The Frontal Cortex

The Stress Vaccine

Stress has been a hot topic lately. In the past week, we’ve looked at how chronic stress can trigger working memory deficits among the poor and lead, eventually, to severe depression. But there’s hope, at least if you’re a stressed out lab rat. (In theory, these findings should apply to humans, but there’s always that nagging gap between theory and reality.) The work is led by Robert Sapolsky, the incredibly engaging and eloquent primatologist and writer.

The experimental strategy strategy is ingenious. The scientists begin by inserting “neuroprotectant” genes, such as estrogen, into a modified version of herpes simplex virus. Why herpes? For starters, the virus is able to quietly enter nerve cells. Ordinarily, this viral invasion would lead to an acute infection and cell death. But Sapolsky and his team have engineered the virus so that it can’t multiply and commandeer the cell. Instead, it just lurks in the nucleus, waiting to be turned on and express these protective snippets of DNA.,

Here’s where the idea really gets brilliant. It’s been known for some time that many viruses, like herpes, wait until our stress hormones are elevated before they become active and multiply. This increases the chances that the viral infection will defeat, at least for a few days, the defensive efforts of our immune system, since stress suppresses the immune response. In other words, when the rat is happy and relaxed, everything is normal – the virus and its estrogen genes are utterly inactive.

But now let’s say something stressful happens. Perhaps the rat is subjected to some fear conditioning, or maybe a cerebral artery is ruptured and the brain is deprived of oxygen. At this point, the herpes virus senses the elevated stress hormones and switches into action. Within hours, it’s able to start generating neuroprotective proteins which, at least in the rat, seem to limit the extent of cell death and damage. The carnage remains local. According to some preliminary experiments, rats given the herpes treatment were able to stave off practically all cell loss, while control rats lost nearly 40 percent of neurons in a given region.

At the moment, of course, such a stress vaccine remains entirely hypothetical, at least for humans. (And this is one of those treatments that I definitely want medicine to perfect before clinical trials begin. It wouldn’t be fun to have errant herpes viruses rampaging through the cortex, pumping out estrogen for no good reason.) But I think there’s good reason to hope that, someday, we might be able to design treatments which eliminate the most devastating parts of the chronic stress response. This vaccine won’t guarantee happiness, or protect against acute stress, but it just might let us outsmart the worst parts of the fight or flight response.

Thanks to Arielle for the tip!

Comments

  1. #1 Pierre Roussin
    April 10, 2009

    People will line up for thi vaccine!!!

  2. #2 Gary Gurney
    April 10, 2009

    I love neuroscience and am all for advances that improve the quality of life in a very hectic and alienating modern culture.

    However, the implication of this post is that there is really nothing we can do about our sympathetic responses to a given situation and the resulting stress of that response. It’s based on a false belief that stress is caused by things and events that we experience. Stress is not what happens to us. Rather, it is how we (our whole organism) respond to any given situation. Does everyone get stressed out by the same set of circumstances? Obviously not, and we can observe that some people are much better at self regulating and not getting “stressed” than others. Much of this has to do with habitual ways of perceiving and relating (and the resulting nervous system response), often learned from infancy, and later, childhood.

    There seems to be an assumption that we have no control over our nervous system and its responses to events. In only the most extreme cases is this true–and that’s good, because our sympathetic response is meant to ensure survival in face of dire threat to the organism.

    In nearly all aspects of life, humans can learn to regulate their nervous systems and find the (internal) resources to opt out of unnecessary sympathetic responses regardless of the external circumstance.

    There are whole fields of somatic therapy that work with learning to become aware of, negotiate skilfully and regulate one’s sympathetic/parasympathetic response. This is not exotic New Age stuff. It is simply re-learning to become aware of our birthright as mammals and pay attention to important signals in our bodies through the felt sense. Sadly, this inherent felt sense (which is critical information for our organism) has been deemed unimportant in our culture to the point many don’t even know about it. The result of this is a widespread lack of feeling healthy and vital coupled with chronic and persistent anxiety for far too many of our fellow humans.

