The Mummy's Club

In the study researchers recorded the speech of three groups of children aged 10-48 months: 106 ‘typically-developing’ young children, 49 children with language delay and 77 children diagnosed with autism. Their fully automated recording devices were able to determine differences in speech between the groups and accurately predict which children were from each group. The technique also follows the child in their natural home setting, providing the opportunity for efficient and effective speech assessment in a familiar environment.

This research is still in the early stages, and further study will determine how this system could work alongside other developmental assessment methods. So far, the system has not been investigated as a method for diagnosing new cases of language or developmental delay. Before it is introduced into practice, the uses and feasibility of this novel approach will need to be explored.

Where did the story come from?

The study was carried out by researchers from the Universities of Memphis, Chicago and Kansas and was funded by the Plough Foundation at the University of Memphis. It was published in the peer-reviewed scientific journal Proceedings of the National Academy of Sciences USA.

What kind of research was this?

This was an observational study that attempted to further the techniques used in researching speech and language development. The aim was to investigate an automated method for assessing young children’s speech development on a large scale by carrying out extended recordings in the homes of infants and young children. The main goal of the research was to isolate each child’s vocalisations from other voices and background noise on candid recordings and automatically identify significant features that could be useful predictors of the child’s developmental level.

What did the research involve?

To gather audio samples, the researchers provided parents with a battery-powered recorder that was then attached to their child’s clothing, recording the child in their natural environment all day. The children recorded were drawn from three different groups: those whose parents self-reported them to be typically-developing, those reported to have language delay and those reported to have autism.

Language delay was confirmed by checking for documentation in medical records or by assessment with a speech and language clinician, and autism was confirmed by checking medical records of the diagnosis. The final sample recorded featured a total of 232 children:

• 106 ‘typically-developing’ children aged 10-48 months
• 49 children with language delay aged 10-44 months
• 77 children with autism aged 16-48 months

The researchers carried out a total of 1,486 all-day recordings across the groups over the three years of the study, which provided a total of 23,716 hours of audio and captured a total of 3.1 million child utterances.

The recording devices were able reliably to differentiate between the child’s vocalisations and other sounds, allowing the researchers to carry out an in-depth analysis of the 12 parameters of speech known to have a role in speech development. These parameters included how the child was able to articulate each syllable, speech rhythm, pitch, their vocal characteristics and duration of speech.

The researchers looked at the relationship between a child’s overall vocalisations and the number of the 12 parameters that were as expected according to their age.

What were the basic results?

The researchers found that the automated analysis was able to predict development.

• In the typically-developing group all 12 of the parameters of speech were as expected according to their age.
• In the language-delayed group 7 of 12 parameters were as expected for their age.
• In the autism group few of the 12 parameters of speech were as expected according to age.

The study also found that in the typically-developing group certain vocal tendencies diminished with age, while this was not seen in the other groups. They also noted that children with autism tended to have quite unpredictable patterns of development, suggesting that they had different vocalisation from both typically-developing children and those with language delay.

Overall, the test correctly identified 90% of children who were in the ‘typically-developing’ group, 80% of those with autism and 62% of those with language delay.

How did the researchers interpret the results?

The researchers considered this research to be a ‘proof of concept’, a type of developmental project designed to test how well a conceptual method translates into real-world use. They demonstrated that their method of automated assessment was able to track children’s development on acoustic parameters known to play key roles in speech, and was also able to differentiate the vocalisations of children with autism or language delay from those of typically-developing children.

They conclude that their study of ‘automated analysis’ has the potential to advance research in speech and language development.

Conclusion

This was valuable research that has carried out extensive all-day recordings of children and found that the automated analyses of their vocalisations could distinguish between children with normal development, language delay and autism.

The advantage of this method is that it is completely automated, requiring no human intervention. As it follows the child in their home, it provides the opportunity for efficient and effective speech assessment in a familiar environment.

This research is still in the developmental stages. Further study will be needed to see how this recording system could supplement developmental assessment of children by health professionals and the standard screening and diagnostic procedures used.

