Examining the association between posttraumatic stress disorder and disruptions in cortical networks identified using data-driven methods

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Authors	YANG Jin HUGGINS Ashley A SUN Delin BAIRD C Lexi HASWELL Courtney C FRIJLING Jessie L OLFF Miranda MIRJAM van Zuiden KOCH Saskia B J NAWIJN Laura VELTMAN Dick J SUAREZ-JIMENEZ Benjamin ZHU Xi NERIA Yuval HUDSON Anna R MUELLER Sven C BAKER Justin T LEBOIS Lauren A M KAUFMAN Milissa L QI Rongfeng LU Guang Ming ŘÍHA Pavel REKTOR Ivan DENNIS Emily L CHING Christopher R K THOMOPOULOS Sophia I SALMINEN Lauren E JAHANSHAD Neda THOMPSON Paul M STEIN Dan J KOOPOWITZ Sheri M IPSER Jonathan C SEEDAT Soraya STEFAN du Plessis VAN DEN HEUVEL Leigh L WANG Li ZHU Ye LI Gen SIERK Anika MANTHEY Antje WALTER Henrik DANIELS Judith K SCHMAHL Christian HERZOG Julia I LIBERZON Israel KING Anthony ANGSTADT Mike DAVENPORT Nicholas D SPONHEIM Scott R DISNER Seth G STRAUBE Thomas HOFMANN David GRUPE Daniel W NITSCHKE Jack B DAVIDSON Richard J LARSON Christine L DEROON-CASSINI Terri A BLACKFORD Jennifer U OLATUNJI Bunmi O GORDON Evan M MAY Geoffrey NELSON Steven M ABDALLAH Chadi G LEVY Ifat HARPAZ-ROTEM Ilan KRYSTAL John H MOREY Rajendra A SOTIRAS Aristeidis
Year of publication	2024
Type	Article in Periodical
Magazine / Source	Neuropsychopharmacology
MU Faculty or unit	Central European Institute of Technology
Citation
Web	https://www.nature.com/articles/s41386-023-01763-5
Doi	http://dx.doi.org/10.1038/s41386-023-01763-5
Keywords	posttraumatic stress disorder; disruptions; cortical networks
Description	Posttraumatic stress disorder (PTSD) is associated with lower cortical thickness (CT) in prefrontal, cingulate, and insular cortices in diverse trauma-affected samples. However, some studies have failed to detect differences between PTSD patients and healthy controls or reported that PTSD is associated with greater CT. Using data-driven dimensionality reduction, we sought to conduct a well-powered study to identify vulnerable networks without regard to neuroanatomic boundaries. Moreover, this approach enabled us to avoid the excessive burden of multiple comparison correction that plagues vertex-wise methods. We derived structural covariance networks (SCNs) by applying non-negative matrix factorization (NMF) to CT data from 961 PTSD patients and 1124 trauma-exposed controls without PTSD. We used regression analyses to investigate associations between CT within SCNs and PTSD diagnosis (with and without accounting for the potential confounding effect of trauma type) and symptom severity in the full sample. We performed additional regression analyses in subsets of the data to examine associations between SCNs and comorbid depression, childhood trauma severity, and alcohol abuse. NMF identified 20 unbiased SCNs, which aligned closely with functionally defined brain networks. PTSD diagnosis was most strongly associated with diminished CT in SCNs that encompassed the bilateral superior frontal cortex, motor cortex, insular cortex, orbitofrontal cortex, medial occipital cortex, anterior cingulate cortex, and posterior cingulate cortex. CT in these networks was significantly negatively correlated with PTSD symptom severity. Collectively, these findings suggest that PTSD diagnosis is associated with widespread reductions in CT, particularly within prefrontal regulatory regions and broader emotion and sensory processing cortical regions.
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