By directly measuring synaptic connections in living human brains, researchers at Rutgers University and Yale University have gained new insight into the biological changes linked to schizophrenia. Using specialized positron emission tomography (PET) imaging, the team examined the key communication points that allow brain cells to connect and exchange signals.
Published in Molecular Psychiatry, the study was led by Abram Holmes, associate professor of psychiatry at Rutgers Robert Wood Johnson Medical School and a core faculty member of the Center for Advanced Human Brain Imaging at the Rutgers Brain Health Institute. Rajiv Radhakrishnan, associate professor of psychiatry, radiology, and biomedical imaging at Yale University, also contributed to the research. Lead author Sidhant Chopra is a former postdoctoral fellow in the Holmes laboratory and a McKenzie Research Fellow at Orygen, the National Centre of Excellence in Youth Mental Health at the University of Melbourne in Australia.
Measuring synaptic connections in the living brain
Synapses are tiny junctions that enable brain cells to communicate through neural circuits. Disruptions in these connections are believed to contribute to the cognitive, emotional, and behavioral symptoms associated with schizophrenia. Until now, however, researchers have been unable to determine precisely where synaptic loss occurs in the living human brain because conventional imaging techniques, including magnetic resonance imaging (MRI), cannot directly measure synapses.
The study included 122 participants, including 29 people diagnosed with schizophrenia, making it one of the largest studies to use synaptic-density PET imaging. Compared with healthy participants, people with schizophrenia showed a widespread reduction in synaptic connections across multiple brain regions. These areas included the frontal and temporal lobes, as well as regions involved in memory and emotion. Synaptic loss was also significantly greater in the left side of the brain than in the right.
The researchers found that the distribution of synaptic loss did not correspond to the brain-volume changes typically detected with standard MRI scans. This finding suggests that synaptic loss and changes in brain volume may represent distinct biological processes rather than different ways of measuring the same underlying changes.
Molecular patterns linked to synaptic loss
Brain regions with the greatest synaptic loss tended to have higher concentrations of receptors for key neurotransmitters, including serotonin, gamma-aminobutyric acid (GABA), and glutamate. These results suggest that the molecular characteristics of individual brain regions may influence their vulnerability to schizophrenia-related changes.
To study how synaptic loss may spread through the brain, the researchers used computer simulations based on the brain’s structural connections. Their models identified a region in the left frontal lobe as a possible starting point from which synaptic loss could extend to connected areas.
“These findings suggest that synaptic loss in schizophrenia is not random,” Chopra said. “Rather, it follows the molecular and connectivity structure of the brain and may ultimately help us identify where and how to intervene.”
“This detailed mapping of synaptic vulnerability may eventually help identify where and how to intervene to preserve or restore brain function, including the development of treatments designed to prevent synaptic loss or support synaptic regrowth,” Holmes added.
Supporting more precise schizophrenia treatment
The researchers plan to build on these findings by examining how synaptic loss changes over time and how it responds to schizophrenia treatments. A clearer understanding of the progression of synaptic changes could help scientists develop more precise and personalized approaches to diagnosing and treating schizophrenia.
Source: www.sciencedaily.com