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The anticholinergic agent scopolamine has also shown promise as a rapid-acting antidepressant. This study applied genome-wide markers to investigate the role of genetic variants in predicting acute antidepressant response to both agents. The ketamine-treated sample included 157 unrelated European subjects with major depressive disorder (MDD) or bipolar disorder (BD). The scopolamine-treated sample comprised 37 unrelated European subjects diagnosed with either MDD or BD who had a current Major Depressive Episode (MDE), and had failed at least two adequate treatment trials for depression. Change in Montgomery\u2013Asberg Depression Rating Scale (MADRS) or the 17-item Hamilton Depression Rating Scale (HAM-D) scale scores at day 1 (24\u2009h post-treatment) was considered the primary outcome. Here, we conduct pilot genome-wide association study (GWAS) analyses to identify potential markers of ketamine response and dissociative side effects. Polygenic risk score analysis of SNPs ranked by the strength of their association with ketamine response was then calculated in order to assess whether common genetic markers from the ketamine study could predict response to scopolamine. Findings require replication in larger samples in light of low power of analyses of these small samples. Neverthless, these data provide a promising illustration of our future potential to identify genetic variants underlying rapid treatment response in mood disorders and may ultimately guide individual patient treatment selection in the future.<\/jats:p>","DOI":"10.1038\/s41398-018-0311-7","type":"journal-article","created":{"date-parts":[[2018,12,14]],"date-time":"2018-12-14T11:55:53Z","timestamp":1544788553000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":29,"title":["Exploratory genome-wide association analysis of response to ketamine and a polygenic analysis of response to scopolamine in depression"],"prefix":"10.1038","volume":"8","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4322-3699","authenticated-orcid":false,"given":"Wei","family":"Guo","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rodrigo","family":"Machado-Vieira","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sanjay","family":"Mathew","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"James W.","family":"Murrough","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dennis S.","family":"Charney","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5940-3478","authenticated-orcid":false,"given":"Matthew","family":"Grunebaum","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maria A.","family":"Oquendo","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bashkim","family":"Kadriu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nirmala","family":"Akula","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ioline","family":"Henter","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Peixiong","family":"Yuan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kathleen","family":"Merikangas","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wayne","family":"Drevets","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maura","family":"Furey","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0265-6586","authenticated-orcid":false,"given":"J. 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Grunebaum\u2019s name was misspelled\/misstated as \u201cGruenbaum M.F.\u201d in the original Article. This has now been updated in the HTML and PDF versions of this Article.","order":7,"name":"change_details","label":"Change Details","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"Funding for this work was supported in part by the Intramural Research Program at the National Institute of Mental Health, National Institutes of Health (IRP-NIMH-NIH; ZIA MH002857, ZIA MH002930), by a NARSAD Independent Investigator Award to C.A.Z., and by a Brain and Behavior Mood Disorders Research Award to C.A.Z. C.A.Z. is listed as a coinventor on a patent for the use of ketamine and its metabolites in major depression and suicidal ideation. C.A.Z. is listed as a coinventor on a patent for the use of (2\u2009<i>R<\/i>,6\u2009<i>R<\/i>)-hydroxynorketamine, (<i>S<\/i>)-dehydronorketamine, and other stereoisomeric dehydro and hydroxylated metabolites of (<i>R,S<\/i>)-ketamine metabolites in the treatment of depression and neuropathic pain. C.A.Z. is listed as coinventor on a patent application for the use of (2\u2009<i>R<\/i>,6\u2009<i>R<\/i>)-hydroxynorketamine and (2\u2009<i>S<\/i>,6\u2009<i>S<\/i>)-hydroxynorketamine in the treatment of depression, anxiety, anhedonia, suicidal ideation, and post-traumatic stress disorders; he has assigned his patent rights to the US government but will share a percentage of any royalties that may be received by the government. J.J.M. and M.A.O. receive royalties for commercial use of the C-SSRS from the Research Foundation for Mental Hygiene. M.A.O.\u2019s family owns stock in Bristol Myers Squibb. In the past three years, J.W.M. has provided consultation services for Fortress Biotech, Inc., Novartis, Janssen Research and Development, Genentech, and ProPhase, and has received research support from Avanir Pharmaceuticals, Inc. J.W.M. is named on a pending patent for lithium to extend the antidepressant effect of ketamine and for the combination of lithium and ketamine for the treatment of suicidal ideation. The Icahn School of Medicine at Mount Sinai (with which J.W.M. is affiliated) is named on a patent, has entered into a licensing agreement, and will receive payments related to the use of ketamine if it is approved for the treatment of depression. J.W.M. is not named on the patent and will not receive any payments. M.F. and W.D. are employees of Janssen Pharmaceuticals and have patent on scopolamine. All remaining authors have no conflicts of interest to disclose, financial or otherwise.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}}],"article-number":"280"}}