (ODS), are interested in promoting innovative research to enhance the quality of measurements of dietary intake and physical activity. Applications submitted under this Funding Opportunity Announcement (FOA) may include development of: novel assessment approaches and/or better methods to evaluate instruments assessment tools for culturally diverse populations across various age groups including older adults; improved technologies and/or applications of existing technologies; and/or statistical methods to assess or correct for measurement errors or biases. -Mechanism of Support. This FOA will utilize the NIH Research Project Grant (R01) award mechanism and runs in parallel with an FOA of identical scientific scope, PAR-06-103, that solicits applications under the Exploratory/Developmental Grant (R21) award mechanism.

NIH

There are >8 million older Veterans (>65 years) in the United States, and nearly half of them self-report having a disability such as impaired mobility that impacts their ability to perform self-care. Among older Veterans with mobility disability, common self-care tasks like food shopping, meal preparation, and cooking are barriers to consuming a healthy diet, resulting in poor dietary intake. Poor dietary intake contributes to chronic disease risk and loss of muscle mass and strength, consequently limiting function and increasing immobility. Teaching older Veterans with impaired mobility how to overcome barriers limiting these diet-related self-care tasks provides an opportunity to significantly impact this group’s dietary intake. Lack of social support has also been associated with negative health outcomes and poor nutritional intake; thus, effective, age-friendly intervention strategies to improve dietary quality as a strategy to delay further progression of disability and maintain functional independence among this population are needed. In this randomized controlled trial, we will determine if a 3-month virtual group nutrition intervention paired with produce delivery and virtual teaching kitchen cooking demonstrations tailored for older Veterans with impaired mobility will improve diet and functional mobility. The intervention group will be compared to a contact control group. Our overarching hypothesis is that virtual group nutrition education classes and cooking demos, personalized to include considerations of this population’s physical limitations, age-related taste changes and technological barriers, will result in favorable improvements in dietary quality and functional mobility while promoting social interaction. In Specific Aim 1, we will determine the impact of our virtual intervention paired with produce delivery and virtual cooking demonstrations on objective measures of diet quality compared to contact control among a diverse sample of older Veterans with impaired mobility. Additionally, we will assess the sustained effects of the program on dietary quality at a 6-month follow-up, 3-months after the virtual intervention ends. If no treatment effects are observed at the end of the 3-month intervention, we will explore reasons why the intervention was ineffective. In Specific Aim 2, we will determine the impact of the 3-month virtual nutrition intervention on measures of social isolation, health-related quality of life and mental health using validated questionnaires. Specific Aim 3 will determine associations with changes in dietary quality and frailty-related physical function outcomes and body composition among those who benefit from a virtual nutrition education and cooking program. Through this randomized controlled trial, we will learn how to improve dietary intake among older Veterans with impaired mobility, and how to provide Veterans with skills that will allow them to connect virtually with their social networks. Identifying strategies that improve dietary quality of older Veterans and maintain social engagement likely will be beneficial not only for chronic disease management; but may also reduce the risk of further functional decline and promote functional independence in the growing aging population.

NIMH - National Institute of Mental Health

The purpose of this K23 Career Development Award is to support the applicant in becoming an independent investigator with expertise in implementation science, to study strategies that increase the uptake and use of evidence-based autism services, and to measure the system-level impact of these efforts. Building on the applicant’s existing background in autism health services research and mixed methods, the proposed career development plan will achieve this long-term goal through a combination of implementation science training program activities, coursework, workshops, seminars, and mentored research. These activities will serve as learning vehicles for new skills and knowledge across the following three short-term training goals: 1.) learn to use human-centered design with embedded community-engaged research methods to improve acceptability and usability of interventions and implementation strategies; 2.) gain expertise in the design and conduct of pragmatic, hybrid clinical trials that target effectiveness and implementation outcomes; 3.) learn to evaluate implementation strategies and interventions at the system-level. Training in these areas will support the applicant’s achievement of the following research aims: 1.) adapt the ECHO Autism: STAT Early Diagnosis (EDx) implementation strategy to utilize a biomarker-based diagnostic tool for patients 16-to 30-months old, in a manner that maximizes acceptability and usability; 2.) examine feasibility and acceptability of testing ECHO Autism: STAT EDx vs. ECHO Autism: Technology-Enhanced EDx through a pilot cluster randomized hybrid type 3 trial; 3.) explore differences in time from autism screen to diagnostic ascertainment between 3 groups of patients with positive autism screening results across a large network of pediatric primary care sites: those served by PCPs assigned to each of the two pilot study conditions, and those from all other network sites that did not enroll in the pilot. These research and training goals will be carried out under the co-primary mentorship of Dr. Lawrence Scahill, an expert in autism clinical trials, and Dr. Sarabeth Broder-Fingert, an expert in applications of implementation science to autism health services research; and co-mentorship from Dr. John Constantino, an expert in biomarker-based and environmental influences of autism as well as system-level change to improve mental and behavioral health care. These career development and research activities will occur within a robust infrastructure for training and community-engaged autism research, leveraging strengths of Emory University School of Medicine, Emory University Rollins School of Public Health, the Marcus Autism Center, Project ECHO, and a network of over 175 pediatric primary care practices across Georgia. This K23 proposal is aligned with the NIMH’s Strategic Plan Goal 4: to advance mental health services to strengthen public health. With further training, the applicant is poised to begin a trajectory of work as an independent investigator to promote accessible, early autism services, ultimately improving outcomes for children.

