What immune markers are associated with negative symptoms in first episode psychosis?

Negative symptoms — such as lack of motivation, social withdrawal, and reduced emotional expression — are a core feature of first-episode psychosis (FEP) and strongly predict poor long-term outcomes. Researchers have been investigating whether immune system dysregulation contributes to these symptoms. The strongest evidence points to two inflammatory markers: interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α). However, the associations are modest, and the field is still evolving.

What the research says

A 2026 systematic review of seven case-control studies found that people with FEP generally have higher levels of inflammatory markers in their blood compared to healthy controls ⁴⁸. The most commonly studied markers were IL-6, IL-1β, and TNF-α. When researchers looked specifically at negative symptoms, IL-1β and TNF-α showed the most consistent positive associations — meaning higher levels of these markers were linked to more severe negative symptoms ⁴⁸. The associations were described as modest, and results varied across studies ⁴⁸.

A 2023 study on drug-naïve FEP patients found that those with an attenuated niacin response (a skin-flushing reaction linked to immune function) had more severe negative symptoms and formed a distinct subgroup with poorer outcomes ⁹. This suggests that immune-related subtypes may exist within FEP.

Another 2024 study examined transdiagnostic dimensions of psychosis and found that high levels of IL-6 and IL-1 were associated with the severity of depressive and negative symptom dimensions in FEP patients ¹⁰. This supports the idea that state inflammatory markers (like IL-6 and IL-1) may play a role in negative symptoms, though the evidence is strongest for IL-1β and TNF-α as trait markers ¹⁰.

It is important to note that the evidence is still limited. The systematic review included only seven studies, and many had small sample sizes ⁴⁸. More research is needed to confirm these findings and to understand whether immune markers could be targets for treatment.

What to ask your doctor

• Could my blood levels of IL-1β or TNF-α be related to my negative symptoms?
• Are there any ongoing studies on immune-based treatments for negative symptoms in first-episode psychosis?
• Should I have any blood tests to check for inflammation as part of my care?
• How do my negative symptoms compare to what is typically seen in first-episode psychosis?
• What are the current best approaches to managing negative symptoms?