N-glycomic Profile in Combat Related Post-Traumatic Stress Disorder.

Lucija Tudor,Gordan Lauc,Oliver Kozumplik,Marcela Konjevod,Suzana Uzun,Dubravka Svob Strac,Nela Pivac,Gordana Nedic Erjavec,Tanja Jovanovic,Matea Nikolac Perkovic

doi:10.3390/biom9120834

Abstract

Post-traumatic stress disorder (PTSD) develops in a portion of individuals exposed to extreme trauma. Glycosylation is a post-translational modification that affects protein functions and is altered in various pathophysiological states and aging. There are still no validated biomarkers of PTSD. The aim of this study was to evaluate the N-glycomic profile in 543 male Caucasian individuals (299 veterans with PTSD and 244 control subjects). The study included discovery (N = 233) and replication (N = 310) cohort. Hydrophilic interaction HPLC and ultra-performance liquid chromatography were used to separate and detect 39 plasma and 24 IgG N-glycan species, respectively. All results were corrected for the effects of age and multiple testing. Significant results included only significantly altered N-glycans in cases/controls in both cohorts, in the same direction. Results showed that six plasma N-glycans (four increased and two decreased) were altered in PTSD vs. controls in both cohorts, but IgG N-glycans were similar between groups. The severity of PTSD was not associated with different plasma N-glycans. This is the first study detecting alterations in plasma N-glycans in PTSD. These N-glycans are also associated with other neuropsychiatric disorders and inflammation, suggesting possible shared glycosylation mechanisms.

Highlights

Post-traumatic stress disorder (PTSD) is a trauma- and stressor-related disorder [1] that develops in a portion of individuals who show distress and functional impairment after experiencing or witnessing a traumatic event
As expected, there was a strong association of N-glycans with age, and all glycan values were corrected for age (Supplementary Tables S3 and S4)
These results suggested that these six plasma N-glycans might be used as biomarkers of

Summary

Introduction

Post-traumatic stress disorder (PTSD) is a trauma- and stressor-related disorder [1] that develops in a portion of individuals who show distress and functional impairment after experiencing or witnessing a traumatic event. PTSD symptom clusters include re-experiencing, avoidance, negative thoughts, negative mood, and hyperarousal [1]. Combat and war-related traumas are associated with 11–20% prevalence in United States combat veterans [2], whereas in Croatian combat exposed veterans, the estimated prevalence of PTSD ranges from 14 to 40% [3]. PTSD is associated with different somatic comorbidities such as metabolic syndrome, increased inflammatory processes, pulmonary, cardiovascular and autoimmune diseases [4,5,6,7], and it is recognized as systemic. Due to its complex etiology, the biological underpinning of PTSD is still not clear, validated and clinically useful biomarkers have not been identified, and various potential suggested biomarkers were not replicated [9]

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