Growing Young

by Marta Zaraska

  Ghosts and Hormones

  It was about ten o’clock at night when SM, a thirty-year-old woman, was on her way home. The area was deserted, with only the sounds of choir music floating out of a nearby church interrupting the stillness. As SM walked past a small park, she noticed a man sitting on a bench. She thought he looked “drugged-out,” but when he motioned her to come over, she obliged. The moment SM approached the man, he jumped up, pulled her by the shirt, and pressed a knife to her throat, shouting, “I’m going to cut you, bitch!”

  If I had been in SM’s place, I would have been shaking with panic. My heart would have raced and my palms would have been drenched with sweat. Yet SM felt no fear. She replied calmly, “If you’re going to kill me, you’re gonna have to go through my God’s angels first.” Then, slowly, she walked away, leaving the stunned man behind. The very next night she strolled home through the same park. No anxiety, no panic, nothing.

  SM, as she is known to medical researchers, suffers from Urbach-Wiethe disease, a rare genetic disorder that has left her with a damaged amygdala. Since this brain region acts as a quick detector of potential threats, SM is basically fearless. She picks up dangerous snakes with her bare hands and watches horror movies without flinching. Even one of the world’s scariest haunted houses, the Waverly Hills Sanatorium in Louisville, Kentucky, wasn’t enough to unsettle her. For one experiment, scientists took SM on a tour of the Waverly Hills Sanatorium hoping to observe her reactions to the local “demons”—Sanatorium’s workers dressed to look scary. What they saw was pure spunk: SM never hesitated to walk around murky corners and laughed at the “demons,” even trying to chat them up. Other people, meanwhile, lagged behind her and screamed in fright whenever “monsters” and “ghosts” startled them.

  SM’s boldness may seem enviable, but unfortunately it has dangerous consequences. SM has fallen victim to numerous crimes, from domestic violence to death threats and assaults. Without fear, she makes mistakes other people tend to avoid—like approaching a drugged-out-looking guy in a dark, empty park. Her fight-or-flight response just doesn’t activate properly.

  If you are like me and most amygdala-lesion-free people, you would likely feel anxious in a deserted public space at nighttime. Faced with a criminal and a knife, you would probably experience a certain mixture of emotions (fear, panic, anger), sharper attention, and physical sensations such as a racing heart, sweaty palms, and difficulty swallowing. That’s a fight-or-flight response, your mind and body interacting to save your life, just as it worked for our ancestors on the savanna.

  The fight-or-flight response evolved to aid us in either wrestling dangerous animals and humans or making a successful escape. The rate and force of heart contractions increase. Blood pressure goes up. More blood is pumped into your skeletal muscles to help you move more quickly, boosting your strength. Your bronchial tubes dilate, which makes breathing easier. The pupils in your eyes dilate as well, so you can focus your sight better. In extreme situations some people may even empty their bladders or bowels—that’s also an evolved part of the fight-or-flight response. After all, if you have no extra weight in your abdomen, you can flee faster.

  Even though these days lions are uncommon on the streets of Manhattan or London, the fight-or-flight response, known also as the “stress response,” is something most of us know well. Your boss says he “needs to talk”? Fear, racing heart. Someone flips you off in traffic? Anger, sweaty palms. Exams are starting? Anxiety, stomach issues (bowels emptying to facilitate fleeing). It all creates a cascade of emotions and physical changes which, if chronic, can result in heart disease, premature aging, and even particularly bad colds. There are four main pathways connecting your mind and your body, all of them related to the stress response: the sympathomedullary axis, the HPA axis, the immune system, and about three pounds of microbes that are living in your gut.

  When you are faced with a lion or with an angry boss, the first changes in your body happen in split seconds. That’s your sympathomedullary pathway activating. It’s a very primitive system that works whether you want it to or not. The amygdala, the fear centre, sends a message down to your adrenal glands, two grape-sized organs that sit on top of your kidneys. The adrenal glands then release a soup of hormones which includes the famed adrenaline. Your blood is diverted away from your gut and kidneys—admittedly rather useless systems in a fight—to those parts of your body that are more vital for saving your life, such as the skeletal muscles and the brain. You feel pumped up.

