Tag: autism spectrum disorder

Categories : PaediatricsTags :

A Quantifiable Model to Explain the Development of Autism

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An explanatory model presented in a thesis from University of Gothenburg may make simplify the understanding of autism development. It provides new insights into how various risk factors give rise to autism and why there is such great variability between individuals.

Autism, a neurodevelopmental condition, affects how people perceive the world around them and how they interact and communicate with others. Among individuals with autism, there are major differences in terms of personal traits and manifestations alike. The disorder is therefore usually described as a spectrum, with numerous subtle variations.

While theoretical, the new explanatory model is also practical in application, since its various components are quantifiable through testing. The model describes various contributing factors and how they combine to prompt an autism diagnosis and cause other neurodevelopmental conditions.

Three contributing factors

The model links three contributing factors. Together, these result in a pattern of behaviour that meets the criteria for an autism diagnosis:

  1. Autistic personality – hereditary common genetic variants that give rise to an autistic personality.
  2. Cognitive compensation – intelligence and executive functions, such as the capacity to learn, understand others, and adapt to social interactions.
  3. Exposure to risk factors – for example, harmful genetic variants, infections, and other random events during gestation and early childhood that adversely affect cognitive ability.

“The autistic personality is associated with both strengths and difficulties in cognition but does not, as such, mean that diagnostic criteria are fulfilled. Still, exposure to risk factors that inhibit people’s cognitive ability may affect their capacity to tackle difficulties, which contributes to individuals being diagnosed with autism,” says Darko Sarovic, physician and postdoctoral researcher at Sahlgrenska Academy, University of Gothenburg, who wrote the thesis.

The model makes it clear that it is the many different risk factors combined that bring about the major differences among individuals on the spectrum. The various components of the model are supported by results from previous research.

Adaptive ability

High executive functioning skills may let people cover up their impairment, reducing their risk of meeting the diagnostic criteria for autism. This may explain why a lower degree of intelligence is observed among people diagnosed with autism, as well as other neurodevelopmental conditions. It also affords an understanding of why intellectual disability is more common among these groups. Thus, the model indicates that low cognitive ability is not part of the autistic personality but, rather, a risk factor that leads to diagnostic criteria being met.

“The autistic personality is associated with various strengths. For example, parents of children with autism are overrepresented among engineers and mathematicians. The parents themselves have probably been able to compensate for their own autistic personality traits and thus not met the criteria for an autism diagnosis. The impact of the disorder has then become more noticeable in their children owing, for instance, to an exposure to risk factors and relatively low cognitive ability,” Sarovic says.

Gender differences affect diagnosis

The diagnosis of autism is more common among boys than girls, and girls often get their diagnosis later in life. Some girls reach adulthood before being diagnosed, after many years of diffuse personal difficulties.

“Girls’ symptoms are often less evident to other people. It’s well known that girls generally have more advanced social skills, which probably means that they’re better at compensating for their own difficulties. Girls also tend to have fewer autistic traits and be less susceptible to the effects of risk factors. Accordingly, the model can help to answer questions about the gender gap,” Sarovic says.

Research and diagnostics

The model also proposes ways of estimating and measuring the three factors, enabling use of the model in research studies. Diagnostics is another conceivable area of ​​use. In a pilot study in which 24 participants had been diagnosed with autism and 22 controls had not, measuring the three factors of the model enabled more than 93% to be correctly assigned to the right category. The model can also be used to explain the inception of other neurodevelopmental disorders, such as schizophrenia.

Source: University of Gothenburg

Categories : NeurologyTags :

Hyperbaric Therapy Reduces Neuroinflammation in Autism

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A new study at Tel Aviv University showed significant improvements in social skills and the condition of the autistic brain through hyperbaric therapy. The study which is reported in the journal International Journal of Molecular Sciences, was conducted on lab models of autism.

Hyperbaric medicine, where patients sit in special high-pressure chambers while breathing pure oxygen, is considered safe and, besides treating decompression sickness in divers, is already in use for other conditions. The use of hyperbaric medicine to treat autism is contentious, with many holding that it is based on pseudoscience. In recent years, scientific evidence has been accumulating that unique protocols of hyperbaric treatments improve the supply of blood and oxygen to the brain, thereby improving brain function.

Changes observed in the brain included a reduction in neuroinflammation, which is known to be associated with autism. A significant improvement was also found in the social functioning of the animal models treated in the pressure chamber. The study’s success has many implications regarding the applicability and understanding of treating autism using pressure chamber therapy.

The breakthrough was led by doctoral student Inbar Fischer, from the laboratory of Dr Boaz Barak of Tel Aviv University.

