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Neuroscience in the 21st Century pp 2431–2443

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Autism
Catherine Barthélémy & Frédérique Bonnet-Brilhault
Reference work entry
2827 Accesses

Abstract

Autism was first described as the earliest form of

schizophrenic psychosis. It is now considered to be a
biologically based pervasive neurodevelopmental
disorder affecting, from the first days of life, social
communication and adjustment to the environment.
Advances in the understanding of its clinical,
neurofunctional and genetic aspects have progressively
modified conceptions and practices for diagnosis,
exploration and therapeutics.
Keywords
Autism Spectrum Disorder

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Diffusion Tensor Imaging Head Circumference

Asperger Syndrome
Neurodevelopmental Disorder

These keywords were added by machine and not by the

authors. This process is experimental and the keywords
may be updated as the learning algorithm improves.
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Brief History

In two distant parts of the world at almost the same time,

two eminent neuropsychiatrists, Leo Kanner in Baltimore
in 1943 and Hans Asperger in Vienna in 1944, published
articles describing children presenting disorders they
named “autism.” The father of the expression “early
infantile autism,” Leo Kanner, put forward the hypothesis
of an innate inherited biological disturbance of affective
contact:
We must, then, assume that these children have come
into the world with innate inability to form the usual,
biologically provided affective contact with people,
just as other children come into the world with innate
physical or intellectual handicaps.
Kanner and Asperger had borrowed the term “autism”
from two adult neuropsychiatrists, Emil Kraepelin and
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Eugen Bleuler, who used it to describe the escape from

reality and withdrawal seen in schizophrenia. Therefore,
for several decades, infantile autism was classified, in
reference to schizophrenia, under the heading “infantile
psychosis” and linked to a psychogenic explanation of its
origin suggesting that pathological maternal behavior
triggered early distortion of self-other relationships.
During the 1970s, neurobiological concepts began to
greatly outweigh the psychodynamic tendencies. When,
in 1980, the category “pervasive developmental
disorders” (PDDs) was introduced in the American
classification, an international debate arose. The
hypotheses put forward on links between peculiar
behaviors and maternal deprivation or brain
development resembled discussions in the early
nineteenth century on the psychopathology of feral
children fostered by Doctor Jean Itard’s efforts in
educating the wild boy, Victor of Aveyron.
The innovative neurobiological concepts influenced
pathophysiological hypotheses and therapeutic
intervention. The first results in neuropathology and
brain imaging were published. In France, the pioneer
Lelord proposed the hypothesis of “cerebral modulation
insufficiency.” According to his work, abnormalities of
the filtering and modulation of sensory, emotional, and
motor perception could explain the characteristics of
autism. From this period on, large international
epidemiological studies were launched. In the United
States and Europe, cohorts and data banks were built
up. Technological progress offered new tools, video
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recording of behavior, molecular biology, and functional

brain imaging and enabled studies linking cognitive
particularities to neurophysiological mechanisms.
The international medical and scientific communities
now consider that autism is the result of a
neurodevelopmental disorder that pervasively alters the
affected children’s capacities to interact with their
environment and to develop means of communication
with others. This leads rapidly to a particularly
disconcerting form of behavioral and social dysfunction
and a lifelong handicap.
Autism Is a Behaviorally Defined Syndrome

Babies with autism do not seem to react to their

mother’s voice; they do not make eye contact. Their face
expresses little emotion. Their muscle tone and posture
are abnormal; sometimes they seem floppy like a rag
doll; at other moments, they are stiff and taut. Caresses
may seem to cause them pain. They do not stretch their
arms toward adults to be picked up out of their crib.
By the age of 3 years, the autistic syndrome is defined
by significant impairments in three behavioral domains:
Social Relationships: Children with autism seem
alone in their own world. They play alone and often
appear to be deaf, reacting to people as if they
were objects, making unusual eye contact, and
showing few expressions. Sharing emotion is
difficult for them.

