Elevated peripheral expression of neuregulin-1 (NRG1) mRNA isoforms in clozapine-treated schizophrenia patients
Bibliographic record
Abstract
Abstract Differential expression of neuregulin-1 ( NRG1 ) mRNA isoforms and proteins has been reported in schizophrenia, primarily in post-mortem brain tissue. In this study, we examined 12 NRG1 SNPs, eight NRG1 mRNA isoforms (type I, type I (Ig2) , type II, type III, type IV, EGFα, EGFβ, pan-NRG1) in whole blood, and NRG1-β1 protein in serum of clozapine-treated schizophrenia patients ( N = 71) and healthy controls ( N = 57). In addition, using cultured peripheral blood mononuclear cells (PBMC) from 15 healthy individuals, we examined the effect of clozapine on NRG1 mRNA isoform and protein expression. We found elevated levels of NRG1 mRNA, specifically the EGFα ( P = 0.0175), EGFβ ( P = 0.002) and type I (Ig2) ( P = 0.023) containing transcripts, but lower NRG1-β1 serum protein levels ( P = 0.019) in schizophrenia patients compared to healthy controls. However, adjusting for smoking status attenuated the difference in NRG1-β1 serum levels ( P = 0.050). Examination of clinical factors showed NRG1 EGFα ( P = 0.02) and EGFβ ( P = 0.02) isoform expression was negatively correlated with age of onset. However, we found limited evidence that NRG1 mRNA isoform or protein expression was associated with current chlorpromazine equivalent dose or clozapine plasma levels, the latter corroborated by our PBMC clozapine exposure experiment. Our SNP analysis found no robust expression quantitative trait loci. Our results represent the first comprehensive investigation of NRG1 isoforms and protein expression in the blood of clozapine-treated schizophrenia patients and suggest levels of some NRG1 transcripts are upregulated in those with schizophrenia.
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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 | 0.000 |
| 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) | 0.001 | 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".