I guess we all know those people who seem to have a super stressful life, yet just don’t seem to care. Others however, are stressed out by literally anything. How come there are such huge differences in how we deal with stressful situations? In this blog post I would like to give you some insight into the behavioral and neural mechanisms of stress, how these can differ between individuals, and finally what you can do to improve your own capacity to deal with stress.

What is stress?

Just to be sure we’re on the same page, here’s how stress is usually defined and how it affects the body: you might not be aware of it, but your body is constantly trying to retain a dynamic equilibrium, or homeostasis. This is highly important for survival, as it ensures that the internal environment stays within the range where important metabolic chemical reactions can occur. This internal homeostasis is continuously challenged by so called stressors. These stressors can originate from inside or from outside your body. They disturb the equilibrium, forcing your body to react in order to restore homeostasis. Stress is therefore defined as a state where the equilibrium is threatened. [1, 2]

Therefore, when a certain threshold in the intensity or the duration of a stressor is reached, your body activates compensatory responses, leading to changes in the central nervous system (like an increase in arousal and attention) and in various peripheral organs and tissues (for example, your brain, heart and muscles receive more oxygen, and your heart rate and blood pressure are increased). This prepares you to either fight or flight the stressor. Maybe you have experienced these changes in your own body when you were stressed?

On a more molecular level, you can see an increase in glucocorticoids, which are a special type of hormones acting in the Hypothalamic-Pituitary-Adrenal axis. That’s a long name, but no worries – you don’t have to remember it, it is commonly abbreviated by HPA-axis anyway. The important thing to remember here is that the HPA-axis is the major hormonal circuit for the stress response. One example of a glucocorticoid released within this circuit is cortisol, which you might have heard of. [2]

Whereas short-term stress may sometimes even be beneficial and for example enhance learning and memory (You know that feeling, when somehow you need the pressure of the deadline being at midnight in order to get your stuff done?), chronic stress can lead to neuropsychiatric conditions such as anxiety and depression, but also to a variety of physical disorders such as diabetes, hypertension or obesity. [2, 3]

But why is this true for some people, while others seem to bounce back from hardship and trauma? In other words, why are some people more vulnerable to stress, while others have more resilience? This question is not so easy to answer – nor to research.

Difficulties in researching individual differences in stress

Imagine you are a neuroscientist and you pick two individuals to compare. The first one is vulnerable to stress, showing symptoms of depression or posttraumatic stress disorder (PTSD) after experiencing a prolonged phase of chronic stress or a traumatizing event. The other person is very resilient, she faced the same adverse events – but doesn’t suffer from them. It would be interesting to find out the reasons for this, but even if you could do any kind of research on them – you will never be able to disentangle what in the subject’s brain activity, brain connectivity or behavior is causing the vulnerability, and what arose because of the vulnerability and subsequent suffering. You would have to look at these two people before, and also after the traumatizing event and maybe you could find baseline differences that predict how they will deal with the stressor and how it will affect them in the long run.

Now of course you could just invite a bunch of people, test them, traumatize them, test them again and see how they dealt with it. Unfortunately, we can’t traumatize people just for the sake of our master thesis. Haha, just kidding. Luckily, we have ethics committees to prevent you from doing that!

However, what about researching a group of people that will very likely experience trauma in a certain period of time that is known in advance (without you as a scientist adding to that)? This is why soldiers are very hard sought subjects for stress research: You can test them before they are sent to a war zone and afterwards. The chances that they will experience traumatic events are very high – but not everyone will develop PTSD. You can thus first look at baseline differences between later to be known vulnerable and resilient subjects, and also look at structural and connectivity changes in the brain after the trauma.

Why are some people more vulnerable to stress?

But now to the interesting question: Why are some people more vulnerable, while others are more resilient? Not surprisingly, this depends on the interaction of both genetic and non-genetic factors. On a behavioral level, coping styles – the way you deal with stress – seem to have a major impact. Active coping, involving actively trying to solve problems and to deal with a challenge, facing fears and seeking social support, leads to greater resilience. Whereas a passive coping style – avoidance of conflicts, suppression of emotions, behavioral disengagement and denial – is maladaptive and does not provide long-term resilience to stress.

Other risk factors for a vulnerability to stress in adulthood are repeated episodes of uncontrollable stress during childhood such as neglect and physical or sexual abuse, whereas mild stressors that can be controlled and mastered even lead to increased resilience to future stressors. A reliable and safe environment during childhood and a secure attachment to the parents were also found to promote resilience. [4-6]

On a neural level, there are different circuits that are associated with inter-individual differences in reactivity to stress. For instance, the finding that women are more prone to stress-related disorders than men can be explained by sex differences in the HPA-axis (remember, the hormonal stress-circuit). Hormone secretion in the HPA-axis is in part mediated by the sex hormones estrogen (increasing stress hormone secretion) and testosterone (attenuating it).

