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Despite an inconclusive efficacy evidence base, antidepressants (ADs) are prescribed for the depressive phase of bipolar disorder (BD) with oftentimes, an inadequate treatment response and or clinical concern for mood destabilization. This study explored the relationship between antidepressant response in MDD and antidepressant-associated treatment emergent mania (TEM) in BD. We conducted a genome-wide association study (GWAS) and polygenic score analysis of TEM and tested its association in a subset of BD-type I patients treated with SSRIs or SNRIs. Our results did not identify any genome-wide significant variants although, we found that a higher polygenic score (PGS) for antidepressant response in MDD was associated with higher odds of TEM in BD. Future studies with larger transdiagnostic depressed cohorts treated with antidepressants are encouraged to identify a neurobiological mechanism associated with a spectrum of depression improvement from response to emergent mania.<\/jats:p>","DOI":"10.1038\/s41398-024-02798-y","type":"journal-article","created":{"date-parts":[[2024,2,13]],"date-time":"2024-02-13T08:02:29Z","timestamp":1707811349000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Pharmacogenomic overlap between antidepressant treatment response in major depression &amp; antidepressant associated treatment emergent mania in bipolar disorder"],"prefix":"10.1038","volume":"14","author":[{"given":"Nicolas A.","family":"Nu\u00f1ez","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4322-5923","authenticated-orcid":false,"given":"Brandon 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BJC reports no financial relationships with commercial interests. LMB reports no financial relationships with commercial interests. AO reports no financial relationships with commercial interests. MGR reports no financial relationships with commercial interests. FRN receives grant support from the National Institute of Mental Health K23 Award (K23MH120503) and from a 2017 NARSAD Young Investigator Award from the Brain and Behavior Research Foundation; has a U.S. Patent and Trademark Office patent # 10,857,356; receives consultant fees from Otsuka Pharmaceutical and has received non-financial research support from Soterix Medical. DJB has received research support from NIDA, NuBiyota, the University of Minnesota Foundation, and the University of Minnesota Department of Psychiatry and Behavioral Sciences MV reports no financial relationships with commercial interests. BS received grant support from Mayo Clinic. KMM reports no financial relationships with commercial interests. HKB reports no financial relationships with commercial interests. SK reports no financial relationships with commercial interests. MFS reports no financial relationships with commercial interests. ME reports no financial relationships with commercial interests. AM reports no financial relationships with commercial interests. JASR reports no financial relationships with commercial interests. GJ reports no financial relationships with commercial interests. AB reports no financial relationships with commercial interests. JGL reports no financial relationships with commercial interests. ACB reports no financial relationships with commercial interests. SJT reports no financial relationships with commercial interests. SLM is or has been a consultant to or member of the scientific advisory boards of Avanir, Allergan (now AbbVie), Bracket (now Signant Health), Idorsia, Intra-Cellular Therapies, Inc., Naurex, Otsuka, Shire (now Takeda), Sunovion, and Takeda. She is or has been a principal or co-investigator on studies sponsored by the Agency for Healthcare Research & Quality (AHRQ), Avenir, AstraZeneca, Cephalon, Forest, Jazz, Marriott Foundation, Medibio, National Institute of Mental Health, Orexigen Therapeutics, Inc., Otsuka, Shire (now Takeda), Sunovian, and Takeda Pharmaceutical Company Ltd. She is also an inventor on United States Patent No. 6,323,236 B2, Use of Sulfamate Derivatives for Treating Impulse Control Disorders, and along with the patent\u2019s assignee, University of Cincinnati, Cincinnati, Ohio, has received payments from Johnson & Johnson, which has exclusive rights under the patent. JMB reports no financial relationships with commercial interests. MAF has received grant support from Assurex Health and Mayo Foundation, received CME travel and honraria from Carnot Laboratories, and has Financial Interest\/Stock ownership\/Royalties from Chymia LLC.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"93"}}