PTSD Recovery: Do genes make the difference?

4. February 2013

Survivors of disasters or abused children: they are all candidates for stress disorder following trauma. Yet some victims brush aside low blows in their lives seemingly effortlessly. Do they have better genes?

He was born early last century as an illegitimate child of a saleswoman and for that reason frequently teased. During the war he had to flee several times and repeatedly establish a new identity. After that he started his political career and became not only Chancellor, but also received the Nobel Peace Prize: he is Willy Brandt. She was held captive for more than 3,000 days – eight years – as a child and tortured repeatedly by her kidnapper. Nevertheless, she is now, four years after her escape, self-confident and full of plans for her future life: she is Natascha Kampusch. What do the two have in common?

PTSD: disrupted communication between reason and emotion

Both seem to be particularly resistant to blows. Just as it is with people who, despite having terrible superiors, bring excellence to their work, or with women who, having been raped, despite everything again feel pleasure in sexuality. Is there such thing as a “resilience gene” which lends protection against post-traumatic stress disorder (PTSD)? In the U.S., more than half of all people at some point in their lives have a traumatic experience, whether it be as victim of a crime, an accident or a natural disaster. Almost one in ten of them develops PTSD. Those who are older master crises more easily than younger people. Twin studies suggest that the genetic contribution to a risk for this condition lies at 32-38 percent.

In the brain, when instances of depression resulting from personal experiences occur, the region including the pituitary gland, the hippocampus and amygdala in particular plays a large role. The amygdala attaches a “feeling-label” to the incoming perceptions, thus linking it to an impulse with pleasant or unpleasant memories. While in depressed people the amygdala is hyperactive, in these people the brain suppresses the operation of the rational mind in the prefrontal cortex (PFC). As PTSD expert Kerry Ressler of Emory University in Atlanta found, the connections between the limbic system and PFC are stronger in resilient people who have experienced a trauma than in those who are sensitive.

Close friendship promotes resilience

One of the pioneers of research on resilience was Emmy Werner. She examined the lives of people who were born in 1955 on the Hawaiian island of Kauai. 200 of them had a very difficult childhood, with parents who were living in poverty or were addicted to alcohol or drugs. One third of these children, however, managed to make a leap into a better world – not just temporarily, but permanently. Werner’s studies recognised several factors that strengthened their internal resistance to external adversities. The children managed to build up a close relationship with at least one adult caregiver: a teacher, neighbour or relative. At least one person served as their role model for how even large problems could be constructively solved. Finally, they had the experience of “self-efficacy”: overcoming external opposition using their own forces, so that the situation turned for the better.

Defective hormone control ensures depression

People who manage not to feel at the mercy of adversity also often have different genes. Avashalom Caspi of King’s College London discovered in a study of 1,000 people on New Zealand South Island a commonality in the genotype for the serotonin metabolism in the brain, the regulatory factor 5-HTTLPR. The short allele and a base exchange in the long allele may increase the risk of depression, especially after traumatic events. The finding is not entirely uncontroversial: a later study found no association between gene and mood. Another candidate is FKBP5, a modulator for the docking of cortisol, a glucocorticoid receptor. In depressed people, a large proportion of these genes are demethylated and thus expressed as protein. Torsten Klengel from Munich’s Max Planck Institute of Psychiatry speculates on the mechanism “Trauma in childhood leaves, depending on genetic predisposition, permanent marks on the DNA. Epigenetic changes in the FKBP5 gene amplify its effect. The presumed consequence is a sustained dysregulation of the stress hormone axis of those affected, which can end up in a psychiatric illness.” In a paper published in Nature Neuroscience he described, together with his colleague Elisabeth Binder, a study of some 2,000 traumatised Afro-Americans in the United States. The result: the worse the trauma, the greater the risk of PTSD, but only for those who possess a particular variant of this gene. In all likelihood the respective allele contributes to the sensitivity of the amygdala-hippocampal-pituitary connection.

Neurotransmitter determines the effect of mutations

Those who want to study the response to adverse life events more than only retrospectively must resort to experiments using animals. A logical way was therefore to breed mice and rats according to their treatment of trauma and then look for specific markers in their genes. Malfunction in the production of CRH (corticotropin releasing hormone) and one of its receptors seems to make the rodents over-anxious and depressed. An elevated level of the hormone is responsible for less sleep and high stress sensitivity. An inactive receptor, however, decreases the fear. All this however depends on which area is disturbed in its hormone metabolism. Knockout mice, in whom the receptor for serotonin or GABA-producing neurons is absent, behave normally, while the same mutation in glutamatergic neurons makes their owners fearless. The amygdala and hippocampus are then less active. With dopamine-producing nerve cells the exact opposite effect occurs. Dopamine production is markedly reduced. Several groups at Munich’s Max Planck Institute are working in the field of neurology of fear and have described in their publications other factors which play a role in the response to stress.

Pill for recurring fear?

What can PTSD therapy aim to achieve? Is there a pill against recurring fear even at low trigger threshold? A Cochrane review from 2009 attests that trauma-focused behavioral therapy and the Eye Movement Desensitisation and Reprocessing approach (EMDR) have the highest chances of success. With children, cognitive behavioral therapy, it seems, acts equally effectively against the shock of abuse or a terrible experience. There is in constrast still a lack of convincing evidence for psychotropic drugs as a promising therapeutic option. With increasing knowledge about the biochemical processing of intrusive experiences in the brain that could however change. German publication on psychology “Gehirn und Geist” quotes Rainer Landgraf from MPI as saying: “A simple resilience pill will not exist, but maybe one day some cocktail may.”

Small window of time for therapy

Previous studies indicate that behavioral training and some antidepressants cause very similar changes in the brain. What is important, Thomas Agren of the University of Uppsala writes in the September edition of Science, is the point in time of “fear release” after the trigger. One can one hour after the confrontation with the key stimulus, potentially erase the memory trace in the amygdala by presenting the stimulus without the associated shock. After half a day that does not work anymore, and particularly not after 24 hours.

In any case, according to statistics, two-thirds of those affected by PTSD recover from it sooner or later. With regard to children, we are still benefiting from what was learnt by Emmy Werner on Kauai. Whoever experiences that a crisis is not insurmountable, but that he or she can overcome it with his or her own resources, has strengthened his or her defenses against future storms – especially if the person knows that in the worst case he or she is not alone, but can rely on the support of trusted friends.

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