FEAT DAILY NEWSLETTER
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February 5, 2002
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[These abstracts are synopsis of medical research that are
peer reviewed. Some contain highly
technical language not intended for the lay reader. ]
·
Functional Neuroimaging And Childhood Autism
·
Impaired Categorical Perception Of Facial Expressions
·
Secretin Study
·
Understanding of Others’ Intentions In Children With
Autism
·
Causes of Death In Autism.
·
On Biological Defects In Autism
·
Towards a Primate Model Of Autistic Symptomology
·
The Abnormal Regulation Of Gene Expression In Autistic
Brain
·
Study of Hippocampal Neurotransmitter Receptors In
Autism
·
Dysregulation of Reelin
·
Current Investigations In Autism Brain Tissue Research.
·
Chromosome 22q11 Deletion Syndrome (CATCH 22):
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ui
ds=11819054&dopt=Abstract <- - address ends here. Boddaert N, Zilbovicius M.
Service Hospitalier Frederic Joliot, DRM, DSV, CEA, Orsay,
France,
Childhood autism is now widely viewed as being of
developmental neurobiological origin. Yet, localised structural and functional
brain correlates of autism have to be established. Structural brain-imaging studies
performed in autistic patients have reported abnormalities such as increased
total brain volume and cerebellar abnormalities. However, none of these
abnormalities fully account for the full range of autistic symptoms.
Functional brain imaging, such as positron emission
tomography (PET), single photon emission computed tomography (SPECT) and
functional MRI (fMRI) have added a new perspective to the study of normal and
pathological brain functions. In autism, functional studies have been performed
at rest or during activation. However, first-generation functional imaging
devices were not sensitive enough to detect any consistent dysfunction.
Recently, with improved technology, two independent groups
have reported bilateral hypoperfusion of the temporal lobes in autistic
children. In addition, activation
studies, using perceptive and cognitive paradigms, have shown an abnormal
pattern of cortical activation in autistic patients.
These results suggest that different connections between
particular cortical regions could exist in autism. The purpose of this review
is to present the main results of rest and activation studies performed in
autism.
PMID: 11819054 [PubMed - in process]
* * *
Impaired Categorical Perception Of Facial Expressions In
High-Functioning Adolescents With Autism.
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ui
ds=11815876&dopt=Abstract <- - address ends here. Teunisse JP, de Gelder B.
Department of Psychology, University Medical Centre St.
Radboud, Nijmegen,
The Netherlands
Categorical perception of facial expressions is studied in
high-functioning adolescents with autism, using three continua of facial expressions
obtained by morphing. In contrast to the results of normal adults, the
performance on the identification task in autistic subjects did not predict
performance on the discrimination task, an indication that autistic individuals
do not perceive facial expressions categorically.
Performance of autistic subjects with low social
intelligence was more impaired than that of subjects with higher social IQ
scores on the expression recognition of unmanipulated photographs. It is
suggested that autistic subjects with higher social intelligence may use
compensatory strategies that they have acquired in social training programs
This may camouflage the deficits of this subgroup in the perception of facial expressions.
PMID: 11815876 [PubMed - in process]
* * *
‘Secretin self-assembles and interacts spontaneously with
phospholipids in vitro.’
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ui
ds=11814635&dopt=Abstract <- - address ends here. Gandhi S, Rubinstein I, Tsueshita T,
Onyuksel H.
Department of Bioengineering, University of Illinois at
Chicago, 60612,
Chicago, IL, USA
Secretin, a 27-amino acid neuropeptide, is a member of the
secretin/glucagon/vasoactive intestinal polypeptide (VIP) superfamily of amphipathic
peptides. The peptide modulates gastrointestinal and neuronal function and is
currently being evaluated for the treatment of autism. However, as most peptides, it has a short
circulation half-life. Previously, we have shown that VIP self-assembles in
aqueous environment and interacts with a biomimetic phospholipid membrane.
These in vitro characteristics increase VIP half-life and bioactivity in vivo.
The purpose of this study was to investigate whether
secretin exhibits similar properties in vitro by forming micelles in aqueous
solution and interacting with phospholipids.
