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The association of matrix metalloproteinase 9 (MMP9) with hippocampal volume in schizophrenia: a preliminary MRI
Johanna Seitz-Holland1, Magdalena Seethaler1, Nikos Makris1,2
1Department of Psychiatry, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
Abstract:
Matrix metalloproteinases 9 (MMP9) are enzymes involved in regulating neuroplasticity in the hippocampus. This, combined with evidence for disrupted hippocampal structure and function in schizophrenia, has prompted our current investigation into the relationship between MMP9 and hippocampal volumes in schizophrenia. 34 healthy individuals (mean age = 32.50, male = 21, female = 13) and 30 subjects with schizophrenia (mean age = 33.07, male = 19, female = 11) underwent a blood draw and T1-weighted magnetic resonance imaging. The hippocampus was automatically segmented utilizing FreeSurfer. MMP9 plasma levels were measured with ELISA. ANCOVAs were conducted to compare MMP9 plasma levels (corrected for age and sex) and hippocampal volumes between groups (corrected for age, sex, total intracranial volume). Spearman correlations were utilized to investigate the relationship between symptoms, medication, duration of illness, number of episodes, and MMP9 plasma levels in patients. Last, we explored the correlation between MMP9 levels and hippocampal volumes in patients and healthy individuals separately. Patients displayed higher MMP9 plasma levels than healthy individuals (F(1, 60) = 21.19, p < 0.0001). MMP9 levels correlated with negative symptoms in patients (R = 0.39, p = 0.035), but not with medication, duration of illness, or the number of episodes. Further, patients had smaller left (F(1,59) = 9.12, p = 0.0040) and right (F(1,59) = 6.49, p = 0.013) hippocampal volumes. Finally, left (R = -0.39, p = 0.034) and right (R = -0.37, p = 0.046) hippocampal volumes correlated negatively with MMP9 plasma levels in patients. We observe higher MMP9 plasma levels in SCZ, associated with lower hippocampal volumes, suggesting involvement of MMP9 in the pathology of SCZ. Future studies are needed to investigate how MMP9 influences the pathology of SCZ over the lifespan, whether the observed associations are specific for schizophrenia, and if a therapeutic modulation of MMP9 promotes neuroprotective effects in SCZ.
Insights
Matrix metalloproteinases 9 (MMP9) levels are elevated in schizophrenia patients and correlate with reduced hippocampal volumes. This suggests MMP9 plays a role in schizophrenia pathology and may be a target for future therapies.
Area of Science:
- Neuroscience
- Psychiatry
- Biochemistry
Background:
- Matrix metalloproteinases 9 (MMP9) are enzymes crucial for neuroplasticity, particularly in the hippocampus.
- Schizophrenia is characterized by disrupted hippocampal structure and function.
- The role of MMP9 in the pathophysiology of schizophrenia remains to be fully elucidated.
Purpose of the Study:
- To investigate the relationship between MMP9 plasma levels and hippocampal volumes in individuals with schizophrenia.
- To explore correlations between MMP9 levels, clinical symptoms, and disease progression markers in schizophrenia patients.
Main Methods:
- Blood samples and T1-weighted MRI scans were collected from 30 schizophrenia patients and 34 healthy controls.
- Plasma MMP9 levels were quantified using ELISA.
- Hippocampal volumes were automatically segmented using FreeSurfer; statistical analyses included ANCOVAs and Spearman correlations.
Main Results:
- Schizophrenia patients exhibited significantly higher plasma MMP9 levels compared to healthy controls.
- Elevated MMP9 levels in patients correlated with negative symptoms but not with medication, illness duration, or episode number.
- Patients showed reduced left and right hippocampal volumes, which negatively correlated with MMP9 plasma levels.
Conclusions:
- Higher MMP9 plasma levels in schizophrenia are associated with smaller hippocampal volumes, indicating MMP9's involvement in the disorder's pathology.
- Further research is warranted to understand MMP9's influence on schizophrenia pathophysiology across the lifespan and its therapeutic potential.
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