An Integrative Model of Autism Spectrum Disorder ASD As A Neurobiological Disorder of Experienced Environmental Deprivation Early Life Stress and

Neuropsychoanalysis
An Interdisciplinary Journal for Psychoanalysis and the Neurosciences
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An integrative model of autism spectrum disorder:

ASD as a neurobiological disorder of experienced
environmental deprivation, early life stress and
allostatic overload
William M. Singletary
To cite this article: William M. Singletary (2015) An integrative model of autism spectrum
disorder: ASD as a neurobiological disorder of experienced environmental deprivation,
early life stress and allostatic overload, Neuropsychoanalysis, 17:2, 81-119, DOI:
10.1080/15294145.2015.1092334
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Date: 03 May 2016, At: 13:06
Neuropsychoanalysis, 2015
Vol. 17, No. 2, 81119, http://dx.doi.org/10.1080/15294145.2015.1092334
An integrative model of autism spectrum disorder: ASD as a neurobiological disorder of

experienced environmental deprivation, early life stress and allostatic overload
William M. Singletary*
Faculty, The Psychoanalytic Center of Philadelphia, Philadelphia, PA
Downloaded by [187.172.80.214] at 13:06 03 May 2016
(Received 1 February 2015; accepted 25 August 2015)

A number of recent convergences within neurobiology, and between neurobiology and psychoanalysis, allow us to
view autism through a new lens. This perspective highlights biological risk factors that might operate through nal
common pathways to produce the ASD syndrome. The goal of this article is to integrate and elaborate upon this
conuence of ndings, and to develop a working model of ASD that could parsimoniously account for central
aspects of ASD, promote greater collaboration in research, and lead to more effective treatment. Converging
evidence suggests that ASD is a potentially reversible neurodevelopmental disorder in which neurobiological
factors not poor parenting interfere with the childcaregiver interaction. The infant then experiences
deprivation of growth-promoting parental input even though it is available. The model proposed here adds what
seems to have been largely unrecognized in the eld of autism: the childs experience of social deprivation and
isolation signals threat to the child and may result in overwhelming stress with signicant psychological
(traumatic or toxic stress) and biological (allostatic overload) components and consequences. Allostatic overload
results when attempts to cope with threat impose too great a burden, resulting in a pathophysiological state or
process that damages the body and predisposes one to the development of disease. Critically, this model
proposes that allostatic overload plays a major role in the course of ASD by amplifying the neurobiological
vulnerabilities generally considered to make primary contributions to the development of autism. Furthermore,
through the process of allostatic overload, neurobiological and psychological factors interact in a nonlinear
fashion and are both seen to underlie the symptoms of ASD which develop through maladaptive coping and
neuroplasticity. Thus, this model might explain both the progression to, and the ongoing symptoms of, the ASD
syndrome. In addition, the model could also account for successful intervention by promoting the reversal of this
process via adaptive coping and neuroplasticity. Factors that may facilitate adaptive neuroplasticity include
providing an enriched environment, increasing social and emotional connection, and decreasing anxiety, stress,
and allostatic load. Personal descriptions of the experience of ASD, as well as psychoanalytic clinical work with
children with ASD, are in accord with this model. Psychoanalysis may thus be considered a research tool that
assists in uncovering the childs inner world of feelings and meanings, an under-appreciated element in autism.
Making sense of the childs experience of isolation and threat helps the ASD child feel understood and less
afraid. Clinical material will illustrate how, for some children on the higher end of the autism spectrum, recovery
is made more likely by increasing the sense of connection and decreasing the experience of stress.
Keywords: autism; psychoanalytic psychotherapy; allostasis; stress; developmental neurobiology; neuroplasticity
The important thing in science is not so much to

obtain new facts as to discover new ways of thinking
about them.
Sir William Bragg (Nobel Laureate in Physics, 1915) in
Hu (2014)
[T]he complicated behavior of the world we see around
us is merely surface complexity arising out of deep
simplicity. It is the simplicity that underpins complexity, and thereby makes life possible []
John Gribbin (2004), quoting phrase attributed to
Murray Gell-Mann.
[A] denitive experiment is a largely mythical concept
in cognitive neuroscience. As in other areas dealing
with behavior, the solution is more a matter of
pattern perception of convergent ndings, than the
uncovering of the totally convincing clue.
Marcel Kinsbourne (2011)
*Email: wsingletarymd@gmail.com
2015 International Neuropsychoanalysis Society
Introduction
Autism spectrum disorder (ASD) is an urgent social
and mental health problem. Individuals with ASD
typically have difculty with social interactions;
exhibit problems with emotional regulation (White
et al., 2014); demonstrate hyper-focus on specic
topics of interest; and often engage in repetitive, selfsoothing, or self-injurious behavior. Recently found
to affect one in 68 children (Baio, 2014), more than
3.5 million people in the USA (Buescher, Cidav,
Knapp, & Mandell, 2014) and approximately 70
million worldwide are estimated to be living with
autism (Feld, 2015). The lifetime economic cost for a
person with autism has been estimated to be between
$1.4 million (Buescher et al., 2014) and $3.2 million
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W.M. Singletary
per individual (Ganz, 2007) with a US national cost of

$236$262 billion dollars each year (Buescher et al.,
2014). Most importantly, autism causes untold
human suffering to individuals with ASD and their
families.
ASD is an extremely complex, heterogeneous neurodevelopmental disorder involving an ever-growing
number of genes and multiple biological mechanisms.
These factors interfere with brain development and
functioning at many levels, leading to the disruption
of brain circuits mediating social interaction and
communication, as well as behavioral exibility
(Abrahams & Geschwind, 2010; Amaral et al.,
2008a; DiCicco-Bloom et al., 2006; Geschwind &
Levitt, 2007). Thus, there are different forms of
autism with numerous neurobiological pathways
(Amaral et al., 2008b; DiCicco-Bloom, et al., 2006;
Greenspan & Shanker, 2004; Herbert & Anderson,
2008; Siegel, 2007; Zimmerman, 2008b). All of
these paths converge to shape the individuals experience and to lead to the clinical manifestations of
ASD, now grouped into two primary areas: (1)
impairments in social communication and interaction
and (2) restricted and repetitive interests and behavior
(DSM-5, 2013).
The heterogeneity and complexity of ASD have

made progress in research and treatment difcult. At
one extreme, Waterhouse (2008, 2013) concludes that
no unifying brain dysfunction exists and that autism is
not a disorder, or even a spectrum of related disorders,
but rather only a collection of symptoms. More commonly, however, investigators do consider ASD to be a
disorder, but tend to focus on specic elements among
the many that contribute to ASD. An emphasis on particular factors has therefore led to a number of somewhat
competing and divergent theories of ASD (see Figure 1).
Some researchers in the eld have thus called for us
to think more broadly and to move beyond simplistic
linear models and unilateral approaches (Zimmerman,
2008a). I agree that multidisciplinary collaboration,
rather than fragmentation, is urgently needed in order
to further our understanding and increase our ability
to intervene effectively. An integrative model of ASD
could bring some degree of order and clarity to the eld.
The integrative model I propose in this paper is
based on a perspective emerging from recent research
in autism that, as Waterhouse (2013) suggested could
be a helpful approach, focuses on risk factors and the
mechanisms of developmental brain disruptions. In
this view, biological heterogeneity can lead to a single
Figure 1. In general, the numerous factors shown to be involved in autism have been considered in isolation from each other,
leading to divergent and competing theories of ASD.
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disorder through nal common pathways, which can
then be the targets of successful interventions (Sugathan
et al., 2014). To take one example, Jones and Klin (2013)
found that in infants who are later diagnosed with
autism, attention to eyes begins at normal levels, but
starts to decline between 2 and 6 months of age. They
consider this to indicate that some basic mechanisms
and neural foundations of social adaptive behavior, for
example, preferential attention to eyes, voices, and biological motion, are initially intact but later disrupted.
Thus, disturbance of a variety of normal developmental
pathways for social engagement may lead to a common
outcome the typical impairments in social functioning
found in ASD. This disturbance may be mediated by
epigenetic changes and maladaptive neuroplasticity.
In this perspective, one begins to see simplicity
arising out of the complexity of biological heterogeneity. Rather than restricting our focus to particular
contributory factors, which inevitably will generate
competing theories, we can now look at the complex
interaction of multiple contributing elements such as
genetic, epigenetic, and neuroanatomical inuences
that affect the development of the social brain and
childcaregiver interactions, and thus lead to the development of ASD (see Figure 2).
An integral aspect of the model I propose, a viewpoint not often discussed in the current work on
autism, is the psychoanalytic perspective. For many
years, psychoanalysis and neuropsychology have been
in completely opposite camps regarding the understanding and treatment of autism. However, my
experiences with clinical work involving intensive psychoanalytic treatment with a relatively small number
of children with ASD has inspired me to try to bring
these camps back into dialogue.
When used with adults, psychoanalysis typically
refers to an interpretive method with an emphasis on
free association, fantasy, and dreams. The crucial
difference compared to more behaviorally oriented
approaches is a central concern with inner, mental
83
experience, which one young boy whose treatment

will be described in some detail later, referred to as
the missing piece in the autism puzzle. With children, psychoanalytic treatment primarily uses play,
where mental events conscious and unconscious
are brought out using dramatizations with dolls or
enactments with the analyst. This intensive, relational
treatment allows access to the inner world of the
child. In addition, the parents are involved with
varying frequency for parental guidance including
helping them to understand the childs inner world
and to learn new ways to engage the child.
Looking at the autism literature through the lens of
what I have found to be the ASD childs central experience feeling alone and threatened in a dangerous
world led me to see new patterns. We can now discern
a remarkable conuence of ndings from multiple disciplines, making possible the construction of an integrative
model of ASD as a neurodevelopmental disorder with
psychological as well as behavioral components that
are potentially treatable and even perhaps preventable.
In what follows, I will be integrating ndings and
perspectives from a number of models of ASD that
have been developed relatively independently (Chevallier,
Kohls, Troiani, Brodkin, & Schultz, 2012; Dawson, 2008;
Greenspan, 1992; Helt et al., 2008; Herbert & Weintraub,
2012; Kinsbourne, 2011; Kliman, 2011; Mahler,
1968; Markram & Markram, 2010; Mehler & Purpura,
2008; Morgan, 2006; Pelphrey & Carter, 2008; Porges,
1994/2011; Ramachandran, 2011; Singletary, 2006,
2009, 2013; Szalavitz & Perry, 2010; Zaki & Ochsner,
2011).1 As I hope to make clear, these disparate lines of
work can be seen to converge under the umbrella of the
integrative model I propose.
In the development of this model which I outline
below, the work of both Dawson (2008) and Herbert
(Herbert, 2010a; Herbert & Anderson, 2008; Herbert
& Weintraub, 2012) has been crucial. First, Dawson
(2008) has proposed that genetic and environmental
risk factors can lead to risk processes. In her view, an
Figure 2. Recent research supports a new integrative model of ASD: heterogeneous biological factors can converge and act
through nal common developmental pathways to produce autism.
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W.M. Singletary
altered pattern of childcaregiver interactions deprives

the child of growth-promoting experiences, which
becomes a nal common pathway that heightens the
underlying vulnerabilities to develop ASD. Thus, in
Dawsons model, the full syndrome of ASD can be
reversed or possibly even prevented by early intervention focusing on optimizing the parentchild interaction. Second, Herbert and Weintraub (2012) have
emphasized the major role played by stress, particularly the physiological aspects of stress and allostatic
load. Third, both Dawson and Herbert highlight the
role of maladaptive and adaptive neuroplasticity in
the development of, and potential recovery from,
ASD. To these I have added an expanded consideration of the psychological dimensions related to the
experience of early deprivation of growth-promoting
parental input and psychological stress.
The proposed model of ASD

As I hope to demonstrate in this paper, the major convergences among these neurobiological models and
psychoanalytic formulations can be organized
around three primary factors: (1) neurobiological dysfunction leads to disruption of childcaregiver interactions, resulting in the early deprivation of crucial
social and emotional experiences; (2) stress both
psychological and biological plays a central role;
and (3) neuroplasticity is a fundamental element in
both the pathway(s) leading to ASD as well as in the
capacity for signicant adaptive development and
positive change in children with ASD (see Figure 3).
Specically, I propose that:
(1) Predisposing neurobiological factors lead to the
experience of environmental deprivation.
(2) This experience of environmental deprivation
leads to toxic levels of early life stress (both
psychological and allostatic overload).
(3) The amplifying interaction between deprivation
and allostatic overload, in the context of predisposing neurobiological factors, drives maladaptive neuroplasticity, leading to the underlying
structural and functional impairments of ASD.
(4) Early deprivation, traumatic psychological
stress and allostatic overload can therefore
account for the symptoms of ASD, as well as
the experience of the person with ASD.
(5) Interventions that address these underlying
factors and processes can lead to an alleviation
of ASD through adaptive neuroplasticity.
After elaborating on these premises, I will add psychoanalytic clinical material to illustrate them. I will
then conclude with a discussion of the potential usefulness of this non-reductionistic way of conceptualizing
ASD.
I hope that others will nd this testable model to
have some signicant explanatory power: it seeks to
parsimoniously accommodate most existing theories
of autism, explain the developmental progression
into the autism syndrome, account for the symptoms
of ASD as well as the individuals experience of
ASD, and elucidate the developmental processes
involved in the effective treatment of ASD. It also
suggests new avenues for research. In addition, I
believe that the proposed model is quite elastic, has
the capacity to readily expand to include new ndings,
and could provide a useful platform for promoting
cooperation and collaboration.
Perhaps most importantly, with an appreciation of
multiple factors, we should be better able to design
effective interventions and harmonize the competing
visions of treatment. In this vein, Jones and Klin
(2013) emphasize that evidence of an early, intact
neural foundation for social development in children
with ASD raises the possibility of successful early
intervention. Furthermore, recent research has
demonstrated adaptive neuroplasticity in ASD. The
model I will propose here has important implications
for establishing an upward spiral based on adaptive
plasticity to reverse the pathological processes in vulnerable children. Recently, Insel (2014) proposed that
both psychosocial and medical treatments can alter
the basic functioning of brain circuits. The challenge
is to bring together a range of things to harness
adaptive neuroplasticity and make sure that
someone with a very complicated problem that
involves not just one but multiple circuits and networks of networks in the brain has the greatest
opportunity to recover (p. 2). I hope that this
model can make a substantial contribution to this
effort.
Neurobiological factors lead to the experience of

environmental deprivation in ASD
Looking at autism through the lens of aloneness and
stress, one nds that independent voices from a
number of perspectives converge in seeing the neurobiologically based experience of environmental deprivation as a primary factor in the development of ASD.
In general, they fall into two major groups. First,
there are those proposing that primary difculties in
social information processing (Pelphrey, Shultz,
Hudac, & Vander Wyk, 2011) and in social motivation
(Chevallier et al., 2012; Dawson, 2008) interfere with
the infantcaregiver interaction and lead to the
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Neuropsychoanalysis
Figure 3. (a) In vulnerable children, several processes interact in a nonlinear manner: neurobiological factors, the experience of
environmental deprivation, the resulting psychological stress, and allostatic overload. Through maladaptive coping and neuroplasticity this interaction leads to ASD. (b) In contrast, interventions that are helpful in relieving the pathological contributions
of any of these interacting factors can contribute to the alleviation of ASD through adaptive coping and neuroplasticity.
experience of early social deprivation. For example,

