Clinical Research Directory

Neurobehavioral Mechanisms Linking Childhood Adversity to Increased Risk for Smoking

The purpose of this study is to evaluate how certain childhood experiences influences brain function and responses to nicotine exposure in a group of nonsmoking young adults. The investigators assess responses to nicotine exposure by giving participants a small amount of nicotine or placebo, and then asking them to answer questionnaires. The investigational drugs used in this study are a nicotine nasal spray (i.e., Nicotrol) and/or a nasal spray placebo (made of common kitchen ingredients, including a very tiny amount of pepper extract also called capsaicin). The investigators assess brain function through function magnetic resonance imaging (fMRI), which is a noninvasive procedure that uses a magnetic field to take pictures of your brain while you are performing certain tasks. This study will help us to learn more about why some childhood experiences (adverse childhood experiences, or ACEs) contribute to increased risk for smoking and other substance use.

Growing Up in Multifactorial Risk Conditions

The perinatal period brings significant physiological and emotional changes in mothers, linked to pregnancy, childbirth, and caring for a newborn. While pregnancy is often experienced positively, various stressors can impact maternal well-being and child health. Maternal stress can lead to vascular issues (e.g., hypertension, preeclampsia) or mental health concerns like depression and anxiety. Recent studies show depressive symptoms occur in 41.45% of women in the first trimester, with clinical depression in 9.85%. Postpartum depression has an estimated incidence of 10-20%, with strong continuity from prenatal depression. Stressors, including adverse childhood experiences (ACEs) and maternal psychological issues, often lead to emotional dysregulation. This, through intergenerational transmission, can impact a child's emotional regulation into adolescence. Intergenerational transmission involves both biological mechanisms (endocrine, neurophysiological, epigenetic) and social mechanisms (parenting style, early relationship quality). Sensitive, reciprocal adult-child interactions are essential for socio-emotional and cognitive development, and a child's emotional regulation abilities predict later emotional-behavioral issues. Understanding perinatal risk predictors is key to developing programs that reduce such risks. For example, factors like ACEs, unfavorable conditions, complications during pregnancy, and neurodevelopmental challenges in children can negatively affect the child's cognitive, emotional, and behavioral functioning, maternal well-being, epigenetic changes, and dyadic synchrony. Yet, risk factors do not prevent adaptation and may coexist with protective factors that support maternal well-being and child development. Early parenting support is thus essential, particularly in cases with multiple risks. Research indicates that challenges in implementing support programs often arise from insufficient identification of women at risk of psychological distress during pregnancy and postpartum. In many cases, these issues go unrecognized and untreated, or intervention happens late. It is crucial that prenatal screenings assess potential risk factors to identify women who could benefit from psychological and parenting support starting early in pregnancy. Such multidisciplinary interventions aim to limit intergenerational transmission of mental health issues, reducing impact on a child's emotional, behavioral, and cognitive development. Evidence increasingly supports that Home Visiting (HV) programs benefit both maternal mental health and child development. These programs help mothers manage psychopathological risks and parenting stress while fostering strong attachment and interactions that promote the child's emotional-behavioral development. Primary Objectives To investigate, at 18 months of child age (adjusted for prematurity), whether for mothers with perinatal risk, an HV-based parenting support intervention affects: 1.1. The child's emotional-behavioral profile, using the Child Behavioral Checklist 1.5/5 (CBCL); 1.2. Maternal mental well-being, using the Mental Health Continuum-Short Form (MHC-SF). Secondary Objectives Considering cumulative perinatal risk factors, examine if the HV program: 2.1. Increases maternal well-being for the ACE+ group from T0 (pre-intervention, first trimester) to T8 (post-intervention, child at 18 months); 2.2. Promotes mother-child synchrony at 3 months, in relational functioning (mother-child behavior) and cardio-respiratory activity (HRV and RSA); 2.3. Enhances child developmental competencies at 3 and 18 months (domains: (1) motor, (2) adaptive behaviors, (3) socio-emotional, (4) cognitive, (5) communication). Exploratory Objectives Examine if the HV program influences the epigenetic status of mothers (pre- and postnatal) and children (at 3 months). DNA methylation variations will be assessed in mothers and children in the HV program group versus controls, focusing on target genes related to stress regulation (SLC6A4, NR3C1, BDNF), neural plasticity (BDNF), social interaction (DRD4, OXTR), and tactile stimulation perception (Piezo1, Piezo2, TRPV1, TRPM8, MRGPRB4). Additional candidate genes will be identified through computational research.

