RESEARCH ARTICLE

The Potential Role for Emergence in Autism

George M. Anderson

Although most research on autistic behavior has considered autism categorically, the increasingly apparent genetic and
phenotypic complexities of autism are prompting a more dimensional approach to this area. The long-standing interest
in a less categorical approach is made clear from a review of literature. The accumulating empirical support for viewing
autism-related phenomena as separable and fractionable is outlined and includes data indicating that many of the
behaviors occur in isolation in family members and the general population, are not highly correlated within individuals,
and appear to be inherited separately. However, it is emphasized that some of the most common and characteristic
phenomena observed in individuals diagnosed with autism do not run in their families. It is suggested that these novel,
‘‘emergent,’’ phenomena may arise in the individual from interacting configurations of co-occurring traits or from the
interaction of genetic and biological factors underlying the traits. A number of autism-related phenomena including
intellectual disability, seizures, persistence of primitive reflexes, stereotypies, self-injurious behavior, savant abilities, and
morphological abnormalities, among others, are discussed as potentially being emergent. It is concluded that
consideration of the role of emergence in autistic behavior and related phenomena should complement a reductionist
approach and might help illuminate the components and complexities of autism.

Keywords: autism; emergence; emergent; dimensional; fractionable; intellectual disability; epilepsy

Introduction Steffenburg et al., 1989]. The family genetic data and

Most research on autistic behavior has considered autism
categorically, but the increasingly apparent genetic and
phenotypic complexities are prompting a more dimen-
sional approach. There is accumulating empirical support
for viewing autism-related behaviors as separable and
fractionable and often occurring in isolation in family
members and the general population. Dissection of
components in autism, as in other areas of neuropsy-
chiatry, appears to offer a fruitful simplifying approach.
On the other hand, some of the most common and
characteristic phenomena observed in individuals diag-
nosed with autism do not run in their families. These
novel, ‘‘emergent,’’ phenomena may arise in the indivi-
dual from interacting co-occurring traits or from the
interaction of underlying genetic and biological factors.
Consideration of the role of emergence in autistic
behavior and related phenomena should complement a
reductionist approach and help illuminate the compo-
nents and complexities of autism.
genome-wide screening studies indicate that the genetics
are complex. In most cases, it appears that multiple genetic
factors are involved, with each likely contributing only a
small amount of risk. There is also good evidence that
autism is genetically heterogeneous, with differing sets of
risk alleles combining in different groups of affected
individuals [Cook, 2001; Folstein and Rosen-Sheidley,
2001; Lauritsen and Ewald, 2001; Risch et al., 1999;
Santangelo and Tsatsanis, 2005; The Autism Genome
Project Consortium, 2007; Veenstra-Vanderweele, Christian
and Cook, 2004]. This apparent polygenetic and hetero-
genetic nature of autism, the possible role of epigenetic
factors and de novo mutations [Gottesman and Hanson,
2005; Jiang et al., 2004; Schanen, 2006; Sebat et al., 2007],
as well as the unclear role of environmental influences on
expression [Herbert et al., 2006], make an elucidation of the
genetic basis of autism extremely challenging.
Dimensional Perspectives on Autism

Although most of the genetic and neurobiological research

Complex Genetics of Autism
Twin and family studies have provided convincing evi-
dence that autism is largely genetically determined [Bailey
et al., 1995; Bolton et al., 1994; Folstein and Rutter, 1977;
has approached autistic behaviors categorically, there has
been a long-standing and ongoing consideration of whether
it is best to consider autism and related behaviors from a
categorical or from a component/dimensional perspective.
Over the years, a number of researchers have suggested that

From the Child Study Center, Yale University School of Medicine, 230 South Frontage Rd., New Haven, Connecticut (G.M.A)
Received September 20, 2007; revised December 22, 2007; accepted for publication January 6, 2008
Address for correspondence and reprints: Child Study Center, Yale University School of Medicine, 230 South Frontage Rd., New Haven, CT, USA.
E-mail: george.anderson@yale.edu
Grant sponsors: Korczak Foundation for Autism Research; Gettner Autism Research Fund
Published online in Wiley InterScience (www.interscience.wiley.com)
DOI: 10.1002/aur.2
& 2008 International Society for Autism Research, Wiley Periodicals, Inc.

