A brain too synchronized or not enough: the consequences

How can we assess the risk of psychosis in an individual? In psychiatry, identifying predictive markers is a major research challenge.


By studying a cohort of patients with the 22q11.2DS gene microdeletion - an anomaly promoting psychotic disorders - a team from the University of Geneva (UNIGE), within the Synapsy Center for Neuroscience Research in Mental Health, shows that these individuals exhibit a unique "coupling" between the structure and activity of their brain areas.

Certain regions of their brains seem to have lost their optimal coherence during development. They are thus either too "coupled" or not coupled enough. This specificity opens the door to identifying reliable risk markers. These results are published in Biological Psychiatry: Cognitive Neuroscience and Neuroimaging.


The 22q11.2DS gene microdeletion is the most common genetic deletion, affecting one in 2,000 people and resulting in the absence of a small DNA sequence on chromosome 22. It can lead to heart malformations and immune dysfunctions. It also causes psychotic disorders in adolescence or adulthood in 35% of carriers.

At UNIGE, the team of Stéphan Eliez, a professor at the Department of Psychiatry and the Synapsy Center for Neuroscience Research in Mental Health at the Faculty of Medicine, has followed for twenty years a cohort of 300 individuals aged 5 to 34 affected by this microdeletion, nearly 40% of whom have developed psychosis. Due to its size and longevity, this Geneva cohort is a unique case study worldwide. It has enabled the publication of numerous works.

An atypical brain development from childhood

In a new study, the UNIGE team focused on the development of "coupling" of brain regions in this cohort, from childhood to adulthood. "Our cognitive processes result from interactions - 'couplings' - between different regions of our brain," explains Silas Forrer, a PhD student in Stephan Eliez's team and the first author of the study. "We wanted to know whether, in individuals with the 22q11.2DS gene microdeletion, less efficient coupling equated to an increased risk of developing psychosis."


This brain "synchronization," particularly its optimization, develops during adolescence and into adulthood. Using magnetic resonance imaging techniques, neuroscientists observed its maturation over a twelve-year period within the cohort and a control group. "We found that patients with the microdeletion exhibited persistent developmental delays from childhood, with regions of hyper- and hypo-coupling throughout the brain," reveals Silas Forrer.


This delay is particularly pronounced in adolescence in three brain regions in 22q11.2DS individuals who developed schizophrenia: in the frontal cortex, responsible for voluntary motor coordination and language; the cingulate cortex, at the interface of the two brain hemispheres, responsible for certain decision-making; and the temporal cortex, the seat of somatosensory functions. There is hypo-coupling in the first two and hyper-coupling in the third.

Towards the identification of reliable markers

The strong correlation between the developmental delay in coupling and the 22q11.2DS gene microdeletion is a significant step towards identifying predictive markers of the disease. "The next step will be to determine how these couplings can constitute an individual brain 'fingerprint,' indicating clearly whether an individual is more at risk of developing psychosis or, on the contrary, is protected from it," explains Stephan Eliez, who led the study.

This study, supported by the Swiss National Science Foundation (SNSF), also presents a methodological novelty by combining observations on both the structure (morphology) and function (efficiency) of the brain to evaluate the developmental trajectory of a population within the context of psychiatric disorders.