New insights into the mystery of autism: Could it be caused at birth by salt in the nerves?

 

Science Editor

High levels of salt in the nerve cells of newborn babies could be the crucial early trigger that results in autism later in childhood according to a study into the fundamental causes of the developmental disorder of the brain.

Scientists believe that high concentrations of chloride – the negatively charged salt ion found naturally within nerve cells – could be responsible for tipping the brain of a newborn child on the path towards autistic development.

Autism affects about one per cent of people and is a lifelong development disorder that begins in early childhood and affects how sufferers communicate and interact with other people. The spectrum of symptoms can range from relatively mild to very severe.

The origins of autism are not understood but in a series of ground-breaking experiments on mice, researchers believe they have found evidence to show how autism results from a failure to quickly lower levels of chloride ions within the neurons of the brain during birth.

Chloride ions are kept deliberately high in the neurons of the foetus while developing in the womb. Under normal birth conditions, however, chloride levels are quickly lowered during delivery, controlled by oxytocin, the birth hormone released by the mother during labour.

Oxytocin acts like a diuretic, reducing chloride levels within the neurons. However, a study by a team of French researchers found that when oxytocin is blocked, chloride ions continue to remain high after birth, which leads to a developmental disorder of the brain and autism.

They also showed that lowering chloride ions in a genetic strain of laboratory mouse that would otherwise develop an animal version of autism – by giving them a diuretic drug which made them lose chloride in their urine – effectively prevents them from developing the brain disorder later in life.

“During birth and delivery there is an extremely abrupt loss of chloride triggered by the release of oxytocin during labour. If you block oxytocin during delivery you block this protective mechanism,” said Yehezkel Ben-Ari of the French National Institute for Health and Medical Research (Inserm).

“Chloride levels during delivery are determinants of the occurrence of autism spectrum disorder,” said Professor Ben-Ari, who led the study published in the journal Science.

The findings could explain the results of a 2012 clinical trial involving 50 autistic children aged between three and eleven who were given the diuretic drug bumetanide, which  made them lose chloride ions in their urine. Their autistic symptoms improved during the treatment, Professor Ben-Ari said.

“We have proven the concept that in autism chloride is elevated and perhaps our diuretic acts by reducing that. The evidence was lacking until now,” he said.

“These data validate our treatment strategy, and suggest that oxytocin, by acting on the chloride levels during delivery modulates [and] controls the expression of autism spectrum disorder,” he added.

The study showed that diuretic drugs given to pregnant mice immediately prior to birth could effectively prevent autism developing in their autism-prone offspring.

“We showed that if you deliver diuretic to the mother before birth and delivery, then the offspring have so to speak been cured… whereas if you block oxytocin, you get autism,” Professor Ben-Ari said.

Although it would not be practical or safe to treat every pregnant women with diuretic drugs immediately before childbirth to try to prevent autism, he said the findings on mice suggest that it is important to diagnose children with autism as early as possible so that diuretics and behavioural therapy could be used together.

“The observation that a single treatment of the mother before delivery prevents the expression of… features of autism in offspring illustrates the importance of conditions at delivery…and the amazing long-term priming consequences of a wrong start,” he said.

“I think that an early diagnosis of autism spectrum disorder, coupled with a [diuretic] drug such as bumetanide or other regulators acting to reduce aberrant brain activities that perturb neuronal activities, are likely future therapies,” Dr. Ben-Ari said.

“Behavioural treatments might be reinforced by these pharmaceutical treatments and might facilitate their success, restoring communication with the child at an early age.”

Case study: Nick Gilling

Tessa Gilling, 46, from Leeds, has an autistic son, Nick, 15

"There’s been an awful lot of new research and findings done on autism so we have to take this latest one with a bit of caution. Nick has high-functioning autism and social interaction is one of his biggest problems. Someone compared having autism to be being thrown into a pool without any armbands and I think that’s a good way of explaining it. He has sensory difficulties, which means his sight and smell are much more prominent for him. We walked past a vegetable stall recently and he said the smells were too confusing for him.

He is wired in a very different way to most people. He has weaknesses, but then he does have some amazing strengths. He’s unbelievable musically – I came home one day and he was playing a song from Oliver on the piano.

There needs to be more support for people in Nick’s condition. He was badly bullied at school and the teachers didn’t think there was anything wrong with him because he used to mask how he was feeling. I suspect he won’t leave with any qualifications apart from music.

Nick’s a Young Campaigner for the National Autistic Society and the work he has done with them has benefited him a great deal.”

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