More targeted and effective treatments for psychosis could be one step closer, as new research published in Nature Molecular Psychiatry by Orygen researcher Dr Sidhant Chopra reveals large and wide-spread loss of synapses – microscopic connections between brain cells – in people diagnosed with schizophrenia.
The human brain has trillions of synapses, which in the past could only be measured post-mortem. However, a new type of brain scan developed by Yale University is now able to measure synaptic density in living people.
The new research, undertaken in collaboration with Associate Professor Avram Holmes from Rutgers University and Associate Professor Rajiv Radhakrishnan from Yale University, is the world’s largest study using this innovative Positron Emission Tomography (PET) imaging to map the number of synapses in people with schizophrenia compared a control group without the condition.
Dr Chopra said that based on genetic and post-mortem findings, researchers have long suspected synapses play a major role in schizophrenia, but until recently brain imaging was unable to map the patterns of synaptic loss in the brains of living people.
“What we’ve been able to show for the first time is a prominent and widespread pattern of lower synaptic density across the brain in people with schizophrenia,” Dr Chopra said.
"We also found unique features of this pattern, with loss occurring predominantly in the left hemisphere of the brain and aligned with maps of multiple neurotransmitters like serotonin.
“We also found – contrary to what we expected – that this pattern was independent of grey matter loss in the brain, often seen using Magnetic Resonance Imaging (MRI) in psychotic disorders.
"Hundreds of studies have shown lower brain volume in people with schizophrenia, and while many assumed these changes were at least in part due to synaptic loss, this doesn’t seem to be the case – and raises a lot of questions about what exactly these commonly reported brain MRI findings are measuring.”
The study also used simulations to identify parts of the brain where synaptic loss might start, finding areas in the frontal and temporal cortex – which help the brain interpret language, emotions and bodily signals.
“These findings are important because they support the idea of early intervention in psychosis to prevent synapse loss – opening the door to new therapies such as medications to repair or regrow synapses, or behavioral interventions such as exercise that could protect against synaptic loss,” Dr Chopra said.
"Better understanding the foundational mechanisms in the brain associated with psychosis is vital to improving outcomes – and could make a huge difference to the lives of young people experiencing early psychosis.
“Currently, most antipsychotic medications change the levels of dopamine in the brain and don't work for many people, with many experiencing debilitating side effects without getting any benefits.
“The next generation of treatments, which can grow and repair synapses, may hold the key to long-lasting impact in the lives of those with psychosis.”
Further research is now needed to investigate what causes synaptic changes, and to examine synaptic density at the very early stages of psychosis to better understand when the process might begin, and what can be done to prevent it.