Unexpected cause of severe depression discovered

Scientists from South Korea have discovered that severe depression with atypical symptoms and psychosis may be rooted in a systemic disorder linking the immune system and neural tissue development. The research results were published in the prestigious scientific journal Advanced Science.

As reported by TUT.AZ with reference to researchers, depressive disorder remains one of the most common and serious mental illnesses of our time. Diagnosis is still conducted exclusively on the basis of clinical observations by doctors due to the lack of objective biological markers. Particular difficulties arise in identifying and treating atypical depression with psychotic manifestations - hallucinations and delusions, which is difficult to treat with standard methods and is associated with a high risk of suicidal behavior.

During the study, scientists concentrated on finding biological signs of this disorder. The experiment involved young women with severe atypical depression, while healthy volunteers formed the control group. Even during standard tests, patients were found to have elevated levels of white blood cells - indicating inflammatory processes. More in-depth proteomic analysis revealed proteins characteristic of nerve tissue in blood plasma, which is an unusual phenomenon.

Among the identified molecules were DCLK3, which is involved in the formation of connections between neurons, and CALY, which affects dopamine transmission. Their presence in the bloodstream may indicate a disruption of the blood-brain barrier or a systemic failure simultaneously affecting neurons and the immune system. In parallel, study participants showed elevated levels of the complement component C5 - a crucial regulator of inflammation. These data support the hypothesis that immune system hyperactivity may play a key role in the development of severe mental disorders.

To understand how such systemic disorders affect the brain, scientists created mini-models of the brain - organoids. For this purpose, patients' blood cells were reprogrammed into stem cells and then directed to develop into neural tissue. In the early stages, it became obvious: organoids develop more slowly, maintain a more compact structure, and when exposed to synthetic stress hormone, they demonstrate an abnormal reaction - genes responsible for cell death are activated, and the process of neuron maturation is disrupted.

Researchers believe that the results obtained open up prospects for the development of objective biomarkers for depression. In the future, the detection of DCLK3, CALY, and component C5 in the blood could become the basis for creating a diagnostic test that will allow more accurate diagnosis and personalized treatment selection taking into account the patient's immunological profile.