Schizophrenia’s lost brain connections follow a surprising pattern
Specialized brain scans reveal that schizophrenia is linked to widespread loss of the synapses that connect brain cells, with the left side of the brain hit especially hard. The damage follows a surprisingly organized pattern tied to the brain’s chemistry and wiring. Researchers also identified a left frontal region that may serve as a starting point for the loss.
A Rutgers-led study has illuminated the biological changes linked to schizophrenia by measuring synaptic connections within living human brains. The work, published in Molecular Psychiatry, was spearheaded by senior authors Avram Holmes and Rajiv Radhakrishnan, with key contributions from Sidhant Chopra. Synapses, the junctions between brain cells, are essential for communication and are believed to contribute to schizophrenia's cognitive and emotional symptoms.
Synaptic loss in schizophrenia patients has been difficult to study using conventional imaging methods like MRI, which do not specifically measure synapses. This study, involving 122 individuals, including 29 with schizophrenia, is one of the largest synaptic density PET imaging studies to date. The researchers observed significant and widespread reductions in synaptic connections across several brain areas, including frontal and temporal regions, in people with schizophrenia compared to healthy controls.
These losses were more pronounced on the left side of the brain. Importantly, the synaptic loss pattern did not align with standard MRI volume changes, indicating synaptic loss and brain volume reduction may reflect distinct biological processes. The team identified high concentrations of neurotransmitter receptors, such as serotonin, gamma-aminobutyric acid, and glutamate, in regions with the greatest synaptic losses, suggesting that an individual brain region's molecular characteristics might influence its vulnerability to schizophrenia-related changes.
The researchers used computer simulations to map how synaptic loss could propagate through the brain, pinpointing an area in the left frontal lobe as a likely starting point. This detailed understanding of synaptic vulnerability could help identify potential intervention points to preserve or restore brain function in schizophrenia.
Future research will explore the progression of synaptic loss over time and its response to clinical treatments, potentially leading to more personalized and precise schizophrenia care.
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