So far, the system has only been used to detect previously-diagnosed conditions, and has not yet been tested as a means of identifying undiagnosed linguistic or developmental delay. This means the accuracy of the test needs further testing. Additionally, there are likely to be many other considerations to be addressed before this could be brought into practice, including the costs and feasibility of distributing recorders on a large scale and then having trained personnel available to interpret the data from these in-depth recordings.

As the researchers say, the ability to study linguistic development in natural home environments could provide a completely objective way of detecting speech-related disorders in early childhood. Such an advance would be a highly valuable medical tool for speech and language therapists.

Links To The Headlines

Autism detected in voice of children. The Daily Telegraph, July 20 2010

Speech pattern can give early clue to autism. The Independent, July 20 2010

Voice technology ‘could help detect autism’. BBC News, July 20 2010

Links To Science

Ollera DK, Niyogic P, Gray S et al. Automated vocal analysis of naturalistic recordings from children with autism, language delay, and typical development. PNAS, July 20 2010

This research compared the chemical profiles of urine samples from a small group of autistic children to those from their non-autistic brothers and sisters, and another group of unrelated non-autistic children. It did find that autistic children had differences in the levels of some chemicals, but those that were most different are not chemicals produced by gut bacteria.

This is encouraging research, but it is too early to say whether it will develop into another diagnostic tool for autism. Importantly, it did not directly investigate the role of gut bacteria in autism, but looked at levels of chemicals in urine. Also, it is not possible to determine whether these differences indicate a cause or consequence of autism. These children were already diagnosed with autism, and the study used urine samples from only one point in time. Further research in a larger group of children over time is needed.

Where did the story come from?

The study was carried out by researchers from Imperial College London and the University of South Australia. It was funded by Cure Autism Now and a grant from the International Study of Macro-Micronutrients and Blood Pressure. The study was published in the peer-reviewed Journal of Proteome Research.

The Daily Express reported that this study had distinguished children with autism by “looking at bugs from their intestinal tracts and the body’s metabolic process in their urine”. The Daily Mail reported that the test “builds on research showing that people with autism have different bacteria in their guts from others”. Additionally, The Daily Telegraph focused on the gut bacteria being a potential therapeutic target based on this research.

However, the research did not actually make any direct measurements of gut bacteria. The extent to which the chemical composition of urine reflects the bacterial population in the gut was not demonstrated in this study.

What kind of research was this?

This was a cross-sectional analysis, in which the researchers conducted chemical analysis of urine samples from children who had been diagnosed with autism, their non-autistic siblings and children without autism. The researchers aimed to assess whether there was any difference in the chemical composition of the urine samples from these children.

What did the research involve?

Urine samples from autistic children, their siblings and unrelated non-autistic children were obtained from the University of South Australia. Further urine samples from non-autistic children were also collected from Switzerland. The children were between three and nine years old. Children with autism met psychiatric criteria for autism disorder or Asperger syndrome.

There were 35 samples from autistic boys and four from autistic girls. The ‘sibling group’ was made up of 17 brothers of these children and 17 of their sisters. The control group consisted of 17 samples from non-autistic boys and 17 from non-autistic girls.

To identify the different types of chemicals in the children’s urine the researchers used a technique called nuclear magnetic resonance spectroscopy.

What were the basic results?

Initial analysis of the chemicals in the urine samples showed that the major source of variation between them was not related to autism, but variation between individuals. However, further statistical analysis indicated that the chemical pattern was different in the autistic children compared with non-autistic children and was partially different between the siblings and the non-autistic children.

The researchers then assessed whether the types of chemical found in the urine samples differed between each group. This analysis involved a statistical test that compared all of the chemicals in the children’s samples at the same time rather than assessing each chemical separately. This showed there were higher levels of some chemicals in autistic than non-autistic children, and vice versa.

For example, autistic children had higher levels of the breakdown products of nicotinic acid, N-methyl nicotinic acid (NMNA), and N-methyl nicotinamide (NMND), but lower levels of chemicals that are suggested to be associated with gut bacteria such as hippurate and phenylacetylglutamine (PAG).

The urine samples of the siblings of the autistic children were not significantly different to those of either of the other groups.

