Fatigue: An Imbalance in Dopamine?

This piece, by Onno Berkan, was published on 04/01/25. The original text, by Dobryakova et al., was published by Frontiers in Neurology on 03/11/15.

This Rutgers study explores a fascinating theory of fatigue based on the neurotransmitter dopamine. The researchers propose that fatigue occurs due to a chemical imbalance. Dopamine's influence on cognition follows a reverse-U-shaped function, wherein too much or too little of it leads to cognitive impairment. The researchers suggest that the same may be true with fatigue. This is called the dopamine imbalance hypothesis.This was tested through multiple sclerosis (MS) patients, who often suffer fatigue as a symptom of their condition. 

Dopamine is produced in specific brain areas and travels through various pathways to movement, motivation, and thinking regions. The study suggests that when these dopamine pathways are disrupted, it can lead to symptoms of fatigue. This disruption can be seen through brain imaging studies. MS patients show structural and functional abnormalities in brain regions that typically receive dopamine signals, such as the striatum and the prefrontal cortex. Additionally, medications that increase dopamine levels in the brain have been shown to help reduce fatigue in various conditions, including traumatic brain injury, chronic fatigue syndrome, and cancer.

The researchers also discuss how dopamine might interact with the immune system, which is particularly relevant for MS patients. They explain that specific immune cells can produce and respond to dopamine, and disruptions in this system might contribute to fatigue. Interestingly, some common MS treatments that affect the immune system might also influence dopamine levels, potentially affecting fatigue levels.

The study suggests that treating fatigue might require finding the right balance of dopamine, as both too much and too little could be problematic. Some clinical trials have shown promise in using dopamine-increasing medications to treat fatigue, though more research is needed to determine the optimal dosage and treatment approach.

This hypothesis provides a new framework for understanding fatigue, which has been challenging to study and treat effectively. The researchers propose that future studies focus on better understanding how dopamine levels affect fatigue and how medications targeting dopamine might be used more effectively to treat fatigue. They also suggest brain imaging studies could help track how dopamine-related brain connections change with treatment.

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