The Mind and Body Connection: The Correlation between Stress and Inflammation

Jill Littrell, PhD
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In their book, Psychiatry Under the Influence (2015), Whitaker and Cosgrove suggest that researchers of the human condition might improve the integrity of their investigations by foregoing connections to marketing interests.  The research examining the ways in which depressive/anxious behaviors correlate with markers of inflammation has been conducted outside of psychiatry, although a few psychiatrists have contributed.  Early studies were conducted by neuroscientists Steven Maier and Linda Watkins and veterinarian Robert Dantzer.  Psychiatrist Michael Maes was also an early pioneer.  Psychiatrist Andrew Miller entered the field later having worked with Robert Dantzer.  Michael Irwin is also a psychiatrist, but he works with Naomi Eisenberger and Matt Lieberman, who are social psychologists.  Chris Lowry is a neuroscientist.

In my reading of this literature and my conversations with some of these luminaries, they seem primarily driven by curiosity.  When these scientists publish their work, they generally talk about their findings in terms of behavioral observations rather than diagnostic categories.  For the most part, they aren’t concerned with diseases. Rather, they examine those conditions which change behavioral outcomes.  An assumption made by all these researchers, is that behavior originates in the brain.  Members of the International Society for Ethical Psychology and Psychiatry call for a day when clinicians will ask “what happened to you?” rather than “what is wrong with you?”  However, what happens to you must change brain function in some way, if a change in behavior results.  Scientists in the field of psychoneuroimmunology have investigated these connections.

Links among depression, stress and inflammation.  An explosion of research has documented the link between the experience of stressful conditions, markers of inflammation in the blood, and the experience of depressive feelings and behaviors.  Inflammatory hormones (called cytokines) are elevated in persons diagnosed with depression (Raison, Capuron, & Miller, 2006).  Persons undergoing the stress of caring for a loved one with Alzheimer’s disease show elevations in inflammatory markers (Kiecolt-Glaser, et al., 2003).  In the Whitehall studies of employees in the British Civil Service system, those who were paid less and had less control over their work schedules, as a group, were higher on inflammatory markers even after controlling for possible differences in diet and smoking (Steptoe et al., 2003). Most recently, Setiawan et al. (2015), using brain imaging strategies, measured the level of activated white blood cells in brain and found a correlation between level of depression and activation of microglia, the brain’s major type of white blood cell.  About 1/3 of persons diagnosed with major depressive disorder exhibit elevations in inflammatory white blood cell hormones (cytokines) (Tartter, Hammen, Bower, Brennan, & Cole, 2015).

Showing Causal Association between Stress and Inflammation.  Beyond the correlational studies, there is research in which animals have been manipulated in some way and then inflammation has been measured.  Animals have been subjected to bouts of foot shock that they were unable to control.  Subsequently, these animals display depressed behavior (not eating sweet foods, avoiding other animals, moving less).  They also had higher amounts of inflammatory cytokines in brain and when the researchers put in a molecular sponge to bind up the inflammatory cytokine in brain, the animals reverted to normal behavior (Maier & Watkins, 1998). These studies showed that stressing the animal results in both more depressive behaviors and that these depressive behaviors are caused by the brain inflammatory factors.

Showing a causal link between infection and depression.  Researchers also know that another way to cause inflammatory factors to rise in the brain is by inducing infection in the periphery.  A number of experimenters have placed the wall of a bacterium into the paw of a rodent.  Subsequently, inflammatory cytokines increase in brain and the animal loses preference for sweet liquids, avoids other animals and moves less.  Again, if the researcher puts in a molecular sponge to bind up the inflammatory factors, the behavior of the animal reverts to normal (Maier & Watkins, 1998).

Showing causal link between inflammation and distress in people.  The accumulation of the animal findings has prompted similar studies in people.  Researchers have placed the wall of a bacterium into the periphery.  The wall of the bacterium in the body results in activation of areas of the brain associated with alarm, less response to money in reward areas, and stronger activation in the amygdala (an anxiety center) in response to scary images (Eisenberger et al., 2009, 2011; Inagaki et al., 2012).  In another approach, researchers arranged for research-participants to feel bad.  They had their research-participants play a computer game with others tossing a frisbee type object around.  Then suddenly the research-participant gets excluded.  Again, activation in the brain’s alarm area is noted.  However, if the research-participant had taken acetaminophen (Tylenol), an anti-inflammatory, before the study, then the alarm area remained quiet and people reported less distress (Dewall et al., 2010).

The causal role that inflammation plays in producing depression and anxiety has many implications.  Many reports of depression preceding dementia, heart disease, strokes, cancer have been published in samples of persons who were not taking antidepressants.  The common factor in all of these conditions is inflammatory processes.