  You are almost ready to go, but your body is not yet done. A second system kicks in, a more complicated one known as the hypothalamus-pituitary-adrenal axis. Once alarmed by the amygdala, a part of the brain called the hypothalamus starts a hormonal cascade that again ends up revving up the adrenal glands, just a different part of them. Another cocktail spills into the bloodstream, this one containing hormones such as cortisol.

  If you’ve heard about stress, you’ve probably heard about cortisol. This hormone has a bad reputation as the evil-incarnate sidekick of stress, to the point that Psychology Today once called it “public health enemy number one.” On the purely physiological side, cortisol has been linked to weight gain, diabetes, cancer, and heart disease. On the psychological side, it’s been shown to spur aggression and antisocial behaviours. Although now it seems clear that cortisol connects the body and the mind in multiple ways, when it was first discovered in the 1940s, it was touted as a miracle cure for stress and rheumatoid arthritis. The knowledge that it has much more complex effects on the body and the psyche came only later. And it all started with a twenty-nine-year-old woman from Kokomo, Indiana.

  Bad Stress, Good Stress

  During World War Two, rumours abounded that the Nazis were developing a miracle cure for stress so that their pilots could zoom around in their Messerschmitts with no regard to speed and altitude. The Germans were, supposedly, importing tons of bovine adrenal glands from Argentina and extracting some “mysterious humour” out of them. By then it was known to science that cows without adrenal glands died when subjected to even minimal stress, so the argument that the extract would make pilots stress-resistant seemed plausible. With hopes for outstanding military gains, the American government invested tons of money into the research on the mysterious humour, giving it the third priority after penicillin and antimalarials.

  The cash injections into research on adrenal glands provided a great boost to the work of three scientists, Americans Phillip Hench and Edward Kendall and their Polish colleague Tadeusz Reichstein. With a steady supply of nine hundred pounds a week of adrenal glands from some unlucky cows, the three researchers perfected the production of something they named “compound E,” which we now call cortisol. But before anyone managed to turn “compound E” into a courage pill, the war ended.

  With less need for pilot superpowers, the scientists went on to experiment with cortisol as a potential cure for rheumatoid arthritis. In 1948 they recruited a Mrs. Gardner from Indiana for experimental treatments. Young Mrs. Gardner’s arthritis was so bad that on most days the pain wouldn’t allow her to walk or even get out of bed. On September 21, 1948, Mrs. Gardner received initial injections of large doses of cortisol. At first, nothing seemed to happen, but after four days of treatment, her pain was completely gone. When the scientists visited her room in Saint Mary’s Hospital in Rochester, Minnesota, they found her exercising, lifting her hands up over her head—a feat she had been previously incapable of. On September 28, Mrs. Gardner left the hospital and went on a shopping spree in downtown Rochester. She appeared completely cured.

  Then, after about two weeks, the problems began. But it wasn’t pain that was troubling Mrs. Gardner this time, it was her mood. It would swing from depressed to euphoric and then back. Occasionally, she would become psychotic, and ended up admitted to Saint Mary’s locked psychiatric ward. Once her cortisol injections were stopped, the troubles with her mind cleared up. She refused to take cort
isol ever again, choosing pain over psychosis.

  For their discovery of cortisol, Hench, Kendall, and Reichstein received the Nobel Prize in 1950, but it took many more decades for researchers to get a better understanding of its role in our stress response and mind-brain connections. Modern science shows that cortisol is just one cog in the machinery of stress, the HPA axis, which involves a whole cascade of hormones. First, there is the corticotrophin-releasing hormone secreted by the brain’s hypothalamus into the blood. The hormone triggers a pea-sized organ at the base of your brain, the pituitary gland, to pump out adrenocorticotropic hormone, which then flows all the way down to the kidneys, where it switches on the production of hormones such as aldosterone and cortisol from the adrenal glands.

