{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,10]],"date-time":"2026-01-10T03:15:11Z","timestamp":1768014911868,"version":"3.49.0"},"reference-count":57,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2021,7,23]],"date-time":"2021-07-23T00:00:00Z","timestamp":1626998400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Health Science Reports"],"published-print":{"date-parts":[[2021,9]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>The purpose of this investigation was to examine heart rate variability (HRV), interbeat interval (IBI), and their interrelationship in healthy controls, bradycardic hyperpolarization\u2010activated cyclic nucleotide\u2010gated channel 4 (<jats:italic>HCN4<\/jats:italic>) mutation carriers, and patients with anorexia nervosa (AN). We tested the hypothesis that neural mechanisms cause bradycardia in patients with AN. Therefore, we assumed that saturation of the HRV\/IBI relationship as a consequence of sustained parasympathetic control of the sinus node is exclusively detectable in patients with AN.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Patients with AN between the ages of 12 and 16\u2009years admitted to our hospital due to malnutrition were grouped and included in the present investigation (N\u00a0=\u00a020). A matched\u2010pair group with healthy children and adolescents was created. Groups were matched for age and sex. A 24\u2010hour Holter electrocardiography (ECG) was performed in controls and patients. More specifically, all patients underwent two 24\u2010hour Holter ECG examinations (admission; refeeding treatment). Additionally, the IBI was recorded during the night in <jats:italic>HCN4<\/jats:italic> mutation carriers (N\u00a0=\u00a04). HRV parameters were analyzed in 5\u2010minute sequences during the night and plotted against mean corresponding IBI length. HRV, IBI, and their interrelationship were examined using Spearman's rank correlation analyses, Mann\u2010Whitney <jats:italic>U<\/jats:italic> tests, and Wilcoxon signed\u2010rank tests.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The relationship between IBI and HRV showed signs of saturation in patients with AN. Furthermore, signs of HRV saturation were present in two <jats:italic>HCN4<\/jats:italic> mutation carriers. In contrast, signs of HRV saturation were not present in controls.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>The existence of HRV saturation does not support the existence of parasympathetically mediated bradycardia. Nonneural mechanisms, such as <jats:italic>HCN4<\/jats:italic> downregulation, may be responsible for bradycardia and HRV saturation in patients with AN.<\/jats:p><\/jats:sec>","DOI":"10.1002\/hsr2.331","type":"journal-article","created":{"date-parts":[[2021,7,23]],"date-time":"2021-07-23T12:57:21Z","timestamp":1627045041000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Pathophysiological mechanisms of bradycardia in patients with anorexia nervosa"],"prefix":"10.1002","volume":"4","author":[{"given":"Reiner","family":"Buchhorn","sequence":"first","affiliation":[{"name":"Department of Pediatrics Caritas\u2010Krankenhaus Bad Mergentheim  Bad Mergentheim Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1263-5594","authenticated-orcid":false,"given":"Christoph","family":"Baumann","sequence":"additional","affiliation":[{"name":"Medical Faculty University of Wuerzburg  W\u00fcrzburg Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christian","family":"Willaschek","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Caritas\u2010Krankenhaus Bad Mergentheim  Bad Mergentheim Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2021,7,23]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1001\/archgenpsychiatry.2011.74"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1176\/ajp.152.7.1073"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1192\/bjp.bp.108.054742"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1055\/s-0033-1334138"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1002\/erv.1081"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1093\/oxfordjournals.eurheartj.a060636"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.amjcard.2013.04.018"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0002-9149(00)00920-6"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.2337\/diabetes.51.12.3524"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9150(99)00052-0"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.1161\/STROKEAHA.110.607697"},{"key":"e_1_2_11_13_1","doi-asserted-by":"publisher","DOI":"10.1111\/anec.12237"},{"key":"e_1_2_11_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.physbeh.2018.10.018"},{"key":"e_1_2_11_15_1","doi-asserted-by":"publisher","DOI":"10.1111\/wvn.12097"},{"key":"e_1_2_11_16_1","doi-asserted-by":"publisher","DOI":"10.3389\/fpubh.2017.00258"},{"key":"e_1_2_11_17_1","doi-asserted-by":"publisher","DOI":"10.1113\/JP277501"},{"key":"e_1_2_11_18_1","doi-asserted-by":"publisher","DOI":"10.1152\/japplphysiol.01126.2012"},{"key":"e_1_2_11_19_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms4775"},{"key":"e_1_2_11_20_1","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.2014.284356"},{"key":"e_1_2_11_21_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10286-013-0208-8"},{"key":"e_1_2_11_22_1","article-title":"What's at the heart of anorexia nervosa? 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