Researchers, including a professor from Rutgers University, gained clearer insight into the biological changes associated with schizophrenia by directly measuring synaptic connections in the living human brain. The team used specialized positron emission tomography (PET) imaging to examine these crucial communication points between brain cells. The study, published in Molecular Psychiatry, was led by Avram Holmes, associate professor of psychiatry at the Robert Wood Johnson School of Medicine and senior faculty member of the Center for Advanced Research in Imaging the Human Brain within Rutgers' Brain Health Institute, and Rajiv Radhakrishnan, associate professor of psychiatry and radiological and biomedical imaging at Yale University.
Synapses are small junctions that allow brain cells to communicate with each other through neural circuits. Problems involving these connections are believed to play a role in the cognitive and emotional symptoms of schizophrenia. Until now, scientists have had limited understanding of exactly where synaptic loss occurs in the brains of living people, since conventional imaging methods such as magnetic resonance imaging cannot specifically measure synapses.
The research involved 122 people, including 29 diagnosed with schizophrenia, making it one of the largest synaptic density PET imaging studies conducted to date. Compared with healthy participants, people with schizophrenia showed a pronounced and widespread reduction in synaptic connections across multiple brain regions, including the frontal and temporal regions, as well as areas involved in memory and emotion. The loss was considerably greater on the left side of the brain than on the right.
The researchers found that this synaptic pattern did not match the brain volume changes typically observed with standard magnetic resonance imaging scans. This distinction suggests 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 also discovered that brain regions showing the greatest synaptic losses tended to contain high concentrations of receptors for important neurotransmitters, including serotonin, gamma-aminobutyric acid and glutamate. The finding suggests that the molecular features of individual brain regions may influence how vulnerable they are to changes associated with schizophrenia. The researchers used computer simulations based on the brain's structural connections to explore how synaptic loss could spread through the brain. Their modelling identified an area in the left frontal lobe as a likely starting point from which synaptic loss could extend to connected regions.
Researchers said that future work will build on these findings by investigating how synaptic loss changes over time and how it responds to clinical treatments. A better understanding of that progression could ultimately help researchers develop more precise and personalized approaches to schizophrenia care.
