Stress and the Brain: What Makes Some of Us More Vulnerable Than Others?

Report from FENS Forum of Neuroscience
Moheb Costandi, M.Sc.
October 4, 2010

Some people can overcome traumatic experiences, while others are less resilient, developing psychiatric conditions such as depression and post-traumatic stress disorder (PTSD). Why such variation? Researchers at a symposium held at the Federation of European Neuroscience Societies (FENS) meeting in Amsterdam this summer tried to tease out some of the reasons.

Exposure to stress causes fundamental changes in the state of the brain, and the brain’s response to stress differs widely among individuals, said Guillén Fernández of the Donders Institute for Brain, Cognition, and Behaviour in Nijmegan, Holland. Traumatic events cause stress hormones such as cortisol to be released from the hypothalamus, leading to the short-term heightened vigilance we need to quickly respond to threats in the surrounding environment. But in people who are more vulnerable to stress, vigilance levels remain high long after the stressful situation has ended. 

In a recent study published in Proceedings of the National Academy of Sciences, Fernández and his colleagues provide the first evidence that a person’s sensitivity to acute stress is determined by variations in the gene encoding the α2b-adrenoreceptor (ADRA2B).

The researchers induced acute stress in their study volunteers by showing them violent movie scenes and asking them to imagine that what they saw in the scene was happening to them. Using functional magnetic resonance imaging (fMRI), they monitored the brain’s response, focusing on the amygdala, which is central to the brain’s stress response and which is also known to be involved in detecting threats and in encoding emotional memories.

The participants who carry a common variation in the ADRA2B receptor had higher amygdala activity in response to the induced stress than those who do not. These subjects also showed more connectivity between the amygdala and other components of the brain’s stress circuitry, leading to heightened responses to photographs of angry, fearful, and happy faces.

“These people are more cautious and probably tend more to stay away from danger,” says Fernández, “and we are currently investigating whether they are also more prone to developing PTSD after experiencing a real trauma.”

Fernández also described new data obtained from soldiers who have returned from deployment that suggest how environmental factors may contribute to stress vulnerability. This study, which is yet to be published, shows that soldiers exposed to more perceived threats during their deployment exhibited increased brain activity in response to emotional stimuli, as well as enhanced connectivity between the amygdala and another brain region, the insula, which also is involved in the stress response.

Research led by Dominique de Quervain of the University of Basel in Switzerland is starting to spell out how stress hormones affect the way memories are stored (consolidated) and retrieved. We remember emotionally arousing memories better than less-emotional ones; de Quervain’s team showed in research published in 2007 that this is due to variations in the ADRA2B receptor.

More recently, de Quervain’s group has demonstrated that acute stress induces elevated levels of the glucocorticoid hormones, leading simultaneously to better consolidation and worse retrieval of emotional memories. These mechanisms appear to help retain important information while at the same time reducing the possible maladaptive behavioral effects of traumatic memories.  

The researchers have also discovered that people who have PTSD have reduced blood levels of the stress hormone cortisol, and that in one case, that of a 50-year-old terrorist attack survivor, cortisol treatment reduced traumatic memories.  So while a variation in the ADRA2B receptor is associated with enhancing the formation of emotionally-laden memories, cortisol appears to be involved in facilitating their extinction. In support of this, de Quervain have also shown that cortisol reduces the fear induced in response to social stressors in people who have social phobias, and that cortisol treatment in combination with behavioral therapy is more effective in reducing the fear of heights than therapy alone.

Passing along sensitivity to stress

Only a small number of people who are exposed to traumatic experiences go on to develop PTSD. Rachel Yehuda, a professor of psychiatry and neuroscience at the Mount Sinai Medical Center in New York, described her research showing that vulnerability to stress can be transmitted from one generation to the next by epigenetic mechanisms (which change the expression of a gene without changing the gene itself).

Several years ago, Yehuda found that the children of pregnant 9/11 evacuees who subsequently developed PTSD have higher cortisol levels than those whose mothers did not develop PTSD. More recently, she and her colleagues have shown that children whose mothers were traumatized as a result of 9/11 show increased distress in response to novel stimuli 2 years later. The children who reacted the most strongly were those whose mother’s trauma was experienced during the second and third trimesters, suggesting that there may be a window of stress vulnerability.   

Fathers who experience PTSD also seem to pass on an increased risk of anxiety, depression, and substance abuse to their children, she said, an effect that also appears to be mediated by the stress hormones. It is still not clear whether affected children can transmit the effects on to their own children.   

 “Epigenetic factors may explain why some people are more vulnerable to developing PTSD following exposure to trauma,” said Yehuda. “Our research helps to identify more precise targets of intervention in PTSD, by knowing the neurobiological cause of the symptoms. If what needs to be ‘reversed’ are biological alterations associated with risk, this will give us a better idea of how to develop biological strategies for treatments.”