A study conducted in partnership with IDOR sought to elucidate biomarkers of the onset of late-life depression. 

According to the World Health Organization (WHO), depressive disorders have a higher prevalence in adults between 55 and 74 years old. Severe depression in the elderly, also called late-life depression (LLD), has a prevalence of 9 to 45%. A study, which had the participation of the D’Or Institute for Research and Education (IDOR), the University of Campinas, and other national and international institutions, has just been published in the Journal of Proteomics, with the aim of better understanding the markers of biological factors that may be participating in the emergence of depression in the elderly population. 

Despite being a very relevant health problem, there is still little information about the molecular mechanisms involved in the development of depression. Doctor Daniel Martins-de-Souza, study coordinator and researcher at IDOR and the University of Campinas, comments that the disease results from a sum of factors. “Depression is known to be a disease resulting from a combination of endogenous and exogenous factors. The genetic and biochemical component added to environmental components trigger the disease. In some people, the endogenous component is more prevalent than the exogenous and vice versa. This environmental or exogenous component comes from life experiences, including biological events such as viral illnesses. A series of endogenous events can accelerate or trigger the development of depression.”, he informs. 

Blood plasma samples from 50 patients were used for the study, 19 patients with LLD and 31 patients in the control group. For the analysis of the samples, a mass spectrometry technique was used, capable of detecting proteins, studying their structure, analyzing their modifications, and observing their biological context. “The advantage of studying proteomics is that we can point out the real participants in a biological function or dysfunction, detect which proteins are being produced and, therefore, which genes are activated or less activated in a given condition”, clarifies the researcher. 

The study observed a reduction in levels of CACNA1C, a gene related to calcium absorption in cells, whose deregulation directly affects brain health, as it compromises neurotransmission, synaptic plasticity, and neuronal development. The study argues that the occurrence of polymorphisms (gene sequence variation) in CACNA1C expression may play an important role in severe depression. “We observed that most of the proteins that we found altered in the patient’s blood are involved in inflammation systems. Another thing we observed was that proteins that play a key role in brain development are also present in different amounts in the patient’s blood,” he adds. 

It was also observed that pathways related to vesicle transport were deregulated. This performance is essential for communication between cells and contributes to the maintenance of the local microenvironment. Alterations in the communication of different groups of cells that make up the nervous system can contribute to different types of neuropsychological disorders. The results of the article point out that this fact and the modifications of adhesion molecules (molecules that allow the connection between cells) can be a mechanism that leads to stress and depression. 

Innate immune response and inflammation control are also associated with LLD patients, especially in older women. Increased pro-inflammatory cytokines and acute-phase inflammatory proteins have been linked to severe depression, cognitive impairment, and high mortality. Furthermore, dysfunctions in the complement system (extremely important for the regulation of the innate immune response) have already been associated with neuropsychological changes, including LLD. The vascular hypothesis may be supported by changes in the hemostasis process (a process responsible for dissolving clots, maintaining blood fluidity, and controlling bleeding through biochemical events). The researchers found 6 proteins that were deregulated, including protein S (vitamin K-dependent plasma glycoprotein) which acts in the protein C pathway, responsible for regulating blood clotting. Thus, this alteration could generate dysfunctions in the tissues that line the veins and blood vessels. 

The authors report that further studies are needed, as the sample was small and mostly female, making it impossible to assess the differentially active profiles between the biological sexes. “We have a set of proteins significantly altered in the blood of patients with late-life depression, whose potential is for the development of a diagnostic test or even prediction of this illness, considering that it appears at a late point in life. So, it is clear that there is still a long way to go. “We need to validate whether these changes in blood proteins remain in more patients with the same illness, and if so, the idea would be to have a test that could help psychiatrists predict or better diagnose this condition.”, Dr. Daniel concludes.