Proefschrift: The war within : Neurobiological alterations in posttraumatic stress disorder
Abstract
For a large number of veterans, war does not end after they are removed from a combat zone. Traumatic stress affects nearly all veterans, but while the majority of veterans learn to live with their experiences, for some veterans traumatic stress seethes inside. In this dissertation posttraumatic stress disorder (PTSD) in Dutch veterans was examined using different neuroimaging techniques and neuropsychological assessment. In the first two chapters, a review of the literature is reported, in which studies on hippocampal volumetry were examined. From this database the methodology of all original manual tracing protocols of the hippocampus were studied, and discussed in relation to optimizing determination of hippocampal volume. In addition, hippocampal volumetric findings in neuropsychiatric disorders were reported, and possible mechanisms of hippocampal volume loss were discussed. Advances in computational image analysis provide new opportunities to use semi-automatic techniques to determine cortical thickness. Veterans with and without PTSD, were examined with structural magnetic resonance imaging (MRI), and individual cortical thickness maps were calculated. Veterans with PTSD revealed reduced cortical thickness in the bilateral frontal gyri, and the left superior temporal gyrus. Differences in the benzodiazepine-GABAA receptor complex in Dutch veterans with and without deployment-related PTSD were examined using [11C]-flumazenil and PET. Region of interest (ROI) analysis using both template-based and manual ROIs revealed significantly reduced [11C]-flumazenil binding in PTSD subjects throughout the cortex, hippocampus, and thalamus. Although clinical studies have described altered pain experience in patients with PTSD, few empirical studies have examined pain processing in PTSD in detail. The neural correlates of pain processing in Dutch veterans with deployment-related PTSD and control veterans were examined with fMRI. Veterans with PTSD revealed increased activation in the left hippocampus, and decreased activation in the bilateral ventrolateral prefrontal cortex, and the right amygdala during stimulation with a fixed temperature compared to controls. The witnessed neural activation pattern is proposed to be related to altered pain processing in patients with PTSD. In another fMRI study, neural correlates of associative learning and memory in veterans with PTSD and control veterans were assessed. Veterans with PTSD revealed underactivation of the frontal cortex, and overactivation of the temporal cortex during encoding of word-pairs compared to control veterans without PTSD. Retrieval of the word-pairs resulted in underactivation of right frontal cortex, bilateral middle temporal gyri, and the left parahippocampal gyrus in veterans with PTSD. Finally, the results of a neuropsychological study on memory performance in PTSD and its relation to social and occupational functioning were reported. Veterans with PTSD had similar total IQ scores compared to veterans without PTSD, but displayed deficits of figural and logical memory. Veterans with PTSD also performed significantly lower on measures of learning and immediate and delayed verbal memory. Memory performance accurately predicted current social and occupational functioning. These neurobiological alterations witnessed in veterans with PTSD show that the problems experienced by them are not just 'figments of the imagination' but very real neurobiological consequences of traumatic stress. It is this neurobiological 'war within' that we should learn to wage and win.