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

Seitz-Holland, Johanna ; Seethaler, Magdalena ; Makris, Nikos ; Rushmore, Jarrett ; Cho, Kang-Ik K ; Rizzoni, Elizabeth ; Vangel, Mark ; Sahin, Olcay Senay ; Heller, Carina and Pasternak, Ofer , et al. (2022) In Neuropsychopharmacology 47(2). p.524-530
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... (More)

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.

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type
Contribution to journal
publication status
published
subject
keywords
Adult, Female, Hippocampus/diagnostic imaging, Humans, Magnetic Resonance Imaging, Male, Matrix Metalloproteinase 9/therapeutic use, Schizophrenia/drug therapy
in
Neuropsychopharmacology
volume
47
issue
2
pages
524 - 530
publisher
Elsevier
external identifiers
  • pmid:33833403
  • scopus:85104053738
ISSN
1740-634X
DOI
10.1038/s41386-021-00997-5
language
English
LU publication?
no
additional info
© 2021. The Author(s), under exclusive licence to American College of Neuropsychopharmacology.
id
b3212480-ae66-43ed-8c8a-88fe968eb3f4
date added to LUP
2022-04-04 12:30:55
date last changed
2024-06-17 18:01:08
@article{b3212480-ae66-43ed-8c8a-88fe968eb3f4,
  abstract     = {{<p>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 &lt; 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.</p>}},
  author       = {{Seitz-Holland, Johanna and Seethaler, Magdalena and Makris, Nikos and Rushmore, Jarrett and Cho, Kang-Ik K and Rizzoni, Elizabeth and Vangel, Mark and Sahin, Olcay Senay and Heller, Carina and Pasternak, Ofer and Szczepankiewicz, Filip and Westin, Carl-Fredrik and Lošák, Jan and Ustohal, Libor and Tomandl, Josef and Vojtíšek, Lubomír and Kudlička, Petr and Jáni, Martin and Woo, T Wilson and Kašpárek, Tomáš and Kikinis, Zora and Kubicki, Marek}},
  issn         = {{1740-634X}},
  keywords     = {{Adult; Female; Hippocampus/diagnostic imaging; Humans; Magnetic Resonance Imaging; Male; Matrix Metalloproteinase 9/therapeutic use; Schizophrenia/drug therapy}},
  language     = {{eng}},
  number       = {{2}},
  pages        = {{524--530}},
  publisher    = {{Elsevier}},
  series       = {{Neuropsychopharmacology}},
  title        = {{The association of matrix metalloproteinase 9 (MMP9) with hippocampal volume in schizophrenia : a preliminary MRI study}},
  url          = {{http://dx.doi.org/10.1038/s41386-021-00997-5}},
  doi          = {{10.1038/s41386-021-00997-5}},
  volume       = {{47}},
  year         = {{2022}},
}