136. Increased Expression of Early Complement Components in Frontal Cortex in Schizophrenia
Bibliographic record
Abstract
Background: The complement system is a key effector of innate immunity, mediating elimination of pathogens and debris via initiation of phagocytosis, inflammation, and cell lysis. Intriguingly, recent studies have identified an additional role for early complement components, including C1q, C3, and C4, in synaptic pruning and remodeling. Mounting evidence suggests that dysregulation of the complement system occurs in schizophrenia. Increased activation and concentration of complement components has been reported in blood, while complement C4 was recently identified as a major genetic risk factor. However, little is known about expression of complement components in brain tissue in this disorder. The aim of this study was therefore to compare protein and mRNA expression of early complement components in frontal cortex in schizophrenia and control subjects. Methods: Protein and/or mRNA expression of the early complement components C1q, C3 and C4, and the regulator C1-inhibitor, was quantified in 35 individuals with SCZ and 35 controls. Samples were obtained from the orbital–frontal and dorsolateral prefrontal regions courtesy of the Stanley Medical Research Institute. Proteins were quantified in dorsolateral prefrontal cortex by immunoblotting, and mRNA expression measured in orbital–frontal cortex using quantitative PCR. Measures were compared between groups using analysis of variance. Results: C1-inhibitor was higher in the schizophrenia group. While C4 mRNA expression was increased in schizophrenia, C4 protein levels did not differ between groups, despite the presence of a positive correlation between protein and mRNA expression. Of note, C4 genotype was associated with C4 protein levels. Furthermore, C4 protein levels were negatively correlated with levels of the synaptic protein SNAP-25. Finally, positive correlations were observed between early complement components and markers of peripheral and/or central inflammation. Conclusion: Overall, our results are consistent with a dysregulation of the complement system in schizophrenia. Increased complement expression may be indicative of an inflammatory response. However, early complement components have also been implicated in synaptic pruning and circuit remodeling. Observed correlations between complement C4 and SNAP-25 suggest the complement system may play a role in triggering the synaptic disturbances previously identified in schizophrenia. Funding: This work was supported by the Canadian Institutes of Health Research.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.001 | 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) | 0.003 | 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 source (direct Gemma or distilled Codex), 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".