1. Hjiej H, Doyen C, Couprie C, Kaye K, Contejean Y. {{[Substitutive and dietetic approaches in childhood autistic disorder: Interests and limits.]}}. {Encephale};2008 (Oct);34(5):496-503.Approches substitutive et dietetique du trouble autistique de l’enfant : interets ou limites ?

INTRODUCTION: Autism is a developmental disorder that requires specialized therapeutic approaches. Influenced by various theoretical hypotheses, therapeutic programs are typically structured on a psychodynamic, biological or educative basis. Presently, educational strategies are recommended in the treatment of autism, without excluding other approaches when they are necessary. Some authors recommend dietetic or complementary approaches to the treatment of autism, which often stimulates great interest in the parents but also provokes controversy for professionals. Nevertheless, professionals must be informed about this approach because parents are actively in demand of it. LITERATURE FINDINGS: First of all, enzymatic disorders and metabolic errors are those most frequently evoked in the literature. The well-known phenylalanine hydroxylase deficit responsible for phenylketonuria has been described as being associated with autism. In this case, adapted diet prevents mental retardation and autistic symptoms. Some enzymatic errors are also corrected by supplementation with uridine or ribose for example, but these supplementations are the responsibility of specialized medical teams in the domain of neurology and cannot be applied by parents alone. Secondly, increased opoid activity due to an excess of peptides is also supposed to be at the origin of some autistic symptoms. Gluten-free or casein-free diets have thus been tested in controlled studies, with contradictory results. With such diets, some studies show symptom regression but others report negative side effects, essentially protein malnutrition. Methodological bias, small sample sizes, the use of various diagnostic criteria or heterogeneity of evaluation interfere with data analysis and interpretation, which prompted professionals to be cautious with such diets. The third hypothesis emphasized in the literature is the amino acid domain. Some autistic children lack some amino acids such as glutamic or aspartic acids for example and this deficiency would create autistic symptoms. However, for some authors, these deficits are attributed to nutritional deficits caused by the food selectivity of children. A fourth hypothesis concerning metabolic implication in autism is the suspicion that a food allergy phenomenon could interfere with development, and it has been observed that Ig levels are higher in autistic children than in control children. Autistic children with a positive reaction to food Ig would have a more favourable outcome with diet excluding some kinds of food; but most of those diets are drastic and ethically debatable. Fifth, glucidic catabolism could be deleterious with an excess of ketonic products that will initiate comitial seizures. Few studies with ketogenic diet have been conducted but, as it has been described with epileptic subjects, those diets would diminish autistic symptoms. Not enough studies have been conducted that would allow one to draw any firm conclusions. The sixth hypothesis is linked with vitamin deficiencies that are a notably important area of research in the treatment of autism. Vitamin B12 or B6 deficiencies have been studied in several articles, and many of them were controlled studies. French teams also emphasize an interest in supplementation with B12 or B6. The two last hypotheses concern auto-immune patterns and the toxic effects of heavy metals like mercury. There is a paucity of methodologically satisfying studies that support these two hypotheses and diet recommendations. Following these assumptions, some dietetic approaches have been recommended, even though the methodological aspects of supporting studies are poor. The most famous diet is the gluten-free and/or casein-free diet. Only two controlled studies attracted our attention. Even if for some autistic children such a diet was positive, for others, gluten-free or casein-free diets were poorly tolerated and, for some authors, not without considerable side effects, the more prejudicial of which was the Kwashiorkor risk. Ketogenic diets have been studied in one non controlled study, but even if positive results have been noted by the authors, the ketogenic diet is very restricting and the long term effects have not been evaluated. Vitamin supplementation is the one and only diet domain where there have been many repeated and placebo-controlled studies. Side effects are rare and mild even if high doses of vitamin B6 are advocated in these studies. In total, as evoked by Rimland, 11 controlled placebo-blind studies have been conducted and 50% of autistic children with this supplementation had improved autistic signs. However, these results still remain debated. Finally, more rarely, enzymatic abnormalities need specific diets which have some positive consequences, but such diets could not be applied by parents alone and are the responsibility of specialized teams. For discussion purposes we can emphasize that, in spite of the amount of studies concerning the effects of specialized diets, few are methodologically satisfying. We can not ignore that some side effects are possible with such approaches and parents need to be informed of them. Some are even potentially serious, such as diets with metal chelators. In spite of those results, vitamin supplementation seems to be the only one that some specialized teams in autism could apply, always with parent agreement. In conclusion, within this scientific field, studies on eating habits of autistic children should be conducted because of their food selectivity or avoidance.

2. Koyama T, Kurita H. {{Cognitive profile difference between normally intelligent children with Asperger’s disorder and those with pervasive developmental disorder not otherwise specified}}. {Psychiatry Clin Neurosci};2008 (Dec);62(6):691-696.

Aim: Asperger’s disorder (Asperger syndrome, AS) and pervasive developmental disorder not otherwise specified (PDD-NOS) are different subtypes of mild pervasive developmental disorders (PDD). Methods: Using the Japanese version of the Wechsler Intelligence Scale for Children-Third Edition (WISC-III), 28 AS children (mean age, 9.3 years, 24 male) were compared with 78 PDD-NOS children (mean age, 7.6 years, 64 male) with normal intelligence (IQ >/= 85), using analysis of covariance (ancova) with the chronological age of a child as a covariate. Results: Verbal IQ tended to be higher in the AS children than in the PDD-NOS children (mean raw scores, AS vs PDD-NOS: 103.9 vs 99.6; P < 0.10), although full-scale and performance IQ did not differ significantly. Compared with the PDD-NOS children, the AS children scored significantly higher on Freedom from Distractibility index (110.1 vs 104.5; P < 0.05) consisting of Arithmetic (11.0 vs 9.9, P = 0.04) and Digit Span (12.4 vs 11.6, P = 0.051), but tended to score lower on Coding (8.5 vs 9.8, P = 0.08). Conclusion: The typical cognitive profile of PDD (i.e. low score on Comprehension and high score on Block Design) was shared by both groups, which may support the validity of the current diagnostic classification of PDD. Relatively better verbal ability in AS children seems to reflect their normal language acquisition in infancy, and strong numeric interest may produce the AS children’s mathematical excellence over PDD-NOS children. A low score on Coding in AS children might reflect their extreme slowness, circumstantiality and/or drive for perfection.

