Finding Adds Another Piece to Autism Puzzle

By Leslie Sabbagh

HealthDay Reporter

MONDAY, Aug. 21 (HealthDay News) -- Contrary to common medical thought, young children with autism do not have accelerated brain growth even though their brains appear enlarged, new research claims.

The finding, published in the Aug. 22 issue of Neurology, confirms some earlier reports and conflicts with others.

Dr. Stephen Dager, of the University of Washington School of Medicine, and his colleagues compared 60 autistic children to 16 children with developmental delay and 10 children with typical development. They used magnetic resonance imaging (MRI) scans to measure the transverse relaxation (T2) of gray and white matter in the children's cortexes. This measures how much water is moving around inside brain tissue, and it gives clinicians an indirect way to measure brain maturation.

The researchers found the autistic children had differences in the gray matter of their brains compared to the children with typical development. A number of studies has suggested the brains of younger children with autism are 10 percent larger, Dager explained. This new research honed in on tissue chemistry and found the abnormality wasn't due to lack of "pruning," which is how the normal developing brain rids itself of unnecessary neurons.

The abnormality is "clearly not accelerated brain growth. An alternative hypothesis could be inflammatory processes. Our data would be consistent with adult studies that found higher levels of cytokines, associated with inflammation, in postmortem studies," he explained.

A popular current theory is that autistic children have more rapid brain growth that plateaus at the age of 5 or 6. "We didn't find evidence for that, just the opposite, in fact," Dager said. "The processes that go along with brain maturation were slower in the autistic brains, particularly in gray matter."

The finding is "tantalizing," said Andrew Shih, director of research and programs at the National Alliance for Autism Research. "This is one of the first attempts to differentiate beyond volumetric difference to really look at what's behind those differences."

The field, he explained, has been "intrigued by reports last year that suggest a model of autism could be premature development or unchecked brain growth leading to disorganized circuitry. The thinking was, synaptic pruning didn't occur, so that noise became predominant over signal itself."

But Dager's study suggests gray matter development in autism involves the same volume as normal brains, but fewer neurons. "The convergence of evidence now seems to suggest a model in which gray matter abnormality could be inflammatory. T2 measures water molecules, and the findings here suggest there's more water in these kids' brains...," Shih explained.

The differences in gray matter were found only in the brains of autistic children, while both gray and white matter differences were found in the brains of children with learning delays. For children with learning delays, the findings suggest slowed neuronal development is to blame, while autistic children have a different kind of neuronal development abnormality, possibly induced by inflammation. Gray matter consists of the brain's neurons, while white matter is the brain's wiring system.

Another important finding, that gray matter seems to be affected differently in autism, supports earlier research. "There's evidence of connectivity problems at older ages; in younger ages, it seems gray matter is problematic. Autism is a developmental problem and evolves as people age," he noted.

Autism affects up to one in every 175 school-age children, according to a recent study from the U.S. Centers for Disease Control and Prevention.

The government researchers also found that boys are nearly four times more likely to be diagnosed with autism than girls, and Hispanic parents were slightly less likely than non-Hispanic whites to report a child with autism, although this may be due to cultural or other factors, including access to medical care.

In the end, the findings only add another piece to the jigsaw puzzle that is autism, Dager said, adding, "We're no closer to a treatment."

Other new research is also starting to unravel common beliefs about this disorder. In addition to social interaction problems, a study in the current issue of Child Neuropsychology found autism prevents different parts of the brain from working together. That makes complex tasks, such as tying shoelaces, much more difficult. The children studied were 8 to 15 years old.

More information

For more information on autism, go to National Institute of Mental Health (www.nimh.nih.gov ).

SOURCES: Stephen Dager, M.D., professor, radiology research, Center on Human Development and Disability, University of Washington School of Medicine, Seattle; Andrew Shih, director, research and programs, National Alliance of Autism Research, Princeton, N.J,; Aug. 22, 2006, Neurology

Un gène lié à l'évolution du cerveau humain

Le Soir en ligne, Sciences et santé.

Une recherche belgo-américaine vient d'aboutir à la découverte de ce qui pourrait être un gène clef de l'évolution du cerveau humain. Ce travail permet d'ouvrir de nouvelles perspectives notamment en médecine et en biologie.

Ce gène clef, appelé HAR1 (Human Accelerated Region 1), a été découvert initialement par des méthodes de comparaison des génomes de l'homme, du chimpanzé et des rongeurs, visant à identifier les portions de notre génome qui ont évolué le plus rapidement depuis la divergence entre l'espèce humaine et ces autres espèces, il y a plusieurs millions d'années.

Le gène HAR1 ne permet pas la production de protéines (qui remplissent des fonctions très diverses dans notre organisme), mais bien la production d'un ARN à la structure élaborée. L'ARN, qui du point de vue de sa structure moléculaire est similaire à l'ADN, se distingue par son rôle essentiel de messager de l'information génétique. L'ARN est un intermédiaire-convoyeur entre l'ADN et les structures cellulaires, chargées de la production des protéines.

Du fait de l'évolution très accélérée de HAR1 dans la lignée humaine, cet ARN a acquis une structure unique, propre à l'homme.

Qui plus est, HAR1 serait particulièrement actif dans le cortex cérébral en développement, au sein de cellules très spécialisées, les neurones de Cajal-Retzius, qui jouent un rôle primordial dans le développement harmonieux du cortex cérébral.

Ces découvertes permettent d'ouvrir de nouvelles perspectives quant à plusieurs aspects importants de médecine et de biologie. En effet, il est possible que les mutations de HAR1 puissent entraîner des anomalies du cortex cérébral, associées à des retards mentaux et des épilepsies, et des anomalies du développement des fonctions cérébrales supérieures propres à certaines affections neuropsychiatriques, comme la schizophrénie ou l'autisme.

Le travail est une collaboration entre des chercheurs belges (groupe de Pierre Vanderhaegen, chercheurs FNRS à l'IRIBHM, Université Libre de Bruxelles) et américains (groupe de David Haussler, Université de Santa Cruz). Les résultats sont publiés dans la revue "Nature".

(D'après Belga)

L'autisme « affecte l'ensemble du cerveau »

Traduction de l'article de la BBC, publié le 16/08/2006, intitulé "Autism 'affects all of the brain"

L'autisme n'affecte pas simplement la façon dont les personnes entrent en relation avec autrui mais il a aussi un large éventail d'effets, ainsi que le suggère, cette étude.

Des chercheurs américains ont comparé 56 enfants avec autisme avec 56 sans autisme.

Ceux qui avaient de l'autisme se sont avérés avoir plus de problèmes avec des tâches complexes, tel qu'attacher leurs lacets, suggérant que beaucoup de secteurs du cerveau étaient affectés.

Un expert anglais de l'autisme précise que l'étude de la neuropsychologie infantile a montré combien le trouble était envahissant :

"Les difficultés sociales ont reçu beaucoup d'attention lors des recherches mais cette nouvelle étude nous rappelle que les causes de l'autisme ont des effets plus larges.", Professeur Simon Baron Cohen, Centre de Recherches sur l'Autisme.

Les personnes avec autisme sont traditionnellement considérées comme ayant des problèmes d'interaction avec autrui et des difficultés dans la communication verbale et non-verbale.

Elles peuvent également avoir des comportements stéréotypés et des intérêts très limités.

Mais cette étude suggère que l'autisme peut affecter la perception, le mouvement et la mémoire sensorielle parce qu'il empêche différentes parties du cerveau travaillant ensemble de réaliser des tâches complexes.

Lacets « difficiles »

Les enfants avec autisme de l'étude étaient tous capable de parler, de lire et d'écrire.

Tout ceux étudiés par l'équipe du Collaborative Program of Excellence étaient âgés de 8 à 15 ans.

Tandis que les enfants avec autisme réussissaient aussi bien, et même parfois mieux, que les autres enfants dans les tests de base, ils ont tous éprouvé des difficultés dans les tâches complexes.

Ainsi dans les tests visuels et spatiaux, les enfants avec autisme étaient très performants pour retrouver des petits objets dans une image complexe, ou bien pour retrouver le personnage Waldo dans les livres de la série « où est Waldo ?». Mais quand ils ont été invités à faire la différence entre les personnes qui se ressemblaient, ils ont trouvé cela très difficile.