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Communication: Some children with autism do not

speak. If language is present, it is not used to
exchange information or converse with others.
Adaptation (Restricted Interests, Repetitive
Movements): Children with autism are attached to
sameness in the environment. The slightest change
or unexpected event may provoke anxiety or
aggressiveness. Their range of activities and
interests is narrow and repetitive. Stereotypic
behaviors such as flapping, spinning, or rocking all
or parts of the body may appear when some
children are alone or even with others.
These qualitative abnormalities are the basis of the
diagnostic criteria used in international classifications:
the American Psychiatric Association Manual of
Psychiatric Diseases, fourth edition text revision (DSM-
IV-TR) and the World Health Organization’s (WHO)
International Classification of Diseases, tenth edition
(ICD-10) (see Table 81.1). In these manuals, autistic
disorder is described under the heading “pervasive
developmental disorders” of which it constitutes the
most typical form. The diagnosis is clinical and based
solely on behavior. No reliable biological markers have
been found, and the cause of autism remains unknown.

Table 81.1 World Health Organization ICD-10

criteria for childhood autism

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If parental concern is often expressed before their child’s

first birthday, it always indicates a probable risk. Large-
scale epidemiological studies and retrospective studies
of family films have guided the elaboration of a
screening instrument called the CHAT (Checklist for
Autism in Toddlers) composed of a series of absolute
signs of concern in simple questions to be asked at the
child’s 18-month medical checkup. These signs concern
essential precursors of communication: reaction to the
human voice, pointing a finger toward a desired object,
and the first elements of language. The questionnaire
allows detection of at-risk children and appropriate early
intervention. But, by definition, a diagnosis of autism
must be confirmed before age 3.
Clinical Assessment Has to Be Completed for Each
Subject with Autism
Autism is frequently associated with other abnormalities,
disorders, or diseases. Their identification does not
question the diagnosis of autism, but provides invaluable
indications concerning intervention and outcome.
Mental retardation of variable severity is classically
described in almost 80% of cases, and 50% of the
children do not develop functional language. These
percentages are now much lower because milder forms
of the disorder are more often diagnosed. Delay,
whether it be mild or severe, is characterized by marked
contrast between weak social-communication abilities
and better nonverbal cognitive performance. This
“disharmony” typical to autism often disconcerts
therapists and teachers.
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It is also important to investigate associated neurological

diseases: epilepsy, diagnosed in over one third of
children with autism and mental retardation, motor
coordination disorders, and sensory impairments.
Most cases of autism are nonsyndromic (of unknown
etiology). However a genetic or metabolic etiology is
identified in 10–20% of affected children. The most
frequent are fragile X syndrome, tuberous sclerosis,
neurofibromatosis type 1, Down syndrome, Angelman or
Prader-Willi syndrome, and phenylketonuria. With rapid
progress in neurogenetics and in molecular biology,
these percentages are constantly increasing.
The Broadening Definition of the Disorder Has Led to the
Concept of Autism Spectrum Disorders
Today, the concept of autism spectrum disorders (ASDs)
is progressively replacing the diagnostic categories of
autism and PDD. Indeed, in the population meeting the
criteria for a diagnosis of PDD, there are many different
clinical profiles. This is not only due to variations in the
severity of the disorder but also to varied early clinical
developmental trajectories, for example, the absence of
language delay in Asperger syndrome or the later onset
of childhood disintegrative disorder. Recently, the
definition of PDD has also been broadened to include
even milder forms of the disorder.
Are these different forms of PDDs separate entities or
points on a single spectrum? This is under discussion. It
is probable that future classification systems such as the
American Psychiatric Association’s forthcoming DSM-V
and the new version of the WHO’s ICD will adopt the
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term “ASD” so as to focus on the specificity of the

disorders of social development and on the considerable
variations of symptoms among individuals. In spite of the
great diversity of clinical presentations, all individuals
with autism have common characteristics:
Their limited capacity for empathy may be
expressed as social detachment or an unusual,
unilateral, or even intrusive manner of relating to
others.
Language is absent or limited or when present
includes unusual content such as echolalia,
neologisms, or pronoun reversal. Their repertory of
emotional expressions is poor.
Their incapacity to develop internal representations
affects their aptitude to predict what is going to
happen next. They often have personal, narrow, and
atypical centers of interest.
Many individuals with autism have hypo- or
hypersensitivity to tactile, auditory, or visual stimuli; they
may also have unusual reactions to heat, cold, and/or
pain.
Anxiety, sleep problems, eating disorders that may lead
to gastrointestinal problems, violent tantrums, and self-
aggression are among other frequent characteristics
often associated with autism.
Is there an “epidemic” of autism? Indeed, prevalence
rates have risen in recent years from 1–4 in 10,000 births
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in the 1980s to 1–4 in 1,000 in 2000. The most recent