3. Lee PS, Yerys BE, Della Rosa A, Foss-Feig J, Barnes KA, James JD, Vanmeter J, Vaidya CJ, Gaillard WD, Kenworthy LE. {{Functional Connectivity of the Inferior Frontal Cortex Changes with Age in Children with Autism Spectrum Disorders: A fcMRI Study of Response Inhibition}}. {Cereb Cortex};2008 (Dec 9)

Unmasking the neural basis of neurodevelopmental disorders, such as autism spectrum disorders (ASD), requires studying functional connectivity during childhood when cognitive skills develop. A functional connectivity magnetic resonance imaging (fcMRI) analysis was performed on data collected during Go/NoGo task performance from 24 children ages 8-12 years (12 with ASD; 12 controls matched on age and intellectual functioning). We investigated the connectivity of the left and right inferior frontal cortex (IFC; BA 47), key regions for response inhibition, with other active regions in frontal, striatal, and parietal cortex. Groups did not differ on behavioral measures or functional connectivity of either IFC region. A trend for reduced connectivity in the right IFC for the ASD group was revealed when controlling for age. In the ASD group, there was a significant negative correlation between age and 2 right IFC correlation pairs: right IFC-bilateral presupplementary motor area (BA 6) and right IFC-right caudate. Compared with typical controls, children with ASD may not have gross differences in IFC functional connectivity during response inhibition, which contrasts with an adult study of ASD that reported reduced functional connectivity. This discrepancy suggests an atypical developmental trajectory in ASD for right IFC connectivity with other neural regions supporting response inhibition.

4. Matevossian A, Akbarian S. {{A chromatin assay for human brain tissue}}. {J Vis Exp};2008 (13)

Chronic neuropsychiatric illnesses such as schizophrenia, bipolar disease and autism are thought to result from a combination of genetic and environmental factors that might result in epigenetic alterations of gene expression and other molecular pathology. Traditionally, however, expression studies in postmortem brain were confined to quantification of mRNA or protein. The limitations encountered in postmortem brain research such as variabilities in autolysis time and tissue integrities are also likely to impact any studies of higher order chromatin structures. However, the nucleosomal organization of genomic DNA including DNA:core histone binding – appears to be largely preserved in representative samples provided by various brain banks. Therefore, it is possible to study the methylation pattern and other covalent modifications of the core histones at defined genomic loci in postmortem brain. Here, we present a simplified native chromatin immunoprecipitation (NChIP) protocol for frozen (never-fixed) human brain specimens. Starting with micrococcal nuclease digestion of brain homogenates, NChIP followed by qPCR can be completed within three days. The methodology presented here should be useful to elucidate epigenetic mechanisms of gene expression in normal and diseased human brain.

5. Molloy CA, Murray DS, Kinsman A, Castillo H, Mitchell T, Hickey FJ, Patterson B. {{Differences in the clinical presentation of Trisomy 21 with and without autism}}. {J Intellect Disabil Res};2008 (Dec 2)

Abstract Background Autism occurs 10 times more often in children with Down syndrome than in the general population, but diagnosing co-occurring autism in Down syndrome with severe intellectual disability is challenging. The objective of this case-control study was to identify characteristics differentiating children with trisomy 21 with and without autism and to determine the extent to which severe cognitive impairment affects the measures of autism symptomatology. Method Twenty children with trisomy 21 and autism (cases) were compared with children with trisomy 21 without autism (controls) matched on chronologic age, race and gender. Communication, cognitive and adaptive behaviour skills were assessed with standardized instruments. Medical history was reviewed and medical records were examined for early head growth. Scores on the diagnostic algorithm of the Autism Diagnostic Interview – Revised (ADI-R) were compared after adjusting for cognitive ability as measured by the Stanford-Binet (Fifth Edition) non-verbal change-sensitive score. Results Cases performed significantly more poorly on all assessments. Mean case-control differences for matched pairs were all significant at P < 0.0001 for receptive and expressive language skills, cognitive skills and adaptive skills. Seven cases had a history of seizures compared with one control (P = 0.01). After adjusting for cognitive ability, the mean scores on the Reciprocal Social Interaction, Communication, and Restricted, Repetitive and Stereotyped Behaviours domains of the ADI-R diagnostic algorithm remained significantly higher in cases compared with controls (P < 0.0001). All participants had decreased head size consistent with Down syndrome, with no case-control differences. Conclusion Children with trisomy 21 and autism have significantly more impaired brain function than children with trisomy 21 without autism. However, the deficits in the core domains of social reciprocity and communication, and the restricted and repetitive interests are not entirely explained by the more severe cognitive impairment. This autism phenotype in children with trisomy 21 which includes an increased risk for seizures may indicate a widespread loss of functional connectivity in the brain.

6. Tateno M, Teshirogi H, Kamasaki H, Saito T. {{Successful olanzapine treatment of anorexia nervosa in a girl with pervasive developmental disorder not otherwise specified}}. {Psychiatry Clin Neurosci};2008 (Dec);62(6):752.