Silva et al. International Archives of Medicine 2013, 622ht.docx

Silva et al. International Archives of Medicine 2013, 6:22
http://www.intarchmed.com/content/6/1/22
REVIEW Open Access
The biopsychosocial processes in autism
spectrum disorder
Edgar Bittner Silva1, Rosangela Filipini1, Carlos Bandeira de
Mello Monteiro2, Vitor E Valenti1,3*,
Sionara Melo Figueiredo de Carvalho1, Rubens Wajnsztejn1,
Maria do Carmo Andrade Duarte de Farias1,4,
Cícero Cruz Macedo1,5 and Luiz Carlos de Abreu1
Abstract
Background: Autism is a disorder characterized by pervasive
social and communicative impairments, repetitive and
stereotyped behaviors and restricted interests. Its causes and
effects have been researched from various
neurocognitive theoretical perspectives and with the aid of
neuroimaging technology. We aimed to describe
biopsychosocial processes characteristic of the Autism
Spectrum Disorders.
Method: Literature review using Medline and Scopus databases
published between 2001 and 2011, with the
keywords "autism", "theory of mind", "executive functions",
"central coherence" and “fMRI”.
Results: The studies found were plotted and organized into
tables and an explanatory diagram of the main
findings was produced.
Conclusions: The most popular neurocognitive theories are still
unable to fully explain the characteristics of the

complications that autistic spectrum disorder causes to the
quality of life of individuals living with autism. The
association of clinical research and neuroimaging may
contribute to a better understanding of the functioning of
the brain affected by the disorder.
Keywords: Autistic disorder, Mental disorder, Central
coherence, fMRI
Background
The Autistic Spectrum Disorders encompass conditions
known as Autistic Disorder, Asperger Syndrome and
Pervasive Development Disorder - Not Otherwise Spe-
cified (PDD-NOS), which is diagnosed based on behav-
ior with differentiation determined by the presence or
absence and intensity (dimension) of symptoms. The
diagnostic criteria stipulate the age of about 3 years as
the basis its identification, but some signals are already
identifiable before that [1].
The etiology of autism is still largely unknown. Despite
the consensus about the biological and genetic basis of
* Correspondence: [email protected]
1Laboratório de Delineamento de Estudos e Escrita Científica,
Faculdade de
Medicina do ABC, Av. Príncipe de Gales, 821, 09060-650,
Santo André, São
Paulo, Brazil
3Departamento de Fonoaudiologia, Faculdade de Filosofia e
Ciências,
Universidade Estadual Paulista, UNESP, Av. Hygino Muzzi
Filho, 737, Marília SP
CEP: 17525-900, Brazil
Full list of author information is available at the end of the
article
© 2013 Silva et al.; licensee BioMed Central Lt

Commons Attribution License (http://creativec
reproduction in any medium, provided the or
the disorder, it is believed that many genes and causes
contribute to the construction of the condition [1,2].
The neurocognitive theories such as the Theory of
Mind which is the ability to analyze the world from the
perspective of the other, the Executive Functions the
level of control the individual exercises over his/her be-
havior, memory and attention and Central Coherence,
the ability to integrate perceived information into a co-
herent whole [2] have contributed to a better under-
standing of the symptoms of the disorder, especially the
social deficit and its roots.
In this review we aimed to describe advances in the
study of biopsychosocial process of people diagnosed
with autism.
Method
The Medline database (via PubMed) and Science Direct
(via Scopus) were searched using the following key-
words: "autism", "theory of mind", "executive functions",
"central coherence" and "fMRI". We used the "related
d. This is an Open Access article distributed under the terms of
the Creative
ommons.org/licenses/by/2.0), which permits unrestricted use,
distribution, and
iginal work is properly cited.
mailto:[email protected]
http://creativecommons.org/licenses/by/2.0
Silva et al. International Archives of Medicine 2013, 6:22 Page
2 of 7

