Advances in scanning have allowed researchers for the first time to exhibit lower levels of protein detected in the relationships between neurons in the living brain of people with schizophrenia.
The researchers who carried out the scanning in a psychiatric unit at the Medical research Council (IIA) of the London Institute of medical Sciences, said that these changes could underlie the cognitive difficulties observed in schizophrenia, and to identify targets for new methods of treatment.
For the first time, it was suggested that in the early 1980-ies schizophrenia was caused by dysfunctional synapses when nerve signals are transmitted between neurons in the brain. However, the researchers were able to study it only indirectly, for example, in samples of the brain after death or in animal and cellular models in the laboratory.
In this study, published in Nature Communications , the researchers first discovered it in a living brain using a tracer that transmits a signal that can be detected when scanning the brain using PET. After injection of the tracer specifically binds to the protein found in the synapses, called SV2A (a synaptic vesicle glycoprotein 2A), which has been shown in animal studies and after death, is a good marker of synaptic density of nerve endings in the brain.
The authors scanned 18 adults with schizophrenia and compared them with 18 people without schizophrenia.
It turned out that the SV2A synaptic protein levels were lower in anterior regions of the brain — the brain areas involved in planning — in people with schizophrenia.
Professor Oliver Howes, who led the study, from the London Institute of medical Sciences, Imperial College London and king’s College London, says: “Our modern methods of treatment of schizophrenia focused on only one aspect of the disease — psychotic symptoms, but the debilitating cognitive symptoms such as loss of ability to plan and remember, often cause much more prolonged disability, and currently they are not treated. It is believed that synaptic loss underlies these symptoms“.
“Our lab at the London Institute of medical Sciences is one of the few places in the world with this new indicator, which means that the first time we were able to show that people with schizophrenia have lower levels of synaptic protein. This suggests that the loss of synapses may underlie the development of schizophrenia“.
“We need to develop new treatments of schizophrenia. This protein SV2A may be a target of new therapies to restore synaptic function”.
“The presence of scans that can characterize the distribution of the approximately 100 trillion synapses in the living brain and find differences in their distribution between individuals with schizophrenia and without it, represents considerable progress in our ability to study schizophrenia“.
People with schizophrenia that were scanned in the new experiment, were receiving antipsychotic medications , so the researchers wanted to rule it out as a factor of synaptic dysfunction. They gave rats antipsychotic drugs haloperidol and olanzapine for 28 days and found that they do not affect the levels of protein SV2A.
Professor Howes says: “This is encouraging, because it suggests that our antipsychotic drugs do not lead to the loss of the brain’s connections. Then, we hope to scan the young people at the earliest stages of the disease, to see how the synaptic levels change during the progression of the disease and establishes whether these changes sooner or evolve over time“.