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.

The Role Of Evolutionary Genomics In The Development Of Autism

Science Daily — Scientists at the London School of Economics, UK and Simon Fraser University, Canada have described the first hypothesis grounded in evolutionary genomics explaining the development of autism.

In an article to be published in a forthcoming issue of Journal of Evolutionary Biology, Dr Christopher Badcock and Professor Bernard Crespi explore the 'imprinted brain hypothesis' to explain the cause and effect of autism and autistic syndromes such as Asperger's syndrome, highlighted by the book The Curious Incident of the Dog in the Night-Time, which involves selective disruption of social behaviour that makes individuals more self-focussed whilst enhancing skills related to mechanistic cognition.

The 'imprinted brain hypothesis' suggests that competition between maternally and paternally expressed genes leads to conflicts within the autistic individual which could result in an imbalance in the brain's development. This is supported by the fact that there is known to be a strong genomic imprinting component to the genetic and developmental mechanisms of autism and autistic syndromes.

Professor Bernard Crespi from Simon Fraser University, Canada explains: "The imprinted brain hypothesis underscores the viewpoint that the autism spectrum represents human cognitive diversity rather than simply disorder or disability. Indeed, individuals at the highest-functioning end of this spectrum may have driven the development of science, engineering and the arts through mechanistic brilliance coupled with perseverant obsession."

The core behavioural features of autism such as self-focussed behaviour, altered social interactions and language and enhanced spatial and mechanistic cognition and abilities -- as well as the degree to which the brain functions and structures are altered -- also supports this hypothesis.

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Read or download the article for FREE: http://www.blackwell-synergy.com/doi/full/10.1111/j.1420-9101.2006.01091.x.

Note: This story has been adapted from a news release issued by Blackwell Publishing Ltd.

Innovative Approach Affords Researchers Clearer View Of Autism

Science Daily — Using new technology and a unique approach, Binghamton University researchers are hoping to help children with autism spectrum disorders (ASD) deal with their most common and problematic areas of deficit - social and life skills.

Raymond Romancyzk, director of Binghamton University's Institute for Child Development, is heading up an intensive research project to learn how children - with and without autism - interact with the world around them. Using a combination of a state-of-the-art eye tracking system, miniaturized psychophysiological monitoring and multiple computers for high-speed processing, Romancyzk and his team are able to ask questions that could help answer how individuals with autism process information and stimuli from the world around them.

The team is using a tracking system that doesn't require the subject to wear a tracking device. Instead a video camera, built into a small desk observes a child. First, reference points are established by having the child watch a short animation, and with the help of a computer, the system overlays the position of a child's eyes onto a second video image of the child's field of vision. While the tracking systems observes the child's face, the eyes are located in the video image and computers record further eye movement.

This allows the team to see where and for exactly how long and where the child is looking, such as at faces, objects, and actions, either live or on video, and permits measurement of an index of physiological anxiety, and the more standard measurement of affect, performance, and behavior. The fact that children don't have any physical contact with the eye tracking system and don't have to wear any special apparatus makes it a great tool even with very young children, whether they have autism or not.

Gathering data from "typical' children will help researchers better distinguish where the differences between non-autistic children and children with autism. The new technology is enabling researchers to ask questions that may have far-reaching implications for educational and clinical approaches for autism.

"Part of the reason for this elaborate scheme is we've also been doing some research on how adults interact with children with autism, how they perceive what they think is going on versus what the child is actually doing," said Romanczyk. "This ties into the subtleties of social interaction that we take for granted. You look at someone and you can tell by their body posture, their gestures, tone of voice, eye gaze and so on, what's being communicated. With children with autism, it's more difficult to do."

The Binghamton University laboratory is the first to achieve simultaneous non-invasive measurement of multiple variables within the full range of individuals with ASD. To support their on-going research efforts, Romancyzk's team recently received funding through the Organization for Autism Research. One aspect of this grant will be to develop a parent-administered assessment of the child's social deficits. The assessment will be validated with the more comprehensive laboratory assessment process, and specific treatment strategies tailored to each child with severe social interaction deficits will be developed based upon the parental and comprehensive laboratory assessments.

