Tag: autism spectrum disorder

Categories : PaediatricsTags :

Anti-diarrhoeal Drug Loperamide Could Treat Autism Symptoms

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At present, there are no effective treatments for the core symptoms of autism spectrum disorder (ASD), which included difficulties with socialising and communicating. Using a computer analysis, researchers have discovered that a common anti-diarrhoeal drug may have potential in treating the social difficulties associated with ASD. Their findings are reported in the journal Frontiers in Pharmacology.

By looking at how different drugs affected ASD-related proteins in a computer model, they identified potential candidates to treat it. The most promising candidate was a commonly used antidiarrhoeal drug called loperamide was , and the researchers have an interesting hypothesis about how it may work to treat ASD symptoms, some of the most common of which involve difficulties with social interaction and communication.

“There are no medications currently approved for the treatment of social communication deficits, the main symptom in ASD,” said Dr Elise Koch of the University of Oslo, lead author on the study. “However, most adults and about half of children and adolescents with ASD are treated with antipsychotic drugs, which have serious side effects or lack efficacy in ASD.”

Repurposing drugs as new treatments

In an effort to find a new way to treat ASD, the researchers turned to drug repurposing, which involves exploring existing drugs as potential treatments for a different condition. The approach has plenty of benefits, as there is often extensive knowledge about existing drugs in terms of their safety, side-effects and the biological molecules that they interact with in the body.

To identify new treatments for ASD, the researchers used a computer-based protein interaction network. Such networks encompass proteins and the complex interactions between them. It is important to account for this complexity when studying biological systems, as affecting one protein can often have knock-on effects elsewhere.

The researchers constructed a protein interaction network that included proteins associated with ASD. By investigating existing drugs and their interaction with proteins in the network, the team identified several candidates that counteract biological process underlying ASD.

The most promising drug is called loperamide, which is commonly used for diarrhea. While it might seem strange that an anti-diarrhoeal drug could treat core ASD symptoms, the researchers have developed a hypothesis about how it may work.

From an upset gastrointestinal system to ASD

Loperamide binds to and activates a protein called the μ-opioid receptor, which is normally affected by opioid drugs, such as morphine. Along with the effects that you would normally expect from an opioid drug, such as pain relief, the μ-opioid receptor also affects social behavior.

In previous studies, genetically engineered mice that lack the μ-opioid receptor demonstrated social deficits similar to those seen in ASD. Interestingly, drugs that activate the μ-opioid receptor helped to restore social behaviors.        

These results in mice highlight the tantalising possibility that loperamide, or other drugs that target the μ-opioid receptor, may represent a new way to treat the social symptoms present in ASD, but further work is required to test this hypothesis. In any case, the current study demonstrates the power of assuming that old drugs may indeed learn new tricks.

Source: Frontiers Blog

Categories : Mental Health PaediatricsTags :

Half of Moms of Autistic Children Have High Depressive Symptoms

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About 50% of all mothers of children with autism spectrum disorder (ASD) had raised levels of depressive symptoms over 18 months, while rates were much lower (6% to 13.6%) for mothers with neurotypical children in the same period, according to a new study in Family Process.

Additionally, thought past studies suggest that having a parent with depression increases the child’s risk of mental health and behaviour problems, this study found something different.

“We found mothers’ higher symptoms of depression did NOT predict increases in children’s behaviour problems over time, including among families with a child with autism who experience a lot of stress,” said first author and UCSF Assistant Professor Danielle Roubinov. “That was surprising and good news.”

“Being the parent of a child with special needs is inherently challenging every day,” noted senior author UCSF Professor Elissa Epel. “It is a prototypical example of chronic stress, which is why we have been focusing on caregiving moms in our studies that examine effects of stress on health.”

“We already know from this sample that mothers with more depression tend to have signs of faster biological aging, such as lower levels of the anti-aging hormone klotho and older immune cells, on average,” added Prof Epel. “Here, we wanted to understand the impact of their depression on their child, and vice versa.”

A One-Way Street

Child behaviour problems predicted higher levels of maternal depression down the road, regardless of ASD status. The inverse effect was not seen, ie prior maternal depression didn’t predict later child behaviour problems.

Asst Prof Roubinov said that mothers of children with ASD need not feel guilty over their depressions impact on their children’s behaviours. “We hope these findings will reassure mothers that it’s both common to struggle with some depression in this high-stress situation of chronic caregiving, and that their depression likely isn’t making their child’s behavioural issues worse.”

