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Exploring the Relationship Between Inflammatory Biomarkers and Negative Symptoms Subtypes in Individuals at
Dulari Hakamuwa Lekamlage1, Ling Min Amelia Ang1, Luba Sominsky1,2
1Institute for Mental and Physical Health and Clinical Translation (IMPACT), School of Medicine, Deakin University, Geelong, Australia.
Early Intervention in Psychiatry
|July 1, 2026
Summary
Inflammation may not broadly distinguish schizophrenia negative symptom subtypes in individuals at Ultra-High Risk (UHR). However, higher sICAM-1 levels were linked to lower odds of primary negative symptoms.
Area of Science:
- Neuroscience
- Psychiatry
- Immunology
Background:
- Negative symptoms are a core feature of schizophrenia, impacting up to 60% of patients.
- These symptoms are categorized into primary (intrinsic) and secondary (external factors) types, with subtypes including diminished expression and amotivation/anhedonia.
- Inflammation is implicated in schizophrenia and linked to negative symptoms, but subtype-specific inflammatory profiles in individuals at Ultra-High Risk (UHR) for psychosis remain unclear.
Purpose of the Study:
- To investigate whether inflammatory marker profiles differ across negative symptom subtypes in UHR individuals.
- To examine the association between specific inflammatory markers and primary negative symptoms (PNS) versus secondary negative symptoms.
Main Methods:
- A secondary analysis of 147 UHR participants from the Staged Treatment in Early Psychosis (STEP) study was performed.
- Six inflammatory markers (Alpha-2-Macroglobulin, IL-6, CRP, sICAM-1, sVCAM-1, suPAR) were assessed.
- Multinomial and binomial logistic regression models, adjusted for covariates, were used to analyze differences across negative symptom subgroups.
Main Results:
- Most inflammatory markers showed no significant association with negative symptom subgroups.
- Elevated soluble intercellular adhesion molecule-1 (sICAM-1) levels were associated with lower odds of primary negative symptoms compared to no negative symptoms.
- Younger age correlated with increased odds of PNS and amotivation, while smoking was linked to higher odds of secondary negative symptoms.
Conclusions:
- Inflammation does not appear to broadly differentiate negative symptom subtypes in UHR individuals.
- sICAM-1 may play a role in the early stages of psychosis related to negative symptoms.
- Larger, longitudinal studies are needed to confirm these findings and explore the contribution of inflammatory changes to specific negative symptom emergence.
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