FEAT DAILY NEWSLETTER Sacramento, California

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

RESEARCH

* Brain Repair: Stem Cells And Neuropoiesis In The Adult Human Brain

* High Motion Coherence Thresholds In Children With Autism

* Psychosocial Adjustment In Siblings Of Children With Autism

* Tuberous Sclerosis & Renal Cancer, Obscure Autism Connection

* Autism: Diagnosis Criteria, Cognitive-Evolutionary Approach

* Move to Ban Dihydrogen Monoxide Picks Up Steam:

In the Guts of Autistic Children

* Cure Autism Now Funds 13 Pilot Research, Young Investigator Awards

[All articles contain technical language.]

Brain Repair: Stem Cells And Neuropoiesis In The Adult Human Brain

[Autism is like a hit and run accident. Something came along, we don't know who, what or when, that caused damage and disruption across the body's medical systems, and left few tracks. Some scientific research is going after finding the driver and vehicle, that is trying to determine the environmental assault(s), poisons, viruses, etc. Other research, like genetic, is trying to find out why some bodies were hit hard and not others, or others not as hard, by whatever it is that's hitting them. Another facet of research that awaits after much is learned from the these others, is what could be repaired in the body, or brain and what can do the repairing. That's where stem cells and neuropoiesis can come into play. Nueropoiesus means brain cell generation. (This article is full of such technical

_and_review.20403.1#ahypotheticalscenarioforadulthumanbraincellrepair <- - address ends here. Dennis A Steindler, David W Pincus Lancet 2002; 359: 1047-54 Departments of Neuroscience and Neurosurgery, McKnight Brain Institute and Shands Cancer Center, University of Florida Program in Stem Cell Biology, College of Medicine, P O Box 100244, 100 S Newell Drive, Gainesville, FL 32610, USA (Prof D A Steindler PhD, D W Pincus MD) Correspondence to: Prof Dennis A Steindler (e-mail:steindler@mbi.ufl.edu)

Stem cells in adult tissues have attracted a great deal of interest. These cells are self-renewing and can give rise to diverse progeny. An extraordinary finding was the presence of stem cells in the mature human brain. This tissue was previously believed incapable of generating new neurons, but neuropoiesis is now an established phenomenon in the adult brains of mammals, including human beings. This persistent neurogenesis has potential therapeutic applications for various neurological disorders as a source for tissue engraftment and as self-repair by a person's own indigenous population of pluripotent cells or biogenic by-products of their proliferation and differentiation.

Stem cells were first described by Leroy Stevens, Gail Martin, and Martin Evans,1 and the presence of these entities was also suspected by early radiation and haemopoiesis biologists who noted bone-marrow repopulation after whole-body ionising radiation;2 these scientists eventually generated long-term cultures of haemopoietic stem cells.3 The discovery of stem cells in the adult mammalian nervous system is a more recent finding. The history of this specialty has been the subject of several reviews. Here, we lay down a set of scenarios within which adult neural stem-cell biology could reach the bedside in the near future.

To what do we owe a recent paradigm shift in stem-cell, and particularly adult stem-cell, biology?1 Advances in molecular genetics and cell biology have resulted in the cloning of candidate stem and progenitor cells and the backwards search for the most pluripotent cell. Even the reversal of differentiation state and redirection of fate is now possible. Astonishing new findings are rapidly coming to light: a possible reversal of Hayflick's limit of replicative senescence;1transformation of cells from one germ layer into another, building on findings that show, for example, that bone-marrow cells can give rise to liver; and the large-scale production of insulin-secreting islet-like cells from embryonic stem cells, extending work on pancreatic stem cells.

+ Article Continues:

_and_review.20403.1#ahypotheticalscenarioforadulthumanbraincellrepair <- - address ends here.

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High Motion Coherence Thresholds In Children With Autism.

ds=11902604&dopt=Abstract <- - address ends here.

Milne E, Swettenham J, Hansen P, Campbell R, Jeffries H, Plaisted K. Dept of Human Communication Science, University College, London, UK. e.milne@ucl.ac.uk

BACKGROUND: We assessed motion processing in a group of high functioning children with autism and a group of typically developing children, using a coherent motion detection task.

METHOD: Twenty-five children with autism (mean age 11 years, 8 months) and 22 typically developing children matched for non-verbal mental ability and chronological age were required to detect the direction of moving dots in a random dot kinematogram.

