Posted on Autism

New research suggests that the number of people with autism could be double the previous estimates.

The true number of autistic people in England may be more than double the number often cited in national health policy documents, suggests a new study by UCL researchers.

To do this, the researchers calculated the number of people who had received an autism diagnosis from anonymised data from more than 5 million individuals registered at GP practices in England between 2000 and 2018. 

They then compared these figures with a lower (c.1%) and upper (c.3%) estimate of how common autism really is in the population.

The lower estimate was based on the widely stated figure that around 1% of people in England are autistic. This came from epidemiological research published in 2011, before changes to the diagnostic criteria for autism that made them more inclusive.

Meanwhile, the upper estimate was based on rates of diagnosed autism in young people (aged 10-19) in the researchers’ dataset. This is because young people are most likely to have had their autism recognised since providers are now very aware of autism in young people.

The team’s estimates suggest that between 150,000 and 500,000 people aged 20 to 49 years-old may be autistic but undiagnosed. Meanwhile, between 250,000 and 600,000 autistic people over the age of 50 may be undiagnosed – more than 9 in 10 of all autistic people.

The midpoint of these figures translates to approximately 750,000 undiagnosed autistic people aged 20 and above, in England. This brings the total autistic population to over 1.2million – approaching double the figure of 700,000 cited by the government for the entirety of the UK*.

Now researchers are calling for better access to diagnostic services for adults, and better support after diagnosis.

They also want to encourage greater acceptance and understanding of neurodiversity in society.

Lead researcher, post-doctoral researcher Elizabeth O’Nions (UCL Psychology & Language Sciences), said: “Historically, autism has been considered as a condition of childhood. But recently, awareness has been growing that it is present across the lifespan – in adults as well as young people.

“Nevertheless, autism is still under-recognised in adults. Our estimates suggest that about 180,000 people aged 20-plus had an autism diagnosis as of 2018, meaning that most autistic adults in England were undiagnosed.

“This matters because autistic people often experience discrimination and exploitation in society. They may have unmet support needs, even when they appear to be coping with life.

“Having a diagnosis means that someone can advocate for their right to reasonable adjustments and the support they need. Recognising that someone with an intellectual disability is autistic can also help people to understand and support them better.”

Autistic people may exhibit signs such as differences in their social communication and social interaction, alongside restricted and repetitive patterns of behaviours, interests and activities.

Many autistic people require adjustments to be made to ensure equal access healthcare, employment, and local authority support.

Dr O’Nions added: “Our findings indicate that there is still a substantial diagnostic gap in adults compared to children and young people when it comes to autism in England.

“This may partly reflect a lack of awareness and understanding of autism in adults on the part of healthcare professionals. Older adults may also be less likely to self-identify as autistic, meaning that they do not come to the attention of services.

“Meanwhile, providers may be hesitant to raise the issue of autism given the uncertainty around waiting times for a diagnosis and the availability of support or specialist services post-diagnosis.”

Posted on Multiple Sclerosis

“A study on discontinuing therapy for multiple sclerosis (MS) patients over the age of 55 is being led by a professor at the University of Colorado.”

Tie One on for Multiple Sclerosis

Multiple sclerosis (MS) is a chronic illness that often begins in young adulthood. At the onset, individuals commonly experience acute attacks, or relapses, of intermittent new neurological symptoms such as vision changes, numbness, and weakness. These symptoms may come and go randomly and then either remit completely or incompletely. These relapses are associated with changes in the brain or spine as shown by Magnetic Resonance Imaging (MRI). As people age, new attacks and MRI changes become less common. Patients may stabilize or enter a phase of slow progressive neurological disability with minimal MRI changes.

There is no cure for MS, but there are over 20 disease-modifying therapies (DMTs) that can reduce the risks of new attacks and MRI changes. Most DMTs have been approved for patients 55 and under, with the greatest impact on younger patients and modest effects on older patients. It’s unclear if older patients benefit, and risks may increase with age. Whether to stop DMTs as people age is an important, unanswered question.

