{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,10]],"date-time":"2026-07-10T02:44:36Z","timestamp":1783651476544,"version":"3.55.0"},"reference-count":57,"publisher":"MDPI AG","issue":"17","license":[{"start":{"date-parts":[[2022,8,25]],"date-time":"2022-08-25T00:00:00Z","timestamp":1661385600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Ministry of Science and Technology of Taiwan","award":["MOST 107-2320-B-006-071"],"award-info":[{"award-number":["MOST 107-2320-B-006-071"]}]},{"name":"Ministry of Science and Technology of Taiwan","award":["MOST 108-2320-B-006-047-MY3"],"award-info":[{"award-number":["MOST 108-2320-B-006-047-MY3"]}]},{"name":"Ministry of Science and Technology of Taiwan","award":["MOST 111-2628-B-006-010-MY3"],"award-info":[{"award-number":["MOST 111-2628-B-006-010-MY3"]}]},{"name":"Ministry of Science and Technology of Taiwan","award":["NCKUH-10802013"],"award-info":[{"award-number":["NCKUH-10802013"]}]},{"name":"Ministry of Science and Technology of Taiwan","award":["NCKUH-10902014"],"award-info":[{"award-number":["NCKUH-10902014"]}]},{"name":"the National Cheng Kung University Hospital","award":["MOST 107-2320-B-006-071"],"award-info":[{"award-number":["MOST 107-2320-B-006-071"]}]},{"name":"the National Cheng Kung University Hospital","award":["MOST 108-2320-B-006-047-MY3"],"award-info":[{"award-number":["MOST 108-2320-B-006-047-MY3"]}]},{"name":"the National Cheng Kung University Hospital","award":["MOST 111-2628-B-006-010-MY3"],"award-info":[{"award-number":["MOST 111-2628-B-006-010-MY3"]}]},{"name":"the National Cheng Kung University Hospital","award":["NCKUH-10802013"],"award-info":[{"award-number":["NCKUH-10802013"]}]},{"name":"the National Cheng Kung University Hospital","award":["NCKUH-10902014"],"award-info":[{"award-number":["NCKUH-10902014"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Patients with bipolar disorder (BD) exhibit individual variability in the treatment outcome, and genetic background could contribute to BD itself and the treatment outcome. Leptin levels significantly change in BD patients treated with valproate (VPA), but whether LEPR polymorphisms are associated with treatment response is still unknown. This longitudinal study aimed to investigate the associations between LEPR polymorphisms and VPA treatment response in BD patients who were drug na\u00efve at their first diagnosis of BD. The single-nucleotide polymorphisms (SNPs) of LEPR (rs1137101, rs1137100, rs8179183, and rs12145690) were assayed, and the LEPR polymorphism frequencies of alleles and genotypes were not significantly different between the controls (n = 77) and BD patients (n = 130). In addition, after the 12-week course of VPA treatment in BD patients, the LEPR polymorphisms showed significant effects on changes in disease severity. Moreover, considering the effect of the LEPR haplotype, the frequency of the CAGG haplotype in BD patients was higher than that in the controls (9.3 vs. 2.9%, p = 0.016), and the LEPR CAGG haplotype was associated with a better treatment response than the other haplotypes in BD patients receiving VPA treatment. Therefore, LEPR polymorphisms might serve as mediators involved in the therapeutic action of VPA treatment.<\/jats:p>","DOI":"10.3390\/ijms23179635","type":"journal-article","created":{"date-parts":[[2022,8,25]],"date-time":"2022-08-25T21:28:12Z","timestamp":1661462892000},"page":"9635","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["A Longitudinal Study of the Association between the LEPR Polymorphism and Treatment Response in Patients with Bipolar Disorder"],"prefix":"10.3390","volume":"23","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7866-5481","authenticated-orcid":false,"given":"Hui Hua","family":"Chang","sequence":"first","affiliation":[{"name":"Institute of Clinical Pharmacy and Pharmaceutical Sciences, College of Medicine, National Cheng Kung University, Tainan 701, Taiwan"},{"name":"School of Pharmacy, College of Medicine, National Cheng Kung University, Tainan 701, Taiwan"},{"name":"Department of Pharmacy, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan 701, Taiwan"},{"name":"Department of Pharmacy, National Cheng Kung University Hospital, Dou-Liou Branch, Yunlin 640, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2584-9380","authenticated-orcid":false,"given":"Yuan-Shuo","family":"Hsueh","sequence":"additional","affiliation":[{"name":"Department of Medical Science Industries, College of Health Sciences, Chang Jung Christian University, Tainan 711, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yung Wen","family":"Cheng","sequence":"additional","affiliation":[{"name":"Institute of Clinical Pharmacy and Pharmaceutical Sciences, College of Medicine, National Cheng Kung University, Tainan 701, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huai-Hsuan","family":"Tseng","sequence":"additional","affiliation":[{"name":"Department of Psychiatry, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan 701, Taiwan"},{"name":"Institute of Behavioral Medicine, College of Medicine, National Cheng Kung University, Tainan 701, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,8,25]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"265","DOI":"10.1176\/appi.ajp.2012.12050620","article-title":"Metabolic syndrome and metabolic abnormalities in bipolar disorder: A meta-analysis of prevalence rates and moderators","volume":"170","author":"Vancampfort","year":"2013","journal-title":"Am. 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