Robert Sapolsky, Ph.D. on the Pervasive Effect of Stress: Is it killing you? – The Peter Attia Drive

Check out The Peter Attia Drive Episode Page & Show Notes

Key Takeaways

  • The main hormone associated with the stress response is cortisol (also known as a glucocorticoid)
    • One downstream side effect of cortisol is that it increases glucose levels in the blood (it facilitates its release from storage sites in the liver and muscle)
  • “What your childhood is like has a lot to do with what sort of adult you’re going to wind up being”
    • Being stressed while pregnant leads to changes in the amygdala of your child’s brain (the part of the brain which controls emotions) (the child’s amygdala increases in size)
      • Because of this, that child will be more prone to anxiety when they get older
  • Sleep and Cortisol
    • When we wake up, that’s when our cortisol levels are highest
    • Cortisol inhibits melatonin secretion
    • Elevated cortisol levels lead to less delta wave (deep) sleep
  • Depression is genetic…to an extent
    • Research has shown that if you’re exposed to childhood stress/trauma AND have the specific gene variants associated with depression, there is a greatly increased chance you’ll experience depression as an adult (~20% increased risk)
  • More negatives from chronic stress:
    • Chronic stress actual makes the amygdala work better than it should (neurons become more excitable and form denser networks) and increases its size
      • (This is a bad thing – it makes you more prone to negative emotions like anxiety and fear)
    • Due to the effect on the prefrontal cortex, chronic stress makes us way less empathic and reduces the control we have over our impulses


The Physiology of the Stress Response

  • When we’re faced with a stressful situation, we output adrenaline (aka epinephrine) from the sympathetic nervous system (aka the fight or flight nervous system)
    • “It’s on the scene in your bloodstream 1-2 seconds after all hell breaks loose”
  • Elsewhere in the brain, the hypothalamus begins secreting CRH (corticotropin-releasing hormone) which in turn causes the pituitary gland to release ACTH
    • ACTH causes our adrenal glands to release a class of hormone known as glucocorticoids (cortisol)
      • Glucocorticoids increase glucose levels in the bloodstream (taking it from storage sites in the liver and muscle)
        • Why? – Think evolutionarily. You probably needed the increase in glucose to help escape from a charging lion.
  • Both glucocorticoids and epinephrine increase cardiovascular tone (heart rate and blood pressure)
    • This makes it easier for glucose to be carried to the muscles that need it
  • Glucocorticoids also aid in shutting down everything that’s not essential to the survival process
    • Things like digestion – “You have better things to do than digest breakfast when you’re trying to avoid being someone’s lunch”

We Don’t Hate Stress, We Hate the Wrong Amount of It

  • “Too much cortisol will eventually kill you and make you miserable as hell on the way; too little of it will also kill you quite quickly” – Peter
    • There are certain diseases, like Addison’s Disease, where people don’t turn on the endocrine stress response and have extremely low levels of cortisol
      • Why would this be harmful?
        • As cortisol causes the liver/muscles to release stored glycogen, you’re prone to hypoglycemic shock after a short burst of energy (like sprinting – you use up all the glucose in your bloodstream and can’t output more from the liver/muscles)
    • “We don’t hate stress, we hate the wrong amount of stress. When it’s the right amount, we love it.”
      •  Think – We pay money to ride a roller coaster and experience the “stress” that comes along with it

Variations in the Stress Response

  • At the same level of cortisol, people might experience different levels of physiologic benefit/harm
    • This probably has to do with the availability/sensitivity of cortisol receptors
  • But also – two people might release different levels of cortisol when faced with the same external scenario
  • It’s just like insulin:
    • Two people can have the same level of insulin but have different physiologic responses due to insulin sensitivity
    • Different people will have a different insulin response to the same exact meal

The Amygdala

  • The amygdala is one of the anchors of the brain’s limbic system
    • This is the part of the brain which deals with emotion (so the amygdala is the part of the brain which controls fear/anxiety/aggression/arousal/fear etc.)
  • The amygdala sits underneath the cortex 
    • On the evolutionary scale, the cortex evolved later
  • In studies where people are shown pictures of faces while in a brain scanner, those who view faces with neutral expressions as threatening have physically larger amygdalas
    • In other words, these people see threats that others don’t

The Different Parts of the Human Brain and How They Interact

  • In simple terms, the human brain has 3 parts
    • The brainstem (aka the regulatory brain) (which handles things like breathing – everything we think about)
    • The midbrain (aka the emotional/limbic brain – this is where the amygdala sits)
    • The cortex (the thinking brain)
  • The different parts of the brain interact
    • When we feel an emotion, like anger (from activation of the amygdala), our heart rate speeds up (directed by the brainstem) 
    • Just by thinking certain thoughts (with the cortex), our heart rate can change 
  • In one study, male participants walked across a suspended/scary bridge
    • 1/2 of participants were met halfway by an attractive female
    • The other half of the participants only encountered the attractive female after crossing the bridge
    • The people who met the attractive female while in the middle of the bridge rated her as more attractive 
      • Why? – Because of their high heart rates (controlled by the brainstem) having an effect on their thinking (aka the cortex)

Epigenetics and How Stress During Pregnancy Affects the Brain of Your Child

  • “What your childhood is like has a lot to do with what sort of adult you’re going to wind up being”
  • Epigenetics = early childhood experience changing the regulation of your genes (how easily you turn certain genes on/off)
  • Being stressed while pregnant leads to changes in the amygdala of your child’s brain (the part of the brain which controls emotions) (the child’s amygdala increases in size)
    • How? – Probably due to excess glucocorticoid (cortisol) secretion
      • The glucocorticoids get into circulation, navigate through the placenta into the child’s circulation, and into their developing brain
    • Hence – that child would be more prone to interpreting a neutral situation as a threatening one (they’ll have higher levels of anxiety)
    • The cycle just continues
      • When that child gets pregnant (assuming she’s a female), her fetus will be exposed to excess levels of glucocorticoids

