Assessment of trimethylamine N-oxide (TMAO) as a potential biomarker of severe stress in patients vulnerable to posttraumatic stress disorder (PTSD) after acute myocardial infarction

Abstract

Background : Posttraumatic stress disorder (PTSD) is a frequently observed stress-related disorder after acute myocardial infarction (AMI) and it is characterized by numerous symptoms, such as flashbacks, intrusions and anxiety, as well as uncontrollable thoughts and feelings related to the trauma. Biological correlates of severe stress might contribute to identifying PTSD-vulnerable patients at an early stage. Objective : Aims of the study were (1) to determine whether blood levels of trimethylamine N-oxide (TMAO) vary immediately after AMI in patients with/without AMI-induced PTSD symptomatology, (2) to investigate whether TMAO is a potential biomarker that might be useful in the prediction of PTSD and the PTSD symptom subclusters re-experiencing, avoidance and hyperarousal, and (3) to investigate whether TMAO varies immediately after AMI in patients with/without depression 6 months after AMI. Method : A total of 114 AMI patients were assessed with the Hamilton-Depression Scale after admission to the hospital and 6 months later. The Clinician Administered PTSD Scale for DSM-5 was used to explore PTSD-symptoms at the time of AMI and 6 months after AMI. To assess patients’ TMAO status, serum samples were collected at hospitalization and 6 months after AMI. Results : Participants with PTSD-symptomatology had significantly higher TMAO levels immediately after AMI than patients without PTSD-symptoms (ANCOVA: TMAO(PTSD x time), F = 4.544, df = 1, p = 0.035). With the inclusion of additional clinical predictors in a hierarchical logistic regression model, TMAO became a significant predictor of PTSD-symptomatology. No significant differences in TMAO levels immediately after AMI were detected between individuals with/without depression 6 months after AMI. Conclusions : An elevated TMAO level immediately after AMI might reflect severe stress in PTSD-vulnerable patients, which might also lead to a short-term increase in gut permeability to trimethylamine, the precursor of TMAO. Thus, an elevated TMAO level might be a biological correlate for severe stress that is associated with vulnerability to PTSD.

Gut–brain axis volatile organic compounds derived from breath distinguish between schizophrenia and major depressive disorder

“… 23 Both TMA and its metabolites are presumed to play a pivotal role in microbiotic pathways relating to the gut–brain axis and have been linked to several psychiatric and neurologic diseases. 24 – 26 However, TMA has also been found to lead to the development of arteriosclerosis and cardiovascular disease. 27 Through the gut microbiome, TMA is synthesized from choline found in eggs, red meat or fish and is subsequently transformed in the liver into its active metabolite trimethylamine N oxide (TMAO), 28 which eventually acts as a neuronal protein stabilizer.…”

Myeloperoxidase as a Potential Biomarker of Acute-Myocardial-Infarction-Induced Depression and Suppression of the Innate Immune System

“…Many previous studies have shown that AMI patients suffer from severe and prolonged stress [ 35 ]. Prolonged AMI-related stress and the concomitant activation of proinflammatory cytokines make AMI patients more vulnerable to depression [ 11 , 22 , 23 , 24 ].…”

“…After AMI, many patients suffer from severe and prolonged stress [ 35 ], which is associated with neuroinflammation and vulnerability to depression. In particular, IL-6 plays an important role in the inflammatory hypothesis of depression.…”

Sex-specific differences in trimethylamine N-oxide (TMAO) concentrations before and after cardiac rehabilitation in acute myocardial infarction patients

“…TMAO is predictive of adverse cardiovascular events, including myocardial infarction (Tang et al, 2013[ 22 ]; Baranyi et al, 2021[ 3 ]). A dose-response meta-analysis by Schiattarella et al (2017[ 21 ]), based on seven studies, also showed that the relative risk (RR) for all-cause mortality significantly increases by 7.6 % per 10 μmol/L increment of TMAO [summary RR: 1.07, 95 % CI (1.04-1.11)] (Schiattarella et al, 2017[ 21 ]).…”