Animal Model of Autism
Solitary Mammals Provide an Animal Model for Autism
Spectrum Disorders

Reser, J. 2013. Solitary mammals provide an animal model for autism
spectrum disorders. Journal of Comparative Psychology.

DOI: 10.1037/a0034519


Dr. Jared Edward Reser Ph.D.
University of Southern California
jared@jaredreser.com




Abstract

Species of solitary mammals are known to exhibit specialized, neurological
adaptations that prepare them to focus working memory on food procurement
and survival rather than on social interaction. Solitary and nonmonogamous
mammals, that do not form strong social bonds, have been documented to
exhibit behaviors and biomarkers that are similar to endophenotypes in
autism. Both individuals on the autism spectrum and certain solitary mammals
have been reported to be low on measures of affiliative need, bodily
expressiveness, bonding and attachment, direct and shared gazing, emotional
engagement, conspecific recognition, partner preference, separation distress,
and social approach behavior. Solitary mammals also exhibit certain
biomarkers that are characteristic of autism including: diminished oxytocin and
vasopressin signaling, dysregulation of the endogenous opioid system,
increased HPA activity to social encounters, and reduced HPA activity to
separation and isolation. The extent of these similarities suggests that solitary
mammals may offer a useful model of autism spectrum disorders, and an
opportunity for investigating genetic and epigenetic, etiological factors. If the
brain in autism can be shown to exhibit distinct homologous or homoplastic
similarities to the brains of solitary animals, it will reveal that they may be
central to the phenotype and should be targeted for further investigation.
Research into the neurological, cellular and molecular basis of these
specializations in other mammals may provide insight for behavioral analysis,
communication intervention, and psychopharmacology for autism.
Keywords: autism, solitary, monogamous, nonmonogamous, oxytocin,
vasopressin



Introduction
Autism is a developmental disorder defined by behavioral symptoms across
three general areas: social reciprocity, communication, and restricted and
repetitive interests (DSM IV TR). It is diagnosed through behavioral
observation using standardized tools as well as clinical judgment (Piven,
2000). The diagnostic indicators are behavioral symptoms rather than
definitive neurological markers. Proposed biomarkers include gene expression
profiling, proteomic profiling, metabolomic profiling, head size, brain structure,
neurotransmission and eye movement (Walsh et al., 2011). Multiple etiologies
are involved in autism and autism spectrum disorders (ASDs), including
genetic susceptibility, multigenic interactions, and interactions between
genetic and environmental factors (Cantor, 2009). Because of the broad range
of biomarkers and etiological factors, well-defined animal models that can
recapitulate core symptoms of the disorder are essential for research into the
nature of the neurological aberrations. Currently, mouse models are the most
widely utilized because of the extensive knowledgebase available for mouse
genetics and neurology and because of the availability of detailed behavioral
phenotyping data available for many mouse strains (Halladay et al., 2009).
Rodent models of autism typically involve mice with specific lesions, mice that
are genetically engineered to carry certain genes, or panels of inbred mouse
strains carrying naturally occurring genetic polymorphisms. Advances have
included the establishment and evaluation of mouse models capable of
reflecting disease symptoms such as impaired social interaction,
communication deficits and repetitive behaviors. Large scale datasets and
biobanks have linked multiple genes to autism spectrum disorders, and
genetic linkage and association studies in humans have begun to inform the
design of mouse models. Transgenic rodent mutants with deletions,
truncations and overexpression of these autism candidate genes have helped
to model the disorder (Moy & Nadler, 2008). However, the rodents used for
these models are primarily social animals that are engineered to have
symptoms characteristic of social deficits. The present article attempts to
place emphasis on the potential importance of naturally occurring phenotypes
found in solitary species in modeling autism. There is a large knowledgebase
in zoology and behavioral neuroscience of naturally existing variation in social
capacities found between mammalian species that can be harnessed as a tool
to inform the development of future animal models and to provide insight into
the biology of autism.

