London researchers are embarking on a three-year study aiming to identify babies at higher than average risk of autism spectrum conditions (ASC) and attention deficit hyperactivity disorder (ADHD).

The work at King’s College London is supported with funding of £199,968 from children’s charity Action Medical Research.

Having one or both of these conditions makes life difficult for children and their families, and can seriously affect children’s education, employment chances and quality of life.

The researchers hope that earlier information to help predict which children may go on to have difficulties with these conditions will open the door for support to be provided from infancy to those most in need, greatly helping children and their families.

Both ASC and ADHD are common in childhood, as lead researcher Dr Tomoki Arichi says: “ASC is estimated to affect one per cent of children in the UK1 and typically leads to impaired social interaction and communication. ADHD is more common, affecting up to five per cent of UK children2 and is characterised by overactivity, impulsive behaviour and difficulties in paying attention.”

It is already known that a family history of ASC or ADHD puts a child at a higher risk of developing these conditions. However it is still not known exactly what makes a baby vulnerable to later have these conditions. This has made it difficult to identify, develop and deliver interventions to those who need it most.

There is now evidence that understanding the balance between two chemical messengers in the brain – known as neurotransmitters – called glutamate and GABA, may be key to unpicking what leads to altered brain development.

Dr Arichi and his colleagues, physicist Dr Enrico De Vita and Professor of Translational Neuroscience Grainne McAlonan, are exploring the role of these two brain chemicals in shaping the developing brain.

Dr Arichi explains: “We want to see if a sophisticated scanning technique which measures the levels of these two particular neurotransmitters in the brain could allow earlier prediction of neurodevelopmental conditions in newborn babies known to be at risk.”

The team will use Magnetic Resonance Imaging (MRI) scanners and a state-of-the-art method called magnetic resonance spectroscopy (MRS) which can measure the levels of chemicals in the living brain safely and precisely.

They will measure glutamate and GABA levels in the brains of 80 newborn babies using an MRI scanner at St Thomas’ Hospital London with special adaptations and staff for scanning babies. They will also pioneer scanning babies on a new, highly powerful 7 Tesla MRI scanner which will be installed at St Thomas’ Hospital in the coming months.

Dr Arichi explains: “Half the babies will be at high risk of developing a neurodevelopmental condition, due to an affected close family member, and half will have no increased risk – this group will be our control.”

The researchers will compare results between the two groups to see if there are any differences.

Studying equal numbers of high-risk babies and those at normal risk, they will:

  • use a state-of-the-art MRI technique to look inside the brains of 48 babies while they are asleep naturally.
  • look inside the brains of the other 32 babies using an even more powerful MRI scanner that can provide much more accurate data. Although there are no health risks from exposure to a strong magnetic field, the researchers will first carry out rigorous safety testing, as these will be the first-ever studies in newborns using this machine.

The researchers will then carry out sophisticated data analyses to calculate the concentration of GABA and glutamate in the babies’ brains, and their ratios to each other and to other important brain chemicals. When the children reach two years of age, they will undergo a thorough neurodevelopmental assessment – and the researchers will then go back to interrogate their earlier scan data to look for alterations to these brain chemicals in babies who later develop difficulties.

Commenting on the project Dr Arichi said: “We appointed a very experienced post-doctoral fellow in November – so we haven’t started any data collection yet but have just done some preliminary tests on the sequence with healthy adults.

“Although there have been studies which have tried to look at GABA levels in adults and older children with ASD, ours will be the first which will look at the levels of GABA and glutamate/glutamine in newborn babies at high risk of developing ASD. We hope that in doing so, we can understand how the condition might directly cause alterations in the levels of these neurotransmitters and alter how the brain develops – and crucially, before environmental effects (other illnesses, family, school, social deprivation etc) kick in and complicate things further. If we do find differences it will agree with what they have started to find in animals (but never before in humans), so it potentially has big implications for trying to develop treatments for ASD and then monitoring how they might influence neurotransmitter levels.

“In addition to being the first study to collect this kind of data in newborn babies, we are planning to innovate on several technical levels as well – we will need to develop the MRI acquisition methods so that they can work optimally with babies and will also be scanning with a 7 Tesla MRI scanner (which has a much stronger magnetic field in comparison to the ones that are standard in the hospitals).”

Dr Tracy Swinfield, Director of Research at Action Medical Research, comments: “We’re very pleased to support this study. This research could lead to a new, safe, non-invasive technique to identify babies who may develop difficulties later in childhood, enabling early support and intervention where appropriate.”

“Studying neurotransmitter levels in the brain in early life could also help to inform new treatment strategies for currently incurable conditions such as ASC,” adds Dr Swinfield.

Cathy Lewsey, whose twin sons Sam and Josh were diagnosed with ASC aged six, knows from personal experience how important an early diagnosis can be.

“When you have children with autism spectrum condition you can’t assume anything about family life. You simply have to tear up the rule book and start again,” she says.

Sam and Josh, now aged 12, are identical twins. In many ways, they are just like other boys of their age, enjoying cub scouts and playing computer games like Minecraft and Skylanders.