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

Experts Question Prevalent Stereotypes About Autism

Science Daily — As theories about autism spread like wildfire in the media and the general public, a panel of autism experts will reflect on the validity of four widely held - and potentially inaccurate - assumptions about the developmental disability.

Drawing on the latest in autism research, a psychologist, an epidemiologist, a psychiatrist and a physician will critically assess widespread stereotypes about autism during a symposium entitled "Science of Autism," at the 2006 Annual Meeting of the American Association for the Advancement of Science (AAAS).

"With the surge in both scientists and society turning their attention toward autism, there comes responsibility," says Morton Gernsbacher, a Vilas Research Professor of psychology at the University of Wisconsin-Madison and the symposium's chair and organizer.

"It behooves us as scientists to distinguish uninformed stereotypes from scientific reality and to move beyond myths and misconceptions."

During her talk, Gernsbacher will cast doubt on the prevalent notion among autism researchers that autistic individuals lack a "theory of mind." The belief that autistic children lack a sense of both their own minds and those of others emerged about 20 years ago, becoming a seemingly undisputed tenet in the literature since then, says Gernsbacher.

When the psychologist began delving into the question, however, she found that scientists usually ascertain how well individuals perceive the mind with tasks that require a relatively sophisticated level of linguistic ability. Since a common diagnostic criteria for autism is the impairment of communication skills, Gernsbacher says it's not surprising that most autistic children don't fare well on such theory-of-mind tests.

"I think we as a society fall prey to a slippery slope when we begin talking about members of our society as not appreciating that they or others have a mind," says Gernsbacher. "An uncritical acceptance of the hypothesis that autistic individuals lack a theory of mind can seriously compromise how autistic individuals are treated in the workplace, the community and society in general."

The other panelists will similarly address other stereotypes about autism. Judith Grether, an environmental epidemiologist who works for the state of California, will contest the popular notion that North America is reeling from an autism epidemic. Grether will make the point that a higher number of reported autism cases - due to looser diagnostic criteria - doesn't necessarily translate into an actual rise in the overall number of cases.

Panelist Irving Gottesman, a psychiatrist at the University of Minnesota, will similarly dispute the idea circulating among some researchers that childhood vaccines potentially cause autism. Recent large-scale literature reviews, he says, fail to support that link.

Finally, Laurent Mottron, an autism researcher and physician at Montreal's Hopital Riviere des prairies, will discuss the common idea that most autistic people are cognitively impaired. Mottron will assert that the numbers of cognitively impaired autistic individuals have been over-estimated - a fact that has important implications for the kind of therapies that autistic individuals receive.

Ultimately, Gernsbacher hopes that events such as today's AAAS symposium will help to set the record straight. "I would like scientists to become more skeptical of the stereotypes that flourish about autism and members of society to become more skeptical of the myths that are circulated."

Note: This story has been adapted from a news release issued by University of Wisconsin-Madison.

Utah Researchers Confirm Chromosome May Harbor Autism Gene

Science Daily — Using technology that allows DNA from thousands of genes to be collected and surveyed on a 3 x 1½-inch chip, University of Utah medical researchers have confirmed that a region on a single chromosome probably harbors a gene that causes autism. The researchers at the U School of Medicine made the finding by tracing variations in the DNA of an extended Utah family that has a high occurrence of the disorder and whose members are descended from one couple.

As part of the study, the researchers also ruled out one gene that appeared to be a good candidate for being linked to autism. They're now looking at other genes for a connection to the disorder.

Published in Human Heredity online, the study is part of the Utah Autism Research Project. The researchers are interested in finding more families with a history of autism to join the study.

The just-published research confirms Finnish studies of families that linked autism to the same region on chromosome 3, according to principal author Hilary Coon, Ph.D., research associate professor of psychiatry. In fact, the results of the U of U research were surprisingly similar to the Finnish studies, Coon said.

"It was remarkable to confirm the Finnish studies," she said. "Our results were so close to their evidence, we thought it was important."

Autism is a behavioral disorder that strikes before age 3 and is characterized by impaired ability in social interactions and communication. Those with autism also display repetitive behaviors and interests.

The study involved 31 members of a family of Northern European ancestry, seven of whom have autism or an autism-related disorder. The family members are part of the Utah Population Database, a computerized set of the genealogies of 170,000 Utah families comprising 1.6 million people. Information on some families goes back to the state's pioneer founders.