Most animals, many mammals and several species of primates are solitary
(Alcock, 2001). Solitary species are known to have specialized, behavioral
adaptations that prepare them mentally to live alone (Decety, 2011). These
behavioral adaptations have been shown to have neural underpinnings
(Young, 2009). Adjustments to neural social circuits and associated
neurotransmitters, neuromodulators and their receptors, fine-tune solitary
animals to direct cognition toward foraging and self-preservation rather than
on interaction with conspecifics (Alcock, 2001). Not all solitary mammals
exhibit the same suite of adjustments. This is because individual species
respond to diverse social concerns particular to their unique environments.
There does, however, seem to be a large amount of convergence in many of
these adjustments (Adolfs, 2001). Social neuroscientists have begun to
elucidate specific neurological pathways that underlie specializations involved
in prosocial behavior, attachment and bonding. Researchers are also
beginning to compare the pathways found in social animals with those in
solitary animals (Shapiro & Insel, 1990), and identify traits that correlate with
group size and social necessity (Dunbar, 1988; 1998). Even though this
research is in its nascent stages and the pathways involved are currently not
well-resolved, continued experimental research may have important
implications for autism spectrum disorders (ASD) because individuals on the
autism spectrum share a variety of traits with solitary species (Reser, 2011a;
2011b). In an effort to promote this comparative approach, the present article
will review literature that points to comparable traits.

Our understanding of the “social nervous system” has been driven by studies
analyzing specific biological markers in species that parent, species that are
socially monogamous, species capable of developing extended families, and
those capable of selective social camaraderie (Porges & Carter, 2010).
Comparisons of the species-typical mating and affiliative strategies between
the socially monogamous prairie vole (Microtus ochrogaster) and the closely
related but nonmonogamous (promiscuous or polygamous) montane vole
(Microtus montanus), has served as the primary model for the mapping of the
neurocircuitry of social behavior in mammals (Carter et al., 1995). These voles
have been closely studied, and exhibit divergent traits in the neuroscience of
bonding and attachment. These and other closely related, but socially
discrepant pairs of species will be discussed in an effort to build a
comparative paradigm.

Individuals on the autism spectrum exhibit both behaviors and biological
markers that are common in solitary and nonmonagomous mammals (Reser,
2011). Both solitary mammals and autistic individuals have been reported to
demonstrate lower measures of: affiliative need, bodily expressiveness,
bonding and attachment, conspecific recognition, emotional engagement,
gregariousness, partner preference, separation distress and social approach
behavior. Individuals with autism also exhibit certain biological markers that
are characteristic of solitary mammals including: diminished oxytocin and
vasopressin action, dysregulation of the endogenous opioid system, increased
HPA activity to social events, and reduced HPA activity to separation, and
isolation owing to anomalies in vagal tone, and parasympathetic response
(some of these mechanisms may be ontogenetically prior to others). See
Tables 1 and 2 below for matched comparisons between: A) neurotypical
humans and humans with autism; and B) the nonmonogamous montane vole,
and the monogamous prairie vole. Are the similarities in these shared
behaviors sufficient to warrant the pursuit of a solitary mammal model of
autism? Before this question can be answered these purported similarities
must be investigated in a variety of species with differing bonding and
attachment strategies.

There are currently no animal models that reflect the entire range of
behavioral and neurological phenotypes in autism; however, some
researchers have advised that studies into the neurobiology of normal social
cognition may provide clarification for understanding the mechanisms
responsible for autism (Hammock and Young, 2006). This article extends this
argument, advising that studies into the neurobiology of solitary cognition may
provide further insight and clarification. Regardless of whether the similarities
between the brains of solitary/nonmonogamous mammals and individuals on
the autism spectrum are coincidental or are partly due to adaptive
convergence to similar ecological demands (as proposed and outlined in
Reser, 2011a), they may help to elucidate the neurobiological and molecular
underpinnings of ASD.


Mammals that Forage Solitarily
Some animal species are obligately social, some are obligately solitary, and
others are facultatively social, and can transition between social and solitary
lifestyles. Species that are obligately social form groups even under very low
population densities (Bothman & Walker, 1999), whereas some species like
whistling rats (Paratomys brantsii) maintain solitary living even under very high
population densities (Jackson, 1999). Obligate solitary living is rare in birds,
but common in mammals, reptiles, amphibians, and invertebrates. Among the
many mammals that have been categorized as solitary are well-known animals
such as armadillos, opossums, orangutans, red pandas, red squirrels,
Tasmanian devils, as well as most bears, cougars, tigers, and skunks. See
Table 3 below for a more extensive list that includes a diverse assortment of
mammals from orders including: primates, lagomorpha, rodentia, carnivora,
insectivora, artiodactyla, perissodactyla, soricomorpha, xenarthra, and also
marsupials and monotremes.