Pelphrey and Carter (2008) propose that:
In the case of the child with autism, there is no doubt
that parents, grandparents, siblings, and educators
provide an abundance of love, warmth, and care, but
the child does not develop the brain mechanisms
that allow him or her to reach out and take hold of
this social fabric. (p. 1084)
Early disruption of the development of the social

brain, the neuroanatomical structures supporting
social information processing, is considered by Pelphrey to be the primary factor leading to the development of ASD. Such abnormal brain development
interferes with the infants ability to make use of opportunities for social reciprocity to develop the capacity
for social engagement and communication (Pelphrey
et al., 2011).
For Dawson (2008) and Dawson et al. (2005), the
numerous difculties involving reduced social engagement, such as problems with face processing, are considered to be secondary to a fundamental impairment
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W.M. Singletary
in social motivation that leads to decreased attention

to and engagement with people. Furthermore, as mentioned earlier, Dawson (2008) has developed a model
whereby genetic and environmental risk factors can
lead to risk processes: for example, an altered pattern
of childcaregiver interactions, which heighten the
underlying vulnerabilities to develop ASD. Such
altered interactions with the environment interfere
with the childs experiencing essential social and prelinguistic input, and result in functional environmental
deprivation. This deciency hinders the development
of social and linguistic brain circuits, further amplifying the effects of early risk factors (Dawson, 2008).
The second group is composed of those who
emphasize the role of excessive fear in leading to the
deprivation of necessary social and emotional experience. Both Perry (Perry, 2006; Szalavitz & Perry,
2010) and the Markrams, who developed the Intense
World Theory of autism (Markram, Rinaldi, &
Markram, 2007; Markram, 2010; Markram &
Markram, 2010), concur that sensory overload, heightened fear, and increased stress could lead to ASD
symptoms, including social withdrawal and impaired
interactions, as well as repetitive behavior. These maladaptive strategies for coping with excessive fear lead to
deprivation of key social experiences necessary for
development. For Perry (Szalavitz & Perry, 2010),
with the lack of social experiences, which exercise
the neuronal pathways of the social brain, this brain
network atrophies like a muscle. Perry concludes
that, as with neglected children, extreme stress and
deprivation of timely appropriate social stimulation
may be the cause of the social problems seen in ASD.
Schultz, Kohls, and Chevallier (2012) provide a
bridge between the group that focuses on the role of
primary difculties in social processes leading to the
experience of environmental deprivation, and the
second group, which focuses on the role of excessive
fear. Schultz and colleagues highlight the nding of a
high prevalence of anxiety as an associated symptom
in autism and emphasize that anxiety has an aversive
inuence on motivation and behavior. Dawson (Sullivan, Stone, & Dawson, 2014) also affords a link
between these groups with an emphasis on the importance of both positive social engagement and arousal
modulation in addressing decits in social motivation.
A recent fMRI study involving pivotal response
treatment, which focuses on social motivation and
communication, of 10 preschool-aged children with
ASD (Ventola et al., 2015) provides some preliminary
support for both the social motivation hypothesis and
the intense world hypothesis. At baseline, in response
to a task involving biological motion perception, ve
children evidenced hypoactivation of the right posterior superior temporal sulcus, which is involved in
social perception, and ve others, who had signicantly

greater difculties with anxiety and behavioral control,
exhibited hyperactivation in the same area. Following
treatment, all children demonstrated substantial gains
in social communication skills, and both groups exhibited more normal activation in the right posterior
temporal sulcus on post-treatment scans. However,
consistent with the social motivation hypothesis, following treatment the hypoactivation group evidenced
increased activation in regions involved in reward pathways, the putamen and ventral striatum. In contrast,
after treatment the hyperactivation group, consistent
with the intense world theory, exhibited decreased activation in subcortical regions involved in regulating the
ow of stimulation to the cortex. Although no strong
conclusions can be drawn from this study, given the
small sample size, the ndings illustrate the possibility
that both factors impaired social motivation and
excessive fear may operate in ASD, perhaps to different degrees in different children.
The experience of environmental deprivation leads to

toxic levels of early life stress (both psychological
and allostatic overload)
During the rst few months of life, the newborn faces a
major developmental challenge maintaining homeostatic regulation outside the womb. Both Bowlby
(1969, 1973) and Mahler (1968) emphasized the
importance of the infants relationship to her mother
for homeostasis, well-being, and survival, and underscored the infants experience of threat and intense
anxiety when the bond with the caregiver is disrupted.
Their work built on the earlier observations of Spitz
(1945, 1946), who had concluded that severe emotional
deprivation in a foundling home led to the deaths of 23
of 88 children up to the age of 2.5 years. Indeed, Perry,
Pollard, Blakley, Baker, and Vigilante (1995) have
argued that deprivation of critical experiences during
development may be the most destructive yet least
understood area of child maltreatment (p. 276).
According to the National Scientic Council on the
Developing Child (2012), since responsive relationships are developmentally expected and biologically
essential, their absence signals a serious threat to a
childs well-being, particularly during the earliest
years, and this absence activates the bodys stress
response systems (National Scientic Council on the
Developing Child, 2012) (p. 1). The stress response
system evolved to help us cope with change and react
to emergencies thereby protecting us and ensuring
our safety and survival (McEwen & Lasley, 2002,
p. 4). Infants, even neonates, can experience intense
physical and psychological pain and can feel an event
Neuropsychoanalysis
to be life-threatening (Coates, in press). For the infant,
separation from mother is considered to represent the
loss of a number of regulatory processes shaping infant
behavior, physiology, development, and adaptive
capacities (Hofer, 1995, 2014). Because the functioning
of the stress response system is critically regulated by
the childcaregiver relationship, deprivation, even
more than physical abuse, can cause disruptions of the
bodys stress response system (National Scientic
Council on the Developing Child, 2012).
Indeed, we are developing an appreciation for the
major role that the social environment plays in homeostatic regulation and the sense of well-being. This is
evidenced by the recent use of the term social allostasis to refer to the crucial inuence of interaction with
the social environment for regulation of the internal
state (Schulkin, 2011). For Eisenberger (2011), social
pain due to the loss of protective social bonds is considered to be among the most painful experiences for
humans. Because of the importance of social ties for
infant survival, threats to social connection may be
just as detrimental to survival as threats to basic physical safety and thus may be processed by some of the
same underlying neural circuitry (2011, p. 3). These
neural substrates of social pain are thought to
include the anterior cingulate cortex, which Eisenberger suggests may be crucial for social motivation.
While homeostasis refers to our need to maintain
a stable internal physiological state, the term allostasis is used to emphasize that our systems of stress
response help provide stability for the body through
their ability to adjust themselves to actively cope with
changes in the environment (McEwen & Lasley,
2002). Allostatic load or overload refers to the
pathological process that occurs when the protective
allostatic response functions improperly and causes
damage due to chronic mobilization of the bodys
stress response system (McEwen, 2012; McEwen &
Lasley, 2002). Children, who are chronically perceiving
and experiencing deprivation due to neurobiological
decits (not actual parental neglect), are likely experiencing a high allostatic load, which must be toxic.
The term toxic stress has been used in the child
development literature to refer to the process of
strong, frequent, or prolonged activation of the
bodys stress management system often provoked
by stressful events that are chronic, uncontrollable,
and/or experienced without children having access to
support from caring adults (National Scientic
Council on the Developing Child, 2005/2014, p. 2).
Over 45 years ago Mahler (1968) brought the
experience of environmental deprivation and early
life stress together. In her theory, ASD results from a
deciency in the infant such that he is unable to perceive and use the mother for homeostatic regulation,
87
resulting in a felt absence of the mother. This perception of early deprivation is experienced by the infant
as a threat to survival and leads to traumatic anxiety
that, in a vicious circle, further interferes with the
infants experience of having a protective parent. The
autistic syndrome is thus seen to represent the childs
defensive use of emergency maintenance mechanisms (Mahler, 1968, p. 52) felt to be essential for survival. In keeping with this perspective, Hofer (1995)
has emphasized the intertwining of the physiological,
nonverbal responses to maternal separation and loss
with the later developing symbolic levels of responding, both of which contribute to the formation of
mental representations of signicant others. In fact,
Hofer states that such events take place in us simultaneously at molecular, cellular, organ systems, cognitive/emotional, and experiential levels (2014, p. 9).
In discussing the experience of social deprivation in
autism, Schulkin (2011) suggests that the social isolation experienced in autism perhaps provokes a propounded sense of fear that goes along with the
isolation (p. 3). Since, as Loman and Gunnar (2010)
have emphasized, deprivation and disruptions in parental care are particularly powerful sources of early
life stress, the neurobiologically based experience of
social and emotional deprivation in ASD can certainly
be considered a form of toxic stress which can lead to
allostatic overload. Again, it is important to emphasize
that the traumatic effects of early life stress would
necessarily include not only disruption of the bodys
functioning, but also maladaptive coping behaviors
as well as a pathological foundation for the developing
childs internal world of human relationships.
The interaction between deprivation and allostatic

overload, in the context of predisposing
neurobiological factors, drives maladaptive
neuroplasticity and leads to the underlying structural
and functional impairments of ASD
Thompson and Levitt (2010) recently proposed that
allostatic overload during early development may
underlie neurodevelopmentally based psychiatric disorders. This is in keeping with McEwens assertion
that the revelation that the brain could be the
target as well as the initiator of the stress response
opened the door to understanding many of the problems and illnesses associated with allostatic load
(McEwen & Lasley, 2002, p. 54).
Since thoughts and emotions can activate the stress
response (McEwen & Lasley, 2002; Sapolsky, 1998,
2010), psychological and general biological factors
interact to either exacerbate or ameliorate the pathological effects of chronic stress on the function of the
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W.M. Singletary
brain. In fact, as I will review here, converging evidence indicates that early life stress and allostatic overload interact with the neurobiological factors and
processes central to autism in a circular fashion, hindering their development and functioning which in
turn leads to increased stress. As noted earlier, the
brain in ASD is the target of both biological and
psychological stress as well as the initiator of the
stress response (McEwen & Lasley, 2002). Through
maladaptive neuroplasticity this interaction then contributes to the progression to ASD.
McEwen (2003) linked unstable parentchild
relationships to allostatic overload and depression
that leads to further allostatic load and structural
changes in the brain. I suggest that a similar process
happens with autism. In describing the process of allostatic load, McEwen (2006) emphasizes the nonlinear
interaction among several systems and processes including psychological stress, the HPA axis, the autonomic
nervous system, the immune system, inammation,
and the metabolic system including the mitochondria
and oxidative stress (see Figure 4). Indeed, these very
factors have been implicated in ASD.
While oxidative stress and mitochondrial dysfunction have been found to be involved in the pathophysiology of ASD (Gu, Chauhan, & Chauhan, 2014),
inammation has been emerging as an area of particular interest and will be briey considered here.2 A
number of years ago, Vargas, Nascimbene, Krishnan,
Zimmerman, and Pardo (2005) demonstrated the presence of active neuroinammation in the brain of
patients with ASD, as well as marked activation of
astroglia and microglia along with a signicant increase
in pro-inammatory cytokines in the cerebrospinal
Figure 4. The same factors that interact to produce allostatic

overload, as emphasized by McEwen (2006), have also been
implicated in ASD.
uid. Since then the role of the immune system and

inammation in ASD has been further explored and
developed by a number of researchers, including
Martha Herbert (Herbert & Weintraub, 2012) whose
work will be described in more detail below. Recently,
Pramparo et al. (2015) found dysregulation of
immune and inammation gene networks in toddlers
with ASD compared to typically developing toddlers
and toddlers with other developmental delays who
were studied around the time of the typical emergence
of the rst clinical risk signs of ASD. Finally, two
recent studies not involving individuals with ASD may
nevertheless be relevant to our understanding of
autism. Eisenberger and colleagues (Moieni et al.,
2015a) found evidence that inammation interferes
with social cognitive processing and can impair the
ability to accurately understand emotional information
from others. Thus, one process involved in allostatic
overload, inammation, has been found to interfere
with an essential aspect of social interactions, a fundamental area of impairment in autism. Furthermore,
this same group (Moieni et al., 2015b) found that individuals who are more sensitive to social disconnection
(such as this model proposes for ASD) show enhanced
pro-inammatory responses and up-regulation of
genes related to inammation.
In a literature review exploring the possibility that
autism is a stress disorder, Morgan (2006) found that
neurobiological factors involved in the stress response
are remarkably similar to those involved in autism.
Such factors include the HPA axis, the autonomic
nervous system, the locus coeruleus-noradrenergic
(LC-NE) system, and the amygdala as well as neuromodulators and neurotransmitters such as the
opioids. Furthermore, Herbert and Sage (2013)
emphasize that a major role for stress in ASD is
nding a growing level of support from both clinical
experience and research. For example, Hirstein,
Iversen, and Ramachandran (2001) suggest, based on
a study of skin conductance in autistic children, that
a child with ASD might prefer sameness and routine,
and engage in self-stimulating behavior, to calm a
hyperactive sympathetic autonomic nervous system.
In addition, from a study of skin conductance in
ASD children compared to typically developing children, Chang et al. (2012) proposed that in ASD, high
sympathetic reactivity to sound may lie beneath problematic responses to sound.
Naviaux (2014) has proposed a model of ASD as a
response to threat focused at the level of the cell. In this
model, the cell danger response, the metabolic
response protecting cells as well as the entire organism
from threats (including psychological trauma, which is
signicant in the present discussion), leads to ASD
through the disruption of mitochondrial functioning.
Neuropsychoanalysis
While human trials have not been completed, treatment aimed at the level of mitochondrial function
and purine metabolism, single-dose antipurinergic
therapy with suramin, has been found to reverse
autism-like metabolism and behaviors in a mouse
model of autism (Naviaux et al., 2013; 2014).
Genetic and epigenetic mechanisms

