Figure 3.

This figure compares sickness behavior with clinical depression. Sickness behavior is energy saving, helps to eradicate the trigger, and has anti-inflammatory effects and as such enhances recovery and is part of a compensatory (anti)-inflammatory reflex system (CIRS). Increases in pro-inflammatory cytokines (PICs) underpin both sickness behavior and clinical depression and thus may explain the partial phenomenological overlap. Depression, however, is a chronic disorder with a specific course and pathophysiology and the presence of a CIRS that downregulates the primary inflammatory response. Disorders in tryptophan catabolites (TRYCATs), cell-mediated immune (CMI) activation, and oxidative and nitrosative stress (O&NS), and, in particular, their sequelae (O&NS damage, sensitization, autoimmunity and neuroprogression) are the specific organic substrates of depression. While sickness behavior is a behavioral response to acute triggers, the onset of depression is associated with multiple less-well defined trigger factors, for example, brain disorders, such as Alzheimer (AD), Huntington (HD), and Parkinson (PD) disorder, stroke and multiple sclerosis (MS); systemic disorders, such as cardio-vascular disorder (CVD), chronic obstructive pulmonary disorder (COPD), rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), inflammatory bowel disorder (IBD), diabetes, metabolic syndrome, HIV infection, cancer, bacterial translocation; and conditions, such as postpartum period, hemodialysis, and interferon-(IFN)α based immunotherapy.