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

The two main workhorses are adrenaline (epinephrine) and glucocorticoids (cortisol). Adrenaline provides a rapid, seconds-long fight-or-flight response, while glucocorticoids initiate slower, minute-to-hour long responses, preparing the body for sustained physical challenges by releasing stored glucose and increasing cardiovascular tone.

While speculative, the two systems are thought to have evolved for different timescales of threat. Epinephrine handles immediate threats (seconds), while glucocorticoids support sustained responses over minutes to hours, such as evading a predator or hunting for food. These systems are ancient, serving vertebrates for a long time, but become problematic when activated by modern psychological stressors like taxes.

There is an optimal level of stress, often called 'stimulation,' that we even pay money to experience. However, the optimal level varies greatly between individuals, with some thriving in intense situations and others preferring calmer environments. Beyond the external scenario, individual differences in hormone receptor sensitivity also play a crucial role in how our bodies respond at the same hormone levels.

Baboons, particularly those in rich ecosystems like the Serengeti, spend only about three hours a day acquiring calories. This leaves them with nine hours of free time to generate psychological stress for each other, making them excellent models for Westernized stress where psychosocial factors, not physical threats, predominantly drive chronic stress and related diseases.

For baboons, higher social rank generally correlates with lower glucocorticoid levels and better health. However, the contextual meaning of rank and individual personality (e.g., how readily a baboon perceives threats) can be more important. In humans, who belong to multiple hierarchies, individuals psychologically define themselves by the hierarchy in which they have the highest status, mitigating some of the effects of lower rank in other domains.

The amygdala is a key structure in the brain's limbic system, central to emotions like fear, anxiety, and aggression. Individual differences in amygdala size and reactivity correlate with how readily people interpret neutral expressions as threatening. Chronic stress causes the amygdala to become more excitable and larger, making individuals more prone to anxiety and perceiving menace where others don't.

Early life stress, even in the fetal stage, can lead to epigenetic changes, altering gene regulation without changing the DNA sequence. For example, high maternal glucocorticoid levels during pregnancy can cause an enlarged, more excitable amygdala in offspring, predisposing them to anxiety and interpreting neutral situations as threatening in adulthood. These effects can be transmitted non-genetically across generations.

Beyond subsistence levels, objective income is not a strong predictor of health or happiness. Subjective socioeconomic status (how one perceives their rank compared to others) is a better predictor. Inequality, especially local inequality amplified by social media, creates psychological stress that significantly impacts health, leading to 'feeling poor' regardless of absolute wealth.

Peter Attia observes a 'dawn effect' where his blood glucose levels are highest in the morning, even after nearly 24 hours of fasting, despite going to bed with low glucose. He attributes this to elevated morning cortisol (glucocorticoid) levels, which are a normal circadian response anticipating daily functioning, but can become disproportionate due to underlying stress.

Effective stress management requires regular, dedicated time, similar to exercise or healthy eating habits. Merely committing to a consistent daily practice, even for 20 minutes, can significantly improve mental health by allowing for recovery from stress. Identifying and limiting personal triggers, like checking email only twice a day, can also reduce chronic stress exposure.

Sapolsky believes genes are often overrated; they primarily modify vulnerability and predispositions, emerging only in certain environments. For example, specific variants of genes related to serotonin transport or aggression (MAOA) only significantly increase the risk of depression or violence when coupled with childhood stress or abuse, highlighting the crucial interplay between genetic tendencies and environmental factors.

Sleep deprivation leads to elevated cortisol levels, particularly when sleep is unpredictably fragmented. Cortisol rises in anticipation of waking and stays high during interrupted sleep, compromising sleep quality by reducing restorative delta sleep and adenosine stores. This chronic elevation of glucocorticoids further damages the hippocampus, worsening memory and accelerating brain aging.

Despite common perception, the actual direct evidence for stress causing cancer, bringing it out of remission, or accelerating tumor growth is minimal in humans. Animal studies show acute stress can accelerate tumor growth in artificial systems (e.g., virally induced tumors), but these are not broadly applicable. However, supportive group therapy for cancer patients has been shown to enhance survival, primarily by improving patient compliance with difficult medical treatments, not by direct biological anti-stress effects.

Chronic stress and elevated glucocorticoids damage the frontal cortex, impairing judgment, impulse control, executive function, and long-term planning. This explains why people make terrible decisions under extreme emotional arousal. Furthermore, stress narrows the 'window' of empathy, making individuals less empathic towards strangers and more parochial, linking chronic stress to negative social behaviors.