Biomolecular Correlates of Chronic Affective Dysregulation in PTSD: A Combined Assessment Using the Cornell Dysthymia Rating Scale (CDRS) and the Serum Markers SUMO1, MDA, CX3CL1, and UCHL1

Post-traumatic stress disorder (PTSD) is frequently comorbid with persistent depressive disorder (dysthymia), indicating shared neurobiological pathways that influence stress modulation, emotional regulation, and neurohormonal adaptation. This study examines the roles of serum biomarkers-small ubiquitin-like modifier 1 (SUMO1), malondialdehyde (MDA), fractalkine (CX3CL1), and ubiquitin C-terminal hydrolase L1 (UCHL1)-involved in oxidative stress management, neuroimmune regulation, and neuronal proteostasis. In this cross-sectional analysis, biomarker expression was assessed in 92 male trauma-exposed participants aged 19-50 years, divided into three groups: PTSD duration ≤ 5 years (n = 33, median age 34.0 years [IQR 31.0-41.0]), PTSD duration > 5 years (n = 31, median age 36.0 years [IQR 29.5-41.0]), and controls without current or past PTSD (n = 28, median age 33.5 years [IQR 24.3-41.5]). Participants were stratified into younger (19-34 years) and older (35-50 years) cohorts to account for age-related neurobiological variability. Dysthymic symptomatology was evaluated using the Cornell Dysthymia Rating Scale (CDRS), focusing on chronic subthreshold depressive features. Results indicated a significant association between PTSD and elevated dysthymic symptom burden (<i>p</i> < 0.001), with both PTSD subgroups demonstrating mild to moderate CDRS severity compared to euthymic controls. Biomarker analysis revealed phase-dependent alterations: SUMO1 levels were significantly elevated in the ≤5 years PTSD group compared to controls (<i>p</i> = 0.002), suggesting early compensatory neuroprotection, whereas UCHL1 was markedly increased in the >5 years PTSD group (<i>p</i> = 0.015), which is indicative of chronic neuronal damage and proteostatic disruption. No significant differences were observed in MDA or CX3CL1 across groups (<i>p</i> > 0.05). These findings highlight PTSD's contribution to sustained affective dysregulation, potentially mediated by temporal shifts in oxidative stress and protein homeostasis markers. Clinically, this supports the utility of biomarker profiling for risk stratification, early intervention, and personalized therapeutic strategies, such as targeted modulation of SUMOylation or UCHL1 activity, to enhance neuroresilience and mitigate progression to severe mood disorders.