Preferential 5-HT1A Autoreceptor Occupancy by Pindolol is Attenuated in Depressed Patients: Effect of Treatment or an Endophenotype of Depression?
Bibliographic record
Abstract
Using positron emission tomography and the selective 5-HT1A receptor radioligand [11C]WAY100635, we previously demonstrated a preferential occupancy of 5-HT1A autoreceptors, compared to postsynaptic receptors by pindolol in healthy volunteers. We have speculated that preferential occupancy may be clinically important for the purported actions of pindolol in accelerating the antidepressant effects of selective serotonin re-uptake inhibitors (SSRIs). In this study, we have examined the preferential occupancy by pindolol of 5-HT1A autoreceptors, following three different pindolol regimes (10 mg single dose, 2.5 mg t.i.d., and 5 mg t.i.d., in 15 depressed patients on SSRIs. In addition, seven healthy volunteers were examined following a single 10 mg dose of pindolol. We found a preferential occupancy of 22.6+/-7.7% following a single dose of 10 mg of pindolol, in the healthy volunteers, which was attenuated in depressed patients on the same dose of pindolol to 2.9+/-10.8% (Student's t=3.94, df=12, p=0.002). In addition, we found a significant negative correlation between the degree of preferential occupancy and the severity of depression as assessed by the Hamilton depression rating score (HAM-D), Spearman's rho=-0.728, N=14, p=0.003, in the depressed sample. A possible mechanism underlying preferential occupancy and the attenuation of this phenomenon in depressed patients on SSRIs may include changes in the proportion of high affinity 5-HT1A sites in the autoreceptor region of the midbrain raphe. Speculatively, the degree of preferential occupancy may serve as a surrogate marker for depression, or the pharmacological effects of antidepressants.
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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 | 0.001 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 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) | 0.002 | 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".