Provided by the National Institute of Mental Health
Autism spectrum disorders (ASD), a broad
continuum of brain illnesses that includes Asperger's syndrome, share common
genetic roots and essential clinical and behavioral features, although they
differ in severity and age of onset. Autism, the most severe of these pervasive
developmental disorders, typically begins in early childhood and impairs
thinking, feeling, language, and the ability to relate to others.
From 1 to 6 in 1,000 Americans suffer from ASDs,1,2 with some recent studies
citing dramatic apparent increases in prevalence in certain locales. Boys with
the disorders outnumber girls three or four to one. Within the first few years
of life, children with ASDs fail to develop normal social interaction and
communication and show restricted, repetitive, or stereotyped behaviors and
interests.
Families coping with ASDs are searching for answers about causes, diagnosis,
prevention, and treatment. The National Institute of Mental Health's (NIMH)
investment in autism-related science has quadrupled over the past 7 years from
$9.4 million in FY 1997 to $36.2 million in FY 2002. The research is supported
through grants and contracts with investigators at university medical centers
and in the Institute's own laboratories in Bethesda, MD. In addition, new
Institute initiatives aimed at advancing basic knowledge of brain development
and genetics hold promise for understanding complex behavioral disorders like
autism. NIMH's autism-related research ranges from efforts to improve awareness,
diagnosis and treatment, to studies involving brain imaging, tissue banks,
animal models, genetics, developmental neurobiology, and neuropsychology.
Implementing the Children's Health Act of 2000
As part of the Children's Health Act of 2000,3 Congress designated the NIMH to
take the lead in expanding, intensifying, and coordinating NIH's expanding
autism research effort, which totaled nearly $74 million in 2002. NIMH has
implemented this landmark legislation, in collaboration with the four other
Institutes represented on the NIH Autism Coordinating Committee (NIH/ACC):
National Institute of Child Health and Human Development (NICHD), National
Institute of Neurological Disorders and Stroke (NINDS), National Institute on
Deafness and Other Communication Disorders (NIDCD), and National Institute of
Environmental Health Sciences (NIEHS).4
NIMH, on behalf of the Department of Health and Human Services (DHHS), also
convenes the Interagency Autism Coordinating Committee (IACC), which serves as a
forum where Federal agencies and public members can share information about
their autism-related activities. In addition to the NIH/ACC members, this panel
includes representatives from several DHHS agencies and the Department of
Education. The IACC also includes four public members, family members or
guardians of people with autism or spectrum disorders.5
Studies to Advance Autism Research and Treatment (STAART) Network. Foremost
among the Children's Health Act's provisions is a collaborative effort to
support development of several broadly based "Centers of Excellence in Autism
Research." In response, the five NIH/ACC Institutes have jointly established the
Studies to Advance Autism Research and Treatment (STAART) Network. This project
is building new infrastructure for autism research by bringing together critical
masses of expertise and resources at eight dedicated research centers across the
country. The Centers are conducting basic and clinical research, including
investigations into causes, diagnosis, early detection, prevention, and
treatment. They include research in the fields of developmental neurobiology,
genetics, clinical developmental psychology, and psychopharmacology.
Interdisciplinary collaborations, including the recruitment of outstanding
investigators who had previously not worked in the autism field, are being
funded in stages over the next several years.
Grants totaling $65 million over 5 years were funded in Fall 2002 and Spring
2003 to support STAART Centers at the following sites:6,7
University of North Carolina, Chapel Hill
Yale University
University of Washington
University of California, Los Angeles
Mount Sinai Medical School
Kennedy Krieger Institute, Baltimore
Boston University
University of Rochester, New York
Each center is pursuing its own particular mix of studies. For example, at the
Kennedy Krieger Institute and four collaborating area institutions, a team of 27
researchers psychiatrists, neuropsychologists, psychologists, speech-language
pathologists, developmental pediatricians and neuroscientists are examining
motor and communication impairments in autism, to find out what goes wrong in
the developing brain, with an eye to early identification and intervention.
Spurred by evidence of a serotonin abnormality in autism, investigators are
studying animals deficient in the chemical messenger to discover its role in
establishing connections between neurons.
