Stress and the Hippocampus

Travis DixonHealth Psychology

Stress can damage the hippocampus. But can a small hippocampus also be a risk factor for chronic stress?

The following is adapted from our eBook for Health Psychology: “Stress and how to cope: A Health Psychology guide for IB Students” (Available here). Not all of this content could make the final cut. So read on if you’re interested in how your hippocampus could be causing you stress. 

IB Psych Health: This content is relevant for biological explanations of health problems (chronic stress and cardiovascular disease) as well as risk/protective factors.

Understanding its role in the stress response helps us explain how abnormalities in the hippocampus it as a risk factor for health issues. Image source.

The Hippocampus and the Stress Response

Stress has mostly been studied in regards to memory. You might have already come across the famous case study of HM. However, it’s also an important part of the brain involved in the stress response whereas the hippocampus has two parts – the dorsal (top) and ventral (bottom). The dorsal hippocampus is important for memory. The ventral hippocampus helps in the regulation of the stress response. This could be why abnormalities in the hippocampus are linked with stress and stress-related disorders (e.g. depression and PTSD).

Numerous human studies have shown that perceived stress is linked with decreased hippocampal volume. For example, post-mortem studies on people with coronary artery disease (CAD), a type of cardiovascular disease (CVD) linked with high levels of stress, have shown a correlation between CAD and reduced volume in the hippocampus. One possible explanation is that stress has caused the reduced volumes in these parts of the hippocampus. In fact, there’s a wealth of evidence to show that stress can damage the hippocampus.

However, longitudinal studies and twin studies have also found that reduced volume in the hippocampus is a risk factor for increased levels of stress. Therefore, a small hippocampus could increase our chances of chronic stress and CVD because of its role in inhibiting our stress response.

Read more:

The level of detail in this post didn’t make it into our final cut of the book on stress because it would be overwhelming content for students in the limited time available. The main biological explanation for stress included in the book is the COMT gene. The limbic system (amygdala and hippocampus) and the PFC are also included. Also, the correlations in these studies aren’t conclusive enough to be overwhelming evidence, which is not as strong as other biological explanations of stress and CVD.

Key Study: Correlations between stress and hippocampal volume (Piccolo and Noble (2018)

MRI studies have shown that stress affects the hippocampus but it also works the other way, too.

Aim: The aim of this study was to see if there was a link between stress and hippocampal volume.

Methodsw: The researchers gathered data from participants across the US regarding their stress levels and their hippocampus volume. They used the Perceived Stress Scale to measure stress and an MRI machine to measure hippocampal volume.

Results: The results showed a negative correlation between perceived stress and left-hippocampal volume, i.e. higher perceived stress was associated with a smaller left hippocampal volume (-0.17). This connection remained consistent when socioeconomic factors like parental education and income were controlled for.

Conclusion: The study shows there’s a statistically significant correlation between perceived stress and hippocampal volume (albeit it’s a weak correlation). This suggests the two are linked and perhaps a small hippocampus is one risk factor for high stress.

Three of the most important parts of the brain in the stress response are the PFC, amygdala and hippocampus. (Image wikicommons: Patrick J. Lynch, medical illustrator; C. Carl Jaffe, MD, cardiologist).

The problem with this study, however, is that it’s correlational. It’s logical that the stress caused the shrinking of the hippocampus.

However, we cannot rule out the possibility that a small hippocampus could be a risk factor for chronic stress. War veterans often have smaller hippocampi than non-veterans and it was long believed to be a symptom of PTSD. However, a case-control study by Gilbertson et al. (2002) showed that the small hippocampus was more likely to be a risk factor for developing PTSD in the first place. These are war veterans and PTSD, though. What about regular chronic stress?

You can read more about Gilbertson et al. (2002) in the PTSD chapter of “IB Psychology: A Student’s Guide” (First Edition), or in this article “Biological Etiology of PTSD: Abnormalities in the brain.”

Key Study #2: Longitudinal study of stress and the hippocampus (Lindgren et al., 2016)

Evidence is emerging that suggests a small hippocampus could be both a symptom and cause of chronic stress. Source.

Aim: To find out if a small hippocampus was a cause or effect of stress.

Methods: This was a study on aging, memory and dementia that gathered data between 1988-2014 from 178 Swedish participants aged between 25-60. The participants filled out the “Perceived Stress Questionnaire” (PSQ) and underwent MRI scans. The researchers split the participants into two groups based on their PSQ scores: low perceived stress and moderate-high perceived stress group. They then compared their MRI results.

Results: The results showed that the participants’ stress levels were consistent over a 15-year period. The MRI data also showed the hippocampal volumes remained consistent between the two time points. However, the moderate-high group had on average smaller right and left hippocampal volumes at two time points. (Note: only the differences in right hippocampus volume was statistically significant (p=0.011), and the left hippocampal differences were not significant (p=0.11) although the trend was consistent).

Conclusion: This suggests that the smaller hippocampus is not an effect of the higher stress, but rather it could be a risk factor for stress.

