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

Yang J, Huggins AA, Sun D, Baird CL, Haswell CC, Frijling JL, Olff M, van Zuiden M, Koch SBJ, Nawijn L, Veltman DJ, Suarez-Jimenez B, Zhu X, Neria Y,
Hudson AR, Mueller SC, Baker JT, Lebois LAM, Kaufman ML, Qi R, Lu GM, Říha P, Rektor I, Dennis EL, Ching CRK, Thomopoulos SI, Salminen LE, Jahanshad N,
Thompson PM, Stein DJ, Koopowitz SM, Ipser JC, Seedat S, du Plessis S, van den Heuvel LL, Wang L, Zhu Y, Li G, Sierk A, Manthey A, Walter H, Daniels JK,
Schmahl C, Herzog JI, Liberzon I, King A, Angstadt M, Davenport ND, Sponheim SR, Disner SG, Straube T, Hofmann D, Grupe DW, Nitschke JB, Davidson RJ, Larson CL, deRoon-Cassini TA, Blackford JU, Olatunji BO, Gordon EM, May G, Nelson SM, Abdallah CG, Levy I, Harpaz-Rotem I, Krystal JH, Morey RA, Sotiras A.

Neuropsychopharmacology. 2024 Feb;49(3):609-619. doi: 10.1038/s41386-023-01763-5. Epub 2023 Nov 28. PMID:38017161; PMCID: PMC10789873.


18 Jan 2024

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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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