RESULTS: The group of children with autism showed significantly higher motion coherence thresholds than the typically developing children (i.e., they showed an impaired ability to detect coherent motion).

CONCLUSIONS: This finding suggests that some individuals with autism may show impairments in low-level visual processing--specifically in the magnocellular visual pathway. The findings are discussed in terms of implications for higher-level cognitive theories of autism, and the suggestion is made that more work needs to be carried out to further investigate low-level visual processing in autism.

PMID: 11902604 [PubMed - in process]

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Psychosocial Adjustment In Siblings Of Children With Autism.

ds=11902601&dopt=Abstract <- - address ends here.

Kaminsky L, Dewey D. University of Calgary, Alberta, Canada.

BACKGROUND: This study investigated psychosocial adjustment in siblings of children with autism compared to siblings of children with Down syndrome and siblings of normally developing children. In addition, the relationships between feelings of loneliness, social support and psychosocial adjustment, and the influence of gender and family size on psychological adjustment were examined.

METHODS: Ninety siblings (30 per group) between the ages of 8 and 18 and one parent of each child participated in this study. RESULTS: Results indicated that siblings of children with autism, as well as comparison siblings, were well adjusted and reported low levels of loneliness. Siblings of children with autism also reported that they received high levels of social support in their lives.

CONCLUSIONS: Large family size appears to facilitate healthy adjustment in siblings of children with autism.

PMID: 11902601 [PubMed - in process]

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* * *

On Tuberous Sclerosis and Renal Cancer, Obscure Autism Connection "Mutational analysis of the von hippel lindau gene in clear cell renal carcinomas from tuberous sclerosis complex patients."

ds=11904337&dopt=Abstract <- - Address ends here.

Duffy K, Al-Saleem T, Karbowniczek M, Ewalt D, Prowse AH, Henske EP. Medical Oncology Division (KD, MK, AHP, EPH) and Department of Pathology (TA-S), Fox Chase Cancer Center, Philadelphia, Pennsylvania.

Tuberous sclerosis complex (TSC) is an autosomal-dominant disorder characterized by seizures, mental retardation, autism, and tumors of multiple organs. Renal disease in TSC includes angiomyolipomas, cysts, and renal cell carcinomas. It is known that somatic mutations in the von Hippel Lindau (VHL) tumor suppressor gene occur in most clear cell renal carcinomas.

To determine whether TSC-associated clear cell carcinomas also contain VHL mutations, we analyzed six tumors for loss of heterozygosity in the VHL gene region of chromosome 3p and for mutations in the VHL gene. Four of the patients were women between the ages of 34 and 68 years, and two were males under the age of 21 years. The loss of heterozygosity analysis was performed using polymorphic microsatellite markers, and the mutational analysis was performed using direct sequencing.

Chromosome 3p loss of heterozygosity was not detected, and no VHL mutations were identified. These findings suggest that mutations in the TSC1 and TSC2 genes lead to clear cell renal carcinogenesis via an alternate pathway not involving VHL mutations.

PMID: 11904337 [PubMed - in process]

* * *

Autism: Diagnosis Criteria, Cognitive-evolutionary Approach.

ds=11907586&dopt=Abstract <- - address ends here.

[Article in Spanish]

Scatolon CI, Ison M.

Instituto de Ciencias Humanas, Sociales y Ambientales, INCHIHUSA, CRICYT-CONICET, Mendoza, Argentina. scatolon@nysnet.com.ar

OBJECTIVE: To get acquainted with the information handled by health professionals regarding autism and its diagnosis criteria in the province of Mendoza, Argentina.

METHODOLOGY: Qualitative. A descriptive and exploratory study was conducted on a non-probabilistic sample of 38 professionals of Mendoza province. The professionals answered a questionnaire on autism and its diagnosis criteria.

RESULTS: Fifty-five percent of the professionals of the sample did not diagnose autism. The professionals that did (45 percent of the sample), though updated as regards diagnosis criteria, did not handle actual information about origin and type of this pathology, its symptoms and characteristics. Since most professionals belong to public institutions of the province, these results become relevant.

PMID: 11907586 [PubMed - in process]

* * *

Move to Ban Dihydrogen Monoxide Picks Up Steam: In the Guts of Autistic Children Month of April hits hardest

[This dubious substance warning was first reported in the FEAT Newsletter July 20, 2000.]

