Person:

Orr, Scott

Background: PTSD is associated with reduction in hippocampal volume and abnormalities in hippocampal function. Hippocampal asymmetry has received less attention, but potentially could indicate lateralised differences in vulnerability to trauma. The P300 event-related potential component reflects the immediate processing of significant environmental stimuli and has generators in several brain regions including the hippocampus. P300 amplitude is generally reduced in people with PTSD. Methods: Our study examined hippocampal volume asymmetry and the relationship between hippocampal asymmetry and P300 amplitude in male monozygotic twins discordant for Vietnam combat exposure. Lateralised hippocampal volume and P300 data were obtained from 70 male participants, of whom 12 had PTSD. We were able to compare (1) combat veterans with current PTSD; (2) their non-combat-exposed co-twins; (3) combat veterans without current PTSD and (4) their non-combat-exposed co-twins. Results: There were no significant differences between groups in hippocampal asymmetry. There were no group differences in performance of an auditory oddball target detection task or in P300 amplitude. There was a significant positive correlation between P300 amplitude and the magnitude of hippocampal asymmetry in participants with PTSD. Conclusions: These findings suggest that greater hippocampal asymmetry in PTSD is associated with a need to allocate more attentional resources when processing significant environmental stimuli.

This study used quantitative volumetric magnetic resonance imaging techniques to explore the neuroanatomic correlates of chronic, combat-related posttraumatic stress disorder (PTSD) in seven Vietnam veterans with PTSD compared with seven nonPTSD combat veterans and eight normal nonveterans. Both left and right hippocampi were significantly smaller in the PTSD subjects compared to the Combat Control and Normal subjects, even after adjusting for age, whole brain volume, and lifetime alcohol consumption. There were no statistically significant group differences in intracranial cavity, whole brain, ventricles, ventricle:brain ratio, or amygdala. Subarachnoidal cerebrospinal fluid was increased in both veteran groups. Our finding of decreased hippocampal volume in PTSD subjects is consistent with results of other investigations which utilized only trauma-unexposed control groups. Hippocampal volume was directly correlated with combat exposure, which suggests that traumatic stress may damage the hippocampus. Alternatively, smaller hippocampi volume may be a pre-existing risk factor for combat exposure and/or the development of PTSD upon combat exposure.

In animals, exposure to severe stress can damage the hippocampus. Recent human studies show smaller hippocampal volume in individuals with the stress-related psychiatric condition posttraumatic stress disorder (PTSD). Does this represent the neurotoxic effect of trauma, or is smaller hippocampal volume a pre-existing condition that renders the brain more vulnerable to the development of pathological stress responses? In monozygotic twins discordant for trauma exposure, we found evidence that smaller hippocampi indeed constitute a risk factor for the development of stress-related psychopathology. Disorder severity in PTSD patients who were exposed to trauma was negatively correlated with the hippocampal volume of both the patients and the patients’ trauma-unexposed identical co-twin. Furthermore, severe PTSD twin pairs—both the trauma-exposed and unexposed members—had significantly smaller hippocampi than non-PTSD pairs.

A biological abnormality found to be associated with post-traumatic stress disorder (PTSD) may be, among other things, a pre-trauma vulnerability factor, that is, it may have been present prior to the event’s occurrence and increased the individual’s likelihood of developing PTSD upon traumatic exposure. Alternately, it may be an acquired PTSD sign, that is, it may have developed after the traumatic exposure, along with the PTSD. We have studied pairs of Vietnam combat veterans and their noncombat-exposed, identical twins in an effort to resolve these competing origins. Combat veterans were diagnosed as current PTSD or non-PTSD (i.e., never had). Average heart rate responses (HRRs) to a series of sudden, loud-tone presentations were larger in Vietnam combat veteran twins with PTSD, but these larger responses were not shared by their noncombat-exposed cotwins, whose responses were similar to those of the non-PTSD combat veterans and their noncombat-exposed cotwins. These results suggest that larger HRRs to sudden, loud tones represent an acquired sign of PTSD. In contrast, increased neurological soft signs (NSSs), diminished hippocampal volume, and presence of abnormal cavum septum pellucidum (CSP) were found in Vietnam combat veteran twins with PTSD and their “high-risk,” unexposed cotwins compared to Vietnam combat veteran twins without PTSD and their “low-risk,” unexposed cotwins. These results support the conclusion that the latter abnormalities represent antecedent, familial vulnerability factors for developing chronic PTSD upon exposure to a traumatic event.