One difference that researchers have discovered between patients with atypical depression vs non-atypical depression and healthy controls is that inflammation appears to be significantly greater in those with atypical depression. In fact, this group of patients could be skewing the numbers: “The elevation in inflammatory markers that has been consistently observed in groups of depressed patients might be due to the subgroup of depressed patients with atypical depression,” Jesse Stewart, PhD, a psychology professor at Indiana University-Purdue University Indianapolis, told Psychiatry Advisor.

In a small study that appeared in the journal Psychiatry Research in June 2014,4 researchers found that participants with atypical depression had higher levels of the proinflammatory cytokine interleukin-6 (which is involved in the immune response) than other patients with depression.  The investigators noted that “some evidence suggests that elevated cytokine levels in patients with major depression are responsible for the development of metabolic syndrome in patients suffering from MDD.”4


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In a study co-authored by Stewart and published in August 2014 in the Journal of Behavioral Medicine,1 researchers tested blood levels of C-reactive protein (CRP) in three groups: participants with atypical depression; those with non-atypical depression; and other with no depression. CRP is a substance produced by the liver that is considered an inflammatory marker; it has been found to predict coronary artery disease, the most common type of heart disease.

Results show that, as compared with the other groups, almost twice the number of participants with atypical depression had CRP levels that placed them in a range suggesting high cardiovascular risk. Levels did not differ significantly between the no-depression and the non-atypical depression groups. As for which comes first, “there is convincing evidence that the relationship between depression and inflammation is bidirectional; depression may precede inflammation in some people, whereas inflammation may precede depression in others,” said Stewart.