Impaired brain cleaning increases the risk of developing psychosis

The focus of scientists was the 22q11.2 deletion syndrome, a genetic condition in which the risk of developing psychosis is 30-40%. This microdeletion (the loss of a small fragment of a chromosome that includes several genes) affects the genes responsible for the integrity of the glymphatic system.

This system ensures the circulation of cerebrospinal fluid and its exchange with interstitial fluid, removing excess neurotransmitters and pro-inflammatory molecules. When the drainage system malfunctions, toxic waste products accumulate in the tissues, leading to inflammation and neuronal damage.

To test this hypothesis, the team analyzed data from a group of volunteers with 22q11.2 deletion syndrome, who were followed from childhood to adulthood over a period of 25 years. Using advanced diffusion magnetic resonance imaging techniques that capture the movement of water molecules, the researchers were able to indirectly assess the functionality of the glymphatic system. It turned out that people with this genetic feature have problems with the brain’s cleaning system already in childhood.

The researchers paid special attention to a subgroup of participants who developed psychotic symptoms during the observation period. Unlike healthy individuals, whose glialphatic system efficiency increases with age, there was no progress in this group. This abnormal developmental trajectory suggests that biological vulnerability develops long before the first clinical signs of the disease appear.

In parallel, scientists studied the balance of excitatory and inhibitory signals in the hippocampus, a region of the brain that is critical for memory and cognitive functions. They found that the lower the efficiency of brain cleaning, the more pronounced the imbalance between glutamate (which stimulates neural activity) and GABA (which inhibits it) becomes. Excessive excitation becomes toxic to nerve cells, leading to structural changes in the hippocampus and the development of psychosis.

The results of the study suggest that the glymphatic system could be a potential target for early intervention. Identifying factors that affect brain drainage, such as sleep quality and systemic inflammation, could help develop strategies for preventing the first psychotic episode. In the future, researchers plan to compare imaging data with blood tests to identify accessible markers of susceptibility to mental disorders.