Results of this study demonstrated that secretin
self-assembles to form micelles in HEPES buffer at 25ntries, a strong
indication for the presence of several new species among the isolates.a],
therefore, relies on the abrogation of both Pro and Asn hydroxylation, which
during normoxia occur at the degradation and COOH-terminal transactivation
domains, respC above [approximate]0.4 [mu]M. Additionally, secretin interacts
with a biomimetic phospholipid membrane as indicated from a significant
increase in membrane surface pressure (from 25.5 [plus minus] 1.3 to 32.5 [plus
minus] 3.0, P < 0.05). Importantly, the peptide undergoes conformational
transition from predominantly random coil in saline to [alpha]-helix in the
presence of phospholipid, distearoyl-phosphatidylcholine-poly(ethylene) glycol
(mol mass 2000) micelles. We suggest that these distinct biophysical attributes
could modulate secretin bioactivity in vivo.
PMID: 11814635 [PubMed - as supplied by publisher]
* * *
Understanding of Others’ Intentions In Children With
Autism.
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ui
ds=11814270&dopt=Abstract <- - address ends here. Carpenter M, Pennington BF, Rogers
SJ.
Max Planck Institute for Evolutionary Anthropology,
Leipzig, Germany.
Many studies have shown that children with autism have
difficulty understanding the thoughts and beliefs of other people. However,
little research has been conducted on what these children understand about
simpler mental states such as intentions. The current study tested the
understanding of others’ intentions in 2 ½- to 5-year-old children with autism
and a control group of children with other developmental delays. We used Meltzoff’s
(1995) test of understanding of others’ unfulfilled intentions in an imitation
context, with an additional “End State” condition.
We found no significant between-group differences on any
measure involving the understanding of others’ intentions. Although
within-group patterns suggested that children with autism may have a slightly
less complex understanding of others’ intentions than do other children, it was
clear that any deficits these children showed in this area were not as marked
as those they typically show on traditional theory of mind tasks.
PMID: 11814270 [PubMed - in process]
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* * *
Causes of Death In Autism.
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ui
ds=11814268&dopt=Abstract <- - address ends here. Shavelle RM, Strauss DJ, Pickett J.
Life Expectancy Project, San Francisco, California, USA.
The objective of this study was to determine which causes
of death are more frequent in persons with autism, and by how much, compared
with the general population. Subjects were 13,111 ambulatory Californians with autism,
followed between 1983 and 1997. The units of study were person-years, each
linked to the subject’s age, sex, and cause of death (if any) for the specific
year.
Observed numbers of cause-specific deaths were compared
with numbers expected according to general population mortality rates.
Standardized mortality rates (SMRs) were computed for each mental retardation
level. Elevated death rates were
observed for several causes, including seizures and accidents such as
suffocation and drowning; elevated mortality due to respiratory disease was
observed among persons with severe mental retardation.
Overall, excess mortality was especially marked for
persons with severe mental retardation, but life expectancy is reduced even for
persons who are fully ambulatory and who have only mild mental retardation.
PMID: 11814268 [PubMed - in process]
* * *
‘Proteomic approach for the elucidation of biological
defects in autism.’
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ui
ds=11814266&dopt=Abstract <- - address ends here. Junaid MA, Pullarkat RK.
Department of Developmental Biochemistry, New York State
Institute for Basic Research in Developmental Disabilities, Staten Island
10314, USA.
Proteomic-based approaches, which examine expressed
proteins in tissues or cells, have great potential in the elucidation of
biological defects in heterogeneous neurodevelopmental disorders such as
autism. In this approach, tissue or cellular proteins from control and affected
subjects are separated on two-dimensional (2-D) polyacrylamide gel electrophoresis,
and those proteins that show marked changes in the concentration between
control and affected subjects are identified by mass spectroscopy.
This method has been successfully applied in the
elucidation of the molecular biological defect in classic late-infantile
neuronal ceroid lipofuscinosis (Sleat et al., 1997).
Unlike the classical methods of genome-wide screening for
chromosomal localization followed by positional cloning, the proteomic approach
requires limited number of tissue samples and the study can be completed in a relatively
short time.
Currently, these methods are available for relatively
abundant proteins and generally are not applicable for hydrophobic proteins
because 2-D gel electrophoresis is not very effective in the analysis of
hydrophobic proteins. The genetic defect results in either total loss of
proteins or changes in molecular weight and/or isoelectric point will be
detectable by the proteomic method.