NIDCD - National Institute on Deafness and Other Communication Disorders

Aphasia is a language disorder caused by acquired brain injury that affects one third of stroke survivors and more than 2 million people in the United States. Improving mental health is identified as the #1 stroke recovery priority. Stroke survivors with aphasia (SSwA) experience disproportionately poor mental health compared to stroke survivors without aphasia, with high rates of depression, anxiety, and general psychological distress. Poor mental health affects aphasia recovery, and poor aphasia recovery affects mental health. Therefore, mental health services need to be offered as part of comprehensive aphasia rehabilitation to maximize recovery. Adjustment counseling is within the scope of practice for speech-language pathologists (SLPs), who are well-positioned to address the bi-directional relationship between mental health and aphasia as primary providers of interdisciplinary psychological care. Our team has developed Acceptance and Commitment Therapy (ACT) for Aphasia, an integrated aphasia- adapted counseling and communication strategy intervention provided by SLPs. ACT improves psychological flexibility, allowing people to lead lives consistent with their deeply held values, even in the face of persistent psychological distress. ACT pairs well with communication skills training because they help SSwA understand and express themselves during counseling. In turn, ACT helps SSwA become more willing to participate in meaningful life activities and apply communication skills in challenging situations, supporting skill generalization. Our completed Phase I pilot found good intervention acceptability, feasibility, and promising preliminary outcomes, with large effect sizes for reducing psychological distress. This proposal will evaluate the effectiveness of ACT for Aphasia for improving mental health and functional communication in stroke survivors with aphasia. Aim 1 will evaluate ACT for Aphasia via a well-powered Phase II Randomized Controlled Trial. Aim 2 will engage clinician and community end users and healthcare system experts in exploratory implementation research to inform future implementation and intervention refinement. We predict that a) ACT for Aphasia will significantly reduce psychological distress (the primary outcome) and improve functional communication (an exploratory secondary outcome), compared to an active control condition consisting of usual care intervention components, and b) will meet defined benchmarks to justify a large-scale Phase III efficacy trial. Study success will support continued development and evaluation of this novel intervention and determine optimal implementation pathways for improving access to interdisciplinary psychological aphasia care in the United States.

