4.

Killing Jiminy: Stress, Fear, and Cortisol

Stress is inevitable. Suffering is not. Your body is built for withstanding acute stresses. Those stresses can be physical (a car accident), adversarial (a lion or a linebacker), medical (high fever), or mental (an English test or forgetting your anniversary). Your body has a protective response to stress, designed to help you fight or flee. It will maintain your blood glucose so that you don’t pass out, protect your blood pressure so that you don’t go into shock, and prevent inflammation. All of these are mediated by the release of the hormone cortisol from your adrenal glands, which sit on top of your kidneys. You need cortisol, perhaps more than any other hormone, in order to survive; without it, the very thought of getting out of bed is an abomination.

Acute, short-term cortisol release is both necessary for survival and is actually good for you. It increases vigilance, improves memory and immune function, and redirects blood flow to fuel the muscles, heart, and brain.1 Your body is designed for cortisol to be released in any given stressful situation, but in small doses and in short bursts. Today, even though our acute stresses are declining in frequency and severity (most of us are far less likely to be chased by a lion in our daily lives), our chronic stresses are going through the roof. Despite (or maybe because of) electricity, computers, cars, indoor climate control, and food everywhere, the prevalence and severity of chronic psychological stress and its attendant cortisol effect is taking its toll.2 I’ll lay 20 to 1 odds it’s the same for you.

Stressed to the Max

Long-term exposure to large doses of cortisol will kill you . . . but slowly. When pressures are relentless, your cortisol response can remain elevated for days, months, or years. Evidence of the associations between job stress, psychological distress, elevated cortisol, depression, and disease is extremely compelling. Psychological stress in adolescence is directly linked to the risk of heart attack3 and diabetes4 in adulthood. Chronic stress also directly impacts the reward pathway as described in Chapter 3, and it has been shown that chronic stress can speed the onset of dementia.5

The Whitehall study looked at the health of twenty-nine thousand British civil servants over the course of thirty years. Those lowest on the socioeconomic scale had the highest rates of chronic disease and also of cortisol levels.6 Even after controlling for behavior (e.g., smoking), death rates were directly related to high stress and the multiple pressures of being financially insecure. Like our friends across the pond, middle- and lower-class Americans also suffer from the highest rates of diabetes, stroke, and heart disease. And if you’re not Caucasian, the stresses associated with racism only exacerbate these effects. There are certainly genetic influences, but the fact is that African-Americans and Latinos tend to suffer from higher rates of morbidity from almost every disease than their white counterparts, and stress plays a huge role in this dichotomy.7, 8

Whatever the mechanism, stress breeds more cortisol. And the more stress, the more breakdown of the endocannabinoid CB1 receptor agonist and anti-anxiety compound anandamide, and the more anxiety.9 This is where marijuana comes in—to curb the anxiety of everyday living (depending on what you got your marijuana prescription for). Like other drugs, marijuana acts on a specific part of the brain and, depending on whether you are a person who gets paranoid from a few tokes, it can, like, seriously, help you to mellow out. However, chronic marijuana users show long-term cognitive decline to the tune of 8 IQ points,10 so, in the end, they may be less stressed about reality anyway.

A Bucket of Nerves

The release of cortisol and your body’s reaction to stress are the result of a cascade of responses. Threat is first interpreted in a walnut-sized area of the brain called the amygdala (see Chapter 2). Whether it’s evading a lion or a line of creditors, your amygdala is scanning the environment for these threats, and talking with other areas of the brain to determine how you should handle it. How your amygdala interacts with the rest of the brain in response to stress determines how you respond, be it curling into a ball or chillaxing. Stress is inevitable. It’s your amygdala scanning the scene and how it connects with your other emotions that determines whether you will be safe or sorry. If you don’t tame your amygdala early, it can become a devastating creature (see amygdala-taming classes online and Chapter 18).

When a threat is detected by the amygdala, several things occur. First, the amygdala activates the sympathetic nervous system (SNS). The SNS raises blood sugar and blood pressure, to prepare you for the acute stress. Second, like the childhood game of telephone, the amygdala tells the Hypothalamus (the brain area that controls hormones), which tells the Pituitary, which tells the Adrenal glands to release cortisol, known as the HPA axis (like the Gossip Girls). But long-term, this can exact a toll on your arteries and your heart, leading to hypertension and stroke. Third, the amygdala is normally in reciprocal communication with the hippocampus, which is the memory center of the brain. The hippocampus is the set of the Pixar movie Inside Out (2015), where memory “bubbles,” colored by associated emotions, are stored. The amygdala and hippocampus are supposed to check and balance and exert feedback on each other.

