FEAT: Balancing Interests In Autism Study/ 7 New Autism Research Abstracts

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Balancing Interests In Autism Study/ 7 New Autism Research

Abstracts

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SCIENCE

* Balancing Interests In Autism Study

Abstracts

* M-100907 (Aventis): Platelet Serotonin Receptor Antagonist

* Open-label Risperidone Treatment Of 6 Kids & Adolescents W/ Autism

* A Genetic Non-Connection to Autism

* Chromosomal Abnormalities In A Clinic Sample Of Individuals

With Autistic Disorder

* Study Checks Autism Criteria Inconsistency

* Psychopharmacologicals Evaluated

* Hand Preference And Motor Functioning In Children With Autism

Balancing Interests In Autism Study

Balancing Interests In Autism Study

http://journals.bmn.com/journals/list/browse?uid=JCUB.ccp03076_09609822_v001

1i16_00001267

Gross Current Biology 2001, 11:R630

Confusion and controversy loom large whenever autistic spectrum

disorders are discussed. A major review commissioned by the British

government should sort the facts from the legends, hopes Gross.

The raging debate on whether or not the combined measles, mumps and

rubella (MMR) vaccine can trigger the onset of autistic spectrum disorders

(latest research suggests it doesn't) has demonstrated one thing very

clearly: that there is a lot of uncertainty and misinformation about autism,

a condition that affects 0.1% of the population.

Parents of autistic children know how difficult it is to filter any

meaningful information from a stream of dubious reports on miracle cures,

horrifying increases in case numbers, newly identified causes, and new

theories. Short of a cure, weeding out the information jungle would be a

major step to make life easier for everybody involved. Similarly, a

future-oriented research policy capable of tackling the disease would need

to be based on a clear understanding of what can presently count as

established knowledge, and what is mythology.

In response to this problem, the British government has recently

commissioned the Medical Research Council (MRC) to provide a report on the

present scientific knowledge about the epidemiology and causes of autism.

The MRC has set up three expert panels and a 'lay group' consisting of

people involved with autism in non-academic ways.

There is first the case definition and epidemiology group. This group

will have to address questions such as whether the apparent increase in case

numbers over the past decade is an artefact of shifting definitions, or

whether there is a real 'epidemic'. If the increase is real, then there must

be biological causes for it, which may be found in the remit of the

physiology and infections group which has possibly the trickiest task,

including the MMR question along with other possible environmental

influences on the condition. While there is a clear genetic component to

autism (around a dozen genes are thought to be involved), the disorder is

also linked to bowel malfunctions, which led to theories that blame the

symptoms on food ingredients such as milk proteins or gluten. Finally, there

is a group dealing with psychology and behaviour. As the psychological

'causes' of autism postulated in the 1950s have by now been ruled out

completely, and educational provision is excluded from the remit of the

review, this last part of the review is likely to stir less controversy

than the others.

Of the six 'lay group' members, two are associated with each of the

review groups. The panels' membership sparked some controversy.

Wakefield, the researcher who claimed that the MMR vaccine triggered autism,

was said to be concerned about the fact that four members, including two

academics and one lay group member serving on the physiology board, had been

involved in the court case brought against manufacturers of the MMR vaccine

by parents. The view that this constitutes a conflict of interest, however,

did not prevail.

The report should become publicly available by the end of this year.

MRC research boards will consider the results with a view to convert its

suggestions into actual research that will put an end to decades of

confusion.

Gross is a science writer and consultant based at the Oxford

Centre for Molecular Sciences. He can be contacted through his web page at

http://www.michaelgross.co.uk.

* * *

M-100907 (Aventis): Platelet Serotonin Receptor Antagonist

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve & db=PubMed & list_ui

ds=11527004 & dopt=Abstract

1: Curr Opin Investig Drugs 2001 Jan;2(1):123-132

de is T.

Psychiatry Department, Vanderbilt University School of Medicine, Nashville,

TN 37232, USA. Tomas.deis@...

M-100907 is a highly selective 5-HT2A antagonist that is being

developed by Aventis Pharmaceuticals, formerly Hoechst n Roussel (HMR),

for the potential treatment of schizophrenia. M-100907 is in phase III

trials for chronic schizophrenia [307936], [307942], [307940].

In August 1999, development was discontinued for acute schizophrenia

(schizoaffective disorder) on the basis of poor results [335083]. M-100907

is a potent antagonist in every putative animal behavioral model of

schizophrenia that involves activation of 5-HT2A receptors [181713].

