Uncovered Non-Obvious Cause of Severe Depression

South Korean scientists have found that severe depression with atypical symptoms and psychotic episodes may be linked to a systemic disorder that combines immune system function and nervous tissue development. The study was published in the journal Advanced Science.

As reported by BAKU.WS with reference to the authors of the work, depressive disorder remains one of the most common and severe mental conditions. The diagnosis is still made exclusively based on doctor observations, as no objective biomarkers exist. It is particularly difficult to identify and treat atypical depression with psychotic manifestations - hallucinations and delusions - which responds poorly to standard therapy and is associated with a high risk of self-destructive behavior.

In the study, specialists focused on finding biological traces of the disorder. The experiment involved young women with severe atypical depression, while the control group consisted of healthy volunteers. Even at the stage of routine analyses, patients showed elevated levels of leukocytes - an indicator of inflammation. More detailed proteomic analysis revealed proteins characteristic of nervous tissue in blood plasma, which is unusual in itself.

Among the molecules detected were DCLK3, which is involved in the formation of neural connections, and CALY, which affects dopamine transmission. Their appearance in the bloodstream may indicate a disruption of barriers between the brain and blood or a systemic failure simultaneously affecting neurons and the immune system. At the same time, participants showed increased levels of complement component C5 - a key regulator of inflammation. These data are consistent with the hypothesis that hyperactive immunity may play a central role in the development of severe mental disorders.

To find out how such systemic failures affect the brain, researchers created mini-brain analogues - organoids. For this, patients' blood cells were reprogrammed into stem cells and their development was directed toward nervous tissue. Already in the early stages it became clear: the organoids grow more slowly, remain more compact, and respond worse to synthetic stress hormone exposure - genes for cell death are activated and neuron maturation is disrupted.

According to scientists, the results obtained give hope for the formation of objective biomarkers of depression. In the future, the presence of DCLK3, CALY, and component C5 in the blood could form the basis of a diagnostic test that would allow for more accurate diagnosis and treatment selection, taking into account the immunological characteristics of the patient.