NIH

Background: Alcohol use disorder (AUD) is the most common non-tobacco substance use disorder among Veterans. Recognizing when patients have AUD is essential to providing appropriate care. Unfortunately, AUD is substantially under-recognized and inequitably recognized across age, race, and ethnicity in VA care. VA has implemented standardized alcohol use screening in primary care. VA clinical guidelines direct primary care providers (PCPs) to determine if patients with heavy alcohol use have AUD, but there is no standardized AUD assessment process. This places burden on PCPs and results in under- and inequitable AUD recognition. Standardized symptom assessment can help PCPs efficiently, consistently, and equitably recognize AUD, may increase AUD recognition and treatment initiation, and is recommended for primary care. An efficient, VA- centered AUD assessment process is needed that uses technology for digital, pre-visit assessment integrated with VA’s electronic health record, meets Veterans’ unique needs, and fits VA-specific primary care structures. Implementation strategies suited to VA are needed to ensure clinics are supported in conducting assessment effectively and consistently. Also, many patients who have AUD identified in primary care will not be ready for treatment immediately, thus a VA-suited tool and process for proactive outreach following AUD recognition is needed to support treatment engagement. This CDA will engage VA patients and personnel to inform Veteran- centered, equitable implementation of AUD assessment in VA primary care. We will develop and pilot a user- centered assessment process and implementation strategies. We will secondarily develop a novel outreach tool/process to support treatment engagement for patients who have AUD identified in primary care. Significance: This research provides a foundation for implementing standardized AUD symptom assessment in VA primary care with the goal of increasing and improving equity in AUD recognition. This work addresses multiple VA HSR priorities: improving mental health (including AUD and associated mental health risks, such as suicide), increasing equity, innovative technology in primary care, and implementation research. Innovation and Impact: This is the first study to examine patient perspectives on AUD assessment in primary care. We will apply innovative user-centered design methods, leverage under-used VA technology for digital, pre-visit assessment, and design a novel tool/process for outreach to support treatment engagement. Specific Aims: 1) Examine patient perspectives on AUD assessment in primary care and potential differences in perspectives across patient characteristics (secondarily, examine perspectives on outreach); 2) Design a user-centered assessment process and implementation strategies (secondarily, design a novel outreach tool/process); 3) Pilot clinic-wide implementation of AUD assessment and conduct mixed-methods evaluation. Methodology: In Aim 1 we will interview ~20 national VA primary care patients with heavy alcohol use to inform a survey, then survey a random sample of ~350; both samples will be balanced on demographics to examine differences across groups. Aim 2 involves qualitative interviews with ~40 personnel from 2 VA primary care clinics, iterative co-design sessions/usability testing to develop a user-centered assessment process (and secondarily, a novel outreach tool/process), and implementation mapping to plan strategies. Aim 3 involves piloting implementation of AUD assessment in 1 clinic and evaluation through qualitative interviews with ~20 clinic personnel and ~20 patients, a brief survey of PCPs, and analysis of electronic health record data. Next Steps/Implementation: This CDA will inform 2 multi-site, hybrid trials: a hybrid type 1 to test effectiveness of the novel outreach tool/process, and a hybrid type 2 to test implementation of AUD assessment. It will provide training in survey research, user-centered design, implementation science, and addressing racial and ethnic disparities, and will support the PI in becoming an independent VA investigator focused on improving substance use-related care through user-centered innovations and implementation.

NIH

SIGNIFICANCE TO VA: In the past decade, the number of women Veterans of childbearing age using VA has nearly doubled, and over forty percent of these women have a diagnosis of serious mental illness (SMI; major depressive disorder, posttraumatic stress disorder, bipolar disorder, schizophrenia, other psychotic disorders). Veterans experience worse pregnancy and birth outcomes than civilians, a disparity largely attributed to their high burden of mental illness and trauma. Pregnant and postpartum Veterans with SMI—who often have numerous mental health, medical, and social challenges—are at high risk for perinatal exacerbation of mental illness, with consequences including maternal morbidity and mortality, poor functioning, and impaired child development. Reach Out, Stay Strong Essentials (ROSE), a brief evidence-based psychoeducational intervention for prevention of postpartum depression in women without mental illness, is being implemented in over two dozen VA facilities; feedback from ROSE implementers supports its use, but with noted limitations for Veterans with SMI. Building on lessons learned from ROSE implementation, I propose to develop and pilot ROSE+, a psychosocial intervention blending ROSE with peer support (i.e., support provided by Veteran peer specialists with personal experience of mental illness). Peer support is a key component of VA mental health care; while evidence exists for peer support in non-SMI perinatal and non-perinatal SMI populations, existing interventions are limited in applicability to the complex social, medical, and mental health needs of perinatal Veterans with SMI. ROSE+ will comprise adapted and combined components of ROSE and evidence-based perinatal and SMI peer support models, tailored to the VA context and the unique needs of perinatal Veterans with SMI. Developed in partnership with VA Office of Women’s Health and Office of Mental Health, this proposal aligns with key VA operations and HSR priorities including women’s health, mental health, maternal health, peer support, and Veteran engagement, and will fill a key gap in care for perinatal Veterans with SMI. INNOVATION & IMPACT: This research will not only set the foundation for the first perinatal mental health intervention for Veterans with SMI, but will also identify additional opportunities to strengthen VA perinatal mental health services and care coordination via an IIR submission in Year 3. SPECIFIC AIMS: 1) Engage Veterans and key VA clinical staff in identifying potential components of ROSE+; 2) Develop and refine the ROSE+ intervention; 3) Assess the feasibility, acceptability, and exploratory outcomes of ROSE+ in a pilot study. METHODOLOGY: Intervention development will be guided by the Transcreation Framework, an implementation science framework for community-partnered development of behavioral interventions for vulnerable populations. Aim 1: To assess the experiences, needs, and care preferences of perinatal Veterans with SMI and inform potential intervention components, I will conduct semi-structured interviews with pregnant and postpartum Veterans with SMI and VA women’s mental health providers, followed by focus groups with VA Maternity Care Coordinators and women VA peer specialists. Aim 2: Using Delphi methodology, I will present potential intervention components—drawn from existing interventions and accompanied by data from the literature and Aim 1 findings—to an expert panel of VA multilevel constituents to identify final components as well as adaptations to optimize fit to the target population and VA women’s health settings. I will then develop and refine the intervention prototype and materials with iterative feedback from partners and mentors. Aim 3: I will conduct a randomized feasibility pilot of ROSE+ compared to usual care including standard ROSE, with approximately 24 perinatal Veteran participants with SMI. The pilot will assess implementation outcomes, including acceptability and feasibility; feasibility of study processes including recruitment and randomization; and exploratory clinical outcomes. PATH TO TRANSLATION/IMPLEMENTATION: Results will inform a subsequent multisite efficacy study, for which I will seek independent VA funding in Year 5.

