Elevated plasma matrix metalloproteinase 9 in schizophrenia patients associated with poor antipsychotic treatment
Xiaojing Li1,2,3,4, Xiujuan Wang1, Yongfeng Yang1,2,3
1Department of Psychiatry, Henan Mental Hospital, The Second Affiliated Hospital of Xinxiang Medical University, Xinxiang, 453002, China.
Abstract:
Oxidative stress and neuroinflammation contribute to schizophrenia (SCZ) pathology and may influence treatment efficacy. Matrix metalloproteinase 9 (MMP9) is a critical molecular node mediating the interaction between oxidative stress and inflammation, and so may influence treatment efficacy. Here we examined the associations of plasma MMP9 concentration with antipsychotic drug responses, clinical symptoms, and brain structure. A total of 129 healthy controls and 124 patients with SCZ were included in this study. Patients were monitored clinically during 8 weeks of antipsychotic treatment and classified as poor responders (n = 49) or good responders (n = 75). We then compared plasma MMP9 concentrations in healthy controls at baseline and both SCZ responder groups at baseline and after the 8-week antipsychotic treatment regimen. Cognitive function was also examined using the MATRICS Consensus Cognitive Battery. In addition, we extracted regional white matter density from magnetic resonance images of patients. Compared to healthy controls, plasma MMP9 levels were significantly elevated in poor responders at baseline and negatively correlated with both white matter density in the right superior temporal gyrus and the change in cognitive symptoms after treatment. Conversely, there was no significant difference in plasma MMP9 between good responders and healthy controls, and no associations of plasma MMP9 with cognitive symptoms or regional white matter density among good responders. Elevated plasma MMP9 is associated with poor antipsychotic drug efficacy and white matter deficits in SCZ patients, and so may be a useful biomarker to guide personalized treatment.
Insights
Elevated matrix metalloproteinase 9 (MMP9) in schizophrenia patients is linked to poorer antipsychotic treatment response and white matter deficits. MMP9 may serve as a biomarker for personalized schizophrenia treatment strategies.
Area of Science:
- Neuroscience
- Psychiatry
- Biochemistry
Background:
- Schizophrenia (SCZ) pathology involves oxidative stress and neuroinflammation, impacting treatment efficacy.
- Matrix metalloproteinase 9 (MMP9) is a key mediator linking oxidative stress and inflammation, potentially influencing treatment outcomes.
- Understanding MMP9's role could lead to personalized treatment approaches for SCZ.
Purpose of the Study:
- To investigate the association between plasma MMP9 concentrations and antipsychotic drug response in SCZ patients.
- To explore the relationship between MMP9 levels, clinical symptoms, cognitive function, and brain structure (white matter density) in SCZ.
- To determine if MMP9 can serve as a biomarker for predicting treatment efficacy in SCZ.
Main Methods:
- Compared plasma MMP9 levels in 124 SCZ patients (49 poor responders, 75 good responders) and 129 healthy controls.
- Monitored patients clinically over 8 weeks of antipsychotic treatment.
- Assessed cognitive function using the MATRICS Consensus Cognitive Battery and analyzed regional white matter density from MRI scans.
Main Results:
- Poor responders exhibited significantly elevated baseline plasma MMP9 compared to healthy controls.
- Higher MMP9 levels in poor responders correlated negatively with white matter density in the right superior temporal gyrus and reduced cognitive improvement.
- Good responders showed no significant difference in MMP9 levels compared to controls, with no associations found with cognitive symptoms or white matter density.
Conclusions:
- Elevated plasma MMP9 is associated with reduced antipsychotic efficacy and white matter abnormalities in SCZ.
- MMP9 may be a valuable biomarker for predicting treatment response and guiding personalized medicine in schizophrenia.
- Targeting MMP9 pathways could represent a novel therapeutic strategy for SCZ.
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