Because autism is a neurogenetic disorder, brain is the
tissue of choice for proteomic study. For an oligogenic disorder such as
autism, at least some of the aberrant (genes) proteins may be identified by
this technology.
PMID: 11814266 [PubMed - in process]
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* * *
Towards a Primate Model Of Autistic Symptomology
‘Functional genomics approaches to a primate model of
autistic symptomology’
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ui
ds=11814265&dopt=Abstract <- - address ends here. Hemby SE, Sanchez MM, Winslow JT.
Department of Pharmacology, Emory University School of
Medicine, Atlanta,
Georgia 30329, USA. shemby@pharm.emory.edu
Several studies indicate a primary dysfunction of the
temporal lobe in autism, specifically the hippocampal formation and entorhinal
cortex (EC). Assessment of gene
expression in the EC and hippocampus will provide insight into the subtle
alterations in neuronal function associated with autism. To this end,
evaluations in a primate model of social attachment, which produces behaviors
associated with autism, in addition to the use of human post-mortem tissue from
individuals diagnosed with autism will provide heretofore unattainable
information of how the complex neural circuitry of this region is altered in
autism.
Identification of altered expression of multiple genes
should provide a molecular “fingerprint” of autism and may provide new targets
for pharmacotherapeutic intervention.
PMID: 11814265 [PubMed - in process]
* * *
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ui
ds=11814264&dopt=Abstract <- - address ends here. Purcell AE, Jeon OH, Pevsner J.
Department of Neuroscience, Johns Hopkins School of
Medicine, Baltimore, Maryland, USA.
Autism is a pervasive developmental disorder of unknown
etiology. It is likely caused by mutations in one or more genes. One approach
to understanding the molecular changes that occur in autism is to measure gene expression
in post-mortem brain samples from individuals diagnosed with autism.
This may be accomplished with techniques such as cDNA
microarrays or subtractive hybridization. In general, gene expression is regulated
as a function of body region, developmental time, and physiological state. A premise
of the approaches we describe is that gene expression is regulated in cells
from autistic individuals as a consequence of the disease process.
It may be useful to detect such changes in order to
identify selective biological markers for autism. Additionally, the abnormal
regulation of gene expression may reveal cellular pathways that have been
disrupted, suggesting strategies for therapeutic intervention.
PMID: 11814264 [PubMed - in process]
* * *
Study of Hippocampal Neurotransmitter Receptors In Autism ‘Density
and distribution of hippocampal neurotransmitter receptors in autism: an
autoradiographic study.’
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ui
ds=11814263&dopt=Abstract <- - address ends here. Blatt GJ, Fitzgerald CM, Guptill JT, Booker
AB, Kemper TL, Bauman ML.
Neurobiology of Developmental Disorders Laboratory, Department
of Anatomy
and Neurobiology, Boston University School of Medicine, MA
02118, USA.
Neuropathological studies in autistic brains have shown
small neuronal size and increased cell packing density in a variety of limbic
system structures including the hippocampus, a change consistent with
curtailment of normal development. Based on these observations in the
hippocampus, a series of quantitative receptor autoradiographic studies were
undertaken to determine the density and distribution of eight types of
neurotransmitter receptors from four neurotransmitter systems (GABAergic,
serotoninergic [5-HT], cholinergic, and glutamatergic). Data from these single concentration
ligand binding studies indicate that the GABAergic receptor system
(3[H]-flunitrazepam labeled benzodiazepine binding sites and 3[H]-muscimol
labeled GABA(A) receptors) is significantly reduced in high binding regions,
marking for the first time an abnormality in the GABA system in autism.
In contrast, the density and distribution of the other six
receptors studied (3[H]-80H-DPAT labeled 5-HT1A receptors, 3[H]-ketanserin
labeled 5-HT2 receptors, 3[H]-pirenzepine labled M1 receptors,
3[H]-hemicholinium labeled high affinity choline uptake sites, 3[H]-MK801
labeled NMDA receptors, and 3[H]-kainate labeled kainate receptors) in the
hippocampus did not demonstrate any statistically significant differences in
binding.
* * *
‘Dysregulation of Reelin and Bcl-2 proteins in autistic
cerebellum.’
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ui
ds=11814262&dopt=Abstract <- - address ends here. Fatemi SH, Stary JM, Halt AR, Realmuto GR.
