Resilience: Seeking Out Rambo-DNA

14. June 2016

What makes up a person who doesn't succumb to a stress load despite it being constant? Resilience is considered a character trait that over the course of life can change again and again. Stress researchers have helped make an ever clearer picture emerge of what happens in the brain.

Only the toughest survive. Those who survive tragedies and crises without major damage are the ones who in the long run will prevail. Not only in evolution, but probably also in their own careers and through their resistance to depression and burnout. Is this hardiness, this capacity to “put up with and deal with things”, congenital or acquired? Can it be learned? The origins of this phenomenon, labelled by specialists with the term resilience, are still largely unknown.

No innate virtue

Until a few years ago the following theory was still a valid one: anybody who, after a serious trauma, comes quickly to his or her feet without mental impairments such as depression or post-traumatic stress disorder (PTSD), should be regarded as being innately resilient. Since then, the view has changed somewhat. Nowadays, resilience is no longer seen as an innate virtue or talent to more easily survive crises. Successfully handling traumatic life events is something able to be learned and is considered a dynamic process – a capability, which can also be lost again. Studies of seemingly mentally tough people and of laboratory animals have helped form an even clearer picture of what happens in the brain – as well as in the periphery of the body.

Stress does not always translate as harm for the body and soul. Similarly to sports, acute stress stimulates the central nervous system to deal with a threat and to seek an appropriate way to get through the challenge. If the threat however becomes a continuous danger, the state of “constantly being on one’s toes” alters the regulatory mechanisms in the brain. The constant tension then not only paves a path for psychological problems, but increases the risk of disturbances in the cardiovascular system. Chronic stress leads in the long run to depression and burnout.

High-affinity and low-affinity receptors

Meanwhile, it seems clear that chronic stress diminishes cortisol and glucocorticoid receptors in the hippocampus of test animals, as it does the production of nerve growth factor BDNF, which also plays a special role in memorisation and recall as mental faculties. The release of BDNF in contrast promotes the capacity to process stress without getting depression.
Between the hippocampus and the ventral tegmental areal (VTA) there exists a closed regulation circuit. BDNF has exactly the opposite effect there and is associated with depression.

Both the hippocampus and amygdala possess a large number of high-affinity cortisol receptors, which react rapidly to acute stress. The corresponding receptors in the frontal lobe, our tool for planning and controlled reaction, have a many times lesser affinity. They only enter into action after the first major stress reaction wave, due to cortisol, has already subsided in the hippocampus and amygdala. Using these two types of receptors, the brain creates a kind of buffer. Up to a certain level of stress the stimuli activate a memory storage, which will facilitate the renewed reaction the next time. Furthermore, in the instance of constant high tension, the low-affinity receptors are also occupied and the memory does not even know how to start dealing with this stimulus flood.

Capped compounds

Short-term stress causes neural stem cells to provide additional neurons that are ready for use within two weeks – in the event that the attack on the mental faculties should recur. Chronic stress not only reduces the formation of new nerve cells, but also suppresses the linking nerve fibres and clips through the dendritic branching of neurons.

In the presence of a constant high stress load, the complex stress-control system dysfunctions. With a shrinking hippocampus and a growing amygdala, the command centre of the body no longer manages to estimate the extent of the threat correctly: for phobia patients everything becomes a threat; with burnout and depression the reaction malfunctions in the presence of any perceived danger.

Methyl groups control stress response

Experts estimate that the risk of depression is 40 – 60 percent hereditary. What might this figure be with respect to resilience? In any case, it seems that stressful life events are reflected in the expression of certain genes – in the form of various methylation specific DNA segments. In mice that were nurtured by solicitous mothers, receptors for stress management in the hippocampus are far less methylated than in individuals with negligent mothers. Their response to the stress is therefore much slower. This observation holds true not only for four legged beings. “The response to stress”, says Daniela Kaufer from the University of California in Berkeley, “is one of the most conserved structures of evolution”. And her colleague Kieran O’Donnell from Montreal provides confirmation: “When making a comparison to mice we see the same DNA methylation changes in the hormone receptors in humans who had a difficult childhood”.

More recent findings show that all along the hypothalamic-pituitary-adrenal axis (HPA) methylation processes help steer subsequent hormone distributions and the response to stress. Yet trauma and continuous stress are astonishingly not only specific to certain control centres in the brain, but can also be detected in the relevant genes in the lymphocytes of the periphery. Might it perhaps be enough in the future to have a blood test in order to detect mental disorders?

Snuggling to counter small causes of trouble

Complete avoidance of all stresses is of no benefit to development and social behaviour. This is shown by experiments on rats [Paywall] which were immobilised briefly in a sack. This rather unpleasant experience induced a rather bonding experience between the respective animal and its cage mates. They helped each other in their grooming and shared a limited water supply. Blood oxytocin-levels rose significantly in their circulatory system. All that however changed abruptly when additional stress loads were forced upon the rats over and above this moderate stress. If the rodents also detected the scent of a fox – their natural enemy – their stress levels jumped over the critical limit. Both social behaviour as well oxytocin-levels indicated that they had become completely terrified animals. It’s well comprehended that the same occurs in the human system as well. Positive social behaviour in the group strengthens the resilience to sporadic stress and the members’ processing of it. If there is too much of this stress, this easily leads to a post-traumatic stress disorder.

Another experiment confirmed the findings: whenever a test animal ends up facing a Goliath animal, one bred for size and aggressiveness, the test animal no longer has a preference for being in a community after this traumatic experience, even if this community is one made up of smaller peaceful companion animals.

Resilience genetic markers?

What has all this to do with resilience? What makes up resilient people? Perhaps, as many stress researchers now believe, the answers to these questions lie in the genes. People who, like other animals, can adapt to a rapidly changing environment are rather likely to show another epigenetic pattern in the stress management centres of their brain. Even among rodents in the laboratory, there are always animals which cannot be so easily intimidated by aggressive cohabitants, which can deal with the presence of the odour of their worst enemy, and despite this are still there for the community. Neurobiologist Eric Nestler of Mount Sinai School of Medicine New York hopes to find recognition of this in the form of typical methylation patterns for hormone receptors.

The trail of clues might then perhaps lead us further and take us to the factors that produce this situation. In any case, this characteristic seems not to be innate, but rather one that over the course of life can change every now and again. For those who possess too little of it, the recommended guidelines in the future might be to take a resilience inducer instead of an antidepressant.

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Medicine, Neurology, Psychiatry

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