Researchers at Emory University have provided compelling evidence supporting the existence of an inflammatory subtype of major depression, a breakthrough that could transform how this complex disorder is diagnosed and treated.
Led by Andrew H. Miller, MD — a pioneer in inflammation research related to depression — Emory investigators highlight inflammation as a key driver of depressive symptoms in approximately 25 to 30% of patients. Their work is featured in three recent journal publications.
“We now understand that inflammation plays a crucial role in a subset of people with depression,” says Miller, William P. Timmie Professor of Psychiatry and Behavioral Sciences in the Department of Psychiatry and Behavioral Sciences at Emory University School of Medicine. “This recognition creates an unprecedented opportunity to develop targeted treatments and deliver personalized care to patients who need it most.”
Miller, who serves as the director of the Behavioral Immunology Program at Emory, leads a team whose expertise in neuropsychiatric and immunological research is driving innovations that promise to reshape diagnosis and treatment for millions affected by major depression.
Their research identifies elevated inflammatory markers — such as C-reactive protein (CRP), tumor necrosis factor (TNF) and interleukin-6 (IL-6) — in the blood, brain tissue and cerebrospinal fluid of affected patients. These biological signals correlate with specific symptoms including anhedonia, fatigue and psychomotor slowing, often described as “sickness behavior.”
Importantly, patients with this inflammatory profile respond differently to treatments. Traditional antidepressants like selective serotonin reuptake inhibitors (SSRIs) may be less effective, while alternatives such as ketamine or electroconvulsive therapy show greater promise. This has significant implications for tailoring treatments to individual patients.
The Emory team stresses future clinical trials must incorporate biomarkers like CRP to identify and enrich patient groups with this inflammatory subtype. Doing so will improve the precision of treatments and accelerate the development of new therapies targeting inflammation-related pathways. This growing body of work marks a significant step toward precision psychiatry, offering hope for improved outcomes in one of the world’s most challenging mental health conditions.
Miller also advocates for the inclusion of an inflammation specifier in upcoming editions of diagnostic manuals such as the Diagnostic and Statistical Manual of Mental Disorders, or DSM-6.
“Including this new category could help doctors better understand the different types of depression, make treatment more personalized and effective, and speed up research into treatments that target the underlying biology of the illness,” Miller explains.
The three publications co-authored by Miller and colleagues include JAMA Psychiatry, where the authors propose adding inflammation as a specifier for major depression in the upcoming DSM-6. In Biological Psychiatry, Miller, along with Emory colleagues Jennifer Felger, PhD, and Ebrahim Haroon, MD, outline a clinical trial framework specifically designed for this inflammatory subtype. In the third publication, The American Journal of Psychiatry, Miller offers a comprehensive perspective on the scientific and clinical implications of inflammation as a core mechanism in a subset of depression.