Chronic inflammation may drive dopamine down, influence motivation

The brain’s dopamine system, which drives motivation, may be directly influenced by chronic inflammation, according to a new paper published in the journal Trends in Cognitive Sciences. T

his connection between dopamine, effort, and the inflammatory response is an adaptive mechanism to help the body conserve energy, researchers said.

In the paper, authors provide a computational method to experimentally test this theory. The computational method will allow scientists to measure the effects of chronic inflammation on energy availability and effort-based decision-making. The method may yield insights into how chronic, low-grade inflammation contributes to motivational impairments in some cases of depression, schizophrenia, and other medical disorders.

It has previously been shown that inflammatory cytokines, signaling molecules used by the immune system, impact the mesolimbic dopamine system. Recent research has revealed more insights into how immune cells can shift their metabolic states differently from most other cells. The researchers built on these findings to develop their theoretical framework.

An immune-system mechanism to help regulate the use of energy resources during times of acute stress was likely adaptive in our ancestral environments, rife with pathogens and predators. In modern environments, however, many people are less physically active and may have low-grade inflammation due to factors such as chronic stress, obesity, metabolic syndrome, aging, and other factors. Under these conditions, the same mechanism to conserve energy for the immune system could become maladaptive, the authors said.

The researchers are now using their computational method to test their theory in a clinical trial on depression. Other studies have provided evidence of an association between an elevated immune system, reduced levels of dopamine and motivation, and some diagnoses of depression, schizophrenia and other mental disorders.

"We're not proposing that inflammation causes these disorders," said Michael Treadway, PhD, corresponding author and an associate professor at Emory University in Atlanta, Georgia. "The idea is that a subset of people with these disorders may have a particular sensitivity to the effects of the immune system and this sensitivity could contribute to the motivational impairments they are experiencing."