Among other STAART Center studies currently underway, researchers at Yale
University are examining eye tracking in children with autism age 5-12, as well
in toddlers. They are studying how a child sees a social situation, relative to
his or her level of social competence. Investigators there are also using
functional brain imaging to assess the effectiveness of a computer-assisted
intervention to improve facial identification and facial expression in autism. A
study of relatives of individuals with autism and Down syndrome at the
University of North Carolina is looking for patterns of thinking about social
situations and "executive functioning" (planning, impulse control and reasoning)
that might provide clues to psychological characteristics shared in common among
families with these highly heritable disorders. A brain imaging study seeks to
discover the neural roots of social and emotional processes as well as executive
functioning and ritualistic-repetitive behaviors in adults and very young
children with autism.8
Public Input
The Children's Health Act of 2000 mandates that the NIH make available
information about its autism activities and facilitate public feedback to the
NIH. Communications Directors, Public Liaison Officers, and other staff from the
NIH/ACC regularly engage with representatives of autism advocacy groups to
exchange information and stay in touch via an internet web site and a
list-serve. Members of the autism advocacy community also serve as public
participants on NIMH scientific review committees. A searchable information
clearinghouse for all NIH autism-related activities is posted on the National
Library of Medicine's MedlinePlus Web site (http://www.nlm.nih.gov/medlineplus/autism.html).
This links to several resources within the DHHS, including NIMH's autism Web
page (http://www.nimh.nih.gov/healthinformation/autismmenu.cfm).
Brain Tissue and Genetics Resources
The Children's Health Act of 2000 also calls on NIMH to take the lead in
expanding a program under which samples of tissues and genetic materials are
donated, collected, preserved, and made available for autism research.
Post-mortem brain tissue, which has been very scarce for the study of autism,
offers a unique, high-resolution window into the inner workings of brain cells.
For example, by using radioactive tracers on thinly sliced sections of brain
tissue, scientists can detect and pinpoint abnormal activity of genes within
cells. Only with access to brain tissue can the underlying neuropathology of
autism be uncovered. To take advantage of emerging opportunities for discovery
in post-mortem tissue made possible by the new molecular methodologies, NIMH, in
collaboration with the autism community and other NIH Institutes, is stepping up
efforts to establish brain bank collections to study autism. For example, NIMH,
NINDS and NIDCD are mounting a joint effort to develop a National Autism Brain
Bank at the Harvard Brain Tissue Resource Center, which is primarily funded by
NIMH and NINDS. It will store and disseminate postmortem human brain specimens
for the study of autism.9
Diagnosis, Training, and Early Identification
People with ASDs show a broad range of impairment, with great variability in
clinical symptoms and levels of functioning. For example, some people with
autism have normal intelligence and develop good basic language skills, while
others lag intellectually and develop little or no language. A common diagnostic
scheme for assessing the complex social and communication deficits that
constitute key features of the disorder has been a critical prerequisite to
scientific progress.
NIMH has supported research that has raised the quality and standardization of
screening and diagnosis in autism. Standard diagnostic interviews and
observational methods developed through this research have become a national and
international "gold standard," ensuring that what is diagnosed in one research
center is comparable to that diagnosed in another. The Institute funds a series
of annual workshops for training researchers in the use of these tools, and is
funding further investigation of measurement tools.10,11
NIMH also supports research aimed at improving early diagnosis of autism.
Institute-supported studies have demonstrated that a reliable diagnosis of
autism spectrum can be made at age 2.12 Yet, the age of onset remains elusive.
Some children seem to develop normally for a couple of years and then regress;
for example, they may lose language skills after developing a small vocabulary.
Others may be affected from birth, but in such subtle ways that diagnosis is
delayed. Earlier identification of children destined to develop symptoms could
hold clues to the underlying neuropathology and would also facilitate early
intervention. NIMH is funding studies that focus on young children at heightened
risk for the disorder, such as younger siblings of children with autism.13,14,15
Brain Imaging
Non-invasive brain imaging techniques, such as MRI (magnetic resonance imaging),
offer great potential for advancing understanding of the neural basis of
emotional and intellectual deficits in autism and other childhood
neuropsychiatric disorders. However, scientists currently have little data on
normal brain function and development to compare with data from individuals with
autism. Such norms have been lacking for brain imaging studies, leading to
non-comparable findings and excessive duplication in scanning control subjects.