18 Autism Research 1: 18–30, 2008 INSAR

autism may be better understood by examining the
component behavioral and cognitive abnormalities of
autism [Adrien et al., 2001; Beglinger and Smith, 2001;
Bolte and Poustka, 2001; Coon, 2006; Dawson et al., 2002;
Goodman, 1989; Gupta and State, 2007; Hollander et al.,
1998; Klin et al., 2000; Kolevzon et al., 2004; Lund and
Jensen, 1989; McBride et al., 1996; Myhr, 1998; Piven, 2001;
Silverman et al., 2002; Skuse et al., 2004; South et al., 2005;
Sung et al., 2005; Szatmari et al., 2002; Tanguay, 1999;
Viding and Blakemore, 2007; Williams, 2006; Wing, 2005;
Wing and Wing, 1971]. As early as 1971, Wing and Wing
[1971] stated that the ‘‘multiple impairments (of autism)
can vary in severity and y can occur independently in
various childhood conditions.’’ In the last 20 years, more
and more support has been voiced for the dimensional
approach. In 1989, Goodman [1989] posed the question:
‘‘Infantile autism: a syndrome of multiple primary deficits?’’
McBride et al. [1996] also argued for a more dimen-
sional approach, saying ‘‘y the components can be
considered individually’’ and adding that ‘‘Progress will
come from careful description and metrification, and
from thorough consideration of the interactions between
domains.’’ Similar sentiments were voiced by Hollander
et al. [1998], who hypothesized in 1998 ‘‘y that specific
genes may be linked to specific behavioral dimensions,’’
and by Folstein and Rosen-Sheidley [2001] who suggested
that ‘‘y several genes that may interact to cause autism
which segregate independently and have distinguishable
manifestations in family members.’’
The dimensional and component approach has con-
tinued to garner support in the past 5 years with
Silverman et al. [2002] concluding that ‘‘y the familiality
of these features (autism-related phenomena) extend to
related conditions of milder severity than autism and
appear to be independent,’’ and with Sung et al. [2005]
pointing out that, ‘‘If several y quantitative traits in
multiple domains lead to diagnosis of a disease, affecta-
tion status contains less information than the values of
the y .quantitative traits.’’ Recently, Gupta and State
[2007] stated that ‘‘If autism is not a single entity but a
collection of overlapping phenotypes resulting from the
combined action of multiple risk alleles, it appears logical
that an approach that parses the clinical presentation
into biologically relevant components might be more
powerful than one that relies on categorical diagnoses.’’
The quotes largely speak for themselves and reflect a
growing dissatisfaction with the rate of progress in
explicating underlying biology and causative factors.
Accumulating Evidence for Fractionable
Components
In their 2006 review, Happé et al. [2006] presented a
compelling case that the behaviors that define the autism
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spectrum disorders should be considered from a compo-
nent perspective and used the term ‘‘fractionable’’ to
emphasize this point. They pointed to accumulating
evidence, much from their own research, supporting the
idea that alterations in the separate defining domains of
social relatedness, language/communication, and re-
stricted interest/repetitive behavior are separable and
suggested that genetic and behavioral approaches that
consider autism as an entity or unitary phenomenon may
be inefficient and counterproductive. Evidence mar-
shaled in support of the separable or fractionable
approach includes the smooth continua of severity seen
for domain traits [Constantino and Todd, 2003; Spiker
et al., 2002], the occurrence of autism-related traits in
isolation in family members and the general population
[Bolton et al., 1998; Murphy et al., 2000; Ronald et al.,
2006a,b], the modest within-individual correlations seen
for the different domains [Ronald et al., 2006a,b], the
different developmental trajectories seen across domains
[Charman et al., 2003, 2005; Lord and Pickles, 1996], and
the apparent independent heritability of relevant traits
[Ronald et al., 2005, 2006a,b].
Despite long-standing interest in the dimensional ap-
proach to autism, it should be noted that hard evidence
supporting the fractionable nature of domain alterations is
relatively limited and further large studies of relevant traits
in family members are needed [Gousse et al., 2002; Micali et
al., 2004]. The complicated nature of each domain has been
largely ignored and it is not clear how a more nuanced view
of each domain will affect the results. For instance, in the
social interaction domain, social motivation, social reward,
social aversion/phobia, joint attention, and face recogni-
tion—among other related aspects of social behavior—may
need to be dissected. Factors related to the restricted
interests and repetitive behavior domain may include
anxiety, obsessionality, rigidity, impulsivity, sensory ab-
normalities, and stereotypic and perseverative behavior.
The language/communication domain may be parsed into
auditory processing deficits, general delay, prosody, specific
language impairments, echolalia, and aphasia. Despite
these caveats, it can be suggested that a more fine-grained
approach would likely provide even greater support for the
fractionable perspective. It should also be pointed out that
autism-related phenomena are not necessarily impairments
or deficits, with strengths in aspects of language function,
sensory processing, and memory often present in indivi-
duals on the autism spectrum.
