Researchers, including a Rutgers professor, have gained a clearer view of the biological changes associated with schizophrenia by directly measuring synaptic connections in the living human brain using specialized positron emission tomography (PET) imaging. The study, published in Molecular Psychiatry and led by senior authors Avram Holmes and Rajiv Radhakrishnan, involved 122 people, including 29 diagnosed with schizophrenia.
The research found that compared to healthy participants, individuals with schizophrenia showed a pronounced and widespread reduction in synaptic connections across several parts of the brain, particularly frontal and temporal regions as well as areas involved in memory and emotion. The loss was also considerably greater on the left side of the brain than on the right. This synaptic pattern did not match changes in brain volume typically seen with standard MRI scans, suggesting that synaptic loss and changes in brain volume may reflect separate biological processes rather than two imaging methods capturing the same underlying change.
The team discovered that the brain regions showing the greatest synaptic losses tended to contain high concentrations of receptors for important neurotransmitters, including serotonin, gamma-aminobutyric acid, and glutamate. This finding suggests that the molecular characteristics of individual brain regions may influence how vulnerable they are to changes associated with schizophrenia. The researchers also used computer simulations based on the brain’s structural connections to identify an area in the left frontal lobe as a likely starting point from which synaptic loss could spread into connected regions. These findings suggest that in schizophrenia, synaptic loss is not random but follows the brain’s molecular and connectivity architecture, potentially helping identify where and how to intervene.