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NIDA - National Institute on Drug Abuse

Project Summary/Abstract The Research Intensive Summer Experience in Dual Diagnosis (RISE-DD) will establish a structured research education and mentoring program that prepares medical students, graduate students, and postdoctoral fellows to pursue careers in substance use and mental health research. RISE-DD will be based at the Institute for Mental and Behavioral Health Research at Nationwide Children’s Hospital and The Ohio State University, leveraging a robust academic–clinical partnership and a proven infrastructure for summer training programs. Participants will complete a ten-week, full-time mentored research experience paired with didactic instruction in measurement-based care, data science, responsible conduct of research, and open-science best practices. Trainees will receive guided experience in study design, secondary data analysis, reproducibility, and dissemination, culminating in scholarly products such as posters, manuscripts, and open-science project pages. The curriculum integrates ethics and best practices, including modules on working with vulnerable populations, promoting transparency in research, and responsible use of artificial intelligence in data workflows. The RISE-DD leadership team—Drs. Eric Youngstrom (Contact PD/PI) and Laura Chavez (MPI)—will co-direct a multidisciplinary mentor network encompassing psychiatry, pediatrics, psychology, data science, and community-based research.

National Institutes of Health

-Purpose. The National Institute of Mental Health (NIMH) encourages research on adherence to interventions for mental disorders. The clinical effectiveness of efficacious interventions for mental disorders is substantially limited by less than optimal adherence to these interventions. Problems of adherence are common across most medical interventions, but are further exacerbated in mental health interventions by the cognitive and motivational deficits often associated with these conditions. Therefore, research is encouraged to further understand the potent and modifiable factors associated with treatment adherence in those with mental disorders and to develop and evaluate strategies to improve adherence to efficacious interventions for mental disorders. -Mechanism of Support. This FOA will utilize the NIH Research Project Grant (R01) award mechanism, but applications under the NIH Small Research Grant Program (R03) and the NIH Exploratory/Developmental Research Grant Program (R21) are also sought. Applicants for the R03 should respond to PA-06-180 and applicants for the R21 should respond to PA-06-181. -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.

National Institutes of Health

Purpose. Insomnia Disorder affects approximately 10% of adults in the U.S. and results in decreased work and academic performance, increased risk of accidents, increased health care costs, and increased risk of depression and other mental disorders. Given the public health significance of this problem, the NIH State-of-the-Science Conference on Manifestations and Management of Chronic Insomnia in Adults was held in June, 2005. The resulting conference statement outlined what is currently known and identified important future directions for insomnia-related research. The purpose of this funding opportunity announcement (FOA) is to encourage research that addresses the research needs outlined in this conference statement. Recommended areas for future research include genetic and neurobiologic mechanisms of insomnia, longitudinal studies of incidence and course of insomnia, improved measures of daytime functioning and quality of life resulting from insomnia, studies of insomnia in special populations, the impact of insomnia on the development of other disorders including depression, drug abuse, and chronic diseases, and the development and evaluation of treatment approaches and their dissemination. Research that translates basic science findings into novel clinical approaches is particularly encouraged.

National Institutes of Health

-Purpose. The purpose of this Funding Opportunity Announcement (FOA) issued by the National Institute of Mental Health (NIMH), National Institutes of Health (NIH), is to invite grant applications for research designed to elucidate the epidemiology, etiology, treatment, and prevention of mental disorders, including emotional and behavioral problems, in persons of any age with intellectual disabilities (mental retardation). Although intellectual disabilities and autism often co-occur, separate FOAs are relevant for investigators interested in autism: RESEARCH ON AUTISM AND AUTISM SPECTRUM DISORDERS under the NIH Research Project Grant (R01) (PA-07-085), the NIH Small Research Grant (R03) (PA-06-391), and the NIH Exploratory/Developmental Grant (R21) (PA-06-392) award mechanisms. -Mechanism of Support. This FOA, Research on Psychopathology In Intellectual Disabilities (Mental Retardation), will use the NIH Research Project Grant (R01) award mechanism. Applications of related or identical scientific scope are also solicited under the NIH Small Research Grant (R03), the NIH Exploratory/Developmental Grant (R21), the NIMH Clinical Exploratory Research Grant (R34), and the NIMH Collaborative Program (R01) award mechanisms, responding to FOAs PA-06-180, PA-06-181, PAR-06-248, and PA-07-092, respectively. (For inquiries, see Section VII, Agency Contacts. ) -Funds Available and Anticipated Number of Awards. Because the nature and scope of the proposed research will vary from application to application, it is anticipated that the size and duration of each award will also vary. The total amount awarded and the number of awards will depend upon the mechanism numbers, quality, duration, and costs of the applications received.

National Institutes of Health

-Purpose. The purpose of this Funding Opportunity Announcement (FOA) is to invite grant applications to stimulate research on mental health, HIV/AIDS and/or drug abuse problems in rural and frontier communities that will: (1) enhance understanding of structural (including community risk and resilience factors), cultural, and individual factors that may enhance the provision and utilization of prevention and treatment services in these communities; and (2) generate knowledge to improve the organization, financing, efficiency, effectiveness, quality, and outcomes of mental health and drug abuse services for diverse populations in rural and frontier populations. -Mechanism of Support. This FOA will utilize the NIH Research Project Grant (R01) award mechanism , but applications for the NIMH Clinical Exploratory/Developmental Research Grant (R34) are also encouraged. Applicants for the R34 mechanism should respond to the PAR-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.

