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Record W4411436568 · doi:10.1002/ajmg.b.33038

Genetics of Response to <scp>ECT</scp>, <scp>TMS</scp>, Ketamine and Esketamine

2025· review· en· W4411436568 on OpenAlexaff
Crystal A. Franklin, Murat Altinay, Kala Bailey, Mahendra T. Bhati, Brent R. Carr, Susan K. Conroy, Khurshid Khurshid, William M. McDonald, Brian J. Mickey, James W. Murrough, Sean M. Nestor, Thomas Nickl‐Jockschat, Irving M. Reti, Gerard Sanacora, Nicholas T. Trapp, Biju Viswanath, Jesse H. Wright, Peter P. Zandi, James B. Potash

Bibliographic record

VenueAmerican Journal of Medical Genetics Part B Neuropsychiatric Genetics · 2025
Typereview
Languageen
FieldMedicine
TopicTreatment of Major Depression
Canadian institutionsUniversity of Toronto
FundersNational Institute of Mental HealthThe Wellcome Trust DBT India AllianceDepartment of Biotechnology, Ministry of Science and Technology, IndiaWellcome Trust
KeywordsKetamineMedicineAnesthesia

Abstract

fetched live from OpenAlex

Treatment-resistant mood disorders are often managed with intensive interventions that include electroconvulsive therapy (ECT), transcranial magnetic stimulation (TMS), ketamine, and esketamine, but the role of genetics in clinical response to those interventions is yet to be clearly determined. Here, we review the current literature on the genetics of response to these treatment modalities. To date, the limited number of studies done to investigate genetic predictors of treatment response have primarily focused on single variants in candidate genes, and none of these have been consistently reproducible. The majority of candidate gene studies examine the effect of variants in the COMT and BDNF genes on treatment response. There are a limited number of genome-wide association studies (GWAS) looking at treatment response, though they are almost all underpowered, with only one study including a sample size > 1000. As a result, there have been few single nucleotide polymorphisms (SNPs) found to be associated with treatment response at a statistically significant level, all in genes other than COMT and BDNF. The challenge is now to generate data from a large group of patients undergoing these therapies in order to more robustly assess the genetic factors affecting treatment response. This will not only help establish genetic predictors of response, but also potentially develop differential predictors of response to available treatments, which could provide clinicians with critical information to aid in deciding which treatment modality to recommend for treatment-resistant depression. We are currently pursuing such a strategy in our 50-site worldwide Gen-ECT-ic consortium.

Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.

How this classification was reachedexpand

Full frame machine prediction

Teacher imitation

Not 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.

metaresearch head score (Codex)0.001
metaresearch head score (Gemma)0.002
Version: metacan-v3-hybrid-931329e0061cValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Not applicable · Consensus signal: none
GenreCandidate signal: Review · Consensus signal: none
Teacher disagreement score0.002
Threshold uncertainty score0.007

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0010.002
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0010.001
Bibliometrics0.0000.001
Science and technology studies0.0000.000
Scholarly communication0.0010.000
Open science0.0000.000
Research integrity0.0010.000
Insufficient payload (model declined to judge)0.0020.000

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.

Opus teacher head0.021
GPT teacher head0.334
Teacher spread0.313 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it

Classification

machine, unvalidated

Machine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.

The models applied no category: nothing in the taxonomy fit this work.
Study designNot applicable
Domainnot available
GenreReview

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".

Quick stats

Citations2
Published2025
Admission routes1
Has abstractyes

Explore more

Same venueAmerican Journal of Medical Genetics Part B Neuropsychiatric GeneticsSame topicTreatment of Major DepressionFrench-language works237,207