Depression and Inflammation: Dr Rhonda Patrick's interview with Dr Charles Raison

[whitecoast]

I recently discovered the website Found my Fitness.com, which can process raw genetic data from various companies that do genetic sequencing. The advice given for some of the results seemed to be coming from an informed place, so I decided to check out the podcast hosted by the website's owner, Dr Rhonda Patrick. I found a very informative interview with Dr Charles Raison. His bio:

Charles Raison, M.D. is a professor at the School of Human Ecology at the University of Wisconsin-Madison and Founding Director of the Center for Compassion Studies in the College of Social and Behavioral Sciences at the University of Arizona. Dr. Raison’s research focuses on inflammation and the development of depression in response to illness and stress. He also examines the physical and behavioral effects of compassion training on the brain, inflammatory processes, and behavior as well as the effect of heat stress as a potentially therapeutic intervention major depressive disorder.

I'd summarize the 2-hour interview, but Rhonda's episode webpage, containing a summary, timeline of show, glossary, and transcript, is so chock-full of information I'm just going to share a bunch of it at length here:

Summary:

In this nearly 2-hour episode, we discuss...

• The reason we may have evolved an immune-mediated depressive response in the first place, a hypothesis Dr. Raison calls the "Pathogen Host Defense" theory of depression or "PATHOS-D." Read Dr. Raison’s paper on PATHOS-D.
• How depression as a disease may be subdivided based on the involvement of chronic inflammation.
• The changes in functional brain connectivity that are associated with the high inflammation subtype of depression.
• The place inflammation may have in the treatment for depression, even among members of the low inflammation subgroup.
• How inflammation can play a somewhat double role where on the one hand immune cells can release beneficial growth factors in response to stimulation from cytokines, but on the other hand, how this response can become reduced from excessive and chronic stimulation over time.
• Ways to naturally elicit a transient but potentially beneficial "hit" of inflammatory cytokines.
• How higher eating frequency may help promote a low-grade inflammation due to a postprandial inflammatory response.
• The potentially therapeutic effects of whole-body hyperthermia for major depressive disorder.
• The physiological similarity of hot yoga with whole-body hyperthermia from the standpoint of potentially therapeutically boosting body temperature.
• Some of the short-term endocrine changes that happen during heat stress, especially related to the opioid pathway, which may help account for some of the anti-depressant phenomena associated with whole-body hyperthermia.
• The role of an important cytokine known as IL-6 in depression and how this cytokine which fluctuates during activities such as exercise and whole-body hyperthermia also exhibits anti-inflammatory properties through another cytokine called IL-10.
• How the anti-depressant effects of whole-body hyperthermia may actually intimately depend on the spike in IL-6.
• The role IL-6 plays as a myokine by conferring beneficial metabolic adaptations in response to exercise, including increased insulin sensitivity.
• How taking an NSAID or even certain antioxidants like vitamin C and vitamin E at the wrong time can diminish some of the benefits of exercise, such as satellite cell migration and improved insulin sensitivity.
• Heat stress as a means to sensitize pathways important to thermoregulatory cooling that also affect brain regions implicated in the regulation of mood.
• The thermoregulatory dysregulation found in other relevant psychiatric conditions outside of depression, such as schizophrenia.
• An evolutionary-biological explanation for why chronic inflammation shunts tryptophan, an important precursor of serotonin, into a neurotoxic pathway that produces a substance called kynurenine, which can become a neurotoxic NMDA agonist known as quinolinic acid that is powerfully associated with depression.
• How kynurenine can then go on to become a metabolite known as quinolinic acid which is powerfully associated with depression.
• How our muscles actually help us shift the metabolism of kynurenine away from quinolinic acid when we exercise, particularly if that exercise is endurance exercise.
• Some of the preliminary evidence that increased expression of a certain heat shock protein in the brain may influence behavior by protecting against stress-induced depression.
• The biological wisdom that may be embedded in traditional spiritual practices when it comes to keeping depression at bay… especially the use of phasic high-heat, often for healing or transcendent purposes, but also potentially other practices like fasting and ultra long distance running.
• The role that heat tolerance played as a unique human adaptation enabling persistence hunting in early humans. Watch a video of persistence hunting.
• The staggering lengths that some indigenous tribes went through to induce a classical psychedelic-like experience as a rite of passage, including subjecting themselves to extensive bites or consuming them for their venom.
• Some of the growing body of literature surrounding the effects of psychedelic-occasioned mystical experiences for depression, end-of-life anxiety among cancer patients, and even as an aid in smoking cessation.
• The ability of meditation to induce real changes in the gray matter of the brain and some of the interesting evidence showing that the effects of meditation can begin to build and show up in as little as 8-weeks.
• The place that some of these lifestyle interventions or hacks may increasingly have in clinical practices for the management of mood disorders.
• The dilemma clinicians face in figuring out which of their patients, around a quarter of the depressed population, will actually be made worse by the current standard of care SSRIs.
• The possibility that antidepressants, by being a type of so-called "unearned grace," may prevent enduring behavioral changes and create a type of long-term reliance and potentially increased vulnerability.
• Dr. Raison’s perspective on so-called ancient wisdom traditions that may offer broad transformative value for creating states of mind that may be inimical to depression.

The role bright light therapy may have in the amelioration of a variety of depressive disorders and how our modern relationships with screens that increase our light at night and office environments that reduce our light during the day may disrupt our natural biological rhythms to our detriment.

I was really fascinated by the information, and also just impressed in general by how comprehensive the podcast website is (especially the courtesy of including a glossary). The transcript is also great if you're interested but don't have two hours to watch a video or listen to a podcast.

 

[Uperios]

Can Ending Inflammation Help Beat Depression?​

Story at a glance:

• Intermittent inflammation is critical to support life, but chronic inflammation is linked to depression and many chronic diseases that are the leading causes of mortality worldwide, such as heart disease, chronic kidney disease and diabetes
• Data show medications that reduce inflammation help reduce symptoms of depression, including in those with treatment-resistant depression. Medications like alpha interferon spike the inflammatory response and increase the risk of psychosis and depression
• Early life stressors that induce inflammation can increase the risk of chronic diseases and are associated with more stubborn forms of depression. Inflammation in the brain is also associated with fibromyalgia and may be linked to reduced cognitive function in older adults
• Black seed oil has anti-inflammatory properties that were studied to help lower the inflammatory response to COVID-19. Other nutrients that help lower inflammation include ginger, omega-3, vitamin E, turmeric and bromelain

 

[heinrich]

i am really thankful for this thread having been initiated.

 

[heinrich]

continued...
i suffer from depression since a long time and i have never understood why, and in spite of my efforts to overcome it.
i have never belived the serotonin hypothesis, because in my opinion it is not verifyable experimentally. but doctors seem to believe it. in my opinion, they just fondle in the dark...
some time ago, i read a book by an english doctor who noticed on himself the correlation between inflammation and depression. i forgot which book.

 

[heinrich]

continued...
but i observe a continuous cold symptoms, clogged nose, throat congestion... a low level of inflammation.
since the serotonin assumption did not heal me, i would be pleased to read about other cases and which anti inflammation medicine you use.