NIMH - National Institute of Mental Health

Project Summary/Abstract As young adults with autism spectrum disorder (YAASD) transition out of the academic supports provided by school, they can experience a degradation of social skills over time. This increases their risk of poor social, academic, vocational, and health outcomes. YAASD require continuous and ongoing skill development in order to maximize their potential; however, there are few services available to YAASD to develop and maintain their skills. While interventions exist in early childhood, mid-childhood, and adolescence, few programs have focused on improving resilience among YAASD. Resilience in ActionTM (RiA): Assessing the behavioral target mechanisms of the RiATM curriculum in young adults with autism, is a proposed research study that will be delivered in both community and academic settings to address the ‘adult world’ needs of YAASD who have exited out of secondary education. RiATM has been pilot-tested with YAASD and found to be highly acceptable (with 100% course completion and high course satisfaction), and contributed to YAASDs’ improved resiliency measured pre/post the course. In the proposed study, we will test the RiA curriculum developed in the San Francisco Bay Area, into 2 new sites (Boston, Massachusetts, and Baltimore, Maryland) – In Aim 1, we will conduct a randomized waitlist control trial with 288 YAASD (between 19-26 years of age) to examine the effectiveness of the RiA curriculum on resiliency targets (e.g. self- determination, self-efficacy, social confidence, emotional regulation). In Aim 2, we will examine whether resilience targets are associated with improvements in mental health and explore the impact on emotional regulation, vocational outcomes, and quality of life over a 12-month follow- up. Aim 3 will focus on studying the implementation of the RiA curriculum across the different sites using an expanded RE-AIM Framework. The proposed study would be the first to test resilience as a mechanism of action of the RiA curriculum for YAASD, and whether resiliency gained contributes to improved mental health and social outcomes in a multi-center trial of community-based partnerships across the US. This study will add to the science of how resiliency interventions can improve YAASD’s mental health, social, educational, and health- related outcomes.

NIMH - National Institute of Mental Health

PROJECT SUMMARY The brain is an extraordinarily complex organ containing many millions of neurons and non-neuronal cells that are organized into highly specialized yet intricately integrated circuits controlling various activities, such as sensory perception, motor control, and cognitive processes. The brainstem is a critical region responsible for regulating essential bodily functions, like heart rate, blood pressure, and digestion, and thus maintaining body homeostasis. The individual neurons in brainstem can be classified into types based on shared characteristics like gene expression. Binning individual cells into cell types is fundamental for advancing our understanding of complex biological systems, like the brain, from normal tissue function to disease processes. The characterization of cell types enables creation of tools to gain genetic access to groups of cells, it enables dissection of cellular heterogeneity, identify key players in various contexts like disease and aging, and lay the groundwork for targeted interventions and therapies. We recently built a comprehensive, high-resolution atlas of cell types across the entire adult mouse brain and the cell type diversity in brainstem exceeded our expectations. Brainstem is home to a highly heterogeneous group of neurons that does not share a specific gene module, yet these neurons are highly similar to one another. In addition, these cell types intermingle in various regions and their function is strongly determined by their input/output relationship. This suggests that a high-dimensional combinatorial gene expression code is needed to resolve the unique transcriptomic cell types in this region. Our goal is to create a refined atlas of cell types in brainstem using a combination of single cell transcriptomic profiling, spatial transcriptomic profiling, and mapping of projection patterns to transcriptomic cell types in brainstem. In addition, we will computationally align brain stem cell types from mouse, non-human primate, and human to define a cross-species consensus atlas of brain stem. Cell type homologies across species can be established based on conserved marker expression. This enables inference of cellular properties, such as long- range projection targets, that are difficult to measure in humans. The proposed efforts will lead to a significantly improved understanding of brainstem cell types and their function and lay the foundation for a better understanding of disease processes related to that region.

