Recherches sur l'autisme

[patic]

_deleted_

http://www.bmj.com/content/358/bmj.j2811

http://www.telegraph.co.uk/science/2017 ... tic-child/


Modération (Tugdual) : Fusion de sujets (message unique).

[thiloup]

Un retour sur le lien entre schizophrénie et autisme ils ont pendant longtemps été liés
https://spectrumnews.org/features/deep- ... zophrenia/

Des variants (=allèles) génétiques dans la population seraient responsables de 1/3 des cas d'autismes
https://spectrumnews.org/news/massive-c ... or-autism/

[olivierfh]

Des variants (=allèles) génétiques dans la population seraient responsables de 1/3 des cas d'autismes
https://spectrumnews.org/news/massive-c ... or-autism/

Cette présentation dans Spectrum (Massive collaboration unearths inherited risk factor for autism) semble un peu exagérée par rapport à
- l'article correspondant Meta-analysis of GWAS of over 16,000 individuals with autism spectrum disorder highlights a novel locus at 10q24.32 and a significant overlap with schizophrenia qui, en titre et en conclusions au début et à la fin, ne parle que d'une nouvelle zone (locus) de variantes de gènes (allèles) et pas d'une seule variante meilleure statistiquement ("Only one variant passed the stringent statistical threshold" dans Spectrum),
- l'article de Franck Ramus plusieurs fois cité sur le forum: Autisme : facteurs génétiques ou environnementaux ? avec la figure "camembert" expliquant au moins 1/2 des cas d'autisme tirée de la figure 2 de Trent Gaugler et al.: Most genetic risk for autism resides with common variation (Nature Genetics 46:881-885, 2014), qui utilise les données suédoises avec 14516 cas de TSA donc tout aussi "massives".

[thiloup]

L'optogénétique (il s'agit d'utiliser certaines longueur d'onde de lumière pour modifier l'expression des gènes dans le cerveau voire les connexions neuronales et donc le comportement d'un individu) arrive à améliorer le comportement social de souris autistes https://spectrumnews.org/news/flash-lig ... tism-mice/

[sylvainm]

https://femmesautistesfrancophones.com/ ... utistique/
Je sais pas si cette étude récente à déjà été postée

[olivierfh]

https://femmesautistesfrancophones.com/ ... utistique/
Je sais pas si cette étude récente à déjà été postée

Là mais c'est bien ici aussi car il ne s'agit pas que des femmes.

[123soleil]

Implication de l’épigénétique dans les troubles du spectre autistique : revue de la littérature

L’étiopathogénie des troubles du spectre autistique (TSA) est complexe et multifactorielle. Le rôle des facteurs
génétiques et environnementaux dans son émergence est bien documenté. Les recherches actuelles
tendent à montrer que ces deux facteurs agissent de manière synergique et que les modifications épigénétiques
pourraient constituer le médiateur qui sous-tend cette interaction. L’épigénétique désigne
les processus moléculaires permettant de moduler l’expression des gènes sans changements dans la
séquence de l’ADN. Il s’agit principalement de la méthylation de l’ADN et de la modification posttraductionnelle
des histones. Dans cet article, nous présentons un état synthétique des connaissances
actuelles sur l’hypothèse épigénétique dans les TSA. Après avoir développé les principaux mécanismes
intervenant dans la régulation épigénétique, nous exposons dans la première partie les arguments en
faveur de cette hypothèse dans les TSA. Les modifications épigénétiques des gènes candidats de l’autisme
seront abordées secondairement ainsi que les facteurs environnementaux qui pourraient augmenter le
risque des TSA par le biais de changement dans les marques épigénétiques. Finalement, nous exposerons
certaines des limites méthodologiques des études épigénétiques conduites dans les troubles
neurodéveloppementaux.

[123soleil]

