Summary: Young adults at risk of psychosis show reduced synaptic density, a critical brain connectivity deficit that cannabis use appears to exacerbate, according to new research. The study revealed lower synaptic density linked to social withdrawal and motivational deficits, symptoms poorly addressed by current medications. Researchers found that cannabis disrupts synaptic pruning, an essential brain development process.
Using advanced brain scanning, the study marks the first real-time measurement of brain structural changes in high-risk individuals, offering insights into psychosis progression. These findings could pave the way for therapies targeting social and functional deficits in psychosis. Next steps include investigating whether these brain changes can predict psychosis development for earlier intervention.
Key Facts:
- Cannabis use disrupts synaptic pruning in young adults at risk of psychosis.
- Lower synaptic density is linked to social withdrawal and motivational deficits.
- This is the first real-time measurement of brain structural changes in high-risk populations.
Source: McGill University
Young adults at risk of psychosis show reduced brain connectivity, a deficit that cannabis use appears to worsen, a new study has found. The breakthrough paves the way for psychosis treatments targeting symptoms that current medications miss.
In the first-of-its-kind study, McGill University researchers detected a marked decrease in synaptic density—the connections between neurons that enable brain communication—in individuals at risk of psychosis, compared to a healthy control group.
“Not every cannabis user will develop psychosis, but for some, the risks are high. Our research helps clarify why,” said Dr. Romina Mizrahi, senior author of the study and professor in McGill’s Department of Psychiatry.
“Cannabis appears to disrupt the brain’s natural process of refining and pruning synapses, which is essential for healthy brain development.”
Hope for new treatments
Using advanced brain scanning technology, the team studied 49 participants aged 16 to 30, including individuals with recent psychotic symptoms and those considered at high risk.
The results, published in JAMA Psychiatry, indicate that lower synaptic density is linked to social withdrawal and lack of motivation, symptoms the researchers say are difficult to treat.
“Current medications largely target hallucinations, but they don’t address symptoms that make it difficult to manage social relationships, work, or school,” said first author Belen Blasco, a PhD student at McGill’s Integrated Program in Neuroscience.
“By focusing on synaptic density, we may eventually develop therapies that enhance social function and quality of life for those affected.”
While cannabis is a known risk factor for developing psychosis, which can progress to schizophrenia, this is the first time researchers have measured structural changes in the brains of a high-risk population in real time.
The team’s next research phase will explore whether these observed brain changes could predict psychosis development, potentially enabling earlier intervention.
Funding: The study was conducted at the Douglas Mental Health University Institute and McGill University’s Montreal Neurological Institute-Hospital. It was supported by the Canadian Institute of Health Research.
About this CUD and psychosis research news
Author: Keila DePape
Source: McGill University
Contact: Keila DePape – McGill University
Image: The image is credited to Neuroscience News
Original Research: Open access.
“Synaptic Density in Early Stages of Psychosis and Clinical High Risk” by Romina Mizrahi et al. JAMA Psychiatry
Abstract
Synaptic Density in Early Stages of Psychosis and Clinical High Risk
Importance
Synaptic dysfunction is involved in schizophrenia pathophysiology. However, whether in vivo synaptic density is reduced in early stages of psychosis, including its high-risk states, remains unclear.
Objective
To investigate whether synaptic density (synaptic vesicle glycoprotein 2A [SV2A] binding potential) is reduced in first-episode psychosis (FEP) and in clinical high risk (CHR) and investigate the effect of cannabis use on synaptic density and examine its relationship with psychotic symptoms and gray matter microstructure across groups.
Design, Setting, and Participants
This cross-sectional study was performed in a tertiary care psychiatric hospital from July 2021 to October 2023. Participants were patients with antipsychotic-free or minimally exposed FEP or CHR and healthy controls with a clean urine drug screen (except cannabis).
Main Outcomes and Measures
Synaptic density was quantified with dynamic 90-minute [18F]SynVesT-1 positron emission tomography (PET) scans across prioritized brain regions of interest (ROIs) delineated in individual magnetic resonance images (MRIs). Cannabis use was confirmed with urine drug screens. Gray matter microstructure was assessed using diffusion-weighted MRI to estimate neurite density.
Results
A total of 49 participants were included, including 16 patients with FEP (mean [SD] age, 26.1 [4.6] years; 9 males and 7 females), 17 patients at CHR (mean [SD] age, 21.2 [3.5] years; 8 males and 9 females), and 16 healthy controls (mean [SD] age, 23.4 [3.6] years; 7 males and 9 females).
Synaptic density was significantly different between groups (F2,273 = 4.02, P = .02, Cohen F = 0.17; ROI: F5,273 = 360.18, P < .01, Cohen F = 2.55) with a group × ROI interaction (F10,273 = 2.67, P < .01, Cohen F = 0.32). Synaptic density was lower in cannabis users (F1,272 = 5.31, P = .02, Cohen F = 0.14).
Lower synaptic density across groups was associated with more negative symptoms (Positive and Negative Syndrome Scale negative scores: F1,81 = 4.31, P = .04, Cohen F = 0.23; Scale of Psychosis-Risk Symptoms negative scores: F1,90 = 4.12, P = .04, Cohen F = 0.21). SV2A binding potential was significantly associated with neurite density index (F1,138 = 6.76, P = .01, Cohen F = 0.22).
Conclusions and Relevance
This study found that synaptic density reductions were present during the early stages of psychosis and its risk states and associated with negative symptoms. The implications of SV2A for negative symptoms in psychosis and CHR warrant further investigation. Future studies should investigate the impact of cannabis use on synaptic density in CHR longitudinally.
