Influence of the extracellular matrix metalloproteinases on Depressive Disorder: study of biochemical and genetic biomarkers

• Grant number: 22/12072-5
• Support Opportunities: Regular Research Grants
• Start date: July 01, 2023
• End date: June 30, 2026
• Field of knowledge: Health Sciences - Medicine - Psychiatry
• Principal Investigator: Riccardo Lacchini
• Grantee: Riccardo Lacchini
• Host Institution: Escola de Enfermagem de Ribeirão Preto (EERP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil
• Associated researchers: Cristina Marta Del-Ben ; Mario Francisco Pereira Juruena

Abstract

Depression is a highly prevalent mood disorder and it generates prejudices both to the patient and the society. Most studies focus inflammation, cortisol, neurothrophic factors as the main causes for depression. One common factors between these different mechanisms is a raise in matrix metalloproteinases(MMP), which lead to tissue remodeling, change in the density of synaptic boutons and loss of the integrity of blood-brain barrier (BBB). The establishment of the relationship between MMP and depression disorder could enable the use of biomarkers within this pathway to support the diagnose of this mood disorder. Our hypothesis is that psychometric parameters in depressive subjects may associate with levels of biochemical markers related to MMP activity and to a marker of BBB integrity. We believe that the increase in MMP2, MMP9, and IL-6, as well as the reduction in TIMP1, TIMP2, alpha2 macroglobulin and IL-10 will correlate to an increase in S100beta (marker of BBB integrity), to worse psychometric parameters and increased risk to depression. It will be included around 100 patients from the psychiatric clinic of the Clinics Hospital of Ribeirao Preto and the Psychiatric Day-Hospital, and 100 controls from extension programs at the Campus. All participants will be clinically evaluated and submitted to clinical interview and assessment of health status, including the use of psychiatric instruments such as Hamilton HAMD21, Beck Suicide Ideation scale, childhood trauma questionnaire. It will be assessed in pplasma of patients the levels of MMP-2 and MMP-9 (zymography), other markers by ELISA (multiplex bead-based) and genetic polymorphisms by real-time PCR. (AU)

Scientific publications

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

KAYZUKA, CEZAR; RONDON-PEREIRA, VITORIA CAROLINA; TAVARES, CECILIA NOGUEIRA; PACHADO, MAYRA PACHECO; MONICA, FABIOLA ZAKIA; TANUS-SANTOS, JOSE EDUARDO; LACCHINI, RICCARDO. Epigenetics is involved in the pleiotropic effects of statins. EXPERT OPINION ON DRUG METABOLISM & TOXICOLOGY, v. N/A, p. 13-pg., 2025-04-19. (20/11740-9, 18/18312-2, 22/12072-5, 22/07921-3, 19/10748-9)

PEREIRA, SHERLIANE CARLA; COELI-LACCHINI, FERNANDA BORCHERS; PEREIRA, DANIELA ALVES; FEREZIN, LETICIA PERTICARRARA; MENEZES, ITIANA CASTRO; BAES, CRISTIANE VON WERNE; LUIZON, MARCELO RIZZATTI; JURUENA, MARIO F.; CLEARE, ANTHONY J.; YOUNG, ALLAN H.; et al. Early life stress unravels epistatic genetic associations of cortisol pathway genes with depression. JOURNAL OF PSYCHIATRIC RESEARCH, v. 175, p. 10-pg., 2024-05-16. (22/12072-5)