Recent evidence suggests that genetic factors can interfere with the functioning of the social brain and
emotional experience through disruptive effects on
the functioning of crucial brain regions, neural pathways, and neuromodulators. Such interferences will
adversely impact emotional regulation (Mazefsky, Pelphrey, & Dahl, 2012) and parentchild interactions
(Dawson, 2008). In addition, Dawson (2008) proposes
that the resulting altered interactions between child
and parents might lead to epigenetic changes which
amplify the inuences of autism susceptibility genes.
Indeed, it is now generally accepted that genetic
factors play a pivotal role in autism (Amaral et al.,
2008a; DiCicco-Bloom et al., 2006). The siblings of
autistic individuals are over 20 times more likely to
have ASD than the general population, and apparently
unaffected siblings have been shown to share with the
autistic sibling similar brain responses to certain
stimuli, including such psychologically meaningful
stimuli as the facial expression of emotion (Belmonte,
Gomot, & Baron-Cohen, 2010; Dalton et al., 2005;
Spencer et al., 2011).
Genetic factors can interfere with the development
and functioning of the brain and can (as in Figure 3a)
disrupt neural systems that process cognition and
social behaviors (Amaral et al., 2008a, p. 385).
Some genetic abnormalities may disrupt synaptic formation and function (neuroligin/neurexin) and therefore produce widespread interference (Amaral et al.,
2008a). For example, variants in the autism risk gene
CNTNAP2 (a member of the neurexin superfamily)
have been found to predispose an individual to
autism through modulation of frontal lobe connectivity, including increased connectivity within the
frontal lobe and decreased connectivity with other
parts of the brain (Scott-Van Zeeland et al., 2010).
This nding is of obvious importance since the
frontal lobe is crucial for a number of higher order cognitive, social, and communication functions and is
implicated in the mirror neuron system as well as in
joint attention (Mundy, 2003). In fact, Geschwind
and Levitt (2007) suggest that autism spectrum disorders be considered disconnection syndromes, proposing that disconnection of dorsolateral prefrontal
regions and anterior cingulate cortex from other
89
regions necessary to develop joint attention in early

infancy, which is the foundation of language and
social behavior, would probably have widespread
reverberations during development (pp. 105106).
Furthermore, these genetic factors can be modied
by social conditions and stress. Chronic early life
stress has been found to lead to long-lasting epigenetic
alterations that negatively impact the stress response
system and development and, in addition, increase the
risk for a number of psychiatric and physical disorders
(National Scientic Council on the Developing Child,
2010). In addition, recent ndings in human social
genomics indicate that certain genes are subject to regulation by different socialenvironmental conditions,
such as social isolation (Slavich & Cole, 2013). For
example, social stress has been found to regulate inammatory gene expression (Powell et al., 2013).
Environmental factors
Recent evidence showing that monozygotic concordance rates are lower and dizygotic rates are higher
than previously believed for ASD has been considered
to highlight the importance of the prenatal and early
postnatal environment for autism susceptibility estimated to be about 55% along with moderate genetic
heritability (Hallmayer et al., 2011; Szatmari, 2011).
These nongenetic risk factors are hypothesized to
include maternal illnesses during pregnancy, environmental toxins during pregnancy, maternalfetal immunoreactivity, parental age, low birth weight, and
twinning (Hallmayer et al., 2011; Szatmari, 2011).
The risk to children posed by environmental toxins
is of particular concern since there is much support for
the idea that the developing brain is extremely vulnerable to the impact of toxins (Herbert & Weintraub,
2012). The evidence that genetic factors in ASD can
heighten the adverse effects triggered by exposures
(Herbert, 2010b; Herbert & Weintraub, 2012; Pessah
& Lein, 2008) makes the threat due to environmental
toxins of even greater concern. Herbert (2005) has postulated that environmental toxins could contribute to an
increased excitationinhibition ratio in ASD and that
the degree of environmental exposure may affect both
whether genetic vulnerability turns into disease and how
severe this disease becomes (p. 2). Furthermore,
McEwen and Tucker (2011) suggest that the network
for the stress response provides a pathway through
which psychosocial stress may interact with toxins and
lead to allostatic load, thereby increasing the health
risks conferred by environmental exposures.
In light of the role that the experience of threat and
heightened anxiety may play in ASD, it is signicant
that prenatal stress, including factors such as prenatal
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W.M. Singletary
exposure to hurricanes and tropical storms, has been

associated with an increased risk of ASD (Kinney,
Munir, Crowley, & Miller, 2008; Kinney, Miller,
Crowley, Huang, & Gerber, 2008). In a similar vein,
Roberts, Lyall, Rich-Edwards, Ascherio, and Weisskopf (2013) found an increased risk of autism in children whose mothers had been exposed to childhood
abuse with the risk for autism increasing directly with
the severity of abuse. Finally, Baron-Cohen et al.
(2015) found elevated levels of fetal cortisol (a
central component of the stress response) as well as
other fetal steroidogenic activity in autism and concluded that fetal steroid hormones may play an important role in epigenetic fetal programming mechanisms
for autism (p. 8).
Neuroanatomy
As in other areas in ASD, the evidence for functional
or structural neuroanatomical considerations in individuals with ASD is certainly not clear-cut. Amaral,
Rubenstein, and Rogers (2008a) emphasize that ASD
does not involve a single region of the brain, and
suggest that there may be phenotypic variations in
brain pathology. Many brain areas and certain types
of neurons play a signicant role in social functioning,
including the anterior cingulate (Di Martino, Ross
et al., 2009; Di Martino, Shehzad et al., 2009), the
anterior insula (Di Martino, Ross et al., 2009; DiMartino, Shehzad et al., 2009; Uddin & Menon, 2009),
mirror neurons (Ramachandran & Oberman, 2006;
Vivanti & Rogers, 2014), and Von Economo neurons
(Allman, Watson, Tetreault, & Hakeem, 2005), and
these have all been implicated in ASD. Here, I will
conne the discussion to the mirror neuron system,
the amygdala, the fusiform face area (as it relates to
the amygdala), and the cerebellum.
First, Ramachandran has proposed that the mirror
neuron system, a large interconnected circuit which
includes small groups of cells in many brain regions,
evolved in order to form internal models of others
actions and intentions as well as to develop self-representations and self-awareness (Ramachandran,
2011; Ramachandran & Oberman, 2006; Oberman &
Ramachandran, 2007).3 Furthermore, he proposed
that the functions of mirror neurons, including
empathy, understanding others feelings, actions and
intentions, imitation, and the use of language for
social communication, are disrupted in ASD because
of a potentially reversible dysfunction in the mirror
neuron system (Ramachandran, 2011; Ramachandran
& Oberman, 2006; Oberman & Ramachandran, 2007).
Also, Ramachandran (2011) suggested possible interactions between the mirror neuron system and neural
pathways (including the amygdala) involved in determining the emotional salience or potential signicance
of others.
In addition, Gallese (2006) and Cossu et al. (2012)
consider early impairment of the mirror neuron system
and the subsequent difculties in motor planning and
in understanding the goals of others actions to
underlie many of the difculties in social cognition
manifested by children with ASD. However, from a
different vantage point, Vivanti and Rogers (2014)
consider the mirror neuron system in the context of
the positive effects of the Early Start Denver Model
on children with ASD. They suggest that impairments
in mirror neuron system functioning might be the
result, rather than the cause, of early difculties in
social interactions. Furthermore, similar to the model
of ASD presented here, they propose that a pathological cascade results in which the dysfunction of the
mirror neuron system then leads to further impairment
at the level of social interactions that, however, could
respond to early interventions such as Early Start
Denver Model (ESDM) which will be described later.
Next, the amygdala, a key mediator of emotional
memory, is a central node in the fear circuits of the
brain, involved with the evaluation of stimuli for
threat, the detection of danger, fear conditioning,
fear extinction (critical to the possibility of change),
and the evaluation of facial expressions (LeDoux,
2000). In addition, the amygdala is linked to the
emotional processing of sensory information and
plays a role in moderating social interactions
(Amaral, Rubenstein, et al., 2008a; Meaney,
LeDoux, & Liebowitz, 2008). The amygdala also projects to the LC-NE system (LeDoux, 2000), a crucial
component of the stress response system, which has
been considered to play a central role in ASD
(Mehler & Purpura, 2008).
While earlier research led to an amygdala theory
of autism which postulated a hypoactive amygdala
(Baron-Cohen et al., 2000), more recent research supports a model of amygdala hyperactivity (Dalton et al.,
2005; Dalton, Nacewicz, Alexander, & Davidson,
2007; Nacewicz et al., 2006). When processing faces,
subjects with autism were found to have hypoactivation in the fusiform gyrus and increased activation in
the amygdala. This nding was considered to suggest
a heightened emotional response to gaze xation and
a hypersensitivity to social stimuli in autism (Dalton
et al., 2005). Such disruptions in processing of social
and emotional stimuli could lead to the problems in
social behavior associated with ASD (Rossman &
DiCicco-Bloom, 2008). Recently, Kleinhans et al.
(2009) found that, in response to socially relevant
stimuli, adults with ASD showed reduced neural
habituation in the amygdala and concluded that the
Neuropsychoanalysis
social decits observed in ASD may be related to sustained amygdala arousal.
The cerebellum is another brain region thought to
play a signicant role in social information processing
(Cozolino, 2006) and to be of importance in ASD,
since it is involved in higher order functions including
attention regulation and speech (Rossman & DiCiccoBloom, 2008). Both neuroanatomically and
functionally, the cerebellum (Courchesne, Webb, &
Schurmann, 2011) has been consistently found to be
abnormal in ASD patients. In fact, the gene
ENGRAILED2, which regulates cerebellar development, has been considered to be an ASD-susceptibility
gene (Rossman & DiCicco-Bloom, 2008). Interestingly, Cozolino (2006) considers the cerebellum to be
a hub of social processing and focuses primarily on
the cerebellum in his consideration of the social difculties found in autism. In addition to the cerebellums
role in the coordination of motor function and in
balance and equilibrium, he suggests that the cerebellum may be important in the timing and modulation
of language and affective regulation. According to
Cozolino (2006), cerebellar damage appears to
disrupt many of the very functions that serve as the
basis for vital interpersonal attunement and to interfere with the development of empathy and interpersonal relationships (p. 288). Obviously, this suggests one
pathway whereby impaired neurobiological functioning could contribute to a pathological experience of
isolation and danger and, thus, to the ultimate development of the ASD syndrome.
Finally, in discussing the role of the cerebellum in
autism, Aamodt and Wang (2011) emphasize that
the cerebellum is essential for translating sensory
events, such as the sight of a mothers smiling face
into a message with social import and therefore that
brains of autistic children may have trouble translating everyday social experiences into a meaningful
signal thereby, depriving themselves of a necessary
experience early in life (p. 234).
These structural differences found in autism may
be related to emotional stress, at least in part. Davidson and McEwen (2012) note that human research
suggests that early life stress leads to structural
changes in the brain. In particular, areas of the prefrontal cortex show decreased volume while there is
an increase in amygdala volume. Such changes could
interfere with the development of emotional regulation
which is thought to involve interactions between the
prefrontal cortex and amygdala (Davidson &
McEwen, 2012; Ochsner & Gross, 2005; Wager, Davidson, Hughes, Lindquist, & Ochsner, 2008). Furthermore, Davidson and McEwen (2012) point out that
early hypertrophy of the amygdala caused by early
life stress may be followed by later atrophy (Davidson
91
& McEwen, 2012; McEwen, 2006) and that this

pattern may occur in autism (Davidson & McEwen,
2012; Mosconi et al., 2009; Nacewicz et al., 2006; Tottenham and Sheridan, 2010).
In addition, Teicher, Polcari, Andersen, Anderson,
and Navalta (2003) conclude that early life stress is
likely to disrupt the functioning of the cerebellar
vermis. Schmahmann (2010) considers the vermis to
be part of the limbic cerebellum, an area which he
suggests may play a central role in ASD. In an fMRI
study of post-institutionalized children who had been
raised in foreign orphanages and adopted, Bauer,
Hanson, Pierson, Davidson, and Pollack (2009)
found that these children had smaller volume
superior-posterior cerebellar lobes, which was related
to poorer outcomes on tests of planning and memory.
Neuromodulators and neurotransmitters

A number of neurotransmitters and neuromodulators
have been implicated in ASD, including oxytocin, glutamate, dopamine, norepinephrine, serotonin, acetylcholine, and the opioids (Panksepp, 1979). Indeed,
the LC-NE system, a widespread neuromodulatory
system which plays a major role in the stress response
system is the central component in a recent model of
ASD; Mehler and Purpura (2008) propose that core
autistic symptoms are the result of developmental dysregulation of a functionally intact LC-NE system
which is transiently restored by fever. Here, I will
limit the discussion to oxytocin and glutamate, both
of which are likely to be involved in crucial ways.
First, based on their roles in forming social attachments in nonhuman mammals, the neuromodulators
oxytocin and vasopressin have long been considered
to be potential factors in ASD (Insel, 1997). A
growing body of evidence has demonstrated oxytocins
role in facilitating human connectedness. In healthy
human subjects, oxytocin has been shown to improve
the ability to understand the mental state of others
from subtle social cues (Domes, Heinrichs, Michel,
Berger, & Herpertz, 2007), reduce amygdala responses
to angry, fearful, and happy facial expressions (Domes
et al., 2007), increase focus on the eye region of human
faces (Guastella, Mitchell, & Dadds, 2008), and
increase trust (Kosfeld, Heinrichs, Zak, Fischbacher,
& Fehr, 2005). Moreover, in healthy subjects, oxytocin
receptor (OXTR) gene variation is linked to increased
stress reactivity and decreased empathy (Rodrigues,
Saslow, Garcia, John, & Keltner, 2009).
At this point, there is considerable interest in
research directly exploring the connection between
oxytocin and ASD. Variations in the OXTR gene
have been linked to an increased risk of autism
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W.M. Singletary
(Gregory et al., 2009; Jacob et al, 2007; Lerer et al.,

