Chronic inflammation removes motivation by reducing dopamine in the brain

Why do we feel listless when we are recovering from an illness? The answer is, apparently, that low-grade chronic inflammation interferes with the dopaminergic signaling system in the brain that motivates us to do things.

This was reported in a new paper published in the journal Trends in Cognitive Sciences.

The research carried out at Emory University explains the links between the reduced release of dopamine in the brain, the motivation to do things, and the presence of an inflammatory reaction in the body. It also presents the possibility that this is part of the body’s effort to optimize its energy expenditure during such inflammatory episodes, citing evidence gathered during their study.

The authors also published an experimental framework based on computational tools, devised to test the theory.

The underlying hypothesis is that the body needs more energy to heal a wound or overcome an infection, for instance, both of which are associated with low-grade inflammation. To ensure that energy is available, the brain uses an adaptive technique to reduce the natural drive to perform other tasks which could potentially drain away the energy needed for healing. This is essentially a recalibration of the specialized reward neurons in the motivation center of the brain, so that ordinary tasks no longer feel like they’re worth doing.

According to the new study, the mechanism of this recalibration is immune-mediated disruption of the dopamine pathway, reducing dopamine release.

The computational technique published by the scientists is designed to allow experimental measurements of the extent to which low-grade inflammation affects the amount of energy available, and the decision to do something based on the effort needed. This could allow us to better understand why and how chronic inflammatory states cause a lack of motivation in other disease conditions as well, including schizophrenia and depression.

Andrew Miller, co-author of the study, says, “If our theory is correct, then it could have a tremendous impact on treating cases of depression and other behavioral disorders that may be driven by inflammation. It would open up opportunities for the development of therapies that target energy utilization by immune cells, which would be something completely new in our field.”

It is already known that immune cells release cellular signaling molecules called cytokines, which affect the functioning of the dopamine-releasing neurons in the area of the brain called the mesolimbic system. This area enhances our willingness to work hard for the sake of a reward.

Dopamine
Image Copyright: Meletios, Image ID: 71648629 via shutterstock.com

Recently, it was discovered that immune cells also enjoy a unique capability to shift between various metabolic states, unlike other cells. This could affect cytokine release patterns in such a way as to signal the brain to conserve available energy for the use of the immune system.

These facts were the foundation of the new hypothesis, which explains it in terms of evolutionary adaptation. In the hypothetical early environment, the immune system, faced with abundant microbial and predatory challenges, needed tremendous amounts of energy. It therefore had its own mechanism to signal other body systems, via the mesolimbic dopamine system, to control the use of energy resources during periods when the organism was undergoing severe or sudden stress.

Modern life is relatively soft and less challenging. With less physical activity, low-grade inflammation is chiefly due to factors such as obesity, chronic stress, metabolic syndrome, aging and other lifestyle illnesses. This could mistakenly cause the mesolimbic dopamine neurons to produce less dopamine. Lower dopamine levels in turn decrease the motivation for work, by reducing the perception of reward while increasing the perception of effort involved. This ultimately conserves energy for use by the immune system.

Previous studies by Miller as well as other scientists have shown that a high level of immune functioning in association with low levels of dopamine and reduced motivation characterizes some cases of schizophrenia, depression and certain other mental health conditions.

The scientists do not think these disorders are caused by the low-grade inflammation, but that some people who have these illnesses are hypersensitive to immune cytokines. This could in turn cause them to lose motivation for daily living.

The scientists are currently performing a clinical trial on people with depression, to test the theory using the computational framework.

Source: Treadway M. T. et al., (2019). Can’t or Won’t? Immunometabolic Constraints on Dopaminergic Drive. Trends in Cognitive Sciences. https://doi.org/10.1016/j.tics.2019.03.003

Dr. Liji Thomas

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Dr. Liji Thomas

Dr. Liji Thomas is an OB-GYN, who graduated from the Government Medical College, University of Calicut, Kerala, in 2001. Liji practiced as a full-time consultant in obstetrics/gynecology in a private hospital for a few years following her graduation. She has counseled hundreds of patients facing issues from pregnancy-related problems and infertility, and has been in charge of over 2,000 deliveries, striving always to achieve a normal delivery rather than operative.

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Comments

  1. Valerie Lamoureux Valerie Lamoureux Canada says:

    How can I be part of this study

  2. Taylor Lucas Taylor Lucas United States says:

    This lack of motivation also can b from parkinsons, which is a lack of dopamine

  3. Taylor Lucas Taylor Lucas United States says:

    Parkinsons is a lack of dopamine as well and when one gets sick, takes forever to get well and it is very hard to get any motivation, I know.

  4. Eric Flores Eric Flores United States says:

    Great read!

  5. tim Driscoll tim Driscoll United States says:

    Brilliant Study! and lends to what the anti vaccine crowd has known for a long time...... connect the dots about inflammation and neurological maladies caused by adjuvents ..... aloha

  6. tim Driscoll tim Driscoll United States says:

    Adjuvents cause inflammation.... connect the dots ;)
    great research study. important information and correlation.

  7. DanteTube Rocks DanteTube Rocks United States says:

    Correlation and Causation are not the same thing........as any scientist or Doctor would tell you. Very interested in the study as I have Ehlers Danlos Syndrome and have consistent inflammation due to joint issues and constant dislocations. I have used nicotine and caffeine as well as other ways to increase energy just to live before I was diagnosed. This now makes a lot of sense as if I was depleted in Dopamine, that is why I was using and addicted to things that increased it in a reward system.

  8. r barbwe r barbwe United States says:

    Have always felt (with fibromyalgia and CFIDS/ME) that my body was fighting so too tired to do anything else, but never thought to relate it to feeling lazy on a good day. Some days I just don’t care about much of anything so this makes sense. Now how do I raise my dopamine levels?

  9. Joel Smit Joel Smit United States says:

    Would supplementing with a source of L-dopa such as mucus prurines off-set this process?  In my experience the answer would be no.  When my chronic pain became elevated my motivation and normal exuberance vanished.   No amounts of mucuna prurines and St. John's Wort alleviated the flatlined mental energy.  It has only somewhat returned as the weather warmed, but other pressures add to the overall stress.

    The big question is how does one fix the problem and get back to living a productive life?  I am rapidly running out of time and resources.

  10. Gerette Pease Gerette Pease United States says:

    Thanks for writing this and for focusing on non-operative births. ( I was named for the Patron Saint of Expectant Mothers-- Saint Gerard)
    I have fibromyalgia ( I suspect this is just a diagnosis of convenience) and
    suffer chronic pain and depression.
    God Bless You
    Peace
    Gerette

  11. tweety hallett tweety hallett United States says:

    Just ask any Lyme patient and you will really understand inflammation and lack of motivation or fatigue. this would be interesting to study for lymies

  12. Jacqui Olliver Jacqui Olliver New Zealand says:

    Interesting article. An increase in cortisol levels due to constantly being emotionally triggered by life's problems will also lead to increased inflammation. Mental and physical illness are often the end result of suppressing your emotions and not dealing with the issues which are triggering them.

  13. rhonda abbott rhonda abbott United States says:

    Very interesting article.  How does one increase their dopamine levels. I have fibromyalgia, chronic fatigue, problems with my adrenal gland, hashimotos autoimmune disease and MTHFR.  I wish someone would do a study on me and help me feel better.

The opinions expressed here are the views of the writer and do not necessarily reflect the views and opinions of News Medical.
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