Rutgers-Yale study maps synaptic loss in schizophrenia
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Rutgers and Yale researchers report that people with schizophrenia show widespread synaptic loss in frontal and temporal brain regions, based on PET scans of 122 people. The loss was greater in the left hemisphere and did not match brain volume changes seen on MRI. Regions with the greatest loss had high concentrations of serotonin, GABA and glutamate receptors.
Key Facts
- People with schizophrenia showed a pronounced and widespread reduction in synaptic connections across frontal and temporal regions and areas involved in memory and emotion, compared with healthy participants.
- The study involved 122 participants, including 29 diagnosed with schizophrenia, making it one of the largest synaptic density PET imaging studies conducted so far.
- Synaptic loss was considerably greater in the left hemisphere than in the right.
- The synaptic loss pattern did not match brain volume changes seen on standard MRI scans, indicating that synaptic loss and brain volume changes reflect separate biological processes.
- Brain regions with the greatest synaptic losses tended to contain high concentrations of serotonin, GABA and glutamate receptors.
Study Cohort and Imaging
Researchers used specialized positron emission tomography (PET) to directly measure synaptic connections in the living human brain. The study involved 122 people, including 29 diagnosed with schizophrenia, and was led by senior authors Avram Holmes of Rutgers Robert Wood Johnson Medical School and Rajiv Radhakrishnan of Yale University. First author Sidhant Chopra is a McKenzie Research Fellow at Orygen and the University of Melbourne. The findings were published in Molecular Psychiatry, and the study is one of the largest synaptic density PET imaging studies conducted so far.
Regional Synaptic Loss
Compared with healthy participants, people with schizophrenia showed a pronounced and widespread reduction in synaptic connections across several brain regions. These included frontal and temporal regions as well as areas involved in memory and emotion, and in the 122-person cohort the loss was considerably greater on the left side than on the right. The synaptic pattern did not match changes in brain volume typically seen with standard MRI scans, indicating that synaptic loss and changes in brain volume reflect separate biological processes.
Molecular Vulnerability Markers
The team discovered that brain regions showing the greatest synaptic losses tended to contain high concentrations of receptors for three key neurotransmitters: serotonin, gamma-aminobutyric acid and glutamate. The finding indicates that the molecular characteristics of individual brain regions influence how vulnerable they are to changes associated with schizophrenia. To explore how synaptic loss moves through the brain, the researchers used computer simulations based on the brain's structural connections.
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Rutgers-Yale study maps synaptic loss in schizophrenia
