Neurovascular Mediators and Psychological Symptoms in Systemic Sclerosis: A Cross-sectional Study

Recent research has demonstrated the role of vascular endothelial growth factor (VEGF) and matrix metalloproteinase-9 (MMP-9) in both systemic sclerosis (SSc) and other neurological disorders. These molecules are central to neuroinflammation, synaptic plasticity, and neurovascular function, all of which are fundamental to the pathophysiology of these diseases. Given the apparent overlap, this study was designed to investigate the relationship between psychological symptoms and serum VEGF and MMP-9 levels in patients with systemic sclerosis (SSc).

This study employed a cross-sectional design and recruited patients with SSc. Serum levels of VEGF and MMP-9 were measured in the blood using certified immunoassays. Psychological symptoms were assessed using the Symptom Checklist-90-Revised (SCL-90-R). Correlation analysis was performed to examine associations between biomarker levels and psychological data obtained from the SCL-90-R. A mediation analysis was conducted to explore potential indirect relationships between biomarkers (VEGF, MMP-9) and psychological symptoms.

Among 34 SSc patients (mean age 49.65 years), psychological distress was prevalent, with somatization and psychoticism showing the highest symptom scores on the SCL-90-R. VEGF and MMP-9 levels were within normal ranges but showed important associations: VEGF correlated with psychological symptoms, particularly paranoid ideation (r = 0.6, p = .01), while MMP-9 was linked to pulmonary artery pressure (r = 0.4, p = .03). Mediation analyses confirmed that VEGF significantly mediated the relationship between MMP-9 and multiple psychological domains.

This study demonstrates significant psychological distress in SS patients and reveals meaningful associations between VEGF levels and psychological symptoms, even within clinically normal ranges, suggesting subclinical biomarker variations may contribute to emotional distress through neurovascular pathways. The findings align with existing literature while extending understanding by identifying VEGF as a mediator between matrix metalloproteinase-9 and psychological domains. However, the cross-sectional design limits causal interpretation, and the sample size was limited; therefore, findings should be interpreted with caution.

These results suggest that dysregulated VEGF and MMP-9, both crucial for vascular and fibrotic functions, can also influence or reflect psychological well-being in individuals with SSc. Further studies are needed to identify the psychobiological pathways involved. Thus, a more integrated, physiological–psychological health-based treatment strategy might improve clinical outcomes and quality of life for SSc patients.