Faculty Bibliography

BACKGROUND: PTSD has been associated with altered hypothalamus-pituitary-adrenal-axis (HPA-axis), immune and sympathetic nervous system (SNS) regulation. The purpose of this study was to evaluate the effect of cognitive stress on these systems in PTSD patients and controls. METHODS: The subjective units of distress score (SUDS), NK-cell response, plasma levels of noradrenalin and ACTH in response to cognitive stress were assessed in male veterans with PTSD (n=15) and age, region and year of deployment matched veterans without psychopathology (n=15). RESULTS: The challenge induced an increase in SUDS, noradrenalin, ACTH and NK-cell response in both groups. Baseline levels of ACTH were lower in PTSD patients. The test was experienced as more stressful by PTSD patients and resulted in an augmented ACTH response in patients. The noradrenalin and NK-cell responses showed no group differences. The ACTH response correlated with the severity of symptoms in patients, and the noradrenalin response correlated with the ACTH and NK-cell response in controls, but not in patients. DISCUSSION: PTSD patients experience more distress and present with an exaggerated pituitary response to this stressor. In addition, our results suggest an altered interaction between the HPA-axis, SNS and immune system in PTSD.

This article provides an overview of the process of developing the 5th edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5) of the American Psychiatric Association with a focus on issues related to the trauma-related disorders, particularly the dissociative disorders (DD). We also discuss the highlights of research within the past 5 years in the assessment, treatment, and neurobiological basis of trauma disorders. Recent research shows that DD are associated with severe symptoms as well as a higher rate of utilization of mental health treatment compared with other psychiatric disorders. As a result, DD, like other complex posttraumatic disorders, exact a high economic as well as personal burden for patients and society. The latest research indicates that DD patients show a suboptimal response to standard exposure-based treatments for posttraumatic stress disorder as well as high levels of attrition from treatment. An emerging body of research on DD treatment, primarily of naturalistic and open trials, indicates that patients who receive specialized treatment that addresses their trauma-based, dissociative symptoms show improved functioning and reduced symptoms. Recent studies of the underlying neurobiological basis for dissociation support a model of excessive limbic inhibition in DD that is consistent with the phenomenology and clinical presentation of these patients. We are optimistic that the forthcoming DSM-5 will stimulate research on dissociation and the DD and suggest areas for future studies.

OBJECTIVE: The development of posttraumatic stress disorder (PTSD) is influenced by preexisting vulnerability factors. The authors aimed at identifying a preexisting biomarker representing a vulnerability factor for the development of PTSD. To that end, they determined whether the dexamethasone binding capacity of leukocytes, as a measure of glucocorticoid receptor (GR) number, before exposure to trauma was a predictor of development of PTSD symptoms. In addition, the authors analyzed mRNA expression for GR subtypes and GR target genes. METHOD: Participants were selected from a large prospective study on deployment-related disorders, in which peripheral blood mononuclear cells (PBMCs) were obtained prior to and 1 and 6 months after military deployment. Participants included armed forces personnel with high levels of PTSD symptoms 6 months after deployment (N=34) and comparison subjects without high levels of PTSD or depressive symptoms (N=34) matched for age, rank, previous deployments, educational level, and function during deployment. RESULTS: Before military deployment, the GR number in PBMCs was significantly higher in participants who developed high levels of PTSD symptoms after deployment relative to matched comparison subjects. Logistic regression analysis showed that the risk for inclusion in the PTSD group after deployment increased 7.5-fold with each GR increase of 1,000. No group differences were observed in mRNA expression of GR-alpha, GR-P, GR-beta, glucocorticoid-induced leucine zipper (GILZ), serum and glucocorticoid-inducible kinase-1 (SGK-1), and FKBP5. The higher GR number in the PTSD group was maintained at 1 and 6 months after deployment. CONCLUSIONS: These results demonstrate that a preexisting high GR number in PBMCs is a vulnerability factor for subsequent development of PTSD symptoms.