When all is working well, the acute stress you experience is transduced into memories in the hippocampus so that you don’t put yourself in the same situation again (a “disgust”-colored memory bubble reminds you that too much tequila leads to an unpleasant morning). Or you are able to realize that, just like last night, the scratching at the door is not a burglar but rather the dog wanting to go out to do his business. Of all the parts of the brain, the hippocampus just might be the most vulnerable to cell death. Almost any brain insult you can imagine (low blood glucose, energy deprivation or starvation, radiation) can knock off the neurons of the hippocampus. And one of the serial killers that attacks the neurons in the hippocampus is cortisol. The longer your cortisol stays elevated, the smaller and more vulnerable your hippocampus gets, which puts you at risk for depression.11 This is likely why chronic stress is associated with memory loss12 and why the mothers of toddlers find their car keys in the refrigerator (and not because the kid put them in there).

Executive Function Dysfunction

Excess and chronic stress impacts your ability to reason. The prefrontal cortex (PFC) is your “high order” or “executive function” conscious part of the brain (see Chapter 2). Each of us has our own personal Jiminy Cricket, like the character from Pinocchio, which keeps us from indulging in bad behavior and keeps our baser desires in check. In an uncontrollable stressful situation, the amygdala–HPA axis commands the release of neurotransmitters including dopamine (yup, that again).13 These flood the PFC, silencing Jiminy, which disinhibits you from doing some wild and crazy things.14 When your PFC is under fire by cortisol, your rational decision-making ability is toast. You can’t differentiate between immediate or delayed gratification.15 So, instead of your Jiminy telling you to “Zen” when someone steals your parking space, you are much more likely to react on impulse and extract your short-lived justice, just as Kathy Bates’s character in the film Fried Green Tomatoes (1991) did (Towanda!).

Worse yet, the more cortisol the amygdala is exposed to, the less it is dampened down by—you got it—the law of mass action. More cortisol means fewer cortisol receptors in the amygdala, and the more likely your amygdala will do the talking from here on.16 Chronic stress day by day weakens your inner Jiminy17 to the point where the amygdala becomes your outer Cricket. You just react to the slightest provocation without any thought of consequences.

So the amygdala is responsible for your reaction to stress and the release of cortisol. It also interacts with the VTA, the site of the dopamine neurons. Stress and cortisol also shift your bell-shaped dopamine curve to the right (see Chapter 3), thereby increasing reward-seeking behaviors. Increased stress can turn a small desire into a big dopamine drive,18 which can be quenched by either drugs or food, or both. This is how the pizza and beer scenario typifies the American food experience.

Experiments in animals emphasize that either stress or corticosterone (the rat version of cortisol) administration increases the drive to consume various drugs of abuse, such as cocaine.19 One way to drive up the stress of rats or monkeys is to house them in groups. Invariably one monkey, through wits, guile, or brute force, will become the alpha male and have the power to maintain social control over the others, especially in regard to food and breeding. The alpha’s cortisol levels are lower than any other member in the social group. When provided access to cocaine for self-administration, those on the lowest end of the pecking order are the ones that become the addicts.20, 21 America’s middle and lower classes suffer from more chronic stress than the rest of the population: not knowing if there will be sufficient money to pay the rent, working two or more jobs, facing mountains of credit card debt, food insecurity, and a general sense of powerlessness—all ramp up your cortisol. One can argue that this population is at higher risk not only for obesity, heart disease, and stroke22 but also for drug use and addiction.23

Faulty Brakes

Stress-induced dopamine release also has the capacity to remodel the PFC, so now Jiminy isn’t even a Cricket anymore; he’s been squashed like a bug.24 These neurons (the ones that house the dopamine receptors) are fewer and farther between.25 And, if you bombard them enough, you kill them off and they don’t grow back (see Chapter 5). You need even more to get less. By driving the stimulation of the amygdala and decreasing your cognitive control centers, stress and cortisol make it much more likely that you will succumb to temptations. Three deep breaths or three doughnuts? Depends on the office you work in.