Dihydrogen monoxide is colorless, odorless, tasteless, and kills uncounted thousands of people every year. Most of these deaths are caused by accidental inhalation of DHMO, but the dangers of dihydrogen monoxide do not end there. Prolonged exposure to its solid form causes severe tissue damage.

For those who have become dependent, DHMO withdrawal means certain death.

Dihydrogen monoxide:

* is also known as hydroxyl acid, and is the major component of acid rain.

* contributes to the "greenhouse effect."

* may cause severe burns.

* contributes to the erosion of our natural landscape.

* accelerates corrosion and rusting of many metals.

* may cause electrical failures and decreased effectiveness of automobile brakes.

* has been found in excised tumors of terminal cancer patients.

* has been found both in the guts of autistic children and in MMR vaccines and passes blood-brain barrier.

* is a pronounced element in internal bleeding, high blood pressure and is present in urine, mucous, sputum, infectious discharge and even breast milk.

Contamination Is Reaching Epidemic Proportions.

Quantities of dihydrogen monoxide have been found in almost every stream, lake, and reservoir in America today. But the pollution is global, and the contaminant has even been found in Antarctic ice. DHMO has caused millions of dollars of property damage in the Midwest, and recently California.

Despite the danger, dihydrogen monoxide is often used:

* as an industrial solvent and coolant.

* in nuclear power plants.

* as a dissolvent in most vaccines.

* in the production of styrofoam.

* as a fire retardant.

* in many forms of cruel animal research.

* in the distribution of pesticides. Even after washing, produce remains contaminated by this chemical.

* as an additive in certain "junk-foods" and other food products.

Companies dump waste DHMO into rivers and the ocean, and nothing can be done to stop them because this practice is still legal. The impact on wildlife is extreme, and we cannot afford to ignore it any longer!

The Horror Must Be Stopped.

The American government has refused to ban the production, distribution, or use of this damaging chemical due to its "importance to the economic health of this nation." In fact, the navy and other military organizations are conducting experiments with DHMO, and designing multi-billion dollar devices to control and utilize it during warfare situations. Hundreds of military research facilities receive tons of it through a highly sophisticated underground distribution network. Many store large quantities for later use.

It's Not Too Late.

Act NOW to prevent further contamination. Find out more about this dangerous chemical. What you don't know can hurt you and others throughout the world. Call 1-800-QUITH2O

[FEAT provides this for our readers reflection only and does not assert that the above report is either factual or genuine.]

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Cure Autism Now Funds 13 Pilot Research, Young Investigator Awards

As part of an overall science budget of almost $4 million in 2002, Cure Autism Now is pleased to announce the funding of 13 pilot and young investigator research awards which represent a commitment of over $1,000,000. This brings the total number of awards Cure Autism Now has given to over 80. During the Scientific Advisory Board grant review meeting, it was generally agreed that the quality of the grants submitted has significantly risen in recent years. The quality and seniority of the researchers applying also continues to rise, and as a result, there is more to be gained from studies funded.

2002 GRANTS FUNDED

GRANT OPPORTUNITIES OVERVIEW

Cure Autism Now funds a variety of awards designed to encourage innovative approaches toward identifying causes, prevention, treatment and cure for autism and related disorders. Scientists already working in the field and investigators expressing a new interest are encouraged to apply. Each February, members of Cure Autism Now's esteemed Scientific Advisory Board meet to review submitted proposals. Their goal is to select outstanding projects for funding that represent a variety of approaches and cutting-edge techniques; encompass both basic science and concrete clinical findings that can make a direct impact on the lives of families; support experienced experts; and encourage talented newcomers to enter the field.

Young Investigator Awards

This grant was created to encourage the brightest new scientists to enter the field of autism research. Young investigator awards are funded at the level of $40,000 per year for one or two years. Grants are reviewed annually.

Studies of a serotonin transporter (5HTT) mutation associates with Asperger's syndrome

Matthew Beckman, University of Alabama at Birmingham

The search for genes associated with autism has been the focus of much attention by researchers in the past few years. Recently this search has led to the discovery of a mutation in the human serotonin transporter (SERT) coding sequence from patients with the following neuropsychiatric triad: Asperger's syndrome, obsessive-compulsive disorder, and anorexia. The function of a cloned serotonin transporter with this mutation (SERT-AS) has been characterized using [3H]5Ht uptake assays, binding assays employing a high affinity SERT ligand, b-CIT, and immunocytochemical methods. When compared to the wild type SERT, mutant SERT-AS exhibits a roughly 1.5 fold increase in both maximum transporter velocity (Vmax) and binding sites