Alors que les enfants avec autisme avaient tendance à être très bons en énonciation et en grammaire, ils ont eu plus beaucoup de mal à comprendre les figures complexes du discours, telles que les idiomes - où la signification de l'expression n'est pas identique à ce que les mots réels suggèrent.

Par exemple, ils ne comprendraient pas l'expression "casser sa pipe" signifiant que quelqu'un était mort puisqu'on ne peut être mort et être susceptible de "casser sa pipe".

Les enfants avec autisme avaient également des problèmes avec leur écriture.

Câblage « défectueux »

Nancy Minshew, une spécialiste en psychiatrie et neurologie de l'Université de Médecine de Pittsburgh , qui a mené cette recherche, a indiqué : « Ces résultats prouvent que vous ne pouvez pas compartimenter l'autisme. Il est beaucoup trop complexe".

Elle a expliqué que les chercheurs qui étudent l'autisme doivent rechercher les causes qui affectent des secteurs multiples du cerveau, plutôt que regarder simplement des secteurs reliés à la communication et aux comportement stéréotypés et compulsifs.

Le docteur Minshew a ajouté : « Notre étude suggère fortement que l'autisme n'est pas principalement un désordre d'interaction sociale mais un désordre global affectant la façon dont le cerveau traite l'information qu'il reçoit - particulièrement quand l'information devient compliquée. »

L'équipe avait précédemment trouvé, en regardant des scanners de cerveau, que les personnes avec autisme avaient des anomalies dans le câblage neurologique par lequel différents secteurs du cerveau communiquent.

Elle a dit que ces anomalies étaient susceptibles d'expliquer pourquoi les enfants avec autisme dans l'étude ont eu des problèmes avec des tâches complexes mais ont bien réussi dans les tâches qui ont seulement exigé la mobilisation d'une seule région du cerveau.

Professeur Simon baron Cohen, chef du Centre de Recherches sur l'Autisme de Cambridge, a dit : « Cette nouvelle étude est importante car elle ne se limite pas au fonctionnement atypique dans des domaines sociaux et non-sociaux, des personnes qui sont dans le spectre autistique.

« Précédemment les difficultés sociales ont suscité beaucoup d'attention de recherches.

« Mais cette nouvelle étude nous rappelle que les causes de l'autisme ont bien plus d'effets. »

BBC, 2006

Autism 'affects all of the brain'

Autism does not simply affect how people relate to others but has a wide range of effects, a study suggests.

US researchers compared 56 children with autism with 56 who did not have the condition.

Those with autism were found to have more problems with complex tasks, such as tying their shoelaces, suggesting many areas of the brain were affected.

A UK autism expert said the Child Neuropsychology study showed how pervasive the condition was.

The social difficulties have received a great deal of research attention but this new study reminds us that the causes of autism have more pervasive effects Professor Simon Baron Cohen, Autism Research Centre

People with autism are traditionally identified as having problems interacting with others and with both verbal and non-verbal communication.

They can also display repetitive behaviours and have very focused interests.

But this study suggests autism can affect sensory perception, movement and memory because it prevents different parts of the brain working together to achieve complex tasks.

Shoelaces 'difficult'

The children with autism all had the ability to speak, read and write.

All those studied by the team from the Collaborative Program of Excellence in Autism were aged eight to 15.

While children with autism performed as well as, and sometimes better than, the other children in basic tests, they all had trouble with complex tasks.

So in the visual and spatial skills tests, children with autism were very good at finding small objects in a busy picture, such as finding the character Waldo in the "Where's Waldo" picture books series.

But when they were asked to tell the difference between similar-looking people, they found it very difficult.

And while children with autism tended to be very good at spelling and grammar, they found it much harder to understand complex figures of speech, such as idioms - where the meaning of the phrase is not the same as the actual words suggest.

For example, they would not understand "He kicked the bucket" as meaning someone had died and were likely to actually hop if told to "hop it".

Children with autism also had problems with their handwriting.

'Faulty' wiring

Nancy Minshew, a specialist in psychiatry and neurology at the University of Pittsburgh School of Medicine, who led the research, said: "These findings show that you cannot compartmentalise autism. It's much more complex.

She said researchers investigating autism needed to look for causes that affect multiple brain areas, rather than simply looking at areas related to communication and repetitive behaviours or obsessive interests.

Dr Minshew added: "Our paper strongly suggests that autism is not primarily a disorder of social interaction but a global disorder affecting how the brain processes the information it receives - especially when the information becomes complicated."

The team has previously found, through looking at brain scans, that people with autism have abnormalities in the neurological wiring through which brain areas communicate.

She said these abnormalities were the most likely explanation for why the children with autism in the current study had problems with complex tasks but did well in tasks that only required one region of the brain.

Professor Simon Baron Cohen, head of the Autism Research Centre in Cambridge, said: "This new study is important in highlighting atypical functioning in both social and non-social domains, by people with autism spectrum conditions.

"Previously the social difficulties have received a great deal of research attention.

"But this new study reminds us that the causes of autism have more pervasive effects."

© BBC MMVI

L'autisme s'accompagne de perturbations du flux sanguin et d'un stress oxydant

Source: Faculté de médecine de l'université de Pennsylvanie

En prenant comme point de comparaison des enfants en bonne santé, des chercheurs de la faculté de médecine de l'université de Pennsylvanie ont découvert que les enfants atteints d'autisme souffraient d'anomalies du flot sanguin ainsi que d'un stress oxydant notable. Ces enfants présentaient des niveaux de substances biochimiques révélateurs d'une vasodilatation insuffisante au niveau de l'endothélium vasculaire (cellules qui tapissent les vaisseaux) avec risque accrû de formation de caillots (par les plaquettes).
________________________________________

En étudiant les rapports existant entre le stress oxydant et l'état des vaisseaux sanguins chez les sujets autistes, les chercheurs espèrent trouver d'autres axes thérapeutiques pour ce syndrome. Ces derniers, qui ont travaillé sous la direction du Dr Domenico Pratico, professeur de pharmacologie, ont publié leurs résultats dans le numéro d'août d'Archives of Neurology.

Selon l'ASA (Autism Society of America), le nombre de cas d'autisme aux Etats-Unis progresse de 10 à 17 % par an. Pathologie neurodéveloppementale, l'autisme se caractérise par une perturbation des interactions sociales, une communication verbale et non verbale limitée, et des comportements répétitifs et restreints. L'intensité et la portée des symptômes sont variables, ce qui évoque l'existence de causes multifactorielles. De précédentes études ont révélé une hypoperfusion du cerveau par rapport aux sujets de groupes de contrôle en bonne santé.

Les échantillons d'urines d'enfants autistes d'âge similaire et de groupes de contrôle ont été fournis par le Pfeiffer Treatment Center (www.hriptc.org) qui avait préalablement procédé au diagnostic d'autisme et à une évaluation. Les patients ayant précédemment reçu un traitement comportant des antioxydants ou présentant des pathologies telles que maladie chronique, dépression, psychose ou troubles inflammatoires, ou encore malades au moment des prélèvements, ont été exclus de l'étude. Ces critères stricts sont la cause du nombre restreint de sujets pris en compte dans cette étude préliminaire : 26 enfants atteints d'autisme et 12 enfants en bonne santé.

L'équipe du Dr Pratico a mesuré l'isoprostane, l'un des marqueurs du stress oxydant, la thromboxane, indice d'activation plaquettaire, et la prostacycline, mesure du tonus des vaisseaux sanguins. "Cette étude est la première à établir que non seulement la synthèse de la thromboxane et de la prostacycline est notablement élevée dans l'autisme, mais qu'il existe en outre une étroite corrélation avec le taux de stress oxydant constaté", a déclaré le Dr Pratico. Les enfants atteints d'autisme présentaient des niveaux d'isoprostane, de thromboxane et de prostacycline supérieurs à ceux des groupes de contrôle.

Le stress oxydant est le résultat d'une formation excessive de dérivés chimiques instables, les radicaux libres, au sein même des cellules. Dans des conditions normales, la cellule est à même de détruire ces radicaux libres. Toutefois, en présence d'une accumulation excessive, ces molécules montent à l'assaut de la cellule pour s'y stabiliser.

