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Last Updated: 14.06.23

Dr. Charles Raison on Depression, the Immune-​​Brain Interface & Whole-​​Body Hyperthermia

Dr. Charles Raison, M.D., is a professor at the University of Wisconsin-​Madison’s School of Human Ecology and the Founding Director of the Center for Compassion Studies at the University of Arizona. His research focuses on inflammation, stress-​​related depression, compassion training, and the potential therapeutic use of heat stress for major depressive disorder.

Key Takeaways

High level takeaways from the episode.

Inflammatory markers (cytokines) found to be elevated in depressed people

  • Exposure to inflammatory chemicals increases the likelihood of developing depression
  • Chronic inflammatory activation can induce changes in the brain and body that increase the risk of depression
  • Human depression may have evolved out of sickness


Significant overlap between symptoms of sickness and depression

  • Depression is associated with shunting iron and zinc, raising body temperature
  • Inflammation induces sickness, which shares many characteristics with depression 
    • Pro-​​inflammatory genes may increase survival in high pathogen areas but increase risk of depression in low pathogen areas

Obesity and inflammation

  • Obese individuals often have higher markers of inflammation and are more likely to be depressed
  • Weight loss may improve mood and decrease inflammation
  • Blocking inflammation before stress exposure can prevent apoptosis and downstream behavioral effects in rodents

Hot yoga elevates core body temperature, similar to hypothermia treatment

  • Many people find hot yoga to be an effective antidepressant strategy
  • Possible mechanism of sauna: Heat stress increases beta-​​endorphins and dinorphin, which may sensitize mu-​​opioid receptors to endorphins

Exercise activates IL‑6 without activating IL-​​1β or TNF

  • Exercise-​​induced IL‑6 activates interleukin-​​10 (IL-​​10), a powerful anti-​​inflammatory cytokine

FDA approval expected for a novel antidepressant that antagonizes kappa opioid receptors

  • Opposite effect of heat stress, which stimulates kappa receptors

Study on hypothermia treatment: real heat treatment group showed significant increase in IL‑6 levels. Higher IL‑6 levels correlated with reduced depression symptoms and increased happiness.

  • Exercise causes branched-​​chain amino acids (BCAAs) to be taken up into muscle cells, allowing more tryptophan to enter the brain and produce serotonin
  • Exercise also causes muscle cells to take up kynurenine, preventing the formation of neurotoxic quinolinic acid
  • Hyperthermia treatment can induce hypothermia, which may help recalibrate and strengthen anti-​​inflammatory pathways in the brain and body

Exercise has various mechanisms that positively affect depression

  • Hormetic effect
  • Increased serotonin
  • Hypothermic effect
  • Anti-​​inflammatory effect

Study on heat shock protein 105 in mice

  • Mice with increased heat shock protein 105 were protected from depressive symptoms after stress tests

Running to the point of exhaustion is considered one of the natural states closest to the mind of a Buddha in Tibetan Buddhist texts.

Humans are the best thermoregulators in the animal world

  • Can outrun any animal for 100 miles in a hot environment

Inflammation may drive rumination

  • Inflammatory molecules change the brain’s rumination center (dorsal anterior cingulate)
  • Rumination is a significant part of depression

Running can help reduce anxiety and improve mood.

About 70% of people do better with antidepressants than with a placebo, while 25% do worse

  • Antidepressants can be a helpful short-​​term solution, but they may not address the root causes of depression

The New Mind-​​Body Science of Depression

  • Book by Dr. Charles Raison and Vladimir Maletic
  • Covers inflammation, evolutionary aspects, risk factors, and neurobiology of depression


Reduce inflammation for Depression


Exercise for Depression


Sauna, Hot Yoga, Hypothermia for Depression


Meditative States and Mystical Experiences for Depression



  • Dr. Charles Raison on Depression, the Immune-​​Brain Interface & Whole-​​Body Hyperthermia

    Found My Fitness #41

    Dr. Charles Raison, M.D., professor at the University of Wisconsin-​​Madison, researches inflammation, stress-​​related depression, compassion training, and heat stress therapy.

Full Notes

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