articles" in PubMed (U.S. National Library of Medicine
National Institutes of Health), which allowed us to get
the references of studies recovered during our research.
Publications were included in the analysis if any of
their titles or abstracts were available in English or
Portuguese. The review had its onset in July 2011 and
was completed in December 2011. Publications were ex-
cluded if published before 2000. Other studies of autism
that offered additional relevant information found in the
same database were also examined. Each publication was
reviewed to identify the author, study period, objective
and main contributions to the theme.
The data were plotted and organized into tables with
the types of selected studies and their indexing (Table 1)
and the summaries of the papers found on neurocognitive
explanatory theories of autism (Table 2) and findings
concerning the neurobiology of autism (Table 3) leading
to the production of a conceptual framework (Figure 1).
Results
In the organization of the data we used the following ab-
breviations: AUT: Autism, ASD: Autistic Spectrum Dis-
order; AS: Asperger Syndrome, HFA: High-functioning
autism; TD: Typical Development; ToM: Theory of
Mind, EF: Executive Functions; CC: Central Coherence;
OCD: Obsessive-compulsive Disorder, ADHD: Attention
Deficit Disorder and Hyperactivity.
Discussion
Autism is a spectrum disorder that affects the overall de-
velopment, characterized by impairments in social devel-
opment, limited verbal and nonverbal communication
skills and repetitive behaviors with restricted interests.
When thinking autism or autism spectrum disorders eti-
ology and pathophysiology should be taken into consid-
eration, besides the symptoms [2].

Functionally, there are different patterns of activation
and synchronization time across the cortical networks
with lowered functional connectivity affecting language,
working memory, cognition and social perception and
problem solving, hypoactivation of the fusiform facial area
[23,26], affecting facial recognition. Deficient activity of
Table 1 Publications and types of study related to the
biopsychosocial process in Autism
Type of study Medline JCR-ISI SJR-Scopus
Review 5 6 5
Comparative Study 11 10 10
Experimental 10 10 10
Clinical Trial 2 1 2
Medline: Medical Literature Analysis and Retrieval System
Online.
JCR-ISI: Journal Citation Reports.
SJR-Scopus: SCImago Journal Rank.
mirror neurons in the inferior frontal gyrus has also been
reported [28].
From birth, the baby gives preferential attention to the
mother or caregiver's face, particularly the eyes, a phylo-
genetically built-in behavior with an important role in
the social development of the child [29]. As early as age
two a preference for paying attention to parts of the face
which have lower social significance than the eyes can
be noticed in individuals with autism.
Unlike what happens with typically developing individ-

uals, who consistently show activation of the fusiform
gyrus for this kind of stimulus, people with autism show
weak or no significant activation in this area, but show
activation of areas not commonly associated with facial
recognition [23]. Thus one can say that individuals with
autism 'see' faces using neural systems different from
those used by people of typical development. Also, it
should be noted that each individual uses a unique sys-
tem for processing the stimulus, reinforcing the notion
that the individual experiences play an important role in
the neurological development [23].
The characteristic symptoms of autism, particularly
the social deficit has received attention from many re-
searchers, with varying success, from three approaches
based on neurocognitive theories, namely the Theory of
Mind, Executive Dysfunction and Weak Central Coherence
[2,18,19].
The Theory of Mind (ToM) relates to our understand-
ing of mental states, whether they are beliefs, desires or
knowledge, which allows us to predict or explain the
behavior and attitudes of others [17]. In typically devel-
oping individuals, nonverbal tasks involving the attribu-
tion of intentionality showed activation, leading to
increased blood flow, especially in the right inferior and
medial prefrontal cortex and also the temporal lobes bi-
laterally and left cerebellum [20]. The studies reviewed
by Castelli et al. [22] also show activities associated with
the anterior cingulate cortex, an area in the anterior
temporal lobes near the amygdala, and in the superior
temporal sulcus (STS) in the temporoparietal junction,
having neuroimaging studies shown greater activation
in regions including the basal temporal area (temporal
gyrus bottom extending to the fusiform gyrus and
temporal pole adjacent to amygdala), and the STS in