  Your body is readying for the fight or flight—and its consequences. Since you need energy to both flee and battle, cortisol will provide you with a fuel boost by breaking down proteins and fat from long-lasting sources, such as your muscles, to raise blood glucose levels. Both cortisol and aldosterone will also raise your blood pressure by constricting your blood vessels (cortisol) and increasing salt and water retention (aldosterone). Lions and angry bosses beware—you are ready to fight.

  If you are lucky and the lion turns around and strides away into the sunset, your stress axis will calm down, and all systems will go back to baseline. The hypothalamus will detect the raised levels of cortisol in the blood and put a halt to its production within forty to sixty minutes after the anxiety-inducing event. Meanwhile, a cousin branch of your sympathomedullary pathway will activate a rest-and-digest response, which calms down all the previous changes in your adrenaline-releasing system. You begin to relax.

  Here is a problem, though. On an African savanna, the things that caused our ancestors anxiety or anger usually happened fast and resolved fast (the lion went away: problem gone); the things that today arouse our negative emotions are, by contrast, often low-intensity but long-lasting. Mortgage stress activates the HPA axis as surely as carnivorous cats do, yet mortgages tend to stick around longer than predators. Same for traffic, work issues, loneliness, overscheduling, worrying about your kids’ college admissions, and so on.

  Unfortunately, when activation of the HPA axis becomes chronic, troubles start to mount. The axis becomes dysregulated and the levels of cortisol stay constantly up. The hypothalamus begins to shrink (yes, you’ve heard it right—stress shrinks your brain, or at least some parts of it). What may grow, though, is your stomach. Since cortisol takes up fat from places such as the legs and arms, and then lets it settle around the waist, you may grow chunkier in your mid-section—that’s why some researchers use a high waist-to-hip ratio as a marker for chronic stress. The interplay between fat and cortisol may also lead to insulin resistance, and then to diabetes, cardiovascular disease, and even cancer.

  By modifying cortisol levels and the activation of the sympathomedullary pathway, your psyche can change your body all the way down to your DNA, changing the expression of your genes. Like a finger on a light switch, stress hormones turn genes on and off. This includes genes related to the immune system. If a person is under chronic stress, the stress pathways flip on genes involved in inflammation, and switch off those responsible for the antiviral response. From the savanna perspective, it made sense. Back then chronic stress usually meant being outside the camp—away from viruses usually carried by fellow tribe members—and at a higher risk of wounds, which can get infected by bacteria. Our chronically stressed ancestors got scratched by thorny branches while chasing prey, mauled by predators, or slashed by enemies. The immune system, like everything in nature, takes energy to run and compromises had to be made. So down went antiviral protection, and up went inflammation, which is great for fighting bacteria in an oozing wound.

  Today, however, this conserved response to adversity is far from helpful. What it means in practice is that persistent worries over jobs, kids, and mortgages make us less resistant to viruses, from the common cold to the flu, and more prone to inflammation, which in the long run leads to diabetes, stroke, heart disease, and cancer. Out of the ten leading causes of death, chronic inflammation contributes to at least seven.

  Intertwined with the stress pathways, the immune system is itself a great connector between our minds and bodies, helping explain how our emotions and thoughts affect our health. This is a hot new area of research, recently christened “immunopsychiatry.” Your immune system is directly wired to your brain via nerves and neurotransmitters. Think of the last time you were sick with a virus. How did you feel, psychologically? Probably gloomy and miserable, wishing to stay bundled up in bed all day. People often assume that such lethargy is a direct result of the virus messing with their bodies, but that’s not really the case. That unpleasant feeling is mostly in your head—you’d quite likely be fine going out to party. This so-called “sickness behaviour” is actually caused by your own immune system, or your pro-inflammatory cytokines, to be precise. Cytokines are proteins that regulate the inflammatory response, helping fight various pathogens and heal wounds. But they also induce the behavioural and psychological changes that tie us to the bed when ill.

  Sickness behaviour likely evolved so that ailing people would not spread the infection to the other members of the tribe, and so that they would not fall easy victim in spats with healthy others. That’s why when you are under the weather you feel like hiding away and you may tolerate only a handful of your most trusted people.

