Poorly ‘Cleaned’ Brains and Psychosis Risk: New Insights into 22q11.2 Deletion Syndrome
Atypical brain waste clearance may be a key factor in the development of psychosis, particularly in individuals with 22q11.2 deletion syndrome (22q11.2DS), according to research published in Biological Psychiatry: Global Open Science in March 2026. The study suggests that dysfunction in the glymphatic system – the brain’s waste removal network – could increase vulnerability to psychotic symptoms.
Understanding the Link Between Brain Clearance and Psychosis
Psychotic disorders, such as schizophrenia, are neurodevelopmental conditions often emerging in adolescence or early adulthood, affecting approximately 0.5–3% of the population 1. These disorders are characterized by hallucinations, delusions, social withdrawal, and cognitive decline. The hippocampus, a brain region crucial for memory and cognition, plays a significant role in the emergence of these symptoms.
The Role of 22q11.2 Deletion Syndrome
Researchers at the University of Geneva focused on 22q11.2DS, a genetic condition linked to a significantly elevated risk of psychosis – estimated between 30–40% 2. This syndrome involves a microdeletion on chromosome 22, impacting genes involved in the glymphatic system’s integrity. The glymphatic system is responsible for clearing metabolic waste, inflammatory molecules, and excess neurotransmitters from the brain via cerebrospinal fluid circulation.
Glymphatic Dysfunction and Neurodevelopmental Trajectories
The research team analyzed a cohort of individuals with 22q11.2DS, tracking them from childhood to adulthood, and compared them to a healthy control group. Re-analysis of longitudinal imaging data, collected over more than 25 years, revealed significant alterations in the brain’s clearance system in individuals with the 22q11.2 deletion, even in childhood. Notably, the typical developmental increase in glymphatic system efficiency was absent in those who later developed psychotic symptoms.
“This atypical trajectory suggests that a vulnerability resulting from an interaction between biological and environmental factors is present well before the onset of symptoms,” explains Alessandro Pascucci, Ph.D. Student at the University of Geneva 1.
Neurotransmitter Imbalance and the Hippocampus
The study also investigated the balance between excitatory (glutamate) and inhibitory (GABA) neurotransmitters in the hippocampus. Researchers found that lower glymphatic system efficiency correlated with a more pronounced imbalance, with excessive excitation potentially leading to neuronal toxicity and contributing to psychosis-related brain alterations. “Our results suggest a link between glymphatic system dysfunction, mechanisms of neurotoxicity, and psychosis,” stated a researcher involved in the study 1.
Implications for Early Intervention
These findings suggest that impaired glymphatic function may increase the brain’s vulnerability to psychosis, potentially through inflammation or excessive neuronal excitation. Future research will focus on analyzing the connections between peripheral inflammation (detectable in blood), sleep quality (known to influence glymphatic function), and the onset of psychosis.
“Identifying such modifiable predictive factors could pave the way for strategies to delay or even prevent a first psychotic episode,” concludes Stephan Eliez, full professor at the University of Geneva 1. Early intervention approaches for individuals with 22q11.2DS and a predisposition to psychosis are also warranted 3.
Individuals with 22q11.2 deletion have a high risk of developing psychosis and should be integrated into early intervention psychiatric programs 3.
1 Medical Xpress. “A poorly ‘cleaned’ brain may increase the risk of psychosis.” March 16, 2026. https://medicalxpress.com/news/2026-03-poorly-brain-psychosis.html
2 Gur, Raquel E, et al. “Pathways to understanding psychosis through rare – 22q11.2DS – and common variants.” Current Opinion in Genetics & Development, vol. 68, Feb. 2021, pp. 35–40. https://pmc.ncbi.nlm.nih.gov/articles/PMC8728946/
3 Clinical management of psychosis in 22q11.2 deletion syndrome. https://pmc.ncbi.nlm.nih.gov/articles/PMC9648635/