The researchers used a gene chip similar to a microarray to search for genetic markers of autism.

They used a coated glass chip from Affymetrix, Inc. This chip has 10,000 short segments of DNA with known gene sequence variations, called single nucleotide polymorphisms (SNPs), attached to 3/8 by 3/8-inch area. The DNA strands of the family members were broken up and then bonded to the DNA on the chip, allowing researchers to compare the variations in the SNPs of the different DNA on an extremely fine scale.

The chance of the same variants of SNPs in a particular region on a chromosome being passed through several generations from a founding couple to multiple affected family members is slight. When such identical blocks of SNPs are found, the chromosomal region often is a good candidate for being linked to a disease.

Other studies, including the Finnish ones, have found a high degree of evidence linking chromosome 3 to autism, so Coon and the other U researchers began their search on that chromosome. The first region of the chromosome they looked at contained 106 SNPs, 70 of which strongly indicated a gene in that region being linked to autism.

One gene, FXR1, appeared to be a likely candidate for a link to autism. FXR1 is similar to the X-chromosome Fragile X gene, FMR1. Mutations in FMR1 cause Fragile X Syndrome, an inherited condition that can cause mental impairments ranging from learning disabilities to severe cognitive problems. Fragile X syndrome has been shown to overlap with autism, and because FXR1 is similar to the gene that causes the syndrome, U researchers suspected FXR1 might be linked to autism. But after analyzing the entire coding sequence of FXR1, the researchers found no alterations in the gene likely to contribute to autism.

Based on statistical evidence, they're now looking at other genes. But evidence that a gene on a particular region of chromosome 3 is linked to the disorder doesn't preclude other genes from being a cause of autism, according to Coon. All in all, the researchers have a daunting search ahead of them.

"We're just looking for the needle in the haystack," Coon said.

Along with the original family, the U researchers are studying two more families with autism in some members, and they'd like to find others in which the disorder occurs. Large and small families with individual or multiple cases of autism are welcome to join. Those interested can call (801) 585-9098.

Other authors of the study are: Nori Matsunami, Jeff Stevens, Judith S. Miller, Ph.D, assistant professor of psychiatry, and Carmen Pingree, all with the Neurodevelopmental Genetics Project in the Department of Psychiatry; Nicola J. Camp, Ph.D., assistant professor of medical informatics; Alun Thomas, Ph.D., professor of medical informatics; Janet E. Lainhart, M.D., associate professor of psychiatry; Mark F. Leppert, professor and chair of Human Genetics; and William M. McMahon, M.D., professor of psychiatry and principal investigator of the Utah Autism Research Project.

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The University of Utah Health Sciences Center is internationally regarded for its research and clinical expertise in the health sciences. Through its four major colleges --the School of Medicine; College of Pharmacy; College of Nursing; and College of Health--the Health Sciences Center conducts leading-edge research in cancer, genetics, pharmaceutical sciences, and numerous other areas of medicine. The Health Sciences Center also is the major training ground for Utah's physicians, pharmacists, nurses, therapists, and other health-care professionals.

Note: This story has been adapted from a news release issued by University of Utah Health Sciences Center.

Charlie Hebdo relaxé pour la critique d'une méthode de communication avec les autistes

Charlie Hebdo, qui avait qualifié la méthode dite de "communication facilitée", censée permettre de retranscrire les pensées des handicapés mentaux et notamment des autistes, de "grotesque charlatanerie", a été relaxé par le tribunal correctionnel de Paris, a-t-on appris lundi auprès du tribunal.L'hebdomadaire était poursuivi par Anne-Marguerite Vexiau, qui a introduit en France cette méthode créée aux Etats-Unis.Selon le jugement rendu par la 17ème chambre du tribunal correctionnel, cette méthode "vise à retranscrire les pensées de personnes déficientes mentales, et principalement autistes, par le truchement d'un thérapeute muni d'un clavier alphabétique sur lequel le patient pianote, livrant ainsi des phrases qui sont présentées comme l'expression de ses pensées tues".Dans un article publié le 17 décembre 2003, Charlie Hebdo s'indignait: "non seulement, c'est une grotesque charlatanerie mais, en plus, elle est remboursée par la sécurité sociale".Mme Vexiau estimait que l'article était diffamatoire à son égard, notamment parce qu'il lui imputait d'être l'animatrice d'un mouvement sectaire qui aurait manoeuvré pour obtenir un remboursement de sa méthode par la sécurité sociale.Or le tribunal n'a relevé dans l'article de Charlie Hebdo aucun propos l'accusant de pratiques sectaires ou de tromperie au détriment de la sécurité sociale.Par ailleurs, le tribunal a considéré que l'hebdomadaire était libre de qualifier ainsi la méthode de Mme Vexiau, cette opinion n'étant qu'un "jugement de valeur, exprimé certes sans nuance, mais que le journaliste présente comme étant son point de vue".

