Schizophrenia synaptic loss follows brain's wiring pattern
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- Avram Holmes of Rutgers and Rajiv Radhakrishnan of Yale co-led one of the largest synaptic density PET imaging studies to date, directly measuring synaptic connections in 122 people including 29 diagnosed with schizophrenia.
- People with schizophrenia showed pronounced, widespread synaptic loss across frontal and temporal regions and areas involved in memory and emotion, with the damage considerably greater on the left side of the brain than the right.
- The synaptic loss pattern did not match changes in brain volume captured by standard MRI, suggesting the two reflect separate biological processes rather than different views of the same underlying change.
- Brain regions with the greatest synaptic loss tended to contain high concentrations of receptors for serotonin, GABA, and glutamate, indicating that a region's molecular makeup shapes its vulnerability.
- Computer simulations of the brain's structural wiring identified the left frontal lobe as a likely origin point from which synaptic loss spreads outward to connected regions.
- First author Sidhant Chopra said the findings show synaptic loss "is not random" but follows the brain's molecular and connectivity architecture, which the team says could guide emerging synapse-regrowing therapies.
Why it matters: By showing synaptic loss diverges from the brain-volume changes MRI has long tracked, the study gives researchers a new, directly measurable target — and a specific left frontal origin point — for emerging synapse-regrowing therapies in schizophrenia.
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