Statistical analysis of individual chemicals showed that autistic children had higher levels of NMNA and NMND compared with non-autistic children. NMNA and NMND, and succinate were also higher in the autistic children’s samples compared with those of their non-autistic siblings. Chemicals typically associated with gut bacteria, such as hippurate and phenylacetylglutamine (PAG), were no longer significantly different between autistic and non-autistic children.

How did the researchers interpret the results?

The researchers suggest that there are significant differences in the metabolic composition of urine between children with autism and unrelated non-autistic children. They say that the breakdown products of nicotinic acid (NMNA and NMND) were the group of chemicals that had the greatest power to indicate differences between autistic and non-autistic children.

However, they say that larger scale, longitudinal studies are needed to determine “whether the metabolic differences are related to the cause or the progression of the disease”.

Conclusion

This small study showed that there were differences between the chemicals in urine samples from autistic children compared with non-autistic children, however there was a degree of variation between all of the children’s samples regardless of whether they had autism or not. Further work is required to see whether the observed differences are consistent in a larger sample. Although the researchers suggest that some chemicals found in urine may be associated with bacteria in the gut, measuring chemicals in urine samples is an indirect way of assessing whether gut bacteria are associated with autism.

The research has several limitations:

• The researchers point out that, as it is not possible to tell whether these differences indicate a cause or consequence of the disease, further research is needed in a larger group of children over time.
• Different statistical analyses had different results, some showing differences in certain chemical levels in autistic children, while others did not.
• The researchers did not assess the medications the children with autism were taking for their condition or the diet they were following. Both would affect the chemicals they found in the children’s urine samples.

Finally, these children had already been diagnosed with autism, and the study design was cross-sectional, looking at their urine samples from only one point in time. It is not possible to say whether there would be any differences in the chemicals found in the urine in younger children prior to standard diagnosis, and whether it could be used as a diagnostic tool.

This is encouraging research, but it is too early to say whether this research would be of benefit in terms of providing an additional diagnostic tool for autism in children.

Links To The Headlines

Revolutionary urine test for autism could soon diagnose children with the condition. Daily Mail, June 4 2010

Autism test could make the condition ‘preventable’. The Daily Telegraph, June 4 2010

New test may spot autism in children. Daily Mail, June 4 2010

Links To Science

Yap IKS, Angley M, Veselkov KA, et al. Urinary Metabolic Phenotyping Differentiates Children with Autism from Their Unaffected Siblings and Age-Matched Controls. Journal of Proteome Research, 2010

The current study looked at more than 5,000 rare genetic differences (called copy number variations, or CNVs) in the DNA of 996 people with autistic spectrum disorders (ASD) and 1,287 people without the condition. It found that people with ASD had a greater number of genes affected by these differences than those without ASD. Some of the CNVs affected genes that were already thought to play a role in ASD, while others affected genes not previously known to play a role.

This important study provides a lot of information about genes that may play a role in the development of ASD. More research will be needed to examine these genes. While this may eventually suggest new targets for drug treatments, their development would still be some way off. The study also showed that different people with ASD had different sets of variations, suggesting that a single, universal genetic test for ASD is unlikely to be developed in the near future.

Where did the story come from?

The study was carried out by a large international consortium of researchers. The main funders were Autism Genome Project Consortium, Autism Speaks (US), the Health Research Board (Ireland), The Medical Research Council (UK), Genome Canada/Ontario Genomics Institute, and the Hilibrand Foundation (US). The study was published in the peer-reviewed journal Nature.

The Independent, Daily Mirror, The Guardian, Daily Mail and The Daily Telegraph have covered this research. The Mirror and Daily Mail suggest in their headlines that a new test for autism could be developed based on these results. Most of the other papers discussed this possibility in their articles. However, not all individuals with ASD carry the same genetic variations, meaning a single diagnostic test based on these results seems unlikely to be developed in the near future. At best, such a test might indicate the chance of developing ASD, but would not be able to predict definitively whether a person would or would not develop ASD. Much more research into how well such a test might perform would be needed before it could become a reality.

