Posted on Fibromyalgia

First study to analyse brain changes associated with juvenile fibromyalgia

UB SCIENTIFIC TEAM


The study is led by the researchers Maria Suñol and Marina López Solà, members of the Pain and Emotion Neuroscience Laboratory at the Faculty of Medicine and Health Sciences and the Institute of Neurosciences of the University of Barcelona. CREDIT UNIVERSITY OF BARCELONA

Juvenile fibromyalgia is a syndrome characterized by a chronic pain affecting the whole body. It also causes fatigue as well as sleep and mood disorders. It affects children and adolescents —mainly girls— worldwide and it appears during a critical period of the brain development. Analysing the brain changes that occur in the first stages of juvenile fibromyalgia could help to better understand the pathophysiology of this syndrome, which had not been approached from this perspective to date.

A study published in the journal Arthritis and Rheumatology characterizes for the first time the alterations in the grey matter volume in adolescents affected by juvenile fibromyalgia, and it analyses its functional and clinical relevance. The study contributes to identifying potential risk factors that will help testing the efficiency of different treatments to reverse these brain alterations. The new research is led by the postdoctoral researcher Maria Suñol and the lecturer Marina López Solà, from the research group Pain and Emotion Neuroscience Laboratory of the Faculty of Medicine and Health Sciences and the Institute of Neurosciences (UBNeuro) of the University of Barcelona.

The study, which applies several neurophysiology study techniques, counted on the participation of 34 adolescent girls affected by the pathology and a control group of 38 healthy adolescents. The new research has been carried out in collaboration with the professors Susmita Kashikar-Zuck and Robert Coghill, members of the Cincinnati Children’s Hospital (United States).

Juvenile fibromyalgia: brain, self-perception and emotions

The study reveals that the adolescents with juvenile fibromyalgia have less grey matter in the anterior-midcingulate cortex (MCC) region, a brain region which is decisive for pain processing. This feature could be related to the excessive engagement of brain circuits that process pain and it points out to the existence of a reorganization with these neuronal circuits.

The most affected patients by the pathology —and with more symptoms— also show an increase of volume in the frontal regions of the brain that is related to the creation of narratives about oneself and the emotional processing and regulation.

This increase in volume could reflect a certain immaturity in the process of the development of frontal circuits involved with emotion and language. “These findings strengthen the need to consider therapeutic strategies aimed at modulating the activity in these circuits in order to reverse the harmful narratives patients might feel about themselves,” notes Maria Suñol, first author of the study.

It also states that some brain alterations associated with related to juvenile fibromyalgia coincide with those identified in adult women with fibromyalgia. “This suggests that both syndromes share part of the pathophysiology,” notes the lecturer López Solà. “Therefore, it is important to promote the early and guided study of the pathology in adolescents in order to prevent the transition from juvenile to adult fibromyalgia.”

Posted on Older people's health

Well-functioning fat may be the key to fewer old-age ailments

Well-functioning fat may be the key to fewer old-age ailments


Anders Gudiksen and one of the participants CREDIT Anders Gudiksen, University of Copenhagen

Fat tissue plays an important role in human health. However, our fat tissue loses function as we age, which can lead to type 2 diabetes, obesity, cancer and other ailments. High levels of lifelong exercise seem to counteract this deterioration. This, according to research at the University of Copenhagen, where biologists studied the link between aging, exercise and fat tissue function in Danish men.

How well does your fat function? It isn’t a question that one gets asked very often. Nonetheless, research in recent years suggests that the function of our fat tissue, or adipose tissue, is central to why our bodies decay with age, and strongly linked to human diseases like diabetes 2, cancer as obesity often develop and fat cells undergo functional changes as we get older. Thus, overall health is not just influenced by the amount of fat we bear, but about how well our fat tissue functions.

A new University of Copenhagen study demonstrates that even though our fatty tissue loses important function with age, a high volume of exercise can have a significant impact for the better.

“Overall health is closely linked with how well our fat tissue functions. In the past, we regarded fat as an energy depot. In fact, fat is an organ that interacts with other organs and can optimize metabolic function. Among other things, fat tissue releases substances that affect muscle and brain metabolism when we feel hungry and much more. So, it’s important that fat tissue works the way it should,” explains Assistant Professor Anders Gudiksen of the University of Copenhagen’s Department of Biology.

Fat cell function worsens with age

Gudiksen and a group of colleagues looked at the role of age and physical training in maintaining fat tissue function. Specifically, they studied mitochondria, the tiny power plants within fat cells. Mitochondria convert calories from food to supply cells with energy. To maintain the life processes within cells, they need to function optimally.  