Therefore, NIMH is co-sponsoring, with NICHD, NIDA and NINDS, a $28 million
initiative that is using aMRI (anatomic magnetic resonance imaging), DTI
(diffusion tensor imaging), and MRS (magnetic resonance spectroscopy) to create
the world's first such large-scale database on normal brain development in
children.16
The NIH MRI Study of Normal Brain Development is cataloging the structural
development of the brain, by age and sex, with seven major research centers
scanning more than 500 infants, children, and adolescents. Children age 5 and
older are being followed up with additional scans and clinical and behavioral
reassessments at 2-year intervals. Younger children are being re-scanned at more
frequent intervals—3-12 months to capture more rapid brain maturational changes
occurring at these ages.
This study will permit the normal growth curves of brain structures to be
charted, revealing the development of circuitry for language, thinking, and
other functions. Individual brains differ enough that only broad generalizations
can be made from comparisons of different individuals at different ages. But
following the same brains as they mature allows scientists a much more detailed
view of developmental changes. By comparing scans of children with
neuropsychiatric disorders with this normative data, researchers will be able to
determine the timing and developmental course of brain structural changes in
childhood disorders. These databases, being developed by an NIMH-funded data
analysis center, will ultimately facilitate early diagnosis and differentiation
of various forms of autism. It will also speed the development of targeted
treatments and evaluations of their effects.
The promise of such a normative brain database for turning up clues about
childhood brain disorders was recently illustrated in a similar, but
smaller-scale, NIMH intramural study.17 In this first longitudinal structural
MRI study to track individual children's developing brains, the researchers were
surprised to discover a second wave of overproduction of gray matter (neurons)
just prior to puberty. Possibly related to the influence of surging sex
hormones, this thickening peaks at around age 11 in girls, 12 in boys, after
which the gray matter actually thins some. Prior to this study, scientists had
thought that the brain overproduced gray matter for a brief period in early
development (in the womb and for about the first 18 months of life) and then
underwent just one bout of pruning. The gray matter growth spurt predominates in
the frontal lobe, the seat of executive functions. This type of normative data
will help researchers contrast typical growth with that in autism spectrum
disorders. A wave of abnormal brain enlargement seen in MRI studies of young
children with autism follows a back-to-front pattern, similar to a wave of
abnormal gray matter loss seen in childhood onset schizophrenia. This may
suggest a process in which the timing and trajectory of various abnormalities
parallels clinical outcome.18,38 In other brain imaging studies, researchers
using MRI and MRS are searching for brain anatomical and biochemical
abnormalities that may underlie impaired social communication in children with
autism. One fMRI study is looking for malfunctioning brain circuits associated
with impaired thinking about human relationships, a problem seen in autism.
While in the scanner, subjects view animated cartoons designed to challenge
their ability to understand a social situation. High-functioning individuals
with autism are being scanned to sort out the neural circuitry of social versus
mechanical knowledge.19,20
Yet another series of MRI studies is pinpointing brain structural abnormalities
associated with the severity of attention deficits in people with autism.21 For
example, the researchers have shown that decreased volume in an area of the
brain's parietal lobe correlates with the degree of behavioral impairment in
detecting stimuli located outside a principal focus of visual attention.
A project at the University of North Carolina has been assessing the relation
between brain anatomy and autism through MRI scans of very young children with
autism.22 The aim is to get a better picture of the development and timing of
the brain enlargement that occurs in autism between 18 and 35 months. To relate
these findings to another developmental disorder of known origin, the
researchers have joined forces with colleagues at Stanford University to
similarly follow the brain development of children with Fragile X syndrome.23,24
These studies will illuminate genetic and environmental factors that influence
normal and abnormal brain development and may help to clarify subtypes of
autism.
