White Matter Microstructure Alterations in Social Anxiety Disorder: A Mega-Analysis Across Twelve Cohorts in the ENIGMA-Anxiety Working Group.
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Roelofs Eline F, Groenewold Nynke A, Farkas Kinga, Zhu Alyssa H, Gao Si, Borgers Tiana, Dannlowski Udo, Flinkenflügel Kira, Grotegerd Dominik, Hahn Tim, Jansen Andreas, Leehr Elisabeth J, Kircher Tilo T J, Meinert Hannah, Nenadić Igor, Stein Frederike, Straube Benjamin, Demiralp Tamer, Tükel Raşit, Westenberg P Michiel, Bauer Jochen, Kraus Anna, Doruyter Alexander G G, Lochner Christine, Hofmann David, Straube Thomas, Zugman André, Calkins Monica E, Gur Raquel E, Gur Ruben C, Larsen Bart S, Satterthwaite Theodore D, Slump Theresa M, Vogler Roman A, Avery Suzanne N, Blackford Jennifer U, Clauss Jacqueline A, Lui Su, Thomopoulos Sophia I, Vermeiren Robert R J M, Jahanshad Neda, Kochunov Peter V, Thompson Paul M, Pine Daniel S, Stein Dan J, van der Wee Nic J A, Bas-Hoogendam Janna Marie
Аннотация
METHODS: We analyzed data from 487 individuals with SAD and 1604 HC participants (ages 8-65 years) from 12 cohorts worldwide. Analyses and quality control were performed using standardized ENIGMA diffusion tensor imaging protocols. We primarily examined fractional anisotropy (FA) as the main parameter of WM microstructure. Linear mixed-effects analyses were conducted to compare individuals with SAD with HC participants in the total sample. Next, adult (age >21) and adolescent (age ≤21) samples were analyzed separately. In sensitivity analyses, additional effects of sex, medication, symptom severity, and comorbid psychiatric disorders were investigated.
RESULTS: In the total sample, individuals with SAD showed lower FA in several tracts, including the corpus callosum and fornix, compared with HC participants. Widespread sex × diagnosis interactions were observed, mostly driven by lower FA in females with SAD. Adults with SAD showed lower FA in multiple tracts, while age × diagnosis interactions were observed in adolescents.
CONCLUSIONS: Using a mega-analytic approach, several differences in WM microstructure were found between individuals with SAD and HC participants, both in the full sample and in age group-specific sensitivity analyses. Some neurobiological changes in WM tracts in individuals with SAD may vary with age and sex, whereas others may relate to broader transdiagnostic neurobiological features underlying psychopathology. Further research should investigate these issues in more detail.