NIMH - National Institute of Mental Health

Autism research is facing a watershed moment that requires serious scientific investigation, similar to the debate in the early 2000s regarding the vaccines-cause-autism controversy. For the past five decades, behavioral approaches to early intervention have been the primary treatment mechanism for autism. These approaches are based on the principles of Applied Behavior Analysis (ABA) and have substantial research support demonstrating their effectiveness for improving communication, adaptive behavior, and cognitive skills. With the proliferation of the neurodiversity (ND) movement, autistic advocates and allies have called into question the safety, validity, and ethics of autism intervention. There is substantial variation in the concerns raised. The majority of these interventions were developed with the goal of ameliorating autistic characteristics or loss of diagnosis which is counter to autistic priorities. While many autistics endorse supports and/or services for promoting optimal quality of life, whether or not standard autism early intervention (EI) practices fit within that framework remains to be studied. Complicating matters is substantial variation in the implementation of EI in the community. Many community-based organizations (CBOs) deliver older, more rigid versions of EI models than are currently being studied and implemented by autism intervention researchers. Naturalistic developmental behavioral interventions (NDBIs) were developed to address previous limitations in EI models, though these are not well-utilized in CBOs. While some autistics support the adaptation of NDBIs to fit within a neurodiversity-affirming intervention (NAI) framework, others call for the cessation of intervention altogether. Disparate opinions coupled with limited data regarding advocates’ concerns have created a confusing landscape for caregivers who are pressured to make decisions regarding enrolling their newly diagnosed autistic children in EI services within developmentally critical periods. Additionally, autistic individuals are likely to suffer from a lack of fit of services to improve their quality of lives. The proposed projects will address these pressing challenges using community-partnered participatory research approaches to (1) gather information from focus groups with autistics, caregivers, and EI providers regarding acceptable practices; (2) identify adaptation targets that align with an NAI framework; (3) collaboratively develop an implementation toolkit to support an NAI framework in EI services; (4) explore differences in child outcomes and ratings of quality of life across EI approaches; (5) assess provider implementation of the NAI adaptations; and (6) assess the validity of the NAI framework. This innovative work addresses critical gaps in the literature related to modernization of autism EI to address significant stakeholder concerns. It lays the groundwork for future studies directly testing the adaptations, supporting the applicant’s career goals of increasing the equity and acceptability of meaningful evidence-based practices and improving service access.

NIMH - National Institute of Mental Health

Project Summary Social information influences many of our daily decisions, yet studies of the neurobiology of decision-making typically overlook social components. Importantly, to make a choice from multiple modalities, social and non- social information must, in principle, converge into a ‘common currency’. However, how these inputs are combined in decision-making circuits is largely unknown. To study how and to what extent social and non-social information are combined in decision-making circuits, we propose to develop a novel social foraging task for mice. In this task, two mice will simultaneously traverse a simple maze, making a left or right choice for water rewards. In contrast to when foraging alone, mice in the social task have additional information (i.e., the choice and reward history of the conspecific, gained through observation) that can be used to influence their decisions. In Aim 1, we will use reinforcement learning framework to model the cognitive and algorithmic process of how mice use social information, and test different learning rules by evaluating how well they fit mouse behavior. We will then use this model to quantify how overarching social relationships, such as biological sex, social familiarity, and hierarchical rank, influence the magnitude of which social information influences choice. In Aim 2, to understand how social information is integrated with other internal variables in decision-making circuits, we will record neurons in the posterior parietal cortex (PPC) and medial prefrontal cortex (mPFC), two central cites for decision-making in the mammalian brain, as mice perform both the social and non-social T-maze task. We hypothesize that social information will be more strongly encoded in mPFC, which has been previously associated with a wide variety of social behaviors, and that PPC will, in contrast, encode more general-purpose information about the moment-to-moment decision. This proposal aims to elucidate the overarching structure and organization of how decision-making circuits incorporate social information, and whether they serve as general ‘common currency’ circuits or support socially specific computations.