The researchers compared mitochondrial performance across a range of young and older untrained, moderately trained and highly exercise trained Danish men. The results demonstrate that the ability of mitochondria to respire – i.e., produce energy – decreases with age, regardless of how much a person exercises. However, Anders Gudiksen explains:

“Although mitochondrial function decreases with age, we can see that a high level of lifelong exercise exerts a powerful compensatory effect. In the group of well-trained older men, fat cells are able to respire more than twice as much as in untrained older men.”

More training means less waste in cells

Just as a car engine produces waste when converting chemical to usable energy, so do mitochondria. Mitochondrial waste comes in the form of oxygen free radicals, known as ROS (Reactive Oxygen Species). ROS that isn’t eliminated damages cells and the current theory is that elevated ROS can lead to a wide range of diseases including cancer, diabetes, cardiovascular disease and Alzheimer’s. Therefore, the regulation of ROS is important.

“The group of older people who train most form less ROS and maintain functionality to eliminate it. Indeed, their mitochondria are better at managing waste produced in fat cells, which results in less damage. Therefore, exercise has a large effect on maintaining the health of fat tissue, and thereby probably keeping certain diseases at bay as well,” says Gudiksen.

The researchers can also see that the older participants who exercised most throughout life have more mitochondria, allowing for more respiration and, among other things, an ability to release more of the fat-related hormones important for the body’s energy balance.

‘Our results show that you can actually train your fat tissue to a very high degree – but that you needn’t cycle 200km a week to achieve a positive effect. What you shouldn´t do, is do nothing at all,” concludes Anders Gudiksen, who hopes that the research world will focus more on what people can do to maintain the health of their fatty tissue.

The next step for the UCPH researchers will be to investigate where exactly cellular damage occurs when people don’t exercise and what impact this has on the body as a whole over time. Concurrently, the researchers are exploring ways to pharmacologically manipulate the mechanism in the mitochondria that converts calories into heat instead of depositing calories as fat, in turn lowering the production of the harmful oxygen radicals.

ABOUT THE STUDY

  • Study subjects were 20-32-year-old untrained men and 62-73-year-old men, who throughout their lives were either untrained, moderately trained or highly trained. All men were healthy, unmedicated and had a BMI below 30.
     
  • The researchers suggest that the study estimates are conservative as the participants are unlikely to represent the population as a whole, where a higher proportion of people are probably in poorer physical shape and suffer from health problems than the participants recruited. None of the study’s older participants took prescription medication, whereas a large proportion of the population in this age group otherwise does.
     
  • The scientific paper about the study is published in The Journals of Gerontology.
     
  • The study was conducted by Anders Gudiksen, Albina Qoqaj, Stine Ringholm and Henriette Pilegaard of the Department of Biology, Jørgen Wojtaszewski of the Department of Nutrition, Exercise and Sports, and Peter Plomgaard of the Department of Clinical Medicine at the University of Copenhagen.
Posted on Rheumatoid arthritis

Continuation versus discontinuation of anti-rheumatic biologics during the perioperative period: What does the evidence support?

For patients with rheumatic arthritis and other chronic inflammatory diseases, discontinuing biologic disease-modifying anti-rheumatic drugs (bDMARDs) prior to orthopaedic surgery does not appear to increase the risk of surgical site infections or delayed wound healing, concludes a review and meta-analysis in The Journal of Bone & Joint Surgery. The journal is published in the Lippincott portfolio in partnership with Wolters Kluwer.

However, patients discontinuing bDMARDs may be more likely to experience a disease flare following orthopaedic surgery, according to the report by Bernard H. van Duren of University of Leeds, UK, and colleagues.

Decisions regarding bDMARD discontinuation must balance the risk of disease flares

bDMARDs have represented a major advancement in the treatment of rheumatic arthritis and other inflammatory diseases. Although effective in slowing disease progression, these biologic agents have traditionally been associated with an increased risk of infection.

In the case of total joint replacement, infections are a potentially devastating complication; thus, some surgeons and other specialists recommend discontinuing  bDMARD therapy during the perioperative period. “[H]owever,” the researchers write, “there has been no definitive evidence showing a clear benefit of discontinuing the use of bDMARDs, and in doing so, patients may be at an increased risk for higher disease activity.”

Toward clarifying the issue, Dr. van Duren and colleagues performed a systematic review of 11 studies that included 4,959 patients who discontinued their bDMARDs and 2,385 patients who continued their bDMARDs. The most common diagnosis among these patients was rheumatoid arthritis, and tumor necrosis factor inhibitors were the most common type of bDMARD. However, other diagnoses and bDMARDs were represented.

