Neurobiology and Treatment of Posttraumatic Stress Disorder

Studies in animals and humans suggest that stress is associated with long-term alterations in brain function and structure. These findings are relevant to understanding the neurobiology of posttraumatic stress disorder (PTSD) and in the development of treatments for this disabling disorder. Studies in animals showed long-term dysregulation in stress-responsive systems, including the norepinephrine and hypothalamic-pituitary-adrenal (HPA) axis systems. These findings have been extended to PTSD, with, for example, findings of increased noradrenergic responsivity in PTSD. The HPA axis and cortisol systems have been shown to be dysregulated in PTSD, and glucocorticoids, which are released during stress, were shown in animal studies to be associated with atrophy to neurons of the hippocampus, a brain area that plays an important role in learning and memory. These findings were extended to PTSD, with findings of smaller hippocampal volume measured with magnetic resonance imaging (MRI) in patients with both childhood abuse and combat-related PTSD, with associated deficits in hippocampal-based declarative memory. Using positron emission tomography (PET) we showed in several studies both dysfunction of the hippocampus and the medial prefrontal cortex, an area that plays an important role in regulation of emotion. Animal studies recently found that treatment with serotonin reuptake inhibitor medications reverses deficits in hippocampal morphology associated with stress and actually promotes the growth of neurons. We recently found improvements of symptoms of PTSD and hippocampal-based verbal declarative memory deficits following one year of treatment with paroxetine. Other findings related to the treatment of PTSD will be reviewed. These results begin to map out a functional neuroanatomy and neurophysiology of PTSD which may be applicable to future treatment directions.