#51 – Robert Sapolsky, Ph.D.: The pervasive effect of stress – is it killing you?

KEYPOINTS

• 01

  The stress response is built for a zebra fleeing a lion, not for chronic worry

  Sapolsky, a Stanford neuroendocrinologist and author of Why Zebras Don't Get Ulcers (first edition 1994), describes two arms. Adrenaline acts within seconds, which he likens to 'handing guns out of the gun locker.' Glucocorticoids like cortisol follow via ACTH in about 30 seconds, like 'building the aircraft carriers.' Cortisol mobilizes glucose, raises cardiovascular tone and triages away non-essential functions. That is ideal for a short sprint but harmful when switched on for psychological reasons day after day.

• 02

  Cortisol has a narrow 'therapeutic window', and sensitivity varies

  Peter calls cortisol the hormone with the narrowest therapeutic index: too little is dangerous, as in Addison's disease, and too much is toxic. Sapolsky notes that New World monkeys such as marmosets have roughly ten times the glucocorticoid levels of Old World monkeys without illness. A receptor mutation gave them about one-tenth the sensitivity, so the system equilibrated at a higher level. People can likewise be cortisol-'resistant' or 'sensitive,' much as with insulin.

• 03

  Serengeti baboons are a model of Western stress

  Baboons in troops of 50 to 200 rarely face lions, have lower infant mortality than neighboring Maasai, and need only about three hours a day to find food. That leaves 'nine hours of free time every day to devote to being miserable to some other baboon.' Over more than 30 years of summers, Sapolsky darted and anesthetized the same animals for blood work, relating rank, personality and social ties to stress-related disease.

• 04

  What a rank means matters more than the rank itself

  Being low-ranking is far worse in some troops than in others, depending on troop culture: how often an angry dominant takes it out on you, or whether you get to finish a meal. Humans belong to many hierarchies at once, so the mailroom clerk can be captain of his weekend softball team. Personality matters too. A baboon who treats a rival napping 100 yards away as a provocation averages about twice the cortisol of a same-ranked peer who can tell the difference.

• 05

  Stress can be passed epigenetically across generations

  Glucocorticoids from an anxious mother cross the placenta and cause epigenetic changes in the fetal amygdala, making offspring more anxious. Sapolsky says such non-genetic transmission of traits can ripple, smaller each time, about half a dozen generations later, and close equivalents have been found in humans.

• 06

  Moderate stress sharpens memory; sustained stress damages the hippocampus

  A little arousal boosts blood flow, glucose and synaptic excitability in the hippocampus, which is why emotional events stick. Prolonged high glucocorticoids reverse this: less oxygen and glucose delivery, disconnected synapses, shriveled neurons, blocked neurogenesis and greater vulnerability to other insults. Sapolsky's two-decade summary: 'you don't want to have a whole lot of it marinating inside your head.'

• 07

  Feeling poor is as harmful as being poor

  Sapolsky cites Nancy Adler's work at UCSF showing that subjective socioeconomic status, where you place yourself on a ten-step ladder relative to people around you, predicts health at least as well as objective wealth. He says income inequality strengthens this effect, and social media amplifies it with constant reminders of people doing better. Childhood SES predicts diabetes risk half a century later, so poor health doesn't simply cause poverty.

• 08

  Genes mostly change vulnerability to environments rather than determining outcomes

  Sapolsky recounts a large birth cohort study of a serotonin transporter variant: on its own it barely changed depression risk by age 25. Combined with childhood trauma, it multiplied risk far beyond the increase seen in people without it. He describes a similar pattern for MAO-A, abuse and aggression. He notes that 300 genes together predict only about 4% of height.

• 09

  The evidence for harm is strongest in heart disease and weakest in cancer

  Peter summarizes that hypercortisolism's damage is best shown in atherosclerosis, through hypertension and endothelial damage, and is plausible but less clear in dementia. Sapolsky says that in humans no good prospective studies have truly ruled out confounding in stress and cancer. Animal studies used artificial transplanted tumors, though his lab showed transformed cells upregulate a glucose transporter that glucocorticoids boost further.

• 10

  Stress makes us less empathic and more impulsive

  Sustained stress enlarges the amygdala, atrophies the frontal cortex and disrupts dopamine, increasing vulnerability to addiction and depression. It hampers the frontal cortex's hardest job, seeing from another's perspective. Sapolsky says stress makes us 'crappier to each other,' more xenophobic and parochial, and more impulsive with our worst impulses.