The article discusses the results of a clinical trial called DISCOMS, which looked at discontinuing MS disease-modifying therapies (DMTs). The study included 259 participants over 55 years old who had not experienced an MS relapse for at least five years and had no new MRI lesions for at least three years. The trial found that discontinuing DMTs could be inferior to staying on the treatment, as there were more new events in the discontinuation group. However, there was no increase in disability, symptom scores, cognitive tests, or adverse events among those who stopped DMT.

John R. Corboy, MD, a professor of neurology at the University of Colorado School of Medicine, led the study and authored the article. “Our study addresses important concerns about the risks and benefits of disease-modifying therapies as people age. The primary objective of our study was to determine whether it is safe to consider discontinuing treatment for older patients with multiple sclerosis who have had no recent relapse or new MRI activity. Our goal was to provide an estimate of disease recurrence in this context,” Corboy said. He and his colleagues concluded that, while they were unable to demonstrate non-inferiority in the primary outcome, many patients aged 55 and older who have not had a relapse for five or more years might find the low risk of new clinical activity makes a personal discontinuation trial a reasonable option for them.

Posted on Multiple Sclerosis

“Multiple sclerosis: Myelin could be harmful to nerve fibres.”

Cross-sectional electron micrographs of individual nerve fibers in MS brain biopsies

The series of images display cross-sectional electron micrographs of individual nerve fibres in brain biopsies of individuals with multiple sclerosis. The images show axons with myelin sheaths (depicted as black rings), illustrating increasingly severe damage from images 1 to 8. The spectrum of damage ranges from the accumulation of individual cellular components in otherwise bright, intact axons (image 1) to advanced degeneration in irreversibly damaged, dark axons (image 8). Photo credit: Leipzig University

Multiple sclerosis (MS) is a serious neurological disease that often leads to permanent disability. It affects approximately 2.9 million people worldwide, with 240,000 cases in Germany alone. The exact cause of the disease is not yet clear, but a key characteristic is the loss of the protective myelin coating on nerve connections in the central nervous system. This loss is caused by autoimmune processes. The myelin is created by specialized glial cells called oligodendrocytes and allows for fast transmission of nerve impulses. In MS, it is believed that immune cells break down oligodendrocytes and myelin, leading to irreversible damage to the vulnerable nerve connections. The loss of these nerve connections is a major factor in the severity and progression of MS.

Recent research suggests that our understanding of diseases needs to change. Myelin, previously thought to be only protective, can actually threaten the survival of axons when attacked by immune cells. Oligodendrocytes not only form myelin but also support the energy metabolism of axons. Myelinated axons rely on metabolic support and need intact myelin architecture for maintenance.

“When oligodendrocytes are exposed to an acute inflammatory environment, they may lose their ability to support the axons, and myelin becomes a threat to the survival of the axons,” says Professor Klaus-Armin Nave from the Max Planck Institute for Multidisciplinary Sciences in Göttingen, Germany. To test their hypothesis, the researchers examined tissue samples from patients with multiple sclerosis, as well as various mouse models of this disease in order to experimentally simulate the autoimmune attack on myelin. For the first time, the researchers were able to demonstrate by electron microscopy in the tissue samples of the patients that irreversible damage almost always occurs in the axons that are still coated with myelin. Conversely, using genetically modified mouse models, the researchers were able to show that “naked” axons in an acute inflammatory region of the central nervous system are better protected from degeneration.

Professor Ruth Stassart from the Paul Flechsig Institute suggests gaining a deeper understanding of myelin and developing new treatment strategies. Dr. Robert Fledrich adds that promoting rapid degradation of damaged myelin might be therapeutically better.

Posted on Fibromyalgia

“Study finds a connection between fibromyalgia and increased risk of mortality.”

Regular monitoring of physical and mental health is necessary to minimize risks of accidents, infections, and especially suicide, based on pooled data analysis.

Please wear a purple tie to help promote fibromyalgia awareness

Fibromyalgia, a condition that causes persistent widespread pain and fatigue, may be associated with an increased risk of death due to vulnerability to accidents, infections, and especially suicide. This information comes from a pooled data analysis of available evidence, published in the open access journal RMD Open.

The researchers urge for regular monitoring of patients’ physical and mental health to minimize these risks.

It’s unclear what causes fibromyalgia, but researchers note its increasing prevalence. There is a growing recognition that the condition often coexists with other health problems, including rheumatic, gut, neurological, and mental health disorders.