temporo-parietal junction medial prefrontal cortex. In
individuals with autism spectrum disorders the authors
found decreased activation in this network.
The ability to understand their own emotional states,
as well as those of others, yet a consequence of deficits
in ToM, is also impaired, which implies consequences
on the ability to 'fit in', hampering their participation in
social contexts and contributing to the increased rates of
depression among these individuals. Even with improve-
ments in self-awareness resulting from experience and
Table 2 Summary of articles related to neurocognitive
explanatory theories of Autism
Author, date Conclusions Contributions
Pisula, 2010 [2] Despite the progress, none of the theories can
fully explain the
neurocognitive complexity and impact of symptoms
characteristic of ASD on the development of the individual.
Sheds light on the importance of research on the interaction
between the various explanatory theories of autism among
themselves and with individual characteristics.
Beaumont,
Newcombe,
2006 [3]
Difficulties in the attribution of mental states by adults with AS
cannot be solely attributed to weak central coherence,
highlighting the need of taking into account aspects related to
the ToM deficit.

Identifies differences between AUT and AS regarding the ToM
and CC.
Miller, 2006 [4] Taking ToM into consideration the may help
clinicians improve
communication and language development of children.
Demonstrates the importance of ToM for language
development, contributing for the practice on speech therapy.
Silani et al.,
2008 [5]
Difficulties in emotional awareness are related to a
hypoactivation of the anterior insula in individuals with AS and
in people with TD, and particular difficulties in emotional
awareness in individuals with AS are not related to impairments
in self-reflection/mentalizing.
Finds evidence that alexithymic symptoms are usually mediated
emotional responses of second order.
Yang et al.,
2009 [6]
ToM is significantly correlated with inhibitory control. The
performance on tasks of inhibitory control did not affect
performance on ToM tasks.
Explores the relationship between EF and ToM emphasizing the
role of inhibitory control.
Bogte et al.,
2008 [7]

The cognitive flexibility in people with high-functioning autism
is similar to people with TD in simpler tasks, but with longer
response time.
Investigates the relevance of slowness of cognitive processes in
the functionality of the person with AUT.
Geurts et al.,
2004 [8]
Children with HFA exhibit more widespread and deep problems
in EF tasks than children with ADHD.
Reveals traits and executive dysfunctions shared among people
with ADHD and HFA.
van Lang et al.,
2006 [9]
Adolescents with intellectual disability and comorbid ASD have
CC weaker than people with equivalent age and IQ.
Presents CC as a possible tool for differential diagnosis between
Intellectual Disability with and without comorbid AUT.
Noens, van
Berckelaer-
Onnes, 2004 [10]
A wealer CC implies problems in making sense of the world
and hence of communication in people with ASD and
intellectual disability.
A better understanding of CC can assist in developing
communicative focused individual interventions.

Happé et al.,
2006 [11]
Findings suggest deficits in EF are less severe and persistent in
people with AUT than people with ADHD.
Describes the existence of different profiles for the deficits in
EF
for people with ADHD and AUT and shows improvement of the
deficits with age and intervention.
Luna et al., 2007
[12]
While executive dysfunction is present throughout
development, there is evidence for developmental progressions
of EF in AUT.
Highlights the need for age-specific interventions aiming at
improving the cognitive abilities of individuals with AUT.
Robinson et al.,
2009 [13]
People with ASD exhibit a specific pattern of executive
dysfunction, difficulties with planning, inhibition of prepotent
responses and self-monitoring that can vary with age.
Proposes a multidimensional notion of EF, with difficulties in
planning, inhibition of prepotent responses and self-monitoring
traits reflecting the ASD that are independent of IQ and verbal
ability, and relatively stable throughout childhood.
López et al.,
2008 [14]

Did not find a significant positive relationship between global
and semantic processing in children with autism and children
with TD.
Findings show that the CC is not a unitary construct, and may
be composed of various skills, and indicate the possibility of
subtypes of AUT.
Teunisse et al.,
2001 [15]
Although not universal in the AUT, a weak CC and poor
cognitive flexibility are significantly more common in people
with AS than in those with TD.
The weak CC does not seem to be related to the severity of
symptoms of AUT.
Belmonte,
2009 [16]
ToM dysfunction is not universal in AUT, and is preceded in the
development and predicted by abnormalities of attention, EF
and language.
Recognizes the importance of ToM, but emphasizes the
relevance of other cognitive functions and social development.
Jarrold et al.,
2000 [17]
There is a relationship between individual differences in CC and
the development of a ToM.
Relates the development and interactions, in individuals with
AUT, of apparently independent cognitive mechanisms.

