What Came First: The Chicken (Chronic Stress) or the Egg (Brain Abnormalities)? 2

Now, on a more serious note…

We live in a society in which other people are constantly putting pressure on us to perform. To be better. To be smarter. To be richer. To be thinner. To be more productive. To be more attractive. To accomplish more at work. To be a leader. To know when to stop coming up with examples because your reader probably gets the point. We often internalize these external pressures in the form of stress and anxiety.

Unlike the acute stressors that I discussed in post #1 and post #2, sometimes these sources of stress don’t go away. Depending on the length and severity of various sources of stress in our lives, we can become chronically stressed. Although there is no universally accepted definition of what constitutes chronic stress, I would define it as prolonged psychological discomfort and associated behavioral changes that are brought on by internal or external sources of stress (Whaddaya think? Worthy of Wikipedia?). In the literature, a lot of different circumstances constitute chronic stress. In one study, chronically stressed adults were diagnosed as so because they had a psychological reaction to working 60-70 hours per week for several years (Jovanovic, Perski, Berglund, & Savic, 2011). If that isn’t chronic stress, I don’t know what is. In another study, childhood poverty was considered a source of chronic stress (Kim et al., 2013). Despite this variety in what researchers have defined as “chronic stress,” findings regarding the effects of chronic stress on the brain have converged in some interesting ways. I’ll briefly review these findings and provide some specific examples, with the goal that you will be better able to understand how chronic stress affects the brain. Lastly, I’ll talk about why chronic stress and the associated brain abnormalities are a “chicken or egg” problem.

Perhaps the most oft-demonstrated brain abnormalities associated with chronic stress are reduced volume and/or functioning of the frontal lobes and hippocampus (see Lupien, McEwen, Gunnar, & Heim, 2009). I find it hard to wrap my head around broad statements like that without proper context, so I’d like to mention a few empirical studies that have demonstrated these findings:

1. In their longitudinal study, Kim et al. (2013) investigated the relationship between childhood poverty at age 9 and brain activation during emotion regulation at age 24. These are the researchers I previously mentioned who considered childhood poverty to be a source of chronic stress. They found that 24-year-olds who were impoverished as children had reduced activity in the pre-frontal cortex and the amygdala, and that this link was mediated by chronic stressor exposure during childhood.
2. Ansell et al. (2012) measured chronic stress by having participants answer questions about stressful life events, and then scanned their brains using fMRI. They found that people who reported more experiences of chronic stress and greater numbers of adverse life events had decreased volume in pre-frontal areas (orbitofrontal cortex, subgenual area, anterior cingulate, and right anterior insula, in case you were wondering).
3. Lupien et al. (2005) followed 51 older adults (ages 60+) over 10 years, measuring their cortisol levels every year. They found that individuals who demonstrated consistently high or temporally increasing cortisol levels (i.e., people who were likely chronically stressed) had a 14% smaller hippocampus than those who demonstrated moderate, non-increasing cortisol levels.

Considering these findings, it’s tempting to attribute the brain abnormalities related to chronic stress as evidence that chronic stress causes these deficits. This would be consistent with the neurotoxicity hypothesis, which posits that when our neurons are chronically assaulted by stress hormones, their ability to resist damage from other toxic influences is diminished (see Lupien et al., 2009). Thus, brain regions that are especially receptive to stress hormones, like the hippocampus and pre-frontal cortex (see post #2), are damaged by stress.

On the other hand, it’s important to consider the opposite perspective: the vulnerability hypothesis. This hypothesis proposes that the smaller hippocampus observed in chronically stressed adults may be a pre-existing abnormality instead of the result of stress (see Lupien et al., 2009). That is, a person’s genetic make up or early-life exposure to stress may result in an underdeveloped hippocampus and/or prefrontal cortex (PFC), which could leave him or her more vulnerable to chronic stress in later life.

So… we’re left with a “chicken or egg” problem. Chronic stress is clearly associated with reduced hippocampal and PFC volume and/or functioning. However, as Lupien et al. (2009) show in their review on the topic, there is substantial research that supports both the neurotoxicity and vulnerability explanations for these findings. To put this debate to rest, it would probably require that researchers follow a large sample of people across their lifespans, taking annual stress measures and fMRI scans. An investigation like this could identify chronically stressed individuals, and then determine when in their lives they began to exhibit brain abnormalities in comparison to “normal” individuals. But until then, I think, based on the logic presented in the scientifically sound cartoon from the beginning of this post, we can assume that abnormalities came before stress. Well, okay. Maybe only in the dictionary.

References:

Ansell, E. B., Rando, K., Tuit, K., Guarnaccia, J., & Sinha, R. (2012). Cumulative adversity and smaller gray matter volume in medial prefrontal, anterior cingulate, and insula regions. Biological Psychiatry, 72(1), 57-64. doi:http://dx.doi.org/10.1016/j.biopsych.2011.11.022

Jovanovic, H., Perski, A., Berglund, H., & Savic, I. (2011). Chronic stress is linked to 5-HT1A receptor changes and functional disintegration of the limbic networks. NeuroImage, 55(3), 1178-1188. doi:http://dx.doi.org/10.1016/j.neuroimage.2010.12.060

Kim, P., Evans, G. W., Angstadt, M., Ho, S. S., Sripada, C. S., Swain, J. E., . . . Phane, K. L. (2013). Effects of childhood poverty and chronic stress on emotion regulatory brain function in adulthood. PNAS Proceedings of the National Academy of Sciences of the United States of America, 110(46), 18442-18447. doi:http://dx.doi.org/10.1073/pnas.1308240110

Lupien, S. J., Fiocco, A., Wan, N., Maheu, F., Lord, C., Schramek, T., & Tu, M. T. (2005). Stress hormones and human memory function across the lifespan. Psychoneuroendocrinology, 30(3), 225-242. doi:http://dx.doi.org/10.1016/j.psyneuen.2004.08.003

Lupien, S. J., McEwen, B. S., Gunnar, M. R., & Heim, C. (2009). Effects of stress throughout the lifespan on the brain, behaviour and cognition. Nature Reviews Neuroscience, 10(6), 434-445. doi:http://dx.doi.org/10.1038/nrn2639

The ‘CHICKEN’ comes before the ‘egg’! Why? (2014, March 1). Retrieved November 18, 2014, from http://kingdomecon.wordpress.com/2014/03/01/the-chicken-comes-before-the-egg-why/