A major unresolved question about brain changes in people with psychosis has been answered for the first time, with new Orygen research showing the loss of grey matter in early psychosis is a result of the illness rather than a side effect of antipsychotic medication.
The world-first, triple-blind, randomised, placebo-controlled longitudinal study, published in Biological Psychiatry, used Magnetic Resonance Imaging (MRI) to analyse the brains of 62 people aged 15-25 with first-episode psychosis, half of whom received antipsychotic medications while half were given a placebo.
The study was the first ever brain imaging study in psychosis where antipsychotics were safely withheld, the specific effects of antipsychotic medication could be examined. The study also included 27 age-matched healthy controls, and MRIs were conducted at baseline, three months and 12 months.
Lead author and Research Fellow in Clinical Neuroscience at Orygen, Dr Sidhant Chopra, said the results were clear, and answered a controversial and long debated question about the brain changes seen in psychosis.
“We’ve long known that thinning of cortical grey matter in the brain is common in people with psychosis – and can progress with ongoing illness – but until now we haven’t known if this is a result of the illness itself, or if it’s due to effects of antipsychotic medication,” Dr Chopra said.
“Compared to a healthy control group, we found that while widespread thinning of cortical grey matter was evident in people with psychosis who did not receive antipsychotic medication, those who did receive antipsychotics had no such thinning.
"Many people, including us, thought the brain changes we see in psychosis were harmful medication effects, but what we’ve found is really the opposite – these medications are not causing the brain changes, and may in fact be preventing harmful effects, at least in the early stages of illness.”
Dr Chopra said the findings represented an important step in the understanding of brain changes in early psychosis.
Alongside the antipsychotic medication or placebo, participants in the study received intensive psychosocial treatment, but this on its own was not enough to prevent the illness-related cortical thinning.
“While psychosocial treatment is an critical part of supporting people experiencing psychosis, this treatment alone was insufficient to mitigate the changes we observed in the placebo group,” Dr Chopra said.
“For the first time we’ve seen clear, gold-standard evidence that – at least during the early stages of psychosis – these medications are not causing grey matter loss and may actually be protecting against it, and more research is now needed to establish exactly how these medications might preserve cortical integrity, and how we can develop even more effective medications.”
Orygen Executive Director and co-author, Professor Patrick McGorry, said the findings were critical to changing the often negative perception of life-changing antipsychotic medications.
“This research is a major step forward in our understanding of how psychosis affects the brain,” Professor McGorry said.
“It clearly shows that it is the illness, not the medications, responsible for brain changes – and could play an important role in how we talk about these medications with young people and their families, and how we manage early psychosis in the future.
“Looking at all the scientific evidence, careful use of antipsychotic medications at minimum effective doses creates the foundations for optimal recovery, a normal life, and extended life expectancy, contrary to what is widely believed and promoted by some critics.”
The study was a collaboration between Orygen and Monash University, with contributions from researchers across Australia, Ireland, the UK and USA.