Human brain represented by cogs

Re-thinking neurodevelopment: How the immune system sculpts the brain

10 November 2023
We’re leading research that helps us better understand children’s brains
Professor Russell Dale is changing the lives of children and their families by understanding the role the immune system plays in brain development.

Professor Russell Dale is a paediatric neurologist who works as both a clinician at Children’s Hospital at Westmead in the Kids Neuroscience Centre as well as an academic at the University of Sydney.

Part of his work is leading research that explores the role of the immune system in common neurodevelopmental disorders such as autistic spectrum disorder, obsessive compulsive disorder (OCD) and Tourette syndrome.

Professor Dale was inspired to work on this research due to a lack of understanding about the impact of infections and stress on children’s brains.

“Research shows that brain connections (called synapses) are sculpted by the immune cells in the brain, called the microglia," says Professor Dale.

"Therefore, brain neurodevelopment should be considered a ‘neuroimmune’ process rather than just a ‘neurological process'.

“The clinical work we are doing at Westmead responds to many family’s observations that infections and stress makes their child’s symptoms worse.

"What this means is that some children can be developing normally and then an infection can provoke a sudden change in their child’s behaviour, such as the development of obsessive-compulsive disorder, or a regression in their developmental skills so that they begin to develop autistic features, known as autistic regression.

“At present there is no specific pathway for these children in the health system, instead they are provided with standard support such as psychology, psychiatry or neurodevelopmental support, often with long waiting lists.

"There is a lack of urgency to protect these young brains.”

Improving our understanding

It is estimated that one in ten children in Australia are impacted by a neurodevelopmental disorder, and 80% will have multiple behavioural diagnoses including anxiety and depression.

Children who experience neurodevelopmental disorders such as autism spectrum disorder, OCD and Tourette syndrome face many challenges.

These can range from sensory sensitivities and problems with social interaction (autism) to intrusive thoughts and compulsions (OCD).

Such behaviours place strain on families, as well as the children themselves.

The role the brain plays in triggering these behavioural changes is poorly understood.

“We still struggle to understand many of the common conditions that cause problems with development other than they are caused by a ‘combination of vulnerability genes plus environmental factors,’” reflects Professor Dale.

According to Professor Dale, most of the current approaches to neurodevelopmental disorders only provide support such as speech therapy or are symptomatic treatments such as prescribing stimulants for ADHD.

“The research we are doing helps children with neurodevelopmental disorders who haven’t responded to conventional treatments,” says Professor Dale.

“These children have also experienced infection provoked deteriorations in their neurodevelopment.

“Parents are making very important observations about the changes they see in their children.

"They recognise that environmental factors such as infection, stress or diet can change the way their children behave.

“Children and families are giving us the information we need, but we must listen.”

Doing better by thinking differently

Professor Dale points out that contemporary medicine is not good enough, because it struggles to acknowledge important observations.

“Medicine only provides limited understanding to health and disease at the moment," says Professor Dale.

"Therefore, trying to help children and families is humbling, but I see the opportunities and possibilities to do better, by thinking differently.”

The work Professor Dale and his team of clinicians and scientists are doing is achieving incredible results.

“Children who were incapacitated by OCD who had failed conventional treatment are showing astonishing results," explains Professor Dale.

"These are children that were unable to go to school for two years who have received anti-inflammatory treatments and are now able to attend university with their friends.”

The advent of new technologies such as single cell RNA sequencing has allowed the team at Westmead the unprecedented opportunity to study patients’ immune systems.

This is giving them insights into how the immune system in children with neurodevelopment is different from neurotypical children, resulting in recurrent infections, and infection provoked deteriorations in neurodevelopment.

“The brain does not operate in isolation, instead our brains are constantly interacting with the immune system," says Professor Dale.

"We cannot ignore the impact that stress and infection has on children’s brains and neurodevelopment.

“New technologies can examine how cells are programmed, and how environmental factors leave epigenetic marks that can increase or decrease gene expression.

"To date we have been focused on DNA variation only, but we need to also focus on the environment and epigenetics, and consequently on RNA expression and protein abundance.

"These technologies are available and can provide remarkable insights in to ‘how immune cells are working’ at an individual level.

“I see a future of using these technologies to open a whole new paradigm in neurodevelopment."