Immune alterations in schizophrenia and the effects of a therapeutic antibody: a neuroimaging study
Bibliographic record
Abstract
Immune dysfunction is implicated in the pathophysiology of schizophrenia. The 18 kDa translocator protein (TSPO), expressed by various cell types, including microglia and astrocytes, is widely used as a marker for neuroinflammation and can be quantified in vivo using PET. However, findings from TSPO PET studies in recent-onset psychosis have been inconsistent, and it remains unknown whether TSPO levels can be modified in schizophrenia. We addressed these questions with a baseline case-control comparison of patients with a first-episode psychotic disorder who were symptomatic despite antipsychotic treatment and healthy volunteers, and a longitudinal study testing the effects of natalizumab (a monoclonal antibody previously shown to reduce TSPO levels in neuroinflammatory conditions) on TSPO levels and symptoms in patients. Baseline and 3-month follow-up brain imaging was carried out using 18F-DPA-714 TSPO PET, quantified as the distribution volume ratio (DVR) in total, frontal lobe and temporal lobe grey matter. A total of 103 volunteers (62 patients and 41 healthy controls) received baseline brain imaging, and 47 patients completed follow-up imaging after receiving natalizumab (n = 31) or placebo (n = 16) infusions. Natalizumab was well tolerated, with no serious treatment-related adverse events. The patient group also received clinical assessments with the Positive and Negative Syndrome Scale at baseline and follow-up. At baseline, DVR was significantly higher in patients relative to controls in total (η2 = 0.04) and temporal lobe (η2 = 0.06) grey matter. However, there was no significant change in DVR across these regions following natalizumab or placebo treatment. Mean ± standard deviation (SD) CSF levels of natalizumab after treatment were 10.7 ± 27.2 ng/ml, indicating that the monoclonal antibody crossed the blood-brain barrier. Patients receiving natalizumab showed a modest but statistically significant improvement in Positive and Negative Syndrome Scale total scores (mean ± SD change: -3.7 ± 9.1, Cohen's d = 0.40, P = 0.017), although there was no relationship between change in DVR and change in symptom severity (P > 0.05). These findings are consistent with elevated grey matter TSPO levels in first-episode psychosis relative to healthy controls. Although natalizumab treatment was associated with a modest reduction in symptoms, the absence of corresponding changes in DVR suggests that higher grey matter TSPO might reflect expression by non-microglial cells. The lack of significant changes in the placebo group indicates that it is a stable trait biomarker. Further work is needed to clarify the functional relevance and cellular specificity of TSPO alterations in psychosis. ClinicalTrials.gov: NCT03093064.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.001 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one teacher head, not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".