Sneezing, coughing, and a sore throat are hallmark symptoms of a common cold, but what keeps you in bed are the accompanying fatigue, inattentiveness, loss of appetite, change in sleep pattern, heightened perception of pain, and apathetic withdrawal. This "sickness behavior" is induced by inflammatory markers released in response to illness. (1), (2) These symptoms are similar to the constellation of symptoms that define depression. Within the inflammatory response to illness, we see the shadow of depression, but the precise relationship remains murky.
Is depression part of a normal somatic inflammatory response run amok? Some researchers have argued that "sickness behavior" is adaptive, forcing the body into a constricted pattern in order to funnel energy into healing. (1), (3) If depression and inflammation are related, depression pushes past these adaptive roots and is less a forced pause than a debilitating withdrawal. Perhaps depression, or a subtype, is a sign of inflammation along with heat, pain, redness, and swelling. In some instances, depression may be a sign of an underlying inflammatory process. (4)
In our progression toward understanding depression's pathophysiology, we see factors that point to a relationship between depression and inflammation:
* depression frequently is comorbid with many inflammatory illnesses
* increased inflammatory biomarkers are associated with major depressive disorder (MDD)
* exposure to immunomodulating agents may increase the risk of developing depression
* stress can activate proinflammatory pathways
* antidepressants can decrease inflammatory response
* inhibition of inflammatory pathways can improve mood.
Exploring these factors and a possible pathway linking inflammation and neurobiologic changes found in depression allows us to look closer at the possible integration of the inflammatory process and depressive symptoms.
Illness and depression rates
Individuals with inflammatory illnesses--autoimmune diseases, cardiovascular disease, diabetes, and cancer--often struggle with depression. Nearly 1 in 5 persons with cardiovascular disease experiences MDD. (5) A diabetes diagnosis doubles the odds of having depression. (6) Up to 70% of patients with autoimmune diseases, such as rheumatoid arthritis or systemic lupus erythematosus, experience depression. (7), (8) In a large-scale longitudinal study, having a prior autoimmune disease increased the risk of depression by 45% and history of hospitalization with infection increased a patient's risk by 62%; the risk more than doubled in individuals with both. (9) Several studies show that 15% to 25% of cancer patients experience depression, (10) compared with 9% in the general population. (11)
Role of inflammatory markersTable Evidence linking inflammation and depression Study Sample Comments Dowlati A meta-analysis of 24 Depressed patients et al, studies measuring had significantly 2010 (14) cytokine concentrations in higher patients with concentrations of MDD TNF-[alpha] and IL-6 compared with controls Maes 15 controls and 35 Serum IL-6 and IL-1 et al, 1997 inpatients with MDD. receptor antagonist (15) Serum IL-6, IL-6 receptor, were higher in IL-1 receptor individuals with antagonist, Clara cell depression protein 16, and or sCD8 were measured at treatment-resistant baseline and at depression compared 5 weeks after with controls antidepressant treatment Raison 162 patients with Thirty-nine percent et al, 2005 hepatitis C infection of subjects (16) were assessed...