"Pendant le stress oxydant, c'est un peu comme si les radicaux libres n'avaient qu'une jambe", explique le Dr Pratico. "Ils sont à la recherche d'une seconde jambe pour ne pas tomber. Malheureusement, ils ne trouvent cet équilibre chimique qu'en infligeant un dommage irréversible aux cellules et à l'organe". Les radicaux libres peuvent endommager les membranes cellulaires, les protéines et les gènes par oxydation, à la manière de cette réaction chimique qu'est l'apparition de la rouille sur le fer.

En mesurant les niveaux d'isoprostane, dérivé chimique de l'attaque des cellules graisseuses par les radicaux libres, le Dr Pratico et son équipe ont constaté que les sujets porteurs d'autisme présentaient un stress oxydant près de deux fois supérieur à celui des sujets du groupe de contrôle.

Les échantillons des patients autistes ont également révélé la présence d'un déséquilibre biochimique dans les vaisseaux sanguins, déséquilibre résultant en des niveaux élevés de thromboxane – indice d'activité plaquettaire – et de prostacycline, indice de vasoconstriction des cellules endothéliales. La thromboxane et la prostacycline opèrent normalement de concert pour assurer l'intégrité des vaisseaux. En réponse à différents types de stress, les plaquettes libèrent la thromboxane, qui entraîne une constriction des vaisseaux. L'endothélium répond à ces niveaux élevés de thromboxane en libérant la prostacycline. L'effet de constriction des vaisseaux est ainsi contré par un effet de dilatation améliorant à son tour le flot sanguin.

L'autisme est une pathologie neurologique complexe dont le déséquilibre oxydant constitue l'une des composantes. Différents aspects bien établis viennent étayer cette hypothèse selon laquelle un déséquilibre oxydant pourrait jouer un rôle dans cette maladie : l'autisme se caractérise par un système de défense anti-oxydants perturbé, une production élevée de radicaux libres, ainsi qu'une amélioration des symptômes comportementaux après la prise d'anti-oxydants.

"Nous savons d'une manière générale que les anomalies constatées dans les vaisseaux sanguins s'expriment d'un point de vue clinique par un flot sanguin anormal", indique le Dr Pratico. "De ce fait, il est intéressant de rappeler que de précédentes études d'imagerie cérébrale ont permis de constater une hypoperfusion du cerveau chez l'enfant autiste. Cet éclairage supplémentaire sur le lien existant entre le stress oxydant et la santé des vaisseaux dans la pathologie de l'autisme permet d'anticiper une amélioration des traitements".

Yuemang Yao (Université de Pennylvanie), William J. Walsh (Pfeiffer Treatment Center) et Woody R. McGinnis (Oxidative Stress in Autism Initiative) sont co-auteurs de cette étude financée pour partie par le Pfeiffer Treatment Center.

Echographie: un danger pour le cerveau des foetus de souris, selon une étude

WASHINGTON (AP) -- Chez la souris, l'échographie perturberait le développement cérébral du foetus, selon une étude publiée mardi dans les annales de l'Académie nationale des sciences aux Etats-Unis. Ce constat qui n'a pas été confirmé chez la femme ne remet pas en cause l'emploi de cette technique chez les femmes enceintes, à condition de ne pas en abuser.

Chez les souris enceintes soumises à des échographies, un petit nombre de cellules nerveuses du cerveau du foetus n'arrivent pas à se développer correctement dans le cortex cérébral.

Toutefois, Pasko Rakic, qui dirige le service de neurobiologie de l'école de médecine de l'Université de Yale, souligne qu'il ne faut pas pour autant "renoncer à une échographie justifiée à des fins de diagnostic et autres raisons médicales". Toutefois, a-t-il précisé lors d'une interview téléphonique, "les femmes devraient éviter les examens inutiles avant le résultat de nouvelles recherches".

De son côté, le Dr Joshua Copel, président-élu de l'Institut américain d'échographie, déclare que son organisation déconseille l'échographie "de divertissement", par opposition au même examen jugé important lorsqu'il est réalisé pour des motifs médicaux. "Nous devons toujours peser le pour et le contre. Il peut être très important de connaître le terme exact de la grossesse, cela nous aide à déterminer l'anatomie du foetus, mais ne devons pas maintenir la sonde des heures et des heures sur l'abdomen de la mère", explique-t-il.

L'Agence américaine du médicament s'oppose elle aussi à la pratique en vogue des "échographies-souvenir".

En ce qui concerne les résultats publiés mardi, le Dr Copel souligne la différence entre une échographie de souris et une échographie de femme: du fait de leur taille, par exemple, la distance entre le foetus et l'appareil est plus important chez la femme que chez la souris, ce qui réduit la puissance des ultrasons; de plus, la densité des os du crâne chez le foetus est elle aussi plus importante que chez la souris, ce qui réduit encore davantage l'exposition.

L'article rappelle par ailleurs que, la période de développement de ces cellules cérébrales étant plus longue chez les humains que chez les souris, le temps d'exposition ne représente qu'un tout petit pourcentage de la période de développement. Toutefois, la période de développement de ces cellules étant plus complexe chez les humains, et la quantité de cellules plus importante, le risque de problème est lui aussi plus élevé.

Dans l'étude de Rakic, les souris étaient soumises à une exposition allant de cinq à 420 minutes. Les cerveaux des bébés souris ont été étudiés après leur naissance et comparés à ceux de souriceaux dont la mère n'avait pas été exposée.

L'étude qui portait sur 335 souris est arrivée à la conclusion que dans le premier groupe (la mère avait été exposée au moins 30 minutes), un nombre statistiquement significatif de cellules cérébrales n'avait pas réussi à se développer à leur place normale et étaient restées dispersées dans des endroits incorrects. Le nombre de cellules concernées croissait proportionnellement au temps d'exposition.

L'étude a été financée par l'Institut national des pathologies neurologiques et de l'accident vasculaire cérébral.

Vaccine avoidance caused measles outbreak

ATLANTA, Aug. 3 (UPI) -- The Atlanta-based Centers for Disease Control and Prevention said a measles outbreak in 2005 was caused by parents who chose not to immunize their children.

The CDC National Center for Immunization study, published in the New England Journal of Medicine, said the outbreak began when a 17-year-old girl attended church in Indiana after visiting an orphanage in Romania, where measles is common, The Wall Street Journal reported Thursday.

The study said all but one of the 34 people involved in the outbreak attended church with the girl; 82 percent were school aged, and 20 were home schooled.

The church's minister estimated that 10 percent of congregants at the church avoided vaccination after hearing that the treatments could cause autism. However, U.S. vaccinations do not include the mercury-based chemical thimerasol, which has been the root of the autism worries.

Kim Mulholland, a professor at the London School of Hygiene and Tropical Medicine, said in commentary accompanying the study that parents should not "respond to spurious claims about the risks of vaccine by refusing to vaccinate their infants."

Copyright 2006 by United Press International. All Rights Reserved.

Malheureusement, les nouvelles de l'innocuité du vaccin ROR et du thimerosal ne font pas la une des journaux, contrairement aux prétentions des spécialistes de l'épouvante et de la pseudoscience.

Different genes may cause autism in boys and girls

Like detectives trying to solve a murder case, researchers searching for the biological cause of autism have come up with some surprising suspects.

They've found that different genes may be responsible for causing autism in boys than in girls.

In addition, the researchers also have discovered that other genes may play a role in the early onset form of the developmental disorder and in the recently verified regression, or late onset, type of autism, according to a new study published today in the online edition of the journal Molecular Genetics.

The study also provides new evidence for the idea that multiple genes contribute to autism, said lead author Gerard Schellenberg, a researcher at the Puget Sound Veterans Affairs Medical Center and a research professor of medicine at the University of Washington. The research team was headed by Schellenberg, Ellen Wijsman, a UW research professor of medical genetics and Geraldine Dawson, director of the UW's Autism Center.

"It is highly unlikely that there is only one gene responsible for autism," said Schellenberg. "There may be four to six major genes and 20 to 30 others that might contribute to autism to a lesser degree.

"If an individual only gets three high-risk variants of these genes, it could mean a less-severe form of autism. And because autism is rarer in females, it may take more risk genes for a female to have autism. There also is the possibility that there might be a biological difference in autism for females versus males," he said.