(Bmax) and an increase in affinity (lower Kd) for b-CIT, a high affinity ligand. Serotonin transporters have been shown to be highly regulated by various intracellular signal transduction pathways and direct phosphorylation of the transporter. Treatment of cells expressing the wild-type SERT with a nitric oxide donor S-Nitroso-N-acetylpenicillamine

(SNAP) suggest a role for nitric oxide in the regulation of wild-type SERT, but the mutant SERT-AS is refractory to this stimulus. This work aims at characterizing the differences between the wild type SERT and the mutant SERT-AS using pharmacological, biochemical, and electrophysiological methods. Further, we hope to delineate the mechanism by which nitric oxide upregulates wild-type SERT with the goal of understanding why SERT-AS is constitutively upregulated. These studies offer the possibility for new insight into the pathogenesis and treatment of autism.

fMRI of perceptual gating and response selection of high-functioning autism and in autism siblings

Matthew Belmonte, McLean Hospital Brain Imaging Center

We propose to apply fMRI to ten-to-fourteen-year-old children with high-functioning autism or Asperger syndrome during performance of a visual attention task designed to factor out demands of perceptual selection from demands associated with response selection. Subjects will perform a two-stimulus color-orientation discrimination in which different properties of each stimulus determine the status of the stimulus pair as a target or a non-target. In the stimulus in which orientation is the relevant property, color will have to be suppressed, and in the stimulus in which color is the relevant property, orientation will have to be suppressed. In a control task, both stimuli in each pair will be identical, and thus no suppression will be required. While both the experimental and the control tasks place demands on response selection, only the experimental task requires perceptual selection within each stimulus pair. We anticipate that perceptual selection will activate intraparietal sulcus, and that response selection will activate dorsolateral prefrontal cortex. We will compare results in autism to results in normal controls and also in autism siblings. The latter comparison is of interest since autism siblings share some of the cognitive characteristics of autism probands, yet they do not, in general, have autism. Siblings may thus offer a glimpse of the neurophysiological roots of the autistic syndrome, unobscured by later developmental sequelae.

Identification of genes involved in autism

Russell Ferland, Beth Israel Deaconess Medical Center

Autism is a neurological, developmental disorder that is characterized by abnormal communication and social interaction, and impaired cognitive development. Studies have demonstrated a clear genetic link with autism and have shown that it affects approximately 5:10000 people (Frombonne, 1999). Many groups have undertaken whole-genome screens in an effort to identify susceptibility loci in idiopathic autistic individuals living in the USA, with moderate success. Our laboratory has had great success in identify genes associated with neurological disorders through the use of families having consanguineous marriages from the Middle East. We are now applying this approach utilizing families with first-cousin marriages that have individuals affected with autism. We currently are examining families with first-cousin marriages in which approximately 25% of the children from these marriages have autism. We have conducted a genome-wide screen of these families and have demonstrated potential linkage to several loci in the genome. Our evidence suggests potential candidate regions on chromosomes 1, 3, 6, 8, 10, and 18 by multipoint analysis (multipoint LOD scores > 1). Currently, we are attempting to test these candidate intervals through homozygosity mapping, marker analysis, and candidate gene identification in these chromosomal regions. Furthermore, our laboratory has initiated a collaboration with a school for autistic children in Kuwait and will obtain DNA from other consanguineous families with multiple autistic children, allowing us to expand our study of recessive autism genes. Overall, these studies aim to identify genes associated with autism, which potentially will lead to improved diagnosis and treatment.

Toward generation of an autism mouse model by making locus-specific duplications homologous to human chromosomes 15q11-q13 region

Yong-hui Jiang, Baylor College of Medicine

The numerous reports of autistic individuals with cytogenetic abnormalities of chromosome 15 have indicated that this region may harbor a susceptibility gene or genes for autistic disorder. The most common abnormalities are interstitial duplications and isodicentric chromosomes of exclusively maternal origin, suggesting that the gene or genes contributing to autism susceptibility may be subject to imprinting. Chromosome 15q11-q13 is an imprinted domain implicated in two neurological disorders, Prader-Willi syndrome (PWS) and Angelman syndrome (AS). Two maternally expressed genes, UBE3A and ATP10C, map within the region. UBE3A is the Angelman-causing gene and is expressed from the maternal allele in brain. We hypothesize that maternal duplication of 15q11-q13 may disrupt the normal expression of imprinted genes such as UBE3A and ATP10C and that abnormal expression of these two genes and/or others may contribute to autism susceptibility. We propose using the Cre-loxP system to prepare mutant mice with a duplication covering the entire 15q11-q13 region; a duplication covering the Ube3a gene and its possible regulatory elements; and a duplication covering the Atp10c gene. We will examine the expression pattern for Ube3a and do neuropathology, neurophysiology, and behavior testing on mutant mice to identify any impairment in morphology and social interaction. We believe there is a great likelihood that this will produce the first valid mouse model for autism. The mouse model will facilitate the genetic dissection of this trait and eventually lead to development of new and effective therapeutic interventions.

