Levels of matrix metalloproteinase 9 (MMP-9) are elevated in persons with major depressive disorder who have had a recent suicide attempt

Brain Behav Immun Health. 2025 Dec 18;51:101163. doi: 10.1016/j.bbih.2025.101163. eCollection 2026 Feb.

ABSTRACT

Matrix metalloproteinases (MMPs) are a diverse set of enzymes associated with tissue remodeling as well as inflammation and tissue destruction. MMP-9 is of interest since it has been associated with psychiatric disorders including major depressive disorder (MDD). Suicide attempts are a major complication of MDD. However, the association between MMP-9 levels and suicide attempts has not been extensively studied in persons with MDD. Sensitive enzyme immunoassays were employed to measure the levels of MMP-9 in blood samples from 186 persons with MDD receiving hospital care, 92 with a suicide attempt within the previous 30 days and 94 without a recent attempt, as well as 79 persons without a psychiatric disorder. Lifetime suicide attempt history in the MDD group was also recorded. Mixed effects models were employed to compare the MMP-9 levels among the groups adjusted for demographic and clinical variables. Wald tests were used to calculate pairwise comparisons. Employing these models, we found that individuals with MDD and a recent suicide attempt had higher levels of MMP-9 than individuals with MDD without a recent suicide attempt as well as individuals without a psychiatric disorder. There was not a significant difference in MMP-9 levels between the non-psychiatric group and individuals with MDD without a recent suicide attempt, regardless of whether they had a lifetime suicide attempt. Therapeutic modalities to modulate MMP-9 activity are currently being developed. The measurement of MMP-9 might be used to inform future clinical trials of these modalities for the prevention of suicide behaviors in high-risk individuals.

PMID:41561479 | PMC:PMC12813312 | DOI:10.1016/j.bbih.2025.101163