Self-blame and guilt among parents of ASD children is common and predicts worsening depression and lower life satisfaction over time, the team’s past research shows.

In the current study, the researchers repeatedly measured maternal depression and children’s behaviour problems in 86 mother-child dyads across 18 months. Half of the mothers had children with ASD and half had neurotypical children. The children were aged 2–17 years old, with 75% being primary school age or younger.

Maternal depression was measured using the Inventory of Depressive Symptoms, a self-report scale completed by mothers. Child behaviour was measured through maternal report on the Child’s Challenging Behavior Scale, which focuses on externalising behaviours such as tantrums, aggression and defiance.

Few studies on maternal depression, child behaviour in ASD context

Bidirectional associations between maternal depression and child behaviour problems have been reported in prior research but few studies have examined these relationships in families with autism.

Families with autism tend to experience more marital conflict, lower relationship satisfaction, and many other challenges, said Ass Prof Roubinov, noting that a “stressful family environment may spill over onto family members” and changing their interactions. “We wanted to see whether the link between maternal and child mental health was different in the context of a high-stress family system, such as when a child has autism.”

Although the study acknowledged that families with a child with ASD experience high levels of stress, the authors were cautious to note that stress is not their only defining characteristic.

“Many mothers of children with autism also report high levels of emotional closeness and positive interactions with their children,” Asst Prof Roubinov said. “These are important experiences that supportive programs can build upon.”

The researchers offered mindfulness classes after the study to the participants to help manage parenting stress, and this improved their mental health.

It is important to experience and notice positive emotions and joy, despite having a more challenging life situation, said Prof Epel.

“Given the effects of chronic stress on health and mood, caregiving parents need extraordinary emotional support in addition to the special services for their child,” she said. “It’s as vital to provide support for parents’ mental health as it is for children’s mental health.”

Physicians should be on the lookout for parental distress and ready to offer resources for parents, especially for parents of special needs children, she said. The researchers said future studies should also look at associations between maternal depression and children’s internalising symptoms (eg, withdrawal, anxiety, emotional reactivity).

Source: University of California – San Francisco

Categories : GeneticsTags :

Identification of 60 Autism-linked Genes Sheds More Light on the Condition

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A new study published in Nature Genetics has revealed 60 genes linked to autism spectrum disorder (ASD) that may provide important clues to the causes of autism across the full spectrum of the disorder. Five of these genes are heritable instead of new mutated versions, helping explain why autism appears to run in some families.

“Overall, the genes we found may represent a different class of genes that are more directly associated with the core symptoms of ASD than previously discovered genes,” said Professor Wendy Chung, MD, PhD.

Previously, several genes have been linked to autism and as a group are responsible for about 20% of all cases. Most individuals who carry these genes have profound forms of autism and additional neurological issues, such as epilepsy and intellectual disability.

To uncover hidden autism genes that can explain the majority of cases, the researchers tapped into data from nearly 43 000 people with autism.

Five of the genes identified by the new study have a more moderate impact on autism characteristics, including cognition, than previously discovered genes.

“We need to do more detailed studies including more individuals who carry these genes to understand how each gene contributes to the features of autism, but we think these genes will help us unravel the biological underpinnings that lead to most cases of autism,” Prof Chung said.

The five newly identified genes also explain why autism often seems to run in families. Unlike previously known autism genes, which are due to de novo mutations, genetic variants in the five new genes were often inherited from the participant’s parents.

Prof Chung said that many more moderate-effect genes are yet to be discovered, which would help researchers better understand the biology of the brain and behaviour across the full spectrum of autism.

Source: EurekAlert!

Categories : Lab Tests and Imaging NeurologyTags :

Retinal Scans May be Able to Detect ASD and ADHD

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By measuring the electrical activity of the retina in responses to a light stimulus, researchers found that they may be able to neurodevelopmental disorders such as ASD and ADHD, as reported in new research published in Frontiers in Neuroscience.

In this groundbreaking study, researchers found that recordings from the retina could identify distinct signals for both Attention Deficit Hyperactivity Disorder (ADHD) and Autism Spectrum Disorder (ASD) providing a potential biomarker for each condition.

