Created:OPEN-QUESTIONS.md (8 seed questions) and this log, completing the existing INDEX.md and wiki/overview.md seed set; aligned the canonical table to the required Pages schema by adding a biomarkers-and-treatment-prediction page in place of the generic measurement/outcomes page.
Searches run (live PubMed E-utilities esummary): STAR*D original report and reanalysis; antidepressant network meta-analysis, severity analyses, publication bias, and relapse prevention; ketamine, esketamine, dextromethorphan-bupropion, psilocybin, ECT, and accelerated TMS trials; psychotherapy/combination and measurement-based care; CANMAT 2023; epidemiology, global burden, treatment gap, GWAS, serotonin-hypothesis umbrella review, and mortality.
Verification: all 24 PMIDs already used by the seed were retrieved from live PubMed in this session before these files were written.
Next: full build queued per CONDITIONS-ROADMAP.md — build the remaining 17 wiki pages and literature layer, and independently audit all claim–citation pairs.
Built: all 18 canonical wiki pages; every page has draft frontmatter, TL;DR, dense body, open questions, canonical related links, and references.
Literature layer: topic-grouped BIBLIOGRAPHY.md; five landmark paper notes (STAR*D, Cipriani 2018, Turner 2008, Berman 2000, SNT); guideline registry; statistics tables; and patient-voice method, verified organizations, themes, and annotated sources.
Evidence searches: live PubMed E-utilities searches for diagnosis/heterogeneity; epidemiology/burden; monoamines, HPA, BDNF, inflammation and circuits; genetics/GWAS/epigenetics; antidepressant efficacy, maintenance, adverse effects, withdrawal, publication bias and severity; psychotherapy/combination/exercise; TRD definitions and augmentation; ketamine/esketamine/dextromethorphan; ECT/TMS/tDCS/VNS; psychedelics; biomarkers/pharmacogenomics; suicide/mortality; guidelines; treatment preferences, functional recovery, and lived experience. All 110 unique wiki PMIDs were retrieved in this session, including every seed identifier retained in overview.md.
Trials: live ClinicalTrials.gov v2 query for MDD studies with recruiting, not-yet-recruiting, active-not-recruiting, enrolling-by-invitation status; selected NCT IDs and status were written only from that response.
Patient organizations: direct HTTP fetch verified DBSA, Mind, Beyond Blue, SADAG, Mental Health America, and Depression Alliance on 2026-08-28; ADAA (403) and SANE (no response) were explicitly excluded from the verified table.
Integration: replaced OPEN-QUESTIONS.md with 20 stable Tier 1/Tier 2 questions and 12 “Dots not yet connected” junctions; rebuilt INDEX.md; marked the condition built in CONDITIONS-ROADMAP.md.
Limitations at that build stage: APA guideline replacement status had not yet been resolved; patient-voice coverage was English-language and high-income weighted; all pages remained draft pending the required separate-session independent citation audit. The APA item and page status were resolved in the 2026-08-30 audit below.
Deepened all 18 canonical wiki pages in place: retained the verified seed/build content; added diagnostic-accuracy and conversion cohorts, stratified epidemiology and treatment coverage, immune/HPA/circuit and multi-ancestry mechanism evidence, comparative pharmacologic harms, efficacy estimands, psychotherapy delivery, TRD sequencing, rapid-acting treatments, neuromodulation, novel therapeutics, prediction standards, mortality, international guideline disagreements, trial-design failure modes, patient-defined outcomes, and quantified safety reassessment.
Resulting depth: 2,900+ wiki lines; every page is 151–183 lines and carries 25–33 unique live-retrieved PMIDs (383 unique wiki PMIDs total, up from 110). All pages remain draft; this was a build/deepening session, not the separate independent claim audit required for promotion.
Live PubMed work: 125 E-utilities searches across 31 query groups (diagnosis, screening, heterogeneity, epidemiology, course, burden, treatment gaps, mechanisms, multi-ancestry genetics, pharmacology/harms/withdrawal, efficacy/reporting bias, psychotherapy, TRD, ketamine/esketamine, neuromodulation, psychedelics/neurosteroids, biomarkers, suicide/mortality, guidelines, trials, experience, and safety). Final exact EFetch in four batches resolved all 386 PMIDs used anywhere in the depression condition; no identifier failed.
Live trial work: re-fetched all 27 NCT identifiers used in the condition through exact ClinicalTrials.gov v2 study endpoints and ran a live active-status MDD query returning 100 studies on its first page. Updated the relevant wiki snapshot language to 2026-08-30; registry status remains time-sensitive and does not establish local enrollment or efficacy.