figures published report 1 in 100. The change is due to
the broadening spectrum of autism. Also heightening
awareness and better training among health
professionals has enabled them to identify even mild
forms of autism at all ages of the life span.
Neurofunctional Models Are Rooted in Clinical
Observations
Over the last 30 years, the neurodevelopmental
hypothesis has been expanded through clinical
observations and studies in anatomy and anatomical
pathology (see Fig. 81.1). In developmental
psychopathology, several hypotheses have been put
forward. They do not exclude each other; some even
share common conceptual components. Abnormalities
in functioning of neural networks play an essential role in
this disorder of the perceptions of others, of their
intentions, emotions, and reactions. The neural theories
of autism can be linked to models proposed by cognitive
psychologists who have described particular intellectual
and social functioning in the syndrome. The aim of many
studies is elucidating the cerebral bases of deficits in
empathy, theory of mind, executive functions, and
central coherence. The principal theories and eventual
underlying neurophysiological dysfunctions are
summarized here.

Fig. 81.1

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Neurophysiological hypotheses are rooted in clinical

observations

Unusual responses to sensory input (hyper- or

hyposensitivity, distortions, cutoffs, shutdowns)
observed in all sensory channels, and also particular
social functioning, could be linked to impaired
processing of auditory and visual stimuli and especially
stimuli with social content such as voices or faces. Data
from functional brain imaging and neurophysiological
measures have also evidenced particular sensory
systems functioning. Nevertheless and especially in the
auditory domain, unusual activation patterns are also
found with neutral stimuli without social content (tones).
A left temporal hyporeactivity was first thus described in
the first electrophysiological studies and further studied
using brain imaging. Interest grew for a specific temporal
area (the superior temporal sulcus) in recent years with
the hypothesis that this area responds specifically to the
human voice. Advances in functional imaging techniques
and further studies evidenced a wider activation of a
network of brain regions. Particularities of visual
processing and multimodal auditory-visual processing
were also observed. Visual stimuli with social content
such as faces were intensively studied, and a
hypoactivation of the fusiform gyrus in response to faces
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was observed in autism. Concurrent to these studies of

cortical sensory processing, observations of particular
ocular behavior (circular gaze, absence of focus on the
eyes, absence of strategies taking into account ocular
dominance) were explored using eye tracking systems.
According to the theory of weak central coherence,
atypical processing of sensory stimuli, privileging local
processing to the detriment of global processing that
integrates separate elements into a coherent whole,
could be implicated. Rather than a genuine impairment,
this particular type of information processing could be
the expression of a distinct cognitive style. This
hypothesis could be linked to abnormalities of long-
distance cerebral connectivity concurrent to
hyperreactivity of local connectivity. The behavioral
domains affected in autism (communication,
socialization, and restricted interests) require rapid
integration of various pieces of information coming from
different brain regions distant one from another. Minor,
though scattered, dysfunction of neurotransmission, on
a synaptic level, for example, could easily disrupt this
type of integration.
A specific impairment of theory of mind, the capacity to
attribute mental states to one’s self and to others, could
be implicated in autism. On a physiological level, the
“social brain” is constituted by neural networks
specialized in processing information on others’
appearance, behavior, and intentions. Although an
ensemble of different regions could be involved, areas
such as the superior temporal sulcus, the fusiform gyrus,
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and the orbitofrontal cortex are more particularly

devoted to processing social stimuli. Dysfunction of this
social brain network could underlie unusual social
behavior. Particularities of the mirror neurons that are
activated when a significant movement is perceived
could also be linked to impaired treatment of social
stimuli. Among recent imaging studies, a study using
diffusion tensor imaging (DTI) shows a decrease in
anisotropy of white matter adjacent the prefrontal
cortex, the anterior cingulate gyrus, and the superior
temporal sulcus, evoking disturbance of white matter
tracts involved in social information processing.
Within the inhibitive, flexible, and generative processes
(spontaneous production of a new behavior in a new
context) involved in planning, flexibility seems to be
most severely impaired. Executive function deficits
evidenced in young teens and adults with autism would
correspond to more complex development patterns in
young children considering the late maturational
processes involved.
The extreme male brain theory makes reference to
cognitive and emotional phenotypes characterizing the
normal population. The “empathizing” phenotype (more
frequent in women) corresponds to the capacity to
attribute mental states to others and to have an
appropriate emotional reaction, whereas the
“systemizing” phenotype (more frequent in men) is
defined by the capacity to understand and predict
abstract, technological, or biological systems’
functioning. A weakness of the first cognitive style,
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combined with an unusually frequent use of the second,