2008; Liu et al., 2010; Wu et al., 2005). Another line
of evidence is related to clinical trials investigating
the effects of intravenous or intranasal oxytocin in
individuals with ASD (Insel, 2010). Initial trials were
only suggestive, showing reduced repetitive behaviors
(Hollander et al., 2003), increased recognition of
social information (Hollander et al., 2007), improved
recognition of emotion in others (Guastella et al.,
2010), and increased social approach and comprehension (Andari et al., 2010).
However, two recent studies involving oxytocin
and ASD are of particular relevance for the model presented here. First, Feldman (Singer, 2012) found that
children with ASD had lower baseline levels of peripheral oxytocin. However, after the children with autism
played with a parent for only 20 minutes, their oxytocin
levels rose and became similar to those of controls for
approximately 40 minutes (Singer, 2012). Next, in
more denitive research to be described later, in an
fMRI study, Gordon et al. (2013) found that the
administration of intranasal oxytocin enhanced functioning of the social brain in children with ASD.
Next, excessive glutamate, the primary excitatory
neurotransmitter, leads to a general overreactivity to
sensory input (Herbert & Weintraub, 2012). Glutamate seems to play a major role driving excitotoxicity,
a pathological process in which excessive levels or
activity of glutamate and other excitotoxins damage
or kill neurons. Also, an imbalance between excitation
and inhibition related to glutamatergic dysregulation
has been proposed to modulate numerous risk
factors in ASD (Evers & Hollander, 2008) and may
play a critical role in causing autism (Herbert & Weintraub, 2012).
Several lines of research indicate that these neurotransmitter systems may be affected by allostatic
load in autism. Chronic stress, especially through the
action of glucocorticoids, affects the glutamatergic
synapse, alters glutamate neurotransmission, and
impairs functioning of the prefrontal cortex (Popoli,
Yan, McEwen, & Sanacora, 2011). Oxytocin and vasopressin neuropeptide systems have been shown to be
affected by early neglect and deprivation in children
reared in foreign orphanages and later adopted
(Wismer Fries, Ziegler, Kurian, Jacoris, & Pollack,
2005). In addition, the structure and function of the
LC-NE system is regulated by diverse stressors and is
considered to play a signicant role in stress-related psychiatric disorders (Valentino & Van Bockstaele, 2008).
Finally, allostatic overload, both acute and
chronic, leads to both structural and functional
changes in serotonergic and dopaminergic neural
systems as well as in the LC-NE system (Beauchaine,
Neuhaus, Zalewski, Crowell, & Potapova, 2011).
Neural networks, connectivity, and sensory

processing
A broad array of factors ranging from the microscopic to the psychological involved in neural networks, connectivity, and processing are implicated in
the development, maintenance, and treatment of
ASD. Minshew, Williams, and McFadden (2008)
have developed a highly useful model, the complex
information processing-disconnectivity-neuronal organization model of autism (p. 383). While there are
differences, Minshew and colleagues note certain similarities to other conceptualizations such as the developmental disconnection syndrome (Geschwind &
Levitt, 2007) mentioned earlier. The model presented
by Minshew et al. (2008) includes cortical connection
disturbances that, in high-functioning ASD, primarily
involve increased local frontal connectivity and lessened connectivity among neural systems. This leads
to impaired complex information processing, including disturbances in processing social information that
are thought to underlie the social impairments seen
in ASD. For example, Kana, Keller, Cherkassky,
Minshew, and Just (2009) found a functional underconnectivity between frontal and posterior regions in
the brain during the attribution of mental states in
adults with autism. In addition, Bachevalier and Loveland (2006) have presented evidence that difculties in
self-regulation of social-emotional behavior in ASD
are related to dysfunction of the orbitofrontalamygdala circuit in the brain. Finally, a recent fMRI study
involving high-functioning adolescents with ASD
compared to normal adolescents found signicant
decreases in connectivity between three regions of the
social brain in those with ASD (Gotts et al., 2012).
Specically, the affective processing limbic region
was less connected with regions more involved in the
language/communication aspects of social behavior
and regions supporting socially relevant sensorimotor
processes, that is, the visual perception of socially relevant form and action (p. 11). Adolescents with ASD
who showed the greatest decreases in connectivity
among the social brain regions were found to have
more severe social symptoms. The thinking brain
does indeed seem to be disconnected from the
feeling brain (Sherkow, personal communication,
May 20, 2007).
In focusing on the autistic mind, Bryson (2005)
links information processing to emotion and thought.
She concludes that in autism, the mind is hypersensitive to sensory stimulation and therefore vulnerable
to sensory overload; the mind then attempts to adapt
to this overarousal by narrowing the focus of attention.
This hypersensitivity extends to the emotions, which
can be experienced as overwhelming and because
Neuropsychoanalysis
of this heightened intensity and difculties in reecting
on thoughts and experiences are poorly modulated
by thought. Thus, emotionally signicant events lead
to narrowed attention and a heightened tendency to
engage in repetitive (self-regulating) behaviors. She
adds that under such circumstances, positive
emotion can readily be experienced as aversive
(p. 41). This observation is of utmost importance in
understanding the experience and behavior of individuals with ASD, which can seem so paradoxical, for
example, pleasurable interactions are often followed
by disruptions.
Supporting the model proposed in this paper, a
series of ndings link early life stress with changes in
connectivity. First, both acute, uncontrollable stress
and chronic stress interfere with synaptic functioning
and disrupt emotional regulatory networks leading to
decreased modulation of emotions by the prefrontal
cortex and increased amygdala activity (Arnsten,
Mazure, & Sinha, 2012). Furthermore, early life stress
is associated with alterations in cortical network connectivity in brain regions associated with social cognition and emotional regulation (Teicher, Anderson,
Ohashi, & Polcari, 2014).
Early neglect is also associated with disruptions in
white matter directional organization in the PFC and
in white matter tracts connecting the PFC and the temporal lobe (Hanson et al., 2013).
In summary, autism is widely considered to involve
increased local connectivity within brain regions and
decreased connectivity among more distant brain
regions, leading to problems in processing tasks requiring large, highly integrated brain networks such as
language and social-emotional functions (Williams,
2008, p. 14). Supporting this conclusion, aberrant
development in white matter ber tracts from 6 to 24
months in infants with autism has recently been
found, suggesting that differences in white matter
pathways could precede the manifestations of ASD
symptoms (Wolff et al., 2012). In addition, eight 12year-old boys with ASD were shown to have decreased
white matter connectivity in sensory pathways, along
with impaired white matter connectivity in tracts
subserving social-emotional processing (Chang et al.,
2014).
Early deprivation, traumatic psychological stress and

allostatic overload can therefore account for the
symptoms of ASD, as well as the experience of the
person with ASD
As noted above, one of the major developments in
neurobiology has been the dramatic rise in our understanding of the brains capacity to change
93
neuroplasticity. According to Hebbs Law (Hebb,

2014), neurons that re together wire together
(Shatz, 1992, p. 21). Thus, the brain operates in a
use it or lose it, fashion referred to as use-dependent plasticity (Cozolino, 2010, p. 325). Considering
brain development to be self-organizing and using a
dynamic systems theory model, Lewis (2005) describes
cortical developmental change as a reorganization of
synaptic connections between neurons, which change
and stabilize based on neuronal activity. Stabilization
in the cortex and limbic system occurs because of
synaptic sculpting so that these synaptic structural
changes become self-perpetuating (Lewis, 2005). The
mechanism of cascading constraints, such that
early developmental structures limit characteristics of
structures evolving later, contributes to the developmental trajectory of an individual (Lewis, 2005).
Thus, alongside of the potential for progressive development of the brain in an optimal fashion, there
exists the possibility for maladaptive plasticity or
pathological brain organization (Helt et al., 2008).
Allostatic overload represents an important
pathway contributing to maladaptive neuroplasticity
in ASD (Herbert & Weintraub, 2012). For example,
Schore (2014) has suggested that allostatic overload
during critical periods of neuronal development
might interfere with the development of neurons and
brain circuits that play crucial roles in emotional regulation and social interactions. In addition, an emerging
body of work on depression has particular relevance to
this model of ASD. The cognitive model of depression
has evolved to include the interaction of genetic and
neurobiological factors with early traumatic experiences and cognitive factors including cognitive distortions and dysfunctional beliefs (Beck, 2008). In
addition, the role of early life stress, inammation,
and allostatic overload in neuroprogression and the
pathway to the development of mood disorders has
received considerable attention recently and sparked
interest in the development of novel biomarkers as
well as prevention and intervention strategies related
to increasing both physiological and psychological
resilience (Walker et al., 2014).
One asset of the model I propose here is its ability
to provide an integrative explanation of the developmental progression to ASD, one that involves both
neurobiological and psychological elements within
the child, as it were, as well as interactions with caregivers. Neurobiological factors and processes, environmental deprivation, psychological stress, and
biological stress or allostatic overload all interact in a
nonlinear way and contribute to the nal outcome
(see Figure 3a).
I suggest that this complex process is as follows.
Neurobiological factors make a child vulnerable to
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W.M. Singletary
respond aversively to subjective experience, for

example, overarousal in response to novel, unpredictable stimuli including, crucially, human interaction
or social information (Dawson & Lewy, 1989). This
aversive response disrupts the functioning of the
social brain and, in a circular way, further impairs
adaptive social interactions. The subsequent impaired
social information processing and social motivation
negatively impacts both the childs relationships with
others and subjective psychological experience. Thus
deprived of appropriate social-emotional input and
the neurobiological consequences of that input, the
child fails to experience mothers comforting presence
and protection, and, instead registers heightened
anxiety, stress, and a sense of threat (Mahler, 1968).
Even with loving reactions from parents, the child
may make inaccurate and pathological meanings of
these experiences and conclude that human interactions are not only unrewarding, but also dangerous
and frightening and must be avoided. Thus, neurobiological elements might obstruct the infants experience
of comforting and rewarding relationships with caregivers and interfere with the childs feeling a sense of
safety and calm well-being. Instead, the experience of
deprivation the absence of human connections
could lead to further overarousal, a sense of threat,
maladaptive coping, and toxic stress or allostatic
overload.
Moreover, the childs efforts to make sense of and
cope with the experience of aloneness and danger
might lead to a defensive withdrawal from others and
to the development of psychological conicts regarding relationships. What originates in the child as an
attempt at an adaptive response to perceived (not
actual) threat is truly maladaptive. Because of fear,
the child shuts out what he needs the most, loving
and helpful human interactions. For example, the
child could feel both a great need for emotional
contact with parents and, simultaneously, a dread of
such closeness. This heightened anxiety and fear surrounding the world of people, and the ensuing social
isolation, both would further hinder accurate social
cognition and empathic accuracy and, to an even
greater degree, interfere with social motivation and
adaptive social interaction.
In a vicious circle, the childs self-regulating and
protective efforts could therefore make it more difcult
for parents to help and, thereby, further constrain
adaptive parentchild interaction and the development
of the social brain. Thus, I suggest that these interlocking neurobiological and emotional/psychological
impairments come together in a nal common
pathway leading to the various clinical manifestations
of the syndrome of ASD, both in its development and
maintenance (Singletary, 2009).
As noted above, in this model, stress from all

sources, including both emotional and biological
stress, plays a central role in the multiple processes
leading to the autistic syndrome. As Herbert and Weintraub (2012) suggest, at the cellular level, emotional
stress can trigger toxic processes, such as the activation
of microglia (a type of glial cell which plays a major
role in the brains immune system) which drives oxidative stress and triggers the release of immune chemicals chemokines and cytokines that promote
inammation. In turn, at the circuit level, neuroinammation can interfere with neural connectivity and
social cognition, which could exacerbate social withdrawal and increase stress, which can further increase
neuroinammation. Through the actions of corticotropin-releasing hormone and the sympathetic
nervous system, emotional stress can lead to immune
suppression and inammation in the entire body,
including the brain. Likewise, oxidative stress and
inammation can contribute to neuronal overexcitability and increased emotional stress.
Herbert and Weintraub (2012) thus outline the
decline into autistic functioning as follows: some
degree of genetic vulnerability plus increased
demands on the whole body from the environment
(toxins, infectious agents, poor nutrition, and stress)
leads to inammation and oxidative stress which interfere with the functioning of the glia, including the
astrocytes. This produces still more oxidative stress
which further impairs glial functioning and leads to
an excessive level of neuronal excitation. A tipping
point then occurs when the allostatic load (the total
load of physical and emotional stress) is too great. At
this juncture astrocytic networks, which, as noted
above, are involved in brain information processing
as well as brain network coordination and connectivity, begin to malfunction. This further impaired
astrocytic functioning then leads to excessive levels of
glutamate, sensory overreactivity, and impaired
complex information processing in the brain. Autistic
behaviors are the nal outcome of this pathway that
involves many different interlocking vicious circles,
including those formed by anxiety (Herbert & Weintraub, 2012).
The symptoms of ASD

