{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T03:00:09Z","timestamp":1792119609759,"version":"4.4.0"},"reference-count":201,"publisher":"Canadian Science Publishing","issue":"3","license":[{"start":{"date-parts":[[2019,5,1]],"date-time":"2019-05-01T00:00:00Z","timestamp":1556668800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/www.nrcresearchpress.com\/page\/about\/CorporateTextAndDataMining"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J Psychiatry Neurosci"],"published-print":{"date-parts":[[2019,5]]},"abstract":"<jats:p> Major depression and anxiety are highly prevalent and involve chronic dysregulation of serotonin, but they remain poorly understood. Here, we review novel transcriptional (genetic, epigenetic) and posttranscriptional (microRNA, alternative splicing) mechanisms implicated in mental illness, focusing on a key serotonin-related regulator, the serotonin 1A (5-HT<jats:sub>1A<\/jats:sub>) receptor. Functional single-nucleotide polymorphisms and stress-induced DNA methylation of the 5-HT<jats:sub>1A<\/jats:sub> promoter converge to differentially alter pre- and postsynaptic 5-HT<jats:sub>1A<\/jats:sub> receptor expression associated with major depression and reduced therapeutic response to serotonergic antidepressants. Major depression is also associated with altered levels of splice factors and microRNA, posttranscriptional mechanisms that regulate RNA stability. The human 5-HT<jats:sub>1A<\/jats:sub> 3\u2032-untranslated region is alternatively spliced, removing microRNA sites and increasing 5-HT<jats:sub>1A<\/jats:sub> expression, which is reduced in major depression and may be genotype-dependent. Thus, the 5-HT<jats:sub>1A<\/jats:sub> receptor gene illustrates the convergence of genetic, epigenetic and posttranscriptional mechanisms in gene expression, neurodevelopment and neuroplasticity, and major depression. Understanding gene regulatory mechanisms could enhance the detection, categorization and personalized treatment of major depression. <\/jats:p>","DOI":"10.1503\/jpn.180209","type":"journal-article","created":{"date-parts":[[2019,5,1]],"date-time":"2019-05-01T08:05:08Z","timestamp":1556697908000},"page":"164-176","source":"Crossref","is-referenced-by-count":61,"title":["Genetic, epigenetic and posttranscriptional mechanisms for treatment of major depression: the 5-HT1A receptor gene as a paradigm"],"prefix":"10.1139","volume":"44","author":[{"given":"Paul R.","family":"Albert","sequence":"first","affiliation":[{"name":"From the Department of Neuroscience, Ottawa Hospital Research Institute, UOttawa Brain and Mind Research Institute, Ottawa, Ont., Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brice","family":"Le Fran\u00e7ois","sequence":"additional","affiliation":[{"name":"From the Department of Neuroscience, Ottawa Hospital Research Institute, UOttawa Brain and Mind Research Institute, Ottawa, Ont., Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Faranak","family":"Vahid-Ansari","sequence":"additional","affiliation":[{"name":"From the Department of Neuroscience, Ottawa Hospital Research Institute, UOttawa Brain and Mind Research Institute, Ottawa, Ont., Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"155","reference":[{"key":"b1-44-3-164\/b1-44-3-164_1","volume-title":"Depression and other common mental disorders: global health estimates","author":"World Health Organization","year":"2017"},{"key":"b2-44-3-164\/b2-44-3-164_1","doi-asserted-by":"crossref","DOI":"10.1126\/science.aap8757","volume":"360","author":"Brainstorm-Consortium","year":"2018","journal-title":"Science"},{"key":"b3-44-3-164\/b3-44-3-164_1","doi-asserted-by":"crossref","first-page":"522","DOI":"10.1038\/sj.mp.4001920","volume":"12","author":"Jans LA","year":"2007","journal-title":"Mol 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