In general, support for a more dimensional and
‘‘phenomic’’ [Freimer and Sabatti, 2003] approach to
behavior, cognition and emotion is gaining strength in
neuropsychiatry [Barrett and Lindquist, 2008; Gottesman
and Gould, 2003; Leboyer et al., 1998; McGuffin et al.,
2001; van Praag, 2000]. A component trait or endophe-
notype approach appears to offer advantages in terms of
metrification and from an individualistic, descriptive,
19
and idiographic standpoint [IGDA Workgroup, 2003;
Meehl, 1979; Mezzich, 2002; Phillips, 2005]. The increas-
ing use of the term endophenotype is a reflection of this
shift, although the term has been used to refer both to
traits underlying behavioral phenotypes as well as to
more finely dissected observable behavioral traits. Strong
arguments have been made for the dimensional approach
across a range of behaviors, and the accumulating
evidence from behavioral and family genetic studies is
difficult to dismiss. It remains to be seen how this will
play out in psychiatry and in the upcoming revision
of the Diagnostic and Statistic Manual-IV [DSM-IV;
Rounsaville et al., 2002; Trull et al., 2007; Widiger and
Samuel, 2005].
In autism research, it can be expected that increasingly
research will be carried out in a manner that at least
considers the separate, perhaps fractionable, domains of
behavior. A number of recent genetic and neurobiological
studies of autism have taken this approach [Alarcon et al.,
2005; Buxbaum et al., 2004; Coon et al., 2005; Duvall
et al., 2007; Ma et al., 2005; Mulder et al., 2005;
Shao et al., 2003; Sutcliffe et al., 2005; Tordjman
et al., 2001; Weiss et al., 2006], and varied efforts
are directed toward the development of measures of
specific domain or component traits [e.g., Klin et al.,
2003; Ozonoff et al., 2004; Sung et al., 2005].
As recommended by many and convincingly argued by
Happé et al. [2006], most autism-related phenomena may
best be assessed and studied separately, and autism
genetics might most fruitfully examine specific aspects/
impairments. Even with a more dimensional approach,
connecting genes to behavior and cognition will remain
difficult, as illustrated by Fisher [2006] for the areas of
language and dyslexia.
Interactions of the Fractionable Components
The potential separability of autism-related traits may
provide especially fruitful reductionist routes to research
on autism. Although the causes may be manifold, they
should be more easily parsed and approached on a
component basis. Furthermore, it can be suggested that
many of the causative factors that are operating in
autistic individuals are also probably playing a role in
social, communicative, and repetitive behavior in family
members, and in the general population. In this way,
research on autism-related behavioral components
should be increasingly relevant to a broad range of
behaviors and a substantial segment of the population.
However, at the same time as components are con-
sidered in isolation, it must be taken into account that
some of the most distinctive, critical, intriguing, and
perplexing aspects of autism might arise from an interac-
tion of the domain phenomena, or of the factors under-
lying these varied, more familial, domain alterations. It is
20 Anderson/The potential role for emergence in autism
this contention and its implications that will be con-
sidered in the following sections.
The possible interactions can be grouped into three
types: the simple additive, the multiplicative, and the
emergent. It is clear that abnormalities can add together
across domains to produce greater overall severity.
Abnormalities in one domain can also contribute to
and amplify abnormalities in another in a multiplicative
manner. These additive and multiplicative interactions
appear to play a large role in the clinical presentation
and day-to-day life of many individuals with autistic
behavior. However, it is the emergent phenomena arising
from the interaction of component factors and behaviors
that deserve greater attention. Here, a relatively stringent
definition of ‘‘emergent’’ is employed, with the word
used to refer to phenomena that are novel, that differ in
type and quality from the interacting components. Thus,
the term is used here to refer to a situation where the
phenomenon or the whole is not merely greater than
the sum of the interacting parts but something substan-
tially different. Emergent phenomena can be beneficial
(e.g., consciousness emerging from neuronal activity) or
detrimental (e.g., cardiovascular disease emerging from
physiological traits).
Concept of Emergence
The concept of emergence can be traced to Aristotle’s
Metaphysics, and the term itself was used by pioneer
psychologist G.H. Lewes in 1874 to refer to ‘‘qualitative
novelty’’. Late Victorian theorists dealt with emergence in
the context of evolution and biological complexity.
Proponents of emergent evolutionism in the 1920s
included C. Lloyd Morgan and Alfred North Whitehead.
For several decades, Gestalt psychologists, ecologists, and
evolutionary biologists were most concerned with emer-
gence. In the 1950s there was a resurgence of emergence
with the development of general systems theory and
increased study of complexity [Blitz, 1992; Corning, 2002;
Goldstein, 1999]. From the mid-1960s onward, the
psychobiologist Roger Sperry was a proponent of emer-
gence and the related concept of downward causation in
neuroscience [Sperry, 1980]. In 1970, James Conway
developed the Game of Life: based on cellular automata,
the simple programs displayed intriguing novel phenom-
ena, including self-assembly and movement [so-called
gliders; Anonymous, 2007]. In the early 1980s, the Sante
Fe Institute was formed to investigate complex phenom-
ena across disciplines including physics, chemistry, biol-
ogy, neuroscience, and economics [Waldrop, 1992].
