- Physiology -

When lab rats are stressed repeatedly, the amygdala – an almond shaped nub in the center of the brain – enlarges dramatically. This swelling comes at the expense of the hippocampus, which is crucial for learning and memory, and shrinks under sever stress. The main job of the amygdala is to perceive danger and help generate the stress response; it’s the brain area turned on by dark alleys and Hitchcock movies. Unfortunately, a swollen amygdala means that were more likely to notice potential threats in the first place, which means we spend more time in a state of anxiety (snowball effect). The end result is that we become more vulnerable to the very thing that’s killing us.

- Chemistry -

When people feel stressed, a tiny circuit in the amygdala triggers the release of glucocorticoids, a family of stress hormones that puts the body in a heightened state of alert. The molecules are named after their ability to rapidly increase levels of glucose in the blood, thus providing muscles with a burst of energy. They also shut down all nonessential bodily processes, such as digestion and immune response. This is the body’s way of being efficient with its resources. When you’re being chased by a lion, you don’t want to waste resources on the small intestine. You’ll digest food some other time. You need every ounce of energy to get away and survive. But glucocorticoids have a nasty side effect. When they linger in the bloodstream (as they might due to chronic stress related to low rank) damage accumulates. It’s the physiological version of a government devoting too many resources to its defense department. The body is so worried about he war that it doesn’t fix the roads or invest in the schools. The effects of stress and glucocorticoids are toxic to the brain. When stress becomes chronic, neurons stop investing in themselves. Neurogenesis slows. Dendrites shrink. Neuronal arbors retreat. A large part of the changes in brain structure and function induced by chronic stress have similar characteristics to those observed in neurodegenerative diseases, most notably Alzheimer’s. The higher the level of stress hormone, the greater the level of cognitive decline.
Stress effects are also transmitted across generations, from parent to child. The offspring of monkeys stressed during pregnancy have smaller hippocampi, suffer form elevated levels of stress hormone and anxiety. Buffers for stress response chemicals are (thought to) be neuromodulators like dopamine (pleasure, reward) and oxytocin (the cuddle hormone) that are released when we experience pleasure. Feelings of enjoyment – the ability to find meaning in our work, even if it’s a stressful work – may counteract the toxic effects of glucocorticoids. THIS is why low ranked employees who spend all day on menial drudgery have such big problems with chronic stress disorders.

Stress has been linked directly to cardiovascular disease, high blood pressure, type 2 diabetes, and clinical depression.

- Whitehall Study –

Michael Marmot, professor of epidemiology and public health at University College of London, has been running the WHITEHALL STUDY for the past 25 years. And exhaustive longitudinal survey which launched in 1967 and has tracked some 28,000 British men and women working in central London. What makes the Whitehall study so compelling is its uniformity, Every subject is a british civil servant, a cog in the vast governmental bureaucracy. They all have access to the same health care sustems, don’t have to worry about getting laid off, and spend most of their workdays shuffling papers. It’s also rigidly hierarchical, with a precise classification scheme for ranking employees. (A human baboon troop.) It ranges from messengers to clerks to powerful administrators. People who are neither very poor or very rich. The differences are dramatic. After tracking thousands of employees for decades, Marmot was able to demonstrate that between the ages of 40 and 64, workers at the bottom of the hierarchy had a mortality rate four times higher than that of people at the top. Even after accounting for genetic risks and behaviors like smoking and binge drinking, civil servants at the bottom of the pecking order still had nearly DOUBLE the mortality rate of those at the top. It’s all about the status when it comes to stress. Even getting promoted form the lowest level in the British civil service reduced the probability of heart disease by up to 13 percentage points. Climbing the social ladder really does make us live longer.

Not just the sheer amount of stress, it’s also the absence of CONTROL. Researches call it the “demand-control” model of stress, in which the damage caused by chronic stress depends not just on the demands of the job but also on the extent to which we can control our response to those demands. While a relentlessly intense job like a senior executive position leads to a slightly increased risk of heart disease and death, a job with no control is significantly more dangerous. It also has to do with finding meaning, purpose, and passion in your job, because these are the feelings which trigger anti-stress neurotransmitters like dopamine to counteract glucocorticoids.

- Oscars Study –

Oscar winners gain control over their careers and are less stressed to perform well. The critical acclaim leads to more choice over job offers, and more creative license with their acting. They are relaxed and confident. So…. They live longer! People with Oscars (compared to those who 1. Appeared in the same film or 2. Had been nominated for an academy award but never won) on average, lives FOUR YEARS longer than their less successful peers - a 28% reduction in death rate. This longevity boost is roughly equal to the effect that would come form curing all cancers in all people for all time.

- ROBERT SAPOLSKY - and the anti-stress virus

Stanford professor. The one who studied the baboon’s hierarchical stress effects in Africa. Beard and crazy hair. He’s on campus now.
The modified herpes simplex virus, which has been used as a viral vector in gene therapy research for two decades. Herpes can slip easily into brain cells, (crossing the blood-brain barrier, the specialized capillaries that prevent blood contaminants form entering the brain).
Sapolsky put genes and proteins in the virus that would counteract the stress response. He deleted all the dangerous genes in the herpes virus and replaced them with an assortment of “neuroprotective” ones, which increase the production of growth factors, various antioxidants, and substances that mimic estrogen. (estrogen counters many of the deleterious effects of stress on the brain.)
What’s so cool is that the natural selection of the virus had already solved Sapolsky’s biggest biological technical problem – that he needed the “anti-stress” virus to take effect only during specific (stressful) moments, and then turn off afterwards. Viruses aren’t dumb – they don’t want to become active until we’re really vulnerable and our immune response is suppressed. So the virus already had the genetic machinery necessary – it automatically monitors the flux of glucocorticoids in the bloodstream. It had evolved to start expressing its genes when ever its host felt overburdened by the world.
He tested it by injecting it into rat’s brains and then later exposing them to high stress situations. Within minutes of the stress, the modified “anti-stress” herpes virus began pumping out neuroprotective proteins, which limited the extent of cell death. As a result the damage of the stress (in this case, massive strokes or extended seizures) was substantially contained. Rats given the herpes treatment were able to stave off practically all cell loss, while controlled rats lost nearly 40% of neurons in some regions. In the hippocampus, in particular, neuronal death was reduced significantly. By injecting the modified herpes virus into their amygdala and monitoring the rats with brain scans, he found that he was also able to dramatically reduce the anxiety the animals suffer when they’re placed in an open space (where they instinctively fear predators). Furthermore, this gene therapy was able to prevent the expansion of neurons in the amygdala after repeated stressors - aka the snowball effect of stress causing more sensitivity to stress was effectively mitigated.
This could be sweet, but its really just a band aid for an inherently societal problem of stress inducing hierarchies in the work force and generally stressful lifestyles.