In proposing this model of ASD arising from a vulnerability to experience social deprivation which is then
exacerbated by attempts to cope with the stress of
that deprivation, one of my main aims is to account
for the common cluster of ASD symptoms. A
number of researchers and clinicians have already
linked ASD symptoms with stress in various ways.
Neuropsychoanalysis
Tustin (1994) considered ASD to be an infantile
version of a post-traumatic disorder with contributions
from both constitutional and environmental factors
which interfere with the motherchild interaction and
ongoing development (Tustin, 1990). More recently,
Kliman (2011) has also noted the symptomatic as
well as neurobiological similarities between autistic
disorders and post-traumatic stress disorder. Kinsbourne sees autistic symptoms, including both repetitive behavior as well as difculties with social
communication and interaction, as attempts to avoid
or to self-regulate in the face of hyperarousal (Kinsbourne, 1987, 2011; Kinsbourne & Helt, 2011).
Groden, Cautela, Prince, and Berryman (1994) highlighted the major role played by maladaptive coping
strategies in response to excessive stress and anxiety
in ASD. Schore (2014) has proposed that autistic
infants, because of early neurobiological difculties
perhaps involving the right amygdala prenatally,
experience a chronic intense state of fear which persists
throughout early childhood and may lead to the defensive use of dissociation as well as to the development of
allostatic overload. Mahler (1968) also considered
ASD to represent maladaptive coping in response to
the traumatic experience of social and emotional
deprivation. And recently Mazefsky et al. (2013)
place maladaptive coping strategies and emotional
dysregulation at the heart of ASD.
Sapolsky (2010) outlines an adaptive response to
stress: seeking social support; trying to obtain a
reasonable degree of predictability, stability, and
control; and utilizing constructive outlets for frustration. It is striking that the symptoms of ASD represent
the opposite or a maladaptive form of coping (see
Figure 5). Instead of turning to others for social
support, the autistic child isolates himself. A reasonable desire for predictability and stability is replaced
by repetitive behaviors and excessive demands for
sameness. The child with ASD requires absolute
control instead of a realistic sense of control.
Figure 5. Symptoms of ASD, such as social isolation and

repetitive behavior, are maladaptive ways to cope with
psychological stress, and represent the opposite of adaptive
coping mechanisms such as turning to others for social
support.
95
Constructive outlets for frustration such as fantasy

and play are replaced by ts of rage and temper tantrums a most maladaptive way to cope with overwhelming stress.
Another line of evidence linking stress with the
symptoms of ASD is the clinical picture of neurotypical infants responding to stress and trauma. It must be
emphasized that the experience of deprivation and
sense of threat in infants who develop ASD arises
from biologically based internal factors, and therefore
has a different outcome (ASD) from infants who do
not have this genetic and neurobiological vulnerability
and are subject to real external threat and trauma.
However, the defensive responses to deprivation and
early trauma in non-autistic infants may still indicate
similarities with the subjective experiences and defensive or coping maneuvers found in ASD. Inspired by
the work of Spitz on maternal deprivation, Fraiberg
(1982) described a group of defensive behaviors in
infants from 3 to 18 months of age who had experienced extreme deprivation and threat. Of particular
interest is her description of avoidance of social interaction, including gaze aversion, beginning as early as
three months of age approximately the age Jones
and Klin (2013) recently found for the onset of
decreased attention to eyes in infants later diagnosed
with ASD. Other defenses included freezing and ghting. Fraiberg (1982) considered all of these to be based
on the biological model of ight or ght.
Coatess (in press) description of the symptom clusters in traumatized infants and Perrys (Perry et al.,
1995; Perry & Pollard, 1998) description of basic
response patterns to threat are particularly relevant.
Coates describes a symptom cluster related to
numbing of responsiveness, and Perry notes a disassociative response pattern; both involve social withdrawal and disengagement from the external world, which
correspond to the characteristic impairments in social
communication and interaction found in ASD. Both
also note a key role for hyperarousal, which has long
been considered to play a major role in ASD, as discussed earlier (Kinsbourne, 1987; Kinsbourne & Helt,
2011). Moreover, Coatess description of the symptom
cluster related to re-experiencing the trauma through
compulsive play and repetitive re-enactment of the
trauma resembles the restricted and repetitive interests
and behavior found in ASD. For example, in my own
clinical experience, a 4-year-old boy with ASD who
was deathly afraid of separation from his parents
showed an extreme preoccupation with stop signs and
exit signs. This interest seemed to express his desire to
have absolute control over the comings and goings of
the people he needed most. His excessive preoccupations could be considered to represent a maladaptive
way of coping with the threat of loss.
96
W.M. Singletary
Finally, Porgess body of work regarding polyvagal

theory links the early experience of threat, defensive
avoidance of social interaction, and withdrawal to
the symptoms of ASD through neurophysiological
pathways. In particular, he focuses on pathways for
autonomic arousal and social engagement. To
survive and develop optimally, humans must be able
to process sensory information from both the external
and internal environments in order to evaluate risk,
distinguish between friend and foe, determine
whether an environment is safe or dangerous, and
communicate and act in an adaptive way with the
social group (Porges, 2004/2011; Porges, 2009; Van
Der Kolk, 2011). This process, which Porges calls
neuroception, connects the evaluation of risk with
social behavior (Porges, 2004/2011). Once the process
of neuroception, which operates outside of conscious
awareness, determines whether people or situations are
safe or dangerous, either prosocial or defensive behaviors result as adaptive responses (Porges, 2004/2011).
In order to form social bonds and lasting relationships, we must be able to inhibit defensive strategies
and become socially engaged under conditions of
safety, for example, with the appearance of a loving
caregiver. The social engagement system depends
upon autonomic regulation of the muscles of the face
and head which play a major role in social and
emotional communication and interaction (Porges,
1994/2011, 2004/2011). These muscles collectively
function as lters that limit social stimuli (e.g.,
observing facial features, listening to the human
voice) and as determinants of engagement with the
social environment (Porges, 1994/2011, p. 220).
With the neuroception of safety comes behavior conducive to social engagement: making eye contact,
making contingent facial expressions, vocalizing with
appropriate rhythm and inection, and a greater
ability to distinguish the human voice from background sounds (Porges, 2004/2011).
Porges (1994/2011, 2004/2011) suggests that there
is an intact, but functionally disrupted, social engagement system in ASD. He raises the possibility that
faulty neuroception an inability to assess accurately
whether the environment is safe or dangerous or a
person is trustworthy or not may be at the heart of
the psychopathology of children with autistic spectrum
disorder, as well as those with reactive attachment disorder. Thus, in children with disrupted social engagement systems, defensive behaviors may occur in safe
environments, and social engagement behaviors may
occur in risky environments.
Quite likely because of the experience of threat,
social engagement behaviors are frequently disrupted
in children with ASD. Porges posits that the neuroception of danger (whether from an internal or external
source) leads to decreased tone in the muscles of the

face and head. In turn, this difculty with muscle
tone is considered to underlie problems which are
common features of ASD and hinder social engagement: difculties with gaze, facial expressions,
hearing the human voice, speech prosody, and state
regulation.
In addition, Porges proposes that this theory also
helps explain a number of other dysfunctions frequently associated with ASD. The autonomic
nervous system and other components of the social
engagement system, especially the vagus nerve, are
involved in the regulation of the HPA axis, the
immune system, and the gastrointestinal system and,
thus, could play a signicant role in their dysfunction
in ASD (Porges, 1994/2011).
The individuals experience of ASD

Personal reports from individuals with ASD dovetail
with the model I am proposing here of maladaptive
coping in response to the experience of environmental
deprivation and early life stress, as well as ongoing traumatic stress. In Nobody nowhere, her widely acclaimed
account of the Aspergers experience, Williams (1992)
virtually restates the model developed here:
I believe that autism results when some sort of mechanism that controls emotion does not function properly an autistic child is unable to receive or
make sense of any message that says there is a connection between itself and its mother. This inability to
comprehend closeness constrains the formation of
attachments Without this the child becomes
a world within itself
Autistic people are trapped in invisible, crippled
emotional responses In my case, my mind knows
that affection and kindness will not kill me, yet my
emotional response dees this logic, telling me that
good things and gentle and loving touch can kill me
or at the very least cause me pain (There is a) subconscious will to escape this emotional prison (pp.
203205)
I believe Williams is describing here the subjective

outcome of the neurobiological factors that lead to
the experience of early deprivation. The ensuing difculties in social relatedness lead to emotional isolation. In this, Williams description helps illustrate
my central point: her isolation is not only a decit,
due to a lack of opportunities for helpful emotional
engagement, but is also a result of a defensive protection felt to be necessary to survive. Most importantly,
she highlights her conicts about developing loving
relationships. She wants to leave her self-constructed
and maintained emotional prison but is terried
of leaving her protective shell and becoming warmly
Neuropsychoanalysis
connected to others. Even though on one level she

knows that it is not true, on another level she believes
that love and affection will kill her. In my clinical
experience, I have found this same set of psychological factors to be of critical importance for the
patients with ASD whom I have treated. Indeed,
my experience is that behind the symptoms of
autism temper tantrums, social isolation and resistance to change lies the pain of loss, fear of annihilation, and traumatic stress. My work with Larry,
which I will discuss later, beautifully illustrates these
concerns.
In their book Grandin and Scariano (ghost writer)
(1996), propose a major role for neuroplastic processes
that relate to the experienced isolation of those with
ASD:
The original fetal defect in brain development is probably responsible for the babys avoidance of being
touched and comforted. The longer a baby lives
without experiencing the feeling of being comforted,
the more likely the brain circuits involved in the development of emotional contact with people will be
damaged Brain circuits which are constantly used
will become larger. Circuits which are used will be
retained and enlarged whereas circuits which are idle
will shrink. If the baby does not use his feeling circuits, they may shrivel up. (p. 182)
As Grandin and Scariano, (ghost writer) (1996)

describe this process, neurobiological factors lead to
infant avoidance of comforting contact with caregivers, with maladaptive neuroplasticity then interfering with the development of the social and emotional
brain due to nonuse.
In Exiting nirvana, Park (2001), the mother of an
adult with autism, considers the isolation and rigid
insistence on sameness to be a safe haven, a defensive
retreat into a place which becomes terrifying to leave.
She describes her difculty making emotional
contact with her daughter as like assaulting a walled
city (p. 10). She had come to understand her daughters isolation as perhaps relating to an impairment
in information processing which led to difculty understanding sensory input, such as:
changing expression on those faces, the tones of those
voices. Might she not prefer the security of a world she
could make sense of, a world that didnt change, or
changed predictably a world not of faces, not of
voices, certainly not of words, but of spots on the
oor ? Of clear, unchanging, identiable shapes
and colors? And when that secure order was disrupted,
might she not be desolate? (p. 11)
In her touching book, The best kind of different,

Shonda Shilling (2010) recounts the familys journey
with her son, Grant, who has Aspergers. Schilling
97
imagines the terror behind her sons excessive desire

for predictability and control, his maladaptive efforts
to cope with traumatic levels of stress:
The mental processes go on total anxiety overload.
Your thoughts and feelings become nearly impossible
to distinguish and blend together into one seemingly
inseparable reaction thats impossible to contain.
This is what kids with Aspergers feel like every day,
in every situation that comes up that they are not prepared for. This is why they like schedules and routines.
Its comforting for them to have details they can count
on when they feel otherwise out of control They like
things to perfectly match their expectations, and have a
very difcult time dealing with any variation on what
they thought was coming. (p. 201)
Similarly, in his recent book, Be different, Robison

(2011), Robison, a self-proclaimed Aspergerian,
describes showing his therapist a documentary featuring a 16-year-old boy with Aspergers. Robison recognized the boys fear as he walked the school halls
constantly Looking for threats Like a lone
deer in a forest lled with wolves I knew exactly
how he felt Alone, scared no one around him
understood him (p. 3). Robison contrasted his
reading of the boys behavior with his therapists supercial response, seeing only furtive eye movements
[that are] common in people with autism. It doesnt
mean anything (pp. 34). Robison felt as if he had
been punched in the gut Every expression and
gesture means something. Its sometimes hard to
gure out what the meaning is, but it always exists
(p. 4).
Here Robison makes clear that not feeling understood at this deeper level, below the surface behavior,
can hurt our patients who have autism. He underscores
my assertion that understanding the deeper meanings
of symptoms and behavior can make a substantial contribution to treatment. This now leads us to a discussion of how a number of strategies, including
attempts to understand the subjective experience of
children with ASD and thinking about their defensive
and coping strategies, can help address maladaptive,
pathological processes and promote adaptive
neuroplasticity.
Successful intervention in ASD is possible through

reversing the pathological developmental process and
promoting adaptive neuroplasticity
It has recently become established that some children
with autism can overcome the central difculties in
ASD with very positive (Anderson, Liang, & Lord,
2014) or optimal outcomes (Fein et al., 2013) and no
longer have a diagnosis of autism. Indeed, in a large
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W.M. Singletary
prospective study of toddlers with ASD, Anderson,

Liang, and Lord (2014) found that by age 19, 9%
met the criteria for very positive outcome. In a recent
review of controlled studies involving the use of behavioral techniques, Helt et al. (2008) conclude that
between 3% and 25% of children with autism
recover, that is, lose the diagnosis of ASD, as well as
become able to function in the normal range socially,
cognitively, and adaptively.
Grandin and Scariano, (ghost writer) 1996) may
have been among the rst to suggest that maladaptive
neuroplastic processes in ASD can be reversed through
the use and exercise of atrophic brain circuits, as illustrated by Grandins personal experience. For example,
being overly sensitive to sensory input led to panic
attacks, which as an adolescent made her feel as if I
were clinging to a greased rope suspended over an
abyss (p. 71). She designed a squeeze machine to
provide a comfortable sense of being held. Through its
use she learned to control her aggression and to
accept affection and had pleasurable sensations and
thoughts about love (p. 112). Grandin described
feeling not only others concern and love for her and
but also was able to express her feelings about herself
and others, as if an accordion folding door had
shoved back revealing my emotions (p. 92). Her experience implies a rapidly, albeit temporary, reversible malfunctioning of the social brain.
Indeed, there is now evidence that the successful
treatment of ASD involves the reversal of the pathological developmental progression described above.
Two recent interventional studies demonstrate that
overcoming environmental deprivation and diminishing psychological stress (Ventola et al., 2015) as well
as reducing allostatic overload (Singh et al., 2014)
may be central factors in promoting adaptive neuroplasticity and therapeutic change in ASD.
The potential for adaptive neuroplasticity in ASD