In the last 20 years, fundamental work has been carried
out by Kauffman [1995], Holland [1998], Arthur [1990],
and Wolfram [2002], among many others. The cited
scientists have often helped popularize complexity
science [Arthur, 1990; Holland, 1998; Kauffman, 1995;
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Wolfram, 2002] and its underlying concept of emergence
[Bunge, 2003; Kim, 2006]. There are now journals
devoted to the area (Transdisciplinary Journal of Emergence;
Emergence: Complexity and Organization; Molecular Systems
Biology; and IET Systems Biology) and a number of
institutes dedicated to the study of complexity (e.g.,
The Center for the Study of Complex Systems at the
University of Michigan, New England Complex Systems
Institute, the Plexus Institute, Center for Complexity
Science—Jerusalem). It has now been clearly demon-
strated that various sorts of complex behavior can arise
from simple systems such as cellular automata and neural
networks, and that this fact has wide-ranging implica-
tions and applications. The idea that simple programs
can model and apparently underlie complex physical and
biological systems has been thoroughly presented by
Wolfram [2002]. An increasing appreciation of the fact
that most genes in the human genome serve to control
other genes in one large reciprocal network [The
ENCODE Project Consortium, 2007] strengthens the
view that life-forms are complex adaptive systems and
that their morphology, physiology, and behavior are
emergent phenomena. Systems biology is focused on
comprehending how system properties ‘‘emerge’’ at and
across the levels of the gene, transcriptome, proteome,
metabolome, cell, tissue, and organism [Sauer et al.,
2007; Tegner and Bjorkegren, 2007].
A number of researchers have promoted the value of
viewing psychiatric problems and mental disorders in the
context of complexity science [Merikangas et al., 2006;
Stewart, 1992]. The concept of emergence is implicit in
much of the thinking about how behavioral styles and
patterns of cognition arise from the non-linear interaction
of underlying factors ranging from the molecular, anato-
mical, and symptom levels. Applications of complexity
science to personality theory [Mandell and Selz, 1995],
anti-social behavior [Warren and Knox, 2000], depression
[Garcia-Toro and Aguirre, 2007], schizophrenia [Bender
et al., 2006; Globus and Arpaia, 1994; Paulus and Braff,
2003], and dyslexia [Fisher, 2006] have appeared. In Down
syndrome, Fidler [2006] has posited the emergence of a
personality-motivation profile from cross-domain interac-
tions of more primary aspects. The complex systems
approach facilitates an examination of how abnormal
behaviors and mental states might arise from the non-
linear dynamic interaction of relevant factors. More
generally, the utility of a complex systems or systemism
approach to pathobiology and disease classification is
being championed [Bunge, 2003; Loscalzo et al., 2007].
Emergence in Behavioral Genetics
The term ‘‘emergenesis’’ was introduced to the field of
behavioral genetics in 1981 by David T. Lykken. As
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reviewed by Li [1987], emergenesis was used by Lykken to
refer to ‘‘y a polygenic mechanism that involves an
extreme type of gene interaction. An emergenic trait is
one that is determined by a particular combination of
genes of a number of loci, thus forming a gene
‘configuration’ or gene constellation. When any one
gene is absent, it destroys the configuration and the
emergenic trait disappears’’. The critical nature of each
component in a configuration and the often isolated
nature of the phenotype were emphasized. The pattern of
emergenic inheritance was considered to be quite
different from the single-locus inheritance pattern ob-
served in many genetic diseases and from the typical
polygenetic inheritance of quantitative traits that are
determined by additive effects of multiple loci.
When recently reviewing the area, Lykken [2006]
defined emergenic (adj) as ‘‘Arising as a novel or
emergent property resulting from the interaction of more
elementary and partly genetic properties. An emergenic
trait may be determined by a configuration of indepen-
dently segregating polygenes interacting in a multi-
plicative rather than an additive fashion y.’’ Lykken
went on to say that ‘‘A growing number of metrical
traits—especially psychological traits such as neuroti-
cism, aggressiveness, impulsiveness, positive emotional-
ity, artistic interests—appear to be determined in part by
configurations of genes, or of partly genetic traits, which
combine multiplicatively rather than additively. This
mechanism y results in high monozygotic (MZ) but low
or zero dizygotic (DZ) correlations.’’ As examples, he
mentioned the isolated mathematical genius of Gauss
and an unpublished study of University of Minnesota
students. Students majoring in music had more musically
talented first-degree relatives than did non-music majors,
but those majoring in voice did not have more vocalists
in their families, suggesting that vocal talent depended
upon a constellation of traits including musical ability,
oral morphology, larynx and pulmonary attributes as
well as stage presence and memory skills. In addition to
behavioral traits of interest, electrophysiological re-
sponses and some social attitudes, such as authoritarian-
ism, have been shown to be not only strongly heritable
but also apparently emergenic, with MZ twins having
very much higher correlations than DZ twins [Lykken
et al., 1988; McCourt et al., 1999].
