Inflammation has been a front-of-mind nemesis for as long as I can remember. Back in the days when I competed in extreme distance races, minimizing proinflammatory cytokines and "the inflammatory reflex" was always a top priority. As an athlete and coach, I knew from scientific literature (Dinarello, 2000; Tracey, 2002) and road-tested experience that inflammation impeded sports performance and hampered recovery.

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For example, at the 135-mile Badwater Ultramarathon through Death Valley, knee-high compression socks and full-body dunks in an 18-gallon Rubbermaid Roughneck ice bath (on the side of the road) were par for the course, when it came to keeping inflammation at bay.

That said, I never thought inflammation might affect someone's motivational mindset until this morning when I read a new theory (Treadway et al., 2019) by scientists at Emory University who posit that chronic inflammation may cause a chain reaction that reduces the brain's supply of , which is necessary for reward-driven . This paper, "Can't or Won't? Immunometabolic Constraints on Dopaminergic Drive," was recently published by Trends in Cognitive Sciences.

This paper adds to converging evidence suggesting that proinflammatory cytokines associated with chronic, low-grade inflammation directly affect the human mesolimbic dopamine system, and subsequently influence psychological motivation.

This theory by Emory scientists speculates that the connection between dopamine levels, motivation, and the inflammatory response might be an adaptive mechanism that evolved to conserve the body's energy reserves in times of severe distress. If their theory is correct, it could help to explain the lack of motivation associated with clinical and other psychological disorders.

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Theoretically, modern-day lifestyle factors such as physical inactivity, processed foods, and constant —which are associated with chronic inflammation—may trigger maladaptive mechanisms that have evolved since ancient times to constrain dopamine-driven motivation and conserve energy while the immune system heals the body.

As the authors explain, "This theoretical framework can inform how the mesolimbic dopamine system responds to increased immunometabolic demands during chronic inflammation, ultimately contributing to motivational impairments in and other medical disorders."

The first author of this paper, Michael Treadway, is a clinical psychologist, and assistant professor in the Department of Psychology at Emory University.

In a statement about his most recent study (2019), Treadway said, "When your body is fighting an infection or healing a wound, your brain needs a mechanism to recalibrate your motivation to do other things so you don't use up too much of your energy. We now have strong evidence suggesting that the immune system disrupts the dopamine system to help the brain perform this recalibration."

The co-authors of this paper are Andrew Miller, who is an internationally recognized professor of Psychiatry and Behavioral Sciences in Emory's School of Medicine and Jessica Cooper, who is a postdoc fellow in Treadway's lab (TReAD Lab).

"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," Miller said in a statement. "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."

The Emory authors used a state-of-the-art computational method which allowed them to test their theory by gauging the impact of low-grade chronic inflammation on effort-based . In the paper's abstract, they conclude: "Here, we suggest that the metabolic demands of chronic low-grade inflammation induce a reduction of striatal dopamine that in turn leads to a steeper effort-discounting curve because of reduced perceived ability (can't) versus preference (won't) for reward."

Author's note: In The Athlete's Way (2007), I recommend that anyone who is second-guessing his or her ability to finish a race ask a simple question: "Is quitting now a matter of can't or won't?" Clearly, this decades-old advice echoes the can't/won't terminology used in the latest paper by Michael Treadway and colleagues. In a follow-up post, I'm going to unpack the role of "can't" or "won't" explanatory styles through the lens of sports and .

Proinflammatory Cytokines May Contribute to Impulsivity

The latest findings on inflammation and motivation by Treadway et al. (2019) dovetail with another new paper, "Experimentally-Induced Inflammation Predicts Present Focus" published in the June 2019 issue of Adaptive Human Behavior and Physiology. This paper posits that there may be a link between proinflammatory cytokine levels and present-focused decision-making.

This research was led by Jeffrey Gassen, who is a member of Sarah Hill's Evolutionary Social Psychology Lab and a doctoral candidate at Texas Christian University (TCU).

In a recent interview with Eric Dolan of PsyPost, "Inflammation Affects Our Decision-Making Patterns, Study Suggests," Gassen said:

"We developed a hypothesis that the immune system may play an important role in calibrating individuals' behavior to their bodily state, given that the immune system both monitors the state of the body and can communicate with the brain. Specifically, inflammation increases when the body is threatened or in poor condition, a time when an individual needs to invest in what's going on right now (whether it be rewards, opportunities, or taking steps to recover) and think less about the future."

Gassen and colleagues are particularly interested in exploring the link between proinflammatory cytokines and delay discounting, which is the impulsive tendency to take an immediately available small reward instead of waiting for a more substantial future reward.

Another recent paper on this topic by Gassen et al., "Inflammation Predicts Decision-Making Characterized by Impulsivity, Present Focus, and an Inability to Delay Gratification," was published in March 2019 by the journal Scientific Reports.

In the Discussion section of this paper, Gassen and his co-authors write:

"In addition to providing support for the hypothesized evolutionarily-grounded model, the results of the current research are consistent with recent theoretical work suggesting that inflammation plays a role in , a construct closely related to present-focused decision-making. This latter model posits that inflammatory activity may impair self-regulation, which is then hypothesized to alter developmental trajectories in ways that further reinforce inflammation and the inability to self-regulate."

Taken together, the latest research and theoretical models relating to proinflammatory cytokines, impulsive decision-making (Gassen et al., 2019) and dopaminergic drivers (Treadway et al., 2019) advances our understanding of the psychological repercussions of chronic low-grade inflammation. However, more research is needed to fully understand these complex mechanisms. As Gassen and co-authors conclude in their recent Scientific Reports paper, "Experimental studies are also needed to make firm conclusions about the causal relationships between inflammation and present-focused decision-making proposed by these models."