Table 1: Abridged List of Solitary Mammals
Armadillo, Baikal seal, Bamboo rat, Bear, Black Rhinoceros, Black-footed Cat, Blind mole rat,
Brown-throated Sloth, Bushbuck, Bushy-tailed Opossum, Clouded Leopard, Coast Mole, Cougar,
Dusky-Footed Woodrat, Eastern Pygmy Possum, European Mink, European Polecat, Fishing Cat,
Four-horned Antelope, Four-toed Hedgehog, Giant Anteater, Grizzly bear, Hog-nosed skunk,
Honey Badger, Jaguar, Japanese Hare, Javan Rhinoceros, Lemming Leopard, Maned Sloth,
Marbled Polecat, Marten, Mountain Weasel, Montane Vole, Meadow Vole, Musk deer, Neotropical
Otter, Northern Bettong, Opossum, Orangutan, Paca, Philippine Mouse-deer, Philippine Tarsier,
Polar bear, Pudú, Red Brocket, Red Panda, Red Squirrel, Rhinoceros, Ringed seal, Scaly-tailed
Possum, Short-beaked Echidna, Siberian chipmunk, Skunk, Solenodon, Southern Tamandua,
Spotted skunk, Steppe Polecat, Striped Hog-nosed Skunk, Striped Polecat, Sumatran Rhinoceros,
Tapeti, Tasmanian Devil, Tiger, Vagrant Shrew, Water deer, Zokor

Behavioral genetics has demonstrated that both social (subsocial, parasocial,
presocial, eusocial etc.) and asocial tendencies have both genetic and neural
underpinnings (Trivers, 1985). Furthermore, these traits can show
considerable variability both between and within animal species (Frank, 1998).
Significant intraspecific variation in social propensities has been observed in
more than a hundred vertebrate species (Lott, 1991). It is not clear if the
variation within species is due to genetic differences between individuals,
differential responses to environmental circumstances, or gene-environment
interactions. Likewise, it is not clear why there might be variation in social
propensities and abilities within our own species (Baron-Cohen, 1995).
However, it is thought that much variation between species is genetic.
Perhaps both intra and interspecific diversity can be utilized to investigate the
autism spectrum; however, the data concerning interspecific diversity is
currently much stronger. Even closely related species can have vastly
divergent social predispositions. In fact, phylogenetic inertia is thought to be
strong for general physiology but not for social behavior, i.e., closely related
species can have very different social organization if they live in different
habitats or eat different foods (Zuk, 2002).

Placed together in a large room, several species of rodents, such as
nonmonagamous montane voles, are content to be loners, and will spread out
uniformly attempting to maximize the distance between themselves and their
conspecifics. Social rodents like monogamous prairie voles, if placed in the
same room, will prefer to huddle together and affiliate in close proximity
(Shapiro and Insel, 1990). It is thought that the wide discrepancy in social
behavior between these voles reflects adaptation to two very different physical
and social environments (Adolfs, 2001). In prairie and pine voles, the males
and females form long-term pair bonds, establish a nest site and rear their
offspring together. In contrast, montane and meadow voles do not form pair
bonds and only the females take part in rearing the young. This is true in the
wild and in captivity. It is believed that this diversity in behavior is maintained
by selection favoring one of two male spatial/paternity strategies: 1) maintain a
small home range and actively defend the female that you are monogamous
with from other males (breeder); or 2) maximize range by wandering in order to
maximize the rate at which unguarded females are encountered (roamer)
(Phelps, 2010).

Nonmonogamous montane and meadow voles do not show partner
preferences that prairie and pine voles do after experimentally induced pair-
bonds are instigated by cohabitation (Lim et al., 2004). This may be likened to
the situation in autism where social bonding and secure attachment behavior
is diminished (Sigman & Ungerer, 1984). Pups of the monogamous prairie
vole, but not the nonmonogamous montane vole, show a robust stress
response to maternal separation along with increased vocalization and
increased serum corticosterone levels (Shapiro and Insel, 1990). This
behavioral pattern is highly analogous to the diminished separation distress
evident in autistic infants and children. In fact, children with autism show
diminished (but existent) preferential proximity seeking and reunion behavior
in the Strange Situation Test and other measures (Buitelaar, 1995; Naber et
al., 2008).

Because of small size and easy maintenance in the laboratory, the
neurobiology of the social differences between these two species of vole has
been carefully examined. The differences are thought to be largely governed
by the regulation of the neuromodulators oxytocin (OXT) and vasopressin
(AVP) (Churchland, 2011). In fact, neuropeptides like oxytocin, vasopressin
and endogenous opioids are known to regulate complex social behaviors in
conjunction with monoaminergic neurotransmitter systems (Miller, 2005).
Interestingly, the same neuropeptides have been shown to be affected in
autism (Gilberg, 1995; Green et al., 2001; Hollander et al., 2003; Machin &
Dunbar, 2011). In fact, preliminary data suggests that allelic variants of genes
necessary for the development of parental and affiliative behaviors in other
species (especially the genes for the oxytocin and prolactin receptors) are
associated with ASD (Yrigollen et al., 2008).