TROIS QUESTIONS À... Patrick Bruderlein

Expert en autisme, Patrick Bruderlein est chargé de cours à l’université de Genève et de Fribourg et intervient auprès du Service éducatif itinérant genevois.

Qu’est-ce que l’autisme?

La définition est donnée par l’Organisation mondiale de la santé. L’autisme est un trouble envahissant du développement, et non un trouble spécifique comme l’incapacité à s’exprimer.

Il se caractérise par trois aspects: une altération des comportements sociaux, une défaillance de la communication et, enfin, une restriction des intérêts. Le trouble doit apparaître avant l’âge de 3 ans.

Comment évolue un enfant autiste?

De manière très hétérogène. Beaucoup d’études montrent que le cadre éducatif est déterminant pour le développement. Les premières écoles pour autistes datent des
années 1970. Des recherches dévoilent que les enfants qui sont passés par ces institutions sont plus indépendants, moins anxieux que les autres enfants autistes. Il est vrai que l’évolution dépend de la sévérité du trouble,mais également de la prise en charge.

Quelle est, selon vous, la prise en charge la plus adaptée pour un enfant autiste?

Une prise en charge éducative. Comme tous les enfants, il faut qu’ils aillent à l’école. Il existe une guerre ouverte en éducation quant à la prise en charge. Chacun défend sa chapelle. Pour moi, la méthode éducative est la plus efficace. Cette approche s’oppose aux prises en charge uniquement thérapeutiques. Elle ne cherche pas à soigner la personne, mais à lui apprendre à mieux vivre. Les parents sont au minimum des collaborateurs. Beaucoup d’experts, dans les années 1950, soutenaient que l’autisme était dû à une mauvaise relation avec les parents, à une mère incapable d’aimer son enfant. Depuis, de nombreuses études ont montré l’absurdité de ces théories. Mais il en existe encore des relents dans certaines institutions. On n’accuse plus les parents directement,mais cela ressort de manière camouflée.

PROPOS RECUEILLIS PAR VPN

L’autisme est-il une forme extrême de la masculinité ?

Article de Simon Baron-Cohen The New York Times

Traduction de Danièle Langloys

Deux importants débats ont beaucoup attiré l’attention l’an dernier. L’un concerne les causes de l’autisme, alors que l’autre vise les différences quant aux aptitudes scientifiques entre les sexes. Au risque d’ ajouter de l ’huile sur les deux feux, je soumets l’idée que ces deux axes de recherche ont beaucoup en commun. En étudiant les différences entre les cerveaux masculin et féminin, nous pouvons apporter des aperçus significatifs sur le mystère de l’autisme.

