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[From the CAN Alert email list.]
Researchers from around the world presented their latest
findings on autism at the recent inaugural International Meeting For Autism
Research (IMFAR). Held at the San Diego Convention Center as a satellite
meeting of the Society for Neuroscience Meeting, IMFAR was jointly sponsored by
the Cure Autism Now Foundation, the U.C. Davis M.I.N.D. Institute, and the National
Alliance for Autism Research (NAAR).
Approximately 120 researchers presented their findings in
a slide/lecture format. In addition over 100 poster presentations were
displayed summarizing other autism-related research developments. The concurrent
slide/lecture presentations were grouped into subject categories such as
Treatment, Neuropsychology, Genetics, Diagnosis, Neuroimaging,
Gastroenterology, Immunology and Animal Models.
Many presentations, including a number of those mentioned
below, involved researchers funded by Cure Autism Now in the present or past,
as well as scientists serving on the Cure Autism Now Scientific Advisory Board.
The following is a brief summary of a few presentations in each category, as a
sampling of the broad range of autism related research currently being
reported.
Abstracts on all the research presentations at IMFAR
can be viewed at www.imfar.org.
Dr. Isabelle Rapin et al, of the Albert Einstein College
of Medicine in New York presented evidence for language disorder subtypes at
school age in children with preschool DSM-IIIR autistic disorder. Dr. Rapin
re-evaluated at school age a number of autistic children who had been studied
several years earlier. Her findings showed persistent phonologic deficits in
some children with autism, but their prevalence appeared to decrease with age.
Furthermore, the language disorders of children on the autistic spectrum fell
into identifiable subtypes.
Adaptability is a temperament characteristic that refers
to the ease with which an individual modifies behavior to adjust to changes in
social context. Hepburn, Rogers, Stone and Shub of the University of Colorado
Health Sciences Center in Denver hypothesized that low adaptability may be an
early manifestation of the restricted interests and strict adherence to
routines that distinguish autistic children from other developmentally
disordered children after age 3. The researchers conducted tests comparing the
adaptability of the autistic children with other developmentally disordered
children at ages two and five. They found that the two year olds with autism
were considerably less adaptable than all their peers. They also discovered
that the younger autistic children were considerably less adaptable than the
5-year-old autistic children.
Dr. D.J. Scambler et al., also from the University of
Colorado Health Sciences Center presented findings on emotional responsivity in
children with autism and other developmental disorders. They measured responses
to emotions expressed by others in children with autism, children with global
developmental delays, and typically developing children. The children with
autism expressed less emotional responsivity than did children in the other two
groups, both in frequency of emotional contagion and degree of hedonic tone
change across six emotionally charged tasks. The researchers believe that their
findings provide focal points for investigation of the genetics and
neuro-psychology/neuro-physiology of autism.
A study performed at UCLA Graduate School of Education and
UCLA Child Psychiatry in Los Angeles compared diadic (adult-child) and triadic
(adult-child-object) social interactions of children with autism. C. Whalen, C.
Kasari, and T. Paparella observed children from 40 to 72 months with their
caregivers in play situations with and without toys. Their results suggested
that children with autism may demonstrate more severe social deficits with
their caregivers in triadic interactions (with toys) than in diadic
interactions (with caregivers and no toys) compared to typically developing
children.
J. M. Winter and L. Schriebman of the Autism Research
Laboratory at UC San Diego, La Jolla, California presented their findings on
fathers as caregivers for children with autism spectrum disorders. In making
the presentation, Jamie Winter said that the findings confirmed that there was
generally more maternal involvement in the caretaking of children with autism.
The fathers surveyed gave as reasons for less involvement that they felt the
mother was more competent, and that fathers often lacked both the time and
understanding of the child. But the survey also revealed that 89 percent of the
non- participating fathers indicated a willingness to participate if
alternative interventions more suited to fathers were developed. The
researchers concluded that the different requirements and preferences of
fathers in training formats and programs needs to be addressed.
