Is PTSD neurotoxic?

In this brief article I will address biopsychological research of Post Traumatic Stress Disorder (PTSD). The study reviewed (Gilbertson, Shenton, Ciszewski, Kasai, Lasko, Orr & Pitman, 2002) utilized a “case-control” monozygotic twin design. This kind of study is used to explore the influence of heredity on a particular trait (in this case hippocampal volume in PTSD discordant twins, one of whom was exposed to combat in Vietnam, see also Gilbertson, et al., 2002) (Carlson, 2010, p. 166).

Briefly, and as temporal background to frame this particular research, structural magnetic resonance imaging (MRI) studies report that hippocampal volume in PTSD patients is noticeable smaller and it is hypothesized that psychological trauma may cause neurological damage due to neurotoxic activation of corticosteroids leading to hippocampal neuronal death (Gilbertson, et al., 2002, p. 1242). (in fact, this was the hypothesis under study). In this monozygotic twin study, the authors tested this neurotoxic hypothesis, by way of examining combat exposed Vietnam veterans and their stay-home twin brothers in order to revealing whether or not smaller hippocampal volume post – combat experience was either a pre-existing condition or a direct result of traumatic experience (p. 1242). Finally, “[b]ecause monozygotic twins are genetically identical, any differences in hippocampal volume between brothers were interpreted as evidence for environmental effects, such as stress-induced neurotoxicity [as a result of combat exposure and not as a result of a exposure to combat with a smaller pre-existing hippocampal volume]” (p. 1242).

While the study also examined several other variables concomitant to a severe PTSD diagnosis, for example, alcohol abuse and depression, the major finding is stated best by the authors themselves: “the key finding here concerns the identical twins of the higher severity PTSD combat veterans who were not themselves exposed to combat; they showed hippocampal volumes that were comparable to their combat-exposed brothers but significantly smaller than those of combat veterans without PTSD and their non-combat–exposed twins” (p. 1245). This clearly indicates that people with genetically (“given”) smaller hippocampal volumes are more likely to develop severe, unremitting PTSD than those with larger volumes (p. 1245), ceteris parabus. In other words – size matters. This effectively refutes the neurotoxicity hypothesis, therefore “reference to hippocampal ‘atrophy’ in PTSD may be a misnomer” (p. 1245).

This seminal study effectively settled a longstanding controversy of biopsychology, that the brain was injured by trauma due to neurotoxicity. While this is not absolutely ruled out by this study, it is clear that even when comorbid alcohol abuse and depression are circumvented via case-control design, that people who have smaller hippocampal volume are at greater risk for developing severe PTSD, especially when exposed to the terror of combat, and even then, independent of combat severity (p. 1245).

It is important to note that the hippocampus is involved in fear processing, memory (especially declarative memory – or, memory that is explicit, factual, and assessable to conscious awareness; this is highly correlated with the hippocampus and the medial temporal lobe, amongst other areas of the prefrontal cortex – the left dlPFC for encoding and the right PFC for retrieval, according to the Hemispheric-Encoding-Retrieval-Asymmetry (HERA) model, Zillmer, Spiers, & Culbertson, 2008, pp. 227-9), and in the important conditioning and extinction mechanism in animals and, likely, humans (having an effect on neuroendocrine regulation of the hypothalamic–pituitary–adrenal axis) (Gilbertson, et al., 2002, pp. 1245-6). Lastly, it is heredity that is likely the responsible etiology of smaller hippocampi observed in this study of twin Vietnam War-era brothers (though with a dizygotic twin study, this might have been further clarified) (p. 1246). Further sealing up the argument is the fact that in the study those veterans who had combat exposure and larger hippocampal volume and did not develop PTSD refutes the neurotoxic and/or shared environment hypotheses (though without a dizygotic study, this remains unclear) and adds strength to the aforementioned findings of this seminal study demonstrating PTSD susceptibility in those with smaller hippocampal volume (p. 1246).

References

Carlson, N. (2010). Physiology of behavior, (10th ed.). Boston: Allyn & Bacon.

Gilbertson, M. W., Shenton, M. E., Ciszewski, A., Kasai, K., Lasko, N. B., Orr, S. P., & Pitman, R. K. (2002). Smaller hippocampal volume predicts pathologic vulnerability to psychological trauma. Nature Neuroscience, 5(11), 1242-1247. doi:10.1038/nn958

Zillmer, E., Spiers, M., & Culbertson, W. (2008). Principles of neuropsychology, (2nd ed.). Belmont, CA: Thomson Wadsworth.