Faculty Bibliography

BACKGROUND: Biological correlates of posttraumatic stress disorder (PTSD) have mostly been studied using cross-sectional or posttrauma prospective designs. Therefore, it remains largely unknown whether previously observed biological correlates of PTSD precede trauma exposure. We investigated whether glucocorticoid receptor (GR) pathway components assessed in leukocytes before military deployment represent preexisting vulnerability factors for development of PTSD symptoms. METHODS: Four hundred forty-eight male soldiers were assessed before and 6 months after deployment to a combat zone. Participants were assigned to the PTSD or comparison group based on Self-Rating Inventory for PTSD scores after deployment. Logistic regression analysis was applied to predict development of a high level of PTSD symptoms based on predeployment GR number, messenger (m)RNA expression of GR target genes FKBP5, GILZ, and SGK1, plasma cortisol, and childhood trauma. We also investigated whether predeployment GR number and FKBP5 mRNA expression were associated with single nucleotide polymorphisms in the GR and FKBP5 genes, either alone or in interaction with childhood trauma. RESULTS: Several GR pathway components predicted subsequent development of a high level of PTSD symptoms: predeployment high GR number, low FKBP5 mRNA expression, and high GILZ mRNA expression were independently associated with increased risk for a high level of PTSD symptoms. Childhood trauma also independently predicted development of a high level of PTSD symptoms. Additionally, we observed a significant interaction effect of GR haplotype BclI and childhood trauma on GR number. CONCLUSIONS: Collectively, our results indicate that predeployment GR pathway components are vulnerability factors for subsequent development of a high level of PTSD symptoms.

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.