NCI - National Cancer Institute

ABSTRACT Acute lymphoblastic leukemia (ALL) is the most common cancer diagnosed in childhood. Although risk-adapted therapy and supportive care have improved survival rates, children who receive chemotherapy continue to experience reduced quality of life, including poor sleep health and fatigue long after treatment. Poor sleep significantly elevates risk for deleterious physical and mental health problems in all children and exacerbates risks in ALL patients. While cognitive-behavioral therapy for pediatric insomnia (CBT-PI) is a ‘gold standard’ intervention, it is severely underutilized in pediatric cancer. Guided by conceptual models of sleep disturbance in pediatric cancer and an intervention mapping framework (IM-ADAPT), we propose to derive and test an adapted, telehealth-delivered CBT-PI protocol, REsolving Sleep Troubles in Childhood Leukemia (REST). The REST protocol will address the unique sleep challenges faced by all children receiving maintenance therapy and the ecologies impacting sleep health among heterogeneous families. To adapt CBT-PI, we will engage in iterative refinements, collaborate with an Expert Panel, gather insights from behavioral health providers, and test the usability of intervention materials. We will then evaluate the preliminary efficacy of REST in a pilot randomized controlled trial (n = 72) comparing REST to a sleep education control group. Participants will be children ages 5-10 years and their caregiver. In addition to feasibility and acceptability, primary outcomes including objective (actigraphy) and subjective (caregiver and child report) sleep patterns, daytime fatigue, and circadian rhythms (diurnal salivary cortisol) will be examined at three timepoints (pre-intervention, post-intervention, and 3-month follow up). We also plan to explore potential predictors of REST’s effects including child and parenting/family characteristics. We hypothesize REST will be feasible and acceptable, and produce greater improvements in sleep, fatigue and circadian rhythms than an education control condition. The proposed project addresses critical gaps in care for children with ALL and will directly inform a larger effectiveness trial.

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

PROJECT SUMMARY Millions of individuals around the world are affected by transfemoral lower limb loss, reducing their mobility and profoundly impacting their quality of life. Reduced mobility is a major contributor to adverse physical and mental health outcomes, including limited social participation, inability to return to work, and increased depression. Restoring the maximum possible mobility is, thus, a critical concern. Prosthetic devices are accepted treatment options for lower limb amputation, but even advanced prostheses like microprocessor-controlled knees (MPKs) fall short of restoring pre-amputation gait function. Powered prosthetic knees offer the potential to restore joint torque and replicate human limb functions. However, their increased mass and inertia often diminish their benefits and limit user adoption. While reducing the mass of a powered prosthesis has a practical limit, a more straightforward and tractable approach to overcome these limitations is to reduce the inertia of the device by placing the powertrain above the knee instead of below it, concentrating the mass more proximal to the trunk. This redistributes, rather than reduces, the mass to improve gait. While studies of have shown that above-knee mass placement is superior to below-knee mass placement in passive prosthetic knees, the build height of current powered devices has prevented direct testing of this approach. Specifically, moving the powertrain above the knee would necessitate moving the prosthetic knee center substantially below the sound knee, introducing a large degree of asymmetry. Although a moderate amount of knee height asymmetry has been shown to actually improve step time symmetry when using a passive prosthesis, the disparity in knee height required for powertrain repositioning in current devices would likely have adverse impacts on gait. However, our new low-profile powered knee prototype has a small build height that makes powertrain repositioning possible. The proposed study seeks to gain fundamental biomechanical insights on how mass placement, knee height, and powered assistance interact to affect gait. In Aim 1, we will utilize predictive simulation and biomechanical modeling technology to perform in silico testing of various knee height and mass placement configurations of a prosthesis on virtual subjects with differing physical characteristics, such as residual limb length. This allows our team to test a wide array of configurations in a rapid and efficient manner. In Aim 2, we will perform human subjects testing to assess how knee height asymmetry and mass placement affect gait when using a passive prosthetic knee. Finally, in Aim 3, we will assess how the placement of the powertrain, which accounts for most of the mass and influences knee joint height in our low-profile powered knee prototype, affects walking performance in lower limb prosthesis users. This work leverages our new device to systematically investigate how mass placement, knee height asymmetry, and powered assistance interact to affect mobility. Unlike prior studies, which examine these factors in isolation and only in passive knees, our work will generate foundational data needed to inform evidence-based design of next-generation powered prostheses to optimize outcomes.

NIMH - National Institute of Mental Health

PROJECT SUMMARY Early identification of autism and access to diagnostic evaluation services are critical priorities within pediatric communities. Efforts to enhance early identification have yielded several successful screening and diagnostic models for toddlers, but less work has focused on the preschool age range. In past work, our team developed the TAP for tele-assessment of toddlers. Research on the TAP has demonstrated high levels of diagnostic accuracy, clinician confidence, and family satisfaction. However, the TAP was not designed for the preschool age group. Many children with autism are not identified until four years of age or later, resulting in a significant need for tools that can meet the needs of a broader age range. Given this need, our team developed the TAP- Preschool (TAP-P) specifically for children from three to six years of age.15 Our preliminary work (R21MH128790- 01) indicated that (1) many children with autism and limited verbal language can be accurately identified using the TAP-P and (2) the TAP-P can support tele-diagnosis of some children with more verbal language. However, this study was limited by a smaller sample size and limited phenotypic variability that precluded detailed psychometric evaluation. Further, differences in tele-assessment diagnostic ascertainment as a function of child expressive language level indicates a need for further investigation into patient and family characteristics that influence for whom the TAP-P is most effective. Specifically, deploying tele-assessment models with preschool- aged children requires understanding who is most likely to benefit from tele-assessment. Without this, large- scale deployment of tele-assessment for this age range risks exacerbating wait times, if a substantial number of children require further in-person evaluation. In the current work, we will recruit a sample of 250 children with varied language and phenotypic profiles to thoroughly evaluate the psychometric properties of the TAP-P. We will additionally investigate child and family factors associated with diagnostic ascertainment and family satisfaction with tele-assessment to inform the creation of a decision support tool intended to recommend families to receive either tele- or in-person assessment. We will test the decision support tool with a novel sample of 100 children with flexible use of verbal language to determine whether there are differences in diagnostic ascertainment, clinician certainty, and family satisfaction for children recommended for tele-assessment and those recommended to receive in-person assessment. If successful, this work will provide crucial information about tele-assessment of autism in preschoolers that could increase access to streamlined diagnostic care for the children and families most likely to benefit from tele-assessment, ultimately serving more children and families in efficient, meaningful ways.

