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Extracellular matrix proteins matrix metallopeptidase 9 (MMP9) and soluble intercellular adhesion molecule 1
Eva Z Reininghaus1, Nina Lackner1, Armin Birner1
1Department of Psychiatry, Medical University of Graz, Graz, Austria.
Objectives:
Matrix metallopeptidase 9 (MMP9) and soluble intercellular adhesion molecule 1 (sICAM-1) are both involved in the restructuring of connective tissues. Evidence also implicates MMP9 and sICAM in cardiovascular and neoplastic diseases, where blood levels may be a marker of disease severity or prognosis. In individuals with bipolar disorder (BD), higher risk for cardiovascular illness has been extensively reported.
Methods:
The aim of this investigation was to measure and compare peripheral levels of serum MMP9 and sICAM in adults with euthymic BD and healthy controls (HC). Furthermore, we focussed on correlations with illness severity and metabolic parameters.
Results:
MMP9 levels among the BD sample (n = 112) were significantly higher than among the HC (n = 80) (MMP9: F = 9.885, p = 0.002, η(2) = 0.058) after controlling for confounding factors. Patients with BD in a later, progressive stage of disease showed significantly higher MMP9 as well as sICAM-1 levels compared to patients with BD in an earlier stage of disease (MMP9: F = 5.8, p = 0.018, η(2) = 0.054; sICAM-1: F = 5.6, p = 0.020, η(2) = 0.052). Correlation analyses of cognitive measures revealed a negative association between performance on the d2 Test of Attention and MMP9 (r = -0.287, p = 0.018) in the BD sample. Despite the sample being euthymic (i.e., according to conventional criteria) at the time of analysis, we found significant correlations between MMP9 as well as sICAM-1 and subthreshold depressive/hypomanic symptoms.
Conclusions:
A collection of disparate findings herein point to a role of MMP9 and cICAM-1 in the patho-progressive process of BD: the increased levels of serum MMP9 and sICAM-1, the correlation between higher levels of these parameters, progressive stage, and cognitive dysfunction in BD, and the positive correlation with subthreshold symptoms. As sICAM-1 and MMP9 are reliable biomarkers of inflammatory and early atherosclerotic disease, these markers may provide indications of the presence of occult cardiovascular disease in this highly at-risk population.
Insights
Elevated serum matrix metallopeptidase 9 (MMP9) and soluble intercellular adhesion molecule 1 (sICAM-1) levels are linked to bipolar disorder (BD) progression and cognitive issues. These biomarkers may indicate underlying cardiovascular disease in BD patients.
Area of Science:
- Neuroscience
- Cardiovascular Medicine
- Biomarker Research
Background:
- Matrix metallopeptidase 9 (MMP9) and soluble intercellular adhesion molecule 1 (sICAM-1) are implicated in tissue remodeling and diseases like cancer and cardiovascular conditions.
- Individuals with bipolar disorder (BD) exhibit an elevated risk for cardiovascular disease.
- MMP9 and sICAM-1 may serve as prognostic markers in various diseases, including potentially BD.
Purpose of the Study:
- To compare serum levels of MMP9 and sICAM-1 in euthymic adults with BD and healthy controls (HC).
- To investigate correlations between MMP9 and sICAM-1 levels and illness severity, cognitive function, and metabolic parameters in BD.
- To explore the potential role of these biomarkers in the path progressive process of BD.
Main Methods:
- Serum samples were collected from adults with euthymic BD (n=112) and HC (n=80).
- Levels of MMP9 and sICAM-1 were measured and compared between groups, controlling for confounding factors.
- Correlations with illness stage, cognitive tests (d2 Test of Attention), and subthreshold mood symptoms were analyzed.
Main Results:
- Serum MMP9 levels were significantly higher in the BD group compared to HC.
- Patients with BD in later, progressive stages exhibited significantly higher MMP9 and sICAM-1 levels than those in earlier stages.
- Higher MMP9 levels correlated negatively with attention performance in BD patients.
- Both MMP9 and sICAM-1 showed significant correlations with subthreshold depressive/hypomanic symptoms in euthymic BD individuals.
Conclusions:
- Increased serum MMP9 and sICAM-1 levels are associated with the patho-progressive nature of BD.
- These biomarkers correlate with disease stage, cognitive dysfunction, and subthreshold mood symptoms in BD.
- MMP9 and sICAM-1 may serve as indicators of occult cardiovascular disease in the high-risk BD population.
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