Brain Structure and Function Before and After Treatment for Post-Traumatic Stress Disorder

Posttraumatic stress disorder (PTSD) is characterized by intrusive recollections, avoidant behavior, anxiety and exaggerated fear response. The pathophysiology of PTSD is largely unknown. Neurophysiological testing in PTSD reveals deficits in memory and attention. Neuroimaging studies report increased amygdala and decreased anterior cingulate activation and reduced hippocampal volume. Clinical observations, psychophysiological measures and animal studies suggest that facilitated fear conditioning, delayed extinction, inescapable shock, sensitization and protracted habituation may contribute to the onset and persistence of PTSD. We propose to use fMRI and the psychophysiology lab to examine the effect of treatment with paroxetine and cognitive behavioral therapy on regional cerebral blood flow (rCBF) in brain regions conceivably involved in evolution and maintenance of PTSD: Amygdala, anterior cingulate and hippocampus. We will use emotional tasks that have elicited differences in perfusion or metabolism between patients with PTSD and trauma exposed and healthy subjects. Tasks performed in the fMRI will include 'masked' and 'unmasked' emotional faces paradigms and differential delay conditioning. Contextual fear provocation and eyeblink trace conditioning will be done in the psychophysiology lab. This evaluation will be performed before and after a 10-week period of treatment with paroxetine and a 10-session course of cognitive behavioral treatment (CBT). Study population will comprise the following matched groups: Patients with PTSD; previously traumatized healthy subjects who have not suffered from PTSD and non-traumatized healthy subjects. Subjects from the 1st group will either be treated with paroxetine for 10 weeks, undergo a 10-week 'prolonged exposure' (PE) CBT course, or will be put on the 'waiting list'. It is assumed that variability in outcome will be observed in both treatment modes, which will enable us to seek treatment response predictors. It is unknown whether cerebral abnormalities in PTSD are state or trait phenomena. In depression and OCD, functional imaging research shows improvement in malfunctioning brain regions after clinically effective psychopharmacological and psychotherapeutic interventions and after administration of placebo in depression. An increase in hippocampal volume was found in patients with PTSD after treatment with paroxetine and after correction of the endocrine abnormality in Cushing's disorder. These findings support our expectation that at least some brain abnormalities in PTSD are state related, and that change in these abnormalities is demonstrable by fMRI.