Improved brain function

“The medical causes of autism are numerous and varied, and ultimately create the diverse autistic spectrum with which we are familiar,” explains Dr Barak. “About 20% of autistic cases today are explained by genetic causes, that is, those involving genetic defects, but not necessarily ones that are inherited from the parents. Despite the variety of sources of autism, the entire spectrum of behavioural problems associated with it are still included under the single broad heading of ‘autism,’ and the treatments and medications offered do not necessarily correspond directly to the reason why the autism developed.”

In the preliminary phase of the study, a girl carrying the mutation in the SHANK3 gene, which is known to lead to autism, received treatments in the pressure chamber, conducted by Prof Shai Efrati. After the treatments, it was evident that the girl’s social abilities and brain function had improved considerably.

In the next stage, and in order to comprehend the success of the treatment more deeply, the team of researchers at Dr Barak’s laboratory sought to understand what being in a pressurised chamber does to the brain. To this end, the researchers used lab models carrying the same genetic mutation in the SHANK3 gene as that carried by the girl who had been treated. The experiment comprised a protocol of 40 one-hour treatments in a pressure chamber over several weeks.

“We discovered that treatment in the oxygen-enriched pressure chamber reduces inflammation in the brain and leads to an increase in the expression of substances responsible for improving blood and oxygen supply to the brain, and therefore brain function,” explains Dr Barak. “In addition, we saw a decrease in the number of microglial cells, immune system cells that indicate inflammation, which is associated with autism.”

Increased social interest

“Beyond the neurological findings we discovered, what interested us more than anything was to see whether these improvements in the brain also led to an improvement in social behaviour, which is known to be impaired in autistic individuals,” adds Dr Barak. “To our surprise, the findings showed a significant improvement in the social behaviour of the animal models of autism that underwent treatment in the pressure chamber compared to those in the control group, who were exposed to air at normal pressure, and without oxygen enrichment. The animal models that underwent treatment displayed increased social interest, preferring to spend more time in the company of new animals to which they were exposed in comparison to the animal models from the control group.”

Inbar Fischer concludes, “the mutation in the animal models is identical to the mutation that exists in humans. Therefore, our research is likely to have clinical implications for improving the pathological condition of autism resulting from this genetic mutation, and likely also of autism stemming from other causes. Because the pressure chamber treatment is non-intrusive and has been found to be safe, our findings are encouraging and demonstrate that this treatment may improve these behavioral and neurological aspects in humans as well, in addition to offering a scientific explanation of how they occur in the brain.”

Source: Tel Aviv University

Categories : Obstetrics & Gynaecology PaediatricsTags :

No Link between Benzodiazepines Use in Pregnancy and Offspring Autism, ADHD

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A large-scale study published in JAMA Network has found no link between benzodiazepines use in pregnancy and subsequent autism spectrum disorder (ASD) or attention-deficit/hyperactivity disorder (ADHD) diagnoses in offspring. When comparing siblings, benzodiazepines use had no effect on ASD or ADHD risk, indicating that the mother’s genetics partly explained the increased risk.

Some 10–30% of pregnant women experience mental disorders, including mood or anxiety spectrum disorders, for which benzodiazepine agents are sometimes prescribed; this occurs in an estimated 1.9% of pregnancies globally.

The safety of these agents to the developing foetus and newborn has been called into question, since benzodiazepines are able to cross the placenta and have been found to be present in amniotic fluid and breast milk. The US FDA includes in the category of possible harm to the foetus.

While rodents studies have tested benzodiazepine exposure during the first trimester of pregnancy, investigations of neurodevelopmental outcomes in humans, such as ASD and ADHD, have been lacking.

One study found no significantly increased risks of ADHD symptoms or fine or greater motor deficits. Those researchers suggested the disorder resulting in benzodiazepine use might partly explain the increased risks. Maternal depressive and anxiety symptoms in pregnancy have also been linked to increased ADHD risk in children.

From the Taiwanese national health database, of over 1 .5 million children born full term who were younger than 14 years of age and followed up to 2017; 5.0% had been exposed to benzodiazepines in utero.

However, no differences were found with unexposed sibling controls during the same time frame for ADHD or ASD.

The researchers concluded that their results “challenge current assumptions of a potential association of neurodevelopmental disorders with maternal benzodiazepine use before or during pregnancy. Better identification of maternal mental health concerns, as well as possible interventions or provisions of guidance to build better nurturing and raising environments for newborns at risk, may be relevant to the prevention of adverse outcomes of neurodevelopmental disorders.”

