Research has shown systemic inflammation causes an increase in depressive symptoms concurrent with changes in glucose metabolism in the parts of the brain responsible for mood and motivation, and the findings could lead to depression treatments for patients who have symptoms related to inflammation in the body or brain, according to a study published in the April issue of the Journal of Nuclear Medicine .
“Depression is associated with systemic inflammation, and the systemic inflammation caused by endotoxin administration elicits mild depressive symptoms such as fatigue and reduced interest,” wrote the authors, including Jonas Hannestad, MD, PhD, of the department of psychiatry at the Yale School of Medicine in New Haven, Conn. However, neural correlates of depressive symptoms resulting from inflammation had not been defined, so the researchers used F-18 FDG PET to determine which brain regions responded to systemic inflammation.
Nine healthy individuals received a double-blind endotoxin, which elicits systemic inflammation and mild depressive symptoms such as fatigue and reduced social interest, and a placebo on different days. After administration, F-18 FDG PET was used to measure the differences in the cerebral metabolic rate of glucose in the insula, cingulate and amygdala regions of the brain, and since the subjects were at rest, changes observed in the brain could only be attributed to systemic inflammation, according to the authors. Behavior changes were assessed on the Montgomery-Åsberg Depression Rating Scale (MADRS).
Results showed that endotoxin administration was associated with higher normalized glucose metabolism (NMG) in the insula and lower NMG in the cingulate compared to the placebo. Seven of nine subjects had an increase in NMG in the insula and a decrease in NMG in the cingulate, and all nine subjects had a decrease in NMG in the right anterior cingulate, suggesting that systemic inflammation induces fundamental physiologic changes in regional brain glucose metabolism. There was, however, no significant difference in the NMG in the amygdala.
The authors found a negative correlation between peak cytokine levels and change in social interest, and also between peak cytokine levels and changes in insula NGM. There was a positive correlation between the change in NGM in the insula and change in social interest.
Ratings on the MADRS increased for each subject after endotoxin administration, while no significant change was noted with the placebo.
Nearly 17 percent of adults experience depression at some point over their lifetimes, with 30.4 percent of cases classified as severe, according to the U.S. National Institute of Mental Health. Most researchers agree there are multiple mechanisms that can lead to depression symptoms.
“If we can show that a subtype of depression is caused in part by inflammation, we can test the ability of treatments that reduce inflammation in only patients in whom we believe inflammation plays a role,” Hannestad said in a statement. “In the future, I expect that researchers in this field will be able to develop more precise PET measures that can be used to distinguish between, for instance, a person with ‘inflammatory depression’ and a person with another kind of depression. PET could then be used as diagnostic biomarker to separate subtypes of depression and as a therapeutic biomarker to detect the response to treatment.”