The role of MMP genes in recurrent depressive disorders and cognitive functions

Acta Neuropsychiatr. 2016 Aug;28(4):221-31. doi: 10.1017/neu.2015.72. Epub 2016 Feb 9.


Objective: Among the 28 metalloproteinases described so far, 23 can be found in the human organism, but only few are expressed in the human brain. The main objective of this study was to analyse the relationship between MMP-2, MMP-9 and TIMP-2 gene expression and cognitive performance.

Methods: The study comprised 234 subjects: patients suffering from recurrent depressive disorder (rDD, n=139) and healthy subjects (HS, n=95). The cognitive function assessment was carried out with the help of the following tests: Trail Making Test, The Stroop Test, Verbal Fluency Test and Auditory Verbal Learning Test. Gene expression on the mRNA and protein level was evaluated for MMP-2, MMP-9 and TIMP-2 in both groups using RNA extraction, reverse transcription and enzyme-linked immunosorbent assay.

Results: Both mRNA and protein expression levels of all the genes were significantly lower in rDD subjects as compared with HS. Having analysed the entire experimental group (N=234), significant interrelations were found between the expression of the analysed genes and the results of the tests used to measure cognitive functions. Increased expression on both the mRNA and the protein level was associated in each case with better performance of all the tests conducted. After carrying out a separate analysis on the people from the rDD group and the HS group, similar dependencies were still observed.

Conclusions: The results of our study show decreased expression of MMP-2, MMP-9 and TIMP-2 genes on both mRNA and protein levels in depression. Elevated expression of MMP-2, MMP-9, TIMP-2 positively affects cognitive efficiency: working memory, executive functions, attention functions, direct and delayed auditory-verbal memory, the effectiveness of learning processes and verbal fluency. The study highlights the important role of peripheral matrix metalloproteinases genes in depression and cognitive functions.

Keywords: MMPs; cognition; depression.

MeSH terms

  • Adult
  • Aged
  • Cognition / physiology*
  • Depressive Disorder / genetics
  • Depressive Disorder / metabolism*
  • Depressive Disorder / psychology*
  • Female
  • Gene Expression Regulation
  • Humans
  • Male
  • Matrix Metalloproteinase 2 / genetics*
  • Matrix Metalloproteinase 2 / metabolism
  • Matrix Metalloproteinase 9 / genetics*
  • Matrix Metalloproteinase 9 / metabolism
  • Middle Aged
  • Neuropsychological Tests
  • Tissue Inhibitor of Metalloproteinase-2 / genetics*
  • Tissue Inhibitor of Metalloproteinase-2 / metabolism
  • Young Adult


  • TIMP2 protein, human
  • Tissue Inhibitor of Metalloproteinase-2
  • MMP2 protein, human
  • Matrix Metalloproteinase 2
  • MMP9 protein, human
  • Matrix Metalloproteinase 9