Disrupted in schizophrenia 1 and phosphodiesterase 4B: towards an understanding of psychiatric illness
Bibliographic record
Abstract
Disrupted in schizophrenia 1 (DISC1) is one of the most convincing genetic risk factors for major mental illness identified to date. DISC1 interacts directly with phosphodiesterase 4B (PDE4B), an independently identified risk factor for schizophrenia. DISC1-PDE4B complexes are therefore likely to be involved in molecular mechanisms underlying psychiatric illness. PDE4B hydrolyses cAMP and DISC1 may regulate cAMP signalling through modulating PDE4B activity. There is evidence that expression of both genes is altered in some psychiatric patients. Moreover, DISC1 missense mutations that give rise to phenotypes related to schizophrenia and depression in mice are located within binding sites for PDE4B. These mutations reduce the association between DISC1 and PDE4B, and one results in reduced brain PDE4B activity. Altered DISC1-PDE4B interaction may thus underlie the symptoms of some cases of schizophrenia and depression. Factors likely to influence this interaction include expression levels, binding site affinities and the DISC1 and PDE4 isoforms involved. DISC1 and PDE4 isoforms are targeted to specific subcellular locations which may contribute to the compartmentalization of cAMP signalling. Dysregulated cAMP signalling in specific cellular compartments may therefore be a predisposing factor for major mental illness.
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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 | 0.001 | 0.001 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.002 | 0.000 |
| Bibliometrics | 0.002 | 0.002 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.001 | 0.002 |
| Open science | 0.001 | 0.001 |
| Research integrity | 0.002 | 0.003 |
| Insufficient payload (model declined to judge) | 0.003 | 0.003 |
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".