"What is meaningful is that we have found evidence for two genetic subtypes of autism, male versus female and early versus late onset," added Geraldine Dawson, a professor of psychology. "This is a critical piece of information. With Alzheimer's disease research, one big breakthrough was segregating the late and early onset forms of the disease, and this led to important genetic discoveries."

Schellenberg said the study came up with "strong support" for an autism gene on chromosome 7 and "less, but still compelling evidence" for genes on chromosomes 3, 4 and 11. These results confirm some data from previous studies, particularly involving chromosome 7.

The search for autism genes is part of a long-term Autism Center effort to uncover the genetic and neurobiological causes of autism. To find regions of the human genome that contain autism genes, the researchers scanned the DNA of 169 families that had at least two siblings who met the strict criteria for autism. They also scanned the DNA of another 54 families that, in addition to having individuals with strictly defined autism, also included members who had less severe forms of the disorder, such as Asperger syndrome.

"We have been working almost 10 years to get to this point," said Schellenberg. "If we can find and confirm that a particular gene is involved in autism the field will explode. We have to find a gene so that molecular biology can be defined and we can understand what's inside autism. Until that happens, we are dancing on the outside."

Dawson said the researchers are looking for autism susceptibility genes, ones that heighten the risk of an individual getting autism, just as there are genes that raise the chances of getting breast cancer.

"Once we discover these susceptibility genes, we can immediately screen infants to identify those at risk early in life. Early identification can lead to early intervention, which could have a much more dramatic effect.

"Also, when a gene is discovered, you discover the underlying biology of autism at the molecular level. Once you understand the biology you can develop a prevention strategy including medical approaches. Genetic research is a good strategy for eventually designing effective medical treatments for autism," she said.

From University of Washington

Autisme: laissez Freud en dehors de tout ça!

VIRGINIE POYETTON
Le Courrier (Genève)

PRISE EN CHARGE - L'autisme: psychose ou handicap? Des parents demandent que cesse la prise en charge psychanalytique et que des écoles spécialisées soient créées à Genève.

«J'avais vu des émissions à la télévision. Un enfant qui, à 3 ans, range ses livres de manière obsessionnelle, aligne des petits cailloux ou sélectionne ses aliments, ce n'est pas normal. Je suis allée à la guidance infantile. J'ai demandé: ''est-il est autiste?'' On m'a répondu: ''Non. Il a des troubles du comportement.'' C'était vague. Mais, du coup, ça m'a soulagée.» Deux ans plus tard, le fils de Marie-Jeanne Accietto est diagnostiqué «autiste».
Déçue par le peu de soutien qu'elle reçoit des institutions, et insatisfaite des soins prodigués à son fils en centre de jour – elle juge l'approche psychanalytique inadéquate –, elle décide de s'occuper partiellement de l'éducation de son enfant.
Avec quelque vingt-cinq familles, Marie-Jeanne Accietto a créé un groupe de parents d'enfants autistes. Ce dernier demande que l'autisme soit reconnu comme handicap à part entière et revendique une prise en charge spécialisée des enfants autistes (lire ci-contre). Dans un premier temps, pour former des professionnels spécialisés en autisme et établir des diagnostics, il demande la création d'un centre de compétence en autisme. Finalement, la création de trois écoles spécialisées pour autistes devrait permettre d'apporter une prise en charge spécifique. Un projet a été mis sur papier et envoyé au professeur Eliez, directeur du Service médico-pédagogique de Genève (SMP).

«Il est difficile de faire admettre la spécificité de l'autisme»

En premier lieu, les parents regrettent l'absence de choix réel dans l'approche thérapeutique/éducative. «La psychanalyse est la seule approche utilisée par les institutions. C'est un vrai diktat.» Selon cette théorie, le rôle des parents doit être minimal, soutient Mme Accietto. De nombreux pères et mères se sentent désarmés. «La psychologue de référence du centre de jour où mon fils a été placé m'a dit: «Pleurez un bon coup et ça passera! On a l'impression de ne pas être entendus. On nous taxe d'anxieux. On nous renvoie une image très culpabilisante de nous-mêmes.» «C'est vrai qu'il y a un besoin spécifique de prise en charge de type éducatif pour les enfants autistes à Genève», affirme Anne Emery-Torracinta, présidente d'insieme-Genève, (association de parents de personnes mentalement handicapées).
Pour le directeur du SMP, une approche uniquement psychanalytique est insuffisante. «L'autisme a une multitude de causalités. Il n'existe pas de traitement unique. Nous devons travailler sur une approche plus cognitive.» De là, le professeur en vient à la proposition des parents de créer un centre de compétence: «L'idée fait sens. Mais un tel centre implique une régionalisation et donc des inégalités d'accès pour les parents qui voudraient faire diagnostiquer leur enfant. Et le réseau de soins genevois a au contraire cherché à développer un réseau de proximité.» L'idée semble donc enterrée. Pourtant, pour Marie-Jeanne Accietto, la régionalisation n'est pas une entrave à sa réalisation. Elle soutient que les éducateurs spécialisés, s'agissant de l'autisme, manquent de formation. Le nouveau centre de compétence permettrait aux professionnels d'être informés des différentes méthodes et des avancées scientifiques en matière de prise en charge des enfants autistes. «Il pourrait servir de centre de diagnostic et d'évaluation», complète Mme Emery-Torracinta. «Il est difficile de faire admettre la spécificité de l'autisme, confie Mme Accietto. Pour les institutions publiques, parler de spécificité, c'est enfermer l'autiste dans un ghetto.» Pourtant, pour la jeune mère, la reconnaissance du handicap est primordiale pour aider l'enfant. «Est-ce que vous allez au service orthopédique quand vous souffrez d'une tumeur?» L'absence de diagnostic est perturbante pour de nombreux parents. «Laisser les parents dans le vague, les empêche d'agir, de se renseigner, de comprendre. C'est absurde. Nous souhaitons que le diagnostic soit posé avant l'âge de 3 ans. Même s'il y a un doute. Il faut au moins avertir les parents.» Pour le professeur Eliez, cette revendication est plus que légitime. «Dans ce sens, il faut souligner le rôle essentiel joué par les pédiatres de ville.» Il y a trois ans, le professeur organisait une formation sur l'autisme pour les pédiatres, «mais ce sont des démarches qui doivent être répétées en boucle». Et qui visiblement rencontrent encore de fortes résistances.

Globalement, tous s'accordent sur la nécessité de faciliter l'accès aux classes dites normales

Dans un deuxième temps, les parents du groupe demandent la création d'écoles spécialisées en autisme (une pour les 4-12 ans, et deux pour les 12-18 ans) avec une intégration partielle dans des classes dites normales pour les enfants les plus avancés. Aujourd'hui, les enfants sont placés dans des centres de jour avec d'autres enfants handicapés ou dans des institutions privées. Le professeur Eliez est fermement opposé à la création de telles écoles: «Il n'est pas souhaitable de regrouper des enfants autistes. Les enfants, de manière générale, interagissent. Il est très positif pour les autistes d'être en contact avec leurs pairs. Ce serait une ségrégation contre-productive.» Plus nuancée, Mme Emery-Torracinta avoue n'avoir pas été complètement convaincue par ce projet: «Nous souhaitons évidemment un personnel spécialisé, mais pas à tout prix une école spécifique. Enfin, ça se discute. Mais comme cela fait des années que les parents demandent une prise en charge adaptée, il est normal qu'ils en viennent à demander une école.»
Globalement, tous s'accordent sur la nécessité de faciliter l'accès aux classes dites normales. Un projet de loi est en discussion au Grand Conseil et une classe intégrée ouvrira aux Crêts-de-Champel à la rentrée prochaine.

Les autistes males ont moins de neurones dans l’amygdale

Par David Biello, Scientific American

De nombreux garçons et hommes atteints d’autisme souffrent d’une diminution de leurs capacités de communication et sociales réduites. Ils pourraient aussi souffrir d’un manque de neurones dans l’amygdale, selon les découvertes d’une nouvelle étude. David Amaral et Cynthia Mills Schumann de l’université de Californie à Davis, ont étudié le nombre de neurones dans l’amygdale de neuf autistes mâles et de 10 mâles non-autistes dont les âges variaient entre 10 to 44 ans. Comptant péniblement leur nombre sous un microscope, ils ont observé une quantité significativement moindre de neurones (des cellules de signalisation électrique) dans cette zone du cerveau associée à la peur et la mémoire.