Some evidence that treatment of ASD can lead to benecial change through adaptive neuroplasticity is now
accumulating. Four recent studies have demonstrated
that both psychosocial interventions and oxytocin
treatment of children with ASD are associated with
functional brain changes (Dawson et al., 2012;
Gordon et al., 2013; Ventola et al., 2015; Voos et al.,
2012; Ventola, Oosting, Anderson, & Pelphrey, 2013).
The rst study assessed the effects of the ESDM, a
developmental intervention for toddlers and young
children with ASD, which focuses on the development
of social and emotional engagement with parents
(Rogers & Dawson, 2010). In a clinical trial, intervention from trained clinicians for 20 hours per week,
parent training, and parent delivery of the ESDM for

more than 5 hours each week was associated with
improvements in social behavior and normalized
EEG patterns of cortical activity in response to faces
(Dawson et al., 2012). A recent follow-up study 2
years later showed that at age 6 years, these children
not only maintained the behavioral gains that had
been made earlier but also demonstrated an important
new nding, improvement in core autism symptoms
(Estes et al., 2015).
Second, pivotal response therapy (PRT), a behavioral treatment designed to improve social motivation
and communication, has been found to have positive
effects on social skills, behavior, and communication
in young children with ASD (Koegel & LaZebnik,
2005; Voos et al., 2012). PRT builds upon applied behavioral analysis (a widespread method of using
reinforcement schedules to modify behavior) but
differs in crucial ways. Rather than a primarily therapist-directed approach focusing on rote learning,
PRT offers the child choices about play activities and
encourages functional communication. Natural
rewards, such as playing with a favorite toy or eating
a preferred food, are utilized to reinforce the childs
attempts in such pivotal areas as social initiation and
responsivity. In a pilot study, four months of 810
hours a week of individual therapeutic work with two
ve-year-old children, along with parent training,
was associated with signicant behavioral improvement in both children, as well as with fMRI evidence
of increased activation to social stimuli in brain
regions involved in social perception (Voos et al.,
2012). In a following study (described in more detail
above), after four months of PRT, 10 preschool-aged
children with ASD evidenced signicant gains in
social communication and exhibited more normal activation in the right posterior temporal sulcus, which is
involved in social perception (Ventola et al., 2015).
In addition to these studies indicating that psychosocial treatment can lead to brain changes, there is
also evidence that impacting brain circuits biomedically
can affect ASD. One line of research suggests that
impacting stress, immune, and inammatory factors
can modify brain functioning in ASD. In recent prospective study (Curran et al., 2007), 83% of the ASD
children studied who experienced a febrile episode
during the follow-up period showed improvements in
behavior, with decreases in stereotypy, irritability, and
hyperactivity, as well as improved speech both during
and briey after signicant febrile episodes. In my
own clinical experience, some parents have reported
dramatic changes in their children with ASD during
fevers. In stark contrast to their usual behavior, during
febrile episodes some children are able to engage in
lengthy, emotionally meaningful conversations.
Neuropsychoanalysis
Curran and colleagues suggested that this rapid but
short-lived change may have been based on alterations
in neuroinammatory processes, modication of neuronal and synaptic function, changes in energy consumption and mitochondrial activity, and involvement of the
HPA axis with resultant modications in neurotransmitters. Such rapid symptomatic improvement associated
with febrile episodes suggests that at least in some children with ASD the malfunctioning neural circuits are
intact, but obstructed by some unknown, but potentially
reversible, factor(s). Subsequently, there has been signicant interest in understanding the neurobiological mechanisms underlying this improvement (Fischbach, 2010;
Mehler & Purpura, 2008; Moorman, 2010) with particular focus on the hypothalamus and its effect both
on the release of oxytocin and vasopressin as well as
on the LC-NE system (Fischbach, 2010; Mehler &
Purpura, 2008; Moorman, 2010).
In keeping with a stress/anxiety model of ASD,
Beversdorf and colleagues have demonstrated rapid,
transient increases in functional connectivity between
brain regions in ASD (Narayanan et al., 2010) and
improved social communication and interaction in
teenagers and young adults with ASD (Louden,
2014) following the administration of propranolol.
Given propranolols use in the treatment of anxiety,
Herbert and Weintraub (2012) suggest that this effect
of propranolol indicates that psychological stress
creates connectivity problems in ASD. This dovetails
with Pelphrey and Carters (2008) emphasis on the
importance of the development of connections among
brain regions involved in social cognition and the
development of the social brain; they hypothesize that
identifying the factors affecting connectivity could
lead to the prevention as well as treatment of ASD.
Finally, Gordon and colleagues, in an fMRI study
(2013), found that a single administration of intranasal
oxytocin led to enhanced activity in social brain circuits
involved in reward, social perception and cognition, as
well as reasoning about the mental states of others in
children with ASD. Because social stimuli seemed to
become more rewarding, these authors suggest that oxytocin may directly increase social motivation. Therefore,
oxytocin could help interrupt the developmental
cascade leading from decreased social motivation to
impaired social information processing and eventually
to ASD (Gordon et al., 2013).
Possible mechanisms of successful intervention
As this review has demonstrated, there now exists some
evidence that treatment can affect brain function in
ASD and that addressing stress and its allostatic consequences can also impact ASD through benecial
effects on connectivity.
99
Helt et al. (2008) provide a detailed hypothesis of

neuroplasticity and eight potential mechanisms for
recovery, the rst four of which are directly related to
overcoming environmental deprivation. They conclude
that effective programs involve the parents and assert
that competent behavioral therapy requires a highly
affective, emotionally positive set of interactions that
promote the reward value of social interactions and
more or less continuous social engagement, especially
in very young children (Helt et al., 2008, p. 350).
Their suggested mechanisms are summarized as follows:
(1) Normalizing input through forcing of attention.
Forcing a child to attend to social stimuli could
help overcome a decit in attention and/or
social motivation due to factors such as overwhelming arousal (Kinsbourne, 1987), sensory
overload, or other aversive reaction to social
engagement and, thereby, interrupt a growth-disturbing process of environmental deprivation.
(2) Promoting reinforcement value of social stimuli.
Helping the child have a positive emotional
reaction to people enables the child to overcome
some underlying difculty in the motivational
and emotional systems promoting social interaction (Dawson, 2008).
(3) Early intervention provides an enriched environment. If the environment experienced by the
ASD child is one of functional deprivation due
to neurobiological processes, the creation of an
enriched environment maybe a crucial component of successful intervention (Dawson, 2008).
(4) Effective intervention suppresses interfering
behaviors. Repetitive or self-stimulatory behavior interferes with connection to others and
results in the experience of environmental deprivation (Bodsh, 2011; Lewis, Tanimura, Lee, &
Bodsh, 2007). As the proposed functions of
repetitive behavior include arousal-reduction
(Kinsbourne, 1987) and avoidance of sensory
overload and stress, Helt and colleagues raise
the possibility that many deviant behaviors
in ASD could be considered attempts at compensation (p. 358). In line with my proposed
model, they conclude that understanding the
specic purposes of such behaviors could be
helpful in their suppression.
(5) Successful early intervention reduces stress and
stabilizes arousal. Kinsbourne (1987) proposed
that social interactions are avoided in ASD
because they are unpredictable and lead to overarousal, while attention to objects and routines
which are more predictable is less arousing.
Helt and colleagues, therefore, suggest that as
the ASD child grows, rather than turning to
100
W.M. Singletary
a nurturing social environment for soothing, he/

she may learn to self-regulate by engaging in
repetitive, self-stimulatory behaviors, thus
making him/her increasingly less available to
the outside world at the risk of being overwhelmed (Helt et al., 2008, p. 358; Lewis
et al., 2007). They further emphasize that
chronic stress during development may lead to
brain damage and interfere with the childs
using neural systems which are initially intact;
they conclude that normalizing the childs
arousal levels could be the critical mechanism underlying effective treatment (Helt
et al., 2008, p. 358).
(6) Early intervention provides intensive practice.
Because one of the primary factors in effective
early intervention is intensity (greater than 20
hours per week), early intervention in ASD
may be similar to Taub, Ramey, DeLuca, and
Echolss (2004) constraint-induced movement
therapy, in which intensive practice is needed
to promote neural development by forcing use
of a malfunctioning neural system which has
atrophied due to learned nonuse.
(7) Compensatory input. Recovery may be facilitated by helping the child learn certain pivotal
skills through alternate strategies that, rather
than facilitating recovery in malfunctioning
systems of the brain, would rely upon recruiting
new compensatory areas of the brain not generally used for such processes.
(8) Boosting recovery via biomedical treatment.
While biomedical interventions alone do not
lead to recovery, these may enhance the effectiveness of behavioral treatment. However, in
the future biomedical interventions may help
increase the possibility for recovery by reducing
the severity of the pathological biological processes that have been proposed here.
In conclusion, targeting the basic factors in the proposed model overcoming environmental deprivation
through increasing social and emotional engagement,
diminishing anxiety and psychological stress, along
with reducing allostatic overload seems to be of signicant value in facilitating therapeutic change in
ASD, likely by promoting adaptive neuroplasticity
(see Figure 3b).
Clinical material to illustrate these premises
Each [research] started from a different point and,
using different approaches, yields ndings which are
mutually explanatory. I have rst spoken of such convergences in a communication on Experimental
Design (1950b), and stated that in psychoanalysis

such a convergence can occupy the place which validation has in experimental psychology.
(Spitz, 1955; p. 215 in Tustin, 1990, p. 77)
Over 30 years ago, Kandel raised the possibility

that psychotherapy works through producing neuroplastic changes (1979). A few years later, Kandel
(1983) emphasized that experience modies the function of the brain through alteration of the strength of
synapses and regulating the expression of genes.
Most importantly, for our consideration of neuroplasticity in the treatment of ASD, Kandel suggested that
psychotherapy could involve the unlearning of anxiety
and lead to long-term structural and functional
changes in the brain resulting from altered genetic
expression.
In general, effective psychotherapy may be considered to represent a type of enriched environment
that stimulates or enhances adaptive neuroplasticity
(Cozolino, 2010) through neural network growth and
integration, epigenetic mechanisms (Kandel, 1983),
moderating levels of stress or states of arousal, affect
regulation, repairing attachment schemas, and the creation of a powerful healing relationship.
A neuroscience workshop sponsored by the
National Institutes of Health Blueprint for Neuroscience Research in 2009 led to the denition of neuroplasticity as the ability of the nervous system to
respond to intrinsic or extrinsic stimuli by reorganizing
its structure, function and connections (Cramer et al.,
2011, p. 1592). It is crucial to recognize that intrinsic
stimuli, for example, thoughts and feelings, have the
capacity to alter brain structure (including connectivity) and function. Thus, Cramer et al. (2011) consider cognitive training to be analogous to physical
therapy, involving the non-motor brain, and conclude
that the evidence suggests that as individuals learn to
modify their cognitive representations and behavioral
responses to distressing stimuli, widespread changes
occur in frontal cognitive control systems and in
limbic system activation (p. 1600). This same
process could be a crucial component of effective psychotherapy and psychoanalysis.
Helt et al.s (2008) central proposed mechanisms of
change described above social and emotional engagement, anxiety reduction, and repeated practice and
effort are compatible with therapeutic intervention
based on my model. Such treatment can help normalize environmental input in several ways. With the
younger child, direct involvement with parents in
dyadic treatment and helping the parents actively
engage their child are crucial (Greenspan & Wieder,
2006). This principle of active engagement (Settlage,
1992) also plays a critical role in childtherapist
Neuropsychoanalysis
interaction. In addition, talking and playing about the

childs inner world can be extremely helpful in normalizing the childparent relationship. For example,
helping the child face and adequately cope with fears
of connectedness, change and loss can be immensely
benecial in promoting adaptive engagement with
others. Such changes can help to reduce stress and
anxiety, which, in a virtuous circle, could lead not
only to more adaptive interactions with parents and
other caregivers, but also to positive neurobiological
changes, for example, decreased neuroinammation
and improved immune function (Herbert & Weintraub, 2012). Intensive treatment is critical in facilitating and continuing such major progress.
Understanding the inner experience of the child with

ASD
In addition to serving as a form of treatment, psychoanalysis can function as a research tool that provides a
unique and deeper understanding the inner world of
the child with ASD that could potentially be useful
to therapists and parents working with autistic children
in other methods of treatment. From this perspective,
one can understand that the childs maladaptive
responses to the experience of early life stress may
internally be experienced as essential to survival. In
fact, Teicher et al. (2003) have proposed that brain
and behavioral changes in response to early life stress
represent an alternative developmental pathway as
an adaptation to facilitate survival and reproduction
in a future world of deprivation and stress.
This adaptive and experiential perspective underscores the importance of addressing the childs inner
world and emotions as well as the biological and behavioral elements in ASD treatment. This approach
is similar to discussions concerning the need to supplement the allostatic overload perspective with considerations of the cognitive and psychological
adaptations to early life stress (Ellis & Giudice, 2013;
McEwen, 2012). Indeed, as I hope to illustrate with
the clinical material that follows, taking this perspective helps us to understand that often our therapeutic
efforts to help the child become more emotionally connected may be experienced as endangering attempts to
deprive him of an essential protection. This allows us
to tailor our interventions to be more useful to the
child over the long run.
Limitations and purpose of clinical material

Although my clinical experience leads me to believe
that psychoanalytic treatment can be helpful to
certain children with ASD, the purpose of including
101
this clinical material is certainly not to argue for the

efcacy of psychoanalytic treatment. A single case is
not sufcient for making denitive statements regarding treatment effectiveness (Kazdin, 1981). However,
this material could help to generate testable hypotheses
regarding not only the efcacy of psychoanalytic
understanding in psychotherapy with ASD children,
but also the potential usefulness of incorporating
such understanding in other forms of treatment.
Fundamentally, the primary purpose is to provide
clinical material that is typical of my experience
working with children with ASD and which illustrates
important aspects of the premises of this model. Such
hypothesis-generating material was most helpful to me
in developing this model. I found intriguing convergences among what I saw in treatment with these children, developmental theory, the ASD literature, and
neuroscience. This conuence helped me build
bridges among areas that could and had seemed to
be disconnected.
Inner world of the child with ASD