It will be interesting to perform further comparative analyses, but it is not
completely clear which genes or which brain systems should be interrogated.
A relevant model of neurobiological regulation of affiliation in mammals (Depue
& Morrone-Strupinsky, 2005) has suggested that dopamine plays an important
role in incentive-reward motivational processes associated with the appetitive
phase of affiliation, endogenous opioids are involved in the consummatory
phase of socialization, and oxytocin and vasopressin enhance the perception
and memory of affiliative stimuli. To begin to make the appropriate
comparisons, let us first take a look at the role of oxytocin signaling in
nonmonogamous rodents, and in autism.



Oxytocin Signaling
Oxytocin is a peptide hormone and neuromodulator involved in reproduction,
social recognition, and pair-bonding in mammals. Animal species that rely on
pair-bonds and social attachment exhibit higher levels of plasma oxytocin,
especially when it is behaviorally relevant, like during monogamous sex,
childbirth, and lactation (Campbell, 2007). Not surprisingly, interspecific,
seasonal and reproductive variation in oxytocin concentrations have been
attributed adaptive significance. High levels are associated with mating,
continued proximity, trust, and pair-bonding in a large number of mammals
(Adolfs, 2001). Oxytocin is capable of down-regulating or buffering the
response to stressors, especially social ones (acting at the level of the
hypothalamus, among other areas). It is released during positive social
interactions, and appears to facilitate capacity for being trusting, and socially
perceptive (Porges & Carter, 2010). Oxytocin knockout mice show
deficiencies in social recognition and social memory, and also in the ability to
manage emotional reactivity due to stress (Takayanagi et al., 2005; Pederson
et al., 2006).

After being synthesized in magnocellular neurons in the paraventricular and
supraoptic nuclei of the hypothalamus, and processed along axonal
projections to the posterior lobe of the pituitary, OXT and AVP are released
into the extracellular space resulting in both local action and diffusion
throughout the brain. OXT and AVP are also synthesized by parvocellular
neurons of the hypothalamus, and from here travel directly, via hypothalamic
projections, to different brain areas including the amygdala, hippocampus,
striatum, suprachiasmatic nucleus, bed nucleus of the stria terminalis, and
brainstem where they take different actions, dependent on the receptors they
bind to. It is not clear if the areas that synthesize, process and distribute OXT
and AVP are affected in autism or in solitary animals although this should be a
topic of future research. It is known that the anatomical sites of oxytocin
synthesis and their projections are highly conserved in mammalian species
(Hammock and Young, 2006), but their quantitative properties may be
divergent. On the other hand, there are significant differences in oxytocin
receptor distribution patterns between monogamous and nonmonogamous
mammals.

Prairie voles and montane voles have very different oxytocin receptor profiles.
The montane vole, relative to the prairie vole, has a much smaller number of
receptors in the brain for oxytocin and unlike the amorous prairie voles, they
do not form pair-bonds (Marler, 1968). The montane voles have fewer
receptors, and thus are less responsive to oxytocin, making them more wary,
suspicious and more easily frightened of other members of their species
(Marler, 1968).

When the two are compared, monogamous species have higher densities of
oxytocin receptors in the caudate, putamen, amygdala, orbitofrontal cortex and
nucleus accumbens (Hammock and Young, 2006).  This may indicate that
these brain regions, and their quality of oxytocin receptivity should be
attended to in autism. The shell region of the nucleus accumbens is especially
abundant in oxytocin receptors in socially monogamous species and prairie
voles but not in nonmonogamous voles (Insel, 2010). Oxytocin receptor
antagonists applied directly to the nucleus accumbens of female prairie voles
inhibit mating-induced partner preference formation, indicating that activation
of oxytocin receptors in this area of the brain is necessary for bonding and
attachment (Young et al., 2001). Other nonmonagamous species such as
marmoset monkeys, rhesus monkeys, titi monkeys, the California deer mouse
and the white-footed mouse, have OXT and AVP receptor distributions that
are highly similar to that of the montane vole (Bales et al., 2007; Wang et al.,
1997). These comparisons suggest that autism research should be focused
on the nucleus accumbens and its role in social motivation. It would be
interesting to compare the details of oxytocin action, such as receptor number
and distribution pattern, in solitary animals with that of people with autism but
again this research has not been done. The comparable data about receptor
density and distribution in humans has not been determined because injection
methods to tag receptors cannot be done in living humans for ethical reasons,
and do not yield results when performed on the brains of cadavers.

