Brain Aging in Specific Phobia: An ENIGMA-Anxiety Mega-Analysis.
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Blake Kimberly V, Hilbert Kevin, Ipser Jonathan C, Han Laura K M, Bas-Hoogendam Janna Marie, Åhs Fredrik, Bauer Jochen, Beesdo-Baum Katja, Björkstrand Johannes, Blanco-Hinojo Laura, Böhnlein Joscha, Bülow Robin, Cano Marta, Cardoner Narcis, Caseras Xavier, Dannlowski Udo, Fredrikson Mats, Goossens Liesbet, Grabe Hans J, Grotegerd Dominik, Hahn Tim, Hamm Alfons, Heinig Ingmar, Herrmann Martin J, Hofmann David, Jamalabadi Hamidreza, Jansen Andreas, Kindt Merel, Kircher Tilo, Klahn Anna L, Koelkebeck Katja, Krug Axel, Leehr Elisabeth J, Lotze Martin, Margraf Juergen, Muehlhan Markus, Nenadić Igor, Peñate Wenceslao, Pittig Andre, Plag Jens, Pujol Jesús, Richter Jan, Ridderbusch Isabelle C, Rivero Francisco, Schäfer Axel, Schäfer Judith, Schienle Anne, Schrammen Elisabeth, Schruers Koen, Seidl Esther, Stark Rudolf M, Straube Benjamin, Straube Thomas, Ströhle Andreas, Suchan Boris, Teutenberg Lea, Thomopoulos Sophia I, Ventura-Bort Carlos, Visser Renee M, Völzke Henry, Wabnegger Albert, Wannemüller André, Wendt Julia, Wittchen Hans-Ulrich, Wittfeld Katharina, Yang Yunbo, Zilverstand Anna, Zwanzger Peter, Schmaal Lianne, Aghajani Moji, Pine Daniel S, Thompson Paul M, van der Wee Nic J A, Stein Dan J, Lueken Ulrike, Groenewold Nynke A
Аннотация
Specific phobia (SPH) is a prevalent anxiety disorder and may involve advanced biological aging. However, limited brain age research has been conducted in anxiety disorders. This mega-analysis investigated brain aging in SPH participants within the ENIGMA-Anxiety Working Group. 3D brain structural MRI scans from 17 international samples (600 SPH individuals, of whom 504 formally diagnosed and 96 questionnaire-based cases; 1134 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-effects models examined group differences in brain-PAD and moderation by age. 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). 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 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.