Cortisol as a Moderator of Acute Distress in Predicting PTSD

Following traumatic injury, approximately one third of patients admitted to the hospital will develop a psychiatric condition, including posttraumatic stress disorder (PTSD; O’Donnell, Bryant, Creamer, & Carty, 2008). It is unknown, however, why some develop PTSD and others recover. Theorists have proposed acute distress as a potential factor that contributes to identifying PTSD risk. Cortisol is a widely used marker of stress reactivity, and prior work has shown that people with inhibited cortisol reactions following trauma are at higher risk for subsequent PTSD (Price, Kearns, Houry, & Rothbaum, 2014). This project investigated the interaction between the acute stress reaction and cortisol with regards to their relation to subsequent PTSD symptoms. No significant interaction was found between cortisol and later PTSD, with the null result likely stemming from measurement related confounds. The data suggest that salivary cortisol collected shortly after the trauma in conjunction with acute distress may be an unreliable biomarker of PTSD. CORTISOL AND ACUTE DISTRESS IN PREDICTING PTSD 3 Cortisol as a Moderator of Acute Distress in Predicting PTSD The majority of US adults will be exposed to a traumatic event in their lifetime (Kilpatrick, Resnick, Milanak, Miller, Keyes, & Friedman, 2013). Although many recover, a substantial minority will develop chronic mental health problems including posttraumatic stress disorder (Bryant, O’Donnell, Creamer, McFarlane, Clark, & Silove, 2010; Zatzick, Rivara, Nathens, Jurkovich, Wang, Fan, & Mackenzie, 2007). Understanding the mechanisms associated with resilience, recovery, or chronic mental illness is necessary in order to create effective prevention strategies. After being admitted to the Emergency Department (ED) following traumatic injury, physicians work to screen patients for injuries and proceed with a specific course of treatment. Despite the fact that approximately one third of traumatic injury patients will develop a psychiatric condition, there are few screening or referral mechanisms in place for these conditions that have been widely used outside of research (O’Donnell et al., 2008). Due to this lack of early detection, many patients who develop PTSD as a result of their traumatic experience will not receive mental health treatment. Indeed, epidemiological studies indicate that two thirds of patients who develop post-trauma mental health conditions do not receive treatment (Bryant et al., 2010). There are a number of factors associated with post-trauma psychopathology including physiological, hormonal, psychosocial, and environmental variables. Although these variables show promise as predictors individually, no single construct has emerged as a reliable and valid predictor of PTSD (for a review, see Bryant, 2006). It is highly likely that the development of PTSD is influenced by multiple factors that interact with one another. The primary aim of the current study is to improve our understanding of the complex interplay of factors that contribute to subsequent PTSD. Salivary cortisol and acute distress have both been individually associated CORTISOL AND ACUTE DISTRESS IN PREDICTING PTSD 4 with the development of PTSD, and the extent to which they interact with one another to predict PTSD was examined. The proposed factors in the current study have been identified as part of the construct of fear load. Fear load is a multidimensional construct defined as the over-expression of a fear response when exposed to a trauma cue and is influenced by many factors including symptom severity at the time of the event, acute distress following exposure to a stressor, physiological response, dissociation, and genomics (Norrholm, Glover, Stevens, Fani, Galatzer-Levy, Bradley, Ressler, & Jovanovic 2014). Norrholm and colleagues found higher fear load in populations that are both extremely symptomatic and in most need of treatment, thus supporting a relationship between fear load and PTSD. Notably, recent research suggests that a highly sensitized fear response is most active and significantly correlated with intrusive thoughts and intense physiological reactions to reminders of the trauma, both of which are characteristic symptoms of PTSD as defined in the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5; APA, 2013). This project will examine two components of the fear load construct by focusing on acute distress and post-trauma physiology as measured by cortisol. Acute stress at the time of the trauma has been associated with subsequent PTSD symptoms (Birmes, Brunet, Benoit, Defer, Hatton, Sztulman, & Schmitt 2005; Nishi, Matsuoka, Yonemoto, Noguchi, Kim, & Kanba, 2010). The severity of this acute distress reaction is of particular importance because it can be more easily assessed in an acute care setting. Such assessments can then guide an immediate course of clinical action. Unfortunately, acute stress has been shown to be