Stress and Brain Atrophy

Abstract

Studies in animals showed that stress is associated with changes in hippocampal function and structure, an effect mediated through decreased neurogenesis, increased glucocorticoids, and/or decreased brain derived neurotrophic factor. Antidepressants and some anticonvulsants block the effects of stress and/or promote neurogenesis in animal studies. Patients with posttraumatic stress disorder (PTSD) have been shown to have smaller hippocampal volume on magnetic resonance imaging and deficits in hippocampal-based memory. Symptom activation is associated with decreased anterior cingulate and medial prefrontal function, which is proposed as the neural correlate of a failure of extinction seen in these patients. Treatment with antidepressants and phenytoin reverse hippocampal volume reduction and memory deficits in PTSD patients, suggesting that these agents may promote neurogenesis in humans. Stress has wide ranging effects on the individual. Traumatic stressors represent the most severe range of the spectrum and are defined by the Diagnostic and Statistical Manual (DSM) as threats to life of self or significant other with intense fear, horror or helplessness [1]. Traumatic stress so defined affects at least half of the US population [2]. Childhood sexual abuse is the most common trauma in women while physical assault is most common in men [3, 4]. Traumatic stress leads to a range of mental disorders, including posttraumatic stress disorder (PTSD), depression, alcoholism, dissociation, anxiety and borderline personality disorder [5]. Based on the high overlap amongst these stress-related disorders, I have argued that they should be considered together as "trauma-spectrum disorders" [5]. Traumatic stress is also associated with a range of poor health outcomes, including increased risk of heart disease, diabetes, stroke, and asthma [6-13]. PTSD is the sine qua non trauma-related disorder, as it requires a trauma exposure for the diagnosis. PTSD is twice as common in women as in men, and affects about 8% of the US population at some time in their lives [14]. Trauma exposure leads to short-term PTSD in about a third of individuals, while 15% develop chronic PTSD [15]. In order to understand mechanisms involved in PTSD we have applied neurobiological findings from studies of the effects of stress on animals. Studies in PTSD patients corroborate findings in animals that stress is associated with changes in brain structure and function. These changes appear to be specific to PTSD, and not a non-specific effect of exposure to traumatic stress. Animal studies show that stress has lasting effects on brain circuits and systems. A network of brain regions are involved in the stress response, including hippocampus, amygdala,