Kimberly V Blake, Kevin Hilbert, Jonathan C Ipser, Laura K M Han, Janna Marie Bas-Hoogendam, Fredrik Åhs, Jochen Bauer, Katja Beesdo-Baum, Johannes Björkstrand, Laura Blanco-Hinojo, Joscha Böhnlein, Robin Bülow, Marta Cano, Narcis Cardoner, Xavier Caseras, Udo Dannlowski, Mats Fredrikson, Liesbet Goossens, Hans J Grabe, Dominik Grotegerd, Tim Hahn, Alfons Hamm, Ingmar Heinig, Martin J Herrmann, David Hofmann, Hamidreza Jamalabadi, Andreas Jansen, Merel Kindt, Tilo Kircher, Anna L Klahn, Katja Koelkebeck, Axel Krug, Elisabeth J Leehr, Martin Lotze, Juergen Margraf, Markus Muehlhan, Igor Nenadić, Wenceslao Peñate, Andre Pittig, Jens Plag, Jesús Pujol, Jan Richter, Isabelle C Ridderbusch, Francisco Rivero, Axel Schäfer, Judith Schäfer, Anne Schienle, Elisabeth Schrammen, Koen Schruers, Esther Seidl, Rudolf M Stark, Benjamin Straube, Thomas Straube, Andreas Ströhle, Lea Teutenberg, Sophia I Thomopoulos, Carlos Ventura-Bort, Renee M Visser, Henry Völzke, Albert Wabnegger, Julia Wendt, Hans-Ulrich Wittchen, Katharina Wittfeld, Yunbo Yang, Anna Zilverstand, Peter Zwanzger, Lianne Schmaal, Moji Aghajani, Daniel S Pine, Paul M Thompson, Nic J A van der Wee, Dan J Stein, Ulrike Lueken, Nynke A Groenewold
{"title":"Brain Aging in Specific Phobia: An ENIGMA-Anxiety Mega-Analysis.","authors":"Kimberly V Blake, Kevin Hilbert, Jonathan C Ipser, Laura K M Han, Janna Marie Bas-Hoogendam, Fredrik Åhs, Jochen Bauer, Katja Beesdo-Baum, Johannes Björkstrand, Laura Blanco-Hinojo, Joscha Böhnlein, Robin Bülow, Marta Cano, Narcis Cardoner, Xavier Caseras, Udo Dannlowski, Mats Fredrikson, Liesbet Goossens, Hans J Grabe, Dominik Grotegerd, Tim Hahn, Alfons Hamm, Ingmar Heinig, Martin J Herrmann, David Hofmann, Hamidreza Jamalabadi, Andreas Jansen, Merel Kindt, Tilo Kircher, Anna L Klahn, Katja Koelkebeck, Axel Krug, Elisabeth J Leehr, Martin Lotze, Juergen Margraf, Markus Muehlhan, Igor Nenadić, Wenceslao Peñate, Andre Pittig, Jens Plag, Jesús Pujol, Jan Richter, Isabelle C Ridderbusch, Francisco Rivero, Axel Schäfer, Judith Schäfer, Anne Schienle, Elisabeth Schrammen, Koen Schruers, Esther Seidl, Rudolf M Stark, Benjamin Straube, Thomas Straube, Andreas Ströhle, Lea Teutenberg, Sophia I Thomopoulos, Carlos Ventura-Bort, Renee M Visser, Henry Völzke, Albert Wabnegger, Julia Wendt, Hans-Ulrich Wittchen, Katharina Wittfeld, Yunbo Yang, Anna Zilverstand, Peter Zwanzger, Lianne Schmaal, Moji Aghajani, Daniel S Pine, Paul M Thompson, Nic J A van der Wee, Dan J Stein, Ulrike Lueken, Nynke A Groenewold","doi":"10.1101/2025.03.19.25323474","DOIUrl":null,"url":null,"abstract":"<p><strong>Introduction: </strong>Specific phobia (SPH) is a prevalent anxiety disorder and may involve advanced biological aging. However, brain age research in psychiatry has primarily examined mood and psychotic disorders. This mega-analysis investigated brain aging in SPH participants within the ENIGMA-Anxiety Working Group.</p><p><strong>Methods: </strong>3D brain <b>s</b> tructural MRI scans from 17 international samples (600 SPH individuals, of whom 504 formally diagnosed and 96 questionnaire-based cases; 1,134 controls; age range: 22-75 years) were processed with FreeSurfer. Brain age was estimated from 77 subcortical and cortical regions with a publicly available ENIGMA brain age model. The brain-predicted age difference (brain-PAD) was calculated as brain age minus chronological age. Linear mixed-effect models examined group differences in brain-PAD and moderation by age.