Neuroimaging of Immune Changes and Natalizumab Effects in First-Episode Psychosis
Overview
This study demonstrates elevated TSPO levels in grey matter of first-episode psychosis patients compared to healthy controls, indicating neuroinflammation. Treatment with natalizumab modestly improved symptoms but did not alter TSPO binding, suggesting TSPO expression may involve non-microglial cells.
Background
Schizophrenia is a disabling psychiatric disorder with limited treatment options targeting its underlying biology. Microglial activation and neuroinflammation, marked by increased TSPO expression, have been implicated in its pathophysiology. PET imaging of TSPO provides a non-invasive measure of neuroinflammation. Natalizumab, a monoclonal antibody effective in reducing TSPO in neuroinflammatory diseases, was tested for its potential to modulate TSPO and symptoms in schizophrenia.
Data Highlights
Group
Sample Size
TSPO DVR (Total GM)
TSPO DVR (Temporal Lobe GM)
Symptom Change (PANSS Total)
Patients (Baseline)
62
Significantly higher vs controls (η2=0.04)
Significantly higher vs controls (η2=0.06)
NA
Healthy Controls (Baseline)
41
Reference
Reference
NA
Patients + Natalizumab (Follow-up)
31
No significant change
No significant change
Mean change −3.7 ± 9.1 (Cohen’s d=0.40, P=0.017)
Patients + Placebo (Follow-up)
16
No significant change
No significant change
No significant change
Key Findings
TSPO binding was elevated in total and temporal lobe grey matter of first-episode psychosis patients compared to healthy controls.
No significant correlation was found between baseline TSPO levels and symptom severity.
Natalizumab treatment for 3 months was well tolerated and crossed the blood–brain barrier as evidenced by CSF levels.
Patients receiving natalizumab showed a modest but statistically significant improvement in overall symptom scores (PANSS total).
There was no significant change in TSPO binding after natalizumab or placebo treatment, and no correlation between TSPO changes and symptom improvement.
TSPO elevation may reflect expression by non-microglial cells, and TSPO binding appears to be a stable trait biomarker in schizophrenia.
Clinical Implications
Elevated TSPO binding confirms neuroinflammatory involvement in early psychosis, but targeting microglial activation with natalizumab did not reduce TSPO levels despite modest symptom improvement. TSPO PET may serve as a stable biomarker but may not directly reflect microglial activity modifiable by current immunotherapies. Further research is needed to clarify TSPO cellular specificity and to develop targeted treatments.
Conclusion
This study confirms elevated TSPO levels in first-episode psychosis and demonstrates that natalizumab can modestly improve symptoms without altering TSPO binding. These findings suggest complex immune alterations in schizophrenia and highlight the need for further investigation into the cellular mechanisms underlying TSPO expression.
by Yuya Mizuno, Ines Carreira Figueiredo, Toby Pillinger, Guy Hindley, Luke Baxter, Sita Parmar, Maria C Lobo, Jacek G Donocik, Ivana Rosenzweig, Anish Gupta, Ilaria Callegari, Sami Jeljeli, Joel T Dunn, Alexander Hammers, Ramla Awais, Kerstin Sander, Erik Årstad, Marios Politis, Julia J Schubert, Mattia Veronese, Federico E Turkheimer, Tiago Reis Marques, Oliver D Howes