Department of Psychiatry, Division of Neuroscience
Research, University of
Minnesota Medical School, Minneapolis 55455, USA. fatem002@tc.umn.edu
Autism is a severe neurodevelopmental disorder with
potential genetic and environmental causes. Cerebellar pathology including
Purkinje cell atrophy has been demonstrated previously. We hypothesized that
cell migration and apoptotic mechanisms may account for observed Purkinje cell abnormalities.
Reelin is an important secretory glycoprotein responsible
for normal layering of the brain. Bcl-2 is a regulatory protein responsible for
control of programmed cell death in the brain.
Autistic and normal control cerebellar corteces matched
for age, sex, and post-mortem interval (PMI) were prepared for SDS-gel
electrophoresis and Western blotting using specific anti-Reelin and anti-Bcl-2
antibodies. Quantification of Reelin
bands showed 43%, 44%, and 44% reductions in autistic cerebellum (mean optical
density +/- SD per 30 microg protein 4.05 +/- 4.0, 1.98 +/- 2.0, 13.88 +/- 11.9
for 410 kDa, 330 kDa, and 180 kDa bands, respectively; N = 5) compared with
controls (mean optical density +/-SD per 30 microg protein, 7.1 +/- 1.6, 3.5
+/- 1.0, 24.7 +/- 5.0; N = 8, p < 0.0402 for 180 kDa band).
Quantification of Bcl-2 levels showed a 34% to 51%
reduction in autistic cerebellum (M +/- SD per 75 microg protein 0.29 +/- 0.08;
N = 5) compared with controls (M +/- SD per 75 microg protein 0.59 +/- 0.31; N
= 8, p < 0.0451). Measurement of beta-actin (M +/- SD for controls 7.3 +/-
2.9; for autistics 6.77 +/- 0.66) in the same homogenates did not differ significantly
between groups. These results demonstrate for the first time that dysregulation
of Reelin and Bcl-2 may be responsible for some of the brain structural and
behavioral abnormalities observed in autism.
* * *
Current Investigations In Autism Brain Tissue Research. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ui
ds=11814261&dopt=Abstract <- - address ends here. Pickett J.
Autism Tissue Program, Princeton, NJ 08540, USA. atp@brainbank.org
Brain tissue research has developed into a high-tech,
multifaceted approach to understanding neurological disorders. Directed toward
autism spectrum disorders, this investigative approach combines with other disciplines,
such as imaging and genetics, to help explain the range and intensity of
behaviors that characterize these disorders.
This report is intended as an update on current autism
brain research efforts and has a dual purpose: first, to disseminate
information to the scientific community in the hope of stimulating more
thinking about autism research and future collaborations; and second, to let
the autism community know what is happening with this precious resource that
was donated in the hope of determining the cause of autism and finding
effective treatments.
PMID: 11814261 [PubMed - in process]
* * *
Chromosome 22q11 Deletion Syndrome (CATCH 22):
neuropsychiatric and neuropsychological aspects.
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ui
ds=11811651&dopt=Abstract <- - address ends here. Niklasson L, Rasmussen P, Oskarsdottir S,
Gillberg C.
Department of Child and Adolescent Psychiatry, University
of Goteborg,
Sweden. ann.nordstrom@pediat.gu.se
Twenty children and young adults (age range 5 to 33 years,
12 females and eight males) with genetically confirmed 22q11 deletion syndrome
(CATCH 22: Cardiac anomaly, Anomalous face, Thymus hypoplasia/aplasia, Cleft palate,
and Hypocalcaemia), recruited from a large ongoing study, were given comprehensive
assessments with a view to determining the pattern of neuropsychiatric and
neuropsychological deficits thought to be part of the syndrome in many cases.
IQ ranged between 46 and 100 with a mean score of 70. Half
the group had an IQ <70. In 13 individuals, attention-deficit-hyperactivity
disorder (ADHD), mainly inattentive or combined type in most cases, and/or
autism spectrum problems were diagnosed.
Many participants, even among those who had an IQ within
the normal range and had neither ADHD nor autistic spectrum problems, showed a characteristic
and pronounced behavioural profile with low mental energy, initiation
difficulties, deficits in sustained attention, and social interaction (often
augmented by limited facial expression and communication and speech problems).
PMID: 11811651 [PubMed - in process]
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