could explain the behavioral phenotype of certain
individuals with autism. This hypothesis leads to the
extreme male brain theory, according to which
individuals with autism function essentially in the
systemizing mode, driven by a high level of the hormone
testosterone.
Autism Results from Abnormal Brain Development
The origin of pervasive developmental disorders is
neurodevelopmental, which means that one or several
stages of brain development are disrupted, as opposed
to a neurodegenerative disorder in which mature nerve
cells are progressively lost. There are nine different
stages of brain development: neurogenesis, neural
migration, differentiation, axonal growth, dendritic
growth, myelinogenesis, synaptogenesis, synaptic
selection, and apoptosis (programmed cell death). All of
these stages could be candidates for disturbance in
autism, but recent studies (supported by results in
genetics) focus more frequently on development and
conservation of synaptic connections, also on axonal
growth and the establishment of tracts connecting
different brain areas.
One of the most robust and frequently replicated
findings in the neuroanatomy of autism is that the mean
volume of the brain of patients with autism is larger than
average. Twenty percent of these patients present a
macrocephaly, as defined by head circumference over
the 98th percentile, in contrast to only 2% of the general
population. Studies of brain volume using measurement
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of head circumference, anatomical magnetic resonance

imaging (MRI), and anatomical pathological analysis
have evidenced a particular pattern of brain growth:
overgrowth during the first 2 years of life followed by a
deceleration. The underlying pathophysiological
mechanisms involved remain unexplained and their
exact chronology unknown. Data on head circumference
at birth are contradictory; some studies have reported
an enlargement, others a decrease, but in general,
recent studies report an average head circumference at
birth. Anatomical brain imaging studies concern both
white matter and gray matter; several studies evidence
the involvement of radiate white matter. This increase
has been found, according to various studies, in the
cerebellum and in different cerebral lobes. Some studies
find an anterior to posterior gradient, whereas others
evidence a significant increase of brain volume in
temporal, parietal, and occipital, but not in the frontal
lobes.
The first anatomical imaging data published in the early
1980s made a major contribution to the emergence of
the neurodevelopmental hypotheses in autism. In 1988,
Courchesne and his colleagues, using the first MRI data,
evidenced hypoplasia of cerebellar vermal lobules VI and
VII in autism. Using conventional MRI, a high prevalence
of nonspecific abnormalities of white matter is also
found in autism as compared to the general population.
Concurrently data support brain enlargement and the
unusual brain growth pattern previously described, and
new techniques allowing fine-grained analyses of brain
structure are now being applied in autism. Data obtained
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by DTI allow studies of white matter tracts, and analysis

by VBM (voxel-based morphometry) allows detailed
studies of brain structure. Preliminary work with these
techniques has evidenced decrease or increase of white
matter density in different brain areas of children with
autism compared to normal controls.
In parallel with these macroscopic data, studies in
anatomical pathology and their description of
cytoarchitectural organization of brain tissue have also
provided arguments in favor of the neurodevelopmental
hypotheses. The small size of the samples studied,
possible methodological bias, and frequent comorbid
mental retardation or epilepsy limit these studies.
Nevertheless, the most frequently replicated findings
concern a decrease of Purkinje cells and signs of an
altered organization of the cortical minicolumns.
Increased number and decreased width of minicolumns
could reflect modifications in the GABAergic systems.
These results support the hypothesis of a connectivity
disorder, showing a local hyperconnectivity to the
detriment of long-distance connections between
different brain regions underlying integrative processes.
Recent studies evidenced a glial reaction, an increase in
immune markers such as TNF-alpha that could sign an
inflammatory process. Nevertheless, these markers are
also involved in synaptic developmental processes and
apoptosis; they could therefore simply reflect the
neurodevelopmental disorder.
The role of environmental factors in autism
pathophysiology or in phenotype variations has been
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suspected for many years. Observations have linked