Rajendran,
Mitchell [18]
Advances in different paths have led researchers to understand
AUT as a complex condition dependent on individual,
qualitative differences.
Highlights how the understanding of AUT has changed over
time and takes into consideration the possibility and
implications of recognizing AUT as a neurodevelopmental
condition rather than a disorder.
3 of 7
motivation, persistent difficulty in learning compensa-
tory strategies in social communication is a barrier diffi-
cult to transpose [4,10].
The development of abilities related to ToM, however,
also depends on some internal mechanisms linked to the
so-called executive functions, cognitive processes that
make possible goal oriented complex behaviors that
evolve throughout development until mid-adolescence
[12]. They include abilities such as planning, working
memory, cognitive flexibility, response inhibition and
initiation, impulse control and action monitoring [13],
seeming to be associated with different regions of the
Table 3 Summary of articles concerning brain
morphophysiological and functional abnormalities
Author,

date
Conclusions Contributions
Levy et al.,
2009 [1]
AUT is not a monogenic disorder, in many individuals may be
the
result of a complex amalgam of multiple simultaneous genetic
variations, and present morphological and functional brain
abnormalities.
Highlights the importance of understanding biological markers,
patterns of cortical organization and connectivity in advancing
the treatment of AUT.
Baron-
Cohen et al.,
2000 [19]
Unlike those with TD in ToM tests, patients with AS or AUT do
not
show activation of the amygdala when making mentalistic
inferences from the eyes. The amygdala may be one of many
abnormal neural regions in AUT.
Highlights the role of the amygdala in the symptoms of ASD.
Castelli et al.,
2002 [20]
The physiological cause for the mentalizing dysfunction in AUT
can be a bottleneck in the interaction between perceptual
processes of higher and lower order.

Relates the difficulties in understanding socially relevant
movements in AUT to information processing in the visual
cortex.
Brunet et al.,
2000 [21]
Attribution of intentions to others is associated with a complex
brain activity involving the right medial prefrontal cortex when
a
nonverbal task is used.
Presents data that validate hypothesis of abnormal brain
activation in patients with impaired mentalizing.
Castelli et al.,
2000 [22]
The regions responsible for processing information about
intentions and the ability to make inferences about the mental
states of others may have evolved from the ability to make
inferences about the actions of other creatures.
Suggests evolutionary history for the abilities that make ToM.
Pierce et al.,
2001 [23]
Compared to typical individuals, autistic "see" faces using
different
neural systems, unique to each individual.
Experiential factors play an important role in the development
of
the fusiform facial area, related to the processing faces.

Scholz et al.,
2009 [24]
There are neighboring but distinct regions in the right temporo-
parietal junction involved in ToM and orientation of attention.
Identifies difficulties in the investigation of brain functions that
occupy regions close to each other or overlapping.
Johnson
et al., 2007
[25]
There is involvement of frontal and parietal attentional
networks
and sub-cortical excitatory systems in ADHD and a prefrontal
cortex dysfunction in children with HFA.
Provides detailed evidence of dysfunction in sustained attention
in ADHD significantly higher than in HFA.
Kana et al.,
2007 [26]
The neural circuit linked to inhibition in individuals with ASD
is
atypically activated and is less synchronized, leaving inhibition
to
be accomplished by strategic control rather than automatically.
Identifies dysfunction in inhibitory cortical level, being
disorganized and desynchronized.
Schultz
et al., 2000
[27]

