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"Healing Autism: No Finer a Cause on the Planet" ________________________________________________________________

RESEARCH

[Abstracts contains technical license.)

* Genetic and Autism

* Autism Spectrum Disorders And Low Body Weight

* MAO A Promoter Region Polymorphism For Linkage To Autism

* Serotonin 5-HT(2A) Receptor Gene (HTR2A) In Autism

* Association Between a GABRB3 Polymorphism And Autism.

* Linkage and Association Of The Glutamate Receptor 6 Gene With Autism.

* Four Candidate Genes For Autism In The 7q32 Region

* Serotonin Transporter Gene (Slc6a4) Misguide In Autistic Disorder

* The Gut – Brain – Herpies - Autism (NIDS?) Connection

* GABA-transaminase, the Liver And Infantile Autism.

* Human Beings, Animals And Inanimate Objects

* Do Computers Help Autistic Students Read?

* Developing a Diagnostic And Intervention Package For 2- To 3-Year-Olds

* The Scottish Centre for Autism Preschool Treatment Programme

* Harrdiness and Social Support As Predictors Of Stress In Mothers. . .

* Iron Deficiency In Autism And Asperger Syndrome.

* What Framework Should We Use For Understanding Developmental Disorders?

Genetic and Autism

ds=11920146&dopt=Abstract <- - address ends here.

Licinio J, I Alvarado I. UCLA Laboratory of Pharmacogenomics. Editorial

PMID: 11920146 [PubMed - in process]

* * *

Autism Spectrum Disorders And Low Body Weight

Is there really a systematic association?

ds=11920999&dopt=Abstract <- - address ends here.

Bolte S, Ozkara N, Poustka F. Department of Child and Adolescent Psychiatry, University of Frankfurt, Frankfurt, Germany.

OBJECTIVE: To examine the relationship between autism spectrum disorders and low body weight.

METHOD: The effect of maladaptive social and communicative behavior as well as stereotyped features on the normative body mass index (BMI) was analyzed in 103 subjects with autism or Asperger syndrome. Statistics were controlled for medication, neurological signs, overactivity, and general intelligence.

RESULTS: Twenty-eight percent of the male individuals had a BMI in the fifth percentile or below. Except for hyperactive behavior, none of the predictors showed a significant association with BMI. None of the subjects met diagnostic criteria for anorexia nervosa.

DISCUSSION: Although low body weight is often present in male subjects with autism or Asperger syndrome, results indicate that this link is inconsistent and partly mediated by hyperactivity. The co-occurrence of autism spectrum disorders and anorexia nervosa is probably due to chance. Copyright 2002 by Wiley Periodicals, Inc. Int J Eat Disord 31: 349-351, 2002; DOI 10.1002/eat.10015

PMID: 11920999 [PubMed - in process]

* * *

MAO A Promoter Region Polymorphism For Linkage To Autism "Family-based and population study of a functional promoter-region monoamine oxidase A polymorphism in autism: Possible association with IQ."

ds=11920849&dopt=Abstract <- - address ends here.

Yirmiya N, Pilowsky T, Tidhar S, Nemanov L, Altmark L, Ebstein RP. Department of Psychology, Hebrew University of Jerusalem, Jerusalem, Israel.

Although the etiology of autism remains to be elucidated, genetic elements significantly contribute to this disorder, and genes on the X chromosome are of special interest because there is a 4:1 predominance of male probands in autism. In the current study, we therefore examined, using the robust transmission disequilibrium test (TDT), possible preferential transmission of variants of a functional monoamine oxidase A (MAO A) promoter region polymorphism for linkage to autism.

In the 49 families examined (33 families with one proband and 15 families with two affected siblings), we did not find preferential transmission of MAO A from 33 heterozygous mothers to affected child (TDT chi-square = 0.29, NS). Nor was any significant difference in MAO A allele frequency observed between 43 male autism subjects versus a group of 108 non-autism control subjects (chi-square = 1.23, P = 0.27, NS).

However, a trend was observed for an association between IQ in the probands and the MAO A genotype that just attained significance (F = 3.5, P = 0.046, N = 28) in the small group of autism subjects recruited from families with two affected siblings. Copyright 2002 Wiley-Liss, Inc.

PMID: 11920849 [PubMed - in process]

A

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* * *

Serotonin 5-HT(2A) Receptor Gene (HTR2A) In Autism "Transmission disequilibrium studies of the serotonin 5-HT(2A) receptor gene

(HTR2A) in autism."

ds=11920848&dopt=Abstract <- - address ends here. Veenstra-VanderWeele J, Kim SJ, Lord C, Courchesne R, Akshoomoff N, Leventhal BL, Courchesne E, Cook EH Jr. Laboratory of Developmental Neuroscience, Child and Adolescent Psychiatry, Department of Psychiatry, University of Chicago, Chicago, Illinois.

