CFS Gene Study Targets Serotonin Function

Journal Highlights, Research News | 18. Jan, 2008 by | 0 Comments

By Suzanne Vernon, PhD, Scientific Director

One of the most recent studies on serotonin in CFS was published last month in the journal Psychoneuroendocrinology. In this study, investigators looked for genetic differences in people with CFS, focusing on several genes important to the function of the serotonergic system. They found that differences in one receptor for serotonin were associated with CFS. Laboratory experiments showed that these variations might cause different levels of this receptor to be available. This is significant because if there aren’t enough receptors for serotonin, an imbalance in the body could result. It’s the first study to show an association of CFS with this specific gene.

Serotonin has been around since the dawn of life. It appears to be evolutionarily conserved among many living organisms, from worms to humans. When something remains relatively unchanged for this long and in this many different organisms, it clearly plays a fundamentally critical role in maintaining life. Serotonin and the serotonergic system are essential for maintaining energy balance and homeostasis—elements people with CFS long to improve and increase.

The serotonergic system is a complex network of nerves, chemicals, transporters and receptors. It might be helpful to think of the serotonergic system like roads (nerves), people (serotonin), cars (transporters) and parking spaces at destinations (receptors). In humans, most of the nerves that respond to serotonin are in the brain and, in fact, highly concentrated in a part of the brain that has been implicated in CFS: the hypothalamus. Receptors on these nerves allow serotonin to temporarily “park,” and this sends a signal to the nerve that then initiates a response.

A well-characterized serotonin response is energy balance, where serotonin helps us regulate our relationship with the environment (such as finding and eating food), which in turn affects what happens inside our body (digesting food for energy storage and use). Though most of the nerves that respond to serotonin are in the brain, 95 percent of the body’s serotonin is found in the gut, and there are even bits of serotonin in our tongue. So, when we initiate a behavior such as eating, serotonin spurs a series of events that is essential for maintaining the body’s overall balance and homeostasis.

As reported in Psychoneuroendocrinology, the study examined 77 differences in genes related to serotonin function, uncovering three markers in the receptor subtype called HTRA2a that appear to be associated with CFS. Further analysis supported the implication that this receptor subtype may play a role in the pathogenesis of the illness.


Smith AK, Dimulescu I, Falkenberg VR, Narasimhan S, Heim C, Vernon SD, Rajeevan MS. Genetic evaluation of the serotonergic system in chronic fatigue syndrome. Psychoneuroendocrinology 2007; Dec 11 [Epub ahead of print]

Suzanne Vernon, PhD, is the Association’s scientific director. She has nearly two decades of experience as a microbiologist.

January 18, 2008