These findings are similar to another longitudinal study on the stress and the hippocampus that followed 50 women for 20 years. They found that after 20 years of measuring stress, the women with higher perceived stress had smaller right hippocampi. (However, this study didn’t do a before and after check of the MRI, so they could not rule out the smaller hippocampus from the beginning.)

Animal studies show how the hippocampus affects the stress response, giving deeper understanding into why a small hippocampus is a potential cause of chronic stress.

While these studies show how the hippocampus is linked with chronic stress, like all correlational studies they give little insight into why. This explanation comes from animal studies. In these studies, lesioning the hippocampus results in higher anticipatory stress responses and prolonged activation of the HPA axis following stress. Similarly, electrical stimulation of the hippocampus helps reduce cortisol levels following a stressor, which suggests it’s helping to inhibit the activation of the HPA axis. From these animal studies, we get a better understanding of why the hippocampus is linked with stress.

It seems when it comes to the hippocampus and stress, it’s both simple and complicated. It seems that there’s a real possibility that reduced hippocampus volume is a risk factor for stress. It is also a consequence of chronic stress. In worst cases, it might be a vicious cycle – smaller hippocampus increases stress which further decreases the hippocampus, which makes stress worse, and so on and so on. The good news is we can apply our psychological knowledge about neuroplasticity to break this cycle. More on this in the following lessons.

Checking In: Can you explain how and why hippocampal volume is linked with perceived stress and cardiovascular disease?

Critical Thinking Considerations

  • Evaluating Correlational Studies: The above studies are correlational. But critical thinking means going beyond saying “correlation does not mean causation.” Can you explain alternative explanations of how either co-variable could be influencing the other, or how a third variable could explain the connection?
  • Correlation Strengths: You must also question the strength of the correlations. In Psychology a correlation above 0.6 is strong, around 0.4 is moderate and 0.2 is considered weak (remember that + or – 1.0 is the highest and 0 means there’s no correlation). Based on this, how confidently would you be explaining to someone that left-hippocampal volume is linked with perceived stress? (The weakness of these correlations is one reason why the studies didn’t make it into the book).

Learn More: An exciting new field of research is neurogenesis – the brain’s ability to grow new cells. Sandrine Thuret explains this phenomenon in her TED Talk, “You can grow new brain cells. Here’s how.”

Bibliography

The level of research needed to write accurately about stress for health psychology is why this eBook is proving very difficult to write. Hopefully it will be worth the wait. 

  • Barekatain, M., Askarpour, H., Zahedian, F., Walterfang, M., Velakoulis, D., Maracy, M. R., & Jazi, M. H. (2014). The relationship between regional brain volumes and the extent of coronary artery disease in mild cognitive impairment. Journal of research in medical sciences : the official journal of Isfahan University of Medical Sciences, 19(8), 739–745. (source).
  • Ebner, K., & Singewald, N. (2017). Individual differences in stress susceptibility and stress inhibitory mechanisms. Current Opinion in Behavioral Sciences, 14, 54–64. https://doi.org/10.1016/j.cobeha.2016.11.016 (source).
  • Gianaros, P. J., Jennings, J. R., Sheu, L. K., Greer, P. J., Kuller, L. H., & Matthews, K. A. (2007). Prospective reports of chronic life stress predict decreased grey matter volume in the hippocampus. NeuroImage, 35(2), 795–803. https://doi.org/10.1016/j.neuroimage.2006.10.045 (source).
  • Gilbertson MW, Shenton ME, Ciszewski A, Kasai K, Lasko NB, Orr SP, Pitman RK. Smaller hippocampal volume predicts pathologic vulnerability to psychological trauma. Nat Neurosci. 2002 Nov;5(11):1242-7. doi: 10.1038/nn958. PMID: 12379862; PMCID: PMC2819093. (source)
  • Lindgren, L., Bergdahl, J., & Nyberg, L. (2016). Longitudinal Evidence for Smaller Hippocampus Volume as a Vulnerability Factor for Perceived Stress. Cerebral Cortex, 26(8), 3527–3533. https://doi.org/10.1093/cercor/bhw154. source.
  • Piccolo, L. R., & Noble, K. G. (2017). Perceived stress is associated with smaller hippocampal volume in adolescence. Psychophysiology, 55(5), e13025. https://doi.org/10.1111/psyp.13025 (source)
  • Tawakol, A., Ishai, A., Takx, R. A. P., Figueroa, A. L., Ali, A., Kaiser, Y., Truong, Q. A., Solomon, C. J. E., Calcagno, C., Mani, V., Tang, C. Y., Mulder, W. J. M., Murrough, J. W., Hoffmann, U., Nahrendorf, M., Shin, L. M., Fayad, Z. A., & Pitman, R. K. (2017). Relation between resting amygdalar activity and cardiovascular events: a longitudinal and cohort study. The Lancet, 389(10071), 834–845. https://doi.org/10.1016/s0140-6736(16)31714-7. (source)