Patients with schizophrenia may have reduced brain connections that affect planning

Researchers have found lower levels of a protein associated with neural connections in the living brains of people with schizophrenia, according to results of parallel clinical and preclinical studies published in Nature Communications.

“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,” Oliver Howes, of the Medical Research Council London Institute of Medical Sciences at Imperial College London and King’s College London, said in a press release. “Synaptic loss is thought to underlie these symptoms.”

According to Howes and colleagues, prior research has suggested that synaptic dysfunction plays a key role in schizophrenia pathogenesis. However, this hypothesis has not been tested directly in vivo. To do so, the researchers used a tracer that emits a signal which can be detected by a PET brain scan to investigate synaptic vesicle glycoprotein 2A, or SV2A, levels and their relationship to structural brain measures and symptoms. They noted that SV2A has been shown in post-mortem and animal studies to be an effective marker of the density of synaptic nerve endings in the brain.

Among 18 adults with schizophrenia and 18 controls, they found that those with schizophrenia had lower SV2A levels in brain regions involved in planning. However, they found no significant difference in the hippocampus. Since all patients with schizophrenia who were scanned had received antipsychotic medication, the researchers gave haloperidol and olanzapine to rats for 28 days to exclude this as a factor in synaptic dysfunction. They reported that its administration had no effects on rats’ SV2A levels.

“This is reassuring as it’s suggesting that our antipsychotic treatments aren’t leading to loss of brain connections,” Howe said. “Next we hope to scan younger people in the very early stages to see how synaptic levels change during the development of the illness and whether these changes are established early on or develop over time.” – by Joe Gramigna

Disclosures: Howe reports receiving investigator-initiated research funding from and/or participated in advisory/speaker meetings organized by 15 pharmaceutical companies. Please see the study for all other authors’ relevant financial disclosures.