The Independent importantly highlights that caution should be applied when interpreting the implications of this study, which the researchers themselves describe as preliminary. They say that “it will take many more years of intensive investigation to understand and treat the genetic alterations that increase an individual’s susceptibility to the disorder”.

What kind of research was this?

This was a case-control study looking for genetic differences that could contribute to the development of autistic spectrum disorders. In particular, they were looking at sections of DNA that can exist in different numbers of copies in different individuals. These are called “copy number variations” or CNVs, and they can arise when pieces of DNA are duplicated or deleted. They wanted to determine whether individuals with autistic spectrum disorders have different numbers of copies at rare CNV sites than people without the condition.

This type of study design is commonly used to investigate the potential genetic causes of disease. This type of study has been made easier by advances in genetic technology, which means that researchers can now look for a large number of differences across multiple DNA samples in a relatively short space of time.

What did the research involve?

The researchers analysed DNA that was collected from 996 people with autistic spectrum disorders (ASD cases) and their parents, plus DNA from 1,287 matched individuals without ASD (the control group). To ensure that people’s ethnic backgrounds did not contribute to any genetic differences seen, the researchers only looked at people with European ancestry.

The researchers looked at CNV sites throughout the DNA and compared these between the cases and controls. They then specifically focused on 5,478 rare CNVs, which occurred in less than 1% of the sample population. They also looked for differences between cases and controls in the number of rare CNVs per individual, how long the CNV DNA regions were, or the number of genes affected by CNVs (that is, where the CNV was within or near to the gene).

What were the basic results?

The researchers found no differences between people with autistic spectrum disorders and controls in the number of CNVs per individual. Cases and controls each had 2.4 CNVs on average. There was also no difference between cases and controls in the length of their CNVs.

However, compared with controls, people with autistic spectrum disorders were found to have 19% more genes affected by CNVs (i.e. a CNV near to or within a gene). In some cases, these variations had been inherited from their parents. In other cases, the variations had arisen spontaneously in the affected individual.

Of the rare CNVs, 226 were found to affect a single gene and were found only in people with ASD, not the controls. Several of these CNVs were in genes or areas of the DNA previously thought to be involved in ASD or intellectual development. Some of the CNVs were in areas of the DNA containing genes not previously suspected to be involved in ASD. Other CNVs were in and around genes with roles in cell division, movement and signalling, and some played roles in nerve cells.

How did the researchers interpret the results?

The researchers concluded that their results “provide strong support for the involvement of multiple rare genic CNVs” in ASD. They say that this and subsequent research “may broaden the targets amenable to genetic testing and therapeutic intervention”.

Conclusion

There is much ongoing research into the genetic risk factors for complex conditions such as ASD, which is helping us to understand their role. One school of thought suggests that the genetic basis of these conditions is due to the cumulative influence of numerous common genetic factors contributing to the overall risk of developing the disease. The current study also suggests a role for rare copy number variations.

This particular study advances researchers’ knowledge of genes that may play a role in ASD, and they will use these results to target specific genetic areas for further study. Ideally, these results should now be verified by replicating the study in other groups of cases and controls.

Some news sources have suggested that these findings could lead to a test for ASD. However, not all individuals with ASD carry the same genetic variations, so a single diagnostic test based on these results seems unlikely in the near future. At best, such a test might indicate the chance of developing ASD, but it would not be able to predict definitively whether a person would or would not develop ASD. Much more research would be needed to look at the practical feasibility of a test, and how accurate and predictive such a test might be before it could become a reality.

Links To The Headlines

Autism and genetics: A breakthrough that sheds light on a medical mystery. The Independent, June 10 2010

Autism find could lead to new test. Daily Mirror, June 10 2010

The genetics of autism. The Guardian, June 10 2010

Autism study means scientists have genetic causes in their sights. The Guardian, June 10 2010

Autism blood test could be available in three years. Daily Mail, June 10 2010

Dozens of genetic mutations linked to autism in children discovered. The Daily Telegraph, June 10 2010

Links To Science

Pinto D, Pagnamenta AT, Klei L et al. Functional impact of global rare copy number variation in autism spectrum disorders. Nature, June 9 2010 [published online]