Bibliographic record
Abstract
Major depressive disorder (MDD) has a high prevalence among Canadians and places extensive burden on the health care system.Due to the heterogeneity of the disorder, adequate treatment is difficult, highlighting a need for new therapeutic strategies to provide symptomatic relief in individuals with treatment-resistant depression.Importantly, the novel antidepressant strategy, ketamine, has been shown to reduce depressive symptoms in a significant proportion of individuals with treatment-resistant depression.Abnormalities in the endocrine and immune systems are well documented in patients with MDD, however, the mechanisms by which repeated ketamine infusions influence these physiological systems are unclear.This study examined the effects of repeated ketamine infusions on the endocrine and immune systems using the peripheral biomarkers C-reactive protein (CRP) and cortisol.Plasma CRP and salivary cortisol were measured from biological specimens collected from participants at various time points during a repeated ketamine infusions clinical trial conducted at the Royal's Institute of Mental Health Research (IMHR) from January 2013 to December 2017.Neither plasma CRP nor salivary cortisol predicted antidepressant treatment response to ketamine.Pre-treatment plasma CRP was correlated with pre-treatment severity of depressive symptom severity and suicidal ideation severity.While both depressive symptoms and suicidal ideation were reduced with repeated ketamine treatment, there was no significant change in plasma CRP levels throughout the clinical trial.Morning salivary cortisol did change throughout the clinical trial in a sexspecific way.At baseline, males exhibited a blunted cortisol awakening response (CAR) compared to females.After ketamine treatment, males exhibited an increase in cortisol upon awakening indicating a reversal (normalization) of their blunted CAR.In contrast, females' morning cortisol output was reduced after repeated ketamine infusions.Further sex-specific iii investigation into ketamine's effect on glucocorticoid expression is needed to advance the knowledge of the underlying mechanisms of ketamine's rapid antidepressant effects to more effectively treat patients with depression.
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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) | 0.000 | 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 | 0.001 |
| 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".