</p><p><strong>Results: </strong>No significant group difference in brain-PAD manifested ( <b>β</b> <sub>diagnosis</sub> (SE)=0.37 years (0.43), <i>p</i> =0.39). A negative diagnosis-by-age interaction was identified, which was most pronounced in formally diagnosed SPH ( <b>β</b> <sub>diagnosis-by-age</sub> =-0.08 (0.03), <i>pFDR</i> =0.02). This interaction remained significant when excluding participants with anxiety comorbidities, depressive comorbidities, and medication use. Post-hoc analyses revealed a group difference for formal SPH diagnosis in younger participants (22-35 years; <b>β</b> <sub>diagnosis</sub> =1.20 (0.60), <i>p</i> <0.05, mixed-effects <i>d</i> (95% confidence interval)=0.14 (0.00-0.28)), but not older participants (36-75 years; <b>β</b> <sub>diagnosis</sub> =0.07 (0.65), <i>p</i> =0.91).</p><p><strong>Conclusions: </strong>Brain aging did not relate to SPH in the full sample. However, a diagnosis-by-age interaction was observed across analyses, and was strongest in formally diagnosed SPH. Post-hoc analyses showed a subtle advanced brain aging in young adults with formally diagnosed SPH. Taken together, these findings indicate the importance of clinical severity, impairment and persistence, and may suggest a slightly earlier end to maturational processes or subtle decline of brain structure in SPH.</p>","PeriodicalId":94281,"journal":{"name":"medRxiv : the preprint server for health sciences","volume":" ","pages":""},"PeriodicalIF":0.0000,"publicationDate":"2025-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11957081/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"medRxiv : the preprint server for health sciences","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.1101/2025.03.19.25323474","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"","JCRName":"","Score":null,"Total":0}
引用次数: 0
Abstract
Introduction: Specific phobia (SPH) is a prevalent anxiety disorder and may involve advanced biological aging. However, brain age research in psychiatry has primarily examined mood and psychotic disorders. This mega-analysis investigated brain aging in SPH participants within the ENIGMA-Anxiety Working Group.
Methods: 3D brain s tructural MRI scans from 17 international samples (600 SPH individuals, of whom 504 formally diagnosed and 96 questionnaire-based cases; 1,134 controls; age range: 22-75 years) were processed with FreeSurfer. Brain age was estimated from 77 subcortical and cortical regions with a publicly available ENIGMA brain age model. The brain-predicted age difference (brain-PAD) was calculated as brain age minus chronological age. Linear mixed-effect models examined group differences in brain-PAD and moderation by age.
Results: No significant group difference in brain-PAD manifested ( βdiagnosis (SE)=0.37 years (0.43), p =0.39). A negative diagnosis-by-age interaction was identified, which was most pronounced in formally diagnosed SPH ( βdiagnosis-by-age =-0.08 (0.03), pFDR =0.02). This interaction remained significant when excluding participants with anxiety comorbidities, depressive comorbidities, and medication use. Post-hoc analyses revealed a group difference for formal SPH diagnosis in younger participants (22-35 years; βdiagnosis =1.20 (0.60), p <0.05, mixed-effects d (95% confidence interval)=0.14 (0.00-0.28)), but not older participants (36-75 years; βdiagnosis =0.07 (0.65), p =0.91).
Conclusions: Brain aging did not relate to SPH in the full sample. However, a diagnosis-by-age interaction was observed across analyses, and was strongest in formally diagnosed SPH. Post-hoc analyses showed a subtle advanced brain aging in young adults with formally diagnosed SPH. Taken together, these findings indicate the importance of clinical severity, impairment and persistence, and may suggest a slightly earlier end to maturational processes or subtle decline of brain structure in SPH.
求助内容：
应助结果提醒方式：
京公网安备 11010802042870号
