Results of neuroimaging datasets aggregated from multiple sites may be biased by site-specific profiles in participants' demographic and clinical characteristics, as well as MRI acquisition... Show moreResults of neuroimaging datasets aggregated from multiple sites may be biased by site-specific profiles in participants' demographic and clinical characteristics, as well as MRI acquisition protocols and scanning platforms. We compared the impact of four different harmonization methods on results obtained from analyses of cortical thickness data: (1) linear mixed-effects model (LME) that models site-specific random intercepts (LME INT), (2) LME that models both site-specific random intercepts and age-related random slopes (LME INT+ SLP), (3) ComBat, and (4) ComBat with a generalized additive model (ComBat-GAM). Our test case for comparing harmonization methods was cortical thickness data aggregated from 29 sites, which included 1,340 cases with posttraumatic stress disorder (PTSD) (6.2-81.8 years old) and 2,057 trauma-exposed controls without PTSD (6.3-85.2 years old). We found that, compared to the other data harmonization methods, data processed with ComBat-GAM was more sensitive to the detection of significant case-control differences (X-2 (3) = 63.704, p < 0.001) as well as casecontrol differences in age-related cortical thinning (X-2 (3) = 12.082, p = 0.007). Both ComBat and ComBat-GAM outperformed LME methods in detecting sex differences (X-2 (3) = 9.114, p = 0.028) in regional cortical thickness. ComBat-GAM also led to stronger estimates of age-related declines in cortical thickness (corrected p-values < 0.001), stronger estimates of case-related cortical thickness reduction (corrected p-values < 0.001), weaker estimates of age-related declines in cortical thickness in cases than controls (corrected p-values < 0.001), stronger estimates of cortical thickness reduction in females than males (corrected p-values < 0.001), and stronger estimates of cortical thickness reduction in females relative to males in cases than controls (corrected p-values < 0.001). Our results support the use of ComBat-GAM to minimize confounds and increase statistical power when harmonizing data with non-linear effects, and the use of either ComBat or ComBat-GAM for harmonizing data with linear effects. Show less
Studies of posttraumatic stress disorder (PTSD) report volume abnormalities in multiple regions of the cerebral cortex. However, findings for many regions, particularly regions outside commonly... Show moreStudies of posttraumatic stress disorder (PTSD) report volume abnormalities in multiple regions of the cerebral cortex. However, findings for many regions, particularly regions outside commonly studied emotion-related prefrontal, insular, and limbic regions, are inconsistent and tentative. Also, few studies address the possibility that PTSD abnormalities may be confounded by comorbid depression. A mega-analysis investigating all cortical regions in a large sample of PTSD and control subjects can potentially provide new insight into these issues. Given this perspective, our group aggregated regional volumes data of 68 cortical regions across both hemispheres from 1379 PTSD patients to 2192 controls without PTSD after data were processed by 32 international laboratories using ENIGMA standardized procedures. We examined whether regional cortical volumes were different in PTSD vs. controls, were associated with posttraumatic stress symptom (PTSS) severity, or were affected by comorbid depression. Volumes of left and right lateral orbitofrontal gyri (LOFG), left superior temporal gyrus, and right insular, lingual and superior parietal gyri were significantly smaller, on average, in PTSD patients than controls (standardized coefficients = -0.111 to -0.068, FDR corrected P values < 0.039) and were significantly negatively correlated with PTSS severity. After adjusting for depression symptoms, the PTSD findings in left and right LOFG remained significant. These findings indicate that cortical volumes in PTSD patients are smaller in prefrontal regulatory regions, as well as in broader emotion and sensory processing cortical regions. Show less
Background In recent years, a new framework for analyzing and understanding posttraumatic stress disorder (PTSD) was introduced; the network approach. Up until now, network analysis studies of PTSD... Show moreBackground In recent years, a new framework for analyzing and understanding posttraumatic stress disorder (PTSD) was introduced; the network approach. Up until now, network analysis studies of PTSD were largely conducted on small to medium sample sizes (N < 1,000), which might be a possible cause of variability in main findings. Moreover, only a limited number of network studies investigated comorbidity.Methods In this study, we utilized a large sample to conduct a network analysis of 17 symptoms of PTSD (DSM-IV), and compared it to the result of a second network consisting of symptoms of PTSD and depression (based on Patient Health Questionnaire-9 [PHQ-9]). Our sample consisted of 502,036 treatment-seeking veterans, out of which 158,139 had fully completed the assessment of symptoms of PTSD and a subsample of 32,841 with valid PCL and PHQ-9 that was administered within 14 days or less.Results Analyses found that in the PTSD network, the most central symptoms were feeling distant or cut off from others, followed by feeling very upset when reminded of the event, and repeated disturbing memories or thoughts of the event. In the combined network, we found that concentration difficulties and anhedonia are two of the five most central symptoms.Conclusion Our findings replicate the centrality of intrusion symptoms in PTSD symptoms' network. Taking into account the large sample and high stability of the network structure, we believe our study can answer some of the criticism regarding stability of cross-sectional network structures. Show less