NIMH - National Institute of Mental Health

The purpose of this mentored career development award is to provide the candidate with rigorous and comprehensive training in preparation for an independent academic research career in molecular neuroimaging. Specifically, the completion of individualized training activities and proposed research over the course of the five-year award term will allow the candidate to develop the requisite expertise for a research career utilizing positron emission tomography (PET) in individuals with severe compulsive and impulsive behaviors, such as hoarding disorder (HD). The three career goals outlined in this training program include intensive, focused training in 1) Neurobiology and pathology of compulsive behaviors (emphasizing HD and relationships to functional outcomes and risk); 2) Intensive training in PET methodology and data acquisition; and 3) Advanced training in biostatistics for integration of PET and behavioral data. Integral to these goals is essential training in responsible conduct of research. The training plan will be executed with oversight from experts in neurobiology, molecular imaging, and psychiatry and performed in a rich academic environment (Yale School of Medicine), offering optimal resources and facilities for the proposed training and research. The proposed research consists of an innovative PET study in individuals diagnosed with DSM-5 HD. HD is a devastating and understudied psychiatric condition characterized by severe and compulsive difficulties with discarding and excessive acquisition, resulting in debilitating levels of clutter. HD is associated with profound personal and public health issues, including medical and psychiatric comorbidity, vast functional impairment, and increased risk for suicide. Alarmingly, studies report that fewer than one-third of patients achieve clinically significant change in treatment due in part to factors such as attrition and low treatment motivation. Currently, no FDA-approved pharmacological therapies for HD are available. Research into novel treatments is necessary to provide symptom relief, reduce risk, and improve quality of life. Moreover, pharmacological interventions addressing acute distress and increasing treatment retention may be needed to impart long-term behavior change. Evidence implicates kappa opioid receptors (KOR) in motivation, emotion regulation, compulsive behaviors, and in pre-clinical models of hoarding. Our promising pilot data show significantly lower KOR availability in subjects with hoarding behaviors (n=5) relative to healthy controls (HC). Here, we aim to extend these exciting findings by examining 1) KOR availability in-vivo using [11C]EKAP PET in individuals with HD relative to demographically matched HC; 2) relationships between KOR availability and clinically meaningful endophenotypes of HD; and 3) associations between KOR and functional outcomes in individuals with HD. Results have potential to significantly impact HD treatment development. Completion of the proposed training plan and research study will optimally position the candidate for a successful career conducting impactful research in psychiatric populations with severe compulsive behaviors.

NIMH - National Institute of Mental Health

PROJECT SUMMARY Stable HIV reservoirs remain a significant challenge for the eradication of HIV-1 (HIV). While several anti- HIV latency strategies have been proposed to control HIV reservoirs, few have proven effective in reducing the size of the HIV reservoir in clinical settings. This suggests that our current understanding of how HIV achieves its persistent infection is limited and underscores the need for the development of alternative innovative tools for HIV cure. Recently, we and others characterized a unique integrated stress response (ISR)/ATF4 signaling pathway that is essential for HIV transcription and early seeding of HIV. Conversely, when ATF4 is knocked down, HIV transcription is inhibited. We further defined ATF4 as a new transcription factor of HIV, exploited by HIV for its own transcription after the recruitment of ATF4 to the ATF/CREB consensus site at the 5’ HIV long-terminal repeat. ATF4 induction leads to HIV activation from latency, indicating that ISR/ATF4 signaling activation promotes HIV transcription while the suppression of ISR signaling is associated with the establishment of HIV latency. Of note, prolonged activation of ISR/ATF4 signaling also induces cell death, mediated by ATF4 binding to the promoter of the CHOP gene, an essential protein driving apoptosis during persistent ISR/ATF4 activation. In a primary CD4+ T cell model of latency, prolonged ISR/ATF4 signaling activation disrupts latent HIV and selectively induces apoptosis in HIV+ CD4+ T cells, without affecting bystander HIV-negative CD4+ T cells. Notably, using viral outgrowth assays, we discovered that prolonged ISR/ATF4 signaling activation reduces replication-competent HIV by up to 2,300-fold in resting CD4+ T cells isolated from people with HIV receiving suppressive antiretroviral therapy (ART). Therefore, we hypothesize that the suppression of ISR/ATF4 signaling is essential for HIV persistence. This will be tested through three specific aims: Aim 1: Investigate how activation of the ISR/ATF4 signaling pathway eliminates HIV-latently infected T cells and brain microglia. Aim 2: Elucidate the unique mechanisms by which ISR/ATF4 signaling controls the stable HIV reservoir for the establishment of HIV latency. Aim 3: Determine the effectiveness of activating ISR/ATF4 signaling in eliminating HIV reservoirs in the hu-BLT mouse model of HIV latency in vivo.

