TY - JOUR
T1 - Levels of Matrix Metalloproteinase 9 Are Elevated in Persons With Schizophrenia or Bipolar Disorder
T2 - The Role of Modifiable Factors
AU - Dickerson, Faith
AU - Vaidya, Dhananjay
AU - Liu, Yisi
AU - Yolken, Robert
N1 - Publisher Copyright:
© 2023 The Authors
PY - 2023/10
Y1 - 2023/10
N2 - Background: Matrix metalloproteinases (MMPs) are a diverse set of enzymes associated with inflammation. MMP-9 is of particular interest because it has been associated with autoimmune and cardiopulmonary disorders, tobacco smoking, and obesity, prevalent in psychiatric populations. Methods: Sensitive enzyme immunoassays measured MMP-9 in blood samples from 1121 individuals (mean age = 35.6 [SD = 13.0] years; 47.7% male; 440 with schizophrenia, 399 with bipolar disorder, and 282 without a psychiatric disorder). We estimated the odds of diagnosis associated with MMP-9, demographic variables, tobacco smoking, and obesity, and also the partial explained variance using regression methods. We also determined the association between psychiatric medications and MMP-9 levels. Results: Individuals with elevated MMP-9 levels had higher odds of schizophrenia or bipolar disorder compared with the nonpsychiatric group adjusted for demographic variables. Partial correlation analyses indicated the demographic-adjusted variance associated with MMP-9, smoking, obesity, and their interaction explained 59.6% for schizophrenia and 39.9% for bipolar disorder. Levels of MMP-9 were substantially lower in individuals receiving valproate, particularly relatively high doses. Conclusions: Individuals with higher levels of MMP-9 have significantly higher odds of schizophrenia or bipolar disorder. Individuals receiving valproate had substantially lower levels of MMP-9, possibly related to its ability to inhibit histone deacetylation. A substantial portion of the variance in clinical disorders associated with MMP-9 can be attributed to smoking or obesity. Interventions to reduce smoking and obesity might reduce the morbidity and mortality associated with elevated MMP-9 levels and improve the health outcomes of individuals with these disorders.
AB - Background: Matrix metalloproteinases (MMPs) are a diverse set of enzymes associated with inflammation. MMP-9 is of particular interest because it has been associated with autoimmune and cardiopulmonary disorders, tobacco smoking, and obesity, prevalent in psychiatric populations. Methods: Sensitive enzyme immunoassays measured MMP-9 in blood samples from 1121 individuals (mean age = 35.6 [SD = 13.0] years; 47.7% male; 440 with schizophrenia, 399 with bipolar disorder, and 282 without a psychiatric disorder). We estimated the odds of diagnosis associated with MMP-9, demographic variables, tobacco smoking, and obesity, and also the partial explained variance using regression methods. We also determined the association between psychiatric medications and MMP-9 levels. Results: Individuals with elevated MMP-9 levels had higher odds of schizophrenia or bipolar disorder compared with the nonpsychiatric group adjusted for demographic variables. Partial correlation analyses indicated the demographic-adjusted variance associated with MMP-9, smoking, obesity, and their interaction explained 59.6% for schizophrenia and 39.9% for bipolar disorder. Levels of MMP-9 were substantially lower in individuals receiving valproate, particularly relatively high doses. Conclusions: Individuals with higher levels of MMP-9 have significantly higher odds of schizophrenia or bipolar disorder. Individuals receiving valproate had substantially lower levels of MMP-9, possibly related to its ability to inhibit histone deacetylation. A substantial portion of the variance in clinical disorders associated with MMP-9 can be attributed to smoking or obesity. Interventions to reduce smoking and obesity might reduce the morbidity and mortality associated with elevated MMP-9 levels and improve the health outcomes of individuals with these disorders.
KW - Bipolar disorder
KW - Endopeptidase
KW - Immune
KW - Schizophrenia
KW - Tobacco smoking
KW - Valproate
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U2 - 10.1016/j.bpsgos.2023.02.007
DO - 10.1016/j.bpsgos.2023.02.007
M3 - Article
C2 - 37881562
AN - SCOPUS:85153326823
SN - 2667-1743
VL - 3
SP - 766
EP - 772
JO - Biological Psychiatry Global Open Science
JF - Biological Psychiatry Global Open Science
IS - 4
ER -