In order to promote my new book, Neuroscience for Psychologists and Other Mental Health Professionals: Promoting Well-Being and Treating Mental Illness, I have launched a website, www.littrellsneuroscienceofwellbeing.org .   My book covers the story on how inflammation influences mood, hearing voices, and depressed/anxious behaviors.  The book covers the pathways through which diet, exercise, meditation, yoga and harmonious relationships with others can influence inflammation and thereby ameliorate distress.  On my website, I will be updating the findings in this fast-changing area.  Since the material should have broad interest, I will after a little editing, post many of these findings and my comments on this site as well.

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References:

Dewall, C. N, Macdonald, G., Webster, G. D., Masten, C. L., Baumeister, R. F., Powell, C., . . . Eisenberger, N. I.  (2010).  Acetaminophen reduces social pain:  behavioral and neural evidence.  Psychological Science, 21 (7), 931-947.

Eistenberger, N. L., Berkman, E. T., Inagaki, T. K., Rameson, L. T., Mashal, N. M., & Irwin, M. R.  (2100)  Inflammation-induced anhedonia:  endotoxin reduces ventral striatum responses to reward.  Biological Psychiatry, 68(8), 748-754.

Eisenberg, N., Inagaki, T. K., Rameson, L. T., Marshal, N. M., & Irwin, M. R.  (2009).  An fMRI study of cytokine-induced depressed mood and social pain:  the role of sex differences.  Neuroimage, 47(3), 881-890.

Inagki, T. K., Muscatell, K. A., Irwin, M. R., Cole, S. W., & Eisenberger, N. I. (2012).  Inflammation selectively enhances amygdala activity to socially threatening images.  Neuroimage 59(4), 3222-3226.

Kiecolt-Glaser, J. K., Preacher, K. J., MacCallum, R. C., Atkinson, C., Marlarkey, W. B., Emery, C. F., & Glaser, r.  (2003).  Chronic stress and age-related increases in proinflammatory cytokine IL-6.  PNAS, 100(15), 9090-9095.

Maier, S. F., & Watkins, L. R.  (1998).  Cytokines for psychologists:  implications of bidirectional immune-to-brain communication for understanding behavior, mood, and cognition.  Psychological Review, 105(1), 83-107.

Raison, C. L., Capuron, L., & Miller, A. H.  (2006).  Cytokine sing the blues: inflammation and the pathogenesis of depression.  Trends in Immunology, 27(1), 24-31.

Setiawan, E., Wilson, A. A., Mizrahi, R., Rusjan, P. J., Miller, L., Rajkowska, G., Suridjan, I., Kennedy, J. L., Rekkas, P. V., Houle, S., & Meyer, J. H.  (2015).  Role of translocator protein density, a marker of neuroinflammation in the rain during major depressive episodes.  JAMA Psychiatry, 72 (3), 268-275.

Steptoe, A., Kunz-Ebrecht, S., Owen, N., Feldman, P. J., Rumley, A., Lowe, G. D., & Marmot, M.  (2003).  Influence of socioeconomic status and job control of plasma fibrinogen responses to acute mental stress.  Psychosomatic Medicine, 65(1), 137-144.

Tartter, M., Hamman, C., Bower, J. E., Brennan, P. A., & Cole, S.  (2015).  Effects of chronic interpersonal stress exposure on depressive symptoms are moderated by genetic variation at IL6 and Il1β in youth.  Brain, Behavior, and Immunity, 46, 104-111.

15 COMMENTS

  1. Thank you for this – this post resonates with me and just gave me an ‘aha’ – namely why problems can be both relationship driven and health driven. Any tips about what to do when someone is not yet willing to help themselves by changing diet, exercise etc, etc,

  2. those who were paid less and had less control over their work schedules, as a group, were higher on inflammatory markers even after controlling for possible differences in diet and smoking (Steptoe et al., 2003).

    How can that controlling really be done ? It seems like an awfully difficult thing to do.

  3. Jill, This is an important subject your writing about. I will check out your website. Have you seen Russell L. Blaylock M.D. retired neurosurgeon’s comprehensive article which can be googled … How Vaccines Can Damage Your Brain …. He has much to say about inflammation and has seen it in autopsies he’s done He’s done 100 or so videos on youtube on various topics of vital interest to our community. He has testified in Congress in the USA and been basically ignored. Such is the power of the Cartels of the Theraputic State to ignore any truths which interfere with business as usual the concentrated power and cash-flow of the elite while evermore subjugating the people.

  4. This is good stuff, and it rings true in my own life. When I had my crack up, I had to use cortisone products on both my face and scalp. My hair was thinning rapidly. I had health problems. Ah, but once hospitalized and shocked…my problems were reduced to psychiatric issues. Was something wrong physically? Absolutely. Did the experts care? Hell no.

    I’m just 1 person with a story like this. Its crazy, really. I’ve recovered, praise God, but…here in the US, “recovery” is damn nigh impossible. For a lot of “mental patients,” the only doc they/we’ll ever see is a shrink. Even if they/we go to a real doc, that doc may just ignore the problems. Just a drain on society…

    Thanks for the article. Weirdly enough, I’m starting to think that having more people on psych meds might prove to be a good thing. I mean, when enough people are failed by “standard treatment,” maybe more resources will be allocated to actually helping people.

