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Sex-dependent risk factors for PTSD: a prospective structural MRI study

Abstract

Female individuals are more likely to be diagnosed with PTSD following trauma exposure than males, potentially due, in part, to underlying neurobiological factors. Several brain regions underlying fear learning and expression have previously been associated with PTSD, with the hippocampus, amygdala, dorsal anterior cingulate cortex (dACC), and rostral ACC (rACC) showing altered volume and function in those with PTSD. However, few studies have examined how sex impacts the predictive value of subcortical volumes and cortical thickness in longitudinal PTSD studies. As part of an emergency department study completed at the Grady Trauma Project in Atlanta, GA, N = 93 (40 Female) participants were enrolled within 24 h following a traumatic event. Multi-echo T1-weighted MRI images were collected one-month post-trauma exposure. Bilateral amygdala and hippocampal volumes and rACC and dACC cortical thickness were segmented. To assess the longitudinal course of PTSD, the PTSD Symptom Scale (PSS) was collected 6 months post-trauma. We investigated whether regional volume/thickness interacted with sex to predict later PTSD symptom severity, controlling for PSS score at time of scan, age, race, and trauma type, as well as intracranial volume (ICV) for subcortical volumes. There was a significant interaction between sex and rACC for 6-month PSS, such that right rACC thickness was positively correlated with 6-month PSS scores in females, but not in males. In examining PTSD symptom subtypes and depression symptoms, greater rACC thickness in females predicted greater avoidance symptoms, while smaller rACC thickness in males predicted greater depression symptoms. Amygdala and hippocampus volume and dACC thickness showed no main effect or interaction with sex. The current findings provide evidence for sex-based differences in how brain volume predicts future PTSD severity and symptoms and supports the rACC as being a vital region regarding PTSD. Gender differences should be assessed in future longitudinal PTSD MRI studies for more accurate identification of future PTSD risk following trauma.

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Fig. 1: Regions of interest and sex-by-region interaction effects predicting subsequent PTSD symptoms.

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Funding

This research was supported by the National Institute of Mental Health (R01 MH094757 [to KJR], R21 MH106902 [to TJ], R01 MH117009 [to JSS], F31 MH126623 [to ARR]), and a NARSAD award from the Brain & Behavior Research Foundation to BOR.

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Design and conceptualization of the study: ARR, SS, VM, BOR, TJ, KJR, JSS. Data collection and recruitment: VM, RH, SJHVR, JSS. Data processing and statistical analyses: ARR, SS, VM, JSS. Initial drafting of the paper: ARR, SS, JSS. All authors revised the paper critically for important intellectual context and agree to be accountable for all aspects of the work, and ensure the accuracy and integrity of the findings.

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Correspondence to Jennifer S. Stevens.

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KJR has received consulting fees or sponsored research support from Alkermes, BrainsWay, and Genomind, and he serves on scientific advisory boards for Janssen, Takeda, and Verily. KJR and JSS are on the NPP Editorial Board. The remaining authors declare no competing interests.

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Roeckner, A.R., Sogani, S., Michopoulos, V. et al. Sex-dependent risk factors for PTSD: a prospective structural MRI study. Neuropsychopharmacol. (2022). https://doi.org/10.1038/s41386-022-01452-9

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