Emergence in Autism
It is the critical notion of configurality leading to
emergence that appears most compelling in the context
of autistic behavior. Application of the concept of
emergenesis as put forth by Lykken and colleagues to
autism seems warranted and especially fitting. There has
been earlier mention of emergence in autism when Bailey
21
and Parr [2003] considered autism as having some of the
key features of complex disease states including emer-
gence and coherence. Referencing earlier work of Sing
and Reilly [1993] that examined cardiovascular disease in
the context of complexity, Bailey and Parr proposed that
similar complex disease models were needed in the
autism field. Keller and Persico [2003]
have discussed the potential importance of complex,
non-deterministic neurobiological and genetic (‘‘multi-
layered’’) interactions in autism. Belmonte and Bourger-
on [2006] have also recently discussed the importance of
considering emergent phenomena in autism at the level
of genes, neurons, and functional modules. Defining and
identifying emergent phenomena in autism, and eluci-
dating the operative emergenic configurations should
give direction to, and hasten, research on the genetics,
biology, and behavior of autism. It might also contribute
to a better understanding of the often expressed sense
that there is some unitary entity or construct that is held
in common across individuals said to ‘‘have autism’’.
An initial step would be to consider how to define
emergent autistic phenomena and how best to identify
such phenomena. As discussed by Lykken [2006] and
colleagues [Li, 1987; Lykken et al., 1988], a simple
operational definition of emergent traits would be those
that are not often seen in family members but that appear
to arise from an emergent interaction once multiple
impairments or attributes coalesce within an individual.
Another closely related potential defining criterion for
emergent phenomena in autism is the presence of a
marked difference in correlation or concordance between
DZ and MZ twins. These first two criteria are not dissimilar
to working definitions for oligogenetic or polygenetic
traits [Frankel and Schork, 1996; Risch et al., 1999]. At the
gene level, an emergent trait can be viewed as arising from
multilocus synergistic epistasis (gene–gene interaction).
An additional and more speculative definition would posit
that phenomena that are discordant or discrepant in MZ
twin pairs might be the product of emergent processes.
Parenthetically, although recessive transmission can pro-
duce apparently novel phenomena within a family, studies
using extended or multiple pedigrees reveal the familial
nature of such mechanisms. Similarly, de novo mutations
certainly produce novel phenomena in those affected
[Sebat et al., 2007]; however, the abnormalities of such
sporadic cases usually can be attributed with confidence to
the mutation, rather than to an emergenic configuration
of multiple, interacting, inherited factors.
The emergence of new and novel phenomena in the
autistic individual is probably best represented by intellec-
tual disability (ID, also termed mental retardation), and the
evidence that can be used to support this contention is
fairly extensive. A number of other autism-associated
phenomena also can be tentatively suggested as being
emergenic, based on their seeming to be comparatively
22 Anderson/The potential role for emergence in autism
rare in relatives. These include seizures, stereotypies,
persistence of primitive reflexes, self-injurious behavior
(SIB), sleep problems, special skills, minor physical anoma-
lies, and abnormal brain size/growth. Other possible
emergent phenomena include gait disturbances, postural
control, clumsiness, and brain alaterality. Although these
various phenomena can be nominated as potentially
emergent based on the impression that they are rarely
seen in siblings, parents, or second-degree relatives, further
careful family studies are needed in most cases to
determine the extent to which particular phenomena can
be considered emergent. It is remarkable (but not surpris-
ing) that most of the phenomena that satisfy these criteria
do not appear to belong to any of the three major domains
of behavior that are taken to define autism.
Once emergent phenomena are identified, a second
daunting step is to determine the configuration of
factors necessary for the emergence to occur. This
will require a thorough investigation of the functional
components that may contribute to the phenomena.
It is hoped that gross dissection at the level of
the fractionable major three domains might be productive
in some instances. Consideration of the interactions
between more finely dissected within-domain traits
will also be required. This finer behavioral dissection
should also be informative regarding how specific config-
urations and constellations of traits influence the quality
and severity of domain abnormality. Complexities
at the behavioral level undoubtedly reflect a myriad of
underlying biological factors whose interactions form the
basis of normal and abnormal mental processes and
behavior. As in systems biology, and as outlined by Sing
and Reilly [1993] and by Gottesman and Gould [2003],
interactions are expected within and across different levels
of analysis from the gene to behavior. The need for the
concepts of complexity science and systems biology, and
for tools such as configuration frequency analysis and
multifactor dimensionality reduction [Mei et al., 2007;
Wiesbeck et al., 2005], is clear.