There are many different types of autism and certainly
no two children with ASD are exactly the same.
However, from working intensively with a small
number of children with ASD as well as from my
reading, fundamental correspondences in their inner
worlds appear to exist. Although it may not be apparent on the surface, in my experience, children in treatment, as well as a number of published accounts of
what autism is like, tell a remarkably similar storyliving with ASD is like living in an emotional prison.
For example (from the translators introduction to an
autobiographical account of autism):
The three characters used for the word autism in
Japanese signify self, shut and illness. My
imagination converts these characters into a prisoner
locked up and forgotten inside a solitary connement
cell waiting for someone, anyone, to realize he or she
is in there. (Mitchell, 2013, p. xvii introduction to
The reason I jump)
Moreover, these children recount the same story about

their emotional growth in treatment described as a
journey from feeling imprisoned and shut off from
love, at the outset of treatment, to emotional
freedom and a sense of ongoing, loving connections.
The complex emotions and meanings engendered
by the infants experience of emotional deprivation
and social isolation, despite the availability of love
and care, play a signicant part in obstructing adaptive
parentchild interaction and in the other ongoing
manifestations of ASD. Tronick and Beeghley (2011)
102 W.M. Singletary

underscore the importance of infant meaning-making
in developmental outcome. While made at a biopsychosocial level and nonsymbolic, these meanings do
shape ongoing parentchild interactions and, when
aberrant, can interfere with adaptive engagement
with others and can contribute to pathological outcomes (Tronick & Beeghley, 2011). Although
outcome studies are lacking, my own clinical experience, as well as that of others (Sherkow & Harrison,
with contributions by W. Singletary 2013), indicates
that psychotherapeutic interventions to deal with
these pathological meanings can be helpful to children
with ASD. Unfortunately, outside of psychoanalysis
little attention has been paid to the inner worlds of
children with ASD and how their internal experiences,
personal meanings, and intense feelings inuence their
current relationships and behavior. Bergman, a true
pioneer in the psychoanalytic treatment of children
with autism (in collaboration with Fahey, 1999), succinctly described such therapy as making sense out
of nonsense (A. Bergman, personal communication,
June 10, 2003). Working to emotionally engage the
child through play or other expressive activities such
as drawing, singing, and talking about childrens
stories or movies are the cornerstone of my work
with such children. With treatment aimed at understanding their inner experience, some children with
ASD are able to eloquently describe their emotional
lives and over the course of treatment become free to
enjoy loving relationships. Here I will focus on the
drawings of one child with whom I have worked,
which can help us make sense of the paradoxical, puzzling, often frustrating, and upside-down quality of the
autistic childs inner world, what he described as the
missing piece to the autism puzzle.
Larry began treatment with me when he was 7
years old. I saw him three times a week in individual
therapy for about one year, and then saw him twice
weekly for another four years, followed by intermittent
once weekly treatment. When he was younger, he had
manifested both echolalia and perseveration, clapped
and spun around when excited, repeated commercials
over and over, and had received the diagnosis of Aspergers Syndrome. Before I saw him, he had received
minimal intervention, aside from social skills training
and an individualized educational program that had
begun during his preschool years. Larry had shown
progress, but still had signicant problems that led
his pediatrician and his school district to refer him to
a local highly respected childrens hospital for consultation immediately before I rst saw him. At that
point he was said to be misinterpreting his peers intentions and was having more difculty with social interactions. He was still described as echolalic and
perseverative, especially regarding his interest in
computers, trains, and sh. He still clapped and spun

around when excited and repeated commercials. An
ADOS was not done. He was given a diagnosis of
mild Aspergers Syndrome.
When I rst saw him, Larry was difcult to engage,
and our rst interactions were dominated by showing
me his home videos of his trains and sh. I soon
learned of his extreme anxiety and many fears, including excessive concern that a tree in his yard was dead
and rotten and would fall over on his home. I concurred with the diagnosis of Aspergers Syndrome.
During treatment he showed rapid growth, and soon
at school he was considered to have lost the diagnosis
of ASD. As I hope to show, Larrys drawings clearly
relate to major components of my proposed model of
ASD, and also poignantly illustrate the therapeutic
factors
promoting
change
and
adaptive
neuroplasticity.
The crucial role played by the childs early and

ongoing experience of deprivation in ASD
This group of drawings illustrates how the child blocks
social and emotional engagement and helps create the
ongoing experience of deprivation.
My world has a wall to block sadness. Here Larry
places a monumental wall in his world to keep
sadness out a tting metaphor for autistic symptoms
(Figure 6). Often the controlling behavior or the retreat
into isolation is an attempt to avoid sadness and potential loss, a most painful feeling. In treatment, the therapist can try to talk about how it is important to feel
sadness because sadness is a large part of being a
person. Sometimes I describe the need to build
feeling muscles by facing the little sadnesses in life,
Figure 6. My world has a wall to block sadness.
Neuropsychoanalysis
such as all the goodbye times during the day like
leaving mother to go to school, stopping a favorite
activity to do something required, even going to bed
at night. All of these are opportunities to talk about
and learn to cope with feelings of sadness, vulnerability, and anxiety associated with growing up,
becoming a separate person, losing people we love,
and becoming aware of death.
People are waste in my world. Here we see Larry
throwing the loving and loved people in his world
into the trash (Figure 7). The boxes going into the
trash have his parents and sisters initials on them,
and my initials. The things that are going into the
grocery cart are trains, TVs, and trucks. People who
matter are discarded as trash. This devaluing of
loved and loving people serves as a defense against
the increasing fears of losing someone who is becoming more loved, needed, and valued. To be treated as
trash is often a sign that the child is actually caring
more for us. This knowledge can help parents and
therapists to not feel discouraged and to respond
helpfully.
I shred love in my world. This seems paradoxical at
rst, but understandable as we consider the ASD
childs point of view (Figure 8). Boxes containing
love are placed on a conveyor belt leading to a shredder. This leads to a world without love. It is crucial
to understand this attitude as a pathological protection
against the fears of losing someone who is loved and
valued, very much because quite often the best
efforts of therapists and parents seem to get torn up
or discarded.
We burn the things we need people, food, and love
but we worship stuff. Here Larry presents the same
theme in a different way (Figure 9). When the child
wants more and more things, we can understand that
it can feel easier to count on replaceable objects
rather than people who can leave or die.
Figure 7. People are waste in my world.
103
Figure 8. I shred love in my world.
The crucial role played by the experience of threat

related to early deprivation and the childs
maladaptive attempts to cope with extreme anxiety
Control or die. Larrys drawings chronicle the emotional roller-coaster and internal battles that were part of
his journey to break free of his debilitating imprisonment (Figure 10). This image conveys a clear
mandate control the world or die! In the inner
world this is no exaggeration. In my experience, children with ASD frequently are preoccupied with
impending death and disasters like the sinking of the
Titanic. Excessively controlling behavior hides
intense fear. We can recognize that the child seems to
be afraid, and try to gently help the child talk about
his fears. At some moments we can be playful, and
laugh and joke about how the child will not die if he
Figure 9. We burn the things we need.
104 W.M. Singletary

me is Larrys term for what he considers to be his
defensive self. As a result of treatment, Larry
comes to realize that through his self-protective but
unrealistic fears and attacks on people who help him,
his mind is actually tricking and imprisoning him.
His wall actually makes him miserable by depriving
him of what he needs the most love, people, and
emotional nourishment.
The process of maladaptive neuroplasticity
Figure 10. Control or die.
gives in to our request, or if he wears a different shirt

today or whatever he seems to be avoiding.
Developing self-control and giving up trying to
control the world is a terrifying process. So often,
right after a child has made some progress in developing self-control that old out-of-control behavior comes
back in full force. For example, a ve-year-old boy
with ASD and severely out-of-control behavior had
become better and better at controlling himself. At
that point he came into our session, started spinning
around and talking about dissolving. As we discussed
this behavior we came to understand that when he
gained self-control and gave up trying to control the
world, he believed that he would just dissolve or die.
This striking reaction is a clear example of the terror
of changing and giving up pathological protections.
When the little me tricks me. Here is Larrys depiction of the emotional prison that he created by blocking out love, people, and food (Figure 11). The little
As described earlier, the potential for a downward

spiral in brain structure and function, whereby neurobiological decits have psychological consequences
that interfere with the infants relationships, increase
psychological and biological stress, and negatively
impact subsequent brain development, has been
described by neurobiologist Michael Lewis as the
mechanism of cascading constraints, or may be
described as canalization. Early developmental
structures limit the characteristics of structures that
evolve later. Thus, maladaptive neuroplasticity
leading to pathological brain organization is a major
component of the developmental trajectory of ASD
(refer to Figure 3a).
The bad peeps stairs. It is fascinating that in this
drawing, 10-year-old Larry seems to depict this very
process (Figure 12). Peeps are a kind of candy (symbolizing love), and he calls this drawing the Bad Peep
Stairs. A child sees someone else with candy, wants
candy for himself, and feels upset that he does not
have any (notice the sad faces with downturned
mouths). Difculties with needing and depending on
others, and with accepting love and help, lead to a
repetitive and never-ending sense of disappointment
and deprivation. Shutting out the help offered by
caring people leads to a progressive downhill course
in life toward psychological imprisonment.
The process of adaptive neuroplasticity
Figure 11. When the little me tricks.
Understanding the inner experiences of autistic children fosters an upward spiral by helping them to
remove psychological obstructions, improve their
relationships, lessen psychological stress and allostatic
load, take in the love and help which parents and
others have to offer, be more open to all therapeutic
interventions and educational opportunities and, consequently, alter brain development in a positive way,
again through the mechanism of cascading constraints (refer to Figure 3b).
Improvement stairs. In this drawing, Larry illustrates this positive progression (Figure 13). This
drawing begins with an unhappy self at the bottom
Neuropsychoanalysis
105
Figure 12. The bad peeps stairs.
Figure 13. Improvement stairs.
who then spent more time with people, making

friends, helped a friend with a problem, stayed
out of my own world, was nice to my sister and
ends with the image of a happy self at the top. Effort,
making helpful choices, active emotional engagement
and caring for others lead to a happy self.
I x my mind. Larry considered this to be one of his

most important drawings (Figure 14). On the left,
Larrys mind is depicted as a tangled mess. However,
on the right Larry has a toolbox and is standing on a
ladder using his good mind to help x the confused
and confusing part of himself. Realistic hope and
motivation to make a real effort in treatment increase
as the child comes to realize that with the help of
The importance of active coping, practice, and effort

in treatment
To cope actively with terrifying fears is a choice that
requires courage. As Taub et al. (2004) suggest,
ongoing effort is necessary to overcome maladaptive
neuroplastic changes due to learned nonuse. I
took what nature gave me and I nurtured the heck
out of it, wrote Grandin and Panek (2013, p. 171).
Because of the positive changes that such effort
brings, children (and parents) learn that they are not
helpless, become more motivated to work hard in treatment, and develop a sense of a strong, competent self.
In addition, the feelings of success that come from
being a good tryer (Kaufman, 2014) help overcome
hopelessness and fear. Larrys drawing illustrates this
adaptive process.
Figure 14. I x my mind.
106 W.M. Singletary

others he can become empowered to help himself.
Again, he comes to develop a sense of a strong and
effective self.
LeDoux and Gorman (2001) have referred to this
mechanism of change in the treatment of post-traumatic anxiety as active coping. Based on experimental work with conditioned fear in rats, they suggest that
rather than helplessness, avoidance, and defensive passivity in the face of fear, making an active coping
response may reroute brain processing of the experience of threat. Passive responding to fear stimuli utilizes pathways through the amygdala to the
hypothalamus and brainstem involving defensive
freezing as well as autonomic and neuroendocrine
responses to fear. Active coping or responding to
fear-arousing stimuli is thought to alter the neural
pathways through the amygdala to the ventral striatum
and motor circuits allowing successful activity in the
face of threat.
The importance of increasing social and emotional

engagement in treatment
To help the child overcome his isolation and become
more engaged, parents and therapists have to actively
engage the child, as well as to try to make social interactions more rewarding. Engaging the child in
relationships, exercising the functions of the social
brain, and helping the child feel safe, all lead to progressive development both the brain and the capacity
for growth-promoting attachments. However, growth
will not be linear. One needs to understand, to
expect, and to tolerate the inevitable back-and-forth
movement from more openness and engagement to
moments of defensive retreat to familiar, protective
symptoms.
Love and the Hermit Crab. Larry had a hermit crab
hand puppet that he often brought to therapy
(Figure 15). We played about how the hermit crab
would go back into his shell after feeling more open
Figure 15. Love and the Hermit Crab.
Figure 16. You do not need things.
and connected and about how he was afraid of changing,

losing someone he loved, and dying himself. Here is his
paper construction of a hermit crab who goes into and
out of his shell toward and away from love.
You Do Not Need things. Again, over time Larry
comes to spend more and more time out of his shell
and comes to value love and people more than things
an inversion of his previous hierarchy (Figure 16).
Team 1 and Team 2. A greater sense of teamwork
of working together in treatment and in the parenting
relationship developed over time (Figure 17). Larry
said that in this drawing, he was showing how if you
work together you get somewhere, but if you try to
do it all alone, you get nowhere. This cleverly illustrates
the importance of reciprocal interactions.
Bridge. Emotional bridges connecting people
become more solid allowing food, people, and love
to be transported from one place to another as he
recognizes how his former monumental emotional
wall imprisoned him, shutting out whats needed
most in life (Figure 18).
Figure 17. Team 1 and Team 2.
Neuropsychoanalysis
Figure 18. Bridge.
Indeed, Morelli, Torre, and Eisenberger (2014)

found in an fMRI study that feeling understood activates areas of the brain associated with social connection and reward and is related to greater feelings of
interpersonal closeness. This demonstrates one possible pathway through which understanding the child
with ASD can lead to adaptive changes both in
social interactions which are experienced as more
rewarding as well as in the functioning of the social
brain, as has been found with PRT (Voos et al.,
2012) and treatment with oxytocin (Gordon et al.,
2013).
The importance of decreasing the childs anxiety

through treatment
Eisenberger and colleagues (Morelli et al., 2014) found
that not feeling understood was associated with
activity in brain regions related to social pain and
negative affect, resulting in feelings of social distance.
They further suggest that individuals may avoid
social interactions in which the social pain of feeling
not understood is anticipated, just as one avoids
threat and physical pain (Lieberman & Eisenberger,
2008). In addition, feeling understood and not
feeling understood were found to activate different
brain regions involved in mentalization (Morelli
et al., 2014). Moreover, social stress has been found
to impair certain components of empathy (Martin
et al., 2015). Again, this underscores the importance
of helping parents and caregivers understand the
inner world of the child with ASD. The experience of
feeling understood could help the ASD child feel less
anxiety and stress about the potential pain of social
interactions. The experience of more accurate social
information processing and improved social cognition
107
and theory of mind, along with more rewarding social

connections, should help the child with ASD gradually
develop the capacity to activate the calm and connection system (which is associated with increased oxytocin) (Uvns-Moberg, Arn, & Magnusson, 2005)
simply through thoughts of positive experience. Thus,
the repeated experience of playful interactions with
parents and others and the associated increase in oxytocin levels as was found by Feldman (Singer, 2012)
could possibly lead to the child developing the capacity
to use the thoughts of loved ones to increase oxytocin
levels, perhaps the biological counterpart of what
Mahler referred to as object constancy.
A lunch box for love is one metaphor that I use in
treatment to refer to object constancy. Helping the
child develop the capacity to maintain the sense of
having loving, comforting, calming, and protective
parents inside, despite absence or disappointment, is
a major goal of treatment. The child becomes able to
use thoughts of the parents to feel safe. I talk to the
child about how he can keep loving parents in his
heart so that he can always have their comforting
love with him. We do not need to have parents physically present in order to feel safe. However, in order
to do this, the child has to realize that the parent
who is absent is not abandoning him. Instead of
hating and rejecting his absent or disappointing
parents, he can miss them or experienced disappointment and feel sadness again consistent with
Mahlers denition of object constancy. He needs to
be able to face sad feelings and not resort to the protection of feeling mad. But this requires choice and effort.
Larry beautifully discussed this struggle and emphasized the importance of being able to experience
sadness instead becoming mad. In one session he
wrote about the choice between sad or mad:
This part is very important its about your attitude.
Like when you have to say goodbye to someone you
love. Normal people get sad but with kids with
autism that is a different story. They get mad and
think that its the people whos leavings fault.
You may think love is leaving you, but its not.