National Institutes of Health

-Purpose. The purpose of this Funding Opportunity Announcement (FOA) issued by the National Institute of Mental Health (NIMH), the National Institute on Drug Abuse (NIDA), and the National Institute on Alcohol Abuse and Alcoholism (NIAAA), National Institutes of Health (NIH), is to invite grant applications involving extensive and innovative use of existing data sets to study the development of psychopathology, including alcohol and drug abuse, in order to guide the development of preventive and treatment intervention strategies. Under this FOA, the NIMH, the NIDA, and the NIAAA encourage research using focused and coordinated analyses of mental health and substance abuse research data that are in public use format or that are privately held by a Project Director/Principal Investigator. -Mechanism of Support. This FOA will utilize the NIH Research Project Grant (R01) award mechanism. Applications of related or identical scientific scope are also sought under the Small Research Grant (R03) award mechanism, responding to FOA PA-06-180. -Funds Available and Anticipated Number of Awards. Because the nature and scope of the proposed research will vary from application to application, it is anticipated that the size and duration of each award will also vary. The total amount awarded and the number of awards will depend upon the mechanism numbers, quality, duration, and costs of the applications received.

NIMH - National Institute of Mental Health

Project summary Living organisms need to interpret various sensory information and implement corresponding instrumental actions to maximize their chances of getting rewards. Alterations of the process of perceptual decision making are associated with several mental illnesses including schizophrenia and substance use disorders. Although both the amygdala and the striatum are implicated in reward seeking and selection of instrumental actions, the neural mechanisms of how these two structures work in concert to regulate sensory-driven decision making remain elusive. With neural tracing and endoscopic calcium imaging, I identified two anatomically and functionally distinct neural populations in the anterior and posterior basolateral amygdala (BLA) that differentially innervated the tail of the striatum (TS) and the nucleus accumbens (NAc). While the NAc projecting BLA neurons (BLANAc) primarily encoded reward acquisition, the TS projecting BLA neurons (BLATS) were activated during instrumental actions and further segregated into separate ensembles that encoded different action choices during perceptual decision making. Building on these findings, I propose to investigate the heterogeneity of BLA striatal projections and interrogate the mechanisms of how BLATS neurons instruct the selection of instrumental actions. In aim1, I will perform single-cell RNA sequencing and monosynaptic rabies tracing experiments to reveal the molecular and wiring principals that govern the BLA functional heterogeneity. In aim2, I hypothesize that choice-encoding BLATS neural ensembles selectively innervate the direct and indirect pathways in the TS to bias action choices. I will leverage the Targeted Recombination in Active Populations (TRAP) approach in combination with optogenetic assisted circuit mapping to test the causal role of biased connection between choice encoding BLATS neurons and the TS direct and indirect pathways in action selection. In aim3, I will test if BLATS neurons broadly control action selection in naturalistic behaviors. This proposal will expand our knowledge of the amygdala and striatum function and provide a mechanistic understanding of the process of perceptual decision making. The proposed research and career development plan will be conducted in the lab of Dr. Guoping Feng at McGovern Institute for Brain Research at MIT, which will prepare Dr. Xin Fu to direct an innovative research program as an independent investigator studying the synaptic and functional organization of neural circuits underlying decision making in reward-seeking behaviors.