"C’est la première preuve quantitative d’un nombre anormal de neurones dans l’amygdale des autistes," note Amaral. "Nous avons pu analyser post-mortem plus du double de cerveaux qu’avant, dont aucun n’avait eu d’attaque ou autres troubles neurologiques, mis à part l’autisme.

Des études précédentes s’étaient appuyées sur des mesures de densité des neurones ainsi que sur le cerveau d’autistes mâles ayant eu des attaques épileptiques--un état que l’ont sait provoquer des défauts de l’amygdale. Amaral et Schumann ont compté des neurones avec une sonde tridimensionnelle à fort grossissement. Ils ont trouvé que bien qu’il n’y ait pas de variation dans le volume de l’amygdale, celle du groupe des autistes mâles avait globalement 1,5 million de neurones en moins que celle de leurs pairs.

D’autres études utilisant l’imagerie cérébrale ont montré que les garçons autistes développent une amygdale adulte vers l’âge de huit ans, alors que les autres garçons l’atteignent à l’adolescence. On ne sait pas encore s’il y a d’autres régions du cerveau des autistes qui pourraient avoir un déficit de neurones. "Il est possible qu’il y ait toujours moins de neurones dans l’amygdale des personnes atteintes d’autisme. Il est aussi possible qu’un processus de dégénérescence se déclenche plus tard dans la vie et conduise à une perte de neurones," dit Schumann. "Des études complémentaires sont nécessaires pour affiner nos découvertes." Celles-ci sont publiées dans un article qui paraît aujourd’hui dans le Journal of Neuroscience.

Un pas de plus dans la recherche sur l’autisme

Laurent Suply (lefigaro.fr)

Les causes de ce trouble psychologique sont encore loin d’être élucidées, mais une étude américaine publié mercredi dans le Journal of Neuroscience démontre que les personnes souffrant d’autisme ont moins de neurones dans une zone du cerveau dont dépend l’expression des émotions et le comportement social.

Dix-neuf cerveaux appartenant à des personnes décédées de 10 et 44 ans, dont neuf souffraient d’autisme, ont été examinés par les chercheurs de l’université américaine de Californie. Grâce à une technique nommée « analyse stéréologique », ces chercheurs ont pu dénombrer les neurones des cerveaux dans une zone appelée « amygdale », pour sa forme d’amande. Résultat: les autistes possèdent un nombre significativement inférieur de neurones dans cette région du cerveau, une conclusion qui vient confirmer le lien pressenti entre cette zone et l’autisme.


Le lien entre l’autisme et l’amygdale était déjà pressenti


L’amygdale est une partie du cerveau qui intervient notamment dans le processus de mémorisation des émotions et dans le développement des comportements sociaux. Elle intervient par exemple dans l’apprentissage de la peur. Elle sert également à décrypter les émotions de nos proches. Une étude précédente a montré que l’amygdale s’active lorsqu’il s’agit de deviner les émotions d’autrui en regardant les expressions de son visage. Chez les sujets autistes, l’activation de cette zone n’a pas lieu dans cette situation.


« Ces découvertes complètent d’autres études qui suggéraient que des anomalies de l’amygdale contribuaient significativement au déficit de fonctions sociales » qui définissent l’autisme, explique Emanuel DiCicco-Bloom, professeur de neurologie pédiatrique à l’Université de médecine du New Jersey. Le résultat de l’étude, publiée par le Journal of Neuroscience est jugé « un peu surprenant » par Cynthia Schumann, un des auteurs de l’étude. Des études d’imagerie magnétique antérieures avaient montré que l’amygdale était sensiblement plus grosse en volume chez les jeunes garçons souffrant d’autisme que les sujets « sains ».


Prochaine étape : observer l’évolution des neurones tout au long de la vie


Grâce à l’étude de l’Université de Californie, le lien semble désormais certain. Mais elle n’assure pas pour autant que la déficience de l’amygdale soit la cause de l’autisme. Plusieurs hypothèses sont envisagées. Le déficit neuronal peut tout d’abord dater de la naissance du sujet, ou au contraire découler d’un processus de dégénérescence causant l’autisme. Autre possibilité, l’atrophie neuronale de l’amygdale est la conséquence de l’autisme : à force de ne pas être « utilisés » par le malade, les neurones chargés des émotions disparaissent. Une telle perte pourrait enfin être causée par le très haut niveau d’anxiété ressenti par les intéressés.


Le lien mystérieux entre l’amygdale et ce trouble du comportement devra donc être exploré plus avant. Pour ce faire, l’une des pistes consiste à développer des techniques permettant de compter les neurones de personnes en vie, afin d’observer l’évolution de leur quantité chez des jeunes sujets autistes. La recherche sur ce trouble psychologique est « un processus à plusieurs étapes », souligne David Amaral, autre membre du groupe d’étude, qui ajoute : « Au moins, nous en avons franchi une de plus ».

Researchers gain insight into why brain areas fail to work together in autism

Researchers have found in two studies that autism may involve a lack of connections and coordination in separate areas of the brain.

In people with autism, the brain areas that perform complex analysis appear less likely to work together during problem solving tasks than in people who do not have the disorder, report researchers working in a network funded by the National Institutes of Health. The researchers found that communications between these higher-order centers in the brains of people with autism appear to be directly related to the thickness of the anatomical connections between them.

In a separate report, the same research team found that, in people with autism, brain areas normally associated with visual tasks also appear to be active during language-related tasks, providing evidence to explain a bias towards visual thinking common in autism.

"These findings provide support to a new theory that views autism as a failure of brain regions to communicate with each other," said Duane Alexander, M.D., Director of NIH's National Institute of Child Health and Human Development. "The findings may one day provide the basis for improved treatments for autism that stimulate communication between brain areas."

The studies and the theory are the work of Marcel Just, Ph.D., D.O. Hebb Professor of Psychology at Carnegie Mellon University in Pittsburgh, Pennsylvania, and Nancy Minshew, M.D., Professor of Psychiatry and Neurology at the University of Pittsburgh School of Medicine and their colleagues. The research was conducted by the Collaborative Program of Excellence in Autism, a research network funded by the NICHD and the National Institute on Deafness and Other Communication Disorders.

People with autism often have difficulty communicating and interacting socially with other people. The saying "unable to see the forest for the trees" describes how people with autism frequently excel at details, yet struggle to comprehend the larger picture. For example, some children with autism may become spelling bee champions, but have difficulty understanding the meaning of a sentence or a story.

An earlier finding by these researchers described how a group of people with autism tended to use parts of the brain typically associated with processing shapes to remember letters of the alphabet. A news release detailing that finding appears at http://www.nichd.nih.gov/new/releases/final_autism.cfm.

Participants with autism in both current studies had normal I.Q. There were no significant differences between the participants with and without autism in age or I.Q.

The first of the two new studies recently was published online in the journal Cerebral Cortex. In that study, the researchers used a brain imaging technique known as functional magnetic resonance imaging, or fMRI, to view the brains of people with autism as well as a comparison group of people who do not have autism. All of the study participants were asked to complete the Tower of London test. The task involves moving three balls into a specified arrangement in an array of three receptacles. The Tower of London is used to gauge the functioning of the prefrontal cortex.

This brain area, located in the front, upper part of the brain, deals with strategic planning and problem-solving. The prefrontal cortex is the executive area of the brain, in which decision making, judgment, and impulse control reside.

A little further back is the parietal cortex, which controls high-level visual thinking and visual imagery, supporting the visual aspects of the problem-solving. Both the prefrontal and parietal cortex play a critical part in performing the Tower of London test.

In the normal participants, the prefrontal cortex and the parietal cortex tended to function in synchrony (increasing and decreasing their activity at the same time) while solving the Tower of London task. This suggests that the two brain areas were working together to solve the problem.

In the participants with autism, however, the two brain areas, prefrontal and parietal, were less likely to function in synchrony while working on the task.

The researchers made another discovery, for the first time finding a relationship between this lower level of synchrony and the properties of some of the neurological "cables" or white matter fiber tracts that connect brain areas.

