Plasma proteomic signature of major depressive episode in the elderly

Author(s)

Silva-Costa, Licia C. ; Smith, Bradley J. ; Carregari, Victor Corasolla ; Souza, Gustavo H. M. F. ; Vieira, Erica M. ; Mendes-Silva, Ana Paula ; Almeida, Valeria de ; Carvalho, Benilton S. ; Diniz, Breno S. ; Martins-de-Souza, Daniel

• Document type: Journal article
• Source: JOURNAL OF PROTEOMICS; v. 269, p. 9-pg., 2022-10-30.

Abstract

Depression is a complex and multifactorial disease, affecting about 6.5% of the elderly population in what is referred to as late-life depression (LLD). Despite its public health relevance, there is still limited information about the molecular mechanisms of LLD. We analyzed the blood plasma of 50 older adults, 19 with LLD and 31 controls, through untargeted mass spectrometry, and used systems biology tools to identify biochemical path-ways and biological processes dysregulated in the disease. We found 96 differentially expressed proteins between LLD patients and control individuals. Using elastic-net regression, we generated a panel of 75 proteins that comprises a potential model for determining the molecular signature of LLD. We also showed that biological pathways related to vesicle-mediated transport and voltage-dependent calcium channels may be dysregulated in LLD. These data can help to build an understanding of the molecular basis of LLD, offering an integrated view of the biomolecular alterations that occur in this disorder.Significance: Major depressive disorder in the elderly, called late-life depression (LLD), is a common and disabling disorder, with recent prevalence estimates of 6.5% in the general population. Despite the public health relevance, there is still limited information about the molecular mechanisms of LLD. The findings in this paper shed light on LLD heterogeneous biological mechanisms. We uncovered a potential novel biomolecular signature for LLD and biological pathways related to this condition which can be targets for the development of novel interventions for prevention, early diagnosis, and treatment of LLD. (AU)

• FAPESP's process: 14/10068-4 - Multi-User Equipment approved in grant 13/08711-3: mass spectrometer waters SYNAPT G2-Si HDMS + nanoACQUITY UPLC
• Grantee: Daniel Martins-de-Souza
• Support Opportunities: Multi-user Equipment Program
• FAPESP's process: 19/05155-9 - The role of the glycoproteome and phosphoproteome during neuronal differentiation in schizophrenia
• Grantee: Victor Corasolla Carregari
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• FAPESP's process: 17/18242-1 - Biochemical pathways affected by cannabinoid drugs of human oligodendrocytes
• Grantee: Valéria de Almeida
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• FAPESP's process: 20/09165-6 - Optimization of a quantitative proteomics platform for blood plasma samples analyses
• Grantee: Licia Carla da Silva Costa
• Support Opportunities: Scholarships in Brazil - Technical Training Program - Technical Training
• FAPESP's process: 16/07948-8 - Relationship between a myelin-associated phosphodiesterase CNP and schizophrenia
• Grantee: Bradley Joseph Smith
• Support Opportunities: Scholarships in Brazil - Master
• FAPESP's process: 19/05747-3 - Maintaining and maturing oligodendrocyte cell line
• Grantee: Bradley Joseph Smith
• Support Opportunities: Scholarships in Brazil - Technical Training Program - Technical Training
• FAPESP's process: 17/25588-1 - From the basic understanding to clinical biomarkers to schizophrenia: a neuroproteomics-centered multidisciplinary study
• Grantee: Daniel Martins-de-Souza
• Support Opportunities: Research Projects - Thematic Grants
• FAPESP's process: 19/00098-7 - Multi-User Equipment approved in grant 2017/25588-1: cromatógrafo Acquity UPLC I-Class
• Grantee: Daniel Martins-de-Souza
• Support Opportunities: Multi-user Equipment Program
• FAPESP's process: 18/03422-7 - Identification of blood-based biomarkers for late-life depression through proteomics
• Grantee: Licia Carla da Silva Costa
• Support Opportunities: Scholarships in Brazil - Master