NIMH - National Institute of Mental Health

PROJECT SUMMARY: Menopause is a pivotal life stage that brings about lasting changes in mental and cognitive functioning, potentially leading to profound negative effects on multiple life domains in females. During this period, many females may experience the worsening of depressive symptoms or onset of major depressive disorder (MDD), the most prevalent and disabling psychiatric disorder worldwide. Despite the fact that females comprise about half of the global population, evidence that neurochemical alterations observed during menopause may be associated with dementia onset, and higher rates of depression and dementia in females, there are currently no effective treatments targeting the mood and cognitive alterations experienced during menopause. Converging evidence from human clinical studies, postmortem analyses, and preclinical research suggests that both depression and menopause may alter the same brain mechanisms that are crucial for maintaining brain health, particularly through synaptic alterations as possible neurochemical mechanisms. Recent advancements in in vivo quantification of synaptic density in humans have made it possible to measure the density of synaptic vesicle glycoprotein 2A (SV2A), a widely expressed marker of synaptic density, using positron emission tomography (PET) imaging. Our prior studies have revealed that synaptic density is lower in individuals with MDD across young to middle adulthood. In the current study, we aim to conduct the first known in vivo human PET imaging study of how menopause affects synaptic density, whether MDD may exacerbate menopause-related alterations in synaptic density, and how these synaptic changes relate to objective and subjective measures of mood and cognition. Our preliminary data reveal significantly lower synaptic density in corticolimbic regions in post-menopausal females compared to their pre-menopausal counterparts. They further indicate substantially more pronounced deficits in synaptic density in post-menopausal females with MDD compared to pre-menopausal females with MDD, suggesting an acceleration of synaptic degradation. In the proposed study, we seek to confirm these findings in a large, well-characterized sample of females, incorporating a Research Domain Criteria (RDoC) approach to evaluate the role of menopause in moderating the relation between synaptic density and the full spectrum of mood and cognition. To assess the clinical significance of these changes, we will examine how menopause- and MDD-related changes in synaptic density are associated with functional neural (i.e., electroencephalography) and behavioral (i.e., clinical interview) measures of negative and positive valence and cognitive systems. Results of the proposed study will provide the first human in vivo data on the effects of menopause and MDD on brain synaptic density, and whether these changes may underlie the mood and cognitive alterations experienced in menopause. In doing so, they will help inform a modifiable, precision medicine-based target for treatments aimed at improving mood and cognitive alterations associated with this significant life change among females.

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

SUMMARY Reliable tools for early prediction and effective treatments of spontaneous preterm birth (sPTB) are missing. This is due to an incomplete understanding of the subclinical pathobiology preceding sPTB. The long-term goal of this project is to integrate pathological, physiological, and psychological domains preceding sPTB to define mind- body crosstalk mechanisms that enable robust sPTB prediction and reveal potential targets for therapeutic intervention. The overall objective in this application is to establish neuroimmunoendocrine pathways as critical modulatory links between maternal mental state, immune imbalance, and sPTB. The central hypotheses are that (i) catecholaminergic (i.e., dopaminergic) signaling in maternal central and peripheral systems mitigates inflammation-induced parturition, supporting pregnancy maintenance, and that (ii) disruptions in neuroendocrine signaling may underlie an immune shift in the maternal circulation as well as at the maternal-placental interface promoting sPTB. The central hypotheses will be tested by pursuing three specific aims: 1) Determine whether central dopaminergic activity mitigates inflammation-induced PTB in mice; 2) Define predictive neuroimmunoendocrine trajectories of sPTB and their placental inflammatory signatures; and 3) Determine the effect of dopamine on the human maternal-placental interface, comparing sPTB vs. TB. Under the first aim, an established murine model of PTB will be combined with targeted neuromodulation of central reward circuitry to evaluate the effect on birth timing and peripheral immune state. In the second aim, human pregnancies at risk for sPTB will be longitudinally evaluated for multiple psychological (psychometric surveys, allostatic load) and physiological (blood immune function, non-invasive urine markers, cerebrospinal fluid markers, placental pathology) domains to define mind-body crosstalk prior to and at manifestation of clinical parturition pathology. In aim three, human endometrial stromal cells will be used to identify and causally link the effect of catecholamines on inflammatory signaling, differentiation, and protein secretion at the maternal-placental interface. The research proposed in this application is innovative because it represents a substantive advancement from the status quo by defining the basic principles of the maternal brain–immune–reproductive system axis in healthy pregnancies and those complicated by sPTB. The proposed research is significant because it is expected to offer a strong scientific framework whereby new strategies for the clinical management of patients at risk for sPTB can be developed.

NIMH - National Institute of Mental Health

PROJECT SUMMARY/ABSTRACT Schizophrenia (SZ) remains one of the most debilitating psychiatric disorders and mechanistic understanding of the disease is minimal. Glutamatergic neurotransmission may play a role in SZ, but this has been difficult to study directly as the developing brain is inaccessible and complicated psychiatric syndromes cannot be easily replicated in non-human animals. Work using neurons derived from patient stem cells (iNeurons) has demonstrated a way to circumvent these limitations, and data from Dr. Anderson’s lab suggest the variable penetrance SZ in a well-defined neurodevelopmental disorder (22q11.2 deletion syndrome; 22qDS) corresponds to impaired oxidative phosphorylation (OXPHOS) in mitochondria. This proposal addresses the fundamental question of how alterations in mitochondrial function lead to complex psychiatric symptoms of SZ. AIM1 will test the hypothesis that mitochondrial dysfunction in presynaptic compartments results in diminished glutamate release in iNeurons from 22qDS individuals with SZ (22q+SZ) relative to those without SZ [22q(-)SZ]. Optical imaging of glutamate (AIM1.1) and synaptic vesicle cycling (AIM1.2) will be used to assess glutamate release from individual nerve terminals by independent methods under both high and low frequency neuronal stimulation. AIM2 will use computational modeling to access how alterations in presynaptic mitochondrial function contribute to circuit connectivity and entropy (disorder) in (22q+SZ) and [22q(-)SZ] iNeurons. This proposal fits within NIMH’s Strategic Plan to define brain mechanisms underlying behavior and mental illness and is expected to generate insights into mitochondrial influence on presynaptic function and glutamatergic neurotransmission in the emergence of SZ symptoms in 22qDS while also establishing a robust model of human cellular, synaptic, and circuit neuropathology in patient derived cells. Dr. Rossano will receive training in induced pluripotent stem cell models, medium-to-high throughput synaptic imaging in patient-derived cells, computational modeling of circuit connectivity, and integration of mitochondrial biology with synaptic physiology. Drs. Anderson and Goldberg possess complementary expertise and are uniquely suited for this proposal. A thoughtfully selected advisory committee will provide further scientific and career mentorship. Together with the world-class resources available at the Children’s Hospital of Philadelphia and the University of Pennsylvania the proposed scientific and training objectives will allow Dr. Rossano to establish an independent research program focused on synaptic neuroscience and mitochondrial biology as therapeutically targetable mechanisms underlying symptoms in SZ, autism, and additional neurodevelopmental disorders.

