Sheila E. Crowell - US grants

[unreadable] DESCRIPTION (provided by applicant): Parasuicidal behavior in adolescence marks significant risk for later suicide and may represent a precursor to the development of borderline personality disorder (BPD). Current theories of parasuicide and BPD suggest that emotion dysregulation underlies the act of self-harm, which serves to regulate overwhelming negative affect. However, no studies have thoroughly explored an emotion dysregulation model of parasuicide, including both cognitive and physiological measures of this trait. The proposed research will compare parasuicidal teens with normal controls and a clinical comparison group with major depressive disorder (n=25/group) on behavioral and physiological measures of emotion regulation. Adolescents and their parent will complete interviews and self-report measures of emotion regulation, psychopathology, substance use and abuse, and histories of parasuicidal behavior. Physiological assessments will be conducted with both the parent and adolescent during baseline, an emotionally evocative film clip from "The Champ," and a problem-solving discussion. Physiological indices include electrodermal responding (EDR), respiratory sinus arrhythmia (RSA), and cardiac pre-ejection period (PEP). [unreadable] [unreadable] [unreadable]

7. Project Summary/Abstract The developmental origins of childhood physical, emotional, and behavioral problems begin in utero. Prenatal experiences ?program? the infant for the context s/he will encounter upon birth, laying a foundation for health outcomes and disease. However, the biological mechanisms linking the prenatal environment to early infant outcomes remain understudied. The application of epigenetic methods to human behavior is a relatively new and innovative endeavor devoted to understanding how environmental influences shape gene expression independent of DNA structure. Infants exposed to extreme stress during pregnancy show epigenetic adaptations, consistent with theories that biological systems calibrate in preparation for a high-risk postnatal environment. Innovative human research on epigenetic processes is sorely needed. There are two major gaps in the literature to date. First, the mechanisms linking maternal stress to epigenetic outcomes are still poorly understood. Second, most epigenetic studies only examine a small number of marks on select (i.e., fewer than 10) candidate genes, rather than a complex interdependent genetic network. The objective of this proposal is to advance the science and technology of prenatal programing research by (1) identifying mothers with the full range of emotional distress and carefully characterizing maternal stress reactivity (e.g., autonomic and neuroendocrine) in a laboratory assessment; and (2) developing a novel, hypothesis-driven assay to assess epigenetic processes within a network of genes. These genes were selected based on rigorous review of published associations with HPA axis functioning. Consistent with the Research Domain Criteria (RDoC) framework, mothers will be screened and enrolled based upon a range of scores on emotion dysregulation (ED) measures. ED is an important transdiagnostic vulnerability that has been linked to nearly every psychiatric diagnosis, high stress exposure, parenting difficulties, health-risk behaviors, and intergenerational transmission of psychopathology. Specifically, we will recruit 158 mothers with a uniform distribution on ED measures, conduct a thorough laboratory assessment of stress, measure epigenetic outcomes in placental samples, assess newborn behavioral outcomes, and develop an assay of stress-related epigenetic markers. This innovative project is both comprehensive and economical; it unites a stellar team of scientists with equipment, many of the necessary supplies, and generous institutional support to conduct the proposed research. When the aims of this project are realized we will have an improved understanding of early outcomes for infants of dysregulated mothers. We will also have created a novel assay, which will promote rapid replication as well as new investigations of stress-related epigenetic marks. This short-term longitudinal study lays the foundation for further follow-up of infants into early childhood and a programmatic line of research devoted to understanding and intervening with dysregulated mothers and children, especially those in highest need of improved preventative care.

PROJECT SUMMARY/ABSTRACT The developmental origins of psychopathology can be traced to in utero experiences. However, there is limited research into prenatal and newborn markers of early psychiatric problems. A promising line of inquiry suggests that exposure to maternal distress during pregnancy can have a lasting effect on child health and disease susceptibility. However, mechanisms associating maternal risk factors with child outcomes remain poorly understood. Emotion dysregulation (ED) is a transdiagnostic vulnerability factor that underlies many devastating and costly psychiatric diagnoses, including personality disorders, anxiety, depression, and suicide risk. Therefore, ED serves as a viable index of complex psychopathology among adults. In children, early signs of ED likely precede formal psychiatric diagnoses, such as anxiety, attention deficit/hyperactivity disorder, and difficulties with impulse or temper regulation. However, there have been few studies examining intergenerational transmission of ED or ED trajectories among mothers and their young children from an innovative Research Domain Criteria (RDoC) perspective. The objective of this proposal is to advance current understanding of ED across generations by (1) enrolling pregnant women with the full range of emotional distress, and (2) examining promising clinical and developmental indices of risk for psychopathology in their children. By adding to an existing, NIMH-funded cohort, the proposed study will follow N=324 mother-child dyads from pregnancy through 18 months, a developmental stage when child behavior problems begin to show rank- order stability. Consistent with the RDoC perspective, mothers will be recruited to meet a uniform distribution of ED scores and will complete a comprehensive prenatal laboratory battery to assess behavioral, psychophysiological, and self-reported measures of ED, stress, and psychopathology. Fetal physiological responses will also be recorded prenatally, as early indices of risk for ED. Within 24 hours of birth, babies will undergo a reliable and valid newborn neurobehavioral exam designed to detect emerging signs of dysregulation (e.g., high arousal and low self-regulation). At 7- and 18-months, mother-child pairs will return to the laboratory to engage in dyadic tasks that reliably elicit co-regulation and/or dysregulation. Behavioral and psychophysiological response patterns will be assessed in mother and child using dynamical systems methods that are appropriate for capturing complex developmental processes. This innovative and rigorously designed study unites a complex clinical sample with a well-established developmental design and advanced statistical approaches to better understand early mental health trajectories. When the aims of this project are realized, we will have an improved understanding of ED in mothers and their children during a critical stage that lays the building blocks for later health, development, and wellbeing. This longitudinal study will lay a foundation for research continuing into childhood and will advance a programmatic line of inquiry devoted to understanding dysregulated women and children to improve early intervention and prevent psychopathology.