NIH

Significance to VA: Elevated symptoms of depression and generalized anxiety disorder (GAD) are present in 10% and 8% of Veterans respectively and are associated with functional impairment and suicidality. Cognitive behavioral therapy (CBT) is a first line intervention for these conditions, yet few Veterans receive this treatment, in part due to the limited availability of mental health providers trained in CBT. The stepped care model offers one approach to addressing access by offering effective yet less resource-intensive treatments upon entry into mental health care for individuals with mild to moderate symptoms, stepping up the intensity and level of care as needed. Guided self-help (GSH) is one low intensity treatment format that could increase accessibility of CBT for depression and GAD. In GSH, patients follow a self-help version of an evidence-based behavioral intervention with coaching from a provider. A meta-analysis found that GSH is as effective as traditional psychotherapy treatments for depression and anxiety disorders. VHA’s Primary Care Mental Health- Integration (PCMHI) Service may be the ideal setting in which to deploy GSH. However, GSH is not widely used within VHA, and existing CBT interventions for depression and GAD would require adaptation to the GSH format and PCMHI setting and would benefit from Veteran input. One critical question is whether GSH can be feasibly delivered by non-psychologists, such as social workers and/or health coaches, to help address mental health access. This research may increase Veteran access to care through the availability of efficient, evidence-based programs at a lower level of the stepped care model of mental health treatment. Building Veteran-centered programs by incorporating Veteran feedback throughout the process may increase engagement with care. Overall, the project aligns with the VA strategic priority of implementation science. Innovation and Impact: This project proposes to innovate current practices in a lower level of the stepped care model of mental health treatment in VHA by providing GSH programs for prevalent conditions. If these programs can be feasibility delivered by non-psychologists, this has the potential to increase access to mental health care for Veterans, reduce costs to VHA over time, and help connect Veterans to soonest and best care. Specific Aims: The specific aims of this project are to 1) Conduct a formative evaluation assessing barriers and facilitators to the use of GSH for symptoms of depression and GAD in PCMHI via a national survey and qualitative interviews with PCMHI providers and clinic administrators, 2) Refine and conduct a pilot randomized trial of Behavioral Activation-GSH (BA-GSH) for depression (15 Veterans assigned to BA-GSH; 15 assigned to treatment as usual) in PCMHI as delivered by a group of non-psychologists. This pilot will evaluate the acceptability and feasibility of BA-GSH and explore preliminary effectiveness, and 3) Through iterative intervention design and adaptation, integrate Veteran feedback to adapt an existing CBT for GAD intervention (GSH-GAD) for delivery in PCMHI and conduct an open trial pilot of GSH-GAD with 10 Veterans in PCMHI. Methodology: For Aim 1, sequential explanatory mixed-methods evaluation will be used to identify barriers and facilitators to implementing GSH programs in PCMHI and as well as which provider type may be best suited to deliver GSH. For Aim 2, a randomized pilot trial will evaluate the feasibility and acceptability of a GSH program (BA-GSH) for symptoms of depression through qualitative interviews and an exploratory pre-post comparison of symptoms. For Aim 3, iterative intervention design and adaptation will be used to adapt a GSH program for symptoms of GAD. The resulting program will be evaluated in 10 Veterans through an open pilot. Path to Translation/Implementation: The training, piloting of methods, preparation of GSH programs for future implementation, and information gathered through this research will prepare Dr. Plasencia for becoming an independent VA investigator. With an initial focus on GSH, her work will seek to increase access to care by developing effective and Veteran-centered programs for mental health in VHA.

