Holly K. Orcutt, Ph.D. - US grants

[unreadable] DESCRIPTION (provided by applicant): Sexual assault on college campuses is a significant social problem and results in significant negative consequences to the victim and society as a whole. Women who have experienced child sexual abuse are a particularly high risk group for later adult sexual assault. Unfortunately, risk-reduction prevention programs on campus have not been particularly effective with this higher risk group. Psychological distress, increased sexual activity, and alcohol use are three such variables that have been both consistently linked to increased risk of adult sexual assault among women with a history of child sexual abuse and may provide an opportunity for developing effective preventive interventions. Among women with a history of child sexual abuse, sexual activity and alcohol use may sometimes serve the function of reducing tension and regulating negative affect. This project will employ a longitudinal design which will follow a large (approximately 1000) culturally-diverse sample of women across 12 months (with five data collection points) in order to investigate whether the experience of psychological distress, secondary to child sexual abuse, and the use of sex and alcohol to regulate negative affect increases college women's risk of experiencing prospective sexual assault. In addition, this project incorporates a novel laboratory-based behavioral forecasting analogue of likelihood to use sex to regulate negative affect. The convergence between the behavioral-forecasting analogue and current questionnaire-based measurement will be examined as well as the ability to predict likelihood of prospective adult sexual assault based on responses to the behavioral analogue. The inclusion of the behavioral-forecasting analogue is designed to elucidate the specific processes through which use of sex to regulate negative affect may increase risk of sexual assault. Understanding the function of sexual behavior and alcohol use as well as the processes through which distress and particular affect regulation strategies may interact to increase risk for adult sexual assault will provide critical information about intervention targets for risk-reduction programming efforts. [unreadable] [unreadable] [unreadable]

[unreadable] DESCRIPTION (provided by applicant): The specific aim of the proposed set of studies is to prospectively examine immediate and long-term (up to 2 years) adjustment outcomes (i.e., posttraumatic stress disorder symptoms, depression symptoms, and anxiety symptoms) following the mass shooting that occurred on the Northern Illinois University (NIU) campus in DeKalb, Illinois, on February 14, 2008. At the time of the shooting, a large sample (N = 816) of female undergraduates at NIU were participating in a longitudinal study of sexual revictimization. Given the trauma- focused nature of the revictimization study, it provided a unique opportunity to examine post-shooting adjustment outcomes while controlling for pre-shooting adjustment levels. To date, 653 women (80% of eligibles) have completed an online survey, NIU Trauma Study (NTS): Time 1, an average of 27 days after the mass shooting. The survey contained assessments of post-shooting adjustment, degree of exposure to the shooting, and additional risk and protective factors (e.g., social support, posttraumatic growth). Additional assessments are proposed for 3.5 months, 7.5 months, 1 year, and 2 years post-shooting. Several factors are hypothesized to influence changes in adjustment in the aftermath of the trauma. These include pre-shooting risk factors [e.g., childhood or other trauma exposure, dysregulation of stress hormones (i.e., pre-shooting salivary cortisol levels), and dysfunctional affect regulation strategies], factors associated with the shooting (e.g., severity of exposure), and immediate reactions to the mass shooting (e.g., peritraumatic dissociation and affect regulation strategies for coping with shooting-related distress). In addition to direct effects of proposed risk and protective factors on changes in adjustment level across the six time points, a number of interactive effects will also be tested. Following the 1-year post-shooting assessment, a subset of participants (N = 160) will be recruited to participate in a clinical reappraisal study in order to calibrate the self-report screening measures to gold-standard face-to-face structured diagnostic interviews. In addition, a unique laboratory-based study [Expressive Writing Study (EWS)] is also proposed for a subset of participants (N = 100) who at NTS: Time 1 report high and low exposure to the shooting. In the EWS, participants will write about the mass shooting and then read their essay aloud to themselves while their physiological data are collected. One aim of the EWS is to examine whether physiological reactivity, salivary cortisol changes, and self-reports of emotional avoidance during the EWS are predictive of longer-term outcomes in adjustment as a function of severity of exposure to the shooting. The specific content of the expressive writing will also be examined. Longitudinal follow-up data on adjustment from the NTS survey will also serve as follow-up data for the EWS. In combination, data from these proposed projects will provide crucial and unique information about the role of risk factors and protective factors in predicting adjustment following a mass shooting. If successful, the proposed research will (i) provide information regarding the psychological consequences of experiencing or witnessing a mass shooting while controlling for pre-shooting levels of symptoms and adjustment; (ii) identify the direct and moderating effects of pre-shooting adjustment (e.g., trauma history, dysfunctional affect regulation, dysregulation of stress hormones) on post-shooting adjustment outcomes; and (iii) provide information regarding the physiological reactivity (and recovery) of engaging in an expressive writing and reading task as a function of exposure to the mass shooting. The proposed set of studies seeks to promote NIH's interests in understanding, from a longitudinal perspective, the factors (risk and protective) that contribute to the development of posttraumatic stress disorder and other trauma-related mental illnesses. [unreadable] [unreadable] [unreadable]

