MRI-based measurement of hippocampal volume in patients with combat-related posttraumatic stress disorder.

TLDR: A smaller right hippocampal volume in PTSD that is associated with functional deficits in verbal memory is consistent with high levels of cortisol associated with stress.

Abstract: Patients with combat-related posttraumatic stress disorder (PTSD) clinically demonstrate alterations in memory, including nightmares, flashbacks, intrusive memories, and amnesia for war experiences. In addition, descriptions from all wars of this century document alterations in memory occurring in combat veterans during or after the stress of battle. These include forgetting one's name or identity and forgetting events that had just taken place during the previous battle (1, 2), as well as gaps in memory that continue to recur for many years after the war (3). Servicemen who had been prisoners of war during the Korean conflict were found to have an impairment in short-term verbal memory, as measured by the logical memory component of the Wechsler Memory Scale, in comparison with veterans of the Korean war who did not have a history of imprisonment (4). We also found deficits in short-term verbal memory, as measured by the logical memory component of the Wechsler Memory Scale, in Vietnam combat veterans with combat-related PTSD in comparison with healthy subjects who were matched for age, years of education, and alcohol abuse (5). Several lines of evidence suggest a relation between stress and damage to the hippocampus (6). The hippocampus and the adjacent perirhinal, parahippocampal, and entorhinal cortex play an important role in short-term memory (7). Studies in humans have shown that reductions in hippocampal volume secondary to either neurosurgery (8) or the pathophysiological effects of epilepsy (9) are associated with deficits in short-term memory as measured by the Wechsler Memory Scale. Monkeys exposed to the extreme stress of improper caging have shown increased glucocorticoid release as well as damage to the CA2 and CA3 subfields of the hippocampus (10). Studies in a variety of animal species suggest that direct glucocorticoid exposure results in a loss of neurons and a decrease in dendritic branching in the hippocampus (11, 12) with associated deficits in memory function (13). The mechanism of action of glucocorticoid toxicity is probably through an increase in the vulnerability of neurons to the toxicity of excitatory amino acids (14–16). Studies using computed tomography in human subjects who are exposed to high levels of glucocorticoids secondary to glucocorticoid steroid therapy (17, 18) or who have affective disorders (also felt to be related to stress) (19) have shown changes in brain structure, including ventricular enlargement and widening of the cortical sulci. Magnetic resonance imaging (MRI) studies in patients with affective disorders have shown a smaller right hippocampal volume (20) and temporal lobe volume (21) in bipolar disorder and abnormalities of the hippocampus, including alterations in T1 (22), but no change in hippocampal volume (23) in major depression. One MRI study (24) found a relation between deficits in short-term memory and smaller hippocampal volume, as well as higher plasma cortisol levels and smaller hippocampal volume, in patients with Cushing's disease. Stress in both healthy human subjects (25) and soldiers undergoing random artillery bombardment (26) results in an increase in urinary cortisol, suggesting the possibility that exposure to the extreme stress of combat may be associated with damage to the hippocampus. The purpose of this study was to use MRI to measure the volume of the hippocampus and comparison brain structures in patients with PTSD and in matched comparison subjects. We hypothesized that PTSD would be associated with smaller hippocampal volume in relation to that of the comparison subjects. We also hypothesized that smaller hippocampal volume would be associated with deficits in short-term verbal memory in patients with PTSD.