exposure to certain pre- or perinatal factors, such as
cytomegalovirus, rubella, thalidomide, and valproic acid,
to autism but rarely and principally in cases where this
exposure has first caused brain damage. Recent
epidemiological studies have shown that vaccines are
not a causal factor in autism.
Moreover, studies in anatomical pathology have
evidenced astroglial and neuroglial reactions, suggesting
the implication of neuroinflammatory phenomena.
Various factors, such as genetic susceptibility, maternal
factors, and exposure to prenatal factors, could account
for these neuroglial reactions. High blood levels of
cytokines have also been observed.
Oxidative stress phenomena could also be involved, as
shown by studies of antioxidant substances in platelets
levels (decrease in levels of superoxide dismutase and
transferrin) or oxidative stress markers (lipid
peroxidation).
Lastly, another research domain concerns the presence
in the serum of mothers of children with autism of
autoantibodies that could react with fetal brain proteins.
A recent study has found an unusual profile of these
antibodies in mothers of children with autism, but in the
results of another study using serum, samples taken
systematically in midpregnancy are not significant.
Nevertheless, studies using animal models of
intrauterine of exposure to this type of antibodies could
be an interesting lead in research.
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Autism Could Be Linked to Abnormal Neurotransmission

and Neuromodulation
Among the monoaminergic hypotheses, the theory
concerning a disturbance of serotonergic transmission
has been further developed in autism, whereas
dopaminergic hypotheses are more frequently advanced
in schizophrenia. The role of neurotransmitters in the
central nervous system is linked not only to synaptic
function but also to cerebral developmental and
maturational processes. One of the most frequently
replicated findings concerns plasmatic
hyperserotonemia (concerning essentially the serotonin
level in platelets) eventually linked to hyperactivity of the
platelet serotonin transporter. Concurrently, genetic
studies have shown an association between autism and
a polymorphism of the SLC6A4 gene encoding the
serotonin transporter. In clinical observation, certain
repetitive behaviors evoke forms of OCD (obsessive-
compulsive disorder), and the efficacy of selective
serotonin reuptake inhibitors in certain cases is another
argument in favor of this theory. Lastly, imaging studies
using positron-emission tomography (PET) and single
photon emission computed tomography (SPECT) have
recently evidenced in children with autism the absence
of a peak in serotonin synthesis (observed normally in
well children around age 2), as well as a decrease 5-
HT2A receptor binding in the cerebral cortex.
Parallel to this monoaminergic hypothesis, glutamatergic
and GABAergic pathways have gained interest. This
interest is focused not only on synaptic transmission but
also on eventual involvement of these systems in
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neurodevelopment. It is, for example, well known that

activation of GABAergic and glutamatergic receptors is
involved in neuronal migration, especially in radial and
tangential migration. Moreover, balance between
excitatory (glutamatergic) and inhibitory (GABAergic)
transmission is essential for normal cerebral
development and functioning. Implication of these
neurotransmitters in the pathophysiology of autism and
PDD is supported by findings in genetics and anatomical
pathology. Certain association studies of candidate
genes encoding glutamatergic and GABAergic receptors
have evidenced association with autism. Studies of
cerebral tissue have also shown an increase of the
expression of certain genes associated with
glutamatergic pathways and a decrease in GABAergic
receptors.
Since 2003, several studies in genetics have evidenced
functional mutations in genes encoding for proteins
localized at the glutamatergic synapse in patients with
autism (and/or mental retardation). The first studies
concerned genes of the neuroligin family (NLGN4,
NLGN3), cell-adhesion molecules, and then their
presynaptic partners, the neurexins. These molecules
are involved in synaptic development and conservation,
playing an important role in the balance between
excitatory and inhibitory transmissions. Other studies
have also pointed to genes encoding proteins localized
at the glutamatergic synapse such as the SHANK3
protein that binds with the neuroligins enabling
membrane proteins to bind to the cytoskeleton of the
synapse and the KCNMA1 gene involved in a
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postsynaptic channel regulating neuronal excitability.

