Patients with schizophrenia have lower levels of a protein crucial to creating strong connections in the brain, according to new PET imaging-based research.
Scientists from the United Kingdom used a rare positron-emission tomography radiotracer to image the bonds between neurons in the living brains of more than 30 participants to reach their conclusions. The findings, published Jan. 14 in Nature Communications, may offer new targets for researching and treating the disorder.
"Having scans that can characterize the distribution of the approximately 100 trillion synapses in the living brain, and find differences in their distribution between people with and without schizophrenia, represents a significant advance in our ability to study schizophrenia,” Ellis Chika Onwordi, with Hammersmith Hospital in London, said in a statement.
Scientists have long believed that schizophrenia is caused by malfunctions in nerve signal transmissions between neurons in the brain, known as synapses, but this has only been proven through post-mortem brain samples or in animal models.
The current study is the first to demonstrate this long-held hypothesis in living humans.
Onwordi and colleagues used a radiotracer that binds specifically to a protein in the synapses called synaptic vesicle glycoprotein 2A (SV2A) in 18 adults with schizophrenia and 18 without the disorder. And when scanning patients with schizophrenia, they found those protein levels were lower in the front regions of the brain, typically involved in the daily act of planning.
All patients with the disorder had received antipsychotic medication, which could have also caused malfunctioning in the synapses. To rule this out, the researchers treated rats with the same drugs for 28 days and found they had no effect on those protein levels.
Oliver Howes, lead professor of the study, said that specific finding was “reassuring,” and demonstrates that these commonly prescribed treatments aren’t damaging brain connections.
The investigators also believe the SV2A protein could become a target for new treatments aimed at restoring lost synaptic function.
“Our current treatments for schizophrenia only target one aspect of the disease—the psychotic symptoms—but the debilitating cognitive symptoms, such as loss of abilities to plan and remember, often cause much more long-term disability and there's no treatment for them at the moment,” the researchers said. “Synaptic loss is thought to underlie these symptoms.”
Going forward, the researchers hope to scan younger patients in the early stages of schizophrenia to understand how their synapses change during the illness, and if any damage is permanent or progresses with age.