Hyperserotonemia in autism is one of the longest-standing biochemical findings in a psychiatric disorder. This well-replicated finding and subsequent studies of platelet serotonin receptors in autism indicate that the serotonin 2A receptor gene (HTR2A) on chromosome 13q is a primary candidate gene in autism. Converging data from recent genome screens also implicates the genomic region containing HTR2A. Based on these lines of evidence, the transmission/disequilibrium test (TDT) was used to assess transmission disequilibrium between autism and haplotypes of three polymorphisms, including the promoter -1438 G/A single nucleotide polymorphism (SNP) in perfect linkage disequilibrium with the 102 T/C SNP in previous studies, a newly identified SNP in intron 1 near exon 2, and the SNP responsible for the His452Tyr amino acid change in exon 3.

Because expression studies have shown HTR2A to be polymorphically imprinted in the brain, secondary analyses were split into maternal and paternal transmissions. No evidence was found for unequal transmission of haplotypes; however, power analysis reveals low power to detect a parent-of-origin effect in this sample size. Copyright 2002 Wiley-Liss, Inc.

PMID: 11920848 [PubMed - in process]

* * *

Association Between a GABRB3 Polymorphism And Autism.

ds=11920158&dopt=Abstract <- - address ends here.

Buxbaum JD, Silverman JM, Smith CJ, Greenberg DA, Kilifarski M, Reichert J, Cook Jr EH, Fang Y, Song CY, Vitale R. Laboratory of Molecular Neuropsychiatry, Mount Sinai School of Medicine, New York, NY 10029, USA, and Department of Psychiatry, Mount Sinai School of Medicine, New York, NY 10029, USA, and Department of Neurobiology, Mount Sinai School of Medicine, New York, NY 10029, USA, and Seaver Autism Research Center, Mount Sinai School of Medicine, New York, NY 10029, USA.

Autistic disorder (OMIM 209850) is a disease with a significant genetic component of a complex nature.(1) Cytogenetic abnormalities in the Prader-Willi/Angelman syndrome critical region (15q11-13) have been described in several individuals with autism.(1) For this reason, markers across this region have been screened for evidence of linkage and association, and a marker (155CA-2) in the gamma-aminobutyric acid type-A receptor beta3 subunit gene (GABRB3) has been associated in one study(2) but not others.(3-5)

We completed an association analysis with 155CA-2 using the transmission disequilibrium test (TDT) in a set of 80 autism families (59 multiplex and 21 trios). We also used four additional markers (69CA, 155CA-1, 85CA, and A55CA-1) localized within 150 kb of 155CA-2. The use of multi-allelic TDT (MTDT) (P < 0.002), as well as the TDT (P < 0.004), demonstrated an association between autistic disorder and 155CA-2 in these families. Meiotic segregation distortion could be excluded as a possible cause for these results since no disequilibrium was observed in unaffected siblings.

These findings support a role for genetic variants within the GABA receptor gene complex in 15q11-13 in autistic disorder.

PMID: 11920158 [PubMed - as supplied by publisher]

* * *

Linkage and Association Of The Glutamate Receptor 6 Gene With Autism.

ds=11920157&dopt=Abstract <- - address ends here.

Jamain S, Betancur C, Quach H, Philippe A, Fellous M, Giros B, Gillberg C, Leboyer M, Bourgeron T; and the Paris Autism Research International Sibpair

(PARIS) Study. Laboratoire d'Immunogenetique Humaine, INSERM E021, Institut Pasteur, 75015 Paris, France.

A genome scan was previously performed and pointed to chromosome 6q21 as a candidate region for autism. This region contains the glutamate receptor 6 (GluR6 or GRIK2) gene, a functional candidate for the syndrome. Glutamate is the principal excitatory neurotransmitter in the brain and is directly involved in cognitive functions such as memory and learning.

We used two different approaches, the affected sib-pair (ASP) method and the transmission disequilibrium test (TDT), to investigate the linkage and association between GluR6 and autism. The ASP method, conducted with additional markers on the 51 original families and in eight new sibling pairs, showed a significant excess of allele sharing, generating an elevated multipoint maximum LOD score (ASPEX MLS = 3.28).

TDT analysis, performed in the ASP families and in an independent data set of 107 parent-offspring trios, indicated a significant maternal transmission disequilibrium (TDTall P = 0.0004). Furthermore, TDT analysis (with only one affected proband per family) showed significant association between GluR6 and autism (TDT association P = 0.008).