An investigation of somatosensory processing in autistic children using magneto-encephalography (MEG)

David McGonigle, University of California, San Francisco

The social and communicative handicaps present in autistic individuals have led a number of researchers to suggest that autistic individuals can be best described as suffering from a deficit in 'theory of mind' (e.g. Boucher, 1989). Others have focused on autistics' disorders of 'executive function' (Russel, 1998). An alternative hypothesis is that the higher-order cognitive deficits observed in autism are caused by disorders of basic sensory processing. Frith (1989) has proposed that the disorders of perception arising in autism may result from weak 'central coherence' (CC), or an inability to extract global features or context from stimuli. To examine sensory processing in people with autism, we propose to investigate the neuromagnetic correlates of the processing of somatosensory stimuli in autistic children using magnetoencephalography (MEG), a non-invasive neuroimaging method. We predict that autistic individuals will have disrupted spatial patterning in their primary somatosensory cortex (SI), and will furthermore show differences in amplitude of their somatosensory magnetic mismatch response when compared to age-matched controls. By quantifying and localizing the neural substrates of this aspect of autism (disorders in sensory processing), we believe our work may suggest novel therapeutic approaches (e.g. Merzenich et al., 1996) to the problem of autism in children.

Mechanisms underlying receptors delivery to synapses in early postnatal development

Takuya Takahashi, Cold Spring Harbor Laboratory

Large deficits in information processing such as learning and memory have been found in autistic patients. It is suggested that disruption of the glutamatergic neurons is responsible for these deficits. Long-term potentiation (LTP), the long lasting enhancement of synaptic strength induced by repetitive activation of glutamatergic excitatroy synapse, is believed to have important roles in learning and memory. One possible mechanism of LTP expression is the rapid delivery of the functional AMPA-type glutamate receptors to synapses from non-synaptic sites. Indeed, GFP-tagged AMPA receptor 1 (GluR1) is delivered to synapses after LTP-inducing stimuli. In contrast, GluR2 is continuously delivered to synapses and replaces existing synaptic receptors. Signaling mechanism of synaptic delivery of AMPA receptors is poorly understood. Interestingly, GluR4 is expressed exclusively in the first postnatal week and delivered to synapses by spontaneous activity. This suggests that GluR4 has a crucial role in information processing during early postnatal development. Considering the early onset of autism, it is important to understand the cellular and molecular mechanism of information processing during early postnatal development. We have characterized the important region for delivery in the carboxyl terminus of GluR4 and isolated Hsc70 as a binding protein of this region. We will analyze the functional role of Hsc70 on the delivery of GluR4.

Pilot Research Award

This award was established to help researchers investigate promising hypothesis, generate new data about the biology of autism, generate preliminary data leading to larger scale studies and federal funding and to replicate or expand previous findings. Pilot awards are funded at the level of $40,000 per year for one or two years. Grants are reviewed annually.

Functional characterization of the SPCH1 gene

Joseph Buxbaum, Mount Sinai School of Medicine

A relationship has been postulated between certain language disorders and autism. The strongest evidence for this relationship is the identification of families with chromosomal abnormalities leading to language disorders in some family members and autism in others. Further support for this has been the genetic linkage of both language disorders and autism to a region of chromosome 7. Recently, a gene that underlies the language abnormality in a family with severe language disorder has been identified as foxp2. This gene is a transcription factor that has not been studied in detail. We and others are examining this gene as a candidate gene for autism, and we are also studying the expression of this gene during development. Given the importance of this gene, we here propose to disrupt this gene in mice ("knockout") and thereby study its role in development of the central nervous system and identify genes that are regulated by foxp2.