Indigenous Services Canada

Funds health promotion, disease prevention, mental wellness, and substance use programs for Indigenous communities.

NYS Office of Mental Health

6140 ? Transformed Business Model (Non-Licensed Program) A Transformed Business Model was designed to transform those employment opportunities offered by a sheltered workshop provider into competitive, integrated jobs. This model may only be funded in an agency that formerly operated a sheltered workshop program and/or currently provides services through a Personalized Recovery Oriented Services program (PROS). A Transformed Business Model is a self-sustaining business such as a small retail or wholesale outlet, or manufacturing and service-oriented business that is owned and operated by an OMH provider; a TBM provides both employment and mental health supports onsite. These businesses provide integrated, competitive, employment opportunities for individuals with serious mental illness. The OMH funding is for the mental health supports* needed for the person to be successful at the job. *Supports may include assisting someone in interpreting and responding appropriately to interpersonal situations at work, or learning to cope with mental health symptoms to enhance their work performance. Financial/Benefits Counseling may be provided. Care should be taken to ensure policies exist to separate the provision of mental health support from work supervision. Note: A PROS program cannot bill for employment services for individuals employed in a TBM. The goal of supported employment is for individuals to work a minimum of 10 hours per week in an integrated, competitive job, with leeway for absence due to illness, vacation, or temporary work stoppages. See Glossary for definitions of "Competitive Employment" and "Integrated Employment". To be considered employed part time, participants should be scheduled to work a minimum of 10 hours each week. Units of Service: Unique number of individuals served per year.

Substance Abuse and Mental Health Services Adminis

The purpose of the Infant and Early Childhood Mental Health program is to develop or enhance evidence-based programs that promote social-emotional development and address mental health needs among infants and young children.

Substance Abuse and Mental Health Services Adminis

Infant and Early Childhood Mental Health

NIMH - National Institute of Mental Health

Suicide is the leading cause of non-accidental death in adolescents in the US, and rates of suicide continue to rise in adolescent populations. Yet, the biological mechanisms leading to adolescent suicide that could inform effective preventive treatments for suicide remain unclear. To understand adolescent suicide, scientists often study suicidal ideation (SI), given that SI is strongly associated with suicidal behavior (SB) and is methodologically more feasible to study in adolescents. This K23 proposal will test a novel and integrative neurobiological model in adolescents with the hypothesis that circulating and stimulated peripheral inflammatory markers (PIMs; e.g. IL-6, TNFα, CRP) contribute to dysfunction in reward-related corticostriatal (CS) circuitry, and that this dysfunction in CS circuitry (and related behavioral correlates) contributes to adolescent SI. Prior research has linked PIM activation to SI/SB, but the biological mechanisms by which PIMs might contribute to SI remain unclear. Existing literature suggests that PIMs might affect CS functional connectivity, and that dysfunction in CS functional connectivity predicts SI and SB, though this integrative model has not been previously tested. Based on conceptual models and early clinical studies, one specific feature of reward processing - effort expenditure for reward (i.e., the amount of effort an individual is willing to expend for a reward) - may specifically be linked to SI/SB. In addition, the described integrative model is particularly relevant in adolescents, who are at a vulnerable developmental epoch for both reward circuitry and immune system maturation. This K23 will test the proposed model in 90 adolescents with unipolar depressive disorders, enriched with adolescents with a history of SI or SB. Adolescents will be followed over four timepoints over twelve months, with measurements of PIMs, CS functional connectivity during a reward task, and SI. This proposal will address key gaps in the field of adolescent suicide research, including understanding (1) the association between PIMs and CS connectivity in predicting future SI, (2) the relationships between PIMs and CS circuitry, and (3) the role of CS circuitry in explaining relationships between PIMs and SI. Understanding these gaps in the literature could elucidate clinically meaningful mechanisms of adolescent suicide, identify biobehavioral markers that could predict future SI, and potentially guide future interventions for adolescent SI/SB. The candidate will receive advanced training from an expert mentorship team, including knowledgeable co-mentors (Drs. Price, Brent, Forbes, and Marsland) and consultants (Drs. Brundin, Treadway, Thoma, and Wallace). The research environment at the University of Pittsburgh provides excellent resources. Consistent with the candidate’s career goals of better understanding biobehavioral mechanisms involved in adolescent suicidality, research findings from this K23 would inform future R01 proposals that could examine mechanisms by which PIMs contribute to SB in large samples, and aid development of interventions targeting PIMs or CS circuitry to reduce SI/SB.

