Structural_Covariance_Network_TopN

Posttraumatic stress disorder (PTSD) is accompanied by disrupted cortical neuroanatomy. We investigated structural covariance (SC)-based network alterations associated with PTSD in cortical regions that demonstrate case-control differences of cortical thickness (CT) and surface area (SA). Neuroimaging data were aggregated from 29 research sites in five countries (PTSD/Non-PTSD: N = 1,344/2,073 for CT, and 1,348/2,066 for SA; 6.2~85.2 years old) by the ENIGMA PGC PTSD working group. FreeSurfer derived estimates of CT and SA were averaged for each of the 148 cortical regions and then rank ordered by effect size of PTSD-related cortical differences. The top-n (n = 2 to 148) regions with the largest differences in effect size for PTSD > non-PTSD formed hypertrophic networks, for PTSD < non-PTSD formed atrophic networks, and formed stable networks for the smallest effect size for between-group differences. The mean SC of a given n-region network was the average of all positive pairwise correlations and was compared to the mean SC of 5,000 randomly generated n-region networks. Global tests showed that, PTSD patients had higher mean SC in CT-based (p < 0.001) and SA-based (p = 0.017) atrophic networks, CT-based (p = 0.029) and SA-based (p = 0.017) hypertrophic networks, and CT-based (p < 0.001) stable networks than in random networks. Non-PTSD participants showed higher mean SC in CT-based (p < 0.001) and SA-based (p < 0.001) atrophic networks, and SA-based (p = 0.014) hypertrophic networks than in random networks. Patients with PTSD relative to non-PTSD controls exhibited lower mean SC in CT-based (p = 0.014) and SA-based (p = 0.024) atrophic networks. Patients with PTSD alone showed lower mean SC in CT-based atrophic networks than patients with depression alone (p < 0.001), and higher mean SC in SA-based atrophic networks than PTSD patients comorbid with depression (p < 0.001) as well as healthy controls (p = 0.014). We also explored the modulations of sex and age on PTSD-related network differences, as well as the structural networks that are associated with PTSD symptom severity. Our findings show that PTSD-related cortical morphometric changes are associated with cortico-cortical SC networks, which are further modulated by PTSD and its associations with comorbid depression, sex and age.