Identifying predictive markers is a key challenge in psychiatry. Is it possible to assess the risk of psychosis in an individual? A team from the University of Geneva (UNIGE), part of the Synapsy Centre for Neuroscience and Mental Health Research, studied a cohort of patients with a 22q11.2DS microdeletion, a genetic abnormality linked to psychotic disorders. The scientists discovered that this population has a unique “coupling” between the structure and activity of their brain regions, with some areas losing optimal coherence during development, leading to over- or under-coupling. This specificity paves the way for identifying reliable risk markers for this mental illness.
Microdeletion of the 22q11.2DS gene is the most common genetic deletion. It affects one in 2,000 people and results in the absence of a small DNA sequence on chromosome 22. It can cause heart defects and immune dysfunction, but also psychotic disorders in adolescence or adulthood in 35% of carriers.
At UNIGE, the team led by Stéphan Eliez, a professor at the Department of Psychiatry and at the Synapsy Centre for Neuroscience and Mental Health Research at the Faculty of Medicine, has been following a cohort of 300 individuals aged 5 to 34 affected by this microdeletion for twenty years. Nearly 40% of them have developed schizophrenia. Due to its size and longevity, this Geneva cohort is a unique case study in the world and has led to the publication of numerous articles.
Atypical brain development from childhood
In a new study whose findings have been published in Biological Psychiatry: Cognitive Neuroscience and Neuroimaging, the UNIGE team analysed the development of “coupling” between brain regions of individuals in this cohort, from childhood to adulthood. “Our cognitive processes are the result of interactions – or ‘couplings’ – between our different brain regions,” explains Silas Forrer, a PhD student in Stephan Eliez’s team and first author of the study. “We wanted to find out whether, in individuals with the 22q11.2DS anomaly, less efficient coupling was synonymous with a higher risk of developing psychosis.”
This brain synchronization, and especially its optimization, develops during adolescence and into adulthood. Using magnetic resonance imaging techniques, the neuroscientists observed their maturation over a twelve-year period within the cohort and a control group. “We found that patients with the microdeletion had a persistent developmental discrepancy from infancy, with regions of hyper- and hypo-coupling throughout the brain,” says Silas Forrer.
This discrepancy is particularly marked in adolescence in three brain regions of individuals with “22q11.2DS” who have developed schizophrenia: the frontal cortex, responsible for voluntary motor coordination and language; the cingulate cortex, at the interface between the two hemispheres of the brain, responsible for making certain decisions; and the temporal cortex, responsible for somatosensory functions. There is hypocoupling in the first two and hypercoupling in the third.
Towards the identification of a reliable marker of schizophrenia
This strong correlation between developmental discrepancy and the microdeletion of the 22q11.2DS gene 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 ‘fingerprint’ of the brain, which will make it possible to clearly know whether an individual is at greater risk than another of developing psychosis, or, on the contrary, is protected from it,” explains Stephan Eliez, who led this study.
This research, funded by the Swiss National Science Foundation (SNSF), is also a methodological innovation by combining observations on both the structure (morphology) and the function (efficiency) of the brain to assess the developmental trajectory of a population in the context of psychiatric illness.
Source: University of Geneva
