High MMP9 Predicts Poor Antipsychotic Treatment Response in Schizophrenia

Plasma matrix metalloproteinase 9 (MMP9) concentration is elevated among patients with schizophrenia exhibiting poor responses to antipsychotic drug regimens, according to study findings published in Schizophrenia.

Previous research findings suggest that elevated MMP9 enzymes promote oxidative stress, inflammation, and synaptic plasticity and contribute to blood-brain barrier damage, cognitive impairment, and white matter injury. However, it remains unclear whether MMP9 influences schizophrenia symptoms or responses to treatment.

To examine the association between plasma MMP9 and antipsychotic treatment response as well as white matter density defects among patients with schizophrenia, researchers conducted an observational cohort study. The population included 129 healthy control participants and 124 patients with schizophrenia from the Department of Psychiatry at The Second Affiliated Hospital of Xinxiang Medical University.

Control participants were of Han Chinese ethnicity and aged 18 to 55 years with no history of psychiatric illness. Inpatient participants were of similar ethnicity and ages with a DSM-IV diagnosis of schizophrenia and a Positive and Negative Syndrome Scale (PANSS) score of at least 60.

Patients were classified as good responders to antipsychotic treatment regimens if their decline in PANSS score from baseline to 8 weeks was 50% and greater (75 participants, 60.48%) or poor responders if their decline in PANSS score was less than 50% (49 participants, 39.52%).

After 8 weeks of antipsychotic treatment, plasma MMP9 was higher at baseline and declined significantly among poor responders (z =-2.661; P =.008) compared with control participants (z =-2.780; P =.005). No significant differences were found between good responders and control participants (z =-0.281; P =.779).

Baseline plasma MMP9 was higher among poor responders than good responders (z =-2.650; P =.008) and was negatively correlated with the reduction in PANSS score (r =-0.224; P =.012). Higher MMP9 was linked to significantly worse antipsychotic treatment response (odds ratio [OR], 1.010; 95% CI, 1.002-1.018; P =.020).

Baseline plasma levels of receptor for advanced glycation end-products (RAGE), an MMP9 substrate, were positively associated with baseline plasma MMP9 among poor responders (r =0.729; P <.001), whereas change in plasma MMP9 after treatment was negatively correlated with the change in RAGE (r =0.523; P =.012).

Among poor responders, baseline plasma MMP9 showed a negative correlation with white matter density in the right superior temporal gyrus (STG; r =-0.607; P =.001), specifically in the 74 (r =-0.617, P =.001) and 80 (r =-0.614; P =.001) subregions.

Change in white matter density from baseline to 8 weeks of treatment was significantly lower among the poor responders than the good responders (t =2.412; P =0.018).

“High plasma MMP9 may be a useful predictive biomarker for antipsychotic drug response and a contributor to the structural brain abnormalities observed in [schizophrenia],” study authors noted.

Limitations of this study include the observational design, the absence of measurements on relevant inflammatory factors, and the fact that patients were receiving medication prior to baseline measurements.

This article originally appeared on Psychiatry Advisor