    Respectfully,
    Gary Gurney
    Portland, Maine

  3. #3 OftenWrongTed
    April 10, 2009

    Stress; as defined by Dr. Hans Selye: “Stress is the nonspecific response to the body to any demand made upon it”. Vaccinated, a user might not be able to respond in a flight or fight situation.
    “The Stress of Life”, by Dr. Hans Selye, ISBN: 0397010265.

  4. #4 OftenWrongTed
    April 10, 2009

    Stress; as defined by Dr. Hans Selye: “Stress is the nonspecific response of the body to any demand made upon it”. Vaccinated, a user might not be able to respond in a flight or fight situation.
    “The Stress of Life”, by Dr. Hans Selye, ISBN: 0397010265.

  5. #5 Ian Bradley
    April 10, 2009

    What an elegant study. There are so many next steps, but one interesting idea would be to link the neuroprotective aspects to behaviour. Fior example, one wonders if such viral “treated” rats might be less vulnerable to a learned helplessness paradigm.

    Great blog!

  6. #6 adina
    April 10, 2009

    Do oral contraceptives reduce stress? I didn’t know that estrogen can be neuroprotective.
    Anti-male joke in 5, 4, 3….

  7. #7 just doug
    April 10, 2009

    …or you could have it instead release testosterone during stress and use it to augment your viagra popping social life. Which version do you suppose would sell for more?

  8. #8 jb
    April 11, 2009

    Amen to Gary. The fact that someone responds to stress by getting phyically or mentally ill is a message from the universe that the person needs to change their behavior. It’s like putting your finger in a flame; it hurts. The proper response to that message of pain is to take your finger out of the fire, not to take a vaccine that will take away the pain. The pain may disappear due to the vaccine but so will your finger as you ignore the message and persist with the behavior.
    For those who have trouble with the universe sending messages, it’s actually one part of your brain talking to another part. And the rats also have a voice.

  9. #9 Martin
    April 11, 2009

    Very good article, nice experimental design.

    I love studies that try to build a bridge between biological processes (inside the cell) and psychophysiological processes (stress). However I have one remark that is probably more philosophical than deep scientific: Stress is not only a symptom, but an important marker, that your system called life includes too many dysfunctional processes.

    As such stress, in my opinion, in neither negative nor positive, but it is just a feedback from the psych and the nervous system that too much information is blocking the data-highway. In terms of the Internet, think: DoS-attack.

    Suppressing this feedback could have bad effects, because you take away important feedback from the system. This might stabilize the system (your body & psyche) for a while, because there is no need te react anymore to external threads. However we can see with complex systems (such as a human being) that bad or missing feedback will ultimately lead to the collapse of the system.

    In that sense: Cool that we gather this knowledge, but lets be prudent with promising an ultimate solutions (which seem to turn out worse that everyone thought…think of nuclear energy…).

  10. #10 jb
    April 11, 2009

    PS Thanks for getting your comment mode up and running again, Jonah! It’s an important part of this blog.

  11. #11 Gary Gurney
    April 11, 2009

    To Martin,
    You make a good point in you comments.

    “As such stress, in my opinion, in neither negative nor positive, but it is just a feedback from the psych and the nervous system that too much information is blocking the data-highway.”

    I don’t agree however that “too much information” blocks the highway. People who have high sympathetic set points frequently pay attention to and spend energy on information that is not helpful to their goals as a human. The nervous system has learned to respond to information that is not necessarily a threat and ends up taking over a large part of one’s attention to the point where she becomes unable to function appropriately.

    For instance, if someone has “social anxiety disorder” they experience anxiety in a crowd of strangers. They are overwhelmed with information from their nervous system (sympathetic response) to the point that they cannot manage the situation in spite of the intellectual information that there is no threat. The body (sympathetics) inappropriately senses a threat when none is present. This is a learned response (most often in infancy) that can also be unlearned (and it’s not overly difficult either).