Several presentations featured the results of various
clinical drug trials being used in the treatment of autism. Holmes et al., in
Private Practice at Baton Rouge, Louisiana, and at the Tulane University
Medical Center in New Orleans, are conducting a trial with over 400 autistic
patients for the removal of heavy metals. They are using meso-2,3-dimercapto
succinic acid (DMSA) and lipoic acid (LA). In general, noticeable improvements
in language, self-help skills, interaction and core autistic features were not
seen until the patient has been on DMSA with LA for two to three months. The
majority of children excreted mercury, lead and other metals, suggesting that
there may be a generalized problem with metal metabolism. The researchers
reported that younger children respond well to this therapy with noticeable
improvement in function.
A presentation of particular interest to researchers,
parents and friends of Cure Autism Now showed the results of a quantitative
genome scan of autism endophenotypes: Language and OCD. The study was conducted
at the Departments of Neurology and Human Genetics at UCLA, Los Angeles, by M.
Alarcon, R.M. Cantor, the AGRE Consortium and Chairman of its Steering
Committee Dr. Dan Geschwind. The Autism Genetic Resource Exchange (AGRE) was
developed by Cure Autism Now. It is the first truly collaborative autism gene
bank offering DNA, serum samples and cell lines from an ever-increasing
collection of well-characterized families to qualified researchers worldwide.
Since autism is comprised of deficits in several distinct
domains, the researchers hypothesized that a quantitative analysis of cognitive
and behavioral endophenotypes with high familiarity would increase their power
to detect susceptible loci. Using the AGRE sample, the research findings
suggest that the putative susceptibility gene on chromosome 7 may be a
quantitative trait loci (QTL) specific for the language deficits associated
with autism.
Dr. A.M. Persico and a large group of international
researchers presented their findings on the reelin pathway and autistic
disorder. Reelin plays a critical role in the development of several brain
structures putatively altered in autistic brains. This study showed
preferential transmission of APO-E2 alleles to both affected and unaffected
offspring in 235 trios, suggesting that APO-E2 may confer protection from
either infertility or miscarriage in families with an autistic proband. These
results were discussed in reference to the role of reelin as a regulator of
cell migration.
Dr. Lisa Croen presented findings on the epidemiology of
autism in California. Children with full syndrome autism born in California
from 1987 through1994 were identified from the Department of Developmental
Services electronic data files and compared to the total California population
of live births. Dr. Croen reported that from a live birth population of greater
than 4.5 million, 5,038 children with autism were identified. This represents a
prevalence rate of 11 in 10,000 live births. Adjustment risk estimates
indicated at 4-fold increased risk for boys and an approximate 1.5-fold
increased risk for multiple births. Noting that children born to immigrant
mothers had similar or decreased risk compared to California mothers, Dr. Croen
said that environmental factors associated with these demographic
characteristics may interact with genetic vulnerability to increase the risk of
autism.
As was noted in the neuroimaging presentation in the
closing “State-of-the-Science” symposium at IMFAR one of the well-established
facts about autism in recent years has been the related increase in brain
volume and head circumference. In a conference slide presentation, Dr. Eric
Courchesne of the Laboratory for Research on the Neuroscience of Autism at the
Children’s Hospital in La Jolla, California, presented his findings on the
subject. Dr. Courchesne and his colleagues recently reported on abnormally
large brain volume in autistic toddlers. In their most recent study, the
researchers examined whether this abnormal overgrowth was present at birth, by
obtaining birth head circumference measures from hospital records. The
estimates of brain volume of the autistic babies was not different from
published MRI brain volumes of normal neonates. Dr. Courchesne concluded that
the study suggests that in autism, there is abnormally accelerated growth of
the head and brain during!
!
the first years of postnatal life.
Cure Autism Now Scientific Review Committee member Dr.
M.K. Belmonte of the Cognitive Neuroimaging Laboratory at McLean Hospital in
Belmont, Massachusetts, presented findings on fMRI for generalized arousal as a
substitute for early selection during conditions of shifting visual spatial
attention. Preliminary data on autism from the study shows an absence of
lateralized attentional activity in the occtipitotemporal region, and a high
level of lateralized attentional activity intraparietally. Dr. Belmonte
suggested that in autism during conditions that demand rapid change in
attentional set, generalized arousal substitutes for impaired early selective
attention, leaving irrelevant stimuli to be suppressed at a later stage.