The hypothesis of a deficit in synaptic development and
functioning is now at the frontline in pathophysiology
research on autism.
Brain activity is modulated by neuropeptides and
neurohormones such as oxytocin and melatonin.
Targeting oxytocin, which plays a role in social behaviors,
in specific stages in development could be promising.
The link between melatoninergic dysregulation and sleep
disturbances common in ASDs also opens new
pathways for therapeutic intervention.
Autism Is a Strongly Genetic Disorder
There is now no doubt that genetic factors are a major
component of the cause of autism. Research was
undertaken on the basis of strong clinical and
epidemiological arguments in favor of this hypothesis,
particularly twin studies finding much higher
concordance rates for the syndrome among
monozygotic than dizygotic twins. The risk of
reoccurrence was also much higher in siblings of
children with autism.
Over 60 chromosomal abnormalities were identified in
candidate regions particularly on chromosomes 2, 7, and
15. These regions each comprise large numbers of
genes involved in central nervous system development
and functioning and in various neurodevelopmental
pathologies: autism, schizophrenia, and mental
retardation. Considering the great heterogeneity of
ASDs, it is necessary to define homogenous subgroups
of affected children regarding clinical and biological
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phenotypes such as head circumference, presence of

developmental regression, epilepsy, sleep problems, or
plasmatic levels of serotonin. Electrophysiological
characteristics measured using cortical evoked
potentials could also prove to be potential phenotypic
markers.
The exact pathophysiological mechanisms involved
remain unknown. Some cases are sporadic,
corresponding to de novo genetic abnormalities. In
others, several members of a same family are affected
by neurodevelopmental disorders involving the
expression of inherited genetic factors.
Autism being a highly inheritable disorder, it seemed
probable that genes linked to the disorder would be
rapidly identified. Even though these hopes were not
fulfilled, research undertaken in the field has been
fruitful. Identification of genes involved in disorders
linked to autism such as Rett syndrome, fragile X, and
tuberous sclerosis, or rare mutations linked to cases of
autism (in particular NLGN, NRXN, and SHANK3 genes),
suggests that pathophysiological pathways common to
various forms of the ASDs may be found.
Each mutation discovered accounts for at the most 1%
of cases suggesting that many genes are involved, each
with a limited effect. Finally, the identification of
abnormalities common to several conditions such as
copy number variations (CNVs), or the fact that certain
mutations are also present in nonaffected individuals,
evokes interaction between these abnormalities and
other genetic, developmental, or environmental factors.
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Future research strategies must take these findings into

account by diversifying their approaches. Thus, a
dimensional framework based on specific traits or
phenotypes instead of diagnostic categories appears
promising. Longitudinal studies in at-risk families could
help define endophenotypes or environmental factors
linked to onset of the disorder. Moreover, innovative
brain imaging techniques allowing identification of
cerebral signatures present among individuals with
autism should be used concurrently with molecular
biological or genetic analysis. Approaches combining
clinical observation, neuroimaging, and molecular
genetics will allow identification of critical periods of
cerebral development and neuronal functioning to
target.
Treatment of Autism Is Essentially Based on Behavioral
Methods and Education
No cure for autism exists to this day. Autistic children
growing up without support and without specific
teaching of basic communication skills and means of
making sense of their environment are at risk of
developing challenging behaviors, a source of exclusion
and of additional handicaps (see Fig. 81.2). Treatment
focuses on improving core deficits in social
communication, as well as improving functional
engagement in appropriate activities. Principal
treatments include behavioral interventions and special
education. Early intervention is paramount, cerebral
plasticity being highest before the age of 4. Early
treatment helps toddlers master basic
neurophysiological functions such as attention,
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perception, association, intention, and imitation. During

sessions in a rewarding environment, the therapists
adjust support to the children’s intellectual and
emotional level, helping them to progressively develop
adequate means of action and communication.
Exchanges between the children and adults are
increasingly synchronized growing into genuine
sequences of social interaction and shared pleasure.
This is a necessary prerequisite for further development
of nonverbal and verbal communication skills.