Using the ‘electroretinogram’ (ERG) – a diagnostic test that measures the electrical activity of the retina in response to a light stimulus – researchers found that children with ADHD showed higher overall ERG energy, whereas children with ASD showed less ERG energy.

Research optometrist at Flinders University, Dr Paul Constable, said the preliminary findings indicate promising results for improved diagnoses and treatments in the future.

“ASD and ADHD are the most common neurodevelopmental disorders diagnosed in childhood. But as they often share similar traits, making diagnoses for both conditions can be lengthy and complicated,” Dr Constable says.

“Our research aims to improve this. By exploring how signals in the retina react to light stimuli, we hope to develop more accurate and earlier diagnoses for different neurodevelopmental conditions.

“Retinal signals have specific nerves that generate them, so if we can identify these differences and localise them to specific pathways that use different chemical signals that are also used in the brain, then we can show distinct differences for children with ADHD and ASD and potentially other neurodevelopmental conditions.”

“This study delivers preliminary evidence for neurophysiological changes that not only differentiate both ADHD and ASD from typically developing children, but also evidence that they can be distinguished from each other based on ERG characteristics.”

According to the World Health Organization, one in 100 children has ASD, with 5–8% of children diagnosed with ADHD.

Attention Deficit Hyperactivity Disorder (ADHD) is a neurodevelopmental condition characterised by being overly active, struggling to pay attention, and difficulty controlling impulsive behaviours. Autism spectrum disorder (ASD) is also a neurodevelopmental condition where children behave, communicate, interact, and learn in ways that are different from most other people.

Co-researcher and expert in human and artificial cognition at the University of South Australia, Dr Fernando Marmolejo-Ramos, says the research has potential to extend across other neurological conditions.

“Ultimately, we’re looking at how the eyes can help us understand the brain,” Dr Marmolejo-Ramos says.

“While further research is needed to establish abnormalities in retinal signals that are specific to these and other neurodevelopmental disorders, what we’ve observed so far shows that we are on the precipice of something amazing.

“It is truly a case of watching this space; as it happens, the eyes could reveal all.”

Source: Flinders University

Categories : PaediatricsTags :

Analysis Finds that Early Interventions in Autism are Effective

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In a Cochrane analysis of therapeutic or educational interventions for very young children with or at high likelihood for autism, researchers found that certain types of interventions were beneficial. The analysis, published in Developmental Medicine & Child Neurology, included seven reviews which summarised the results of 63 studies from 2009 to 2020.

The analysis found that naturalistic developmental behavioural interventions, developmental interventions, and behavioural interventions were effective.

Heterogeneity in design, intervention and control group, dose, delivery agent, and measurement approach was noted. Inconsistent methodological quality and potential biases were identified.

“We have a growing evidence base that supports the importance of early intervention and its ability to promote communication, adaptive behavior, and facilitate social interactions and relationships. However, there are limitations to this evidence base, which leaves families with some work to do in order to understand which approach is the best fit for themselves, their child, or their family,” said lead author Lauren Franz, MBChB, MPH, of Duke University Medical Center.

Source: Wiley

Categories : Gastrointestinal Mental Health PaediatricsTags :

GI Issues and Anxiety Linked in Children with Autism

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A new study has found a bi-directional relationship between gastrointestinal (GI) issues and internalised symptoms such as anxiety in children and adolescents with autism, which means the symptoms seem to be affecting each other. The findings could inform future precision medicine research aimed at developing personalised treatments for people with autism experiencing gastrointestinal issues. The study appears in the Journal of Autism and Developmental Disorders.

Autism is known to be often associated with GI issues, and is often overlooked in children despite being a source of pain and anxiety. Food preferences are often for carbohydrates and processed foods. The most common cause of GI issues in children with autism are abdominal pain, constipation, chronic diarrhea and gastroesophageal reflux disease (GERD).

“Research has shown gastrointestinal issues are associated with an increased stress response as well as aggression and irritability in some children with autism,” said Brad Ferguson, an assistant research professor. “This likely happens because some kids with autism are unable to verbally communicate their gastrointestinal discomfort as well as how they feel in general, which can be extremely frustrating. The goal of our research is to find out what factors are associated with gastrointestinal problems in individuals with autism so we can design treatments to help these individuals feel better.”