DESCRIPTION (provided by applicant): The specific aim of the proposed study is to utilize innovative translational research methods to examine the association between fear physiology, molecular genetics and posttraumatic stress symptoms (PTSS) using a gene-environment interaction approach. Inhibition of fear has been conceptualized as an intermediate neurobiological phenotype of posttraumatic stress disorder (PTSD), commonly viewed as a disorder of fear. PTSD is an ideal Candidate for a gene-environment interaction approach; however, existing molecular genetics research is hampered by the limitation of gene-environment correlation (which recognizes the fact that trauma exposure is in part determined by heritable factors). The proposed study utilizes a unique cohort of females enrolled in a longitudinal study at the time of a mass shooting at Northern Illinois University on February 14, 2008. The fateful nature of this trauma exposure minimizes the problem of gene-environment correlation. The proposed study builds upon the extensive trauma and mental health history available prior to the mass shooting and predicts that fear physiology and the pituitary adenylate cyclase-activating polypeptide (PACAP) will mediate the relationship between a fateful, shared trauma and PTSS. Recent research (Ressler et al., 2011) has reported a link between PACAP and PTSD symptoms in females but not males. For example, females demonstrated an association between PACAP38 blood levels and significantly increased startle reflexes to both the danger cue (CS+) and the safety cue (CS-), while the ADCYAP1R1 receptor SNP rs2267735 demonstrated significant association with PTSD and fear conditioning in females, but not males. Utilizing a subset (proposed N = 150) of this unique cohort exposed to a mass shooting, it is hypothesized that current fear physiology (e.g., laboratory fear potentiated startl to a fear conditioned cue, fear discrimination and fear extinction, as well as dark enhanced startle), combined with genetic and peripheral blood level markers (e.g., PACAP), will predict differential risk for PTSS as assessed from pre- to post-shooting (approximately 27 days post-shooting at Time 2), particularly among females who reported a more extensive trauma history prior to the mass shooting. The location of SNP rs2267735 within an estrogen response element holds promise in terms of explanatory power for sex differences in PTSD. To examine the impact of estrogen on PACAP-PAC1 gene expression, it is hypothesized that ADCYAP1R1 methylation levels will be most strongly related to PTSS among individuals with higher, as opposed to lower, levels of peripheral blood levels of estrogen. It is anticipated that findings wil inform understanding of the link between molecular genetics and the risk for PTSD, particularly with regard to sex differences in PTSD, ultimately leading to better tailoring of treatment methods for PTSD. PUBLIC HEALTH RELEVANCE: The proposed research aims to advance understanding of the underlying causes of posttraumatic stress disorder (PTSD), which is a recognized public health problem with significant societal and individual costs. The proposed research will explain the role that exaggerated physiological reactivity to startling stimuli, in combination with peripheral blood level markers of pituitary adenylate cyclase- activating polypeptide and estrogen, genetic factors, and past trauma history, plays in predicting posttraumatic stress following a campus shooting. This research will broaden understanding of the causes of PTSD and will shed light in particular on the nature of women's greater risk for PTSD.

Project Summary/Abstract Despite decades of research, current psychological treatments designed to treat a variety of mental illnesses are not effective for all who receive them. Specifically, well-supported treatments for mental illnesses that involve fear (e.g., PTSD, panic) appear to be effective for the majority of individuals, but consistently leave a group of ?treatment non-responders.? One potential explanation for the observed discrepancy in treatment response may be the focus of modern psychotherapies on relieving symptoms specific to categorical diagnoses, rather than mechanisms underlying why the individual is experiencing the symptoms. Recently, fear-based psychological disorders (e.g., PTSD, specific phobia, panic disorder, social anxiety) have been identified as sharing a distinct set of biomarkers, including genetic biomarkers of acute fear (i.e., fear in the moment) and impairments in controlling attention. Neurobehavioral interventions are therefore a promising class of treatments designed to target the biological markers that may be maintaining the symptoms of various psychological disorders. The Attention Training Technique (ATT) is a neurobehavioral intervention that has garnered attention through its demonstrated effectiveness in reducing symptoms across a variety of psychological diagnoses. While grounded in well-established theory, the mechanisms of change in ATT are largely unknown. One proposed mechanism may be that ATT promotes functional connectivity between regions in the brain implicated in top-down executive control over attention (ventromedial prefrontal cortex [vmPFC] and dorsolateral prefrontal cortex [dlPFC]) and bottom-up attention networks (dorsal anterior cingulate cortex [dACC] and amygdala), resulting in increased top-down regulation of potentially problematic bottom-up attentional processes. The same brain regions implicated in both top-down and bottom-up attentional processes have also been associated with fear responding (i.e., startle response) and fear learning (i.e., how quickly one learns that a stimuli is safe or to be feared). Taken together, the research suggests that acute fear responding may be decreased through increased executive control over attention through engagement in ATT. The proposed randomized clinical trial will test whether a self-administered brief neurobiological intervention (ATT) to increase attentional control will decrease acute fear responding, and whether this change is associated with normative dACC functioning, measured by behavioral proxy. It is expected that those who engage in ATT will show greater attentional control efficiency, which will decrease their acute fear response. It is also expected that those who engage in ATT will also show greater dACC functioning, measured by behavioral proxy and will exhibit decreases in their reported fear as their attentional control increases over the course of the intervention. Additionally, it is expected that the intervention (ATT) will indirectly decrease symptoms of categorical fear-based psychological diagnoses through the identified biomarkers (i.e., attentional control, dACC functioning, acute fear response) to decrease reported symptoms.