In contrast to maternal transmission, paternal transmission of GluR6 alleles was as expected in the absence of linkage, suggesting a maternal effect such as imprinting. Mutation screening was performed in 33 affected individuals, revealing several nucleotide polymorphisms (SNPs), including one amino acid change (M867I) in a highly conserved domain of the intracytoplasmic C-terminal region of the protein.

This change is found in 8% of the autistic subjects and in 4% of the control population and seems to be more maternally transmitted than expected to autistic males (P = 0.007). Taken together, these data suggest that GluR6 is in linkage disequilibrium with autism.

PMID: 11920157 [PubMed - in process]

* * *

Four Candidate Genes For Autism In The 7q32 Region

"Mutation screening and imprinting analysis of four candidate genes for autism in the 7q32 region

ds=11920156&dopt=Abstract <- - address ends here.

Bonora E, Bacchelli E, Levy ER, Blasi F, Marlow A, Monaco AP, Maestrini E; and the International Molecular Genetic Study of Autism Consortium (IMGSAC). The Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK.

Genetic studies indicate that chromosome 7q is likely to contain an autism susceptibility locus (AUTS1). We have followed a positional candidate gene approach to identify the relevant gene and report the analysis of four adjacent genes localised to a 800 kb region in 7q32 that contains an imprinted domain: PEG1/MEST, COPG2, CPA1 and CPA5-a previously uncharacterised member of the carboxypeptidase gene family.

Screening these genes for DNA changes and association analysis using intragenic single nucleotide polymorphisms (SNPs) provided no evidence for an etiological role in IMGSAC families.

We also searched for imprinting mutations potentially implicated in

autism: analysis of both DNA methylation and replication timing indicated a normal imprinting regulation of the PEG1/COPG2 domain in blood lymphocytes of all patients tested. The analysis of these four genes strongly suggests that they do not play a major role in autism aetiology, and delineates our strategy to screen additional candidate genes in the AUTS1 locus.

PMID: 11920156 [PubMed - in process]

* * *

Serotonin Transporter Gene (Slc6a4) Misguide In Autistic Disorder "Transmission disequilibrium mapping at the serotonin transporter gene

(SLC6A4) region in autistic disorder."

ds=11920155&dopt=Abstract <- - address ends here.

Kim SJ, Cox N, Courchesne R, Lord C, Corsello C, Akshoomoff N, Guter S, Leventhal BL, Courchesne E, Cook Jr EH. Laboratory of Developmental Neuroscience, Child and Adolescent Psychiatry, Department of Psychiatry MC3077, University of Chicago, Chicago, IL, USA.

The serotonin transporter gene (SLC6A4, MIM 182138) is a candidate gene in autistic disorder based on neurochemical, neuroendocrine studies and the efficacy of potent serotonin transporter inhibitors in reducing ritualistic behaviors and related aggression. An insertion/deletion polymorphism (5-HTTLPR) in the promoter region and a variable number of tandem repeat polymorphism (VNTR) in the second intron, were previously identified and suggested to modulate transcription.

Six previous family-based association studies of SLC6A4 in autistic disorder have been conducted, with four studies showing nominally significant transmission disequilibrium and two studies with no evidence of nominally significant transmission disequilibrium.

In the present study, TDT was conducted in 81 new trios. A previous finding of transmission disequilibrium between a haplotype consisting of the 5-HTTLPR and intron 2 VNTR was replicated in this study, but not preferential transmission of 5-HTTLPR as an independent marker. Because of inconsistent transmission of 5-HTTLPR across studies, SLC6A4 and its flanking regions were sequenced in 10 probands, followed by typing of 20 single nucleotide polymorphisms (SNPs) and seven simple sequence repeat

(SSR) polymorphisms in 115 autism trios.

When individual markers were analyzed by TDT, seven SNP markers and four SSR markers (six SNPs, 5-HTTLPR and the second intron VNTR from promoter 1A through intron 2 of SLC6A4, one SSR from intron 7 of SLC6A4, one SNP from the bleomycin hydrolase gene (BLMH, MIM 602403) and one SSR telomeric to BLMH) showed nominally significant evidence of transmission disequilibrium. Four markers showed stronger evidence of transmission disequilibrium (TDT(max) P = 0.0005) than 5-HTTLPR.

PMID: 11920155 [PubMed - in process]

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* * *

The Gut – Brain – Herpies - Autism (NIDS?) Connection

"Anterior insular cortex: linking intestinal pathology and brain function in autism-spectrum subgroups."

ds=11918432&dopt=Abstract <- - address ends here.

