{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,28]],"date-time":"2026-07-28T10:29:52Z","timestamp":1785234592001,"version":"3.55.0"},"reference-count":64,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2018,1,24]],"date-time":"2018-01-24T00:00:00Z","timestamp":1516752000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"name":"Tri-Service General Hospital, Taipei, Taiwan","award":["TSGH-C103-130"],"award-info":[{"award-number":["TSGH-C103-130"]}]},{"name":"Beitou Branch, Tri-Service General Hospital, Taipei, Taiwan","award":["TSGH-BT-105-008"],"award-info":[{"award-number":["TSGH-BT-105-008"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Acta Psychiatr Scand"],"published-print":{"date-parts":[[2018,3]]},"abstract":"<jats:sec><jats:title>Objective<\/jats:title><jats:p>The G\u2010allele of the \u20101019C\/G (<jats:italic>rs<\/jats:italic>6295) promoter polymorphism of the serotonin receptor 1A (<jats:italic><jats:styled-content style=\"fixed-case\">HTR<\/jats:styled-content>1A<\/jats:italic>) gene has been implicated in anxiety; however, the underlying neurophysiological processes are still not fully understood. Recent evidence indicates that low parasympathetic (vagal) tone is predictive of anxiety. We thus conducted a structural equation\u00a0model (<jats:styled-content style=\"fixed-case\">SEM<\/jats:styled-content>) to examine whether the <jats:italic><jats:styled-content style=\"fixed-case\">HTR<\/jats:styled-content>1A rs<\/jats:italic>6295 variant can affect anxiety by altering parasympathetic nervous activity.<\/jats:p><\/jats:sec><jats:sec><jats:title>Method<\/jats:title><jats:p>A sample of 1141 drug\u2010free healthy Han Chinese was recruited for <jats:italic><jats:styled-content style=\"fixed-case\">HTR<\/jats:styled-content>1A<\/jats:italic> genotyping. Autonomic nervous function was assessed by short\u2010term spectral\u00a0analysis of heart rate variability (<jats:styled-content style=\"fixed-case\">HRV<\/jats:styled-content>). Anxiety and stress levels were evaluated by the Beck Anxiety Inventory (<jats:styled-content style=\"fixed-case\">BAI<\/jats:styled-content>) and the Perceived Stress Scale (<jats:styled-content style=\"fixed-case\">PSS<\/jats:styled-content>) respectively.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The number of the <jats:italic><jats:styled-content style=\"fixed-case\">HTR<\/jats:styled-content>1A<\/jats:italic> G allele was inversely correlated with high\u2010frequency power (<jats:styled-content style=\"fixed-case\">HF<\/jats:styled-content>), a parasympathetic index of <jats:styled-content style=\"fixed-case\">HRV<\/jats:styled-content>. The <jats:styled-content style=\"fixed-case\">HF<\/jats:styled-content> index was negatively associated with <jats:styled-content style=\"fixed-case\">BAI<\/jats:styled-content> scores. Furthermore, the good\u2010fitting <jats:styled-content style=\"fixed-case\">SEM<\/jats:styled-content>, adjusting for confounding variables (e.g., age and <jats:styled-content style=\"fixed-case\">PSS<\/jats:styled-content> levels), revealed a significant pathway linking <jats:italic>rs<\/jats:italic>6295 variant to <jats:styled-content style=\"fixed-case\">BAI<\/jats:styled-content> scores via <jats:styled-content style=\"fixed-case\">HF<\/jats:styled-content> index modulation.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>These results are the first to show that <jats:italic><jats:styled-content style=\"fixed-case\">HTR<\/jats:styled-content>1A<\/jats:italic> \u20101019C\/G polymorphism influences anxiety levels by modulating parasympathetic tone, providing a neurophysiological insight into the role of\u00a0<jats:italic><jats:styled-content style=\"fixed-case\">HTR<\/jats:styled-content>1A<\/jats:italic> in human anxiety.<\/jats:p><\/jats:sec>","DOI":"10.1111\/acps.12853","type":"journal-article","created":{"date-parts":[[2018,1,24]],"date-time":"2018-01-24T05:27:37Z","timestamp":1516771657000},"page":"263-272","source":"Crossref","is-referenced-by-count":15,"title":["Serotonin receptor 1A promoter polymorphism, <i>rs<\/i>6295, modulates human anxiety levels via altering parasympathetic nervous activity"],"prefix":"10.1111","volume":"137","author":[{"given":"J.\u2010H.","family":"Huang","sequence":"first","affiliation":[{"name":"Department of Psychiatry Beitou Branch Tri\u2010Service General Hospital National Defense Medical Center Taipei Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"H.\u2010A.","family":"Chang","sequence":"additional","affiliation":[{"name":"Department of Psychiatry Tri\u2010Service General Hospital National Defense Medical Center Taipei Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"W.\u2010H.","family":"Fang","sequence":"additional","affiliation":[{"name":"Department of Family and Community Medicine Tri\u2010Service General Hospital National Defense Medical Center Taipei Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"P.\u2010S.","family":"Ho","sequence":"additional","affiliation":[{"name":"Department of Psychiatry Beitou Branch Tri\u2010Service General Hospital National Defense Medical Center Taipei Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Y.\u2010P.","family":"Liu","sequence":"additional","affiliation":[{"name":"Laboratory of Cognitive Neuroscience Departments of Physiology and Psychiatry National Defense Medical Center Taipei Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"F.\u2010J.","family":"Wan","sequence":"additional","affiliation":[{"name":"Department of Psychiatry Tri\u2010Service General Hospital National Defense Medical Center Taipei Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"N.\u2010S.","family":"Tzeng","sequence":"additional","affiliation":[{"name":"Department of Psychiatry Tri\u2010Service General Hospital National Defense Medical Center Taipei Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J.\u2010F.","family":"Shyu","sequence":"additional","affiliation":[{"name":"Department of Biology and Anatomy National Defense Medical Center Taipei Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9639-6158","authenticated-orcid":false,"given":"C.\u2010C.","family":"Chang","sequence":"additional","affiliation":[{"name":"Department of Psychiatry Tri\u2010Service General Hospital National Defense Medical Center Taipei Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2018,1,24]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"crossref","first-page":"3738","DOI":"10.2174\/13816128113196660740","article-title":"Transcriptional dys\u2010regulation in anxiety and major depression: 5\u2010HT1A gene promoter architecture as a therapeutic opportunity","volume":"20","author":"Albert PR","year":"2014","journal-title":"Curr Pharm Des"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.95.18.10734"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.95.24.14476"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molbrainres.2004.06.028"},{"key":"e_1_2_9_6_1","doi-asserted-by":"crossref","first-page":"6250","DOI":"10.1523\/JNEUROSCI.5219-07.2008","article-title":"L, GROSS C. 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