Schizophrenia's Synaptic Loss Follows a Distinct Pattern, Brain-Imaging Study Finds

Researchers including a Rutgers University professor have produced one of the clearest pictures yet of how schizophrenia changes the living human brain, by directly measuring synapses -- the tiny junctions that let brain cells communicate with each other. The study, published in the journal Molecular Psychiatry, used positron emission tomography (PET), a brain-imaging technique that can track specific molecules, to examine synaptic density in 122 people, including 29 diagnosed with schizophrenia, making it one of the largest studies of its kind.

The senior authors were Avram Holmes of Robert Wood Johnson Medical School and the Rutgers Brain Health Institute, and Rajiv Radhakrishnan of Yale University; first author Sidhant Chopra carried out the work as a postdoctoral fellow in Holmes's lab and is now at Orygen, Australia's Centre of Excellence in Youth Mental Health, and the University of Melbourne. Compared with healthy participants, people with schizophrenia showed a pronounced and widespread reduction in synaptic connections across the brain's frontal and temporal regions, as well as areas involved in memory and emotion, with the loss considerably greater on the left side of the brain than the right.

The synaptic losses did not line up with the brain-volume changes typically seen on standard MRI scans, suggesting that synaptic loss and volume change reflect separate biological processes rather than the same change viewed through two different imaging methods. The brain regions with the greatest synaptic losses also tended to contain high concentrations of receptors for the neurotransmitters serotonin, gamma-aminobutyric acid (GABA) and glutamate, indicating that a region's molecular makeup may influence how vulnerable it is.

Using computer simulations based on the brain's structural connections, the researchers traced how synaptic loss might spread through the brain and identified an area in the left frontal lobe as a likely starting point, from which the loss could travel into connected regions.