NIMH - National Institute of Mental Health

Abstract The medial prefrontal cortex (mPFC) is critical for executive function, yet how its dorsal (dmPFC) and ventral (vmPFC) motor-projecting (MP) neurons coordinate behavioral initiation, inhibition, and cognitive flexibility remains poorly understood. This R21 leverages four translational behavioral paradigms (head-fixed Persistent Licking/Shock-Escape; freely moving FED3-based Reversal Learning/Stop-Signal), high-density neural recordings, circuit manipulations, and Brian2 spiking neural network modeling to test our central hypothesis: dmPFC MP neurons drive action initiation and adaptive switching, while vmPFC MP neurons suppress impulsivity and perseveration. In Aim 1a, we quantify behavior using kinematic analyses (jerk, velocity, z-scored) aligned with human executive dysfunction metrics (Action Latency [AL], Reversal Accuracy [RA], Perseveration Errors [PE], Stop-Signal Reaction Time [SSRT]), combined with optogenetic (stGtACR2/ChR2) and chemogenetic (PSAM/varenicline) perturbations. Aim 1b employs optotagging and population analyses (PCA, SVM, Total Spiking Probability Edges) to decode dmPFC/vmPFC MP dynamics across tasks, resolving specialized versus mixed functional roles. Aim 1c integrates these datasets into Brian2 spiking network models to predict neural-behavioral correlations, validated through cross-validation. Exploratory analyses will link murine kinematic signatures to human stop-signal/reversal learning metrics. By elucidating strain-specific (C57BL/6 vs. CD1) circuit mechanisms and delivering translatable biomarkers (AL, RA, PE, SSRT, kinematics), this work addresses a critical gap in understanding neuropsychiatric disorders like ADHD (impulsivity) and schizophrenia (perseveration). The study’s innovative combination of recurrent neural network theory, FED3-based assays, and New Approach Methodology (NAM)-compliant computational modeling pioneers high-risk, high-reward tools for circuit dissection, fully aligning with NIH’s 2025 priorities.

Health Resources and Services Administration

The RCORP-Child and Adolescent Behavioral Health Program provides funding to rural communities to establish and expand behavioral health care services, including mental health and substance use disorder for rural children and adolescents.

Health Resources and Services Administration

<p>The RCORP-Child and Adolescent Behavioral Health Program provides funding to rural communities to establish and expand behavioral health care services, including mental health and substance use disorder for rural children and adolescents.&nbsp;</p>

NIMH - National Institute of Mental Health

Project Summary Despite widespread prevention efforts, suicide is the second leading cause of death among teens and young adults, and increasingly, suicide has become a public health concern among children <12-years-old. The emergency department (ED) often serves as the primary contact point for youth to receive care for suicide risk. Yet, among adolescents receiving inpatient or ED care, 10% will attempt suicide and 30% will exhibit suicidal behaviors within 3 months of discharge. This study aims to map the landscape of early suicide risk among children seeking ED care to facilitate the development of actionable intervention targets/methods. We will recruit N=250 children (8-12 years old) via multiple pediatric EDs (NewYork-Presbyterian, Montefiore) with diverse catchment areas and patients with typically less access to care. Children and their guardian will complete clinical interviews to probe suicide and related risk factors. Electronic health records will be probed for structured data on risk factors as well as using natural language processing of clinician notes. Children will also complete brief MRI scanning at baseline to assess brain structure (using clinically relevant MRI protocols) and midbrain dopamine (novel neuromelanin MRI). We focus on brief, clinically relevant sequences that are readily harmonized across site/scanners and can be assessed from brain imaging ordered as part of clinical practice. During a 6-month follow-up period, guardians will complete low-burden, weekly check-in surveys (via their personal smartphone) as well as brief 3- and 6-month remote interviews to characterize fluctuations in their child’s suicide risk, difficulties with safety plans, changes in risk factors (e.g., sleep, familial disruptions, impulsive behaviors), and any subsequent of suicide behaviors. These multi-faceted data will be leveraged to examine clinical and neural risk factors that predict post- discharge suicide events (e.g., suicide attempts, return to ED, or psychiatric hospitalization) in high-risk children. Weekly parental reports will help to map post-discharge changes over 6 months related to suicide events post- discharge. We anticipate that greater psychiatric comorbidity, sleep problems, and family stress will be critical risk factors for post-discharge suicide outcomes. Further, smaller prefrontal, striatal, and cingulate volumes relative to population levels as well as reduced midbrain dopamine will predict greater risk for future suicide events. Difficulty implementing safety plans, maintaining regular routines (e.g., bedtimes, home environment), and excessive family conflict in the post-discharge period will relate to subsequent suicide events. This work will inform the development of new screening (to ensure that key risk factors are clearly ascertained and documented), improve discharge plans for clinicians, and help families detect risk post-discharge. Improving care for high-risk young children is an urgent priority. Findings from this work may be able to address suicide risk in other settings (e.g. primary care) and populations.