The THRIVE Study: Teaching Healthy Regulation in Individuals & Vulnerable Environments

The goal of this 2-arm randomized control trial is to determine the impact of a community health worker delivered coaching intervention, GRIT, on preventing the early initiation of regular use of alcohol and cannabis among adversity-impacted adolescents ages 11-14 who do not regularly use alcohol or cannabis at baseline. The specific aims include: * Aim 1. Examine the effect of GRIT on preventing the early initiation of regular alcohol and cannabis use over time. * Aim 2. Examine the role of youth and caregiver self-regulation in mediating the effect of GRIT on adolescent rates of alcohol and cannabis use. Researchers will compare participants who are randomized to the GRIT intervention to an active control group, receiving a Digital Citizenship Curriculum, to see if those who participate in GRIT experience greater improvements in self-regulation and lower cardiometabolic risks. Participants will: * Be randomized to either receive the GRIT intervention (experimental group) or the Digital Citizenship Curriculum (active control group) * Complete 3 in-person visits at baseline, post-intervention, and 12-month post intervention * Complete HRV assessments using emWave Pro Plus and survey assessments on REDCap during in-person visits. * Participate in six 60-minute sessions conducted over 8 weeks via Zoom with an assigned community-health worker * Be invited to complete a booster session at 6-months post-intervention * Complete online measures at baseline, post-intervention, 6-month, and 12-month post-intervention

Assessing the Gut Microbiome and Its Association With Pediatric Stress and Cognition

Using a metabolomics approach in combination with eye-tracking data, this research study proposes to gather evidence from two interrelated body systems (gut and brain) in order to assess how the microbiome is involved in stress modulated symptoms in children with autism and children exposed to repeated stress in comparison to a control group.

Early Life Exposures Among Children With Sickle Cell Disease

This study is being conducted to determine the relationship between early childhood exposures, such as Adverse Childhood Experiences, Social Determinants of Health and nutrition/breastfeeding, among children with sickle cell disease, and behavioral interventions aimed to reshape psychological resilience and lifestyle factors towards positive health outcomes.

Study of Transition in Real-life Experiences Affecting Micturition and Well-being in Adolescent Years

With this study, we would like to interview 16-25-year-olds who have experienced urinary problems since childhood and who are still experiencing symptoms in young adulthood. The transition from childhood, through puberty, to young adulthood is a time period marked by many psychological ans physiological changes, during which it can be difficult to properly monitor certain symptoms. With this study, we aim to gather opinions and experiences of adolescents and young adults in order to improve urological care for other patients in the future.

The Iowa ACEs and Sleep Cohort and Manipulating Sleep in Young Adults With ACEs Studies

