Schneidcrman ct al97 found that combat-incurred mild TBI approximately doubled the risk for PTSD and that a PTSD diagnosis was the strongest factor associated with persistent post-concussive symptoms. Belanger et al98 studied patients with mild and moderatc-to-scverc TBI and found, as expected, that mild TBI was associated with higher levels of postconcussion complaints Inhibitors,research,lifescience,medical approximately 2 years after injury. However, after adjusting for PTSD symptoms, these betwecn-group differences were no longer significant. These studies are consistent with the literature cited above that suggests that mild TBI may increase the relative risk for psychiatric disorders,
and that these disorders can interfere with recover}’ from the TBI. There is reason to believe Inhibitors,research,lifescience,medical that part of the explanation for the complex interaction between biomechanical and psychological trauma relates to overlap in the neural substrates of both conditions (see refs 93-95,99 for discussion). For example mesial temporal structures are Selleckchem GSK1349572 vulnerable in TBI from both contact/impact Inhibitors,research,lifescience,medical forces, as well as increased sensitivity to excitotoxic injury. Hippocampal and amygdala injury
are common. Both of these regions play key roles in PTSD as well, both in terms of contextual memory consolidation and fear conditioning. The hippocampus is also felt to be vulnerable to the effects of chronic stress presumably through the mediating effects of the HPA axis. Thus biomechanical Inhibitors,research,lifescience,medical and neurochemically
mediated damage could conceivably interact with neurohumoral dysrcgulation to create a milieu that lends itself to the development of PTSD. Orbitofrontal cortex is also vulnerable to TBI through impact forces as well as frontal subcortical axonal injury. Relationship to dementia Several studies have raised a concern about the relationship of TBI to progressive dementia.100 For example, TBI-associated disruption of axonal transport results in the rapid accumulation of amyloid precursor protein (APP) in animals100,101 and humans.102,103 APP, A-beta, and other proteins associated with Alzheimer’s disease and Inhibitors,research,lifescience,medical other neurodegenerative disorders accumulate rapidly after a TBI.104-106 Some (but not all) autopsy studies have shown increased amyloid plaques and neurofibrillary tangles in individuals with TBI.106,107 This variation has prompted Amisulpride exploration of the role of genetic factors in modulating risk for Alzheimer’s disease after TBI. For example, Mayeux et al108 retrospectively studied 113 older adults with AD, comparing them with a control group of 123 healthy older individuals. They found that the combination of APOR-e4 and history of TBI increased the risk of AD by a factor of 10. However, not all studies have found such a relationship. A large, prospective population-based study of 6645 individuals 55 years and older and free of dementia at baseline found that mild brain trauma was not a major risk factor for the development of AD.