summary: People with the 22q11.2DS gene deletion show unique patterns of brain activity and structure that may predict risk of psychosis. By studying brain “connections” from childhood to adulthood, scientists have found discrepancies in brain regions associated with schizophrenia.
These findings pave the way for identifying reliable markers of psychosis risk and aiding in early diagnosis and intervention. This study highlights the importance of understanding brain structure and function in psychiatric disorders.
Key Facts:
- The 22q11.2DS microdeletion is associated with a higher risk of developing schizophrenia.
- Differences in brain “coupling” in people with 22q11.2DS may indicate risk for psychosis.
- The study combines analysis of brain structure and function to obtain predictive markers.
sauce: University of Geneva
The 22q11.2DS gene microdeletion is the most common genetic deletion. It affects 1 in 2000 people and results in the absence of a small sequence of DNA on chromosome 22. It can cause heart defects and impaired immune function, while 35% of carriers will develop a psychiatric disorder in adolescence or adulthood.
At UNIGE, a team led by Professor Stéphane Eliez, professor in the Department of Psychiatry and from the Faculty of Medicine’s Centre for Synaptic Neuroscience and Mental Health Research, has been following a cohort of 300 people affected by the microdeletion, aged between 5 and 34, for 20 years.
About 40% of them develop schizophrenia. The Geneva cohort is a unique case study in the world due to its size and longevity, and has been the subject of numerous published papers.
Atypical brain development begins in early childhood
In the new study, the UNIGE team investigated the development of “connections” between brain regions in individuals from this cohort from childhood through to adulthood.
“Our cognitive processes are the result of interactions, or ‘couplings’, between different areas of the brain,” explains Silas Forrer, a doctoral student in Stephane Eliez’s team and first author of the study.
“We wanted to investigate whether reduced binding efficiency is synonymous with an increased risk of developing psychosis in people with 22q11.2DS abnormalities.”
This brain “synchronization,” and especially its optimization, develops throughout adolescence and adulthood, and neuroscientists used magnetic resonance imaging techniques to observe its maturation over a 12-year period within a cohort and a control group.
“We found that patients with microdeletions have hyperconnected and hypoconnected regions throughout the brain, and have persistent developmental mismatches from early childhood,” says Silas Forrer.
This discrepancy is particularly evident in three brain regions in adolescents with 22q11.2DS who develop schizophrenia: the frontal cortex, which is responsible for voluntary motor coordination and language, the cingulate cortex, which sits on the border between the brain’s two hemispheres and is responsible for making certain decisions, and the temporal cortex, which is responsible for somatosensory functions. The first two show low connectivity, while the third shows high connectivity.
Towards identifying reliable markers
This strong correlation between developmental discordance and microdeletions in the 22q11.2DS gene is an important step towards identifying predictive markers for this disease.
“The next step is to understand how these connections form an individual’s brain ‘fingerprint’, which will allow us to clearly understand whether some individuals are at higher risk than others for developing psychosis or, conversely, whether they are protected from it,” explains Stephen Ellies, who led the study.
The study, funded by the Swiss National Science Foundation (SNSF), also represents a methodological innovation, combining observations of both brain structure (morphology) and function (efficiency) to assess the developmental trajectory of a population in the context of psychiatric disorders.
About this Psychosis Research News
author: Antoine Guenault
sauce: University of Geneva
contact: Antoine Guénault – University of Geneva
image: Image courtesy of Neuroscience News
Original Research: Open access.
“Longitudinal analysis of brain function and structure dependence in 22q11.2 deletion syndrome and psychiatric symptoms” by Silas Forrer et al. Biological Psychiatry Cognitive Neuroscience and Neuroimaging
Abstract
Longitudinal analysis of brain function and structure dependence in 22q11.2 deletion syndrome and psychiatric symptoms
background
Compared to traditional unimodal analyses, understanding how brain function and structure are interrelated allows for biologically relevant new assessments of neural mechanisms. However, how function-structure-dependent disorders (FSDs) evolve through typical and abnormal neurodevelopment remains unclear. 22q11.2 deletion syndrome (22q11.2DS) provides an important opportunity to study the specific associations of FSD development with the pathophysiology of psychiatric disorders.
Method
We previously used graph signal processing to combine brain activity and structural connectivity indices to quantify FSD in adults. Here, we combined FSD with longitudinal multivariate partial least squares correlations to assess change in FSD between groups and between patients with and without mild-to-moderate positive psychotic symptoms. We assessed 391 longitudinal repeated resting-state functional and diffusion-weighted magnetic resonance images of 194 healthy control participants and 197 deletion carriers (ages 7-34 years, data collected over 12 years).
result
Compared to controls, 22q11.2DS patients showed persistent developmental deviations from early childhood, with regions of hyperconnectivity and hypoconnectivity throughout the brain. Furthermore, the second deviant developmental pattern worsened during adolescence, with 22q11.2DS patients showing hypoconnectivity in the frontal and cingulate cortices and hyperconnectivity in the temporal lobe. Interestingly, the deterioration observed during adolescence was strongly driven by the group with positive psychotic symptoms.
Conclusion
These results support a central role for FSD maturational changes in the emergence of psychotic symptoms in adolescents with 22q11.2DS. FSD deviations precede the onset of psychotic episodes and therefore represent a potential early indication for behavioral interventions for at-risk individuals.