Animal Models
Studies in monkeys hold great potential for understanding autism, since their
brains resemble those of humans thus offering valuable clues. For example, NIMH-funded
investigators are continuing to examine monkeys in which early injury to the
brain's limbic system, or emotional hub, interfered with the establishment of
social and emotional bonds.25 Experiments in monkeys by NIMH intramural
scientists found that loss in infancy of two key limbic structures, the amygdala
and hippocampus, results in social and emotional abnormalities strikingly
similar to autism, in both nature and time course, by 6 months of age. The
monkeys with brain lesions, like some autistic children, showed an absence of
social interactions, lack of normal facial expressions and body language, and
stereotyped behaviors. Also as in autism, the problems emerged only after early
infancy and remained permanent. Other monkeys in which a lower part of the
temporal lobe was removed developed milder symptoms that substantially abated as
they grew older. This study, combined with clinical findings, point to the
limbic system structures as likely sites of damage in autism.26 Such behavioral
and neuroanatomical research may help to pinpoint brain circuit abnormalities in
autism and ultimately lead to intervention strategies. Findings relevant to
autism may also emerge from planned studies of proteins in the animal brain.
Assuming there is a developmental abnormality in autism, due to a gene defect or
gene/ environment interaction, some genes are likely to turn on too much or too
little or in the wrong place. This may interfere with the migration and wiring
of embryonic brain cells during early development, or with the way cells
function. In collaboration with other NIH Institutes and the private sector,
NIMH is mounting efforts to expand the set of available tools for discovering
such molecular mistakes.
For example, studies in mice are identifying the neural basis of complex
behaviors. The mouse has become a critical model in studying human disease
because scientists have access to many specially bred strains each expressing
distinctive physiological and behavioral characteristics and know an enormous
amount about mouse genetics. Rapidly-evolving technologies now make it possible
to insert, knock out, or mutate mouse genes, quickly breed a generation that
expresses the change, and then see how it affects behavior. When autism-linked
genes are discovered, they will be inserted and expressed in mice to find out
what they do at the molecular, cellular, and behavioral levels. Researchers will
be able to track a wiring abnormality, a cell migration abnormality, or other
anomaly that may lead to symptoms in humans.
Clinical Genetics
While it is known that heredity plays a major role in complex behavioral
disorders like autism, the identification of specific genes that confer
vulnerability to such disorders has proven extremely difficult. Detecting
multiple genes, each contributing only a small effect, requires large sample
sizes and powerful technologies that can associate genetic variations with
disease and pinpoint candidate genes. And even after human disease vulnerability
genes are found, sophisticated techniques will be needed to find out what turns
them on, what brain components they code for, and how they affect behavior.
Although by no means assured, the prospect of acquiring such molecular knowledge
holds great hope for the engineering of new therapies.
Evidence suggests that some family members of people with autism may share with
them milder, but qualitatively similar, behavioral characteristics of autism.27
For example, they may have mild social, language or reading problems. A
multi-site team of NIMH-supported investigators has been studying such families
to characterize these behavioral traits in hopes of discovering sites in the
genome associated with them. In the latest phase of these studies,
neuropsychological characteristics of relatives of individuals with autism and
autism spectrum will be compared with those of people with injuries to brain
areas implicated in autism, such as the amygdala and frontal cortex. Patterns of
co-occurrence of the characteristics will be examined in individuals and
families.28
Four previously undetected chromosomal sites strongly linked to autism have been
discovered by the largest and methodologically most sophisticated genome-wide
screens to date, funded, in part, by NIMH. Two studies, led by investigators at
Columbia University and the University of Oxford, add regions on chromosomes 2,
5, 8, and 17 to a growing list of areas likely harboring autism-predisposing
genes. They also add to previous evidence implicating areas on chromosomes 7,
16, and 19.29,30
Although one chromosomal region, 7q, had turned up consistently in such screens,
no specific candidate gene there had yet been pinpointed until NIMH-funded
researchers, led by a team at the University of Iowa, discovered that variants
of a particular gene in the 7q region, expressed in human thalamus, may be
associated with autism susceptibility.31 It is a member of a family of genes
that influences brain development.
To increase the likelihood of finding genes for autism, researchers are
increasing the statistical power of human data sets. One genome-wide screen of
autism vulnerability genes in 110 families showed suggestive evidence for
linkage to ASD on several chromosomes. In a follow-up analysis, the researchers
increased the sample size threefold while holding the study design constant, so
that 345 families (each with at least two siblings affected with autism or ASD),
were included. The most significant findings were on chromosome 17q
conspicuously near the gene that codes for the serotonin transporter and on 5p.