Vitamin D and autism, what’s new?
An increasing amount of evidence points to the
possibility that gestational and early childhood vitamin D deficiency
[25(OH)D < 40 ng/ml] cause some cases of autism.
Vitamin D is metabolized into a seco-steroid hormone that
regulates about 3% of the 26,000 genes in the coding human
genome. It is also a neurosteroid that is active in brain development,
having effects on cellular proliferation, differentiation,
calcium signaling, neurotrophic and neuroprotective actions;
it also appears to have an effect on neurotransmission
and synaptic plasticity. Children who are, or who are destined
to become, autistic have lower 25(OH)D levels at 3 months of
gestation, at birth and at age 8 compared to their unaffected
siblings. Two open label trials found high dose vitamin D
improves the core symptoms of autism in about 75% of autistic
children. A few of the improvements were remarkable. The
vitamin D doses used in these children were 300 IU/KG/day
up to a maximum of 5000 IU/day (highest final 25(OH)D
level reached was 45 ng/ml). The other study used
150,000 IU/month IM as well as 400 IU/day [highest final
25(OH)D level was 52 ng/ml]. These two open label trials
were recently confirmed with a randomized controlled trial
(RCT) using 300 IU/kg/day with a maximum of 5000 IU/
day and resulted in effects similar to the two open label studies.
In terms of prevention, a recent small study showed vitamin
D supplementation during pregnancy (5000 IU/day) and
during infancy and early childhood (1000 IU/day) significantly
reduced the expected incidence of autism in mothers who
already had one autistic child from 20% to 5%. Vitamin D is
safe; for example, over the last 15 years, Poison Control reports
there have been approximately 15,000 cases of vitamin
D overdose. However only three of these 15,000 people developed
clinical toxicity and no one died. Given those facts,
practitioners might consider treating autism with 300 IU/kg/
day, and seek to prevent autism by supplementing pregnant
and lactating women (5000 IU/day) and infants and young
children (150 IU/kg/day) checking 25(OH)D levels every
3 months. These doses will increase 25(OH)D blood levels
to those recommended by the Endocrine Society. As the
American Academy of Pediatrics recommends vitamin D supplementation
during infancy and childhood, pediatricians and
family practitioners should evaluate the current evidence on
autism and vitamin D and act accordingly.


Vitamin D-related genes are subjected to significant de novo mutation burdens in autism spectrum disorder
Vitamin D deficiency is a putative environmental risk factor for autism spectrum disorder (ASD).
Besides, de novo mutations (DNMs) play essential roles in ASD. However, it remains unclear
whether vitamin D-related genes (VDRGs) carry a strong DNM burden. For the 943 reported
VDRGs, we analyzed publicly-available DNMs from 4,327 ASD probands and 3,191 controls.
We identified 126 and 44 loss-of-function or deleterious missense mutations in the probands
and the controls, respectively, representing a significantly higher DNM burden (p = 1.06 × 10−5;
odds ratio = 2.11). Specifically, 18 of the VDRGs were found to harbor recurrent functional
DNMs in the probands, compared with only one in the controls. In addition, we found that 108
VDRGs with functional DNMs in the probands were significantly more likely to exhibit
haploinsufficiency and genic intolerance (p < 0.0078). These VDRGs were also significantly
interconnected and co-expressed, and also with other known ASD-risk genes (p < 0.0014),
thereby forming a functional network enriched in chromatin modification, transcriptional
regulation, and neuronal function. We provide straightforward genetic evidences for the first
time that VDRGs with a strong degree of DNM burden in ASD and DNMs of VDRGs could be
involved in the mechanism underlying in ASD pathogenesis.

[olivierfh]

seek to prevent autism by supplementing pregnant and lactating women (5000 IU/day)

Quelques doutes sur l'objectivité quand il y a en bas de 1^e page:

John Jacob Cannell^1
1Vitamin D Council Inc., 1411 Marsh Street, Suite 203, San Luis Obispo, CA 93401, USA

et en plus en première phrase de l'intro:

An epidemic of autism appears to be underway in the United States, reminiscent of another epidemic that swept Europe 250 years ago

[Tugdual]

Quelques doutes sur l'objectivité [...]

Très bonne remarque !

C'est le soucis des archives ouvertes :
on trouve de tout, et n'importe quoi ...

[123soleil]

seek to prevent autism by supplementing pregnant and lactating women (5000 IU/day)

Quelques doutes sur l'objectivité quand il y a en bas de 1^e page:

John Jacob Cannell^1
1Vitamin D Council Inc., 1411 Marsh Street, Suite 203, San Luis Obispo, CA 93401, USA

et en plus en première phrase de l'intro:

An epidemic of autism appears to be underway in the United States, reminiscent of another epidemic that swept Europe 250 years ago

Selon leur site web 80% des revenus proviennent des abonnements de membres et des donations individuelles; et c'est une organisation à but non lucratif.

Quelques extraits :

Significant positive association between latitude and the prevalence of autism has recently been reported [35]. A 2013 study confirmed that children who livein low UVB light have almost three times the prevalence of ASD compared to children who live in sunny areas.[9].
...
If adequate amounts of vitamin D prevent autism, onewould expect children with rickets to have an increased risk of autism. At least two old papers addressed it, [36, 37] both published before Kanner described autism in 1943. Both papers describe Bweak mindedness,^ Bfeeble minds,^ Bmental dullness,^ Bodd introverted behavior,^ unresponsiveness and developmental delays [38]. Even more intriguing, both papers report that the mental condition in rachitic children improved with vitamin D treatment. More recently, a 2015 study of 35 rachitic children found 25% of the rachitic children also have autism as detected by standardized autism ratings scales [39].
...
The sun phobia and dramatic increase in sunblock use [49] is mainly the result of the 1989 American Medical Association Council on Scientific Affairs report, which warned Americans
against sun exposure, but did not include a word about vitamin D [50]. The AMA did not recommend that Americans take vitamin D supplements to make up for what the sun was no longer making in the skin. In fact, in 2001, researchers at the Centers for Disease Control reported that most children were Badequately protected^ from sunlight.^ [51] That is, the sun scare worked. Couple this with our movement from playing outside to playing video games, and the fear modern mothers have to let their child roam around the neighborhood, and you have the perfect storm for the development of vitamin D deficiency in infancy and toddlerhood.
...
Ensuite il y a un chapitre entier sur les mécanismes d'actions possibles où tout est intéressant. Ensuite vient la génétique.

