2014 — 2015 |
Deroon-Cassini, Terri A. Hillard, Cecilia J (co-PI) [⬀] |
R21Activity Code Description: To encourage the development of new research activities in categorical program areas. (Support generally is restricted in level of support and in time.) |
Role of Ecs in Resilience & Psychopathology After Trauma @ Medical College of Wisconsin
DESCRIPTION (provided by applicant): Predicting who develops Posttraumatic Stress Disorder (PTSD) after a traumatic injury has remained elusive. The long-term research goal is to identify the biological mechanisms involved in maintenance of or protection against the development of chronic PTSD. Emerging research suggests that the endocannabinoid signaling system (ECSS) modulates the stress response to reduce anxiety. The ECSS consists of the CB1 cannabinoid receptor (CB1R) and two endogenous ligands (N- arachidonylethanolamine (AEA) and 2-arachidonoylglycerol (2-AG). The objective of this proposal is to determine the involvement of the ECSS in acute and long-term psychological distress following traumatic injury. The central hypothesis is that high endocannabinoid signaling increases the likelihood of resilience following trauma. The specific aims of the proposed project are to: 1) Characterize the circulating endocannabinoid signaling response (AEA, 2-AG) specific to traumatic injury (acute stressor) for chronic PTSD and resilience trajectories; 2) Determine the genotype variants of CNR1 and fatty acid amide hydrolase (FAAH) across chronic and resilient trajectories of PTSD symptom levels after traumatic injury. The ECSS engages the central (brain) nervous systems potentially impacting the fear conditioned response that occurs during a trauma that leads to the development of PTSD. Based on basic science research, greater activation of the ECSS after a traumatic effect may prove to be protective, leading to greater resilience after trauma, and ultimately helping to reduce the significant burden of PTSD. This study proposes a longitudinal prospective cohort study of single incident assaultive trauma survivors admitted to a level 1 trauma center for medical care. Participants will receive two blood draws in the hospital, a structured clinical interview to assess PTSD symptom severity, and a cheek swab for analysis of genetic material. At six months posttrauma, participants will return for an additional lab draw and the same structured clinical interview to assess for PTSD. Standardized laboratory techniques will be used to assess the serum for 2-AG and AEA, and standard techniques will evaluate the genotype variants of CNR1 and FAAH. Statistical analysis will compare endocannabinoid content for resilience and chronic PTSD, and will assess the genotype variants of CNR1 and FAAH for these two groups.
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0.958 |
2019 |
Deroon-Cassini, Terri A. Hillard, Cecilia J (co-PI) [⬀] |
R56Activity Code Description: To provide limited interim research support based on the merit of a pending R01 application while applicant gathers additional data to revise a new or competing renewal application. This grant will underwrite highly meritorious applications that if given the opportunity to revise their application could meet IC recommended standards and would be missed opportunities if not funded. Interim funded ends when the applicant succeeds in obtaining an R01 or other competing award built on the R56 grant. These awards are not renewable. |
Acute Endocannabinoid Activity Involved in Hyperarousal, Memory Formation, and Non-Remitting Ptsd: a Dense Sampling Approach @ Medical College of Wisconsin
Predicting who develops posttraumatic stress disorder has remained elusive, as acute neurobiological mechanisms of posttraumatic stress pathology are not well understood. The endocannabinoid signaling system (ECSS) is: involved in the stress response, connected with the limbic and neuroendocrine systems, and has been linked with behavioral responses consistent with anxiety in preclinical studies. The ECSS consists of the cannabinoid receptor (CB1R) and two endogenous ligands (endocannabinoids, eCBs), N-arachidonoylethanolamine (AEA) and 2-arachidonoylglycerol (2-AG). For those with non-remitting posttraumatic stress disorder (PTSD), there is evidence of endocannabinoid signaling dysregulation. Less well understood is the ECSS role in risk for PTSD in the acute period after trauma. The objective of this proposal is to characterize ECSS functioning early after trauma and to investigate its link to stress regulation circuitry, HPA axis functioning, affective memory formation and risk for non- remitting PTSD. The specific aims of the proposal are to: 1) Determine trajectories of circulating eCBs following trauma and their relationships with cortisol, arousal symptoms, neural circuits supporting and regulating arousal, and PTSD outcome; 2) Characterize challenge-elicited 2-AG & AEA response as a predictor of PTSD outcome; and 3) Explore the link between AEA with fear memory formation, neural activity in the hippocampal affective memory circuit, and PTSD. This study proposes a longitudinal prospective cohort study of traumatic injury survivors (ie, motor vehicle crash, gunshot and stab wound) evaluated at a level 1 trauma center. Participants will receive a risk screen for PTSD and if risk positive, an initial blood draw in the hospital (2-AG, AEA, cortisol). Acute blood draws and symptom assessments will occur at 1 and 2 weeks, amygdala and medial prefrontal cortex (mPFC) functioning utilizing functional magnetic resonance imaging (fMRI) and structured clinical interview to assess PTSD, depression, and other psychological disorders, along with a challenge task to evaluate eCB responding will occur at 1 month, with additional blood draws and structured clinical interviews occurring at 3, 6, and 12 months. Standardized laboratory techniques will be used to assess the serum for 2-AG, AEA, and cortisol. Statistical analysis will evaluate trajectories of eCBs, their relationships with cortisol, fear and affective memory circuitry, and collectively the capacity of these measurements to predict non-remitting PTSD.
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0.958 |