  While “lying miserably in bed” and “no energy” may be a good description of someone with a flu, it may also be a fitting description of someone with depression. Science is beginning to uncover the surprising links between depression, stress, and inflammation. When your body spews pro-inflammatory cytokines in particularly large quantities or for long periods of time, you are at a higher risk of becoming depressed.

  One meta-analysis showed that about a quarter of patients with hepatitis C who are treated with the cytokine interferon-alpha develop depression as a side effect. In animals, injections with both infectious bacteria and pro-inflammatory cytokines cause depression, too. Who will succumb to the immune system–induced gloom likely depends on their stress resilience and coping style. Studies on mice and rats show that only those who are susceptible to stress and deal with challenges passively, instead of grabbing their rodent lives by the horns, end up with elevated levels of pro-inflammatory cytokines, depression and, as a consequence, heart disease. In humans, too, depression is associated with early mortality. When this is not the result of suicide, it is often caused by cardiovascular problems, with inflammation the likely culprit.

  The links between the psyche, depression, and inflammation are complicated and bidirectional. Chronic stress can raise levels of pro-inflammatory cytokines and result in depression. Yet inflammation per se can make you feel desolate, too. For this reason anti-inflammatory drugs are now being proposed as treatment for depression in patients who don’t respond to traditional remedies. Should you then take ibuprofen whenever you feel a touch of blues? Research has not addressed this question yet, but my guess would be: probably not, since in my opinion routine downing of pills is rarely a solution. But for those with major depression, anti-inflammatory drugs may offer real hope.

  How, exactly, can tiny, inflammation-inducing proteins that circulate in your blood affect the thoughts and emotions in your brain? The answer isn’t completely clear, but research reveals that they can both cross into the brain directly and also transmit the message to your central computer via a nerve called the vagus. The vagus, which is the longest nerve that emerges directly from the brain, seems crucial in the connections between the mind and the body. It may even be behind the ultimate mind-body events: psychogenic or “voodoo” deaths.

  Deadly Hens, Drownings, and HRV Monitors

  In 1682, Girolamo Merolla da Sorrento, an Italian missionary, travelled through the Congo and reported a story of a young African man who stayed at a fr
iend’s house. The host offered wild hen for breakfast—a food that was taboo in the young African’s culture—yet lied about it, claiming the bird was something else. The young African ate happily and soon forgot about the whole thing. But years later the two met again and the cook asked if the young man would like to taste some wild hen. When faced with stern refusal—after all, the food was strictly banned by a local “wizard”—the cook informed the youth that he had broken the taboo already in the past. The young man began to tremble, completely overcome by fear. Within twenty-four hours, he was dead.

  Meat consumption may be bad for your cholesterol levels and cardiovascular health in general, but by itself it can’t make you collapse on the spot. The young Congolese likely fell victim to a psychogenic or “voodoo” death—a sudden, unexplained demise initiated by a belief in a mortal curse. Reports of psychogenic deaths abound across the planet, from the islands of the Pacific to South America, Africa, Australia, and New Zealand.

  The clue to what may be causing psychogenic deaths comes from some cases of drownings. About 10 to 15 percent of people who die plunging into an ocean or a river have no water in their lungs, indicating that they haven’t, in fact, drowned at all. In animal experiments similar cases have been attributed to the overstimulation of the vagus nerve. Such sudden vagal death, some scientists believe, could also explain the mortal power of voodoo curses.

  The vagus nerve goes from the base of your skull down your neck and along your trachea to your heart and then wanders lower to your abdomen, where it innervates the gastrointestinal tract. It’s responsible for your breathing, swallowing, and digestion. It’s also responsible for the way your heart beats. The vagus is a major nerve of the autonomic nervous system and as such also plays a role in the fight-and-flight response. In a way, it’s on the flip side of the sympathomedullary pathway and the HPA axis—it calms down the system after stress, bringing on relaxation once an adrenaline-pumping event is over. Your heart slows down, your breathing steadies, your digestion picks up again.