The Right Amount Cortisol Amplifies Learning & Memory (but too much or too little inhibits both)

  • The part of the brain that deals with learning/memory is the hippocampus
    • The hippocampus has a high level of glucocorticoid receptors (so it’s very sensitive to cortisol)
  • The right amount of cortisol tends to amplify learning & memory
    • If your glucocorticoid levels are very high (from something like a lack of sleep) – you won’t effectively consolidate information
    • “The optimal amount of glucocorticoids, something that’s moderately stressful, does great stuff for your hippocampus. It increases blood delivery (and in turn glucose and oxygen) to the brain, and makes the synapses between neurons more excitable.”
      • “A little bit of arousal and alertness is a good thing for learning and memory”
      • (Excess cortisol does the opposite of the above)

Health and Socioeconomic Status

  • “You look at the quarter poorest places on Earth and indeed people there don’t live very long and are miserable. But once you get past sort of the subsistence level, there’s not a great relationship between the wealth of a country and levels of happiness or life expectancy.”

Managing Stress

  • “10 minutes of deliberate, mindful practice of meditation daily would probably be better than one hour once a week”
    • Why? – Factor in the recovery period after the meditation (you’re recovering 7x compared to 1x) 
  • Peter has noticed email is a HUGE stressor in his life
    • To combat this – he now only checks email twice a day for 30 minutes
    • Even if you only check your email for 2 minutes – the after effect (“I should have said X”, “I can’t believe he/she didn’t get this done”) sits with you for long after
      • This can only be harmful for your stress levels

The Severity of PMS Symptoms

  • AKA premenstrual syndrome – the irritability/fatigue/bloating/moodiness many women experience during their periods
    • What’s going on biologically? – When a woman is in her luteal phase, her progesterone levels rise for the placenta 
      • But it’s a false alarm, her uterine lining is shed, and her progesterone level comes crashing down – this is what causes the symptoms
      • BUT – women have different sensitivities to this crash and thus experience different symptoms (or a lack thereof)
  • Research has shown that in baboons (and humans), culture largely influences the severity of a woman’s PMS symptoms
    • If you’re in a culture where it’s acceptable to bitch/moan to your friends when you’re feeling lousy….that’s what you’ll do

Is depression genetic?

  • There are certain gene variants (particularly with the serotonin transporter gene) associated with depression
    • Let’s dive further:
      • It’s been shown that having these genetic variants doesn’t necessarily increase the chances you’ll experience symptoms of depression
      • What HAS been shown is that if you’re exposed to childhood stress/trauma AND have the gene variant, there is a greatly increased chance you’ll experience depression as an adult (~20% increased risk)
  • (This same thing happens with the genetics for aggression)
    • Childhood stress in conjunction with childhood abuse/trauma results in an increased likelihood of an aggressive personality as an adult

Sleep and Cortisol

  • Peter’s highest blood glucose level is always in the morning (besides after eating a carb-based meal)
    • Why? – When we wake up, that’s when our glucocorticoid levels are highest (an hour before you wake up, your cortisol levels begin to rise)
      • Remember – cortisol increases the release of stored glucose
  • When people are sleep deprived, their cortisol levels are greatly elevated
  • A cool study:
    • When you tell people prior to putting them to bed that you’ll wake them up at 4 AM, around 3 AM their cortisol levels start to rise
    • If instead you tell these same people you’re going to wake them up at some point during the night, but not specifically when – their cortisol levels start to rise after just one 90-minute sleep cycle
      • Why does this matter?
        • Elevated cortisol levels lead to less delta wave (deep sleep)
  • Cortisol inhibits melatonin secretion

Stress and Cancer

  • “The actual evidence for the role of stress in causing cancer, bringing it out of remission, or accelerating tumor growth is very, very minimal”
  • But…what has been found
    • When injecting glucocorticoid into a mouse tumor, tumor growth is accelerated
    • And – GLUT4 (a glucose transporter) is upregulated on the tumor cells (resulting in more of an intake of glucose)
  • Related – supportive group therapy among cancer patients increases survival
    • “People in their cancer therapy, when they have supporters also going through the same hell, become more compliant”

Does stress accelerate other diseases/disorders?

  • Definitely cardiovascular disease (resulting from hypertension and endothelial disruption)
  • As melatonin is a pro-neurogenic molecule (and stress/cortisol inhibits melatonin release) – age-related cognitive decline is probably accelerated by stress
  • You can accelerate aspects of hippocampal aging with chronic stress (neuron loss and memory problems)
  • Chronic stress actual makes the amygdala work better than it should (neurons become more excitable and form denser networks) and increases its size
    • Remember the amygdala regulates our emotions – hence the relationship between stress/anxiety and stress/fear
  • PTSD patients have a notably enlarged amygdala as well as an atrophied hippocampus 
    • “Glucocorticoids probably play a driving role in both”
  • Chronic stress leads to more of a vulnerability to addiction
  • Chronic stress can increase the likelihood for episodes of major depression
  • Glucocorticoids have an adverse effect on the prefrontal cortex (which controls judgement, impulse control, long-term planning, and strategizing)
    • When we’re very stressed, it’s hard for the prefrontal cortex to take the view of the world from someone else’s perspective (aka empathy)
      • To sum up – chronic stress makes us way less empathetic and reduces the control we have over our impulses

These notes were edited by RoRoPa Editing Services

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