by Summary: Individuals with the 22q11.2DS genetic deletion have unique patterns of brain activity and structure that may predict their risk of psychosis. By studying brain “coupling” from childhood to adulthood, scientists have discovered divergences in brain regions linked to schizophrenia.
These findings pave the way for the identification of reliable markers of psychosis risk, facilitating early diagnosis and intervention. The research highlights the importance of understanding brain structure and function in psychiatric disorders.
Highlights:
- The 22q11.2DS microdeletion is linked to an elevated risk of developing schizophrenia.
- Differences in brain “coupling” in individuals with 22q11.2DS may indicate risk for psychosis.
- Study combines analysis of brain structure and function for predictive markers.
Source: University of Geneva
The 22q11.2DS gene microdeletion is the most common genetic deletion. It affects one in 2,000 people and results in the absence of a small sequence of DNA on chromosome 22. It can lead to 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, full professor in the Department of Psychiatry and at the Synapsy Neuroscience and Mental Health Research Center of 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 developed schizophrenia. Due to its size and longevity, this Geneva cohort constitutes a unique case study in the world and has given rise to the publication of numerous articles.
Atypical brain development in childhood
In a new study, the UNIGE team looked at the development of “coupling” between the 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 doctoral student in Stephan Eliez’s team and first author of the study.
“We wanted to know whether, in individuals with the 22q11.2DS abnormality, less efficient coupling was synonymous with an increased risk of developing psychosis.”
This brain “synchronization”, and especially its optimization, develops during adolescence and adulthood. Using magnetic resonance imaging techniques, neuroscientists observed its maturation over a period of twelve years in the cohort and a control group.
“We found that patients with microdeletion had a persistent developmental lag since childhood, with regions of hyper- and hypo-coupling throughout the brain,” says Silas Forrer.
This discordance is particularly marked in adolescence in three brain regions in “22q11.2DS” individuals 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. Hypo-coupling is observed in the first two and hyper-coupling in the third.
Towards the identification of a reliable marker
This strong correlation between developmental difference and 22q11.2DS gene microdeletion constitutes an important step towards the identification of predictive markers of the disease.
“The next step will be to determine how these couplings can constitute an individual “fingerprint” of the brain, making it possible to clearly know whether an individual is more at 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), also constitutes a methodological innovation by combining observations on the structure (morphology) and function (efficiency) of the brain to assess the developmental trajectory of a population in the context of psychiatric illnesses.
About this news on psychosis research
Author: Antoine Guenot
Source: University of Geneva
Contact: Antoine Guenot – University of Geneva
Picture: Image credited to Neuroscience News
Original research: Free access.
“Longitudinal analysis of dependencies between brain function and structure in 22q11.2 deletion syndrome and psychotic symptoms” by Silas Forrer et al. Biological psychiatry Cognitive neuroscience and neuroimaging
Abstract
Longitudinal analysis of dependencies between brain function and structure in 22q11.2 deletion syndrome and psychotic symptoms
Background
Compared with conventional unimodal analysis, understanding the relationship between brain function and structure opens a new biologically relevant assessment of neural mechanisms. However, how structure-function dependencies (SFDs) evolve during typical and abnormal neurodevelopment remains elusive. The 22q11.2 deletion syndrome (22q11.2DS) offers an important opportunity to study the development of SFDs and their specific association with the pathophysiology of psychosis.
Methods
Previously, we used graphical signal processing to combine brain activity and structural connectivity measures in adults, thereby quantifying FSD. Here, we combined FSD with partial least squares multivariate longitudinal correlation to assess FSD alterations across groups and among patients with and without mild to moderate positive psychotic symptoms. We evaluated 391 longitudinally repeated resting-state functional and diffusion-weighted magnetic resonance images from 194 healthy control participants and 197 deletion carriers (aged 7–34 years, data collected over a 12-year period).
Results
Compared to control participants, patients with 22q11.2 Down syndrome showed a persistent developmental mismatch since childhood, with both hyper- and hypo-coupling regions in the brain. In addition, a second deviant developmental pattern showed exacerbation during adolescence, showing hypo-coupling in the frontal and cingulate cortices and hyper-coupling in temporal regions in patients with 22q11.2 Down syndrome. Interestingly, the worsening observed during adolescence was strongly influenced by the group with positive psychotic symptoms.
Conclusions
These results confirm the central role of impaired FSD maturation in the emergence of psychotic symptoms in the 22q11.2DS gene in adolescence. FSD deviations precede the onset of psychotic episodes and thus offer a potential early indication for behavioral interventions in at-risk individuals.
