Abstract
Introduction: Post traumatic stress disorder (PTSD) is a common psychiatric disorder among individuals exposed to traumatic experiences with a lifetime prevalence of 8%. Among veterans of war the lifetime prevalence is 22–30%. Neurobiological studies have identified indirect evidence of neuroreceptor and neuro-endocrine abnormalities. The GABA-Benzodiazepine receptor complex is of particular interest as it is an important modulator of stress responses in animals and humans, and it has been shown to have a central role in other anxiety disorders such as Panic Disorder. Positron Emission Tomography (PET) has recently been used to estimate the density of GABA-BZD receptors (Bmax) and the affinity of these receptors (Kd) in vivo using the BZD antagonist PET ligand [11C]-flumazenil.
This current study aims to compare the Bmax and Kd of BZD receptors in subjects with PTSD and normal control subjects.
Methods: 13 male subjects with war-related PTSD and 13 age and sex matched controls between the ages of 44 and 65 were successfully scanned. A Partial Saturation Method was used in which a tracer dose of [11C]-flumazenil is intravenously co-injected with non-radioactive flumazenil to obtain Bmax and Kd images. Regions of interest were chosen in 12 cortical and subcortical brain regions. Bmax and Kd values were calculated from Scatchard plots per pixel. Analysis of variance and statistical parametric mapping methods were used to determine significant changes in Bmax and Kd between subject groups.
Results: There were no significant group differences in measurements of receptor density (Bmax) for any brain region. The affinity of GABA-BZD receptors for Flumazenil was significantly increased (i.e. lower mean Kd values) in PTSD subjects compared with control subjects over all brain regions apart from the Thalamus.
Conclusions: These results suggest that either there is a conformational change in the GABA-BZD receptor or a change in the genetic material coding for the receptor protein in patients with PTSD. It is possible these changes pre-date trauma exposure and act as a risk factor for PTSD. Alternatively the increased affinity of the receptors may be a consequence of the condition. Further imaging and molecular biological studies are required to explore these possibilities.