The development of perceptual integration in autism

Chantal Kemner, University Medical Center Utrecht

It is well known from clinical practice that subjects with autism are preoccupied with details, and they are usually found to excel in certain visuospatial tasks, which have in common that a tendency towards detail processing is advantageous. Extensive detail processing also seems to play a role in the social problems of people with autism, such as face processing. Also, in autism structural as well as functional abnormalities are found in the occipital lobe. It is hypothesized that these findings indicate specific problems in early visual processing, viz. in visual perceptual integration. This is the ability to spatially integrate details of stimuli. An already funded study was started on perceptual integration in school age and adult autistic subjects. Two tasks are being used; one on texture segregation and one on face processing. During the tasks event-related brain potentials are measured, in order to get detailed information on the course of the perceptual integration process. However, there are indications that the abnormalities in autism are subjected to developmental influences. Therefore, it is warranted to study perceptual integration in autism as early as possible. In this project, the tasks will be presented to children with autism of about three years of age, who are recruited from a large screening study on early detection of autism in our department. The requested support will be used to accommodate the testing procedure for young children, to do the testing, and for analyzing the data.

Sensory experience, behavioral therapy, and neural plasticity: Implications for autism remediation

Michael Kilgard, Ph.D., University of Texas at Dallas

Autism is characterized by impairments in social interaction, disordered communication, repetitive behavior, and stereotyped interests. We propose that these symptoms lead to a form of isolation that disrupts the development of normal brain responses and in turn hinders the acquisition of critical language skills. Anatomical studies have established that even mild isolation during development can lead to significant weakening of cortical circuits. Although behavioral therapy and auditory training appear to improve language skills in autistic children. The neural basis of these improvements is not known. We have recently demonstrated that early sensory enrichment in rats leads to a profound increase in the sensitivity, frequency selectivity, response strength, and processing speed of neurons in primary auditory cortex. Similar brain plasticity may explain training-induced improvements of language function in autistic children. This proposal outlines experiments 1) to more completely characterize what specific aspects of an enriched environment strengthen cortical circuits, 2) to document how daily behavioral training improves cortical processing, 3) to establish the time course of developmental plasticity, and 4) to determine how dysfunction in the central cholinergic system affects auditory cortex maturation. Our preliminary findings indicate that during development cortical circuits are highly susceptible to degradation, and that targeted sensory enrichment can be extremely effective at restoring these circuits to normal performance. Results from the proposed experiments and others from the Autism Neural Plasticity Initiative will significantly influence the development of behavioral and pharmacological treatments for autism.

Using event-related potentials (ERP) to characterize auditory processing deficits in autism spectrum disorder and epilepsy

Elizabeth Pang, Ph.D., The Hospital for Sick Children (Canada)

Autism Spectrum Disorder (ASD) is a childhood neuropathology affecting language, social interaction, behavior and play. Landau-Kleffner Syndrome

(LKS) is an acquired epileptic aphasia where normal children develop a devastating loss, or regression, of language. Two important similarities exist between ASD and LKS: 1) over one-third of the children with ASD also report a language regression, and 2) both ASD and LKS manifest auditory processing deficits. The question raised whether ASD and LKS are biologically distinct entities or whether LKS is a later manifestation of regression seen along the spectrum of ASD. Examination of these auditory processing deficits may shed light on the pathoaetiology of these disorders. Auditory processing in the cerebral cortex can be examined using event-related potentials (ERP), in particular, the N1. Our ERP Lab has recently published the developmental N1 norms. Our feasibility studies suggest that a specific and consistent N1 abnormality can be observed and appeared over one cerebral hemisphere in ASD and over both hemispheres in LKS. This raises the possibility that the N1 abnormality may be a biological marker for ASD and LKS and that the pattern of appearance of this abnormality may be an important diagnostic toll for differentiating these disorders. Objectives: (1) Verify whether the N1 abnormality is a biological marker for ASD and LKS. (2) Test whether the N1 abnormality can discriminate ASD and LKS. (3) Look for other consistent abnormalities in the N1 related to ASD. (4) Test whether more complex auditory stimuli are better markers for these disorders.