That could explain why 31% of women, but only 19% of men who experience traumata develop PTSD. In a recent study with only male participants, within-sex-differences have also been found: Whereas those participants with high stress-induced cortisol responses were also more sensitive to stress, a higher basal cortisol level was associated with stress resilience. Thus, high basal cortisol might be a protective factor, while those individuals with low basal levels need to have a larger homeostatic adjustment in response to the stressor. [4, 7, 8]

Two brain areas are tightly intertwined with HPA-axis functioning: the hippocampus (a region that is important for storing memories) and the medial prefrontal cortex (mPFC; also commonly associated with memory consolidation and emotion regulation). The hippocampus seems to be modulated by stress hormones and in turn exerts a regulatory control over the HPA-axis. Specific receptors of the neurotransmitter glutamate located in the hippocampus are more present in vulnerable individuals, while other glutamatergic receptors are more abundant in resilient ones. Moreover, the expression of certain proteins in the hippocampus has been associated with resilience as well.

Likewise, the mPFC suppresses HPA-axis activity, thus attenuating stress. The ventral (lower) part of the mPFC is suggested to play a role in the acquisition of resilience as a complex cognitive process involving the learning of a coping response. The implication of these two areas in both memory and stress might suggest a connection between the two. Maybe that could explain the paradox that, although emotional events are usually better remembered than unemotional ones, some people have no memories of traumatizing (surely very emotional!) events. What do you think? [4]

Lastly, there are also genetic and epigenetic factors involved in stress resilience and vulnerability. Specific genes have been identified that are associated with either stress susceptibility or resilience and there are also natural variations in the epigenetic profile leading to an innate predisposition to stress. So what is epigenetics? Imagine the DNA being a long rope with some knots in it. Wherever these knots are, the information contained in the rope cannot be read, however, it is still there. These knots can be untied or formed without affecting the rope itself.

Coming back to cells and genes, this means that some parts of the DNA are “switched off” and not expressed, or “switched on” and expressed. The addition of one knot at a specific location of the rope is equivalent to the methylation of a specific part of the DNA. Importantly, changes in gene expression can be produced by environmental conditions and can be made without having actual changes in the DNA. But not only does your epigenetic profile determine how you react to stress; stress can also lead to changes in the “pattern of knots”. And these changes in the epigenetic profile can even be inherited to your children and grandchildren! So whether you are stressed out by that upcoming exam or not might depend on what your grandmother experienced when she was a child. Fascinating, right?! [4, 9]

What can you do to improve resilience?

Okay, I know – you are waiting for the answer to the big question: What exactly can you personally do to improve your own resilience or reduce your vulnerability to stress? On the level of genetics or brain physiology, probably not much – at least not directly. You would have to tackle the problem behaviorally, thus leading to changes on a neurophysiological and epigenetic level.

In the treatment of depression and PTSD, there are some strategies shown to be very efficient in improving resilience – why shouldn’t they improve your resilience preventively? Observing your own cognitive and behavioral reactions to stress and detecting distorted negative appraisal can help you to replace these distortions with more realistic and positive appraisals. Another effective strategy is to adapt an active coping style: If you remember, this means facing your fears, trying to solve your problems and dealing with challenges. Looking at things from an optimistic angle. If you realize you are not able to solve this problem alone, seeking social support. At last, experiences with situations where you were able to deal with the stress can furthermore strengthen your resilience to future threats. By surviving these mild stressors, you will be steeled for future ones. [4, 6]

What can we conclude from this? First of all, there are inherited differences and early environmental influences that you will probably not be able to change. However, there are a couple of things you can do on a behavioral or cognitive level which might even have an impact on neurobiology that might help you to strengthen yourself against future stress.

References

1. Chrousos, G.P. and P.W. Gold, The concepts of stress and stress system disorders. Overview of physical and behavioral homeostasis. JAMA, 1992. 267(9): p. 1244-52.
2. Chrousos, G.P., Stress and disorders of the stress system. Nat Rev Endocrinol, 2009. 5(7): p. 374-81.
3. Yuen, E.Y., et al., Acute stress enhances glutamatergic transmission in prefrontal cortex and facilitates working memory. Proc Natl Acad Sci U S A, 2009. 106(33): p. 14075-9.
4. Franklin, T.B., B.J. Saab, and I.M. Mansuy, Neural mechanisms of stress resilience and vulnerability. Neuron, 2012. 75(5): p. 747-61.
5. Sherrer, M.V., The role of cognitive appraisal in adaptation to traumatic stress in adults with serious mental illness: a critical review. Trauma Violence Abuse, 2011. 12(3): p. 151-67.
6. Southwick, S.M. and D.S. Charney, The science of resilience: implications for the prevention and treatment of depression. Science, 2012. 338(6103): p. 79-82.
7. Young, E. and A. Korszun, Sex, trauma, stress hormones and depression. Mol Psychiatry, 2010. 15(1): p. 23-8.
8. Henckens, M.J., et al., Interindividual differences in stress sensitivity: basal and stress-induced cortisol levels differentially predict neural vigilance processing under stress. Soc Cogn Affect Neurosci, 2016. 11(4): p. 663-73.
9. Kellermann, N.P., Epigenetic transmission of Holocaust trauma: can nightmares be inherited? Isr J Psychiatry Relat Sci, 2013. 50(1): p. 33-9.

Picture 1: Jean Pierre Gallot (flickr.com)

Picture 2: Defense-Imagery (pixabay.com)

Picture 3: Henry Vandyke Carter [Public domain], via Wikimedia Commons

Picture 4: Giraphic_Design (pixabay.com)