Advancing an Inflammatory Subtype of Major Depression

Chronic inflammation plays a prominent role in multiple medical disorders, including psychiatric diseases such as major depression. Exposure to inflammatory stimuli leads to changes in neurotransmitter systems and neurocircuits in the brain that are associated with depressive symptoms. Blockade of inflammatory cytokines can reduce depressive symptoms in medically ill and medically healthy individuals with depression. Increased levels of biomarkers of inflammation are associated with an overrepresentation of neurovegetative symptoms, including anhedonia, fatigue, and psychomotor slowing, and can predict response to antidepressant treatments. Importantly, however, increased inflammatory biomarkers occur in only a subgroup of individuals with depression. Thus, there appears to be a subset of patients with depression with a unique symptom presentation and treatment response whose disease is primarily driven by inflammation. Further identifying and characterizing this inflammatory subtype of depression can foster the development of treatments targeting the immune system and its effects on the brain. Moreover, by using this mechanism-based approach to parsing the heterogeneity of depression, we can refine our diagnostic nosology and model a strategy for precision medicine and targeted therapeutics in psychiatry.