Analyses from this largest data set studied to date implicate brain serotonin
systems in autism. This finding is congruent with those from other studies which
show evidence of elevated blood serotonin levels both in patients with autism
and in their unaffected first-degree relatives. Studies also show that drugs
that selectively target 5-HTT can ameliorate some autism-related symptoms.
Serotonin-related neural circuits may thus provide targets for new drug
development.32
Continued progress in molecular genetic studies of autism will require very
large sample sizes, and the pooling of ever larger numbers of families. In
addition, future studies likely will require the identification and
characterization of autism-related traits correlated with liability to produce
disease. NIMH is supporting efforts to reach out to families to build a library
of DNA samples and clinical data that can be broadly distributed to researchers
through the NIMH Human Genetics Initiative (http://www.nimhgenetics.org/). For
example, in March of 2002 NIMH announced the awarding of a grant totaling more
than $6 million, over 5 years, to researchers at the University of California,
Los Angeles, for a major expansion of the Autism Genetic Resource Exchange (AGRE)
gene bank, a collaborative effort with the citizens group Cure Autism Now (CAN).
The goal is to add 300 more families to this resource, which conducts 2-hour
in-home screenings of families that have more than one member diagnosed with
autism, PDD or Asperger's syndrome.33 A similarly ambitious $5 million
public/private collaboration between the National Alliance for Autism Research (NAAR)
and NIMH, NICHD, NINDS, NIDCD was recently announced. The NAAR Autism Genome
Project is also focused on finding genes associated with the autism spectrum
disorders.
Using the AGRE data set, researchers at Rutgers University recently discovered a
strong association between a gene in the 7q region and autism. Among 167
affected families, children with autism were twice as likely as unaffected
children to have inherited a particular variant of a gene called ENGRAILED 2.
The team is now attempting to replicate the finding in a much larger sample,
using data sets funded in part by NIMH.34
Developmental Neurobiology
To function properly, the brain must be wired correctly during critical periods
in early development. Mistakes in this process, resulting in circuitry gone
awry, are hypothesized to occur in neuro-developmental disorders like autism.
NIMH-funded researchers recently developed a way to discover the normal wiring
diagram of the mammalian brain.35 The technique, a type of "gene trap," provides
a shortcut for identifying from among the tangled trillions of neural
connections just the machinery involved in brain wiring. The trick for finding
the needle in a haystack: attach a molecular tag to the needle. Through genetic
engineering, lines of mice are bred to express telltale mutations. Brain neurons
harboring particular wiring molecules are revealed by a blue tint, while their
tentacle-like extensions, or axons, are colored purple.
By breeding strains of mice in which particular genes are knocked-out, other
Institute-funded researchers have been discovering the molecular machinery of
the guidance systems used by such migrating embryonic neurons. When they
knocked-out the cell's antennae for receiving vital signals from guidance
chemicals, the tentacle-like axons failed to make the proper connections.36
After reviewing evidence pointing to abnormal brain development in autism,
researchers at the University of California, supported in part by NIMH, have
proposed that the disorder stems from mechanisms gone awry that normally
regulate brain growth. This "growth dysregulation hypothesis" holds that the
anatomical abnormalities seen in autism are caused by genetic defects in brain
growth factors. Due to abnormal timing in the starting and stopping of growth in
neurons and supportive tissue, there is premature overgrowth in some brain
structures and reduced growth or excessive cell loss in others, the researchers
suggest.37 Although the head size and brains of children with autism are
slightly smaller than normal at birth, they undergo a spurt of excessive brain
growth soon thereafter. Increased head circumference by the end of the first
year predicted an enlarged cerebrum and cerebellum by 2 to 5 years of age.
Sudden, rapid head growth in an infant may signal for risk of developing autism,
the researchers propose.38
Neuropsychology
NIMH-supported neuropsychologists are dissecting the nature of cognitive
deficits in autism and related disorders. Since identification of the syndrome
more than 60 years ago, clinicians and researchers have been intrigued with the
uneven ability profiles of individuals with autism. While many affected
individuals show generalized deficits, many also show areas of intact
functioning. The nature of these deficits and strengths, their relationship to
clinical symptoms, implications for treatment, and implications for underlying
neurobiology, are the focus of these studies.