Individuals with ASD demonstrate during facial discrimination,
a
pattern of brain activity consistent with strategies based on
characteristics or traits more typical of the perception of non-
facial
objects.
Highlights possible dysfunction in processing stimuli related to
biological and inanimate objects in ASD.
Dapretto
et al., 2006
[28]
A dysfunctional mirror neuron system may underlie the social
deficits of autism.
Substantiates hypothesis of the importance of mirror neurons in
the development of social functions.
Jones et al.,
2008 [29]
The behavior of eye contact is already noticeably compromised
in
children two years of age with ASD, accompanying the person
with autism for life.
Subsidizes and highlights the importance of early diagnosis of
ASD.
4 of 7
frontal lobes, with connections between the frontal and

posterior areas as well as subcortical and thalamic path-
ways; neural networks along the prefrontal cortex also
play an important role in executive functions [12].
Difficulties in planning, inhibition and self-regulation
during childhood seem to reflect the symptoms of aut-
ism [7,13]. Robinson et al. [13] found poor performance
in planning, response inhibition and self-regulation, but
preserved mental flexibility in people with ASD com-
pared with TD peers. Bogte et al. [7] found no significant
differences between people with high-functioning autism
(IQ ≥ 70) and controls regarding cognitive flexibility,
finding, however, longer response times for the first
when under medication.
Central coherence, another theory that attempts to ex-
plain the social deficit in autism is the ability to integrate
information into a coherent whole in perceptual and
conceptual level [14]. Seeing a wooden object in a rect-
angular shape, with a pair of doors with locks and han-
dles, one immediately recognizes it as a closet, as well as
eyes, nose and mouth in a particular arrangement is a
face. When there is a failure in this integrative mechan-
ism it is said that there is a weak central coherence.
A weak central coherence makes it hard for this indi-
vidual to recognize the stimuli that surround him glo-
bally, making the world a series of parts, instead of an
integrated whole, as in typical development subjects.
The impaired and limited communication skills of people
with autism are characterized by a lack of intentionality and
symbol formation, which may indicate that a specific cogni-
tive style underlies the development of deviant communica-
tion in autism. The central coherence theory may offer
insight into the communication problems specific to people

with autism assuming a lesser tendency towards a central
Figure 1 Conceptual framework of Autism.
5 of 7
coherence leads to problems in trying to make sense of the
world and, consequently, communication [10].
In autism information processing seems to be prefe-
rably local, rather than global [9], there are indications
of excessive preservation of unnecessary connections of
short distance and relative lack of long distance connec-
tions, leading to low efficiency in information processing
that may help explain the tendency to focus on details
instead of the whole [7].
The results of Schultz et al. [27] regarding the poor acti-
vation of the fusiform gyrus may support the theory of
weak central coherence suggesting that, in individuals with
autism, processing the stimulus of sight of a face occurs so
that attention is paid to details, consistent with the pro-
cessing of non-facial stimuli, such as objects - elements
that depend on specific characteristics for identification,
rather than a configurational focus, the set of elements
which we call a face [30].
The three aspects studied, however, do not seem to act
alone, influencing each other. Jarrold et al. [17] found a
relationship between dysfunction in theory of mind and
a weak central coherence. The results of Beaumont and
Newcombe [3] support the explanation of autism by
ToM, also finding evidence of the influence of the

central coherence. For Yang et al. [6], ToM was signifi-
cantly correlated with inhibitory control. Performance
on tasks of inhibitory control, however, did not affect
performance on tasks ToM.
There are conflicting results. A weak central coherence
and poor cognitive switching for Teunisse et al. [15] do
not seem to be related to measures of the severity of
symptoms, to social understanding and social competence.
Even seeming to be significantly more common than in
typically developed individuals, a weak central coherence
and poor cognitive switching do not seem to be universal
for autism. For Belmonte [16], ToM dysfunction is not
universal in autism and is developmentally preceded and
predicted by changes in attention, executive function and
language.
None of these features is exclusive Autism, appearing
in other disorders such as ADHD [8,11,25] and also in-
tellectual disability [9], demanding an even more thor-
ough understanding of how these dysfunctions and
deficits are manifested specifically in these individuals.
Rajendran and Mitchell [18] have also done an extensive
review on the subject of both uniqueness and universal-
ity of the major cognitive theories coming to similar
conclusions.
6 of 7
Advances in studies using positron emission tomography
(PET) [20,22] and functional MRI (fMRI) [5,18,24,26,27]
have brought new information about the functioning of the
autistic brain, providing clues for building programs

