New research from BBRF-funded scientists shows how a sad mood can change the inflammatory environment in the body, potentially contributing to the process by which depression becomes chronic. These moods also may worsen other illnesses such as diabetes and heart disease, as well as pain.

According to a study published August 18th in the journal Molecular Psychiatry, a sad mood drives up levels of an immune-signaling molecule called interleukin 18 in the blood. This effect, the scientists found, depends on the activity of opioid neurotransmitters and is most pronounced in people suffering from major depression.

Even though researchers know that certain diseases occur more commonly in people with major depression, the biological link between mood and health has remained poorly understood. Identifying that link could lead to better treatment and prevention for such diseases.

Interleukin 18 helps trigger a variety of immune functions in the body and can strongly induce inflammation. It is known to be elevated in people with major depression, and has also been associated with heart disease. The opioid system, which produces pain-relieving neurotransmitters, is also disrupted in people with major depression. NARSAD 2013 Young Investigator Alan Rodney Prossin, M.D., of the University of Texas Health Sciences Center at Houston, wondered whether interactions between the opioid system and interleukin 18 might underlie the impact of depression on physical health.

To investigate, Dr. Prossin, the first author of the newly published research, and colleagues, measured the amount of interleukin 18 in the blood of 28 women, during both sad and neutral moods. Thirteen of the women had major depressive disorder. PET scans were used to analyze opioid release in specific brain regions. To provoke a sad mood, the scientists asked study participants to focus on emotions they had experienced during the death of a loved one, for example. They evoked a neutral mood by asking the women taking part in the study to simply focus on sensations they experienced in the PET scanner.

The researchers, who also included Jon-Kar Zubieta, M.D., Ph.D., a 2013 NARSAD Distinguished Investigator at the University of Michigan who also received NARSAD grants in 1998, 2002 and 2004, found that interleukin 18 levels in the blood were highest during a sad mood, and that levels dropped when participants adopted a neutral mood. Although the changes occurred in all study participants, they were most dramatic among the women with major depression. Further analyses showed that in people with major depression, the sadness-induced increase in interleukin 18 was accompanied by an increase in opioid release in the amygdala, a brain region that helps control emotion.  

Read the paper.