In the study, Ferguson and his team analysed health data from more than 620 under-18 patients with autism who experience gastrointestinal issues. Then, the researchers examined the relationship between the GI issues and internalised symptoms. Ferguson explained the findings provide more evidence on the importance of the ‘gut–brain axis’ in GI disorders in individuals with autism.

“Stress signals from the brain can alter the release of neurotransmitters like serotonin and norepinephrine in the gut which control gastrointestinal motility, or the movement of stool through the intestines. Stress also impacts the balance of bacteria living in the gut, called the microbiota, which can alter gastrointestinal functioning,” Ferguson said. “The gut then sends signals back to the brain, and that can, in turn, lead to feelings of anxiety, depression and social withdrawal. The cycle then repeats, so novel treatments addressing signals from both the brain and the gut may provide the most benefit for some kids with gastrointestinal disorders and autism.”

Ferguson is collaborating with David Beversdorf, a neurologist who also studies gastrointestinal problems in individuals with autism. Beversdorf had recently helped identify specific RNA biomarkers linked with gastrointestinal issues in children with autism.

“Interestingly, the study from Beversdorf and colleagues found relationships between microRNA that are related to anxiety behaviour following prolonged stress as well as depression and gastrointestinal disturbance, providing some converging evidence with our behavioural findings,” Ferguson said.

Ferguson and Beversdorf are now together investigating the effects of a stress-reducing medication on GI issues in a clinical trial. Ferguson cautioned that treatment could be effective for certain people with autism but not others.

“Our team uses a biomarker-based approach to find what markers in the body are common in those who respond favourably to certain treatments,” Ferguson said. “Our goal is to eventually develop a quick test that tells us which treatment is likely to work for which subgroups of patients based on their unique biomarker signature, including markers of stress, composition of gut bacteria, genetics, co-occurring psychological disorders, or a combination thereof. This way, we can provide the right treatments to the right patients at the right time.”

Source: University of Missouri-Columbia

Categories : NeurologyTags :

Mental Processing of Autistic and Non-autistic People is Similar

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Findings published in Journal of Psychopathology and Clinical Science reveal there are fundamental similarities between autistic and non-autistic people in mental processing. The study findings were made available online ahead of ahead of World Autism Day on the 2nd of April.

The brain uses two systems to process information: System 1 for quicker intuitive judgements, and System 2 for slower rational thinking. In autistic people, these systems are thought to work differently ad underlie difficulties they may have in daily life and the workplace.

Yet, this landmark study reports that these fundamental psychological systems are not impaired in autistic people as once thought. The study, involving more than 1000 people, tested the link between autism and ‘quick’ intuitive and ‘slow’ rational thinking.

In three experiments, they analysed the link between autistic personality traits and thinking style. In the fourth, they compared 200 autistic and over 200 non-autistic people. Overall, their results showed that autistic people think as quickly and as rationally as non-autistic people.

Based on these findings, the researchers conclude that certain, fundamental mental processes are more similar between autistic and non-autistic people than prior belief. In light of these findings, they call for a shift in the way that society thinks about autism as a mental processing disorder.

They also recommend that it might be important to redesign educational, clinical, and workplace support for autistic people and their families. Support should be much more targeted, instead of assuming that autistic people all have mental processing difficulties, they say.

The research team argue that the requirement to make ‘reasonable adjustments’ such as allowing extra time in exams and extending deadlines, is not an evidence-based way to support neurodivergent people.

Instead, more fundamental changes could be necessary – for example, changing social and sensory environments, making them more equitable autistic people.

Source: University of Bath

Categories : Neurology PaediatricsTags :

Amygdala Enlargement in Kids with ASD Starts Early

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The amygdala, which is enlarged in two-year-old children with autism spectrum disorder (ASD), begins its accelerated growth between 6 and 12 months of age, suggests a study appearing in the American Journal of Psychiatry. The findings indicate that therapies to reduce the symptoms of ASD might have the greatest chance of success if they begin in the first year of life, before the amygdala begins its accelerated growth.

The amygdala, which is involved in processing emotions, such as interpreting facial expression in typically developing children increases substantially in volume from 7.5 to 18.5 years of age. The amygdala in children with autism is initially larger, but does not undergo the age-related increase observed in typically developing children.

