The association of PTSD symptom severity with amygdala nuclei volumes in traumatized youths

Ousdal, Olga Therese; Milde, Anne Marita; Hafstad, Gertrud Sofie; Hodneland, Erlend; Dyb, Grete; Craven, Alexander R.; Melinder, Annika; Endestad, Tor; Hugdahl, Kenneth

doi:10.1038/s41398-020-00974-4

Cited by 38 publications

(36 citation statements)

References 56 publications

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“…By looking into the relationship of GMV and severity of PTSS, we found negative correlations for the left amygdala and hippocampus in COVID-19 survivors but not in controls. This result was consistent with previous observations of the neurological impairments in the amygdala and hippocampus in patients suffering from PTSS [13,30,31].…”

Section: Discussionsupporting

confidence: 94%

Post-traumatic stress symptoms in COVID-19 survivors: a self-report and brain imaging follow-up study

Zhang

Liu

et al. 2021

Mol Psychiatry

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Previous coronavirus pandemics were associated elevated post-traumatic stress symptoms (PTSS), but the self-report and neurological basis of PTSS in patients who survived coronavirus disease 2019 (COVID-19) are largely unknown. We conducted a two-session study to record PTSS in the COVID-19 survivors discharged from hospitals for a short (i.e., about 3 months, Session 1) to a medium period (i.e., about 6 months, Session 2), as well as brain imaging data in Session 2. The control groups were non-COVID-19 locals. Session 1 was completed for 126 COVID-19 survivors and 126 controls. Session 2 was completed for 47 COVID-19 survivors and 43 controls. The total score of post-traumatic stress disorder (PTSD) checklist for DSM-5 (PCL-5) score was significantly higher in COVID-19 survivors compared with controls in both sessions. The PCL-5 score in COVID-19 survivors was positively correlated with the duration after discharge (r = 0.27, p = 0.003 for Session 1), and increased by 20% from Session 1 to Session 2 for the survivors who participated both sessions. The increase was positively correlated with individual's test-retest duration (r = 0.46, p = 0.03). Brain structural volume and functional activity in bilateral hippocampus and amygdala were significantly larger in COVID-19 survivors compared with controls. However, the volumes of the left hippocampus and amygdala were negatively correlated with the PCL-5 score for the COVID-19 survivors. Our study suggests that COVID-19 survivors might face possible PTSS deteriorations, and highlights the importance of monitoring mental wellness of COVID-19 survivors.

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Section: Discussionsupporting

confidence: 94%

Post-traumatic stress symptoms in COVID-19 survivors: a self-report and brain imaging follow-up study

Zhang

Liu

et al. 2021

Mol Psychiatry

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“…First, to our knowledge, this is the first evidence for shared genetic aetiology between PTSD and MRI-derived amygdala and putamen volumes. Importantly, imaging studies have previously identified consistent associations between smaller amygdala volumes and PTSD diagnosis 30,31 , in line with the direction of effect in our study; however, such studies necessarily occur after PTSD onset, making causality and direction of effect difficult to infer. Demonstrating shared genetic aetiology between these traits therefore provides novel and vital context to these existing analyses.…”

Section: Discussionsupporting

confidence: 87%

Polygenic regulation of PTSD severity and outcomes among World Trade Center responders