The meta-analysis found no significant difference in the rate of surgical site infections between patients who discontinued (3.06 percent) versus continued their bDMARDs (2.90 percent). The rates of delayed wound healing were also similar between those discontinuing (2.28 percent) and continuing their bDMARDs (0.99 percent). Subgroup analysis of patients undergoing total joint arthroplasty also showed no significant difference in the rate of surgical site infection.

However, patients who discontinued their bDMARDs were substantially more likely to experience a disease flare during the postoperative period: 25.71 percent compared with 7.32 percent among patients who continued their bDMARDs. The pooled analysis suggested a 78 percent reduction in the odds of having a flare for patients who continued bDMARD therapy.

Disease flares compromise patient rehabilitation following orthopaedic surgery. In addition, patients who experience a flare often require treatment with corticosteroids, introducing an additional risk of infection. “It is therefore important to balance the risk of flares against the risk of infection if bDMARDs are continued during the perioperative period,” Dr. van Duren and coauthors write.

The researchers note that their review is among the first “to comprehensively investigate the effect of continuing or discontinuing bDMARDs perioperatively across inflammatory diseases in patients undergoing orthopaedic surgery.” However, although the analysis included data on a large number of patients, the ability to draw conclusions is limited by the “generally low” quality of the available studies, as reflected by the inconsistency of current guidelines regarding perioperative bDMARD discontinuation. Dr. van Duren and colleagues emphasize the need for randomized controlled trials “to provide definitive answers in this important area.”

Posted on Autism

Survey heightens concern about pandemic’s impact on education of autistic students

Helen M. Genova, PhD


Dr. Genova is associate director of the Center for Autism Research at Kessler Foundation. CREDIT Kessler Foundation

Kessler Foundation scientists conducted an online survey of parents of school-aged children to compare the effects of pandemic-related school closures on autistic vs neurotypical students. Their findings indicate that children on the autism spectrum are at greater risk for negative educational outcomes.

The article, “Effects of school closures resulting from COVID-19 in autistic and neurotypical children,” (doi: 10.3389/feduc.2021761485) was published open access on November 23, 2021, by Frontiers in Education. This open access article is available at:https://www.frontiersin.org/articles/10.3389/feduc.2021.761485/full The authors are Helen Genova, PhD, Aditi Arora, PhD, and Amanda Botticello, PhD, MPH, of Kessler Foundation.

Using the COVID-19 Adolescent Symptom and Psychological Questionnaire, survey data were collected from May 2020 to August 2020 from parents/guardians of school-aged children – autistic and neurotypical – aged 4 to 15 years. Final sample was N=250, including respondents with neurotypical children (65%), and those with autistic children (35%).

The survey revealed differences in the psychological impact of the pandemic on neurotypical and autistic children, as reported by their parents. Overall, parents of autistic children were more likely to report negative effects of the pandemic. For neurotypical children, being isolated from friends was the most negative experience; for autistic children, disruption of their routine schedule was the most negative.

While neurotypical children turned to virtual experiences to connect socially, autistic children were less likely to participate in virtual experiences. This finding has implications for the shift to online delivery of education, medical treatment, and therapy precipitated by the pandemic. “Children on the autism spectrum may benefit less from virtual services,” noted Dr. Genova. “While remote delivery of educational and therapy services may be a convenient way for schools and facilities to remain open when in-person attendance carries risks, the long-term negative effects for children on the autism spectrum may be significant. To help them continue to achieve their educational goals, autistic children may need alternative ways to keep pace with their peers.”

The study also revealed that parents of children on the autism spectrum had specific concerns related to their children’s diagnosis. “Addressing these concerns is important for the mental health of parents and children,” added Dr. Genova, “since stress levels of caregivers can influence stress levels of autistic children.”

Funding: None

Posted on Autism

Stanford Medicine study shows differences between brains of girls, boys with autism

Happy children playing head over heels on green grass in spring park




Brain organization differs between boys and girls with autism, according to a new study from the Stanford University School of Medicine. 
 
The differences, identified by analyzing hundreds of brain scans with artificial intelligence techniques, were unique to autism and not found in typically developing boys and girls. The research helps explain why autism symptoms differ between the sexes and may pave the way for better diagnostics for girls, according to the scientists.


 
Autism is a developmental disorder with a spectrum of severity. Affected children have social and communication deficits, show restricted interests and display repetitive behaviors. The original description of autism, published in 1943 by Leo Kanner, MD, was biased toward male patients. The disorder is diagnosed in four times as many boys as girls, and most autism research has focused on males. 
 
“When a condition is described in a biased way, the diagnostic methods are biased,” said the study’s lead author, Kaustubh Supekar, PhD, a clinical assistant professor of psychiatry and behavioral sciences. “This study suggests we need to think differently.”