Binstock T. Institute for Molecular Introspections, Estes Park, Colorado 80517, USA. aspergerian@yahoo.com

Autism includes deficits in communications skills and is associated with intestinal pathology. Numerous parents and some physicians report that an autistic child's attention and language improve in response to treatments which eliminate certain dietary antigens and/or which improve intestinal health. For at least some autism-spectrum children, the link between intestinal pathology, attention, and language may derive from shared neuroanatomic pathways within the anterior insular cortex (aIC); from a neurotrophic virus such as herpes simplex (HSV) migrating within afferents to the insular cortex; and/or from synaptic exhaustion in the aIC as induced by chronically inappropriate neuronal activity in the enteric nervous system and/or its vagal efferents.

PMID: 11918432 [PubMed - in process]

* * *

GABA-transaminase, the Liver And Infantile Autism.

ds=11918424&dopt=Abstract <- - address ends here.

Cohen B I. ED Laboratories, S. Hackensack, New Jersey 07606, USA. EDS@Pipeline.com

Gamma-aminobutyric acid (GABA) is a major inhibitory neurotransmitter of the mammalian brain and the enzyme responsible for catabolism (breakdown in the liver during regulation) is GABA-Transaminase (GABA-T).

Recently, Cohen has shown that extremely high GABA levels in the urine and blood were observed for an autistic child. The finding that elevated levels of GABA in the urine and blood are present for an autistic child could explain why autistic features (such as self-stimulatory behavior and language delays, etc.) are found.

Increasing the GABA-T enzyme activity for this autistic patient could result in less plasma GABA (after liver regulation) entering into the bloodsteam and brain and it is postulated that this could result in a reduction of the autistic features (such as self-stimulatory behavior and language delays, etc.) due to abnormal development of the axon(s) in the corpus callosum.

PMID: 11918424 [PubMed - in process]

* * *

Human Beings, Animals And Inanimate Objects

What Do People With Autism Like?

ds=11918112&dopt=Abstract <- - address ends here. Celani G. University

of Bologna, Italy. celani@psibo.unibo.it

An experimental strategy based on the 'sorting by preference' approach was used to obtain information about the nature of the autistic syndrome. Twelve participants with autism (mean age 11:9 years), 12 with Down's syndrome (mean age 11:5 years) and 12 typically developing children (mean age 6:2 years) were matched on gender (M:F 9:3) and on verbal mental age.

In a forced choice procedure they had to choose between: human beings or inanimate objects (relatedness condition); animals or inanimate objects (animate condition); drawings of a child handling a thing or of the same child in contact with another person (interpersonal relationship condition); pleasant or unpleasant situations without living beings (control condition).

The performances of the groups differed only on the relatedness condition and on the interpersonal relationship condition. The results are discussed in the context of the social difficulties experienced by individuals with autism.

PMID: 11918112 [PubMed - in process]

* * *(

Do Computers Help Autistic Students Read?

"Do children with autism learn to read more readily by computer assisted instruction or traditional book methods? A pilot study."

ds=11918110&dopt=Abstract <- - address ends here.

Williams C, Wright B, Callaghan G, Coughlan B. York NHS Trust, UK. christine.williams@exch.yhs-tr.northy.nhs.uk.com

The study evaluates the progress of eight children aged 3-5 years with autism attending a specialist teaching unit in their development of reading skills in two conditions: computer instructed learning and book based learning. The authors developed a direct observation schedule to monitor autistic behaviours using computerized techniques.

The children were matched by age, severity of autistic symptomatology and number of spoken words. They were initially randomly allocated to the computer or book condition and crossed over at 10 weeks. All of the children spent more time on task in the computer condition than in the book condition. By the end of the study after computer assisted learning, five of the eight children could reliably identify at least three words. It was found that children with autism spent more time on reading material when they accessed it through a computer and were less resistant to its use.

PMID: 11918110 [PubMed - in process]

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Developing a Diagnostic And Intervention Package For 2- To 3-Year-Olds with autism: outcomes of the frameworks for communication approach.

ds=11918109&dopt=Abstract <- - address ends here.

Chandler S, Christie P, Newson E, Prevezer W. Early Years Diagnostic Centre, Nottingham, UK.

The aim of the research was to develop and evaluate a model of good practice which would make an explicit link between diagnosis and intervention, and so give parents a very clear rationale for the autism-specific yet individualized programme that they were carrying out. It employed an action research design, which essentially is responsive to participants, thus developing a user-friendly model of service.