The study included 408 infants, 270 of whom with an increased ASD risk from having an older sibling with ASD, 109 typically developing infants, and 29 infants with Fragile X syndrome. The researchers conducted MRI scans of the children at 6, 12 and 24 months of age. They found that the 58 infants who went on to develop ASD had a normal-sized amygdala at 6 months, but an enlarged amygdala at 12 months and 24 months. Moreover, the faster the rate of amygdala overgrowth, the greater the severity of ASD symptoms at 24 months. The infants with Fragile X syndrome had no differences in amygdala growth but enlargement of the caudate, which was linked to increased repetitive behaviours.

The researchers suggested that difficulty in processing sensory information during infancy may stress the amygdala, leading to its overgrowth.

Source: NIH

Categories : Substance UseTags :

Many Youths with Substance Use Disorder Also Have Autism Traits

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One in five teens and young adults seeking treatment for substance use may have traits characteristic of a previously unrecognised autism spectrum disorder (ASD), according to a study by researchers at Massachusetts General Hospital (MGH).

The study, published in The American Journal on Addictions, found that among patients with an average age of 18.7 years being treated in an outpatient substance use disorder (SUD) clinic, 20% had elevated scores on the Social Responsiveness Scale-2 (SRS-2), a parent- or teacher-reported measure that has been shown to reliably identify the presence and severity of social impairment among individuals along the autism spectrum, and to distinguish autism from other disorders.

Lead author James McKowen, PhD, said this is the first study examining the prevalence of autistic traits among young people with SUD.

“Usually studies of substance use disorder in autism are done in those with an autism diagnosis already,” he said. “We have looked at this question from the other side, asking how many people with substance use disorder have autism.”

The researchers asked parents of 69 youths reporting for the first time to a specialty outpatient psychiatric SUD clinic to fill out the SRS-2 form. The form is designed to measure an individual’s social awareness, cognition, communication and motivation, and restricted interests and repetitive behaviours.

Though few differences were found between those with elevated autistic trait scores and those with lower, non-autistic scores in terms of demographic or psychiatric factors, adolescents with higher SRS-2 scores had a nearly eightfold higher likelihood of stimulant use disorder, and a fivefold higher risk for opioid use disorder.

According to the researchers, the findings highlight the importance of assessing patients in a SUD treatment setting for autistic traits.

“For clinicians, the big takeaway point from this study is that we need to get better at screening and certainly training in the presence of autism spectrum disorder,” said Dr McKown. Clinicians treat the SUD “but don’t have specialty developmental training, particularly for issues around autism.”

The researchers are developing a free clinical therapy protocol that can help clinicians better address the issues of autistic traits in patients with SUD.

Source: Massachusetts General Hospital

Categories : Neurology PaediatricsTags :

Scientists Find Epilepsy Biomarker in Autistic Children

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Scientists have discovered that an important brain protein that quiets overactive brain cells and is abnormally low in children with autism, which may explain why so many children with autism also have epilepsy. The findings were published in Neuron.

This protein can be detected in the cerebrospinal fluid, making it a promising marker to diagnose autism and potentially treat the epilepsy that accompanies the disorder.

Mutated versions of this gene were known to cause autism combined with epilepsy, and epilepsy appears in 30% to 50% of children with autism. Autism, which is 90% genetic, affects 1/58 children in the US.

Appropriately nicknamed ‘catnap2’, the protein, CNTNAP2, is produced by the brain cells when they become overactive. Because the brains of children with autism and epilepsy lack sufficient CNTNAP2, scientists found, their brains become overactive, leading to seizures.

For the study, the researchers analysed the cerebrospinal fluid in individuals with autism and epilepsy, and in mouse models. Though, cerebrospinal fluid has been used in researching disorders such as Parkinson’s, this is the first study showing it is an important biomarker in autism.

The new finding about CNTNAP2’s role in calming the brain in autism and epilepsy may lead to new treatments.

“We can replace CNTNAP2,” said lead study author Peter Penzes, the director of the Center for Autism and Neurodevelopment at Northwestern University Feinberg School of Medicine. “We can make it in a test tube and should be able to inject it into children’s spinal fluid, which will go back into their brain.”

Penzes’ lab is currently working on this technique in preclinical research.

The level in the spinal cord is proxy for the level in the brain, explained Penzes. When brain cells are too active because of overstimulation, they produce more CNTNAP2, which floats away and binds to other brain cells to calm them. The protein also leaks into the cerebrospinal fluid, where scientists were able to measure it, giving them a clue for how much is produced in the brain.

Source: EurekAlert!