White matter consists of fibers that, like cabling, connect brain areas. The largest of the white matter tracts is known as the corpus callosum, which allows communication between the two hemispheres (halves) of the brain.

"The size of the corpus callosum was smaller in the group with autism, suggesting that inter-regional brain cabling is disrupted in autism," Dr. Just said.

In essence, the extent to which the two key brain areas (prefrontal and parietal) of the autistic participants worked in synchrony was correlated with the size of the corpus callosum. The smaller the corpus callosum, the less likely the two areas were to function in synchrony. In the normal participants, however, the size of the corpus callosum did not appear to be correlated with the ability of the two areas to work in synchrony.

"This finding provides strong evidence that autism is a disorder involving the biological connections and the coordination of processing between brain areas," Dr. Just said.

He added, however, that the thickness, or extent, of connections between brain areas may not be the basis for the disorder. Although the neurological connections between the prefrontal cortex appear to be reduced in autism, the brains of people with autism have thicker connections between certain brain regions within each hemisphere.

"At this point, we can say that autism appears to be a disorder of abnormal neurological and informational connections of the brain, but we can't yet explain the nature of that abnormality," Dr. Just said.

In the second study, published online in the journal Brain, the researchers examined the extent to which brain areas involved in language interact with brain regions that process images. Dr. Just explained that earlier studies, as well as anecdotal accounts, suggest that people with autism rely more heavily on visual and spatial areas of the brain than do other people.

In this study, the researchers used fMRI to examine brain functioning in participants with autism and in normal participants during a true-false test involving reading sentences with low imagery content and high imagery content. A typical low imagery sentence consisted of constructions like "Addition, subtraction, and multiplication are all math skills." A high imagery sentence, "The number eight when rotated 90 degrees looks like a pair of eyeglasses," would first activate left prefrontal brain areas involved with language, and then would involve parietal areas dealing with vision and imagery as the study participant mentally manipulated the number eight.

As the researchers expected, the visual brain areas of the normal participants were active only when evaluating sentences with imagery content. In contrast, the visual centers in the brains of participants with autism were active when evaluating both high imagery and low imagery sentences.

"The heavy reliance on visualization in people with autism may be an adaptation to compensate for a diminished ability to call on prefrontal regions of the brain," Dr. Just said.

The second study also confirmed the observations in the first study--that the prefrontal and parietal brain regions of the cortex in people with autism were less likely to work in synchrony than were the brains of normal volunteers. The second study also confirmed that the extent to which the two parts of the cortex could work together was correlated with the size of the corpus callosum that connected them. Dr. Just and his colleagues are conducting additional studies to ascertain the nature of the abnormality of the connections in the brains of people with autism.

New Model Of Brain Sheds Light On Triggers Of Autism

Science Daily — Approximately 1.5 million children and adults in the U.S. have autism and it is estimated to be the fastest growing developmental disability with a 10 – 17 percent increase each year. While much is known about the symptoms of autism, the exact cause of the condition is not yet defined.

A new model of the brain developed by Dr. Stephen Grossberg, professor and chairman of the Department of Cognitive and Neural Systems at Boston University, and Dr. Don Seidman, a pediatrician with the DuPage Medical Group in Elmhurst, IL, sheds light on the triggers of behaviors commonly associated with autism. The paper, “Neural Dynamics of Autistic Behaviors: Cognitive, Emotional, and Timing Substrates,” appears in the July issue of the journal Psychological Review, published by the American Psychological Association.

“Autism involves multiple genes and correspondingly, people with autism are known to have multiple cognitive, emotional, and motor symptoms – such as impaired development of speech and difficulty expressing emotions,” said Dr. Grossberg. “The iSTART model describes the various brain mechanisms that underlie autism and how they may give rise to the symptoms of the condition.”

iSTART, which stands for Imbalanced Spectrally Timed Adaptive Resonance Theory, is derived from the earlier START model developed by Grossberg to explain how the brain controls normal behaviors. The new model describes how brain mechanisms that control normal emotional, timing, and motor processes may become imbalanced and lead to symptoms of autism. START and its imbalanced version iSTART are a combination of three models, each one of which tries to explain fundamental issues about human learning and behavior.

The first, called Adaptive Resonance Theory, or ART, proposes how the brain learns to recognize objects and events. Recognition is accomplished through interactions between perceptually-driven inputs and learned expectations. Inputs attempt to match expectations which helps prompt the brain to anticipate input/expectation patterns.

“When a match occurs, the system locks into a resonant state that drives how we learn to recognize things; hence the term adaptive resonance,” explained Grossberg.

The degree of match that is required for resonance to occur is set by a vigilance parameter which controls whether a particular learned representation will be concrete or abstract. Low vigilance allows for learning of broad abstract recognition categories, such as a category that is activated by any face; high vigilance forces the learning of specific concrete categories, such as a category that is activated by a particular view of a familiar friend’s face. iSTART proposes that individuals with autism have their vigilance fixed at such a high setting that their learned representations are very concrete, or hyperspecific.

“Hypervigilance leads to hyperspecific learning which perpetuates a multitude of problems with learning, cognition, and attention,” said Grossberg.

The second model, called the Cognitive-Emotional-Motor, or CogEM, model, extends ART to the learning of cognitive-emotional associations, or associations that link objects and events in the world to feelings and emotions that give these objects and events value. Under normal circumstances, arousal of the circuits in the brain that control emotion are set at an intermediate level. Either under-arousal or over-arousal of these circuits can cause abnormal emotional reactions and problems with cognitive-emotional learning.

“If the emotional center is over-aroused, the threshold to activate a reaction is abnormally low, but the intensity of the emotion is abnormally small,” said Grossberg. “In contrast, if the emotional circuits are under-aroused, the threshold for activating an emotion is abnormally high, but when this threshold is exceeded, the emotional response can be over reactive. The iSTART model proposes that individuals with autism experience under-aroused emotional depression which helps explain symptoms like reduced emotional expression as well as emotional outbursts.”

The third model, called the Spectral Timing model, clarifies how the brain adaptively times responses in order to acquire rewards and other goals. iSTART shows how individuals with autism experience failures of adaptive timing that lead to the premature release of behaviors which are then unrewarded.

“iSTART depicts how autistic symptoms may arise from breakdowns in normal brain processes, notably a combination of under-stimulated emotional depression in the amygdala and related brain regions, learning of hyperspecific recognition categories in the temporal and prefrontal cortices, and breakdowns of adaptively timed attention and motor circuits in the hippocampal system and cerebellum,” said Grossberg. “The model clarifies how malfunctions in these mechanisms can, though a system-wide vicious circle, cause and maintain problems with them all.”

According to the researchers, iSTART is a breakthrough in the understanding of the many factors that contribute to autism and provides a unifying perspective that connects autistic symptoms to brain mechanisms that have no obvious connection to the condition.

"This approach should make it easier for scientists studying normal behavior to connect their work to autism research," said Grossberg. "iSTART opens up a wide range of possible new experiments to evaluate autistic behaviors and further test and develop the model.”

More information about iSTART and its component models can be found at http://www.cns.bu.edu/Profiles/Grossberg.

Note: This story has been adapted from a news release issued by Boston University.

Study clears MMR vaccine of autism link

Pervasive developmental disorders (PDD) like autism and Asperger Syndrome have been on the rise for years. Measles Mumps Rubella (MMR) vaccines and thimerosal–containing vaccines (which are approximately 50 percent ethylmercury) have been suggested as possible causes. A new MUHC study published in the scientific journal Pediatrics tomorrow, assesses the link between childhood immunizations and PDD in 28,000 Quebec children and finally clears MMR vaccines and thimerosal–containing immunizations as risk factors.

"There is no relationship between the level of exposure to MMR vaccines and thimerosal–containing vaccines and rates of autism," says Dr. Eric Fombonne, Director of Pediatric Psychiatry at The Montreal Children's Hospital of the MUHC and lead investigator of the new study. Thimerosal was used to prevent bacterial and fungal contamination in the manufacture of various vaccines until its elimination from vaccine formulas in 1996 in Quebec. "According to our data, the incidence of autism was higher in children who were vaccinated after thimerosal was eliminated from vaccines," says Dr. Fombonne.