But they have a strong need for routine, find it hard to understand other people’s feelings and viewpoint, and their behaviour can be challenging.

Sam and Josh had a remarkably calm start in life: despite being born at just over 34 weeks, they came home after only four days in hospital, weighing 5lbs 8.5 ounces and 5lbs 3.5 ounces respectively.

“They ate, slept and rarely cried,” Cathy remembers. “They were the easiest babies ever.”

It was only when the boys started pre-school that their difficulties became apparent. Cathy recalls: “Josh would have to be peeled off me and would then sit facing the wall, rocking. Sam would run for the back door and he’d be off up the road if no-one stopped him.”

Fortunately, the nursery staff were, Cathy says, ‘absolutely amazing,’ gently expressing their growing concerns about little Josh and Sam and working hard to help them cope with the transition to primary school.

But without a diagnosis that could explain the boys’ behavioural difficulties, Sam and Josh started Reception class with no formal support in place.

And, sadly, things quickly became very difficult.

Often upset and frustrated, Sam and Josh would scream, shout, lash out and throw things.

“Josh spent most of the first 18 months sitting under the teacher’s desk,” Cathy recalls. “Even at just four or five years old, both boys were frequently excluded from school, sometimes every week.”

“They were not allowed to join the other children at playtime, lunchtime or for sports,” Cathy adds. “The school said it was for their own safety and that of others, which of course we understood, but it was very upsetting.”

“It was a time of utter desperation,” Cathy says. “Our parenting skills were openly called into question, even though we’d raised three other children. We just didn’t know what to do.”

Teaching assistants were brought in to work with the boys on a one-to-one basis but they were, Cathy felt, babysitting rather than teaching the boys.

“Sam and Josh do not have learning disabilities; in fact, they are now on the Gifted and Talented register for maths and science,” she points out.

The boys were not diagnosed with ASC until they were six.

After they moved to a small specialist school where teachers understand their needs, Sam and Josh thankfully started to thrive. They now attend a secondary school that is residential from Monday to Friday. “They are home every Wednesday night for scouts, which has been a fantastic outlet for Sam especially,” Cathy says. “Sam has made amazing friends from mainstream schools, who completely support, understand and encourage him. He has done things we never thought he would be able to do, like a 12-mile walk, a two-day camping trip and throwing a tomahawk!”

As Sam and Josh grow up, it’s becoming apparent that sadly Josh has much more complex needs, and many challenges lie ahead.

As Dr Arichi notes, neurodevelopmental conditions like ASC or ADHD have a long-term, wide-ranging impact on the lives of children and their families, making research into this area as important as it is rewarding.

It was only when the boys started pre-school that their difficulties became apparent. Cathy recalls: “Josh would have to be peeled off me and would then sit facing the wall, rocking. Sam would run for the back door and he’d be off up the road if no-one stopped him.”

Fortunately, the nursery staff were, Cathy says, ‘absolutely amazing,’ gently expressing their growing concerns about little Josh and Sam and working hard to help them cope with the transition to primary school.

But without a diagnosis that could explain the boys’ behavioural difficulties, Sam and Josh started Reception class with no formal support in place.

And, sadly, things quickly became very difficult.

Often upset and frustrated, Sam and Josh would scream, shout, lash out and throw things.

“Josh spent most of the first 18 months sitting under the teacher’s desk,” Cathy recalls. “Even at just four or five years old, both boys were frequently excluded from school, sometimes every week.”

“They were not allowed to join the other children at playtime, lunchtime or for sports,” Cathy adds. “The school said it was for their own safety and that of others, which of course we understood, but it was very upsetting.”

“It was a time of utter desperation,” Cathy says. “Our parenting skills were openly called into question, even though we’d raised three other children. We just didn’t know what to do.”

Teaching assistants were brought in to work with the boys on a one-to-one basis but they were, Cathy felt, babysitting rather than teaching the boys.

“Sam and Josh do not have learning disabilities; in fact, they are now on the Gifted and Talented register for maths and science,” she points out.

The boys were not diagnosed with ASC until they were six.

After they moved to a small specialist school where teachers understand their needs, Sam and Josh thankfully started to thrive. They now attend a secondary school that is residential from Monday to Friday. “They are home every Wednesday night for scouts, which has been a fantastic outlet for Sam especially,” Cathy says. “Sam has made amazing friends from mainstream schools, who completely support, understand and encourage him. He has done things we never thought he would be able to do, like a 12-mile walk, a two-day camping trip and throwing a tomahawk!”

As Sam and Josh grow up, it’s becoming apparent that sadly Josh has much more complex needs, and many challenges lie ahead.

As Dr Arichi notes, neurodevelopmental conditions like ASC or ADHD have a long-term, wide-ranging impact on the lives of children and their families, making research into this area as important as it is rewarding.

1. National Institute for Health and Care Excellence, Clinical Knowledge Summaries: Autism in Children https://cks.nice.org.uk/autism-in-children#!backgroundsub:2

2. Sayal, K., et al, ADHD in children and young people: prevalence, care pathways, and service provision. Lancet Psychiatry. 2018; 5(2): 175-186.