Neurons and white blood cells differ greatly in shape, function, and location in the body. However, researchers at the University of São Paulo (USP) in Brazil found that certain genes were similarly dysregulated in both cell types in patients with depression.
The findings not only confirm the systemic nature of depression, which has implications beyond mental health, but also pave the way for future blood tests that can identify the type and severity of depression. The study was published in the journal scientific report.
This research was supported by FAPESP through four projects (18/18886-9, 24/21635-9, 23/07806-2, and 23/06086-6).
We mapped this gene network that drives interactions between the immune and nervous systems. Depression is a systemic phenomenon and spreads throughout the body. And the immune system is one of the systems that disperses this condition and spreads the infection beyond the central nervous system. Therefore, it is not uncommon for people with depression to exhibit other symptoms such as skin irritation and loss of appetite. ”
Otavio Cabral Marquez, USP Medical School (FM-USP) Professor, Research Coordinator
To arrive at this genetic mapping, scientists analyzed data from more than 3,000 blood samples from public banks in the United States, Germany, and France. Based on their data, they identified changes in gene expression in white blood cells (defense cells) of patients with major depressive disorder.
Of the 1,383 altered genes, 73 are traditionally associated with synapses, connections between neurons, such as the transmission of neurotransmitters and the formation of neural connections. In white blood cells, these genes are involved in immune and inflammatory pathways throughout the body. Eighteen of these genes allow us to consistently distinguish between depressed and non-disordered individuals.
Each person has a unique genome, which contains the entire sequence of genetic material. Gene activation is what distinguishes neurons from white blood cells, or skin cells from heart cells. That is, which genes are turned “on” or “off” depending on the cell’s function, state, or environment.
“Although this is a data science study that still needs to be confirmed biologically, it opens interesting possibilities for the future development of panels that identify genes present in immune system cells circulating in the blood that are involved in depression. Because blood is more readily available than brain tissue, the genes identified could serve as biological markers of the presence and severity of depression,” says Annie Silva Adri, who conducted the study as part of her doctoral research.
systemic disease
The research group has been studying the relationship between the immune system and the nervous system. In a recent study, they demonstrated the role of a single gene (PAX-6), present in both neurons and leukocytes as a predictor of depression in animal models.
“What we found in these studies is that there is a very strong connection between the immune system and the nervous system, which is created by the network of genes that we are studying. They are all closely related, and the distinction between these systems is only for educational purposes,” Cabral-Marquez says.
Researchers say the link between peripheral inflammation (in the blood) and central symptoms (in the brain) opens the door to treatments that target inflammation to reduce depressive symptoms.
Genetic mapping has revealed strong links between depression and other diseases. “Our analysis suggests that these same genes are involved in the vascular and inflammatory comorbidities common to depression. Depression is not limited to the brain, but affects the body in an integrative and molecular manner,” Adri said.
These genes are also associated with bipolar disorder, psychosis, anxiety, high blood pressure, arterial disease, inflammatory diseases, and psoriasis. The mapping also identified associations with gastrointestinal symptoms, erectile dysfunction, and complications associated with the coronavirus.
“Inflammation and molecular dysregulation affect not only the brain but also various organs and systems, amplifying the effects of disease and suggesting new approaches for diagnosis and treatment,” the researchers said.
sauce:
São Paulo Research Foundation (FAPESP)
Reference magazines:
DOI: 10.1038/s41598-026-39284-y