Alors Lawrence Summers, le président de l’Université d’Harvard, avait-il raison de remarquer que les femmes, par nature, avaient moins d’aptitudes que les hommes à être des scientifiques de haut niveau ? A en juger par la recherche actuelle, oui et non. Il est vrai que les scientifiques ont montré les différences physiologiques et psychologiques entre cerveau masculin et cerveau féminin. Mais Summers avait tort d’en déduire que ces différences rendent une femme moins capable individuellement qu’un homme de devenir un scientifique de haut niveau.
En fait, les différences qui ressortent dans la recherche sur le cerveau reflètent des moyennes, c’est-à-dire qu’elles apparaissent seulement si on étudie des groupes d’hommes et de femmes et qu’on compare les moyennes des deux groupes sur des tests psychologiques ou des mesures physiologiques particuliers. A ce jour, ce qui ressort ne nous dit rien sur les individus, c’est-à-dire que si vous êtes une femme, il n’est pas sûr d’en inférer que vous ne pourriez jamais devenir un prix Nobel dans le domaine de recherche scientifique que vous avez choisi. Un bon scientifique est un bon scientifique, quel que soit le sexe.
Cependant, avec l’imagerie cérébrale, on peut observer des différences entre le cerveau moyen d’un homme et celui d’une femme. Par exemple, le cortex moyen d’un homme ( la partie en haut du cerveau concernée par l’activité intellectuelle de haut niveau) est de 9% plus gros que celui d’une femme. De même, bien que moins distinct, on trouve une différence positive de taille dans tous les lobes du cerveau masculin. En moyenne, les hommes ont aussi une amygdale plus importante ( structure en forme d’amande au centre du cerveau impliquée dans les processus de peur et de l’émotion) et plus de cellules nerveuses. Comment exactement ces différences de taille affectent le fonctionnement, si du moins c’est le cas, n’est pas encore connu.

Chez les femmes cependant, les connexions qui permettent la communication entre les deux hémisphères du cerveau ont tendance à être plus denses, ce qui facilite peut-être les échanges. Cela peut expliquer pourquoi une étude de l’Université de Yale a trouvé que dans l’ exécution des activités langagières, les femmes probablement activent les deux hémisphères alors que les hommes, en moyenne, activent seulement l’hémisphère gauche.

Des tests psychologiques révèlent aussi des exemples de différence entre les sexes. En moyenne, les hommes terminent plus vite et avec un score plus élevé que les femmes un test qui demande à celui qui le passe de visualiser l’apparence d’un objet après qu’il a tourné en trois dimensions. La même chose est vraie pour des tests de lecture de carte et pour les tests de figures encastrées qui demandent aux sujets de trouver une forme de pièce cachée dans un dessin plus grand. Les hommes sont surreprésentés dans les pourcentages élevés aux tests mathématiques de niveau universitaire et ont tendance à obtenir des scores plus élevés dans les tests de mécanique que les femmes. Les femmes, en revanche, font en moyenne des scores plus élevés que les hommes aux tests de reconnaissance des émotions, de perception sociale et de capacités langagières.

Beaucoup de ces différences entre les sexes s’observent chez des adultes, ce qui pourrait conduire à la conclusion que tout ce qu’elles reflètent, ce sont des différences de socialisation et d’expérience. Mais quelques différences s’observent de manière extrêmement précoce dans le développement, ce qui peut suggérer que la biologie joue aussi un rôle. Par exemple, les filles ont tendance à parler plus tôt que les garçons, et dans la seconde année de leur vie, leur vocabulaire augmente plus rapidement. Les filles d’un an ont plus de contacts visuels que les garçons de leur âge.

Dans mon travail, j’ai résumé ces différences en disant que les hommes en moyenne instinctivement systématisent mieux et que les femmes ont plus d’ empathie. La systématisation entraîne l’identification des lois qui gouvernent le fonctionnement d’un système. Une fois qu’on connaît les lois, on peut contrôler le système ou prédire son comportement. L’empathie, elle, entraîne la reconnaissance de ce qu’une autre personne peut être en train de ressentir ou de penser, et la réponse à ces sentiments avec une émotion personnelle appropriée.

Et l’autre affirmation de Summer que de telles différences entre les sexes sont innées ? Nous savons que la culture joue un rôle dans la différenciation sexuelle mais la biologie aussi. Par exemple, au premier jour de la vie, les nouveau-nés garçons et filles font attention à des choses différentes. En moyenne, à l’âge d’un jour, plus de garçons vont regarder un mobile suspendu au-dessus d’eux, alors que plus de filles vont regarder un visage humain.

On a aussi trouvé que la quantité de testostérone prénatale, qui est produite par le fœtus et mesurable dans le liquide amniotique où baigne le bébé dans l’utérus, prédit comment un enfant sera sociable. Plus le niveau de testostérone est élevé, moins l’enfant manifestera de contacts visuels tout-petit et plus lentement il développera le langage. C’est relié au rôle de la testostérone fœtale dans l’influence sur le développement du cerveau.