The overall purpose of this study is to understand the role of disrupted sleep in the association of exposure to early life adversity (adverse childhood experiences (ACEs)) with vascular endothelial (dys)function. In Aim 1 (The Iowa ACEs and Sleep Cohort Study), the investigators will utilize a cross-sectional cohort design with a state-of-the-art translational approach. Participants will be recruited to objectively characterize the degree to which lower sleep quality and quantity contribute to ACEs-related endothelial dysfunction, inflammation, and oxidative stress in young adults using: 1. rigorous at home sleep monitoring using 7-nights of wrist actigraphy and 2 nights of home-based polysomnography to objectively measure sleep quality (sleep efficiency, wakefulness after sleep onset and sleep depth), and total sleep duration, 2. in vivo assessment of endothelial function via flow-mediated dilation testing, and 3. in vitro determination of endothelial cell inflammation and oxidative stress from biopsied endothelial cells. This study to achieve this Aim. In Aim 2, approximately 70 eligible participants from Aim 1 (The Iowa ACEs and Sleep Cohort Study) will then be randomized to either a 6-week behavioral sleep intervention (cognitive behavioral therapy for insomnia) or a wait-list control to determine the mechanistic contribution of sleep disruption to vascular dysfunction in young adults with moderate-to-high exposure to adverse childhood experiences (ACEs). Following the intervention, participants will again complete: 1. rigorous at home sleep monitoring using 7-nights of wrist actigraphy and 2 nights of home-based polysomnography to objectively measure sleep quality (sleep efficiency, wakefulness after sleep onset and sleep depth), and total sleep duration, 2. in vivo assessment of endothelial function via flow-mediated dilation testing, and 3. in vitro determination of endothelial cell inflammation and oxidative stress from biopsied endothelial cells.

Building Resilient Families

Prior research suggests that it is possible to improve health outcomes in children with ACEs through multi-component interventions. The challenge for most communities is that health and education systems are fragmented and fail to accommodate families based upon different levels of need. This study utilizes cross-sectoral partnerships to mobilize three vectors (pediatricians, community health workers and parenting educators) to optimize the delivery of vital information and resources to a diverse population of families with ACEs. All vectors are trained in an evidence-informed curriculum to strengthen families and build youth resilience. The study design is a randomized controlled trial of 340 families of children between the ages of 3 to 11 who are generally healthy and have recently seen a pediatrician for a well-child visit. To evaluate the efficacy of this intervention, pediatric patients are invited to participate in repeat evaluations within 2 weeks, 3 months, 6 months, and 12 months after their well-child visit. The study will evaluate the following: 1) the association between Child-ACE scores and biomarkers of toxic stress at baseline in children age 3-11 years old; 2) whether the intervention reduces toxic stress and child health and psychosocial problems at follow-up for children with ACEs compared to usual well-child care for children with ACEs; and 3) the impact of mediating and moderating variables. These results will demonstrate that for families with ACEs the intervention will decrease toxic stress associated with ACEs, improve health outcomes, and reduce health disparities.

School Violence Exposure as an Adverse Childhood Experience

This study hypothesize that school safety strategies may contribute to poor mental health and distress among various school populations and proposes the following research questions to be answered through this study: 1. Is there a significant difference in the prevalence of mental health outcomes, perceived school safety, and academic engagement between early adolescent and adolescent students (grades 6 - 12) at schools that have experienced a school shooting and those that have not? 2. Are existing interventions to promote school safety and security associated with poor mental health outcomes among students and school staff? 3. Does the strength of this association between school safety interventions and mental health outcomes differ among students and teachers in those schools who have experienced a school shooting versus among students and teachers in those schools who never experienced a school shooting? And, among our sample of students, are these associations moderated by their ACE history? Participants will be asked to self-report data on their mental health and wellness, and perceived school safety through a survey. Researchers will compare the surveys from the participants from exposure schools (those who experienced a gun shooting incident) with surveys from the participants from non-exposure schools (those who have not experienced a gun shooting incident)