Given the extent of pain experienced by these patients and the likelihood of other debilitating conditions, they are probably at heightened risk of premature death.

In order to support this hypothesis, the researchers examined the results of 8 pertinent studies that were published between 1999 and 2020, out of an initial group of 33. They combined the findings from 6 of these studies, which included a total of 188,751 adults, all of whom had other concurrent conditions.

The analysis revealed that fibromyalgia was linked to a 27% increased risk of death from all causes over time, although this did not apply to those diagnosed using the 1990 criteria.

But the diagnostic criteria for fibromyalgia have evolved since 1990 in tandem with an increasing understanding of the array of clinical symptoms associated with the condition. They were consequently revised in 2010, 2011, and 2016, as pointed out by the researchers.

Specifically, the analysis indicated that the risk of cancer-related death was 12% lower than that of the general population of the same age, and only marginally higher (5%) for accidents.

But the infection rate was 44% higher, including pneumonia and septicaemia, and more than 3 times as high for suicide.

The researchers note that it is not clear whether the increased risk is due to fibromyalgia itself or the accompanying conditions, as their research was not designed to evaluate this. They emphasize that this is an important issue that requires further research.

They caution that their findings should be interpreted in the light of differing study designs and the small number of participants included in their analysis.

“Due to significant differences among the studies, which were also limited in number, no definitive conclusions can be made from the available data,” they wrote. “However, it is possible that for the subgroup of patients diagnosed using the 1990 criteria, there is no increased risk of mortality, and for those diagnosed using later versions, the risk is higher,” they added.

“Plausible explanations exist for their findings,” they suggest. The increased mortality associated with accidents may be linked to fatigue, unrefreshing sleep, and concentration difficulties that accompany fibromyalgia. These are also a component of its diagnostic criteria since 2010.

More evidence supports immune system involvement and inflammation in fibromyalgia pathophysiology, explaining the increased mortality from infections. Physical comorbidity may be an additional factor.

And the reduced risk of a cancer death may be due to these patients’ extensive use of health services, they suggest.

The analysis has identified risks that could pose a significant public health concern, given the condition’s high prevalence, which clinicians do not always take seriously.

“Studies have shown that medical staff are often hesitant to acknowledge fibromyalgia as a legitimate medical condition. They also encounter emotional and psychological challenges when interacting with these patients and managing their disorder,” the researchers state.

“Fibromyalgia is often referred to as an ‘imaginary condition,’ sparking ongoing debates about the legitimacy and clinical usefulness of this diagnosis. However, our review offers additional evidence supporting the need to take fibromyalgia patients seriously. We particularly emphasize the importance of screening for suicidal ideation, preventing accidents, and addressing the prevention and treatment of infections,” the researchers conclude

Posted on Autism

New research has provided more clarity on the connection between autism and the microbiome.

A SFARI initiated and funded reanalysis of previous studies reveals consistent biological signals in the human microbiome and other physiological signals associated with autism
A SFARI-initiated and funded reanalysis of previous studies reveals consistent biological signals in the human microbiome and other physiological signals associated with autism

The biological roots of autism continue to perplex researchers despite a growing body of studies looking at an increasing array of genetic, cellular and microbial data. Recently, scientists have homed in on a new and promising area of focus: the microbiome. This collection of microbes that inhabit the human gut has been shown to play a role in autism, but the mechanics of this link have remained awash in ambiguity. Taking a fresh computational approach to the problem,sheds new light on the relationship between the microbiome and autism. This research — which originated at the Simons Foundation’s Autism Research Initiative (SFARI) and involved an innovative reanalysis of dozens of previously published datasets — aligns with a recent, long-term study of autistic individuals that centred on a microbiome-focused treatment intervention. These findings also underscore the importance of longitudinal studies in elucidating the interplay between the microbiome and complex conditions such as autism.

“We were able to harmonize seemingly disparate data from different studies and find a common language with which to unite them. With this, we were able to identify a microbial signature that distinguishes autistic from neurotypical individuals across many studies,” says Jamie Morton, one of the study’s corresponding authors, who began this work while a postdoctoral researcher at the Simons Foundation and is now an independent consultant. “But the bigger point is that going forward, we need robust long-term studies that look at as many datasets as possible and understand how they change when there is a [therapeutic] intervention.”

