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. 2021 Sep 15;11(9):1365.
doi: 10.3390/biom11091365.

Association of Lipid Peroxidation Product 4-Hydroxynonenal with Post-Traumatic Stress Disorder

Matea Nikolac Perković  1 , Lidija Milković  2 , Suzana Uzun  3   4 , Ninoslav Mimica  3   4 , Nela Pivac  1 , Georg Waeg  5 , Neven Žarković  2
Affiliations

Association of Lipid Peroxidation Product 4-Hydroxynonenal with Post-Traumatic Stress Disorder

Matea Nikolac Perković et al. Biomolecules. .

Abstract

Repeated activation of the hypothalamic-pituitary-adrenal axis system, sleep disturbances, and other symptoms related to posttraumatic stress disorder (PTSD) elevate reactive oxygen species, increase inflammation, and accelerate cellular aging, leading to neuroprogression and cognitive decline. However, there is no information about possible involvement of 4-hydroxynonenal (4-HNE), the product of lipid peroxidation associated with stress-associated diseases, in the complex etiology of PTSD. Therefore, the aim of this study was to compare the plasma levels of 4-HNE between war veterans with PTSD (n = 62) and age-, sex- and ethnicity- matched healthy control subjects (n = 58) in order to evaluate the potential of HNE-modified proteins as blood-based biomarker of PTSD. The genuine 4-HNE-Enzyme-Linked Immunosorbent Assay (HNE-ELISA), based on monoclonal antibody specific for HNE-histidine (HNE-His) adducts, was used to determine plasma HNE-protein conjugates. Our results revealed significantly elevated levels of 4-HNE in patients with PTSD. Moreover, the accumulation of plasma 4-HNE seems to increase with aging but in a negative correlation with BMI, showing specific pattern of change for individuals diagnosed with PTSD. These findings suggest that oxidative stress and altered lipid metabolism reflected by increase of 4-HNE might be associated with PTSD. If confirmed with further studies, elevated 4-HNE plasma levels might serve as a potential biomarker of PTSD.

Keywords: 4-hydroxynonenal (4-HNE); ELISA; biomarker; human plasma samples; lipid peroxidation; oxidative stress; posttraumatic stress disorder (PTSD).

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Conflict of interest statement

The authors declare no conflict of interest. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, or in the decision to publish the results.

Figures

Figure 1
Figure 1
Plasma concentration of 4-HNE-protein adducts (pmol/mg protein) in samples of healthy controls (n = 58) and PTSD subjects (n = 62). Results are presented as a box and whisker plot. The median is represented by the line in the box, while the interquartile range (IQR) box represents the middle quartiles (the 75th minus the 25th percentile). The whiskers on either side of the IQR box represent the lowest and highest quartiles of the data. The ends of the whiskers represent the maximum and minimum of the data. ** p = 0.006. 4-HNE, 4-hydroxynonenal; PTSD, posttraumatic stress disorder.
Figure 2
Figure 2
Correlation of 4-HNE-protein adducts plasma concentration (pmol/mg protein) with age (A) and BMI (B) in samples of healthy controls (n = 58) and PTSD subjects (n = 62). BMI, body mass index; 4-HNE, 4-hydroxynonenal; PTSD, posttraumatic stress disorder.
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