Categories : NeurologyTags :

Exploring the Avoidance of Eye Contact in Autism

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A reluctance to make eye contact is a hallmark of autism spectrum disorder (ASD). By simultaneously imaging the brains of people making eye contact, Yale University researchers found that eye contact between two individuals was associated with a specific area associated with social interaction, which synchronises when two people with normal neural development gaze at each other. The results, published in the journal PLOS ONE, showed that in people with ASD, there was less activity in this region when they attempted eye contact.

People with ASD have been showed to have reduced or altered neurological arousal from looking at images of faces or even robots. Although eye contact is a critically important part of social interactions, scientists have been limited in studying the neurological basis of live social interaction with eye-contact in ASD because of the inability to image the brains of two people simultaneously.

Now, using an innovative technology that enables imaging of two individuals during live and natural conditions, Yale researchers have identified specific brain areas in the dorsal parietal region of the brain associated with the social symptomatology of autism. The study finds that these neural responses to live face and eye-contact may provide a biomarker for the diagnosis of ASD as well as provide a test of the efficacy of treatments for autism.

“Our brains are hungry for information about other people, and we need to understand how these social mechanisms operate in the context of a real and interactive world in both typically developed individuals as well as individuals with ASD,” said co-corresponding author Joy Hirsch, Elizabeth Mears and House Jameson Professor of Psychiatry, Comparative Medicine, and of Neuroscience at Yale.

The Yale team, led by Hirsch and James McPartland, Harris Professor at the Yale Child Study Center, analysed brain activity during brief social interactions between pairs of adults – each including a typical participant and one with ASD – using functional near-infrared spectroscopy, a non-invasive optical neuroimaging method. Both participants were fitted with neuroimaging caps which measured brain activity during face gaze and eye-to-eye contact.

The investigators found that during eye contact, participants with ASD had significantly reduced activity in a brain region called the dorsal parietal cortex compared to those without ASD. Further, the more severe the overall social symptoms of ASD as measured by ADOS (Autism Diagnostic Observation Schedule, 2nd Edition) scores, the less activity was observed in this brain region. Neural activity in these regions was synchronous between typical participants during real eye-to-eye contact but not during gaze at a video face. This typical increase in neural coupling was not observed in ASD, and is consistent with the difficulties in social interactions.

“We now not only have a better understanding of the neurobiology of autism and social differences, but also of the underlying neural mechanisms that drive typical social connections,” Hirsch said.

Source: Yale University

Categories : Gender Mental HealthTags :

Women with Autism have a Greater Mental Illness Risk

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Autistic young men and women are more affected by psychiatric conditions and have an increased risk of hospitalisation as a result of their mental illness. Autistic women are particularly vulnerable, as shown in a study published in JAMA Psychiatry.

Autistic people have an increased risk of suffering from mental illness. Current data indicates that autistic women are more vulnerable than autistic men, but few studies have been able to establish that there are sex differences.

The researchers, from Karolinska Institutet, conducted a register-based cohort study with more than 1.3 million people in Sweden who were followed from the age of 16 to 24 between 2001 and 2013. Just over 20 000 of these were diagnosed with autism.

“We saw an increased risk of eleven different psychiatric conditions, including depression, anxiety disorders, self-harm and difficulty sleeping,” says Miriam Martini, a doctoral student in psychiatric epidemiology at Karolinska Institutet and first author of the study.  

High hospitalisation rates 

Something that Miriam Martini finds particularly worrying is that 32 out of 100 autistic women had been hospitalised as a result of their mental illness, compared with 19 out of 100 autistic men. For non-autistic people, the corresponding figure was less than five out of 100.   

The study focuses on young adults who are at a crucial time in their life when many mental health problems increase, while the transition to adulthood often means poorer access to care, says Miriam Martini.   

“Healthcare for young adults needs to be expanded, especially for autistic women, so that mental illness can be detected in time to avoid worsening of symptoms resulting in hospitalization,” says Miriam Martini.  

The reason why autistic women are more affected by mental illness than autistic men is not clear, but in the study, the researchers point to several possible factors. Previous research has shown that autistic women to a greater extent use compensatory behaviours to camouflage their autism, which may be due to the fact that women generally tend to adapt to the expectations of those around them. This delays diagnosis and the provision of assistance, which can negatively affect their mental health.  

Overlooked by the healthcare system 

Another possible explanation may be that it could be difficult to detect autism in women using diagnostic criteria.  

“It may be that autism manifests differently in women than in men, which means that women are not detected using today’s diagnostic criteria. This is something we need to do more research on,” says Miriam Martini.  

Source: Karolinska Institutet

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