With 43 authors, this study brought together leaders in computational biology, engineering, medicine, autism and the microbiome who hailed from institutions in North America, South America, Europe and Asia. “The sheer number of fields and areas of expertise in this large-scale collaboration is noteworthy and necessary to get a new and consistent picture of autism,” says Rob Knight, the director of the Center for Microbiome Innovation at the University of California San Diego and a study co-author.

Autism is inherently complex, and studies that attempt to pinpoint specific gut microbes involved in the condition have been confounded by this complexity. First, autism presents in heterogeneous ways — autistic individuals differ from each other genetically, physiologically and behaviorally. Second, the microbiome presents unique difficulties. Microbiome studies typically report simply the relative proportions of specific microbes, requiring sophisticated statistics to understand which microbial population changes are relevant to a condition of interest. This makes it challenging to find the signal amongst the noise. Making matters more complicated, most studies to date have been one-time snapshots of the microbial populations present in autistic individuals. “A single time point is only so powerful; it could be very different tomorrow or next week,” says study co-author Brittany Needham, assistant professor of anatomy, cell biology and physiology at the Indiana University School of Medicine.

“We wanted to address the constantly evolving question of how the microbiome is associated with autism, and thought, ‘let’s go back to existing datasets and see how much information we may be able to get out of them,’” says co-corresponding author Gaspar Taroncher-Oldenburg, director of Therapeutics Alliances at New York University, who initiated the work with Morton while he was a consultant-in-residence for SFARI.

In the new study, the research team developed an algorithm to re-analyze 25 previously published datasets containing microbiome and other “omic” information — such as gene expression, immune system response and diet — from both autistic and neurotypical cohorts. Within each dataset, the algorithm found the best matched pairs of autistic and neurotypical individuals in terms of age and sex, two factors that can typically confound autism studies. “Rather than comparing average cohort results within studies, we treated each pair as a single data point, and thus were able to simultaneously analyze over 600 ASD-control pairs corresponding to a de facto cohort of over 1,200 children,” says Taroncher-Oldenburg. “From a technical standpoint, this required the development of novel computational methodologies altogether,” he adds. Their new computational approach enabled them to reliably identify microbes that have differing abundances between ASD and neurotypical individuals.

To the researchers’ surprise, their analysis identified autism-specific metabolic pathways associated with particular human gut microbes. Importantly, these pathways were also seen elsewhere in autistic individuals, from their brain-associated gene expression profiles to their diets. “We hadn’t seen this kind of clear overlap between gut microbial and human metabolic pathways in autism before,” says Morton.

Even more striking was an overlap between microbes associated with autism, and those identified in a recent long-term fecal microbiota transplant study led by James Adams and Rosa Krajmalnik-Brown at Arizona State University’s Biodesign Center for Health Through Microbiomes. “Another set of eyes looked at this, from a different lens, and they validated our findings,” says Krajmalnik-Brown, who was not involved in the study published today.

“What’s significant about this work is not only the identification of major signatures, but also the computational analysis that identified the need for future studies to include longitudinal, carefully designed measurements and controls to enable robust interpretation,” says Kelsey Martin, executive vice president of SFARI and the Simons Foundation Neuroscience Collaborations, who was not involved in the study.

“Going forward, we need more long-term studies that involve interventions, so we can get at cause-and-effect,” says Morton. Taroncher-Oldenburg, who cites the compliance issues often faced by traditional long-term studies, suggests that study designs could more effectively take into account the realities of long-term microbiome sampling of autistic individuals. “Practical, clinical restrictions must inform the statistics, and that will inform the study design,” he says. Further, he points out that long-term studies can reveal insights about both the group and the individual, as well as how that individual responds to specific interventions over time.

Importantly, researchers say these findings go beyond autism. The approach set forth here could also be employed across other areas of biomedicine that have long proved challenging. “Before this, we had smoke indicating the microbiome was involved in autism, and now we have fire. We can apply this approach to many other areas, from depression to Parkinson’s to cancer, where we think the microbiome plays a role, but where we don’t yet know exactly what the role is,” says Knight.