Interestingly, M-100907 is also active in animal models involving

blockade of NMDA glutamatergic channel receptors, an effect known to

resemble some behavioral symptoms of schizophrenia in man [390328]. M-100907

belongs to a series of piperidine derivatives, which were originally

disclosed in the associated patent, EP-00208235. M-100907 is specifically

claimed in a later patent, EP-00531410. This patent describes superior in

vivo potency for M-100907 and its claims include the use of M-100907 for

the treatment of thromboembolic disorders.

The use of M-100907 for the treatment of various developmental

neurological disorders such as autism and attention deficit hyperactivity

disorder is disclosed in WO-09956750. In 1996, this product was designated

one of HMR's nine top priority products, serving an unmet medical need and

addressing a potential market in excess of US $500 million per year

[221118].

In January 1999, BT Brown predicted sales of US $30 million in

2000 rising to US $220 million in 2002 [318220]. In April 1999, ABN Amro

predicted annual sales of DM 50 million in 2000, rising to DM 150 million in

2002 [328676].

PMID: 11527004 [PubMed - in process]

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* * *

Open-label Risperidone Treatment Of 6 Children And Adolescents With Autism

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve & db=PubMed & list_ui

ds=11526814 & dopt=Abstract

Can J Psychiatry 2001 Aug;46(6):559-560 Books, LinkOut

Vercellino F, Zanotto E, Ravera G, Veneselli E.

Publication Types: Letter

PMID: 11526814 [PubMed - in process]

* * *

A Genetic Non-Connection to Autism

No association between the 4g/5G polymorphism of the plasminogen activator

inhibitor-1 gene promoter and autistic disorder

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve & db=PubMed & list_ui

ds=11525425 & dopt=Abstract

1: Psychiatr Genet 2001 Jun;11(2):99-103 Related Articles, Books

Persico AM, Militerni R, Bravaccio C, Schneider C, Melmed R, Trillo S,

Montecchi F, Palermo M, Pascucci T, Puglisi-Allegra S, Reichelt KL,

Conciatori M, Keller F.

Department of Physiology and Neuroscience, Universita Campus Bio-Medico,

Rome, Italy.

Plasmin, a serine protease, is involved in many physiologically

relevant processes, including haemostasis, cellular recruitment during

immune response, tumour growth, and also neuronal migration and synaptic

remodelling. Both tissue-type and urokinase-type plasminogen activators can

be efficiently inhibited by plasminogen activator inhibitor-1 (PAI-1), a

protease inhibitor of the serpin family.

The human PAI-1 gene is located on chromosome 7q, within or close to a

region that has been linked to autism in several linkage studies. Autism

seems to be characterized by altered neuronal cytoarchitecture,

synaptogenesis and possibly also cellular immune responses. We began

addressing the potential involvement of the PAI-1 gene in autistic disorder

with this linkage/association study, assessing transmission patterns of the

4G/5G polymorphism in the PAI-1 gene promoter that was previously shown to

significantly affect PAI-1 plasma levels.

No linkage/association was found in 167 trios with autistic probands,

recruited in Italy and in the USA. We thus found no evidence that this

polymorphism, or putative functionally relevant gene variants in linkage

disequilibrium with it, confer vulnerability to autistic disorder.

PMID: 11525425 [PubMed - in process]

* * *

Chromosomal Abnormalities In A Clinic Sample Of Individuals With Autistic

Disorder

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve & db=PubMed & list_ui

ds=11525418 & dopt=Abstract

1: Psychiatr Genet 2001 Jun;11(2):57-63

Wassink TH, Piven J, Patil SR.

Department of Psychiatry, University of Iowa College of Medicine, Iowa City,

USA. thomas-wassink@...

We examined data from the largest reported sample of autistic

individuals who have been karyotyped with the aim of providing additional

information in the search for autism disease genes. Individuals seen in the

University of Iowa's Child and Adolescent Psychiatry Clinic since 1980 who

had been diagnosed with autism were cross-referenced with the University of

Iowa's Cytogenetics Laboratory database.

We determined the number of individuals referred for cytogenetic

testing and, of these, the number found to have gross cytological

abnormalities. Medical records were reviewed for all cases with such

abnormalities. Between 1980 and 1998, 898 subjects seen in the clinic were

diagnosed with autism.

Of these, 278 (30.1%) were referred for cytological studies; 25 (9.0%)

of these were found to have chromosomal abnormalities. The most common

chromosomal abnormalities were Fragile X, other sex chromosome anomalies,

and chromosome 15 abnormalities. These data support the contribution of

chromosomal abnormalities to a small but significant number of cases of

autism, and highlight the involvement of chromosome 15 and the sex

chromosomes.