When cognitive control is lost, the ability to inhibit the drive to seek pleasure is lost. Stress promotes faster addiction to drugs of abuse26 and is likely the reason why drug addicts find it so impossible to quit. Chronic stress kills off neurons in the PFC, which is a predictor of addicts relapsing.27 Why do you think rehab centers are generally in scenic areas and designed to be low-stress? It’s upon leaving treatment, when addicts are confronted with the stresses of the real world, that some will start using again. This occurs with food as well.28 Obese people have been shown to have a thinning of their PFCs, likely secondary to long-term dopamine and chronic cortisol bombardment.29

And what is America’s preferred drug of choice in dealing with stress? The one that is closest at hand. And that would be—you guessed it—sugar. Both animals and humans increase their food intake when stressed or when experiencing negative emotions, regardless of whether or not they are hungry. The boss is yelling at you? Krispy Kreme seems as good a solution as any. And there’s actually a reason for this. High-energy dense food, aka comfort food (think chocolate cake)30 increases acute energy to the brain and thus reduces the amygdala’s output and subsequent stress.31 Stress may affect food intake in several ways. For instance, people with eating disorders tend to show higher levels of cortisol or greater cortisol reactivity.32

Alternatively, if stress becomes chronic, and eating is the preferred coping behavior of the individual, then highly palatable food, especially food laced with added sugar, may also become addictive. Cortisol is an appetite stimulant; infusion of cortisol into humans rapidly increases food intake.33 Those who put out more cortisol in response to chronic stress also consume the most comfort food in response to stress.34 It gets worse. Cortisol actually kills neurons that help to inhibit food intake. Thus the stress and reward systems are linked, with food (usually sugar) being the drug,35 breeding a new generation of stress eaters.36 Break out the Ben & Jerry’s.

If Only I Could Sleep at the Switch

Another outcome of increased stress is reduced sleep duration and impaired sleep quality, both of which are contributors to, and consequences of, obesity (see Chapter 10). BMI (body mass index) increases over time among short sleepers.37 A recent study showed that sleep deprivation increases caloric intake by 300 kcal/day, although energy expenditure was unaffected.38 You’re more likely to eat Oreos and watch infomericals about weight loss in those extra hours spent awake than you are to actually work out. Scientists are constantly conducting research to better understand the different parts of the brain. You’ve likely seen at least one horror or action movie in which a person is strapped to a bed with an electrical helmet, being monitored by men in white lab coats. In real life these types of studies are well monitored for safety and are incredibly valuable in understanding how we tick. When healthy people were asked to spend the night in a lab and deprived of sleep, their brain imaging showed less activation in the PFC but greater activation in the amygdala when choosing foods. Do you think they went for the carrots or the cookies?39 On nights back in pediatric residency (post-doctoral training where you ostensibly sleep in the hospital), mint Milanos were my only true and unflagging companion that I could always rely on. Poor sleep is common among obese individuals. They often suffer from obstructive sleep apnea (see Chapter 18). They retain more carbon dioxide, which makes them even hungrier, and makes their obesity and diabetes even worse and puts an extra strain on their heart.40 So stress leads to sleep deprivation. Sleep deprivation causes more reactivity and cortisol release. Cortisol release alters your dopamine response curve. Increased dopamine makes you more likely to eat. The more you eat, the more likely you are to become obese. Obesity leads to sleep deprivation, which can cause stress. A truly vicious cycle.

The Vulnerable Child

Stress and cortisol play an even bigger role in children, a time when eating patterns are programmed.41 Adverse childhood experiences and early life stressors, such as child abuse, dramatically change the brain,42 and these changes predispose children to adult obesity and related disorders.43 Several studies have shown relationships between stress and unhealthy dietary practices, including increased snacking in adolescents.44 In a study of nine-year-olds, children who felt more stressed by lab challenges ended up eating more comfort food.45 Not only are stressed kids setups for obesity, they’re setups for future abuse of other substances as well.46

When you’re under stress, your cortisol is up, your PFC is inhibited, your dopamine is firing—all of which will drive you to the chocolate cake or another drug of choice. The more chocolate cake you eat in response to stress, the less pleasure you will get and the sicker you will start to feel, which will drive even more stress. Those dopamine receptors need more, but deliver less. You’ll soon become tolerant or, worse yet, addicted.