Faculty Bibliography

This paper provides a brief review of the developments in neurobiological research of posttraumatic stress disorder (ptsd), particularly into the link between the disorder and the central and peripheral stress-regulating processes. ptsd is an impairment of neuronal circuits and stress-regulating systems in the brain, where a critical note is played by limbic structures such as the hippocampus, the amygdala and the medial prefrontal cortex. In patients with ptsd the 'behaviour' of these neuronal circuits and systems is chronically disturbed. Characteristic symptoms are increased stress reactivity, reduction of declarative memory performance, high emotionality in response to trauma-related stimuli and over-representation of traumatic memory, all of which can be described as chronic dysregulated processes. Because of improvements in research designs and stratification of research populations, the specificity of research findings has improved and the developmental trajectories of specific ptsd parameters have been described more clearly. One of the most promising developments in the field of research designs is the current shift away from cross-sectional research designs to 'true prospective' research designs.

Group therapy can effectively reduce posttraumatic stress symptoms. However, the available literature on multifaceted programs for military samples is limited and available studies typically do not evaluate outcomes on a broad range of related problems. This study describes a retrospective evaluation of a multimodal, exposurebased group treatment program for posttraumatic stress disorder (PTSD) and associated symptoms in 22 peacekeeping veterans who successfully completed treatment. Treatment consisted of exposure-based CBT, case management, psycho-education, creative arts therapy, psychomotor therapy, psychodrama, and socio-therapy, which were provided one day a week for approximately 21 months. Analysis of pre- and posttreatment assessments showed that coping styles and professional and personality functioning had improved and that anxiety, somatic, depressive, and PTSD symptoms were reduced after treatment. Because significant improvement was observed on several parameters, the program may have successfully addressed a broad range of problems frequently reported by veterans with complex and chronic PTSD.

Hostility is a risk factor for adverse health outcomes as diverse as cardiovascular disease and post-traumatic stress disorder (PTSD). Cytokines have been suggested to mediate this relationship. We investigated whether in healthy men a relation existed between hostility and T-cell mitogen-induced cytokines and chemokines. Male Dutch military personnel (n=304) were included before deployment. Eleven cytokines and chemokines were measured in supernatants of T-cell mitogen-stimulated whole blood cultures by multiplex immunoassay. Factor analysis was used to identify clusters of cytokines and chemokines. In a regression analysis hostility was related to the cytokine/chemokine clusters, and the potential risk factors age, BMI, smoking, drinking, previous deployment, early life trauma and depression. Explorative factor analysis showed four functional clusters; a pro-inflammatory factor (IL-2, TNFalpha, IFNgamma), an anti-inflammatory factor (IL-4, IL-5, IL-10), IL-6/chemokine factor (IL-6, MCP-1, RANTES, IP-10), and MIF. Hostility was significantly related to decreased IL-6/chemokine secretion and increased pro- and anti-inflammatory cytokines. There was an inverse relation between age and hostility scores. Early life trauma and depression were positively and independently related to hostility as well. This study represents a novel way of investigating the relation between cytokines and psychological characteristics. Cytokines/chemokines clustered into functional factors, which were related to hostility in healthy males. Moreover this relation appeared to be independent of reported depression and early trauma.

Structural neuroimaging studies in posttraumatic stress disorder (PTSD) have focused primarily on structural alterations in the medial temporal lobe, and only a few have examined grey matter reductions in the cortex. Recent advances in computational analysis provide new opportunities to use semi-automatic techniques to determine cortical thickness, but these techniques have not yet been applied in PTSD. Twenty-five male veterans with PTSD and twenty-five male veterans without PTSD matched for age, year and region of deployment were recruited. All the subjects were scanned using MRI. Subjects' brains were aligned using cortex-based alignment in a region of interest based approach. Individual cortical thickness maps were calculated from the MR images. Regions of interest examined included the bilateral superior frontal gyri, bilateral middle frontal gyri, bilateral inferior frontal gyri, bilateral superior temporal gyri, and bilateral middle temporal gyri. In a large number of patients and controls, IQ scores and memory scores were also obtained. Individual cortical thickness maps were calculated from the MR images. Veterans with PTSD revealed reduced cortical thickness in the bilateral superior and middle frontal gyri, the left inferior frontal gyrus, and the left superior temporal gyrus. Veterans with PTSD performed significantly worse on memory measures compared to control veterans. Cortical thickness correlated with memory measures in the veterans without PTSD, but not in the veterans with PTSD. Cortical thinning in these regions may thus correspond to functional abnormalities observed in patients with PTSD.

Exposure to early trauma has frequently been linked to adult psychopathology, including personality disorders. This cross-sectional study explored the relationship between personality and retrospectively rated levels of early trauma in 242 soldiers. Multiple regression analyses showed a significant relationship between early trauma and adult personality as exposure to emotional trauma predicted levels of self-directedness and cooperativeness on the Temperament and Character Inventory (TCI; C. R. Cloninger, T. R. Przybeck, D. M. Svrakic, & R. D. Wetzel, 1994). Overall, these results suggest that early emotional trauma may be related to personality dimensions associated with poor impulse control and interpersonal behavior. These results are noteworthy considering that they were obtained in a healthy sample. They show that early trauma may become ingrained in personality and hamper the potential to effectively engage in social interactions, increasing the risk of emotional and cognitive problems.

Impaired attention and memory are symptoms frequently associated with posttraumatic stress disorder (PTSD). Although patients with PTSD frequently report memory difficulties and empirical research provides support for a memory deficit in PTSD, as of yet, no fMRI study has adequately investigated the neural correlates of learning and memory of neutral (i.e. not trauma related) material in patients with PTSD compared to controls. Twelve male veterans with PTSD, and twelve male veterans without PTSD, were recruited, and matched for age, region and year of deployment. Encoding and retrieval of 12 word-pair associates was assessed during fMRI in both experimental groups. Compared to controls veterans with PTSD revealed underactivation of the frontal cortex, and overactivation of the temporal cortex during the encoding phase. Retrieval of the paired associates resulted in underactivation of right frontal cortex, bilateral middle temporal gyri, and the left posterior hippocampus/parahippocampal gyrus in patients with PTSD. Deficits in memory performance in PTSD appear to be related to altered activity in fronto-temporal areas during both the encoding and retrieval phase of memory processing.