PMID: 11525418 [PubMed - in process]

* * *

Study Checks Autism Criteria Inconsistency

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve & db=PubMed & list_ui

ds=11524898 & dopt=Abstract

1: Z Kinder Jugendpsychiatr Psychother 2001 Aug;29(3):221-229

[Article in German]

Bolte S, Poustka F.

Klinik fur Psychiatrie und Psychotherapie des Kindes- und Jugendalters des

Klinikums, Johann Wolfgang Goethe-Universitat furt am Main.

Boelte@...

OBJECTIVES: This study investigated whether empirically derived

dimensions of autistic behavior are consistent with the content-valid

construction of the autistic behavior domains according to ICD-10 and DSM-IV

(social interaction, communication and repetitive, stereotyped behavior).

METHODS: A principal component exploratory factor analysis routine

with varimax-rotation and extraction of factors following the Scree

criterion was run using data from the Autism Diagnostic Interview-Revised

(ADI-R) of N = 262 individuals exhibiting autism or autistic features.

RESULTS: A three-factor solution consisting of two socio-communicative

and one language dimension and accounting for 46.1% of the total variance

was found to best describe the data. These factors yielded only vague

correspondence with the idea of behavior domains described in ICD-10 and

DSM-IV. In addition, factor loadings of items representing repetitive,

stereotyped patterns were generally weak.

CONCLUSIONS: The factor-analytic approach to autism indicates a

conception of the disorder divergent from that defined in the contemporary

psychiatric classification systems, especially regarding the area of

repetitive, stereotyped behavior.

PMID: 11524898 [PubMed - in process]

* * *

Psychopharmacologicals Evaluated

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve & db=PubMed & list_ui

ds=11524896 & dopt=Abstract

1: Z Kinder Jugendpsychiatr Psychother 2001 Aug;29(3):189-205

[Article in German]

Baving L, Schmidt MH.

Klinik fur Kinder- und Jugendpsychiatrie, Otto-von-Guericke-Universitat

Magdeburg. lioba-baving@...

OBJECTIVES: The principle of evidence-based medicine is to integrate

data concerning the efficacy of interventions into clinical practice. This

article assesses the level of evaluation of psychosocial,

psychopharmacological and combined interventions for mental disorders in

childhood and adolescence (autistic disorders, hyperkinetic disorders,

conduct disorders, tic disorders, enuresis, and encopresis).

METHODS: Three different levels of evaluation were defined for both

psychosocial and psychopharmacological interventions: A (> or = 2 randomized

controlled studies), B (1 randomized controlled study), and C (open studies

and case studies). The level of evaluation was judged on the basis of

original papers found in a comprehensive literature search.

RESULTS: For most disorders presented in this article there are

several A-level treatments. The efficacy of both psychosocial and

psychopharmacological interventions that target specific problem behaviors

or symptoms, respectively, has been repeatedly demonstrated w ith regard to

autistic disorders. Many studies have evaluated treatment approaches for

hyperkinetic disorders and conduct disorders. With regard to the treatment

of tic disorders in children and adolescents, far more studies evaluated the

efficacy of pharmacotherapy than of psychotherapy.

CONCLUSIONS: Further research should compare the efficacy of different

treatment approaches, examine specific and differential treatment effects

and investigate combined treatment approaches.

PMID: 11524896 [PubMed - in process]

* * *

Hand Preference And Motor Functioning In Children With Autism

J Autism Dev Disord 2001 Jun;31(3):265-77

Hauck JA, Dewey D.

University of Calgary, Alberta, Canada.

This study examined three theories that have been proposed to explain

the high rates of ambiguous hand preference in young children with autism.

Twenty children with autism were matched with 20 children with developmental

delays and 20 normally developing children. The groups were compared on

measures of hand preference and motor skills.

Results indicated that the lack of development of a hand preference in

children with autism was not a direct function of their cognitive delay, as

the children with developmental delays showed a dissimilar pattern of hand

preference. The lack of a definite hand preference in the children with

autism was also not due to a lack of motor skill development, as the

children with developmental delays displayed similar levels of gross and

fine motor skills without the accompanying lack of a definite hand

preference.

The finding that children with autism with a definite hand preference

displayed better performance on motor, language, and cognitive tasks than

children with autism who did not display a definite hand preference,

however, provided support for the bilateral brain dysfunction hypothesis.

PMID: 11518481 [PubMed - in process]

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