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Psychiatry"],"abstract":"<jats:sec><jats:title>Objective<\/jats:title><jats:p>This study aimed to test the hypothesis that the relationship between glutamic acid decarboxylase (GAD) 1 gene methylation and severity of clinical symptoms of panic disorder (PD) is mediated by the effect of GAD1 gene methylation on gray matter volume (GMV) and the effect of GMV on PD.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Panic disorder (<jats:italic>n<\/jats:italic> = 24) patients were recruited consecutively from the Affiliated Brain Hospital of Nanjing Medical University through outpatient and public advertising, eligible healthy controls (HCs) (<jats:italic>n<\/jats:italic> = 22) were recruited from public advertising. We compared GMV and GAD1 gene methylation in PD and HCs to estimate the differences, and on the basis of the relationship between gray matter volumes and GAD1 gene methylation in PD patients was evaluated, the role of GMV as a mediator of GAD1 gene methylation and PD clinical symptoms was analyzed.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Panic disorder patients had significantly lower methylation in the GAD1 promoter region on Cytosine-phosphate-guanine (CPG) 7 than HCs (<jats:italic>t<\/jats:italic> = 2.380, <jats:italic>p<\/jats:italic> = 0.021). Pearson correlation analysis found a significant negative association between cg171674146 (cg12) site and clinical severity (<jats:italic>n<\/jats:italic> = 24, <jats:italic>r<\/jats:italic> = \u22120.456, <jats:italic>p<\/jats:italic> = 0.025). Compared to HCs, patients with PD had decreased gray matter volumes in several brain regions, which were also associated with PD severity. Left postcentral gyrus (PoCG) GMV mediated the association between cg12 methylation and PD severity, and there was a significant mediation effect of right angular gyrus (ANG) gray matter volumes on the relationship between cg12 methylation and PD severity.<\/jats:p><\/jats:sec><jats:sec><jats:title>Limitation<\/jats:title><jats:p>No direct results can be derived for methylation patterns in different brain regions; the study is cross-sectional; relatively small size.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fpsyt.2022.853613","type":"journal-article","created":{"date-parts":[[2022,5,24]],"date-time":"2022-05-24T05:57:35Z","timestamp":1653371855000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":3,"title":["Glutamic Acid Decarboxylase 1 Gene Methylation and Panic Disorder Severity: Making the Connection by Brain Gray Matter Volume"],"prefix":"10.3389","volume":"13","author":[{"given":"Huiqin","family":"Wu","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yuan","family":"Zhong","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Huazhen","family":"Xu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Huachen","family":"Ding","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shiting","family":"Yuan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yun","family":"Wu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gang","family":"Liu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Na","family":"Liu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chun","family":"Wang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2022,5,24]]},"reference":[{"key":"B1","first-page":"191","article-title":"Diagnostic and statistical manual of mental disorders (DSM).","volume":"25","author":"Battle","year":"2013","journal-title":"Codas."},{"key":"B2","doi-asserted-by":"crossref","first-page":"211","DOI":"10.1016\/S2215-0366(18)30511-X","article-title":"Prevalence of mental disorders in China: a cross-sectional epidemiological study.","volume":"6","author":"Huang","year":"2019","journal-title":"Lancet Psychiatry."},{"key":"B3","doi-asserted-by":"publisher","first-page":"1568","DOI":"10.1176\/appi.ajp.158.10.1568","article-title":"A review and meta-analysis of the genetic epidemiology of anxiety disorders.","volume":"158","author":"Hettema","year":"2001","journal-title":"Am J Psychiatry."},{"key":"B4","first-page":"108","article-title":"Structural neuroimaging in patients with panic disorder: findings and limitations of recent studies.","volume":"25","author":"Del Casale","year":"2013","journal-title":"Psychiatr Danub."},{"key":"B5","first-page":"133","article-title":"The role of GABA in the pathophysiology and treatment of anxiety disorders.","volume":"37","author":"Nemeroff","year":"2003","journal-title":"Psychopharmacol Bull."},{"key":"B6","first-page":"167","article-title":"Selective GABAergic treatment for panic? 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