Schizophrenia Linked to Organized Pattern of Synaptic Loss in Brain

Researchers from Rutgers University and Yale University used specialized positron emission tomography (PET) imaging to directly measure synaptic connections in the living human brain. The study, published in Molecular Psychiatry, included 122 participants, 29 of whom were 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 frontal and temporal regions and areas involved in memory and emotion. The loss was considerably greater on the left side of the brain than on the right.

The synaptic loss pattern did not match the changes in brain volume typically seen with standard MRI 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.

Brain regions showing the greatest synaptic losses tended to contain high concentrations of receptors for neurotransmitters including serotonin, gamma-aminobutyric acid, and glutamate. The finding suggests that the molecular characteristics of individual brain regions may influence their vulnerability to changes associated with schizophrenia.

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

The researchers said future work will investigate how synaptic loss changes over time and how it responds to clinical treatments. A better understanding of that progression could help develop more precise and personalized approaches to schizophrenia care.