A study involving a Rutgers professor sheds new light on the biological basis of schizophrenia by directly measuring synaptic connections in the human brain using specialized positron emission tomography (PET) imaging, according to a Jul. 14 announcement.
The research, published in Molecular Psychiatry, was led by Avram Holmes, associate professor of psychiatry at Robert Wood Johnson Medical School and core faculty member of the Center for Advanced Human Brain Imaging Research within the Rutgers Brain Health Institute, and Rajiv Radhakrishnan, associate professor of psychiatry and radiology and biomedical imaging at Yale University. Sidhant Chopra, formerly a postdoctoral fellow in the Holmes Lab and now a McKenzie Research Fellow at Orygen and the University of Melbourne in Australia, served as first author.
The study included 122 individuals—29 diagnosed with schizophrenia—and is among the largest synaptic density PET imaging studies conducted to date. Researchers found that people with schizophrenia showed prominent and widespread reductions in synaptic connections across multiple brain regions compared to healthy individuals. These affected areas included frontal, temporal, memory-related, and emotion-related regions. The left side of the brain was found to be substantially more affected than the right.
Researchers noted that this pattern of synaptic loss differed from brain volume changes typically detected by standard MRI scans, suggesting two separate biological processes are involved rather than different measurements of one problem.
Additionally, researchers observed that areas with significant synaptic loss were those normally rich in receptors for neurotransmitters such as serotonin, gamma-aminobutyric acid (GABA), and glutamate. Computer simulations indicated that a region in the left frontal lobe may serve as an initial point from which synaptic loss spreads through connected regions.
"This detailed mapping of synaptic vulnerability could eventually help identify where and how to intervene to preserve or restore brain function, such as emerging therapies to prevent and regrow synapses," Holmes said. The team said future studies would further characterize how synaptic loss progresses over time and responds to clinical interventions.