"In the past, concern about a potential link between MMR vaccinations and autism led some parents to take the drastic step of refusing to inoculate their children against dangerous childhood diseases like measles," says Dr. Fombonne. "This action resulted in resurgence of the measles, which caused the deaths of several young children in Europe." Dr. Fombonne's study indicates that autism rates continued to increase even with reductions in the use of MMR vaccinations. "We hopes this study will finally put to rest the pervasive belief linking vaccines with developmental diseases like autism," says Dr. Fombonne.

Autism is a neuropsychiatry disorder that impairs a child's ability to communicate and interact with others. The prevalence is about 65 cases per 10,000 people (about 1 child in 155) making autism one of the most common childhood disorders. The Psychiatry Department at The Montreal Children's Hospital sees about 350 new cases of autism each year. However, Dr. Fombonne stresses that there is no demonstrated autism epidemic. He attributes the rise in autism rates to a broader definition of autism and greater awareness of the disorder.

From McGill University

Des défauts du placenta pourraient être un signe précoce d'autisme

Par Tracy Staedter, Scientific American

Les scientifiques ont découvert que le plus précoce des indicateurs d'autisme à ce jour, pourrait être la présence de cellules défectueuses dans le placenta. Cette découverte pourrait mener à un diagnostic plus précoce du trouble du développement qui touche environ un enfant sur 200 et peut avoir comme conséquence des difficultés d’apprentissage, des problèmes de parole et une difficulté dans les relations interpersonnelles.

"Plus vite nous le diagnostiquerons, plus nous le comprendrons et plus efficaces seront nos interventions," dit le chercheur scientifique Harvey Kliman, de l’Ecole de Médicine. Kliman et son équipe décrivent leur découverte dans l’édition en ligne du 26 juin de Biological Psychiatry.

Cette recherché s’appuie sur les travaux antérieurs de Kliman, qui décrivaient des crevasses anormales dans l’enveloppe externe du placenta. Dans le passé, ces anomalies ont été mises en relation avec une longue liste de défauts génétique, y compris les syndromes de Down et de Turner.

Kliman soupçonnait qu’ils pourraient aussi être lies à l’autisme. Alors, dans cette étude, lui et d’autres chercheurs de Yale ont utilise un microscope pour examiner des échantillons de tissu du placenta, conservés par plusieurs hôpitaux de recherche. Treize de ces échantillons provenaient d’enfants ayant été plus tard diagnostiqués nt une forme d’autisme; 61 échantillons provenaient d’enfants chez qui la maladie n’avait pas été diagnostiquée. Lorsque Kliman a compare les deux groupes de tissus, il s’est aperçu que les placentas des enfants autistes avait trois fois plus de chance d’avoir les crevasses microscopiques anormales.

Kliman pense que ces recherches pourront conduire à un examen de routine du placenta des nouveau-nés à risque, notamment ceux ayant un frère ou une sœur autiste. Tous les autistes n’ont pas nécessairement cet aspect anormal du placenta. Mais, dit Kliman, "Si vous observez ces défauts, il est improbable que l’enfant soit parfaitement normal."

Draw line under MMR scare, plead top doctors

· 'More children will die' unless jabs get all-clear
· Warning as England faces big measles epidemic

Ian Sample,
science correspondent
Tuesday June 27, 2006
The Guardian

A group of Britain's leading paediatricians and childhood vaccination experts has warned that more children will die unless a line is drawn under the autism and MMR (measles, mumps and rubella) vaccine controversy.

In an open letter, 30 scientists, including some of the country's most eminent child health experts, say that an overwhelming body of evidence shows the vaccine is safe. They add that urgent immunisations are necessary to prevent potentially devastating outbreaks among schoolchildren.

The warning comes as England faces its biggest measles outbreak in 20 years, fuelled by the refusal of some parents to have their children immunised because of now discredited claims linking the MMR jab and autism.

The letter, whose signatories include Patricia Hamilton, president of the Royal College of Paediatrics and Child Health, and Professor Sir David Hall, a paediatrician at Sheffield University, says: "The time has come to draw a line under the question of any association between the MMR vaccine and autism. The UK's children are in danger of serious illness or death if they are left unimmunised."

This month, the Health Protection Agency reported 449 cases of measles so far this year - more in just six months than the 438 reported cases in 2003. In 2005, there were only 77 reported cases.

Confidence in the MMR vaccine slumped in 1998 when a team led by Andrew Wakefield at the Royal Free hospital, north London, published research in the Lancet on bowel disease and autism. Dr Wakefield later suggested that there might be a link between autism and the MMR jab. He now faces professional misconduct charges brought by the General Medical Council.

In the letter, the scientists raise concerns that many children born during the height of the MMR scare are now set to enter schooling without the immunisation. "We are now faced with a potentially serious situation. Years of low uptake mean large numbers of unprotected children are now entering school. Unless this is rectified urgently, and children are immunised, there will be further outbreaks and more unnecessary deaths," it says.

Although immunisation rates are rising, they are still below the 95% level the World Health Organisation says is needed for "herd immunity". A year ago MMR uptake stood at 70.8% in London and 83% for the whole of the UK. The letter adds: "It is not too late to avert this predictable tragedy. It is time that due weight is given to the overwhelming body of scientific evidence in favour of the vaccine. Misguided concepts of "balance" have confused and dangerously misled patients. We all, media, politicians and health professionals, have a responsibility to protect the health of our children."

David Elliman, a consultant in community child health at Great Ormond Street Hospital, and a signatory of the letter, said that a vast body of research now vindicated the MMR vaccine, but he added that some media reports remained "partisan" in their coverage of research into the vaccine.

"Parents should be wary of simplistic headlines and information they read on the internet," he added.

Publish or be damned

Ben Goldacre

The Guardian

MMR is back. "US scientists back autism link to MMR," squealed the Telegraph. "Scientists fear MMR link to autism," roared the Mail. "US study supports claims of MMR link to autism," croaked the Times, a day later.

Strap me to the rocket and print my home address in the paper, I'm going after them again. So what was this frightening new data? Well it's hard to tell, since it hasn't been properly published anywhere yet. This is now standard operating procedure for all scare stories, because journalists have learnt that informed and informative public debate on unpublished research is basically impossible. So it turns out that these three stories were all about a poster presentation at a conference that had yet to occur on research not yet completed by a man with a track record of announcing research that then does not appear in academic journals.

The story is that Arthur Krigsman may have found genetic material (RNA) from vaccine-strain measles virus in some gut samples from children with autism and bowel problems. Some believe that this could implicate the vaccine in causing health problems.

But let's not forget, the Mail was promoting Dr Krigsman's research back in 2002: at that time, he was putting endoscopes into the bowels of young children with autism, and said he had found evidence of inflammation. Four years later, looking on PubMed, the standard database for all medical papers, it seems this research still has not been published in a peer-reviewed academic journal. Forgive my bluntness, but it seems a shame to go poking around up there if you're not going to write up your findings properly.

Meanwhile the Telegraph says his latest unpublished claim replicates similar work from 1998 by Andrew Wakefield, and from 2002 by Professor John O'Leary. But there is no such work from 1998 by Dr Wakefield, at least not on PubMed. Meanwhile it is well documented that other labs have tried to reproduce the 2002 study and come back with different results, and that the protocol was likely to have problems with false positives because of the tests used: two perfect examples of the importance of research being fully written up and published, so it can be replicated and assessed.

I could go on, but instead, here is the news you didn't read: in the May issue of the Journal of Medical Virology there was a similar study, only this one has actually been published. It looked for measles RNA in children with regressive autism after MMR vaccination but found no evidence of the magic vaccine-strain measles RNA to implicate MMR, and perhaps because of that unfrightening result, the study was loudly ignored by the press. Like all science in the real world it has its flaws, but because it has been published in full, I can read it, and pick holes in it.

In the spirit of science, the least opponents of MMR could do is share their data, and most importantly publish their scientific work, in full, openly, before their peers, rather than the press.

Study Shows Autism-related Developmental 'Red Flags' Identifiable At Age Two In Children

Science Daily — Early detection of autism is critical for early intervention, yet autism spectrum disorders (ASD) are typically not diagnosed until after three years of age. However, a study published today in the Journal of Child Psychology and Psychiatry found differences between typically developing children and those with ASD are detectable by two years of age. Because there are currently no medical diagnostic tests for autism, identifying developmental disruptions in infants and very young children with ASD may allow for earlier detection and critical intervention.