NIMH - National Institute of Mental Health

PROJECT SUMMARY During sickness, the immune system and central nervous system coordinate to generate physical and behavioral changes, such as lethargy, anorexia, anhedonia, and social withdrawal, that can vary significantly in severity between individuals. While these symptoms help aid in sickness recovery, severe responses can be harmful and possibly life-threatening. What drives this symptomatic variation in sickness manifestation is still unclear, however, external factors such as social support may be a contributing factor. Prolonged social isolation not only impacts the immune response but is also associated with adverse physical and mental health outcomes. Previous studies have identified bi-directional interactions between immune signals and the central nervous system, suggesting a direct link between immune-activated neural circuits and sickness outcomes. Moreover, social isolation can have a dramatic effect on neuronal activity in specific brain regions. My preliminary studies demonstrate that social isolation exacerbates symptoms of sickness, such as body temperature and appetite, and increases circulating levels of immune factors known to mediate sickness state. Using activity pattern analysis, I found that activity in the insular cortex (IC) is dependent on both sickness and social isolation, suggesting integration of both social and immune signals. Therefore, I hypothesized that social isolation increases the severity and recovery time of sickness through specific neuronal and circuit mechanisms that integrate social behavior and sickness. I will address my central hypothesis by inducing sickness in isolated or group-housed mice through peripheral administration of bacterial lipopolysaccharides (LPS). In Aim 1, I will employ cell-type-specific functional manipulation approaches, including chemogenetic activation and permanent neuronal silencing, to determine the function of the “sickness neurons” in the IC. In Aim 2, I will identify the upstream neuronal inputs that convey social context to sickness-activated IC neurons using retrograde tracing and determine how these social inputs modulate sickness symptoms and behaviors using projection-specific activation. Together, the completion of this project will determine how the social environment influences sickness manifestation and recovery, revealing critical insight into long-standing observations linking isolated social environments with poor health.

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

PROJECT SUMMARY/ABSTRACT The goal of the F99/K00 award is to provide Talia Kieu, MSPH, with the training needed to become an independent investigator focused on using advanced methods to identify the risk and protective factors of mental health outcomes among populations with multiple marginalized identities across the life course, as well as provide resources to augment and support researcher diversity. In 2019, the economic burden of major depressive disorder in the United States was estimated at $333.7 billion. Those with multiple marginalized identities (e.g., a low-income Black woman) are more likely to experience severe and persistent depression than those with a single or no marginalized identities. Depressive symptoms may be reflective of experienced life events; therefore, examining social conditions from adolescence and their effect into adulthood is critical to understand. Current literature on depression outcomes primarily sums the effects of social identities (e.g., race, sex) without exploring their multiplicative effects (i.e., how being both Black and a woman may uniquely compound risks for depression compared to each identity alone), often relying on cross-sectional analyses, which may contribute to the mixed findings in the current depression disparities literature. These conflicting findings highlight the need for a more nuanced understanding of how depression manifests longitudinally in marginalized populations. It is equally important to identify protective factors, such as social integration—the degree in which an individual is connected to their social environment. Research in the F99 phase (Aim 1) addresses these gaps by investigating 1) how depression evolves over the life course in those with multiple marginalized identities; 2) how multiple marginalized identities can have compounding, multiplicative effects on depression outcomes; and 3) how social integration manifests as a protective factor. Findings from this study will have implications for practice by identifying vulnerable populations and exploring strengths-based, protective factors for mental health interventions. Mental health interventions should also be well timed. Some marginalized populations, such as sexual/gender minority (SGM) communities, experience off-time sensitive periods due to multiple forms of stigma, which may result in overlooking optimal timing for mental health interventions. There is a need to examine how early-life experiences and off-time sensitive periods shape the mental health of SGM populations. Research in the K00 phase (Aim 2) will address these gaps by collecting mixed-methods data to 1) retrospectively explore the impact of holding multiple marginalized identities on the sensitive periods and mental health trajectories of older, SGM individuals of color; 2) explore the long-term impacts of adolescent experiences; and 3) validate findings through intergenerational member-checking sessions with adolescent and older SGM individuals. Findings from this study will have practical implications for timing mental health interventions effectively, and tailoring interventions to facilitate the protective qualities of SGM communities.

National Institutes of Health

Innovative Mental Health Services Research Not Involving Clinical Trials (R01 Clinical Trials Not Allowed)