Epigenetic RELN Dysfunction in Schizophrenia and Related Neuropsychiatric Disorders
Why this work is in the frame
A frame that forgets how it found something cannot be audited. These are the routes that admitted this work.
Bibliographic record
Abstract
REELIN (RELN) is a large (420 kDa) glycoprotein that in adulthood is mostly synthesized in GABAergic neurons of corticolimbic structures. Upon secretion in the extracellular matrix (ECM), RELN binds to VLDL, APOE2, and α3β2 Integrin receptors located on dendritic shafts and spines of postsynaptic pyramidal neurons. Reduced levels of RELN expression in the adult brain induce cognitive impairment and dendritic spine density deficits. RELN supplementation recovers these deficits suggesting a trophic action for RELN in synaptic plasticity. We and others have shown that altered RELN expression in schizophrenia (SZ) and bipolar (BP) disorder patients is difficult to reconcile with classical Mendelian genetic disorders and it is instead plausible to associate these disorders with altered epigenetic homeostasis. Support for the contribution of altered epigenetic mechanisms in the down-regulation of RELN expression in corticolimbic structures of psychotic patients includes the concomitant increase of DNA-methyltransferases and the increased levels of the methyl donor S-adenosylmethionine (SAM). It is hypothesized that these conditions lead to RELN promoter hypermethylation and a reduction in RELN protein amounts in psychotic patients. The decreased synthesis and release of RELN from GABAergic corticolimbic neurons could serve as a model to elucidate the epigenetic pathophysiological mechanisms acting at pyramidal neuron dendrites that regulate synaptic plasticity and cognition in psychotic and non-psychotic subjects.
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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 | 0.001 | 0.001 |
| Meta-epidemiology (narrow) | 0.001 | 0.001 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.003 | 0.006 |
| Science and technology studies | 0.000 | 0.002 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.002 | 0.001 |
| Research integrity | 0.000 | 0.002 |
| 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 it