'Can Biomarkers Distinguish Psychosis From Depression?'

 New research suggests that depression and psychosis may be distinguishable in the earliest stages of illness by analyzing inflammatory markers in the blood and structural changes in the brain gray matter. A study published in JAMA Psychiatry reported that the two disorders exhibit distinct biological signatures, even at disease onset.

Currently, diagnosis is made based largely on clinical symptoms. Identifying reliable biomarkers could support earlier targeted interventions and potentially reduce the risk for severe disease progression.

PRONIA Study 

This study was based on the Personalized Prognostic Tools for Early Psychosis Management (PRONIA) project, an EU-funded initiative that uses machine learning to develop predictive models for psychotic and affective disorders.

For this multicenter study, David Popovic, MD, PhD, of the Max Planck Institute of Psychiatry in Munich, Germany, and colleagues analyzed data from 678 participants in the PRONIA project to clarify the role of inflammatory biomarkers and brain structure in the early stages of depression and psychosis. 

The participants included individuals with recent-onset depression (n = 163), psychosis (n = 177), or a clinical high-risk state for psychosis (n = 172), along with 166 healthy individuals.

Most participants had minimal prior exposure to psychiatric medications. Data were collected between 2013 and 2018.

Biological Signatures 

The researchers evaluated inflammatory signatures in the blood by measuring cytokine levels and assessed structural brain changes using MRI to quantify gray matter volume. Particular attention was focused on limbic brain regions, which play a significant role in processing emotions.

The analysis showed disease-specific patterns of cytokine alterations in early-stage conditions in the study participants. Importantly, the biological signatures associated with depression and psychosis did not overlap. Across all datasets and analytical models, the researchers observed consistent differences between the two disorders in inflammatory markers and brain structure.

Intervention Implications 

“These signatures open up novel approaches for both biologically and psychosocially grounded early interventions in depression and psychosis. This paves the way for tailored therapies, depending on whether the young person is on a depression or psychosis developmental curve,” Popovic said in a press release.

However, Lana Kambeitz-Ilankovic, PhD, a study author with the Department of Psychiatry and Psychotherapy, University of Cologne, and Faculty of Psychology and Educational Sciences, Ludwig Maximilian University of Munich, Germany, said, “Our findings are not intended to replace established clinical diagnoses based on symptoms and treatment, which also takes into account the psychosocial situation of the patients. However, our findings on the respective biomarkers could enable clinicians to better differentiate between the two diseases at an early stage in the future.”

https://www.medscape.com/viewarticle/can-biomarkers-distinguish-psychosis-depression-2026a100080b