Literature integration: expanded BIBLIOGRAPHY.md to cover all 386 PMIDs cited anywhere in the condition with cited-by fields; no condition PMID is missing from the bibliography. Expanded statistics/STATISTICS.md with diagnostic accuracy, longitudinal conversion, population heterogeneity, coverage, genetics, immune findings, treatment effects, adverse effects, and cause-specific mortality—keeping incompatible methods separate.
Guidelines: expanded the registry from 9 to 18 records with RANZCP, German NVL/S3, AFPBN/FondaMental, Korean Medication Algorithm, BAP, WFSBP, Japanese Society of Mood Disorders, USPSTF, and international tDCS guidance. Added an explicit international comparison to wiki/guidelines.md; re-fetched NICE NG222 successfully (HTTP 200) on 2026-08-30. Legacy documents are labeled rather than silently treated as current.
Research agenda: sharpened withdrawal, inflammatory-selection, and mortality questions with competing quantitative evidence; added OQ-21–OQ-25 on screening pathways, bipolar conversion, patient-weighted medication harms, task-sharing supervision, and accelerated-TMS dismantling; added four new “dots not yet connected.”
Mechanical verification: all page frontmatter remains status: draft; all 18 pages satisfy the 150–400-line and 25–60-citation targets; every body PMID has a page reference entry; every final PMID resolved live; all 27 NCT IDs resolved live; and every condition PMID appears in the bibliography.
Follow-up for the independent audit: verify every numerical claim against full text where abstracts do not report the estimand; independently reassess review overlap and sponsorship; inspect possible ePub/print year differences; rerun time-sensitive NCT statuses and the APA replacement watch item. The evidence ledgers deliberately preserve design limits but do not substitute for the separate claim-to-source audit.
Scope checked: every claim–citation pair across all 18 canonical wiki pages and the complete literature layer. Mechanical closure covered 2,964 wiki lines, 632 inline PMID occurrences, and 496 page-level unique claim–citation mappings; each page retained 151–183 lines and 25–33 unique cited PMIDs.
Live identifier verification: final exact PubMed E-utilities retrieval resolved 388/388 condition PMIDs with zero failures. Final exact ClinicalTrials.gov API retrieval resolved 27/27 NCT identifiers with a current overall status present for every study. No PMID or NCT identifier was supplied from memory.
Claims and numbers corrected: narrowed MDD heritability from 35–40% to approximately 35% to match the cited review; removed PMID 10770484, a duplicate letter/erratum record incorrectly presented as the underlying meta-analysis; and corrected six overstated study-design labels (two patient-experience studies, one psychedelic follow-up, and three safety reviews).
Stale absences re-searched: reran 16 junction searches plus targeted searches for diagnostic/predictive biomarkers, bipolar conversion thresholds, and TRD sequencing. Two former no-study claims were obsolete. Added the exploratory inflammation–iTBS study (PMID 42364721) and two randomized post-ketamine/esketamine CBT studies (PMID 34186531; PMID 42095692), while positively restating the remaining gaps as lack of externally validated clinical utility, powered interaction evidence, or definitive sequencing evidence as of 2026-08-30.
Literature artifacts repaired: the bibliography now covers exactly all 388 condition PMIDs, including 385 unique wiki PMIDs, with zero missing or extra entries; 85 stale cited-by reverse mappings were corrected. All five landmark-note DOI/PMID pairs and the statistics ledger's quantitative claims were rechecked against live PubMed records.
Guidelines and patient voice: resolved the prior APA ambiguity by distinguishing the American Psychiatric Association's 2010 legacy MDD guideline from the American Psychological Association's active 2019 guideline and 2025 update-panel notice. Re-fetched named patient organizations; removed Depression Alliance because its domain now redirects to an unrelated site, retained dated access results, and preserved the English-language/high-income sampling limitation.
Errors found and fixed: 1 wrong citation, 1 numeric overstatement, 6 study-design mislabels, 2 stale absence claims, 1 stale organization record, 1 unresolved guideline item, and 85 bibliography reverse-map defects. Every identified item was repaired in place.
Final disposition: zero unresolved substantive verification flags; all 18 pages promoted to status: curated; the condition promoted to audited in CONDITIONS-ROADMAP.md. Registry status, guideline currency, and organization availability remain explicitly dated and require future refresh rather than constituting unresolved audit failures.