Schizophrenia: More dopamine, more D <sub>2</sub> receptors
Bibliographic record
Abstract
Schizophrenia is a major therapeutic challenge of modern medicine, and one of the last frontiers of brain research. The illness is defined by delusions, hallucinations, disorganized behavior, and cognitive difficulties such as memory loss. It occurs in ≈1% of the world population and usually first appears in early adulthood. Although antipsychotic medications have dramatically improved the lives of patients with schizophrenia, the causes of the illness remain unknown. Of the many contemporary theories of schizophrenia, the most enduring has been the dopamine hypothesis. As originally put by Van Rossum in 1967 (ref. 1, p. 321), “When the hypothesis of dopamine blockade by neuroleptic agents can be further substantiated, it may have fargoing consequences for the pathophysiology of schizophrenia. Overstimulation of dopamine receptors could be part of the aetiology … [emphasis added].” Indeed, this speculative sentence by Van Rossum foreshadows the title of the important work by Abi-Dargham et al . (2) in this issue of PNAS: “Increased baseline occupancy of D2 receptors by dopamine in schizophrenia.” The discovery of the antipsychotic/dopamine receptor (3, 4), now commonly known as the dopamine D2 receptor, led to repeated confirmation that it is the primary site of action for all antipsychotics (3–5), including clozapine and quetiapine (6). All these drugs have different potencies at the receptor. The potency depends on the drug's dissociation constant at D2, which, in turn, relates to the rate of release of the drug from the D2 receptor. For example, the dopamine D2 receptor releases clozapine and quetiapine more rapidly than it does any of the other antipsychotic drugs (7, 8). Given the tight correlation between the clinical potency and the D2-blocking action of the antipsychotic medications, dopamine overactivity could be the common denominator in the …
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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 | 0.000 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.001 | 0.002 |
| Scholarly communication | 0.002 | 0.003 |
| Open science | 0.000 | 0.001 |
| Research integrity | 0.002 | 0.003 |
| Insufficient payload (model declined to judge) | 0.009 | 0.002 |
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".