pharmacological intervention to reduce symptoms and
psychosocial programs aiming at increased and improved
social participation of the individual with benefits for his/
her development.
The findings support Levy et al. [1] which propose,
from revised neurological studies seeing of autism as a
disorder of cortical organization that causes neuronal
deficits in information processing in the nervous system,
ranging from organization to synaptic connectivity and
brain structure.
An interesting new take on Autism has been provided
by the mnesic imbalance theory [31], according to
which, an imbalance between declarative and proced-
ural memory may answer for the symptoms of the dis-
order. Here, a faulty procedural memory, possibly due
to brain abnormalities and cerebellar maldevelopment,
hinders the development of functions related to ToM,
EF and CC and leads to an overuse of declarative mem-
ory as compensation. This theory is still disputed as there
is a lack of studies on declarative and non-declarative
memory in people with moderately low-functioning
autism [32].
Understanding Autism as a condition rather than a
disorder is also on the spotlight [18]. Findings related to
morphology, genetics and the most popular cognitive
theories on Autism have led some to see it as a different
“way of being”, which may, in the future, have impact on
policies, laws and interventions as people with Autism
become a vocal group such as the Deaf.
Our study is also interesting for others neurological
disorders [30,33-38]. A better understanding of brain
functioning and the consequences of autism for individ-

ual development may help us develop strategies better
attuned to its particularities [10], contributing to the re-
habilitation process of the person with autism.
Conclusion
We conclude that individuals living with autism present
symptoms that set them apart from the contemporary
social model, reducing their quality of life. None of the
neurocognitive theories can fully explain the complica-
tions that the disorder brings to the quality of life of in-
dividuals with autism. Together they offer essential clues
to develop interventions. Neuroimaging studies contrib-
ute greatly to a better understanding of the functioning
of the brain affected by the disorder.
Competing interests
The authors declare that they have no competing interests.
Authors’ contributions
All authors participated in the acquisition of data and revision
of the
manuscript. All authors conceived of the study, determined the
design,
interpreted the data and drafted the manuscript. VEV and LCA
determined
the design and drafted the manuscript. All authors read and gave
final
approval for the version submitted for publication.
Acknowledgements
This group received support from School of Medicine of ABC.
Author details
1Laboratório de Delineamento de Estudos e Escrita Científica,
Faculdade de
Medicina do ABC, Av. Príncipe de Gales, 821, 09060-650,
Santo André, São
Paulo, Brazil. 2Escola de Artes, Ciências e Humanidades da
Universidade de

São Paulo, Av. Arlindo Béttio, 1000 Ermelino, Matarazzo, São
Paulo SP CEP:
03828-000, Brazil. 3Departamento de Fonoaudiologia,
Faculdade de Filosofia
e Ciências, Universidade Estadual Paulista, UNESP, Av. Hygino
Muzzi Filho,
737, Marília SP CEP: 17525-900, Brazil. 4Universidade Federal
de Campina
Grande, R. Aprígio Veloso, 882, Cajazeiras PB CEP 58900-000,
Brazil.
5Departamento de Pediatria. Faculdade de Medicina de
Barbalha, CE.
Universidade Federal do Ceará, Av. da Universidade, 2853,
Fortaleza CE, CEP:
60020-181, Brazil.
Received: 26 November 2012 Accepted: 4 May 2013
Published: 8 May 2013
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http://dx.doi.org/10.1006/nimg.1999.0525AbstractBackgroundM
ethodResultsConclusionsBackgroundMethodResultsDiscussionC
onclusionCompeting interestsAuthors’
contributionsAcknowledgementsAuthor detailsReferences
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