The relationship between cognitive and brain changes in posttraumatic stress disorder.

Preclinical studies show that stress is associated with changes in structure of the hippocampus, a brain area that plays a critical role in memory, inhibition of neurogenesis, and memory deficits. Studies in animals showed that both serotonin reuptake inhibitors (SSRIs) and the epilepsy medication phenytoin (dilantin) block the effects of stress on the hippocampus. Imaging studies in posttraumatic stress disorder (PTSD) have found smaller volume of the hippocampus as measured with magnetic resonance imaging (MRI) in patients with PTSD related to both combat and childhood abuse. These patients were also found to have deficits in memory on neuropsychological testing. Functional imaging studies using positron emission tomography (PET) found decreased hippocampal activation with memory tasks. In an initial study, we found that a year of treatment with paroxetine led to a 5% increase in hippocampal volume and a 35% increase in memory function. A second study showed that phenytoin was efficacious for symptoms of PTSD and led to a significant 6% increase in both right hippocampal and right whole brain volume, with no significant change in memory. These studies suggest that medications may counteract the effects of stress on the brain in patients with PTSD.