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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 <jats:italic>COMT<\/jats:italic> and <jats:italic>BDNF<\/jats:italic> genes on treatment response. There are a limited number of genome\u2010wide association studies (GWAS) looking at treatment response, though they are almost all underpowered, with only one study including a sample size &gt;\u20091000. 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 <jats:italic>COMT<\/jats:italic> and <jats:italic>BDNF<\/jats:italic>. 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\u2010resistant depression. We are currently pursuing such a strategy in our 50\u2010site worldwide Gen\u2010ECT\u2010ic consortium.<\/jats:p>","DOI":"10.1002\/ajmg.b.33038","type":"journal-article","created":{"date-parts":[[2025,6,29]],"date-time":"2025-06-29T10:10:16Z","timestamp":1751191816000},"page":"88-102","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Genetics of Response to <scp>ECT<\/scp>, <scp>TMS<\/scp>, Ketamine and Esketamine"],"prefix":"10.1002","volume":"198","author":[{"ORCID":"https:\/\/orcid.org\/0009-0002-8187-756X","authenticated-orcid":false,"given":"Clio E.","family":"Franklin","sequence":"first","affiliation":[{"name":"Department of Psychiatry and Behavioral Sciences Johns Hopkins University School of Medicine  Baltimore Maryland USA"},{"name":"Department of Psychiatry Mass General Brigham  Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Murat","family":"Altinay","sequence":"additional","affiliation":[{"name":"Department of Psychiatry and Psychology Cleveland Clinic  Cleveland Ohio USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kala","family":"Bailey","sequence":"additional","affiliation":[{"name":"Department of Psychiatry University of Texas Southwestern Medical Center  Dallas Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mahendra T.","family":"Bhati","sequence":"additional","affiliation":[{"name":"Department of Psychiatry and Behavioral Sciences Stanford University  Stanford California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7771-4886","authenticated-orcid":false,"given":"Brent R.","family":"Carr","sequence":"additional","affiliation":[{"name":"Department of Psychiatry University of Florida Health  Gainesville Florida USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susan K.","family":"Conroy","sequence":"additional","affiliation":[{"name":"Department of Psychiatry Indiana University School of Medicine  Indianapolis Indiana USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Khurshid","family":"Khurshid","sequence":"additional","affiliation":[{"name":"Department of Psychiatry University of Massachusetts Memorial Health  Worchester Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William M.","family":"McDonald","sequence":"additional","affiliation":[{"name":"Department of Psychiatry and Behavioral Sciences Emory University School of Medicine  Atlanta Georgia USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brian J.","family":"Mickey","sequence":"additional","affiliation":[{"name":"Department of Psychiatry Huntsman Mental Health Institute, University of Utah Health School of Medicine  Salt Lake City Utah USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James W.","family":"Murrough","sequence":"additional","affiliation":[{"name":"Departments of Psychiatry and Neuroscience Icahn School of Medicine at Mount Sinai  New York New York USA"},{"name":"VISN 2 Mental Illness Research, Education, and Clinical Center (MIRECC), James J. 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