Adults with autism show more executive function deficits than those with other
developmental disabilities. Executive functions include the ability to plan
ahead, work toward a goal and to hold a mental representation "on-line" in
working memory. To see if such deficits might underlie the syndrome, NIMH-funded
researchers at the University of Denver compared the performance of preschoolers
with autism with age-matched controls on eight executive function tasks.
Surprisingly, the children with autism performed as well or better than the
control group, suggesting that developmental lags in this area are not specific
to autism. A second study that tracked children's progress in performing a
spatial reversal task over a year found no evidence that children with autism
were growing into an executive deficit over time. Rather, the children without
autism seemed to be growing out of a deficit. The two groups seemed to be on
diverging developmental trajectories. These results cast doubt on the notion
that autism stems exclusively from executive function deficits.39
Co-occurring Disorders
In addition to cognitive impairments, individuals with autism and other ASDs
often suffer from multiple and severe mental and emotional problems. These
include impulse-control disorders, obsessive-compulsive disorder, mood and
anxiety disorders, mental retardation, and genetic disorders such as Fragile X.
Such co-existing problems start early in life, are chronic, and account for a
substantial portion of outpatient, inpatient, and residential services. They
present immense challenges to clinicians and families, and the complexity of the
psychopathology presents enormous research challenges. NIMH is developing and
testing treatment and rehabilitative interventions for such co-occurring
psychopathology.40 Individuals with autism may also have co-occurring seizures
and tuberous sclerosis, a genetic disorder that causes benign tumors to form in
many different organs, primarily in the brain, eyes, heart, kidney, skin, and
lungs.
A key set of proteins involved in synaptic plasticity and neuronal growth, some
of them likely implicated in ASDs, has been discovered by an NIMH-funded
scientific team. Researchers at the University of Pennsylvania and the
University of Illinois developed a new technique that revealed, in living
neurons, a swath of secondary damage caused by the primary protein defect in
Fragile X syndrome, the most common inherited form of mental retardation. Mental
retardation is common in people with autism, and the new findings suggest that
ASDs too may be traceable to this protein pathway. Gene knockout mice modeling
the protein defect showed abnormalities in the distribution and quantities of
some of the affected secondary proteins and the genetic material that makes
them. A melding of genomics and proteomics, the new method, called Antibody
Positioned RNA Amplification (APRA), can be applied in similar studies of other
systems and cells.41
Defective fragile X mental retardation protein (FMRP) can have devastating
effects because as an "RNA binding protein" it influences many other proteins in
critical brain centers, like the hippocampus, a memory hub. FMRP regulates the
synthesis and transport of a bevy of heretofore unknown associated proteins.
Like a dispatcher in a truck depot, FMRP manages the shuttling of these "cargo
proteins" from the cell's nucleus to supply the needs of its working parts, or
cytoplasm. Much of the cargo turns out to be the genetic material (RNA) that
makes proteins vital to synaptic maturation and communication between neurons
which breaks down if the 'dispatcher' can't do its job.
To discover FMRP's cargo proteins in cultured mouse hippocampal neurons, the
researchers devised an intricate methodology (APRA) that takes advantage of the
specific affinity that antibodies and short strands of genetic material have for
particular genes and proteins. They joined an antibody that binds to FMRP with
genetic material that, in turn, binds to genes associated with FMRP. The
antibody positions the molecular probe close to the FMRP cargo so that it can be
detected. Among genes expressed in the human brain, about 60 percent detected by
the probe were directly associated with FMRP again, many involved in synaptic
plasticity and neuronal maturation.
Since some people with Fragile X syndrome show autistic behavior, the
researchers suspected that some FMRP cargo proteins might also be associated
with autism. Among the 81 proteins, 15 mapped to the same chromosomal locations
as candidate autism genes. Mutations in some of the genes that code for these
proteins may contribute to autism and other disorders characterized by
autistic-like social impairment and stereotyped behavior.
