Publication details

The association of matrix metalloproteinase 9 (MMP9) with hippocampal volume in schizophrenia: a preliminary MRI study

Authors	SEITZ-HOLLAND Johanna SEETHALER Magdalena MAKRIS Nikos RUSHMORE Jarrett CHO Kang-Ik K. RIZZONI Elizabeth VANGEL Mark SAHIN Olcay Senay HELLER Carina PASTERNAK Ofer SZCZEPANKIEWICZ Filip WESTIN Carl-Fredrik LOŠÁK Jan USTOHAL Libor TOMANDL Josef VOJTÍŠEK Lubomír KUDLIČKA Petr JÁNI Martin WOO T. Wilson KAŠPÁREK Tomáš KIKINIS Zora KUBICKI Marek
Year of publication	2022
Type	Article in Periodical
Magazine / Source	Neuropsychopharmacology
MU Faculty or unit	Faculty of Medicine
Citation
web	https://www.nature.com/articles/s41386-021-00997-5
Doi	http://dx.doi.org/10.1038/s41386-021-00997-5
Keywords	matrix metalloproteinase 9 (MMP9); hippocampal volume; schizophrenia
Description	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.