Damion J. Grasso, Ph.D. - US grants

DESCRIPTION (provided by applicant): The primary objective of the proposed research is to study psychophysiological reactivity in traumatized children receiving treatment for posttraumatic stress disorder (PTSD) so as to better inform the assessment and treatment of posttraumatic stress in youth. Towards this goal, three specific aims will be addressed via procedures appended to a larger community-based effectiveness study of Trauma-Focused Cognitive Behavioral Therapy (TF-CBT). Given the plethora of research documenting enhanced physiological reactivity in adults with PTSD (Karl, 2006;Pole, 2007) and the scarcity of such research in youth, the first aim is to compare physiological peripheral and neural responses to threat-related pictures and acoustic startle probes in traumatized youth and non-traumatized youth and to examine the relation between physiological reactivity and PTSD severity. Given that treatment of PTSD in adults has demonstrated significant changes in physiological reactivity (Shalev, Orr, &Pitman, 1992), the second aim is to determine if completion of TF-CBT is associated with a reduction in physiological responses to threat-related pictures and acoustic startle probes, relative to the passage of time in non-traumatized youth. Parental support and engagement in treatment is a key feature of TF-CBT and reflects a body of work linking social support with resiliency and protection from the adverse effects of trauma (see Luthar &Cicchetti, 2000). Compared to youth participating in TF-CBT without a parent, youth with a participating parent have shown greater reductions in internalizing and externalizing problems following treatment (Cohen, Mannarino, Berliner, &Deblinger, 2000). The third aim is to examine the relation between perceived parental support and pre- to post-treatment changes in physiological reactivity to threatening stimuli. PUBLIC HEALTH RELEVANCE: The proposed research focuses on a seriously at-risk population of youth. The high prevalence of childhood trauma and its deleterious effects on emotional and cognitive development in youth implores efforts to improve the assessment and treatment of child traumatic stress. The proposed research informs such efforts by exploring potential physiologically-based markers of child traumatic stress and the potential for physiological reactivity to change following trauma-focused treatment. Further, the proposed research strives to elucidate the role of parental support and engagement, an important component of TF-CBT, in facilitating potential changes in physiological reactivity following treatment.

PROJECT SUMMARY: Evidence suggests that the effects of trauma exposure can be transmitted across generations to shape pathways to psychological impairment in offspring, with the perinatal period identified as pivotal to these processes. Although the mechanisms and timing of these effects are not well elucidated, an emerging literature focuses on the influence of maternal posttraumatic stress (PTS) during pregnancy. PTS affects up to 40% of pregnant women, particularly those from low-income, minority populations with documented health disparities. Maternal PTS may interrupt healthy development of biological stress systems in offspring, namely the Hypothalamic-Pituitary-Adrenal (HPA) axis, a well-defined biological pathway that is modulated by environmental and genetic factors. Recent studies have begun to link maternal PTS with biobehavioral indicators of stress reactivity in offspring, and these so-called intermediate phenotypes may serve as early markers of stress-related psychopathology, which can emerge in infancy and have cascading and disabling effects across the lifespan. Epigenetic modifications, such as DNA methylation, are hypothesized to play a critical role in influencing these processes. This hypothesis builds on studies, mainly in adults, linking PTS with DNA methylation of genes implicated in HPA axis functionality and candidate gene studies showing effects of maternal trauma exposure on DNA methylation in adult offspring. Notably, pilot data from our lab link maternal PTS during pregnancy with newborn infant DNA methylation of a single gene (FKBP5) implicated in the stress response. No study has yet applied an epigenomic approach, which offers a more holistic and unbiased method of discovery, for examining intergenerational transmission of trauma. We propose an exploratory study to prospectively explore predictive relationships between maternal pregnancy PTS, genome- wide methylation patterns in offspring at birth, multi-level biobehavioral indicators of infant stress reactivity at 6 months (i.e., respiratory sinus arrhythmia, heart rate, cortisol, observed distress), during a laboratory stress challenge, and key elements of the caregiving environment (i.e. observed maternal sensitivity, family support, family stressors), which may moderate these intergenerational effects. We build from extensive pilot work in our laboratory and an established research infrastructure for recruitment and retention. This work, which aligns well with the priorities of the National Institute of Child Health and Development is essential for delineating the origins of stress-related psychopathology and informing the optimal targets and timing for effective preventative interventions.

PROJECT SUMMARY: Interpersonal violence (IV) affects more than 1 in 5 young children in the United States annually. For young children, IV exposure most commonly occurs within the family context in the forms of partner violence and harsh/abusive parenting. Children exposed to IV represent a heterogeneous group. A portion of children develop psychological problems that cut across multiple diagnostic categories characterized by fear and distress symptoms. Existing models broadly implicate disruptions in biological stress systems in the etiology of violence-associated symptoms, but lack specificity for explaining heterogeneous symptom presentations in young children. Advancing this science requires novel laboratory and analytic methods for assessing and synthesizing threat reactivity across multiple biobehavioral levels. Inspired by the Research Domain Criteria (RDoC) initiative, we propose to achieve this by leveraging person-centered methods to identify unique profiles of threat reactivity across multiple levels of biobehavioral functioning never before studied together in young children: observed behavior, attention bias, autonomic reactivity, startle, event-related brain potentials. The fundamental scientific premise of the proposed work is that threat reactivity is a central intermediate phenotype linking early IV to this clinical vulnerability in young children. The proposed sample will include 360 children, ages 4 to 6 years, with (n = 240) and without (n = 120) IV exposure followed over 1 year. We advance three aims. Aim 1 is to map biobehavioral threat reactivity profiles to dimensional patterns of fear and distress in IV exposed and non-exposed young children. We hypothesize that we will identify hyper- and hypo-reactive profiles that link to greater symptoms relative to a non-extreme profile, and that hyper-reactivity will relate to fear, whereas hypo-reactivity will relate to distress at baseline and over 1 year. Aim 2 is to test whether threat reactivity profiles serve as intermediate phenotypes in explaining the link between violence exposure and symptoms over time. We hypothesize that children exposed to more severe IV will more likely be classified as hyper- or hypo-reactive and that profile type will mediate the link between IV and symptoms at baseline and 1 year later. Further, given high dependency of young children?s self-regulation on caregiving relationships and threats to regulatory capacity in violent environments, we hypothesize that mothers? ability to co-regulate their children?s negative affect will shape these risk pathways. Thus, Aim 3 is to test the hypothesis that maternal responsiveness to child negative affect will play a unique role in shaping threat reactivity pathways over time. We hypothesize that emotionally-responsive parenting (assessed with a multi-method protocol) will buffer the associations between IV and threat reactivity profiles and between exposure and symptom trajectories over 1 year. This study will provide critical insight into the etiology of violence-related psychopathology with key implications for developing novel approaches for identification, prevention, and intervention for these highly vulnerable young children.