Investigating the Role of Gut-Derived Neurotoxin TMAO in PTSD Risk Following Traumatic Brain Injury.

Abstract

Background: Post-traumatic stress disorder (PTSD), comorbid with traumatic brain injury (TBI), severely affects the mood state of patients. Trimethylamine N-oxide (TMAO), one of the key intestinal flora metabolites, strongly correlates with TBI. This study aimed to explore the role of TMAO in the development of TBI-related PTSD and assess its predictive significance.

Methods: This study included 120 TBI patients treated at the Affiliated Hengyang Hospital of Hunan Normal University & Hengyang Central Hospital between February 2022 and April 2024. The clinical data were obtained from the hospital's medical record system. Patients were divided into a PTSD group (n = 56) and a non-PTSD group (n = 64) based on the post-traumatic stress disorder self-rating scale (PTSD-SS). Furthermore, patients in the PTSD group were divided into mild and severe subgroups. Blood samples were collected, and serum TMAO levels were assessed. Additionally, the correlation between TMAO levels, PTSD incidence, and PTSD severity was evaluated. The risk factors for PTSD comorbid with TBI and its severity were evaluated using univariate and multivariate logistic regression analyses. Finally, receiver operating characteristic (ROC) curve analysis was performed to assess the diagnostic effectiveness of TMAO as a predictive marker for PTSD.

Results: Multivariate analysis showed that female gender, lower per capita monthly household income, depression, anxiety, and higher serum TMAO levels were significant risk factors for PTSD. Depression, anxiety, and higher serum TMAO levels were associated with severe PTSD, and higher per capita monthly household income and intracranial infection were protective factors. Serum TMAO levels were significantly higher in PTSD patients than in non-PTSD patients (p < 0.001), with its level profoundly elevated in severe PTSD patients than in mild PTSD patients. Furthermore, the correlation analysis revealed that TMAO was positively correlated with the severity of PTSD (r = 0.8582, p < 0.0001). ROC curve analysis indicated TMAO's sensitivity of 67.86% and specificity of 93.75% for predicting PTSD, with an area under the curve (AUC) of 0.8175.

Conclusion: Serum TMAO levels were significantly elevated in PTSD patients comorbid with TBI and were closely associated with PTSD severity. Furthermore, TMAO may aid in the early identification of high-risk, severe PTSD patients following TBI, thus helping to optimize intervention strategies.