Brain Imaging Biomarker Shows How Inflammation Can Predict Poor Treatment Response in Psychiatric Disorders

Psychiatric disorders like schizophrenia, major depressive disorder, and bipolar disorder often look similar on the surface. Patients may share overlapping symptoms, receive the same diagnosis, and even be prescribed identical medications. Yet, their responses to treatment can be dramatically different. Some improve quickly, while others show little to no progress despite following standard care. This long-standing puzzle has raised a critical question in psychiatry: are there hidden biological differences beneath similar symptoms?

A new study published in the journal Biological Psychiatry offers a compelling answer. Researchers have identified a distinct brain-based biomarker linked to immune inflammation that helps explain why some patients respond poorly to conventional psychiatric treatments. Even more importantly, this marker can be detected using noninvasive brain imaging, opening the door to more personalized and biologically informed mental health care.

Why Similar Psychiatric Symptoms Don’t Always Mean the Same Biology

Traditional psychiatric diagnoses rely heavily on clinical symptoms and behavioral observations. While this approach is essential, it does not always reflect what is happening biologically inside the brain. Over the last decade, research has increasingly shown that conditions like depression, schizophrenia, and bipolar disorder may share overlapping brain network abnormalities despite being classified as separate disorders.

This study set out to move beyond symptom-based labels and identify what researchers call “biotypes”—biological subgroups of patients that cut across traditional diagnoses. The focus here was on inflammation, a biological process already suspected to play a role in psychiatric illness but notoriously difficult to measure directly in the living brain.

Using Brain Connectivity to Detect an Inflamed Brain Type

The researchers used functional brain connectivity scans, which analyze how different regions of the brain communicate with each other. Instead of examining isolated brain areas, they focused on whole-brain networks, an approach that better reflects how the brain operates in real life.

To strengthen the biological relevance of these scans, the team combined neuroimaging data with blood-based DNA methylation profiles. DNA methylation is an epigenetic mechanism that influences gene activity, including genes involved in immune and inflammatory responses.

By integrating these two data sources, the researchers identified a specific brain connectivity pattern associated with immune system dysfunction. This pattern represented a clear immuno-inflammatory brain signature, distinct from other connectivity profiles.

Two Independent Cohorts Strengthen the Findings

One of the study’s strongest features is its two-stage design, which helped ensure that the results were not accidental or limited to a single group of patients.

In the first stage, researchers analyzed brain scans and blood samples to identify neuroimaging patterns linked to immune-related DNA methylation changes. This step allowed them to uncover a candidate biomarker tied to inflammation.

In the second stage, the team tested this biomarker in a separate, longitudinal patient cohort. These patients were followed over time during hospitalization, allowing researchers to examine how the biomarker related to real-world clinical outcomes.

The results were striking. Patients who showed the immuno-inflammatory brain signature also had higher levels of systemic inflammation in their blood, including elevated neutrophil-to-lymphocyte ratios, a well-established marker of immune activation.

Poorer Response to Standard Treatments

Perhaps the most clinically important finding was how this brain biomarker related to treatment outcomes. Patients with the inflamed brain signature consistently showed less improvement when treated with standard psychiatric medications during hospitalization.

This finding helps explain why some patients appear “treatment resistant” despite receiving appropriate care. It suggests that inflammation may interfere with the effectiveness of conventional psychiatric drugs, which are not designed to target immune pathways.

By validating both the biological and clinical relevance of the biomarker, the study provides strong evidence that this is not just a theoretical discovery, but a finding with real predictive value.

A Shared Marker Across Multiple Psychiatric Disorders

One of the most fascinating aspects of the study is that the immuno-inflammatory biomarker was found across multiple diagnoses, including schizophrenia, major depressive disorder, and bipolar disorder. This supports the idea that inflammation is a transdiagnostic process, meaning it operates across traditional diagnostic boundaries.

Rather than viewing psychiatric disorders as completely separate entities, this research reinforces a growing scientific view that many mental illnesses may share common biological mechanisms, even if their symptoms differ.

What This Means for Precision Psychiatry

Psychiatry has long lagged behind other medical fields when it comes to biomarker-guided treatment. In oncology or cardiology, biological tests routinely guide therapy choices. Mental health care, by contrast, often relies on trial and error.

This study represents an important step toward precision psychiatry. A simple brain scan could eventually help clinicians identify patients who are unlikely to respond to standard medications and who may benefit from alternative approaches.

One particularly promising avenue is anti-inflammatory treatment. If inflammation is driving symptoms and treatment resistance in a subset of patients, therapies that target immune pathways could be more effective than traditional drugs alone.

Anti-Inflammatory Treatments and Mental Health

Interest in anti-inflammatory treatments for psychiatric disorders has been growing for years. Studies have explored the use of nonsteroidal anti-inflammatory drugs, cytokine inhibitors, and even lifestyle interventions like diet and exercise to reduce inflammation and improve mental health outcomes.

However, results have been mixed, partly because these treatments were applied broadly rather than selectively. The biomarker identified in this study could serve as a filter, helping clinicians determine which patients are most likely to benefit from inflammation-targeted therapies.

The Role of Neuroimaging in Future Diagnosis

Another key takeaway from this research is the expanding role of neuroimaging in psychiatry. Functional connectivity analysis allows scientists to move beyond static brain images and examine dynamic communication patterns between brain regions.

As imaging technology becomes more accessible and analytical tools improve, brain-based biomarkers like this one could become part of routine psychiatric assessment. This would represent a major shift away from symptom-only diagnosis toward a biology-augmented diagnostic framework.

Important Limitations and Next Steps

Despite its promise, the research is still at an early stage. The authors emphasize that the findings require independent replication and prospective validation before being used in everyday clinical practice.

The identified subtypes should be viewed as an intermediate step, not a final answer. Psychiatric disorders are complex, and inflammation is likely just one of several biological pathways involved. Still, the clarity of the signal found in this study makes it a strong candidate for further investigation.

Why This Study Matters

This research helps answer one of psychiatry’s most persistent questions: why do patients with similar symptoms respond so differently to the same treatment? By identifying a measurable brain signature linked to immune inflammation, the study shifts the conversation from descriptive diagnosis to mechanistic understanding.

In the future, a noninvasive brain scan combined with simple blood tests could help guide treatment decisions, shorten the time to effective care, and reduce the frustration of trial-and-error prescribing.

Most importantly, it brings psychiatry closer to the broader medical goal of matching the right treatment to the right patient, based on biology rather than guesswork.

Research paper:
https://doi.org/10.1016/j.biopsych.2025.10.004