Treatment
Both psychosocial and pharmacological interventions can improve the behavioral
and cognitive functioning of individuals with ASDs.42 The increasing use of
psychotropic medications to treat symptoms of autism and other childhood-onset
psychiatric disorders has spotlighted an urgent need for more studies of such
drugs in children. To meet this need, NIMH established a network of Research
Units on Pediatric Psychopharmacology (RUPPs) in 1997 that combined expertise in
psychopharmacology and psychiatry at several research sites. The network was
expanded to include psychosocial interventions with the funding of additional
network projects called the RUPP-PI (Research Units on Pediatric
Psychopharmacology and Psychosocial Interventions) network. The RUPP and RUPP-PI
networks are intended to become a national resource that will expedite clinical
trials in children.43,44,45 They include five groups specifically funded to
evaluate treatments for autism. Studies are examining dose range and regimen of
medications, and their mechanisms of action, safety, efficacy, and effects on
cognition, behavior, and development. The RUPP network is nearing completion of
a study examining the efficacy of methylphenidate for treating hyperactivity and
impulsivity in children and adolescents with a variety of behavioral disorders.
In one recent study, risperidone, one of a newer class of anti-psychotic
medications, was successful and well tolerated for the treatment of serious
behavioral disturbance in children with autism aged 5-17.46
The RUPP-PI network has launched a multi-site study investigating the effect of
combined parent training and medication treatment on disruptive behavior in
children with autism spectrum disorders. The study will test whether adding a
program to teach parents behavior management techniques to a regimen of
risperidone will add to treatment response and/or maintain treatment effects
after discontinuation of the medication.47,48, 49
Among other studies of psychosocial treatments in autism, two NIMH-funded
research teams are evaluating parent training interventions that are tailored to
the particular characteristics of the child and family. The investigators have
demonstrated that an individualized approach enhances the effectiveness of their
Pivotal Response Model, and that this, in turn, leads to positive changes in
parents' confidence and feelings of empowerment.50,51,52 The investigators are
continuing their line of research on interventions development with a study
investigating the efficacy of visual augmentation strategies for teaching
communication skills to nonverbal children with autism.53,54,55
The NIH Autism Coordinating Committee (NIH/ACC) coordinates efforts of NIMH,
NICHD, NINDS, NIDCD, and NIEHS to facilitate research on interventions for
individuals with autism and autism spectrum disorders. In November 2000, six
grants were funded in response to an RFA (Request for Applications)56 for
innovative methods and feasibility studies. These projects included behavioral
and pharmacological treatments and are nearing completion. The STAART Centers
funded in 2002 and 2003 (described above) include eight treatment projects that
are in development or underway. Foci of the intervention projects include
efficacy of early interventions, efficacy of treatments for social deficits,
efficacy trials for pharmacotherapy, and understanding the variability of
response to treatments. Through these and other initiatives, the Institutes hope
to encourage multi-disciplinary partnerships to develop and improve treatments
for individuals with autism spectrum disorders.
The NIH/ACC sponsored a workshop "Research on Psychosocial and Behavioral
Interventions in Autism: Confronting the Methodological Challenges" in September
2002.37 The purpose of the meeting was to review the state-of-the-science with
regard to psychosocial, behavioral, and educational interventions for children
with autism; to examine the barriers to progress in the field; and to discuss
potential strategies for overcoming the barriers. An outcome of the meeting was
the formation of ongoing working groups of scientists focusing on methodology
and design issues.
Services
As part of its initiative on Child and Adolescent Interdisciplinary Research
Networks, NIMH awarded a grant in FY 2003 to the University of California-Davis,
"Enhancing Mental Health Services to Children with Autism." This innovative
effort will create, for the first time, a formal, interdisciplinary research
network of faculty and community representatives focused on an understudied
population, children with autism and their families in rural communities. The
network will review barriers and develop guidelines for implementing telehealth
technologies such as clinical telemedicine, distance learning, and information
distribution for the delivery of high quality, empirically supported, and
coordinated mental health services.
NIH Collaboration
NIMH supports research on autism in collaboration with the National Institute of
Child Health and Human Development, the National Institute of Neurological
Disorders and Stroke, the National Institute on Deafness and Other Communication
Disorders, and the National Institute of Environmental Health Sciences.
