Self-criticism predicts antidepressant effects of intermittent theta-burst stimulation in Major Depressive Disorder
Bibliographic record
Abstract
BACKGROUND: Self-criticism is a risk factor for depression and depressive symptom persistence, however higher degrees of self-criticism have been associated with greater antidepressant benefits from repetitive transcranial magnetic stimulation (rTMS), suggesting that self-criticism may act as a proxy for function of the targeted circuit. We test this hypothesis using secondary data from an rTMS treatment trial where an NMDA receptor agonist (D-Cycloserine) was used to enhance TMS synaptic plasticity to improve efficacy. We hypothesized that self-criticism would be more strongly associated with treatment outcome when stimulation was paired with D-Cycloserine than with a placebo. METHODS: In a 4-week single-site double-blind randomized placebo-controlled trial, fifty adults with Major Depressive Disorder (MDD) (NCT03937596) were randomized to receive placebo or D-Cycloserine (100 mg) with daily intermittent theta-burst stimulation (iTBS) to the left dorsolateral prefrontal cortex (DLPFC). At baseline and after treatment, self-criticism was assessed using the Depressive Experiences Questionnaire as a secondary trial outcome and depressive symptoms were assessed using the clinician rated Montgomery Asberg Depression Rating scale (MADRS). Clinical response was defined as a ≥50 % decrease on the MADRS. RESULTS: Self-criticism differentially predicted antidepressant effects when operationalized as both percent decrease on the MADRS and clinical response (≥50 % decrease), with a statistically significantly stronger association in the iTBS+D-Cycloserine group than the iTBS+Placebo condition. Self-criticism did not significantly change in either condition over the course of treatment. CONCLUSIONS: Our data suggests that iTBS to the left DLPFC engages a circuit related to self-criticism. Higher levels of self-criticism predicted better response to iTBS with an adjuvant that enhances synaptic plasticity. This suggests that personality traits may be used to tailor non-invasive neurostimulation treatments.
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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 | 0.002 | 0.004 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| 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".