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Stress Precedes Volume Reductions in the Hippocampus in PTSD

Posted in Health, Psychology, Science, Uncategorized by farmerjaneusa on October 14, 2010

from Science Blogs

There was a debate in the post-traumatic stress disorder (PTSD) for some time about whether the shrinkage observed in the hippocampus — a structure involved in learning and memory — was the result of the stress or was a vulnerability factor for the disease.

We know that high levels of cortisol — a stress hormone — can kill neurons. So you could argue that the stress and stress hormones that cause PTSD could also result in the reduction in hippocampal volume. This is the so-called neurotoxicity hypothesis.

On the other hand, individuals who get PTSD could have some underlying genetic or structural susceptibility, one characteristic of which could be an already smaller hippocampus. This is the so-called vulnerability hypothesis.

Researchers at Stanford have published a paper that adds credibility to the neurotoxicity hypothesis.

The researchers followed a cohort of 15 recently diagnosed PTSD patients age 7 to 13 over the course of 12 to 18 months. They tracked the sizes of their hippocampi at the beginning and the end of the interval using MRI images and also measured their cortisol levels.

The researchers found that over the interval the sizes of the hippocampi in the patients went down.

Our results support the hypotheses that PTSD symptoms and cortisol levels at baseline are associated with changes in hippocampal volume over an ensuing 12- to 18-month interval. Specifically, we found that severity of PTSD symptoms and cortisol levels predict a reduction in hippocampal volume from baseline to follow-up when controlling for pubertal maturation and gender in children with a history of traumatic stress. This is the first longitudinal study in PTSD to document an association between hippocampal changes with PTSD symptoms and with a marker of stress, cortisol levels. These longitudinal findings help elucidate previous cross-sectional reports of smaller hippocampal volumes in PTSD populations. Our results are also in accord with animal literature reporting on the neurotoxic effects of glucocorticoids in the hippocampus. Our results stand in contrast, however, with studies identifying hippocampal volume as a vulnerability factor. Although, this study was not designed to address the vulnerability factor hypothesis, our exploratory analyses suggest that hippocampal volume was not a risk factor for development of PTSD symptoms….

Our cortisol findings address a potential mechanism by which stress can alter the hippocampus. There is substantial animal literature demonstrating the neurotoxic effects of glucocorticoid in the glucocorticoid receptor-rich hippocampus. Glucocorticoids can also exert their neurotoxicity indirectly via accumulation of extracellular glutamate. High levels of glucocorticoids have been reported in children with history of maltreatment and PTSD. Elevated cortisol levels suggest that high levels of stress lead to activation of the HPA axis and cortisol production and that this leads to hippocampal toxicity, which results in poor inhibitory activity from the hippocampus unto other centers, such as the HPA axis itself. The putative neurotoxic effects of cortisol on the hippocampus may depend on at least 3 factors: (1) the developmental stage of the structure (the hippocampus glucocorticoid receptors density may change throughout development), (2) the level and sustainability of cortisol released, and (3) the severity and/or chronicity of the stressful events.

Other studies have attempted to follow patients with PTSD, but they have been done on older patient populations that have often had PTSD for much longer. This is a confound in the ability to measure hippocampal volume changes because chronic stress may not cause changes and stress that is far removed may have given the brain time to recover.

The recognition that stress does shrink the hippocampus rather than that a small hippocampus is a susceptibility factor for PTSD may have consequences in terms of patient treatment. In theory, we would like to short circuit the shrinkage of the hippocampus by some pharmacological means, or maybe we could improve function by providing cognitive training.

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