ACEs, SIRT1, and Premature Vascular Aging in Humans

Adverse childhood experiences (ACEs) are directly related to cardiovascular morbidity and mortality, and impaired vascular endothelial function (VEF) is an independent predictor of future cardiovascular disease (CVD) risk \[1, 2\]. Previous work from our lab (IRB 202010095) and others \[3\] demonstrates impaired VEF in young adults with prior exposure to ACEs even in the absence of clinical CVD risk factors. Sirtuin 1 (SIRT1) is a class III histone deacetylase (HDAC) that plays a role in regulating vascular homeostasis and reductions in SIRT1 are associated with age-related endothelial dysfunction \[4\]. We have shown that ACEs-related impairments in VEF are accompanied by reductions in SIRT1 \[5\]. However, the mechanisms by which ACE exposure promotes VEF remain unknown. The goal of this project is to establish proof of concept that alterations in vascular SIRT1 expression and activity mediate premature vascular aging in individuals with \>=4 ACEs compared to those with 0 ACEs and that, because NAD+ is an essential substrate for SIRT1, increasing NAD+ bioavailability will restore VEF in those with \>=4 ACEs. Thus, we will use a robust translational approach coupling in vivo and in vitro measures of endothelial function, inflammation, oxidative stress, and SIRT1 expression and activity in young adults with (n=30-35) versus without (n=30-35) ACE exposure in a cross-sectional study, and during a randomized controlled trial employing a novel 4-week nicotinamide riboside (NR) supplementation approach to increase SIRT1 activity by increasing cellular NAD+ in ACE+ (n=15/group) to accomplish the following specific aims: 1. Determine the mechanisms by which ACE exposure alters the regulation of VEF by SIRT1. We hypothesize that compared to those without ACEs (ACE-), ACE+ will have (H1a) elevated endothelial oxidative stress and inflammation, (H1b) accompanied by reduced endothelial SIRT1 expression and increased p66SHC expression and acetylation of p65 and p53, (H1c) in association with lower VEF. 2. Determine how targeting SIRT1 by increasing NAD+ bioavailability affects VEF in young adults with ACEs. We hypothesize that systemic NR supplementation will (H2a) augment cellular SIRT1 activity and (H2b) improve VEF in ACE+. \[1\] Felitti, V.J., Anda, R.F., Nordenberg, D., Williamson, D.F., Spitz, A.M., Edwards, V., Koss, M.P., \& Marks, J.S. (1998). Relationship of childhood abuse and household dysfunction to many of the leading causes of death in adults: The adverse childhood experiences (ace) study. American Journal of Preventive Medicine, 14(4), 245-258. https://doi.org/10.1016/S0749-3797(98)00017-8. \[2\] Jenkins, N.D.M., \& Robinson, A.T. (2022). How do adverse childhood experiences get under the skin to promote cardiovascular disease? A focus on vascular health. Function (Oxf), 3(4), zqac032. PMC9279110. 10.1093/function/zqac032. \[3\] Rodriguez-Miguelez, P., Looney, J., Blackburn, M., Thomas, J., Pollock, J.S., \& Harris, R.A. (2022). The link between childhood adversity and cardiovascular disease risk: Role of cerebral and systemic vasculature. Function. 10.1093/function/zqac029. \[4\] Thompson, A. M., Wagner, R., \& Rzucidlo, E. M. (2014). Age-related loss of SirT1 expression results in dysregulated human vascular smooth muscle cell function. American Journal of Physiology-Heart and Circulatory Physiology, 307(4), H533-H541. \[5\] Jenkins, N.D.M., Rogers, E.M., Banks, N.F., Tomko, P.M., Sciarrillo, C.M., Emerson, S.R., Taylor, A., \& Teague, T.K. (2021). Childhood psychosocial stress is linked with impaired vascular endothelial function, lower sirt1, and oxidative stress in young adulthood. Am J Physiol Heart Circ Physiol, 321(3), H532-H541. PMC8461842. 10.1152/ajpheart.00123.2021

Effects of Online Mindfulness Therapy on Pain and Stress in Adults With Chronic Migraine and Adverse Childhood Experiences

This study aims to evaluate the effectiveness of an online Mindfulness-Based Cognitive Therapy (MBCT) program in reducing pain, stress-related symptoms, and improving functionality in adults with chronic migraine and a history of adverse childhood experiences (ACE). Participants will be randomly assigned to either the MBCT intervention group or a control group. The intervention is delivered entirely online over eight weeks. The study hypothesizes that MBCT will result in significant improvements in pain perception and stress-related symptoms compared to the control condition.

