Faculty Bibliography

BACKGROUND: In an attempt to avoid unknown influence, most neuroimaging studies examining the pathophysiology of posttraumatic stress disorder (PTSD) exclude patients taking medications. Here we review the empirical evidence for relevant medications having a confounding effect on task performance or cerebral blood flow (CBF) in this population. The evidence for potentially confounding effects of psychotherapy in PTSD are also discussed. METHODS: The literature that we reviewed was obtained through a PubMed search from 1980 to 2009 using the search terms posttraumatic stress disorder, PTSD, psychotropic medications, neuroimaging, functional magnetic resonance imaging, positron emission tomography, cerebral blood flow, CBF, serotonin-specific reuptake blocker, benzodiazepine, ketamine, methamphetamine, lamotrigine and atypical antipsychotic agents. RESULTS: The empirical evidence for relevant medications having a confounding effect on task performance or CBF in relevant areas remains sparse for most psychotropic medications among patients with PTSD. However, considerable evidence is accumulating for 2 of the most commonly prescribed medication classes (serotonin-specific reuptake inhibitors and benzodiazepines) in healthy controls. Compelling data for the potentially confounding effects on brain areas relevant to PTSD for psychotherapeutic interventions are also accumulating. CONCLUSION: Neuroimaging studies examining the pathophysiology of PTSD should ideally recruit both medicated (assuming that the medication treatment has not resulted in the remission of symptoms) and unmedicated participants, to allow the findings to be generalized with greater confidence to the entire population of patients with PTSD. More research is needed into the independent effects of medications on task performance and CBF in regions of interest in PTSD. Neuroimaging studies should also take into account whether patients are currently engaged in psychotherapeutic treatment.

The newly proposed criteria for posttraumatic stress disorder (PTSD) in the Diagnostic and Statistical Manual (DSM-V) include dysregulation of a variety of emotional states including fear, anger, guilt, and shame, in addition to dissociation and numbing. Consistent with these revisions, we postulate two models of emotion dysregulation in PTSD in which fear is not the prevailing emotion but is only one of several components implicated in a dysregulated emotional system that also mediates problems regulating anger, guilt, shame, dissociation, and numbing.We discuss whether there is a relationship between fear and other emotion regulation systems that may help further our understanding of PTSD and its underlying neurocircuitry. Two pathways describing the relationship between fear and other emotion regulation systems in PTSD are proposed. The first pathway describes emotion dysregulation as an outcome of fear conditioning through stress sensitization and kindling. The second pathway views emotion dysregulation as a distal vulnerability factor and hypothesizes a further exacerbation of fear and other emotion regulatory problems, including the development of PTSD after exposure to one or several traumatic event(s) later in life. Future research and treatment implications are discussed.

The paper discusses the design and evaluation of a multimedia software application, which can be used in the treatment of combat-related posttraumatic stress disorder (PTSD). The application allows patients and therapist to visualize the patients' past experience using maps, personal photos, stories and self-created 3D virtual worlds. The tool aims to allow patients to restructure and relearn about their past experience involving the problematic stressors. Findings of a first experiment with non-patients (N=18) suggests that the tool can facilitate more detailed storytelling. Participants stated that using the application was appealing and enjoyable. Insights were also acquired with a case study of a veteran suffering from combat-related PTSD. This case study showed how a patient uses and interacts with the system in a therapeutic setting.

In this study we tested for a protective effect of secure attachment representations in the development of posttraumatic stress disorder (PTSD). In a design with a control group, we replicated and extended a recent study that found no underrepresentation of secure attachment representations in veterans with PTSD (Nye, Katzman, Bell, Kilpatrick, Brainard, & Haaland, 2008). Furthermore, we examined the association of the Adult Attachment Interview (AAI) classification of unresolved loss or trauma and PTSD symptomatology. The Adult Attachment Interview and the Clinician Administered PTSD Scale (CAPS) were administered with 31 veterans with PTSD and 29 trauma-exposed veterans without PTSD of similar age and country of deployment. Patient and control groups did not differ in the prevalence of secure attachment representations, neither did unresolved and not unresolved subjects differ in prevalence of secure attachment representations. Unresolved state of mind with respect to deployment related trauma was found to correlate strongly with total CAPS score. This study shows no protective effect of secure attachment representations in the development of PTSD. AAI unresolved state of mind with respect to deployment related trauma and PTSD correlate strongly, due to the common core phenomenon of lack of integration.

Severe fatigue and co-morbid depressive symptoms are frequently reported by recently deployed military personnel. Stress can induce lasting changes in the negative feedback regulation of the hypothalamic-pituitary-adrenal axis (HPA-axis) and the regulation of the immune system by cortisol. Since these actions of cortisol are modulated via glucocorticoid receptors (GR), we investigated the effect of deployment and of deployment-related fatigue on glucocorticoid binding to peripheral blood mononuclear cells (PBMCs) in a prospective design. Psychological assessments and blood sample collection took place before and one and six months after deployment. Participants were selected from a larger group and assigned to three groups based on their level of fatigue and depressive symptoms six months after deployment. We compared fatigued participants without depressive symptoms (n=21), fatigued participants with depressive symptoms (n=14) and non-fatigued participants without depressive symptoms (n=21). Fatigued participants with depressive symptoms at six months after deployment had higher glucocorticoid binding to PMBCs than the other two groups at all three time points. Notably, this difference was already present before deployment. There was no effect of deployment on glucocorticoid binding to PBMCs. The observed differences in glucocorticoid binding were not related to pre-existing group differences in psychological symptoms. No group differences were observed in the composition of the PBMC population and plasma cortisol levels. These results indicate that high glucocorticoid binding to PBMCs might represent a vulnerability factor for the development of severe fatigue with depressive symptoms after a sustained period of stress, such as deployment.