Fig. 81.2

Behavioral interventions and special rehabilitations are

based on clinical and neurophysiological analysis

Medical treatments comprise a variety of pharmacologic

agents and address specific symptoms associated with
the disorder such as epilepsy, anxiety, attention
difficulties, or sensory problems.
Outlook

Systematic studies from birth on of younger siblings of

children with autism, at higher risk for ASDs than the
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general population, are promising. They will not only

allow a detailed description of very early signs but also
the identification of early phenotypic variants in single
families. Scientific training of future professionals
involved in health services for babies and toddlers is
crucial for early detection of the disorder. Studies of
atypical developmental trajectories of at-risk children
and links between certain forms of epilepsy with
language disorder are potential fields for
pathophysiological studies. Advances in the
understanding of the clinical, neurofunctional, and
genetic aspects of autism have progressively modified
conceptions and practices for diagnosis, investigation,
and therapeutic interventions. But the exact
pathophysiology of autism remains unknown. This
lifelong complex disorder presents major challenges.
The body of data collected in multiple research fields
(clinical observation, imaging, electrophysiology,
biochemistry, genetics) supports the idea of a
heterogeneous group of neurodevelopmental disorders
probably with different pathophysiological pathways.
The unusual pattern of cerebral growth and the
involvement of the frontal and temporal lobes are among
the most frequently replicated findings. The corpus of
results reinforces the hypotheses that a disturbance in
neurocortical organization leads to impairment of
information treatment processes at various levels of the
nervous system, from the synapse to structural and
functional neural networks. Future work will require
concurrent investigation of clinical, biological, genetic,
and imaging markers both in large populations and in
single case studies in order to progress toward
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identification of the pathophysiological cascades

involved.
Indeed, each individual with ASD has a unique profile
that varies among individuals over the life span. There is
no standard protocol of treatment for this social
communication disorder. Nevertheless, several
fundamental principles underlie educational,
rehabilitative, therapeutic, and social interventions: early
intervention, accessibility of appropriate services, and
diversity of means and methods. The family is, from the
beginning and all through their child’s life, an active
partner in a flexible, continuous, and coherent system of
multidisciplinary intervention.
Further Reading

Anagnostou E, Taylor MJ (2011) Review of

neuroimaging in autism spectrum disorders: what have
we learned and where do we go from here. Mol Autism
2:4 (pdf ahead of print)

Coleman M (ed) (2005) The neurology of autism.

Oxford University Press, Oxford

Fombonne E (2009) Epidemiology of pervasive

developmental disorders. Pediatr Res 65(6):591–598

Goines P, Van der Water J (2010) The immune system’s

role in the biology of autism. Curr Opin Neurol 23:111–
117

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9/6/23, 3:23 PM Autism | SpringerLink

Haesen B, Boets B, Wagemans J (2011) A review of

behavioural and electrophysiological studies on
auditory processing and speech perception in autism
spectrum disorders. Res Autism Spectr Disord 5:701–
714

National Autism Center (2009) National standards

project – addressing the need for evidence-based
practice guidelines for autism spectrum disorders.
National standards report. National Autism Center,
Randolf

Ospina MB, Krebs Seida J, Clark B et al (2008)

Behavioural and developmental interventions for autism
spectrum disorder: a clinical systematic review. PLOS
One 3(11):e3755

Rapin I, Tuchman RF (2008) What is new in autism?

Curr Opin Neurol 21:143–149

Volkmar FR, Paul R, Klin A, Cohen DJ (eds) (2005)

Handbook of autism and pervasive developmental
disorders. Wiley, Hoboken

Wing L, Gould J, Gillberg C (2010) Autism spectrum

disorders in the DSM-V: better or worse than the DSM-
IV? Res Dev Disabil 32:768–773
Author information

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9/6/23, 3:23 PM Autism | SpringerLink

Authors and Affiliations

Center of Child and Adolescent Psychiatry,
University Hospital, Université François Rabelais de
Tours, UMR Inserm U930, 37044 Tours cedex 9,
France
Prof. Catherine Barthélémy & Prof. Frédérique Bonnet-
Brilhault
Corresponding author
Correspondence to Catherine Barthélémy .
Editor information

Editors and Affiliations

Laboratory of Neurobiology and Behavior, The
Rockefeller University, New York, NY, USA
Donald W. Pfaff
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Barthélémy, C., Bonnet-Brilhault, F. (2013). Autism. In: Pfaff,
D.W. (eds) Neuroscience in the 21st Century. Springer, New
York, NY. https://doi.org/10.1007/978-1-4614-1997-6_91
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