Intellectual Disability in Autism as an
Emergent Trait
It is generally accepted that family members of indivi-
duals with autism do not have scholastic difficulties or
cognitive impairment (or advantage) at rates much or at
all above those seen in the general population. This
appears to be the case irrespective of the level of cognitive
impairment in the index autistic individual [Bailey et al.,
1998; Fombonne et al., 1997; Starr et al., 2001]. This lack
of family loading for cognitive impairment as reflected in
intelligence quotient (IQ) test performance or in achieve-
ment and the absence of specific reading/spelling
difficulties in the families at higher than base rates are
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strong indications that the ID often associated with
autism is an emergent product of interacting factors
associated with autism-related phenomena. On a group
basis, siblings and parents of probands with autism do
have higher than expected delayed speech onset and
exhibit subtle problems on language tests [Folstein et al.,
1999]; however, this is as expected given the defining
abnormalities in the language and communication
domain. The evidence from twin studies further supports
the idea that autism-related ID is non-familial (in the
usual sense), as IQ is much more highly correlated in MZ
twin pairs than in DZ twins, in pairs with at least one
autistic twin [Starr et al., 2001].
Although, in general, IQ is highly correlated within MZ
twin pairs, large differences in IQ have been observed in
some autistic MZ twin pairs [Le Couteur et al., 1996;
Smith and Bryson, 1988]. Although trait discrepancy
within MZ twins is the most speculative of the definitions
offered above for emergent phenomena, emergence does
provide a plausible explanation for the puzzling discre-
pancies seen in MZ twin pairs. It can be suggested that
the larger than expected differences seen for IQ within
certain autistic MZ twin pairs may be owing to a
dependence of mental retardation on a critical config-
uration of abnormalities or factors. Such an underlying
configural cause may be sensitive to subtle differences in
gene activation (epigenetics) that begin with the very
earliest events of embryonic development. The exact
timing and allocation of progenitor cells involved in a
specific MZ twinning may lead to subtle, but non-trivial,
differences in gene activation and development. The
genetic and epigenetic mechanisms that might contri-
bute to MZ differences in linguistic ability have been
thoroughly reviewed [Stromswold, 2006]. More readily
apparent differences in MZ twins are seen in placentation
status (mono or dichorionic, placement, size) and
amniotic cavity [mono or diamniotic; Sadler, 2006].
Available autism twin data suggest that there may be a
group of twin pairs that are quite similar on cognitive
measures, whereas a second group is more discrepant
than expected [Le Couteur et al., 1996]. Although
twinning itself is not a risk factor for autism [Hallmayer
et al., 2002], it can be speculated that these two groups
may reflect symmetric or asymmetric twinning or be
related to the timing of the twinning process.
If ID in autism is indeed emergent, it seems unlikely
that the underlying etiological mechanisms would be
similar to those operating in ‘‘single-gene’’ disorders
such as 15q11–q13 duplication or Fragile X, even
when those disorders are said to be associated with
autistic-like behaviors. This is not to say that single-gene
disorders do not produce ID through emergent mechan-
isms, only that it is doubtful that the emergenic
configurations operating are similar to those that might
produce ID in autism. Recent attempts to link causative
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aspects across idiopathic autism, Fragile X, and maternal
15q duplication based on gene expression profiles face a
difficult task and may be examining, at best, late points
of pathophysiological convergence on the ID phenotype
[Nishimura et al., 2007].
Seizures as Potentially Emergent Phenomena
in Autism
As reviewed by Tuchman and Rapin [2002], seizures occur
at an approximate rate of 25–33% in individuals meeting
the criteria for autism. The rate is substantially higher in
individuals who also have ID and there is an apparent
bimodal distribution in age of seizure onset in autism
[Danielsson et al., 2005; Rossi et al., 1995, 2000; Volkmar
and Nelson, 1990]. Although the rate (lifetime prevalence)
is substantially higher than the general population rate of
1–3%, it is not clear whether bimodality in the age of
onset is more marked in autism. Although the rate of 33%
or more in autistic individuals also appears to be much
higher than the rate in family members, the degree of
loading for seizures in families of individuals with autism
has not been thoroughly investigated [Starr et al., 2001]. A
recent study found epilepsy to occur in parents of
probands at rates seen in the general population, thus
tending to support an emergenic origin in autism
[Mouridsen et al., 2008]. The degree of concordance in
MZ and DZ twins is also little studied, with one twin study
reporting discordance in DZ twins and concordance in
four of six MZ twin pairs with at least one twin
with seizures and autism [Le Couteur et al., 1996]. It can
be noted that seizures do not appear to occur at above
base rates in individuals meeting criteria for Asperger’s
syndrome [Cederlund and Gillberg, 2004]. This latter
observation may provide clues about the combination
of factors necessary for seizures to occur. Further investiga-
tion in this general area is needed to assess seizure types
and rates in family members, to improve estimates of
concordance in MZ and DZ twins, to determine whether
late onset seizures are of a special sort, and to understand
better the relationship of early and late onset seizures to ID
in autism.