unreliable as a predictor of PTSD when examined alone. Indeed, studies that have shown a unique relation also included additional variables in the model such as peritraumatic dissociation, heart rate, and other physiological variables (Kuhn, Blanchard, Fuse, CORTISOL AND ACUTE DISTRESS IN PREDICTING PTSD 5 Hickling, & Broderick, 2006). These results suggest that acute distress may be most useful as a predictor when used in conjunction with other variables. The present study will also examine one of the physiological responses that occurs as a result of the acute reaction. Although the degree of activation may vary depending on the situation, experiences of traumatic events initiate a response of the hypothalamic-pituitaryadrenal axis (HPA; Hellhammer, Wüst, & Kudielka, 2008). During an acute stress response and subsequent activation of the HPA axis, glucocorticoids, namely cortisol, are produced in the adrenal cortex (Meewisse, Reitsma, de Vries, Gersons, & Olff, 2007). The release of cortisol terminates the stress response through a negative feedback loop and as such one of its major functions is to contain the stress reaction (Yehuda, McFarlane, & Shalev, 1998). Cortisol levels are thus generally considered to be a reliable measurement of HPA activity, however, certain sources of variability are acknowledged. Prior trauma exposure, for example, has been shown to attenuate the acute cortisol reaction in response to subsequent traumas, as supported by the results of a study that found women with a previous history of assault tended to display lower mean cortisol levels after rape (Resnick, Yehuda, Pitman, & Foy, 1995). The lowered cortisol response was associated with a higher probability of subsequent PTSD. Acute distress and cortisol may thus be important factors to examine in a combined model as predictors of PTSD symptomology. The present study aims to understand the complex relationship between acute distress and the cortisol response, and their association with subsequent PTSD in the acute aftermath of a trauma. Elevated cortisol has been identified as a potential protective factor against PTSD symptoms, and as such was examined as a moderator of the association between acute distress and PTSD. Specifically, it was hypothesized that (1) acute distress would be positively associated with PTSD symptoms, (2) cortisol would be negatively CORTISOL AND ACUTE DISTRESS IN PREDICTING PTSD 6 associated with PTSD symptoms, and (3) that there would be an interaction between cortisol and acute distress such that elevated cortisol would reduce the strength of the relation between acute distress on PTSD symptoms. Methods Participants Patients who presented to the Emergency Department of The University of Vermont Medical Center immediately following a trauma were screened for eligibility in the study through cooperation with the Emergency Medicine Research Associate Program (EMRAP) and Trauma Center staff. Patients were also recruited through the UVM Medical Center Trauma Clinic. Patients who presented after an event meeting Criterion A for the DSM-5 diagnosis of PTSD were approached for enrollment (APA, 2013). Patients were excluded based on current suicidal ideation, current psychoses, being in police custody, and/or altered state of mind as determined by the attending physician. A total of 72 participants were enrolled. Participants in the current sample were M = 35.15, SD = 13.91 years of age. The majority of the sample self-identified as White (67.2%) and approximately one fourth of the sample identified as African American (26.9%). The majority of the sample was male (64.2%). Most participants identified that they had private insurance (41.8%). Measures The following measures were administered to enrolled participants. Peritraumatic Distress Inventory (PDI; Brunet et al., 2014). The PDI is a measure aimed at quantitatively measuring the amount of distress experienced as a direct result of a traumatic experience. Participants completed this 13-item self-report measure, rating each item on a scale of 0-4 relative to the amount of distress experienced at the time of trauma; total scores CORTISOL AND ACUTE DISTRESS IN PREDICTING PTSD 7 ranged from 0 to 52 with higher scores being representative of greater distress. Research indicates that the PDI is an accurate predictor of post-traumatic stress symptoms and PTSD at follow-up several days after the traumatic event (Nishi et al., 2010). Peritraumatic Dissociative Experiences Questionnaire (PDEQ; Marshall et al., 2002). The PDEQ is a 10-item self-report measure designed to assess of the amount of dissociation experienced at the time of trauma. Items are rated on a scale of 1-5 based on extent of dissociation experienced with total scores ranging from 10-50 and higher scores indicating more dissociation. Psychometric analyses have found that the PDEQ total score is significantly correlated with other measures of acute dissociation and thus finds peritraumatic dissociation to be a valid pre