Very recently, researchers in China found the lowest quartile of 25(OH)D levels of women in their first trimester were associated with a fourfold risk of ASD in the subsequent offspring [78]. In the same study, higher levels of 25(OH)D were associated with decreasing severity of ASD (R = −0.302, P = 0.001). Maternal 25(OH)D in the lower 3 quartiles [1–3] compared to the highest quartile [4] was associated with increased odds of ASD diagnosis in offspring: [Odds Ratio (OR), Q1: OR =3.99, (P = 0.001); Q2: OR =2.68, (P = 0.006); Q3: OR =1.36, (P = 0.25)]. The above studies imply that at least some of the genes that code for vitamin D’s metabolic pathways interact with vitamin D in the environment to influence the ASD phenotype. Ambient vitamin D overcomes genetic influences as evidenced by a study of 510 Vietnamese twins. [79] In this study, the heritability of 25(OH)D was found to be 70% in the winter (other studies have found a lower heritability) but during the summer 25(OH)D became 100% environmentally determined due to sunshine. It appears likely that vitamin D is both the long sought environmental and genetic factor that interacts with the environment to determine some ASD phenotypes. If one is born with the genetic tendency for ASD, that tendency may interact with environmentally or genetically determined low 25(OH)D, as the above studies imply. The result of such inheritance is low 25(OHD, starting in the first trimester, continuing at birth and early childhood, as shown by the decreased 25(OH)D levels in ASD children. It is important to point out that most fetuses and infants and toddlers with low vitamin D levels will not get autism; one still needs the genetic predisposition. For those who do, the clinical trials below imply that high dose vitamin D during gestation (enough to obtain 25(OH)D between 40 and 60 ng/ml) and during infancy and early childhood (40–60 ng/ml) may prevent most ASD by overcoming the significant heritability of 25(OH)D levels.

Ensuite on parle de ce qui se passe quand on prescrit de la vitamine D et notamment : In terms of prevention, an open label study of 20 infants born to mothers who already had one child with ASD, found 5000 IU/day of vitamin D given to the pregnant mothers and 1000 IU/day to the resultant child up to the age of 3 years reduced subsequent ASD incidence to 5% instead of the 20% rate consistently reported in the literature for mothers who already had one or more autistic children [90]

La dernière phrase : The scientific data that vitamin D will prevent or help treat autism is preliminary. However, that does not relieve practitioners from using all current available scientific evidence to make a risk benefit analysis of whether or not to treat or supplement their patients with vitamin D up to 40 - 60 ng/ml, the levels recommended by the Endoccrine Society.

[olivierfh]

Ensuite il y a un chapitre entier sur les mécanismes d'actions possibles où tout est intéressant.

Oui les mécanismes sont plausibles: (référence 52)
Asad Ali, Xiaoying Cui, Darryl Eyles: Developmental vitamin D deficiency and autism: putative pathogenic mechanisms, The Journal of Steroid Biochemistry and Molecular Biology, 2017

Apparemment on ne se met pas assez au soleil pour fabriquer de la vitamine D dans la vie moderne...

[olivierfh]

Une étude sur 9 autistes et 10 non-autistes entre 9 et 16 ans, en vue d'une méthode de diagnostic par électroencéphalogramme (EEG):

Ridha Djemal et al.: EEG-Based Computer Aided Diagnosis of Autism Spectrum Disorder Using Wavelet, Entropy, and ANN, BioMed Research International 2017:9816591

The highest classification accuracy is obtained with combination of DWT [discrete wavelet transform] and Shannon entropy for feature extraction. After some optimization process we obtained classification accuracy up to 99.71%.

[Tugdual]

À confirmer sur un échantillon plus grand, parce
que là, c'est quand même vraiment ultra léger ...

[123soleil]

How Useful Is Electroencephalography in the Diagnosis of Autism Spectrum Disorders and the Delineation of Subtypes: A Systematic Review


un truc dans la m^me veine mais avec les pupilles : https://www.nature.com/articles/s41598-017-06829-1