Researchers at the University of California, San Diego School of Medicine have shed new light on the changes in metabolism that occur between birth and the presentation ofautism later in childhood.
Researchers have found that a small number of biochemical pathways are responsible for most of these changes, which could help shape new strategies for early diagnosis and prevention of autism spectrum disorder (ASD).
The study was published in the journal Communications Biology .
“At birth, the physical appearance and behavior of a child who will develop autism in the next few years are indistinguishable from those of a neurotypical child. Indeed, in most cases, the child’s fate regarding autism is not determined at birth,” said Robert Naviaux, M.D., Ph.D., professor in the Departments of Medicine, Pediatrics and Pathology at the School of Medicine from UC San Diego.
“We are starting to understand the dynamics that govern the transition from risk to the actual appearance of the first symptoms of ASD. Early diagnosis opens the possibility for early intervention and optimal outcomes.”
ASD is a developmental disorder characterized by difficulties in socialization and communication, as well as repetitive and/or restrictive behaviors. For most people with ASD, the condition represents a significant disability, with only 10-20% of children diagnosed before age 5 years able to live independently as adults.
While autism is known to have strong genetic risk factors, there are also environmental risk factors that play a role in the development and severity of ASD. Naviaux and other researchers are finding that the development of autism is governed by the real-time interaction of these various factors. By studying the developmental biology of metabolism and its differences in autism, new insights into ASD and other complex developmental disorders are emerging.
“Behavior and metabolism are linked: you can’t separate them,” Naviaux added.
To learn more about the early metabolic changes that occur in children with autism, researchers studied two groups of children. One cohort consisted of newborns, in whom autism could not be detected. The second group consisted of 5-year-olds, some of whom had been diagnosed with autism.
Comparing the metabolic profiles of children in the group who were ultimately diagnosed with autism with those who had developed a neurotypical, they found striking differences. Of the 50 different biochemical pathways studied by the researchers, only 14 were responsible for 80% of the metabolic impact of autism.
The most modified pathways are related to the cellular response to danger, a natural and universal cellular reaction to injury or metabolic stress. The body has biochemical protections that can shut down the cellular response to danger once the threat has passed, and Naviaux hypothesizes that autism occurs when these defenses fail to develop normally. The result is increased sensitivity to environmental stimuli, and this effect contributes to sensory sensitivity and other symptoms associated with autism.
“Metabolism is the language that the brain, gut and immune system use to communicate, and autism occurs when the communication between these systems is changed,” Naviaux added.
The cellular response to danger is regulated primarily by adenosine triphosphate (ATP), the body’s chemical energy currency. Although these ATP signaling pathways do not develop normally in autism, they may be partially restorable with existing medications. In 2017, Naviaux and his team completed the first clinical trials for suramin, the only drug approved in humans that can target ATP signaling and is normally used to treat African sleeping sickness.
Now, the researchers hope that by revealing the specific ATP-related pathways that are altered in autism, their work will help scientists develop more drugs targeting these pathways to manage ASD symptoms.
“Suramin is just a drug that targets the cellular danger response,” he said. “Now that we are taking a closer look at how metabolism changes in ASD, we may be at the beginning of a drug renaissance that will create new treatment options that have never existed before.”
The first signs of autism
When children suffer from autism it is possible to recognize the symptoms as early as 18 months. While a doctor is needed to diagnose the condition, parents and caregivers should be aware of the signs, advises the Autism Research Institute, offering a few other tips for noticing early symptoms.
Children with autism may exhibit a variety of social, communication, and behavioral symptoms.
This can include difficulties communicating with other people, which often manifests itself during early childhood, according to the California-based institute.
A qualified specialist can evaluate any delays in language development and nonverbal communication.
Another clue can be the tone of voice. According to the institute, some people with autism may have difficulty regulating or modulating their tone of voice. They may speak too loudly, too softly, or in a monotone voice.
Poor eye contact or avoiding eye contact is another common symptom. A child with autism may also have difficulty recognizing and using facial expressions, physical gestures, and body language in general.
Repetitive behaviors are common behavioral symptoms, which may include rocking, spinning, or flapping the hands and arms or shaking the fingers in front of the eyes.
Children with autism may also play with toys or other objects in atypical ways. This might include repeatedly flipping light switches or tirelessly flipping coins.
Ritualistic behaviors, such as eating the same foods at every meal or getting angry immediately after any change in plans, may be another sign.
Some people on the autism spectrum may hurt themselves by banging their head against a wall, biting their hands, or scratching their skin. The institute notes that there are many medical, sensory, nutritional and behavioral approaches to treating these behaviors.
Parents should speak to their child’s doctor immediately if their child is engaging in self-harm.
Some conditions can occur along with autism, including seizures, sensory sensitivity, anxiety, sleep disturbances, and gastrointestinal, metabolic, and immune dysregulation. Call your doctor to diagnose autism and treat co-occurring behaviors and conditions.
Adults with these symptoms may also be diagnosed as autistic. This is likely due to increased awareness and screening.
Connection between repetitive behaviors and intestinal problems
In children with autism, repetitive behaviors and gastrointestinal problems may be linked. One study found that greater severity of other autism symptoms was also associated with more severe constipation, stomach pain and other intestinal problems.
The research, published in the journal Autism, found no association between social and communication difficulties and gastrointestinal symptoms.
The study does not explain the biological mechanism for the relationship between repetitive behaviors, such as rocking back and forth and hand flapping, and intestinal problems. But it helps establish that gastrointestinal symptoms can exacerbate repetitive behaviors, or vice versa, a finding that could one day help lead to helpful interventions, said Payal Chakraborty, a graduate student at the Ohio State University College of Public Health who led I study.
Children with autism spectrum disorder are more likely than their typically developing peers to experience a variety of gastrointestinal abnormalities, including chronic diarrhea, constipation, food sensitivities, and abdominal pain.
These symptoms have been associated with higher levels of irritability and aggressive behavior, but less is known about their relationship to other symptoms of autism spectrum disorder.
“In the general population, there is a fair amount of evidence about the connection between mood, mental disorders and gastrointestinal difficulties. In autism, we ask whether the gut problems experienced by children are a core part of the disease itself or whether they are caused by other symptoms experienced by children with autism,” Chakraborty said.
Chakraborty began the study as a student at Duke University, where she worked at the Center for Autism and Brain Development and became interested in the potential connection between the gut and other features of developmental disabilities.
Using data from a study designed to test the feasibility of cord blood transplants as a treatment for autism, Chakraborty examined detailed clinical measures and reports provided by the families of 176 children between the ages of two and seven to see if he could find some insight into this. the causes of gastrointestinal problems. Almost all children, 93%, had at least one gastrointestinal symptom.
“Gastrointestinal problems are a significant problem for many people with autism, and there is evidence that these symptoms may exacerbate some autistic behaviors, which can lead to greater developmental challenges,” she said.
The details of the relationship are unclear, but it’s possible that repetitive behaviors in children with autism may be a coping mechanism that helps them manage their gastrointestinal distress, Chakraborty said, adding that autism symptoms often emerge in a moment in which children are unable to adequately communicate their physical suffering with words.
“Gastrointestinal problems are a major concern for many children with autism, and we still have much to learn about the complicated gut/brain axis,” she said.
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