    The person in this scenario is receiving wrong information from their nervous system that conflicts with their rational mind. The conflict is too much to bear, and anxiety results.

    Once a person begins to decouple the sympathetic response with social situations through somatic awareness, they can begin to utilize their awareness to attenuate the sympathetic response and the anxiety will ebb.

  12. #12 Tony Landreth
    April 11, 2009

    Is this the same treatment that disrupts consolidation of fear memories? If yes, then you have to wonder whether the treatment would disrupt your capacity to learn from negative experiences.

  13. #13 Sophia Eudemon
    April 12, 2009

    If you want to see the effects of high estrogen relative to stress round up a few male to female transsexuals who have went through shear living he..l during their gender transition (which is accomplished with a high estrogen level in our bodies). Lots of prejudice ensures an abundant supply of us that have lost jobs, marriages, children, financial assets, friends, our church affiliation, etc. Most of us do well in the long run.

    My experience is estrogen decreases the long term effects of anxiety. However, it increases anxiety level substantially during the time the stressor is present. Therefore, estrogen does not take away the warning system of stress.

    Incidentally, a quirk of having high estrogen is it allows a person to adapt better to a given stressor. I.E. somewhat like the Borg. After being hit with the same stressor a few times it is not a problem anymore. Part of learning to live well as a female is to expose oneself to as much stress as possible to toughen oneself.

  14. #14 Mercy Nwankama
    April 12, 2009

    Great article. The Stress Vaccine will be yet another wonder of medicine, if the theories eventually match the realities.

  15. #15 Neuroskeptic
    April 14, 2009

    It’s a very clever piece of biology, but we already know how to block stress-induced changes to the brain – Prozac. At least, that’s what happens in animals, and presumably it also happens in humans.

  16. Stress vaccine sounds great. Yes, but… There are always some ‘buts’.
    I agree with G. Gurney that stress is always very personal -we can’t predict what can be stressful for an individual, but it’s still individual’s body reaction, so I guess it’s not the main point. But, as for me, it implicates that it is possible to learn how to cope with stess (it they can, why not me?). Moreover, as Martin emphasised, stress is NOT something ‘evil’. It’s just an information that something in our surroundings is unusual and it’s worth to be watchful about – both in positive and negative meanning. Just as T. Landreth said – without stress we are not able to learn from negative experiences.
    I also want to add some ‘buts’ to the discussion. As it was writen – stress is about ‘fight’ and ‘flight’ reaction. Human’s body response is the same both for negative and positive situations, and it’s brain that interpret it as ‘+’ or ‘-’. As long as we are immunised against dis-stress (‘negative’ stress) we can’t experience eu-stress (‘positive’ stress) as well. It means becoming impoverished in our emotional life in general.
    My second ‘but’ is about… health. Do we know what other changes it draws? What about short- and long-lasting results not only in our bodies, but also bahaviour, way of thinking and life in the end?
    I don’t mean to devaluate such a promising research area – I really support it wholeheartedly. Yet as for me it’s just to early to be happy about that kind of news. And I’m strongly against uncritically accepting it as some people do.

  17. #17 Sapolsky fan
    April 16, 2009

    For those who aren’t familiar with Robert Sapolsky’s work, he has, for decades, studied the deleterious effects of prolonged stress, particularly on the hippocampus. The point of this vaccine would not be to eliminate stress responses, but to reduce the duration of a stress response to prevent long-term brain damage. Unfortunately, our bodies stress responses evolved as a means to deal with situations that were resolved quickly (predator) and currently most of us face more long-lasting stressors (bad economy, straining job) that our stress responses deal poorly with. A vaccine similar to the one discussed above would help us better deal with the stressful realities of daily lives, especially for individuals who react particularly badly to the stress of modern life.

  18. #18 Anne
    May 12, 2009

    Pressure is part of their lives, if you do not want something too serious, it will feel much better.

    http://www.000health.com