 
The study was published online Feb. 15 in The British Journal of Psychiatry. 
 
“We detected significant differences between the brains of boys and girls with autism, and obtained individualized predictions of clinical symptoms in girls,” said the study’s senior author, Vinod Menon, PhD, a professor of psychiatry and behavioral sciences and the Rachael L. and Walter F. Nichols, MD, Professor. “We know that camouflaging of symptoms is a major challenge in the diagnosis of autism in girls, resulting in diagnostic and treatment delays.” 
 
Girls with autism generally have fewer overt repetitive behaviors than boys, which may contribute to diagnostic delays, the researchers said. 
 
“Knowing that males and females don’t present the same way, both behaviorally and neurologically, is very compelling,” said Lawrence Fung, MD, PhD, assistant professor of psychiatry and behavioral sciences, who was not an author of the study. 
 
Fung treats people with autism at Stanford Children’s Health, including girls and women with delayed diagnoses. Many autism treatments work best during the preschool years when the brain’s motor and language centers are developing, he noted.
 
“If the treatments can be done at the right time, it makes a big, big difference: For instance, children on the autismspectrum receiving early language intervention will have a better chance of developing language like everyone else and won’t have to keep playing catch-up as they grow up,” Fung said. “If a child cannot articulate themselves well, they fall behind in many different areas. The consequences are really serious if they are not getting diagnoses early.”
 
New statistical methods unlock differences
 
The study analyzed functional magnetic resonance imaging brain scans from 773 children with autism — 637 boys and 136 girls. Amassing enough data to include a sizeable number of girls in the study was challenging, Supekar said, noting that the small number of girls historically included in autism research has been a barrier to learning more about them. The research team relied on data collected at Stanford and on public databases containing brain scans from research sites around the world. 
 
The preponderance of boys in the brain-scan databases also set up a mathematical challenge: Standard statistical methods used to find differences between groups require that the groups be roughly equal in size. These methods, which underlie machine-learning techniques in which algorithms can be trained to find patterns in very large and complex datasets, can’t accommodate a real-world situation in which one group is four times as large as the other. 
 
“When I tried to identify differences [with traditional methods], the algorithm would tell me every brain is a male with autism,” Supekar said. “It was over-learning and not distinguishing between males and females with autism.”
 
Supekar discussed the problem with Tengyu Ma, PhD, assistant professor of computer science and of statistics at Stanford and a co-author on the study. Ma had recently developed a method that could reliably compare complex datasets, such as brain scans, from different-sized groups. The new technique provided the breakthrough the scientists needed. 
 
“We happened to be lucky that this new statistical approach was developed at Stanford,” Supekar said.
 
What differed?
 
Using 678 of the brain scans from children with autism, the researchers developed an algorithm that could distinguish between boys and girls with 86% accuracy. When they verified the algorithm on the remaining 95 brain scans from children with autism, it maintained the same accuracy at distinguishing boys from girls.
 
The scientists also tested the algorithm on 976 brain scans from typically developing boys and girls. The algorithm could not distinguish among them, confirming that the sex differences the scientists found were unique to autism.
 
Among children with autism, girls had different patterns of connectivity than boys did in several brain centers, including motor, language and visuospatial attention systems. Differences in a group of motor areas — including the primary motor cortex, supplementary motor area, parietal and lateral occipital cortex, and middle and superior temporal gyri — were the largest between sexes. Among girls with autism, the differences in motor centers were linked to the severity of their motor symptoms, meaning girls whose brain patterns were most similar to boys with autism tended to have the most pronounced motor symptoms.
 
The researchers also identified language areas that differed between boys and girls with autism, and noted that prior studies have identified greater language impairments in boys. 
 
“When you see that there are differences in regions of the brain that are related to clinical symptoms of autism, this seems more real,” Supekar said.
 
Taken together, the findings should be used to guide future efforts to improve diagnosis and treatment for girls, the researchers said.
 
“Our research advances use of artificial intelligence-based techniques for precision psychiatry in autism,” Menon said.
 
“We may need to have different tests for females compared with males. The artificial intelligence algorithms we developed may help to improve diagnosis of autism in girls,” Supekar said. At the treatment level, interventions for girls could be initiated earlier, he added.
 
The study’s other Stanford Medicine co-authors are scientific data analyst Carlo de los Angeles; senior research scientist Srikanth Ryali, PhD; and graduate student Kaidi Cao. Co-authors include members of Stanford’s Maternal and Child Health Research Institute, Stanford Bio-X, the Stanford Wu Tsai Neurosciences Institute and the Stanford Wu Tsai Human Performance Alliance, and the Stanford Institute for Human-Centered Artificial Intelligence.