The programme was based on the developmental perspective that the pragmatics of language are the precursors of speech itself and enable both communication and relationship between child and parents. Since these are impaired in autism they should therefore be prioritized in early intervention. Ten children aged 1:10 to 2:9 at assessment, and with a diagnosis of autism, underwent an intervention based on home visits, modelling, workshops and written information, with parents as 'therapists' in naturally occurring situations. Within 18 months all children made substantial progress in social interaction and expressive communication, including gestural and verbal communication.

PMID: 11918109 [PubMed - in process]

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* * *

The Scottish Centre for Autism Preschool Treatment Programme.

II: The results of a controlled treatment outcome study.

ds=11918108&dopt=Abstract <- - address ends here.

Salt J, Shemilt J, Sellars V, Boyd S, Coulson T, McCool S. Scottish Centre for Autism, Department of Child and Family Psychiatry, Glasgow, UK. jeff_salt@hotmail.com

This article evaluates the effectiveness of a developmentally based early intervention programme. Two groups of children were compared, a treatment group and a no-treatment control group. Standardized assessments were administered before and after the intervention period by an independent clinician.

Pre-treatment comparisons revealed that the control group had a significantly higher pre-treatment IQ; but the two groups were comparable for age, mental age, socioeconomic status and number of hours of non-experimental therapy.

Results demonstrated that children in the treatment group improved significantly more than those in the control group on measures of joint attention, social interaction, imitation, daily living skills, motor skills and an adaptive behaviour composite.

A measure of requesting behaviour fell short of statistical significance. The total stress index reduced for treatment group parents and increased for the control group parents (but not significantly). The results of the study are considered to support the efficacy of this treatment approach.

PMID: 11918108 [PubMed - in process]

* * *

Harrdiness and Social Support As Predictors Of Stress In Mothers. . . of typical children, children with autism, and children with mental retardation.

ds=11918107&dopt=Abstract <- - address ends here.

Weiss MJ. Rutgers, The State University of New Jersey, Douglass Developmental Disabilities Center, New Brunswick 08901-8512, USA. mjweiss@home.com

This study assessed the effects of social support and hardiness on the level of stress in mothers of typical children and children with developmental disabilities. One hundred and twenty mothers participated (40 mothers of children with autism, 40 mothers of children with mental retardation, and 40 mothers of typically developing children).

Results indicated significant group differences in ratings of depression, anxiety, somatic complaints and burnout. Regression analyses were conducted to determine the best predictors of the dependent measures. Both hardiness and social support were predictive of successful adaptation. The relationships among hardiness, support and coping are discussed.

PMID: 11918107 [PubMed - in process]

* * *

ds=11918106&dopt=Abstract <- - address ends here.

Latif A, Heinz P, Cook R. Children Centre, Royal Glamorgan Hospital, Mid Glamorgan, UK. abbas.latif@pr-tr.wales.nhs.uk

This research considers the prevalence of iron deficiency in children with autism and Asperger syndrome and examines whether this will influence guidelines and treatment. Retrospective analysis of the full blood count and, as far as available, serum ferritin measurements of 96 children (52 with autism and 44 with Asperger syndrome) was undertaken.

Six of the autistic group were shown to have iron deficiency anaemia and, of the 23 autistic children who had serum ferritin measured, 12 were iron deficient. Only two of the Asperger group had iron deficiency anaemia and, of the 22 children who had their serum ferritin measured, only three were iron deficient.

Iron deficiency, with or without anaemia, can impair cognition and affect and is associated with developmental slowing in infants and mood changes and poor concentration in children. This study showed a very high prevalence of iron deficiency in children with autism, which could potentially compromise further their communication and behavioural impairments.

PMID: 11918106 [PubMed - in process]

* * *

What Framework Should We Use For Understanding Developmental Disorders?

ds=11892952&dopt=Abstract <- - address ends here.

Frith U. Institute of Cognitive Neuroscience, University College London, England. u.frith@ucl.ac.uk

The neuropsychology of dyslexia has made great strides in the last decade. In particular, a consensus views dyslexia as a developmental disorder with a basis in the brain and in the genes, where the interaction of genetic and environmental factors is taken for granted. However, problems in defining the phenotype continue to bedevil research.

The main conceptual problems can be expressed in three main questions:

(a) Is dyslexia based on a specific brain abnormality or is it merely part of a continuum of atypical brain development? (b) When can we speak of comorbidity? (c) Why does so much individual variability occur? These questions can be tackled in a common framework that takes into account simultaneously three levels: the biological, the cognitive, and the behavioral.

PMID: 11892952 [PubMed - in process]

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APRIL 21, 2002 - 12 Noon to 5pm

THIRD NATIONAL AUTISM AWARENESS RALLY:

"The Power of ONE! I.D.E.A."

FREE and OPEN TO THE PUBLIC

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