During a family meeting after about four years of treatment, Larry moved to hug his mother, then drew back
(Figure 19). After moving toward her and backing off
several times, Larry nally embraced her. Immediately
he began sobbing, and eventually he was able to
exclaim through his tears, I nally get it! I nally get it!
I nally get it! Im not going to die if I love someone!
It is so paradoxical that feeling loving and loved can be
experienced as so threatening to the child with ASD. To
choose to face this terror and give up the protective
shell requires great courage. Larry illustrates this powerful
108 W.M. Singletary

Organizing framework for new ndings
Figure 19. You may think Love is leaving you, but its not.
choice in this drawing that reads You may think Love is

leaving you but its not. Its in your heart 24/7/365.
Conclusion
All of the systems of the brain are organized and work
together with one overarching purposesurvival.
(Perry et al., 1995, p. 273; Goldstein, 1995)
To briey restate the proposed model, ASD may

result when a genetically vulnerable fetus or infant
experiences biological stress (allostatic overload) that
leads to the postnatal experience of environmental
deprivation and psychological stress. Subsequently,
diminishing social connectedness and increasing
anxiety interact in a nonlinear way with allostatic overload and the developing brain, leading to progressive
disruption of development. Conceivably, both genetic
and other neurobiological factors, along with the
earlier experience of biological stress and felt environmental deprivation, are what differentiates the infant
who develops ASD from the infant who develops an
attachment disorder in response to actual environmental deprivation in an orphanage.
Advantages of proposed model

In the previous sections of this paper, I have argued
and presented evidence that this new model can: (a)
parsimoniously accommodate and organize most
existing theories of ASD, (b) describe the pathway(s)
of progression to ASD syndrome and the paths
involved in the effective treatment of ASD, as well as
(c) account for the symptoms of ASD, associated conditions such as anxiety and health problems, and the
individuals experience of ASD (see Figure 20).
I will now illustrate how this model can accommodate

and provide an organizing framework for what might
on the surface appear to be a quite divergent and
bewildering array of recent ndings:
(1) Alteration of self-representation
Based on an fMRI study, Just, Cherkassky, Buchweitz, Keller, and Mitchell (2014) concluded that in contrast to heterogeneity in autism, one consistent nding is
that in neural representations of social interactions the
representation of self is largely absent (p. 11). Furthermore, the degree of alteration of self-representation is
correlated both with the quality of brain connectivity
and with behavior. Understanding how the sense of self
(Mahler, 1968) as well as the organization of the brain
(Schore, 2014) develops in the context of early relationships, provides a clear link between two elements of
this model, neurobiological factors and the experience
of environmental deprivation.
(2) Impairment of emotional regulation
A body of recent work has focused on the quite
common symptom of anxiety and on impairments in
emotion regulation in ASD (White et al, 2014). Multiple neural, physiological, social, and cognitive mechanisms are considered to play a role in emotional
regulation impairments in ASD (Richey et al., 2015;
White et al., 2014). In addition, emotional regulation
is considered to be a likely parsimonious target for
effective treatment (White et al., 2014). The proposed
model, which includes neurobiological factors as well
as psychological and biological stress, can certainly
accommodate the ndings regarding dysfunctional
emotional regulation in ASD. In fact, McEwen
(Wachs, Georgieff, Cusick, & McEwen, 2014) has
stated that stress alters brain architecture so that
regions involved in self-regulation are weakened
while those important for anxiety are strengthened.
(3) Environmental toxins
New studies report that exposure to environmental
toxins, such as trafc-related air pollution (Volk,
Lurmann, Penfold, Hertz-Picciotto, & Mcconnell,
2013) as well as agricultural pesticides (Shelton et al.,
2014) during pregnancy is associated with autism. The
links between exposure to environmental toxins and
autism may be simply incorporated into this model
through the process of allostatic overload. As noted
earlier, McEwen and Tucker (2011) suggest that allostatic overload may interact with chemical exposures
to increase the risk of adverse health outcomes.
(4) Effective treatment with broccoli sprouts extract
In a controlled study, Singh et al. (2014) found that
an extract from broccoli sprouts, sulforaphane, signicantly and reversibly improved core clinical features of
the ASD, social interaction, verbal communication,
Neuropsychoanalysis
109
Figure 20. The Emotional and Allostatic Overload Model of ASD offers numerous advantages in understanding and treating
ASD. The integrative and inclusive aspects of this model could hopefully promote greater collaboration in the eld of autism.
and abnormal behavior in teenagers and young men

with ASD. The fact that sulforaphane was selected
because of its capacity to reverse components of the
process of allostatic overload, for example, inammation and oxidative stress, provides a direct link to
this model.
(5) Increased incidence of bone fractures
Neumeyer et al. (2014) found an increased incidence of bone fractures in children and adults with
ASD. Although other factors may contribute to
this increased risk of bone fractures, the relationship
among adverse childhood experiences, chronic stress
and allostatic overload, and health outcomes, including an increased incidence of skeletal fractures
(Felitti et al., 1998; Felitti & Anda, 2010) provides
a direct connection to the proposed model. The
experience of environmental deprivation as well as
psychological stress and allostatic overload may all
be important factors and could play a signicant
role in a number of the health problems associated
with ASD.
The small number of studies cited above represents
only a limited sample of the wide range of ndings that
could have been mentioned. An easily understood,
integrative, and inclusive model should help promote
collaboration and cooperation in research rather
than competition and isolation since new evidence
and theories are seen as converging and complementary rather than divergent and mutually exclusive.
Treatment
As mentioned earlier, this integrative model provides
an organizing framework which can help bring
together a range of psychosocial and medical treatments and, through adaptive neuroplasticity, make
sure that someone with a very complicated problem
that involves not just one but multiple circuits and networks of networks in the brain has the greatest
opportunity to recover (Insel, 2014, p. 2). Rather
than autism-specic treatments, more generic interventions available now may be particularly useful (Herbert
& Weintraub, 2012) as well as of low toxicity, for
example, broccoli extract (Singh et al., 2014). Effective
treatment and prevention measures for some children
need not wait for the discovery of the ultimate causes
of ASD. Examples of such nonspecic interventions
for other populations that may have some applicability
to the treatment of autism are presented below.
First, McEwen and colleagues (Wachs et al., 2014)
have highlighted the importance of considering both
psychosocial stress and allostatic load in designing
early intervention programs for children exposed to
multiple developmental risks. Furthermore, Davidson
and McEwen (2012) emphasize that interventions
designed to promote prosocial behavior and to
decrease stress can impact brain function and structure, that is, increase prefrontal cortex activation and
volume and decrease amygdala activation and
volume. Davidson and McEwen also suggest that
110 W.M. Singletary

such early interventions could enhance self-regulation
and self-control in children, which, as noted above,
are now being recognized as important targets for
treatment in ASD.
Next, recent research by Bredesden (2014) involving a novel therapeutic program for Alzheimers
disease (AD) as well as cognitive impairment could
serve as a useful model for the treatment of ASD. In
fact, the thoughts expressed by Insel quoted above resonate with the hypothesis guiding the design of this
system of interventions:
Based on the hypothesis that AD results from an imbalance in an extensive plasticity network, the therapy
should address as many of the network components as
possible, with the idea that a combination may create
an effect that is more than the sum of the effects of
many monotherapeutics. (Bredesen, 2014, p. 709)
Interventions were individualized and included such

components as diet, exercise, and stress reduction, as
well as vitamins, and supplements targeting such
factors as inammation, mitochondrial function, and
oxidative stress. While this was a small study involving
only 10 patients, the results were impressive. Nine
patients showed objective or subjective improvement
in cognitive functioning. Most importantly, all of the
six patients whose work performance had been signicantly impaired by their cognitive decline were able to
either return to work or continue working with no
further difculty. While these ndings need replication
in a larger study, the implication is that comprehensive
intervention programs can have a signicant benet on
neurobiological disorders and could offer substantial
help to some children with ASD. A comparable intervention designed for autism that incorporates the components of the new model presented here seems worthy
of investigation.
Concluding remarks
ASD is an urgent social and mental health problem
with enormous economic and human costs. Often considered to be a relatively xed, genetic disorder, recent
research has demonstrated the possibility of signicant
change and adaptive neuroplasticity in ASD. This
remarkable development has led to much realistic
hope regarding the potential success of early intervention and perhaps even prevention of ASD for a signicant number of children. With so much at stake, the
fragmentation in research and treatment that has
been commonplace in the eld becomes itself, in
turn, an urgent scientic problem. However, the complexity of autism need not be a barrier that impedes
collaboration, cooperation and progress in the eld.
My goal here has been to bring a fresh perspective
and to develop a unifying and cohesive working

model of ASD to help the eld overcome divisions
and move forward. In highlighting the social pain
and traumatic stress accompanying the deprivation
of human connections, the Emotional and Allostatic
Overload Model provides potentially unifying and
organizing targets for research and treatment.
Bringing together my clinical experience and recent
research in the eld of autism reveals that, at least for
some children on the higher end of the autism spectrum, recovery is made more likely by increasing the
sense of connection and decreasing the experience of
stress. This may well apply to children farther along
the spectrum. Understanding the childs inner world
of experience could be included in, and perhaps facilitate, more standard and empirically supported interventions directed toward the provision of an enriched
environment and the development of social connections. This hypothesis can and should be tested. The
autism eld could benet from the wisdom Larry
expressed in his drawing: You need a team to go
somewhere. No team will get you nowhere. Working
together, clinicians and researchers can potentially
afford many more children with ASD the opportunity
to have a journey from social isolation to human
connections.
Acknowledgments
The author wishes to thank Larry and his parents for
their major contributions to this article through allowing me to discuss Larrys treatment and to use his
invaluable drawings. In addition, over many years
Anni Bergman has been a source of inspiration,
wisdom, and support guiding my work with children
with autism. Susan Coates provided astute comments
on several versions of this article. Also, an anonymous
reviewer provided most helpful feedback. Finally, the
author wants to thank Lyle Berman of Ground
Control for his graphic design and technical support.
Disclosure statement
No potential conict of interest was reported by the author.
Notes
1.
2.
See Singletary (2013) for a more comprehensive

overview.
Unfortunately, a detailed consideration of the substantial
literature linking neuroinammation, immune function,
as well as mitochondrial function and oxidative stress to
ASD is beyond the scope of this paper. For some coverage
of the topic (see Estes & McAllister, 2015; Herbert, 2013;
James, 2008; Pardo-Villamizar, 2008).
Neuropsychoanalysis
3.
I regret that due to limitations in space I am unable to

provide an adequate account of the development of
the concept of the mirror neuron system and its functions but the interested reader may refer to Rizzolatti
and Sinigaglia (2006).
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Date: 03 May 2016, At: 13:06

An integrative model of autism spectrum disorder: ASD as a neurobiological disorder of

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(Received 1 February 2015; accepted 25 August 2015)

The important thing in science is not so much to

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per individual (Ganz, 2007) with a US national cost of

The heterogeneity and complexity of ASD have

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experience, which one young boy whose treatment

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altered pattern of childcaregiver interactions deprives

The proposed model of ASD

Neurobiological factors lead to the experience of

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experience of early social deprivation. For example,

Early disruption of the development of the social

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in social motivation that leads to decreased attention

social perception, and ve others, who had signicantly

The experience of environmental deprivation leads to

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The interaction between deprivation and allostatic

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Figure 4. The same factors that interact to produce allostatic

uid. Since then the role of the immune system and

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Genetic and epigenetic mechanisms

regions necessary to develop joint attention in early

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exposure to hurricanes and tropical storms, has been

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& McEwen, 2012; McEwen, 2006) and that this

Neuromodulators and neurotransmitters

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(Gregory et al., 2009; Jacob et al, 2007; Lerer et al.,

Neural networks, connectivity, and sensory

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Early deprivation, traumatic psychological stress and

neuroplasticity. According to Hebbs Law (Hebb,

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respond aversively to subjective experience, for

As noted above, in this model, stress from all

The symptoms of ASD

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Figure 5. Symptoms of ASD, such as social isolation and

Constructive outlets for frustration such as fantasy

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Finally, Porgess body of work regarding polyvagal

source) leads to decreased tone in the muscles of the

The individuals experience of ASD

I believe Williams is describing here the subjective

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