Additional Potentially Emergent Phenomena
in Autism
Persistence of Primitive Reflexes
Minderaa and colleagues reported on the persistence of
primitive reflexes in children and young adults with
autism [Minderaa et al., 1985]. The snout and visual
rooting reflexes normally disappear in the first few months
of life, but these reflexes were observed in 81 and 79%,
respectively, of the 42 9–29-year-old autistic individuals
studied. Remarkably, 23 of the 24 autistic subjects 21 years
old or younger displayed a visual rooting reflex, whereas
23
the reflex was seen in none of the controls. Although
family members have not been studied, it seems unlikely
that they would display rates much above the general
population. Concordance for persistence of primitive
reflexes in twin pairs is unexamined.
Stereotypies and Self-Injurious Behavior
Stereotypies and SIB are frequently reported in autism
but are not a requisite part of autism spectrum diagnostic
criteria. Given the often striking nature of stereotypies
and SIB [Poustka and Lisch, 1993; Stoppelbein et al.,
2006], it seems obvious that the behaviors do not
occur to nearly the same extent or degree in relatives.
However, a careful study of rates of stereotypies
or of frank SIB and related self-harm behaviors in siblings
and parents has not been performed, nor has concor-
dance in twin pairs been examined. Determining their
degree of emergence will require further clarification of
the relationships of the behaviors to one another, to
other behaviors included in the restricted and repetitive
behaviors domain of DSM-IV, and to IQ [Richler et al.,
2007; South et al., 2005].
Sleep Problems
Problems with sleep are often present in individuals
diagnosed with autism. The nature of the problems
can vary but may largely consist of difficulties in
falling asleep or sleep latency [Allik et al., 2006; Liu
et al., 2006]. Perhaps more than the other potentially
emergent phenomena, sleep problems may usually
represent a difference in degree rather than kind. In
addition, the observed increased sleep latency may
actually be related to difficulties with novelty and
separation [Weiskop et al., 2005]. A more thorough
examination of sleep architecture could point to specific
aspects that are qualitatively altered in autism [Thiruma-
lai et al., 2002]. There are only limited data regarding
sleep latency, other behavioral aspects of sleep, or sleep
architecture in autism; and no information regarding
family members or twin pairs.
Special Skills
Mathematical genius has been proposed as a paradig-
matic example of an emergent behavior in the general
population [Lykken, 2006], at times appearing in indivi-
duals whose families displayed little similar talent in
earlier or subsequent generations. Similarly, the savant
skills [Pring, 2005; Tadevosyan-Leyfer et al., 2003; Thioux
et al., 2006] that have been observed to occur in
individuals with autism do not appear at first glance to
occur in family members. However, there is some limited
evidence that relatives may exhibit increased rates of
savant skills [Nurmi et al., 2003]. The fascinating issue of
concordance for savant skills in MZ twins with autism is
24 Anderson/The potential role for emergence in autism
unaddressed. A number of other less striking special
abilities including heightened perception of details,
hyperlexia, enhanced memory skills, and the acquisition
of large bodies of knowledge can be present in autism.
The familiality of these various traits and their associated
processes have been little studied.
Morphological Abnormalities
There is an increasing number of reports of early brain
growth abnormality in a substantial proportion of
individuals with autism. The basic finding of brain
overgrowth in the first few years of life is now well
replicated, although the regional specificity, relative gray
and white matter contribution to the overgrowth, and
issues of laterality remain to be clarified [Courchesne
et al., 2003; Dementieva et al., 2005; Hazlett et al., 2005;
Klimkeit and Bradshaw, 2006; Minshew et al., 2005; Piven
et al., 1992]. It now appears that overall body growth may
be similarly affected [Dissanayake et al., 2006; Lainhart
et al., 2006; Miles et al., 2000; Sacco et al., 2007; Torrey
et al., 2004]. It is particularly noteworthy in the context
of this commentary that recent studies indicate that
family members also often display macrocephaly
[Folstein, personal communication, December 2007;
Geschwind, 2007; Sacco et al., 2007], making it less likely
that brain overgrowth is an emergent phenomenon (as
defined here).
Observations of abnormalities based upon neuropatho-
logical examination of postmortem tissue are generally
limited by power and difficulties in clinical phenotyping
and would need to be accessible using neuroimaging
techniques to adjudge comparative rates in family
members. Major congenital and minor physical anoma-
lies have also been established to occur at elevated rates
in autism [Hardan et al., 2006; Wier et al., 2006], and
rates in family members do not appear elevated [Rodier
et al., 1997]. A placental morphological abnormality, the
trophoblast inclusion, recently has been reported to
occur at 3- to 4-fold elevated rates in autism spectrum
disorders compared with the general population, and
ongoing studies of at-risk infants may permit a compar-
ison with rates in siblings [Anderson et al., 2007].