A pilot cross-cultural study of autism phenotypes in Puerto Rico

Jeremy Silverman, Mount Sinai School of Medicine

The Mount Sinai Autism Family Studies Research Center recently studied a very large number of primarily non-Hispanic affected sibling pair families for genetic and phenotypic studies. In one study we identified several autism related clinical features that show evidence of familiality (i.e. the level of clinical expression among affected members in the same family are more likely to be similar than between unrelated affected individuals). Indeed, to date, we have looked at one of these features (phrase speech

delay) and found substantially increased evidence for genetic linkage on chromosome 2 among affected sibships who share this characteristic. In the present pilot project we will recruit affected sibling pair families from Puerto Rico, a distinct population from the families previously studied, to begin to examine whether similar patterns of familiality are evident in affected sibling pair families in this culture as well. If so, the familiality of such features are more likely to be explained by similar underlying genetic factors as opposed to cultural/environmental ones. Blood samples too will be collected for our genetic studies and shared with AGRE, under the terms of our ongoing collaboration, and to examine lead levels in Puerto Ricans with autism. Puerto Rico is especially valuable as a separate recruitment site because the genetics of Puerto Rico is largely distinct from the U.S. mainland population and relatively homogeneous. In addition, families are frequently very large and highly cooperative, yet understudied despite the fact that Puerto Rican people constitute a major minority group in the United States.

Cellular mechanisms controlling central oxytocinergic activity: Role in the pathophysiology of autism

Javier Stern, Wright State University

Autism, a behavioral syndrome characterized by impairments in socialization, communication and stereotyped behaviors, has been the subject of substantial investigation. While major advances have been made, no pharmacological treatment has yet been found to consistently improve the symptoms or course of the disease. Developing a more effective treatment for autism requires research on the underlying pathophysiology. Even though autism is recognized as a neurodevelopmental syndrome, its neurobiological basis is poorly understood. Growing evidence indicates that the neuropeptide oxytocin plays an important role in social behavior, cognition and motor stereotypes. Furthermore, an abnormal function of oxytocinergic systems has been proposed to be involved in the pathogenesis of autism. Little is known about the cellular and functional properties of central oxytocin neuronal circuits, and how abnormal changes in these properties might be involved in the pathophysiology of autism. Using the oxytocin knock out mouse as an animal model for autism, we aim to determine a) the cellular mechanisms controlling neuronal excitability in oxytocin neurons that innervate limbic structures involved in behavioral and social functions, b) the cellular mechanisms by which oxytocin modulates neuronal activity in these areas, and

c) the mechanisms underlying altered neuronal function in limbic areas in the oxytocin knock out mouse. This work will provide fundamental information on the cellular mechanisms regulating central oxytocin activity. Furthermore, it will lead to a better understanding of the cellular mechanisms that contribute to the pathophysiology of autism, providing a basis for the development of therapeutic strategies for the treatment of this disease.

Analysis of candidate genes in autism

Enrique Villacres, University of Washington

Current evidence suggests that autism is a polygenic disorder with at least five or more genes causing the disease. We hypothesize that chromosomal translocations found in some autistic patients cause or contribute to autism. The genes disrupted by these translocations are candidate genes for autism. These genes may be major effect loci coincident with chromosomal regions identified by linkage analysis or minor effect loci not detectable by standard family-based methods. Point mutations or polymorphisms in the genes identified may contribute to autism in subjects with normal karyotype. We have performed molecular analysis of a balanced chromosomal translocation t(7;20) (q11.2; p11.2) in a pair of twins with autism. Specifically, we have identified a novel gene (AUTS2) at 7q11.2, that spans this breakpoint. Two recent searches for susceptibility loci in autism using genetic linkage methods yielded positive evidence for an autism locus on chromosome 7q (Barret et al., 1999; IMGSAC, 2001). AUTS2 is expressed in fetal brain, suggesting that alterations in this gene could result in abnormal development leading to autism. Preliminary evidence does not support allelic association with autism with only two SNPs studied. The goals of this proposal are to 1) identify the chromosome 20 gene/genes disrupted by t(7;20) in the monozygotic autistic twins; 2) identify genes disrupted by all the breakpoints in an autistic boy with a complex rearrangement t(1;7;21); and 3) screen translocation breakpoint genes for mutations in non-breakpoint subjects. Finding one or more genetic cause of autism will provide clues to the treatment of this disorder.

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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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FEAT'S "Night of Caring" April 27

Sacramento FEAT is holding its' 9th Annual "Night of Caring" Dinner and Auction fundraiser on April 27, 2002. If you have been helped by the FEAT and the Daily Newsletter and would like to show your appreciation you can by supporting our fundraiser. Make an auction contribution or sponsorship donation. Please call 916-843-1536 for more information. Thank you.

FEAT is a tax-exempt non-profit corporation

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