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

PROJECT SUMMARY/ABSTRACT Youth in high school typically do not get enough sleep, and this lack of sleep can exacerbate the academic challenges of starting high school, as well as the risk for poor mental health, which is already elevated in this period. Youth with attention-deficit/hyperactivity disorder (ADHD), who make up ~9% of high school students, are more likely to struggle academically, develop comorbid mental health problems, and experience poor sleep compared to their peers. This combined risk makes the transition to high school an especially vulnerable period for youth with ADHD. Delaying high school start times is one approach to alleviate sleep-related challenges that youth face when starting high school, and there is mounting evidence suggesting that delayed start times improve academic and health outcomes. Critically, the neurobiological and behavioral mechanisms conveying the benefits of delayed school start times are still unclear. Further, it is unknown if youth with ADHD will see enhanced benefits from delayed school start times. This proposal will address these gaps by capitalizing upon a Florida state law mandating a delay in high school start times to no earlier than 8:30am in the 2026-2027 school year. To leverage this upcoming change, we propose a two-cohort quasi-experimental design with an ‘early-start’ (7:30am) cohort of 9th grade students to be collected in the 2025-2026 school year and a ‘delayed-start’ (8:30am) cohort to be collected in the 2027-2028 school year. Each cohort will include 50% youth with ADHD, and we will conduct a follow-up assessment of 80% of each cohort in 10th grade. Using rich behavioral data and sophisticated modeling of functional MRI (fMRI) data, we will test the following hypotheses: First, the delayed-start cohort will have better subjective and objective sleep, more structured morning routines, fewer mental health problems, including ADHD symptoms, and better academic achievement (Aim 1). Second, during resting state and reading fMRI tasks the delayed-start cohort will have more segregation between opposing brain networks that facilitate externally- and internally-focused attention (dorsal attention and default mode, respectively), as well as more integration of these two networks with a third network (fronto-parietal) that flexibly orchestrates the balance between the two attention-related networks (Aim 2). Third, youth in the delayed-start cohort will see more developmentally-appropriate changes in brain networks, increased grades, and decreased mental health problems in the transition from 9th to 10th grade (Aim 3). Throughout our aims, we hypothesize to see greater benefits of delaying school start times in youth with ADHD. Together, the findings from the proposed project will clarify how delaying school start times protects youth with and without ADHD during a pivotal transition period and, critically, will provide evidence for how delayed start times confer benefits to short- and long-term outcomes via modulation of sleep quality, morning routines, and functional brain networks supporting attention. This proposal stands to provide a comprehensive characterization of large-scale policy changes impacting youth during a vulnerable period.

NIMH - National Institute of Mental Health

Reducing the age at autism diagnosis is a crucial public health priority, as early diagnosis is associated with better developmental and mental health outcomes. Though autism can be reliably diagnosed in children as young as fourteen months, the average age at diagnosis in the United States is around four to five years. Documented differences in diagnostic timeliness exist by sociodemographic features. However, more research is needed on the modifiable, or scalable, aspects of the service system that can facilitate earlier access to autism diagnosis. Autism screening in primary care holds promise to reduce the average age at diagnosis, as autism-specific screening and attendance at well-child visits are associated with earlier age at diagnosis. Yet, to date, no comparative studies have been conducted to understand the differences in diagnostic timeliness between those screened versus those not screened for autism in primary care. Optimizing early identification of autism in primary care is crucial, as primary care is often children’s entry point on their pathway to a diagnosis. Of parallel importance, more research is needed on children’s complete pathway through services to the receipt of a diagnosis so that optimal pathways that facilitate earlier diagnosis can be identified. Therefore, the present study aims to understand what services work and in what context to lower the age at autism diagnosis, with a particular focus on autism screening in primary care. Prior studies of age at diagnosis have been limited by an over-reliance on Medicaid claims data, retrospective caregiver-report, and analysis of discrete variables in relation to age at diagnosis (e.g., number of appointments). The present study leverages the MarketScan Commercial Claims Database—a national claims database comprised of over 10 billion records from 70 million privately insured individuals. The present study is the first to examine autism screening in primary care using claims data. Analyzing data from a sample of children diagnosed with autism in early childhood, we aim to: 1) evaluate the effect of autism screening in primary care on child age at autism diagnosis using propensity score matched samples, 2) compare the effect of autism screening in primary care on child age at diagnosis in resource-poor or resource-rich areas, and 3) discover service pathways to a formal autism diagnosis using discrete sequence clustering analysis. A highly experienced mentorship team of investigators will support the principal investigator’s research and training plan to further her independence as a behavioral health services researcher, with a focus on autism-related services. Through a combination of carefully curated training activities, the principal investigator will: 1) deepen her understanding of autism-specific service disparities in early childhood and identify targets for intervention, 2) develop expertise in behavioral health services research methodology, 3) build mastery in administrative claims data management, 4) gain knowledge in rigorous analytic approaches for use in observational data, and 5) strengthen skills in scientific writing and related skills to bolster her independence as a scientist.