Eight presentations explored the incidence and
significance of gastrointestinal (GI) symptoms among children with autistic
spectrum disorders. J. Perrault and a group of researchers from the Mayo Clinic
in Rochester, Minnesota, presented their findings characterizing
gastrointestinal dysfunction in autistic children. They evaluated 126 children
in a clinical trial lasting 12 weeks. Twenty-one percent of the subjects had an
extensive constellation of GI symptoms. Diarrhea was present in 42 percent of
the patients, 29 percent had abnormally low chymotrypsin in stool, and 26
percent had elevated calprotectin in stool. Dr. Perrault said that overall, the
studies provide suggestions of specific abnormalities, either in pancreatic
secretion or mucosal inflammation.
C. Halloway and a group of Arizona-based researchers
presented preliminary work on heavy metal toxicity in people with autism. They
hypothesize that there may be a statistically significant association between
levels of heavy metal toxicity and the severity of autism, as measured by the
GARS. If such an association is observed, it could warrant further research
into the mechanism of effect that involves exposure to one or more heavy metals
and the development of autism.
Cure Autism Now Scientific Advisory Board member Dr.
Geraldine Dawson of the University of Washington presented findings on
high-density event-related potentials to fear and neutral facial expressions by
children with autistic spectrum disorders. Dr. Dawson is also a Cure Autism Now
research grantee. In this study, high-density event-related potentials (ERPs)
were used to measure brain activity in response to digitized photos of the same
woman posing either a fear or a neutral facial expression. Previous fMRI
studies have shown activation of the amygdala by fear expressions. Dr. Dawson
said that the present finding that typically developing children, but not
children with autism, show differences in the right temporal ERP component to
fear stimuli supports the hypothesis that dysfunction of the amygdala is
involved in autism spectrum disorders.
Eight presentations explored the use of animal models in
autism research. Cure Autism Now grantee S. Akbarian of the Whitehead Institute
for Biomedical Research in Cambridge, Massachusetts presented findings on the
expression pattern of the Rett disease gene MECP2 in the developing and mature
primate prefrontal cortex, complimented by comparative studies on mouse cerebral
cortex. The researchers concluded that MECP2 expression in rodent and primate
brain is not limited to the developmental period. MECP2 may be important for
neuronal maintenance both in the developing and in the adult brain. This is
consistent with their observation that mutant mice with a neuron-specific
deletion of Mecp2 in the early postnatal period developed a Rett-like phenotype
in adulthood.
Patricia Rodier of the Departments of OBGYN and Pathology
at the University of Rochester School of Medicine in New York spoke about
stereology and the inferior olive (a part of the brain) in an animal model of
autism. Reduction of Purkinje cell (PC) numbers is the most frequently reported
abnormality in postmortem studies of individuals with autism. Exposure of rat
embryos on the 12th day of gestation to sodium valporate (NaVP), a
drug known to increase the risk of autism, leads to reduced PC numbers and
changes in cerebellar volume. The most likely candidate for a structure whose
alteration might disrupt cerebellar development is the inferior olive. So the
researchers compared the inferior olives of exposed rats and controls. They
found that neuron density was normal in treated animals, but the shape and
volume of the inferior olive was significantly altered paralleling observations
in human cases of autism. They suggest that autism may result from an early
injury to th!
!
e inferior olive.
Eight presentations explored the role of immune
dysfunction in autism and related subjects. Cure Autism Now grantee Dr. Andrew
Zimmerman presented on the increased incidence of HLA-B60 and maternal DR-4 in
autism. Since autoimmune disorders frequently have human lymphocyte antigen
(HLA) associations, genes coding for HLA may provide markers of genetic
determinants for brain development. Dr. Zimmerman and his colleagues found that
HLA-B60 and DR-4 may serve as markers for genes on chromosome 6p, possibly in
linkage disequilibrium, that are important for development and function of both
the immune and nervous systems. Maternal HLA-DR4 might predispose the fetus to
a maternal immune reaction or infection. High resolution typing may clarify
these relationships in autism.
D.A. Trauner et al., of UC San Diego School of Medicine in
La Jolla, California have explored markers of immune function in children with
autism and epileptiform EEG abnormalities. They found that these children had
an increased production of pro-inflammatory cytokines by CD-4+ T cells,
suggesting an altered immune system. Studies are underway to determine whether
these immune changes predict response to steroid treatment.
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