Neurochemical Alterations
A range of neurochemical abnormalities has been
reported for autism, including alterations in serotonergic,
glutamatergic, gabaergic, cholinergic, and stress response
systems [Anderson and Hoshino, 2005; Lam et al., 2006;
McDougle et al., 2005; Pickett and London, 2005; Polleux
and Lauder, 2004]. However, many of the observations
are not fully replicated and few have been examined in
family members. Exceptions are the well-replicated
platelet hyperserotonemia of autism [McBride et al.,
1998; Mulder et al., 2004] and the related finding of
INSAR
reduced expression of central and peripheral 5-HT2A
receptors [Cook et al., 1993; Goldberg, personal commu-
nication, July 2007; McBride et al., 1989; Murphy
et al., 2006]. Although platelet serotonin levels appear
highly heritable [Ober et al., 2001], the family studies do
not clearly indicate whether the increased platelet
serotonin in autism is familial [Abramson et al., 1989;
Piven et al., 1991]. Decreased 5-HT2A expression does
appear to occur in family members [Cook et al., 1993;
Goldberg, 2007], but data are limited. Decreased plasma
levels or urinary excretion of the pineal hormone,
melatonin, have also been replicated [Kulman et al.,
2000; Nir et al., 1995; Tordjman et al., 2005] and would
be quite suited to examination in relatives.
Conclusions
Emergence appears to be a useful concept when con-
sidering the behaviors and phenomena that occur in the
autism spectrum disorders. The concept may have
particular relevance to those behaviors that appear novel
in the autistic individual, which do not strongly run in
their families. Emergent phenomena can be defined as
those phenomena that are sensitive to a particular
configuration of risk alleles, factors, or traits. At the level
of the gene, emergent phenomena can arise from multi-
locus synergistic epistatic interactions.
Criteria for operationally defining emergent phenom-
ena in autism need to be established. An initial approach
would be to define the degree of emergence based on the
extent to which behaviors are rare in relatives and,
perhaps, on the amount of discrepancy seen within MZ
twin pairs. Comparing rates in relatives of probands with
and without the trait in question should also be
informative. Identifying specific phenomena as emergent
should enhance their study and lead to the subsequent
elucidation of the factors that need to co-occur for the
phenomena to ‘‘emerge’’. Many of the phenomena
nominated as potentially emergent appear to be asso-
ciated with, and perhaps require, substantial impairment
or abnormality from across the three major domains of
autistic behavior. Although the present domain-based
DSM-IV diagnostic criteria for autism define a hetero-
geneous group, it is a group highly enriched in indivi-
duals displaying novel and non-familial (emergent)
phenomena. Individuals with impairments in only one
or two domains would provide crucial contrasts. Studies
of at-risk siblings and other family studies also should be
designed in a way that allows a full consideration of
potentially emergent phenomena.
Biological systems depend on emergent phenomena at
all levels and the loss of emergence, termed submergence
by Bunge [2003], might also contribute to abnormality in
autism. Thus, while an emergent abnormality requires
INSAR Anderson/The potential role for emergence in autism
the combination of multiple factors in an affected
individual, the final observed effects on phenotype and
development could be due to the abnormality’s submer-
gence of a normal (and emergent) process. In addition,
the familial components, factors or traits that combine in
an emergenic manner to produce novel abnormality
could themselves arise from submergent processes.
The genetic study of emergent phenomena can be
predicted to be especially difficult owing to the evanescent
nature of the phenotypes, and it is probably best to avoid
standard genetic approaches to such phenomena. In
contrast to this cautionary note, it can be pointed out
that the sensitivity of emergent phenomena to configura-
tion offers hope in terms of behavioral and pharmacother-
apeutic intervention. The potential for small changes to
produce large non-linear effects on emergent phenotypes
is exciting and should provide impetus to this area of
research. Future genetic, biological, behavioral, and ther-
apeutic investigations in autism may well be guided to a
large extent depending on the emergent or non-emergent
nature of the trait being studied. Autism is unmistakably a
complex disorder and there can be little doubt that autism
research would benefit from the application of the
concepts and approaches of complexity science.
Acknowledgments
Support of the Korczak Foundation for Autism Research
and the Gettner Autism Research Fund is gratefully
acknowledged. Drs. Susan Folstein, John Holahan, Flavio
Keller, Kathy Koenig, Sarah Paterson, Mikle South, Sherin
Stahl, Julie Wolf, anonymous reviewers, and Charles F.W.
Anderson are thanked for their helpful comments on
versions of the paper. Portions of the paper were
presented at the Colloque International/Traiter les
Inclassables, Université Rennes 2, Rennes, France,
November 24–25, 2006.
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