Identification of an Immuno-Inflammatory Biomarker in the Brain Supports Potentially More Effective Personalized Treatment for Major Psychiatric Disorders

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 studyopens in new tab/window in Biological Psychiatryopens in new tab/window, 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.

Notes for editors

The article is "Identification and Validation of Immuno-Inflammatory Neuroimaging Markers Across Major Psychiatric Disorders,” by Lili Tang, MD, PhD, Xiaohong Gong, PhD, Xinru Wei, PhD, Rui Tang, BM, Yongxia Ren, MM, Pengfei Zhao, MM, Chao Xie, PhD, Wei Cheng, PhD, Rongxin Zhu, MD, PhD, Yanqing Tang, MD, PhD, Xizhe Zhang, PhD, and Fei Wang, MD, PhD (https://doi.org/10.1016/j.biopsych.2025.10.004opens in new tab/window). It appears online in Biological Psychiatry, published by Elsevier.

The article is openly available for 60 days at https://www.biologicalpsychiatryjournal.com/article/S0006-3223(25)01524-0/fulltextopens in new tab/window.

Copies of the full text and additional information are also available to credentialed journalists upon request; please contact Rhiannon Bugno at [email protected]opens in new tab/window. Journalists wishing to interview the authors should contact Fei Wang, MD, PhD, at [email protected]opens in new tab/window (for clinical perspectives), and Xizhe Zhang, PhD, at [email protected]opens in new tab/window (for computational perspectives).

The authors’ affiliations and disclosures of financial and conflicts of interests are available in the article.

This study was an interdisciplinary collaboration between a clinical team led by Dr. Fei Wang (with Dr. Lili Tang) and a computational team led by Prof. Xizhe Zhang (with Dr. Xinru Wei). All authors and their contributions are listed in the article.

John H. Krystal, MD, is Chairman of the Department of Psychiatry at the Yale University School of Medicine, Chief of Psychiatry at Yale-New Haven Hospital, and a research psychiatrist at the VA Connecticut Healthcare System. His disclosures of financial relationships and conflicts of interests are available hereopens in new tab/window.

The authors were supported by research grants from NSFC-Guangdong Joint Fund (U20A6005), Jiangsu Provincial Key Research and Development Program (BE2021617), National Natural Science Foundation of China (62176129), National Key Research and Development Program (2022YFC2405603), National Key Research and Development Program (2022YFC2405603), Key Project supported by Medical Science and Technology Development Foundation, Jiangsu Commission of Health (ZD2021026), and Jiangsu Provincial Key Research and Development Program (BE2022160).

About Biological Psychiatry

Biological Psychiatryopens in new tab/window is the official journal of the Society of Biological Psychiatryopens in new tab/window, whose purpose is to promote excellence in scientific research and education in fields that investigate the nature, causes, mechanisms, and treatments of disorders of thought, emotion, or behavior. In accord with this mission, this peer-reviewed, rapid-publication, international journal publishes both basic and clinical contributions from all disciplines and research areas relevant to the pathophysiology and treatment of major psychiatric disorders.

The journal publishes novel results of original research which represent an important new lead or significant impact on the field, particularly those addressing genetic and environmental risk factors, neural circuitry and neurochemistry, and important new therapeutic approaches. Reviews and commentaries that focus on topics of current research and interest are also encouraged.

Biological Psychiatry is one of the most selective and highly cited journals in the field of psychiatric neuroscience. It is ranked 9^th out of 156 Psychiatry titles and 17^th out of 271 Neurosciences titles in Journal Citation Reports^TM, published by Clarivate. The 2024 Impact Factor score for Biological Psychiatry is 9.0.www.sobp.org/journalopens in new tab/window

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