Animal studies demonstrated that repeated and prolonged stress for an animal can produce damage to the hippocampus. The hippocampus is an area of the brain that has been implicated in declarative memory for humans. Declarative memory include memories that were created from our school learning as an example, and those personal memories such as what our 12th birthday was like.
Given the intriguing findings about the effects of extreme stress on the hippocampus in animals, MRI researchers looked into the structural aspects of the hippocampus in humans who suffered chronic unremitting forms of posttraumatic stress disorder (PTSD). They found that those persons who had been diagnosed with PTSD had smaller hippocampal volume. Given these findings, 2 questions remained: was smaller hippocampal volume a neurotoxic effect of combat stress, or 2) was smaller hypocampal volume a pre-existing condition that rendered the person vulnerable to PTSD?
To address this question, Mark Gilbertson, of the Dept of Psychiatry at Harvard University, and colleagues obtained a sample of monozygotic (or identical) twins who were discordant for combat duty (one twin had been in combat, the other had not).
Gilbertson, et al. found that there was a positive correlation between the volume of the hippocampus in the twin pairs irrespective of the presence of PTSD in one of the twins. Further correlations showed significant negative relationship between hippocampal volume and PTSD symptom severity; also there was a significant negative correlation between hippocampal volume in the unexposed (to combat) twin and PTSD severity in the exposed brother (a smaller volume in the unexposed brother = greater PTSD symptom severity in the exposed co-twin).
To further test for the neurotoxic vs. pre-existing condition question, Gilbertson, et al. set up a series of four contrasts. 1) The first contrast examined if there was a significant volume difference in those veterans with PTSD vs. those without PTSD? (a replication of earlier findings). 2) a comparison of hippocampal volume between the exposed twin vs. the unexposed twin (neurotoxic effect test). 3) contrast of hippocampal volumes in the two groups of combat-unexposed co-twins whose combat exposed brothers did versus did not develop PTSD (this interaction effect was a test for the pre-existing vulnerability hypothesis).
The contrast results confirmed a vulnerability model and not a neurotoxic model. Given the diathesis of reduced hippocampal volume, and given the sufficient condition of combat exposure, the person is at risk for developing a severe form of PTSD. This outcome remained even when rival hypotheses including – prior traumatic experience, severity of alcoholism history, history and severity of depression history, and the severity of combat experience were controlled.
Heredity is the most likely explanation for these results. However, this design did not allow for an assessment of shared enviornment effects. An addition of a sample of dizygotic (fraternal) twins discordant for combat experience would allow for a separation of heredity and shared environment effects.
Gilbertson, M.W., Shenton, M.E., Ciszewski, A., Kasai, K., Lask, N.B., Orr, S.P., & Pitman, RK. (2002). Smaller hippocampal volume predicts pathologic vulnerability to psychological trauma. Nature Neuroscience, 5, 1242 – 1247.
An abstract of this study can be obtained here. The email address of the lead author is available at the preceding link.
I sincerely thank Dr. Gilbertson for promptly emailing me a copy of the full study.