The study examined development in 87 infants at 6, 14 and 24 months of age using a standardized development test. Based on data and clinical judgment at 24 months, participants were classified as: unaffected, language delayed (LD) or ASD. Researchers compared development across groups at the three target ages and observed statistically significant differences between the ASD group and the unaffected group at 14 months. By 24 months, significant differences were detectable between the ASD group and both the unaffected and LD groups.

"Introducing behavioral interventions even one year earlier can make a tremendous difference in the lives of children with autism and their families," said Dr. Rebecca Landa, Director of the Center for Autism and Related Disorders at the Kennedy Krieger Institute in Baltimore, MD and lead author of the study. "If we are able to educate professionals to identify red flags in development we can then recognize and diagnose the disorder at one-and-a-half or two years of age, instead of three or four, allowing for earlier intervention and ultimately better outcomes."

Participants in the study included infants at high risk for autism (siblings of children with autism), and infants at low risk (no family history of autism). Researchers measured development using the Mullen Scales of Early Learning (MSEL), a standardized test which assesses five domains of development, including: gross and fine motor; visual reception; and receptive and expressive language. At 14 months, four of the five mean MSEL scores were significantly lower in toddlers with ASD than those in the unaffected group. By 24 months, the ASD group performed significantly worse than the unaffected group in all domains of development, and worse than the LD group in three domains. Nearly half of the ASD group showed developmental worsening between 14 and 24 months.

This study and previous research studies conducted by Dr. Landa found that developmental red flags for parents and physicians to watch for include: poor eye contact; reduced responsive smiling; diminished babbling; reduced social responsivity; and difficulty with language development, play and initiating or sustaining social interaction.

"With so many unanswered questions in the autism arena, we need to tackle this condition on many different fronts," said Dr. Gary Goldstein, President and CEO of the Kennedy Krieger Institute. "For this reason, experts at Kennedy Krieger are not only conducting early diagnosis and intervention research, but also investigating the genetic and environmental causes of autism, as well as other potential treatment options."

Autism is the fastest growing developmental disorder in the United States. This year more children will be diagnosed with autism than AIDS, diabetes and cancer combined, yet profound gaps remain in our understanding of both the causes and cures of the disorder. Increasing our knowledge about developmental disruptions in individuals with ASD is crucial, since early detection and intervention can lead to improved outcomes in individuals with ASD.

About the Kennedy Krieger Institute
Internationally recognized for improving the lives of children and adolescents with disorders and injuries of the brain and spinal cord, the Kennedy Krieger Institute in Baltimore, MD serves more than 12,000 individuals each year through inpatient and outpatient clinics, home and community services and school-based programs. Kennedy Krieger provides a wide range of services for children with developmental concerns mild to severe, and is home to a team of investigators who are contributing to the understanding of how disorders develop while pioneering new interventions and earlier diagnosis. For more information on Kennedy Krieger Institute, visit www.kennedykrieger.org.

Note: This story has been adapted from a news release issued by Kennedy Krieger Institute.

Mutant Mice Show Key Autism Traits

Science Daily — While the causes of autism remain complex and mysterious, researchers are steadily adding pieces to its intricate puzzle. In what they believe to be a significant new approach to understanding "autism spectrum disorders" (ASD), researchers have developed a mouse that shows abnormal social interactions and brain hypertrophy characteristic of the disease.

In an article in the May 4, 2006, Neuron, Luis Parada and his colleagues report the results of removing (knocking out) a single gene associated with brain disorders in mice. The gene, called Pten, had been associated with a broad array of such disorders when knocked out throughout the animals' bodies. However, Parada and colleagues engineered mice to knock out the gene only in mature, or "postmitotic," neurons of the cerebral cortex and hippocampus in the brain. These regions are associated with higher brain function such as learning and memory.

The mutant mice showed major abnormalities in a variety of social interactions normally undertaken in mice, found the researchers. For example, they were far less likely to approach and sniff new mice introduced into their cage, compared to normal mice. And while normal mice show markedly less interest when such new mice are later reintroduced, the mutant mice did not show such a reduction in interest. This abnormality indicated "impaired social learning or inability to identify the juvenile due to the low level of initial interaction," wrote the researchers.

In other tests of social behavior, the researchers found that--when given the choice of investigating a cage holding another mouse or an empty cage--the mutant mice showed similar preference for the two. Normal mice by far prefer investigating the caged mouse.

The researchers also found the mutant mice to be deficient in nest-forming and sexual and maternal behavior. In tests of their reaction to such sensory stimuli as bright environments, the mutant mice showed hyperactivity and increased anxiety. They also showed sporadic seizures.

The researchers concluded that "the mutant mice exhibited deficits in all social paradigms tested and also showed exaggerated reaction to sensory stimuli, anxiety-like behaviors, seizures, and decreased learning, which are features associated with ASD."

Finally, the researchers found that the mutant mice showed the same kind of abnormal overgrowth of neurons and their interconnections seen in some people with ASD that also show increased brain volume and enlarged heads.

Wrote Joy Greer and Anthony Wynshaw-Boris in a preview in the same issue of Neuron, "caution is warranted because there are aspects of ASD that are not recapitulated in the Pten mutants. For example, the Pten mutants do not display the expression of abnormal repetitive behaviors seen in ASD, although it is unreasonable to expect perfect phenotypic overlap of human ASD with any mouse model."

Also, they wrote, "as appropriately pointed out by the authors, Pten deletion is restricted to postmitotic neurons in the CNS [central nervous system] in their model, and current evidence suggests that ASD is a developmental rather than a neurodegenerative disorder."

Greer and Wynshaw-Boris concluded that "Whether or not the findings . . . have direct relevance to ASD, the experimental results described are intriguing and represent an important entry point to understanding the role of Pten in postmitotic neurons of the hippocampus and cortex as well as providing new insight into the molecular correlates mediating social- and anxiety-related behaviors in the postnatal CNS."

The researchers include Chang-Hyuk Kwon, Bryan W. Luikart, Craig M. Powell, Jing Zhou, Sharon A. Matheny, Wei Zhang, Yanjiao Li, and Luis F. Parada of the University of Texas Southwestern Medical Center in Dallas, TX; Suzanne J. Baker of St. Jude Children's Research Hospital in Memphis, TN. This work was supported in part by the American and Lebanese Associated Charities, NIH grant NS44172 (to S.J.B), and NIH grant R37NS33199 and the American Cancer Society (to L.F.P.).

Kwon et al.: "Pten Regulates Neuronal Arborization and Social Interaction in Mice." Publishing in Neuron, 50, 377-388, May 4, 2006. DOI 10.1016/j.neuron.2006.03.023 www.neuron.org

Vulnerability To Measles Among Nursery School Children Risen Sharply

Science Daily — Vulnerability to measles infection has risen sharply among nursery school children in Scotland since 1998, despite recent increases in MMR uptake, reveals research published ahead of print in the Archives of Disease in Childhood.

There are now 25 postcode districts. where more than one in five nursery school children is potentially at risk of catching measles, compared with just three in 1998, when unfounded claims that the vaccine might be linked to autism provoked widespread alarm.

MMR was introduced across the UK in 1988. The recommended schedule is for the first dose to be given at the age of 13 months, with the second dose at between 3 years and 5 years of age.

The researchers looked at the vaccination records for Scotland for all children born between 1987 and 2004, accounting for over one million children.

The records show that the sharpest decline began for children born from 1999 onwards, rather than for those born in 1997 as might be expected. This suggests that the negative publicity had a gradual but cumulative effect, say the authors.

The most affluent sectors of the population tended to either have their children vaccinated early or not at all, the figures show. But parents in the most deprived areas of Scotland tended to delay vaccinating their children.

The increased risks of measles to nursery school children are concerning, particularly in the areas of greatest deprivation, where the risk of measles outbreaks would add to existing health inequalities, say the authors.

Although rates of MMR vaccine uptake have increased across Scotland, these have not yet reached the levels before 1998, and are not expected to reach the levels required for population protection among young schoolchildren, say the authors.

Note: This story has been adapted from a news release issued by BMJ Specialty Journals.