NIMH - National Institute of Mental Health

Approximately 4.5 million children in the United States (US) display severe emotional and behavioral disturbance. While it is not unusual for preschoolers to have occasional temper tantrums, it is considered symptomatic when temper outbursts (characterized by sudden, violent expression of strong feeling, anger, and aggression) occur most days that are severe enough to impair their academic, social, and family functioning. Evidence-based therapies such as parent child interaction therapy (PCIT) reduce behavioral challenges in children by improving parent-child relationships through parenting practices taught over a multi-week period. Despite the widespread availability of behavioral interventions, there are significant challenges: (a) the effectiveness of interventions is contingent upon parents remembering parenting practices taught during weekly therapy sessions to engage with their children, (b) there is limited education for affected children and their parents to help preempt temper outbursts and regulate their emotion, and (c) families from rural areas and populations with limited specialized pediatric mental health providers are less likely to have access to and utilize evidence-based therapies when it is available. The overarching goal of this convergent research proposal is to investigate the development of generative methods with closed-loop feedback from parents to individualize real-time interventions for children when a temper outburst is predicted. The project will accomplish the goal through the following aims. Aim 1: This project will develop generative algorithms with closed-loop feedback using 5.4 million minutes of smartwatch data collected from 50 children (aged 3 – 7 years) and parent-provided timestamps (closed-loop feedback) of disruptive behavior (characterized by temper outbursts). Aim 2: The developed technology will then be evaluated in a cohort of 50 new children to assess if parenting practices combined with child-initiated mindfulness (i.e., new patient-education) upon a predicted temper outburst could improve behavioral outcomes. Aim 3: Elucidate the perspectives of stakeholders (e.g., parents, schoolteachers) on the use of continuous monitoring devices for adaptive generative intelligence algorithms.

Education Department

The Department of Education (Department) announces final priorities, requirements, and definitions under the School-Based Mental Health Services (SBMH) Program, Assistance Listing Number (ALN) 84.184H. We may use one or more of these priorities, requirements, and definitions for competitions in fiscal year (FY) 2025 and later years. These final priorities, requirements, and definitions are designed to target activities with the purpose of increasing the number of credentialed school-based mental health services providers, specifically school psychologists, in high-need local educational agencies (LEAs) available to provide mental health services to students. These priorities, requirements, and definitions replace the Notice of Final Priorities, Requirements, and Definitions published in the Federal Register on October 4, 2022 (87 FR 60092). However, those priorities, requirements, and definitions remain in effect for previous grant competitions in which the notices inviting applications (NIAs) were published before the Department finalized the proposed priorities, requirements, and definitions in this notice.

NIMH - National Institute of Mental Health

PROJECT SUMMARY PTEN (Phosphatase and Tensin Homolog) is one of the strongest genes associated with autism spectrum disorders (ASDs) and one of the most highly pleiotropic. PTEN encodes a negative regulator of mTOR signaling – a central metabolic pathway controlling protein synthesis, cell growth, and survival, yet the mechanisms contributing to the considerable pleiotropy of PTEN mutations are not well understood. Here, we propose a highly innovative approach that leverages the unique features of zebrafish to illuminate basic neurodevelopmental mechanisms downstream of PTEN loss of function and rapidly screen the functionality of human PTEN variants and pharmacological candidates targeting these mechanisms. Our central goals are: (1) to screen the functionality of human PTEN variants in the developing vertebrate brain in vivo; and (2) to identify novel pharmacological suppressors of PTEN-associated phenotypes. Our central hypotheses are: (1) the in vivo functional effects of PTEN mutations will reveal novel genotype-phenotype correlations, expanding on existing in silico and in vitro analyses; and (2) targeting specific components of the mTOR pathway will selectively reverse these phenotypes. To test our hypotheses, we will perform in vivo zebrafish screens to assess the functionality of human PTEN variants in a developing vertebrate brain informed by multiple in silico and in vitro predictions (Aim 1); and conduct high-throughput pharmacological screens of mTOR-targeting compound libraries in zebrafish (Aim 2). Our team is uniquely suited to perform these experiments, given our complementary expertise in high-throughput zebrafish ASD gene mutant analyses (MPI Hoffman) and computational modeling of ASD gene variants (MPI Turner). The broader impact of this research is to establish a proof-of-principle for in vivo human variant and pharmacological screens in zebrafish and to illuminate basic mechanisms contributing to pleiotropy across neurodevelopmental disorder genes.