Identification of an immuno-inflammatory biomarker in the brain supports potentially more effective personalized treatment for major psychiatric disorders

December 11, 2025 – Individuals with psychiatric disorders exhibiting seemingly similar symptoms often respond very differently to the same treatment, suggesting that distinct biological processes are at work beneath the surface of similar clinical presentations. Researchers have now identified a distinct immuno-inflammatory biomarker across major psychiatric disorders that can be detected using non-invasive brain imaging. Patients exhibiting this brain signature showed systemic inflammation and poorer response to standard treatments. The findings of the new study in Biological Psychiatry, published by Elsevier, lay the foundation for a biology-augmented diagnostic framework in psychiatry and detail the potential for biomarker-guided, anti-inflammatory precision therapies.

Neuroimaging links diverse biological mechanisms to clinical manifestations, providing compelling insights into the neural mechanisms underlying brain function implicated in psychiatric diseases. Through neuroimaging, shared neural correlates have been increasingly identified across major psychiatric disorders such as schizophrenia, major depressive disorder, and bipolar disorder. While subtypes within and across psychiatric diagnoses have been identified, the biological underpinnings remain unclear. This study aimed to uncover these hidden “biotypes,” focusing particularly on brain inflammation—a mechanism thought to drive illness in a subset of patients, but which is difficult to measure directly in the living brain.

The research was conducted in two independent cohorts. In the first stage, brain connectivity scans were combined with blood-based molecular (DNA methylation) data to identify a brain network pattern linked to immune system dysfunction. In the second longitudinal stage, investigators validated that patients with this brain marker had higher blood inflammation indices—such as neutrophil-to-lymphocyte ratios—and showed less improvement with conventional treatments during hospitalization.

“This two-step validation establishes both the biological relevance of the marker and its potential value for clinical prediction,” says lead investigator Fei Wang, MD, PhD, Early Intervention Unit, Department of Psychiatry, Affiliated Nanjing Brain Hospital, and Functional Brain Imaging Institute, Nanjing Medical University, China. “Our study fills a critical gap in understanding psychiatric heterogeneity. By linking a specific brain network pattern to immune dysregulation, we move beyond describing symptoms to uncovering a biological ‘why.’”

Co-investigator Lili Tang, MD, PhD, Early Intervention Unit, Department of Psychiatry, Affiliated Nanjing Brain Hospital, and Functional Brain Imaging Institute, Nanjing Medical University, China, adds, “For the first time, we can visualize an ‘inflamed brain type’ shared across multiple psychiatric disorders. What excites us most is the clinical promise—helping doctors quickly identify patients unlikely to respond to standard therapies and guide them toward treatments that truly help.”

This study bridges brain imaging and molecular immunology by directly linking a measurable brain connectivity pattern to an immune-inflammatory pathway that cuts across traditional diagnostic boundaries. Psychiatry is moving toward biologically informed precision medicine, and anti-inflammatory treatments are emerging as promising new interventions. These findings provide the biomarker needed to match the right therapy with the right patient.

Co-lead investigator Xizhe Zhang, PhD, Early Intervention Unit, Department of Psychiatry, Affiliated Nanjing Brain Hospital, Functional Brain Imaging Institute, and School of Biomedical Engineering and Informatics, Nanjing Medical University, China, notes, “Subtyping complex psychiatric disorders is inherently challenging. The data-driven subtypes we report should be viewed as an intermediate step toward mechanistic stratification. While the early biological and clinical signals are encouraging, they remain preliminary and will require independent replication and prospective validation.”

John Krystal, MD, Editor of Biological Psychiatry, concludes, “Inflammation is a critical disease process that crosses psychiatric disorders. Pinpointing the ‘inflammatory subtypes’ of these disorders may help to refine treatments for this group. In the future, a simple brain scan could help clinicians identify patients less likely to respond to standard drugs and more likely to benefit from targeted anti-inflammatory interventions—potentially shortening the time to effective treatment.