Playing Playfully to Overcome Adversity

This research project was developed in an effort to support teachers of young children exposed to adversity and to assist them with enhancing children's development through play. The project utilizes an occupational therapist-led teacher training program manual and an accompanying fidelity checklist. This training is provided via virtual group sessions (Telehealth) and consists of five 45-minute-long sessions addressing ways to promote children's play and playfulness in the classroom and techniques to reduce teacher/caregiver burnout. The training was facilitated via Zoom with eleven teachers employed by an agency serving children exposed to adversity. The fidelity raters scored the fidelity checklist while reviewing video recordings of the training sessions. Participants responded to a Background Questionnaire via Qualtrics and were interviewed before and after the training. The interview data was used to analyze the impact of the training.

Evaluating an Adverse Childhood Experience-Targeting Advocate Model of a Substance Use Prevention Program

Primary Objective: Conduct a rigorous evaluation of a prevention-based intervention designed to mitigate the harms of adverse childhood experiences (ACEs) exposure and prevent future ACEs, substance use, and overdose within 36 communities experiencing a disproportionate burden of substance use and ACEs. The study has three aims: (1) use a cluster randomized controlled trial to test effectiveness of the Strengthening Families Program (SFP) + Family Advocate (FA) intervention on substance use, overdose, and ACEs in 18 communities compared with SFP-only in 18 communities; (2) conduct a robust process evaluation informed by the Consolidated Framework for Implementation Research (CFIR) to explore implementation barriers and facilitators; and (3) conduct a cost evaluation to accurately estimate the costs required to implement SFP and SFP+FA and assess the cost-effectiveness of SFP+FA relative to SFP alone. Findings will provide a roadmap about the best ways to help disproportionately affected communities prevent substance use, overdose, and ACEs.

Effects of Parent-Adolescent Joint Interventions for Adolescents With Adverse Childhood Experiences

The study aims to examine the effectiveness of joint parent-adolescent intervention in improving the mental health outcomes of participants, specifically by reducing symptoms of depression, anxiety, and PTSD, as measured by the Patient Health Questionnaire (PHQ-9), the Generalized Anxiety Disorder-7 scale (GAD-7), and the Child PTSD Symptom Scale for DSM-5 (CPSS-5). Adolescents will be recruited from middle schools and randomly assigned to one of three groups: (a) psychoeducation, (b) psychoeducation + emotional skills enhancement, or (c) psychoeducation + emotional skills enhancement + positive childhood experience promotion. The school-based intervention will consist of 4-8 sessions, with assessments conducted at baseline, post-treatment, and a 3-month follow-up. Investigators will conduct multilevel models (MLMs) and structural equation models (SEMs) to investigate the impact of Adverse Childhood Experiences (ACEs), Positive Childhood Experiences (PCEs), alexithymia, and emotion regulation abilities on mental health outcomes in adolescents.

The ACCEPT Study: Improving the Process of Disclosing Adverse Childhood Experiences in Community Mental Health

Experiences of abuse, neglect, domestic violence, severe bullying and community violence in childhood are very common among people who use mental health services. These often have serious and long lasting impacts on people's mental health.When a person decides to disclose or talk about these traumatic experiences it can help healing. However, mental health staff often lack confidence and organisational support to ask about childhood traumatic events and struggle to know how to respond to disclosures or how best to offer follow up support. A research method called experience-based co-design will be used to find different ways of supporting staff to safely have conversations about childhood trauma with service users. Experience-based co-design involves; 1. Exploring experiences of service users' and staff through in-depth interviewing, observations and group discussions; 2. Creating a short film of service users' experiences which helps staff and service users work together to identify areas for improvement and explore potential solutions; 3. Staff and service users working together in teams to develop the ideas into actionable changes to service delivery The co-designed intervention could include: * A training package for community mental health team staff * A toolkit for clinicians to help them to safely talk about childhood trauma with service users. * Changes to the physical environment to make it feel safer * A reflective practice group for staff Anticipated impacts: For service users: Improved experience of disclosing ACEs; improved access to trauma treatment; improved therapeutic relationships; improved mental health outcomes. For staff: Improved confidence and competence to sensitively explore ACEs; improved compassion; greater job satisfaction