Huckins

Johnson

Cancelmo

et al. 2020

Preprint

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Post-traumatic stress disorder (PTSD) is a debilitating psychiatric condition occurring in individuals exposed to trauma. The study of PTSD is complicated by highly heterogeneous presentations and experiences of trauma.Here, we studied genetic correlates of PTSD and resilience among a group of responders to the World Trade Center (WTC) 9/11/2001 attacks. This cohort represents a unique opportunity to study genetic risk factors for PTSD, and resilience, following a single, shared, well-documented trauma. We calculated polygenic risk scores associated with PTSD among these 375 individuals, and demonstrated a significant genetic association with social cognition traits, brain volumetric phenotypes, and PTSD-GWAS-derived PRS.Our results demonstrate significant genetic regulation of PTSD severity (CAPS scores) and chronicity (past-month CAPS). PRS derived from GWAS of ADHD, ASD, and brain imaging phenotypes (Amygdala and Putamen volume) were associated with multiple PTSD traits in this study. Interestingly, we find greater genetic contribution to PTSD among cases compared to our full cohort. In addition, we tested for associations between exposures to traumatic stressors, including WTC-related exposures, childhood trauma, and traumatic life events since 9/11. Together, polygenic risk and exposures to traumatic stress explain ∼45% of variance in lifetime CAPS among the full cohort (R2=0.454), and ∼48% of variance in past-month CAPS (R2=0.480). These participants represent a highly vulnerable population, with exposures to severe trauma during 9/11 and the following days. Identifying individuals at heightened risk for PTSD, or who may be suited to particular therapies, is of special importance and relevance in this group. In particular, the identification of MRI imaging phenotypes indicates that coupling of neuroimaging with genetic risk score calculations may predict PTSD outcomes.

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“…In adult military veterans, PTSD is linked with smaller paralaminar and lateral subnuclei, but larger central, medial, and cortical nuclei which are critical to the behavioral and physiological outputs of fear (Morey et al, 2020). In contrast, in youth exposed to a terror attack, PTSD symptoms were associated with smaller volumes across all major subnuclei (Ousdal et al, 2020). These findings suggest that the developmental timing and type of trauma exposure may have important effects on neural phenotypes in PTSD.…”

Section: Introductionmentioning

confidence: 71%

Elastic Shape Analysis of Brain Structures for Predictive Modeling of PTSD

Wu¹,

Kundu²,

Stevens³

et al. 2021

Preprint

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There is increasing evidence on the importance of brain morphology in predicting and classifying mental disorders and behavior. However, the vast majority of current shape approaches rely heavily on vertex-wise analysis that may not successfully capture complexities of subcortical structures. Additionally, the past works do not include interactions between these structures and exposure factors when modeling clinical or behavioral outcomes. Predictive modeling with such interactions is of paramount interest in heterogeneous mental disorders such as PTSD, where trauma exposure and other factors interact with brain shape changes to influence behavior. We propose a comprehensive framework that overcomes these limitations by representing brain substructures as continuous parameterized surfaces and quantifying their shape differences using elastic shape metrics. Using the elastic shape metric, we compute shape summaries (mean, covariance, PCA) of subcortical data and represent individual shapes by their principal scores under a PCA basis. These representations allow visualization tools that help understand localized changes when these PCs are varied. Subsequently, these PCs, the auxiliary exposure variables, and their interactions are used for regression modeling and prediction. We apply our method to data from the Grady Trauma Project (GTP), where the goal is to predict clinical measures of PTSD using shapes of brain substructures such as the hippocampus, amygdala, and putamen. Our analysis revealed considerably greater predictive power under the elastic shape analysis than widely used approaches such as the standard vertex-wise shape analysis and even a volumetric analysis. It helped identify local deformations in brain shapes related to change in PTSD severity. To our knowledge, this is one of the first brain shape analysis approaches that can seamlessly integrate the pre-processing steps under one umbrella for improved accuracy and are naturally able to account for interactions between brain shape and additional covariates to yield superior predictive performance when modeling clinical outcomes.

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The association of PTSD symptom severity with amygdala nuclei volumes in traumatized youths

Cited by 38 publications

References 56 publications

Post-traumatic stress symptoms in COVID-19 survivors: a self-report and brain imaging follow-up study

Post-traumatic stress symptoms in COVID-19 survivors: a self-report and brain imaging follow-up study

Polygenic regulation of PTSD severity and outcomes among World Trade Center responders

Elastic Shape Analysis of Brain Structures for Predictive Modeling of PTSD

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