Levels Of MMP-2 and TNF-α May Be Associated With The Inflammatory Processes Underlying Schizophrenia

1. Inflammatory markers MMP-2 and TNF-α were higher in treatment-resistant (TRS), and chronically medicated schizophrenia (CMS) groups, respectively compared to a healthy control group.
2. MMP-2 and TNF-α showed no correlation to cognitive function in individuals with schizophrenia.

Evidence Rating Level: 2 (Average)

The role of inflammation in the pathogenesis of many psychiatric illnesses is an ongoing area of research. Schizophrenia is classified as a severe mental illness that affects approximately 0.5% of the American population. Understanding the physiological mechanisms underlying schizophrenia can help researchers create targeted therapies for this life-altering illness. The specific inflammatory markers underlying the pathophysiology of schizophrenia remain to be further explored.

This was a cross-sectional study with a case-control design that compared the levels of tumor necrosis factor-α (TNF-α), and matrix metalloproteinase-2 (MMP-2) of male patients with schizophrenia to that of a healthy control group. Thirty-one individuals with treatment-resistant schizophrenia (TRS), 49 individuals with chronically medicated schizophrenia (CMS), and 53 healthy individuals were enrolled in the study. Han Chinese males between the ages of 18-60, with a confirmed diagnosis of schizophrenia by DSM-IV criteria, and who have not been on anti-inflammatory medication or antibiotic therapy for the past 4 weeks were included in the study. Individuals with any major medical issue, an endocrinological disorder, degenerative brain disease, or substance abuse disorder were excluded. TRS criteria required a poor response to 6 months of therapy with two antipsychotics, and a Positive and Negative Syndrome Scale (PANSS) score over 3 on each subscale. CMS was defined as those who experienced effective treatment on one antipsychotic for 6 months with PANSS<3 on each subscale. Serum MMP-2 and TNF-α were measured from blood drawn in the morning. A clinical assessment was performed by two psychiatrists immediately after which consisted of PANSS to assess for symptom severity and Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) to assess cognitive function. The primary outcome measured levels of MMP-2 and TNF-α.

The results showed that compared to the control group levels of MMP-2 were higher in the TRS group and levels of TNF-α were higher in the CMS group. The levels of both of these markers were not significantly different between the TRS and CMS groups. Interestingly, the levels of MMP-2 and TNF-α had no association with cognitive function. A limitation of this study is that people with schizophrenia tend to be on different medications. The researchers made their best efforts to control differences in medication by converting dosages of these medications to a chlorpromazine-equivalent. However, this cannot control for the different mechanisms of action of these drugs and therefore, cannot control for the way these differentially affect levels of MMP-2 and TNF-α. Nevertheless, this is likely the first study of its kind to provide insight into the associations between these specific inflammatory markers and schizophrenia potentially opening new paths for investigation and future treatment.

Click here to read this study in BMC Psychiatry

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