The Broad NIMH Research Program
NIMH supports and conducts a broad-based, multidisciplinary program of
scientific inquiry aimed at improving the diagnosis, prevention, and treatment
of mental disorders in people of all ages. Increasingly the public, as well as
health care professionals, are recognizing these disorders as real and treatable
medical illnesses of the brain. Still, there is a need for more research that
examines in greater depth the relationships among genetic, behavioral,
developmental, social, and other factors to find the causes of these illnesses.
NIMH is meeting this need through a series of research initiatives.
NIMH Human Genetics Initiative
This project has compiled a large repository of clinical information and DNA
obtained from families affected by schizophrenia, bipolar disorder, autism,
Alzheimer's disease, and other mental disorders. Qualified scientists are given
access to these data and genetic materials in order to characterize the genetic
bases of mental disorders.
Neuroinformatics: Human Brain Project
This Federal effort is using state-of-the-art computer science technologies to
organize the immense amount of data being generated through neuroscience and
related disciplines, and to make this information readily accessible through the
World Wide Web for simultaneous study by interested investigators. Because the
scope of the Human Brain Project extends to all facets of brain and behavioral
research and includes a range of technology sciences, this initiative is
sponsored, in a coordinated fashion, by 15 Federal organizations across four
Federal agencies: the National Institutes of Health, National Aeronautics and
Space Administration, National Science Foundation, and U.S. Department of
Energy.
Prevention Research Initiative
Prevention research can be broadly characterized as seeking to understand the
development and expression of mental illness throughout the course of life so
that appropriate interventions can be designed and applied in order to prevent
mental disorders and promote mental health. Advances in biomedical, behavioral,
and cognitive sciences led NIMH to formulate a plan, Priorities for Prevention
Research at NIMH, which marries these sciences to prevention efforts. Focusing
on the expansion of prevention research to include the prevention of relapse,
disability, and co-occurring conditions, the plan provides a blueprint for NIMH
prevention research in the years to come.
Key Areas of NIMH Research
In total, NIMH supports more than 2,000 research grants and contracts at
universities and other institutions across the nation and overseas. It also
conducts basic research and clinical studies at its own facilities on the
National Institutes of Health campus in Bethesda, MD, and elsewhere. Key areas
of NIMH research include:
basic research on behavior, emotion, and cognition to provide a knowledge base
for a better understanding of mental illnesses;
basic sciences, including cellular and molecular biology, developmental
neurobiology, neurochemistry, neurogenetics, and neuropharmacology, to provide
essential information about the anatomical and chemical basis of brain function
and brain disorders;
neuroscience and behavioral aspects of acquired immune deficiency syndrome
(AIDS) and behavioral strategies to reduce the spread of human immunodeficiency
virus (HIV);
clinical trials to test interventions to treat, prevent, and reduce the
frequency of mental disorders and their disabling consequences;
mental health services research, including mental health economics and improved
methods of services delivery;
co-occurrence among mental disorders and with substance abuse and other medical
conditions, such as depression and heart disease;
the prevalence of mental disorders;
risk factors for mental disorders and protective factors against them;
suicide, suicidal behavior, risk and protective factors, and preventive
interventions; differences in mental health and mental illness among special
populations;
children and adolescents who suffer from or who are at risk for serious mental
disorders and learning disabilities;
aging and mental health, including the impact of caregiving;
responses to terrorist acts and major traumatic events; and
psychotherapies and pharmacotherapies for specific disorders.
For More Information
The NIMH Office of Communications carries out educational activities, such as
the Real Men Real Depression campaign (http://menanddepression.nimh.nih.gov),
and publishes and distributes research reports, press releases, fact sheets, and
informational materials intended for researchers, health care providers, and the
general public. All of these materials, and this fact sheet, are in the public
domain and may be copied or reproduced without permission from the Institute,
although citation of NIMH as the source is appreciated. Materials may be
downloaded directly from the NIMH Web site, or hard copies may be ordered
through the mail.
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About NIMH
Visit the following link for more information about NIMH.
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copied without permission from the Institute. Citation of the National Institute
of Mental Health as the source is appreciated.
NIH Publication No. 04-4508
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