  5. Thanks for this article – I will order the book, as I have noted a significant improvement since I started looking at pro and pre-biotics and shifting to a diet rich in fish, greens and wholly unprocessed foods. After a few weeks on the changed regime, I found it interesting that within hours of eating a large helping of fructose/corn syrup-rich candy I was in significant pain (arthritis) and felt very emotionally “rough” indeed. I’ll not do that again in a hurry.

    While I am still sorting out the long term aftermath of cruel psychiatric treatment and resultant trauma, I have found that it is far easier to understand and digest material that surfaces regarding what happened when my body isn’t attacking itself and making me feel like crap because of the food I have eaten!

    My whole system, inside and out, feels “cooler” – I really don’t know how else to describe it – and I am excited to hear that so much valuable research in being done into this field.

    Very glad that you will share you work on this site.

  6. An assumption made by all these researchers, is that behavior originates in the brain.

    The trouble is that however convenient it is for these researchers to make that assumption it is not one that stands up. The assumption that the mind body problem is solved is one of the biggest mistakes in psychiatry. And even they know its not true.

    It leads straight back to “what is the mind?” and therefore “what does it mean to be a person, a human”.

    The mind could just as easily be leading the brain. They ignore this because its just to difficult to contemplate even though it could just as easily be true. And just as likely is. Uncomfortable as it sounds all this “research” while potentially interesting is ultimately dehumanising for precisely this reason. Understandably they won’t want to hear this. But its the truth, even if its an uncomfortable one for them.

    • A very interesting comment above by the ever articulate , Theinarticulatepoet .
      It sends me to so many thoughts and ideas and truths.
      A book I have somewhere on Sri Ramana Maharishi has an introduction written by Carl Jung. He wrote to paraphrase ,
      “On the white spiritual plane that India is Sri Ramana Maharishi is it’s whitest spot.” He was a great sage of India and even Mahatma Gandhi came to him with questions. He was teaching that a person should first inquire who they themselves are . That wherever a person is from, whatever language they speak, within whatever culture anywhere on the globe, when they point to themselves they all touch the same spot on their body. A place that is to the right of the heart. I always found that very interesting.
      The Sage taught a meditation technique whereby a person sitting silently would silently ask themselves “Who Am I ? Whatever answer came up or sound or phenomena he was then instructed to ask “And To Whom Has This Occurred ? ” Then the answer “To Me” was again followed by the question “Who Am I ? And round and round and round until the mind quieted and the person was in an awakened state of awareness of all that was there peacefully aware without a thought , feeling most excellent and completely awake . And definitely not afraid of their own inner quietness and state of awareness .
      In Kam Yuen’s Chinese energy healing system , which combines the teachings from the East from Tai Chi, Qigong, Acupuncture, Chinese Traditional Medicine , and from the West from Quantum Physics, Biology,and Psychology . It looks at the human being as a biological computer that most all of us have no instruction manual to show us how to operate. Within the system the human being operates on 6 different levels simultaneously . Spiritual, Psychic, Physical , Emotional, Psychological,and Mental. Each level can effect any of the others and at a subconscious level a human being knows every thing about themselves . If they are weakened in some way this system can quickly in acute conditions strengthen them and in chronic conditions help or strengthen them over a longer time . See http://www.YuenMethod.com for more info.
      So much cones to mind see Robert Young’s book “Sick And Tired”. It is a must read.
      The spinal cord is really an extension of the brain . It is made up of the same tissue as the brain.
      I once put together a necklace out of various gemstones that acted definitely like a gemstone tranquilizer . Yes I tried it on other people about 5 at different times . They all said it worked without side effects . Yes I can tell you how to make one but you’d have to believe a psych survivor enough to ask. I also figured out other things that can help people in distress.
      As survivors we are gona have to make available to the people our best usable ideas somehow cause if Murphy passes, psychiatry will have grown even more dangerous tentacles. They’ve gone way far enough and need to be stopped and rolled back for the good of humanity.
      Inflammation on the skin most anywhere on the body if strongly suppressed with strong chemical meds or chemical ointments can turn into a mental emotional distress extreme state quick.

      • Another quote comes to mind by another sage that people from all over the world came to India to learn from. My favorite quote of his, Sri Nisargadatta Maharaj …” In wisdom I am nothing In love I am everything and my life moves between these two”…
        Or as a psychiatrist would say ” The wisdom is all within my skull ” “I learned it from the DSM which was copied from the instructional manual for conducting the Spanish Inquisition .” “Anyways, what’s love got to do with it ?”
        Did they take that from Tina Turner’s song?

  7. Jill,

    Although remotely connected to your promotional responsibilities and your recently published works’s individual value to us, the way that scholarship in philosophy of mind plays out in reply to cognitive neuroscience and the related programmatic issues that interest researcers in both of these diverse fields, certainly suggests to me that your book is important to read. Thank you for the timely and intelligent help you offer survivors and all mentally ill people and those who care about them by showing you care about the science they have to trust.