Les hommes produisent manifestement beaucoup plus de testostérone prénatale que les femmes, mais les niveaux varient considérablement même à l’intérieur du même sexe. En fait, ce n’est pas le sexe en lui-même qui détermine quel type de cerveau on a, mais le niveau d’hormone prénatale. A partir de là, c’ est un petit bond vers l’idée intrigante qu’un homme peut avoir un cerveau typiquement féminin ( si son niveau de testostérone est bas), alors qu’une femme peut avoir un cerveau typiquement masculin ( si son niveau de testostérone est élevé).

Qu’est-ce que tout cela peut avoir à voir avec l’autisme ? En accord avec ce que j’ai appelé la théorie du cerveau masculin extrême de l’autisme, les personnes avec autisme simplement vont avec un profil masculin extrême, avec une tendance particulièrement forte à systématiser et une inhabituellement basse à l’empathie.

Et cette analyse a un sens. Elle aide à expliquer l’incapacité sociale dans l’autisme, parce que les difficultés d’empathie rendent plus difficile de construire et maintenir des relations avec les autres. Elle explique aussi les îlots de capacité que les personnes avec autisme manifestent dans des sujets comme les maths, la musique ou le dessin – toutes aptitudes qui bénéficient de la systématisation.

Les personnes avec autisme développent souvent des obsessions qui peuvent n’ être rien d’autre qu’une intense systématisation à l’œuvre. Les enfants peuvent devenir obsédés par des interrupteurs électriques ( un système électrique), ou des horaires de train (un système temporel) ou des objets qui tournent (un système physique), ou les noms des poissons des fonds marins (un système naturel, taxinomique). Les enfants avec un autisme sévère qui peuvent avoir des difficultés d’apprentissage associées et peu d’ aptitudes verbales, peuvent exprimer leurs obsessions par des bonds constants sur un trampoline ou en tournant sur eux-mêmes parce que le mouvement est extrêmement appuyé sur des lois et prévisible. Quelques enfants avec un autisme sévère alignent des objets pendant des heures de suite. Ce qui a l’habitude d’être écarté par les cliniciens comme « sans but, conduite répétitive, peut en fait être le signe d’un esprit qui est extrêmement adapté pour systématiser.

Il faut être extrêmement prudent quand on avance une cause de l’autisme, parce que ce domaine abonde en théories qui se sont écroulées sous l’effet d ’un examen minutieux de l’expérience. Cependant, mon hypothèse est que l’ autisme est le résultat génétique d’un appariement par similarité entre des parents qui sont tous les deux fortement aptes à systématiser. L’expression convient quand le semblable est attiré par le semblable, et il y a quatre raisons importantes de croire que les choses se passent ainsi:

1. à la fois les mères et les pères d’enfants avec autisme terminent le test des figures encastrées plus vite que les hommes et les femmes de la population générale.
2. à la fois les mères et les pères d’enfants avec autisme ont plus fréquemment des pères qui ont des talents de systématisation (ingénieurs par exemple).
3. quand on observe l’activité du cerveau par imagerie (RMN), les hommes et les femmes en moyenne montrent des schémas différents quand ils font des tâches de systématisation ou d’empathie. Mais à la fois les mères et les pères d’enfants avec autisme montrent des modèles fortement masculins d’ activité cérébrale.
4. à la fois les mères et les pères d’enfants avec autisme obtiennent des scores supérieurs à la moyenne à un questionnaire qui mesure combien un individu a de traits autistiques. Ces résultats suggèrent une cause génétique de l’autisme avec une contribution génétique des deux parents qui se rapporte finalement à une forme similaire d’esprit : celle avec une affinité pour la pensée organisée de manière systématisée.

Pour vérifier pleinement cette théorie, nous avons encore besoin de beaucoup de travail. Les gènes spécifiques en cause doivent être identifiés. C’est une théorie qui peut être discutée et peut-être mal reçue parmi ceux qui croient que la cause de l’autisme est partiellement ou totalement environnementale. Mais la controverse n’est pas une raison pour ne pas la vérifier – systématiquement, pourrions-nous dire.

Simon Baron-Cohen est directeur du centre de recherche sur l’autisme à l’ université de Cambridge et l’auteur de « La différence essentielle : la vérité au sujet du cerveau masculin et féminin ».