Faculty Bibliography

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.

BACKGROUND: Neuroendocrine studies have shown profound alterations in HPA-axis regulation in posttraumatic stress disorder (PTSD). Based on baseline assessments and the response to dexamethasone, a hypothalamic overdrive with enhanced glucocorticoid feedback inhibition has been suggested. The dexamethasone-corticotrophin releasing hormone (DEX-CRH) test has shown to be a more sensitive test to assess HPA-axis dysregulation in major depression and therefore may provide a useful test tool to probe HPA-axis regulation in PTSD. METHODS: To evaluate the effect of PTSD on HPA-axis regulation, we compared the response to a DEX-CRH test between male veterans with PTSD (n=26) and male veterans, who had been exposed to similar traumatic events during their deployment, without PTSD (n=23). Patients and controls were matched on age, year and region of deployment. Additionally, we compared the response of PTSD patients with (n=13) and without co-morbid major depressive disorder (MDD) (n=13). RESULTS: No significant differences were observed in ACTH and cortisol response to the DEX-CRH test between patients and controls. PTSD patients with co-morbid MDD showed a significantly lower ACTH response compared to patients without co-morbid MDD. The response to the DEX-CRH test did not correlate with PTSD or depressive symptoms. CONCLUSION: The DEX-CRH test did not reveal HPA-axis abnormalities in PTSD patients as compared to trauma controls. PTSD patients with a co-morbid MDD showed an attenuated ACTH response compared to PTSD patients without co-morbid MDD, suggesting the presence of subgroups with different HPA-axis regulation within the PTSD group. Altered sensitivity of the CRH receptors at the pituitary or differences in AVP secretion might explain these differences in response.

BACKGROUND: Posttraumatic stress disorder (PTSD) is associated with altered hypothalamic-pituitary-adrenal (HPA) axis functioning. Arginine vasopressin (AVP), in conjunction with corticotrophin releasing hormone, has shown to be an important modulator of the HPA axis. In order to evaluate the effect of trauma and PTSD on central AVP secretion we assessed plasma AVP levels in equally trauma exposed veterans with and without PTSD and a non-traumatized healthy control group. METHODS: Assessment of plasma AVP in 29 male veterans with PTSD, 29 traumatized veterans without PTSD, matched for age, gender, year and region of deployment (trauma controls), and 26 age matched healthy controls. RESULTS: Plasma AVP levels were higher in PTSD patients compared to both healthy controls (p = 0.004) and trauma controls (p < 0.001). In PTSD patients without a comorbid MDD a significant correlation was observed between plasma AVP levels and symptoms of avoidance measured with the Clinician Administered PTSD Scale (CAPS). CONCLUSION: Elevated plasma AVP levels are specifically related to PTSD and not to exposure to traumatic stress during deployment. Our results indicate that AVP may play a role as an anxiogenic factor, but they do not support a role for AVP in the altered response to dexamethasone in PTSD.

Gamma-aminobutyric acid (GABA(A)) receptors are thought to play an important role in modulating the central nervous system in response to stress. Animal data have shown alterations in the GABA(A) receptor complex by uncontrollable stressors. SPECT imaging with benzodiazepine ligands showed lower distribution volumes of the benzodiazepine-GABA(A) receptor in the prefrontal cortex of patients with post-traumatic stress disorder (PTSD) in one, but not in another study. The objective of the present study was to assess differences in the benzodiazepine-GABA(A) receptor complex in veterans with and without PTSD using [(11)C]flumazenil and positron emission tomography (PET). Nine drug naive male Dutch veterans with deployment related PTSD and seven male Dutch veterans without PTSD were recruited, and matched for age, region and year of deployment. Each subject received a [(11)C]flumazenil PET scan and a structural magnetic resonance imaging scan. Dynamic 3D PET scans with a total duration of 60 min were acquired, and binding in template based and manually defined regions of interest (ROI) was quantified using validated plasma input and reference tissue models. In addition, parametric binding potential images were compared on a voxel-by-voxel basis using statistical parametric mapping (SPM2). ROI analyses using both template based and manual ROIs showed significantly reduced [(11)C]flumazenil binding in PTSD subjects throughout the cortex, hippocampus and thalamus. SPM analysis confirmed these results. The observed global reduction of [(11)C]flumazenil binding in patients with PTSD provides circumstantial evidence for the role of the benzodiazepine-GABA(A) receptor in the pathophysiology of PTSD and is consistent with previous animal research and clinical psychopharmacological studies.