Results interpreted as supporting the hypothesis that baseline cerebrospinal
fluid (CSF) oxytocin concentrations are related to species-typical
social/affective behavior patterns comes from comparisons between bonnet
macaques (Macaca radiata) and pigtail macaques (Macaca nemestrina). The
bonnet macaques, which have significantly higher levels of CSF
concentrations of oxytocin when laboratory-born than the pigtail macaques,
are described as gregarious affiliative and affectively stable, while pigtail
macaques are described as socially distant and temperamentally unstable
(Rosenblum et al., 2002). Furthermore, the pigtail macaques exhibited
elevations in CSF corticotropin releasing factor, elevations of which promote
social vigilance in both solitary and territorial mammals. Within a species, the
early environment may play a role. When rhesus macaques (Macaca mulatta)
are separated from their mothers at birth and reared with peers in a small
cage they develop a wide range of behavioral abnormalities that have been
associated with autistic symptoms. These monkeys exhibit low affiliation, high
aggression, and high self-directed and repetitive activities. These genetically
very social monkeys also had a significantly lower concentration of CSF
oxytocin (Winslow et al., 2003).

Oxytocin, the neuropeptide thought to enhance social learning, social
expressiveness, direct eye gaze, and the ability to remember faces in humans
(Savaskan et al., 2008), is reduced in the blood plasma of autism subjects.
Diminished circulating levels of oxytocin may play a large role in retuning
multiple social brain modules in autism and increasing fear and avoidance
responses to social stimuli (Green et al., 2001). It has been shown that
intravenous oxytocin produces a significant reduction in stereotypic behaviors
in adult autism subjects and increases empathy and generosity in people
without autism (Hollander et al., 2003). After treatment with intranasally
inhaled oxytocin, autistic patients have been reported to exhibit more
appropriate social behavior (Andari et al., 2010), increased attention to the
eye region of faces (Andari et al., 2010), increased emotion recognition
(Guastella et al., 2010), diminished repetitive behavior (Kosfeld et al., 2005),
and diminished social fear (Kirsch et al., 2005). Likewise, oxytocin infusions
into the brain increase side-by-side contact and decreased aggressive
behavior in female prairie voles (Witt et al., 1990), increased social contact in
male rats (Witt et al., 1992), and in squirrel monkeys (Winslow & Insel, 1991).
While this research is promising, further clinical trials are necessary to
demonstrate potential benefits and side-effects in the treatment of autism
(Bartz & Hollander, 2008).

Humans and all eutherian mammals have only one receptor for oxytocin,
OXTR, but humans have several alleles for the receptor which differ in their
binding effectiveness. Individuals homozygous for the “G” allele (which
produces the high affinity receptor) when compared to carriers of the “A”
allele, show higher empathy, lower overall stress response, as well as lower
prevalence of autism (Rodrigues et al., 2009). Two single nucleotide
polymorphisms in the third intron of the oxytocin receptor have emerged as
candidate genes for autism. In fact, several studies have shown that these
polymorphisms were overtransmitted by families to offspring with ASD (Wu et
al., 2005; Wermter et al., 2010). Other genes seem to be involved as well.
Recent work on CD38, a transmembrane protein that is involved in oxytocin
secretion in the brain, has shown that several genetic variants of the gene
show a significant association with high functioning autism (Munesue et al.,
2010). Although several studies point to function of the oxytocin receptor
(Jacob et al., 2007; Wermter et al., 2009), the underlying problem with
oxytocin signaling in autism remains unclear.


Vasopressin Signaling
Arginine vasopressin is a peptide hormone found in most mammals that plays
a key role in homeostasis and the regulation of water, glucose and salts in the
blood. Stored in vesicles in the posterior pituitary, most AVP is released into
the bloodstream, although some AVP is released directly into the brain where
it plays a significant role in social behavior and bonding. Humans and all
eutherian mammals have three receptors vasopressin, AVP receptor 1A
(AVPR1A), AVP receptor 1B and AVP receptor 2. Experimental studies in
several species have indicated that the precise distribution of vasopressin
receptors in the brain is associated with species-typical patterns of social
behavior. Specifically, there are consistent differences between monogamous
and nonmonogamous voles in the distribution of AVP receptors and the
distribution of AVP containing axons (Young, 2009). AVP release during social
interaction and mating in prairie voles leads to increased activation of brain
areas with high levels of AVP receptors, such as the ventral pallidum. High
density of receptors in the ventral pallidum is also found in the monogamous
marmoset, evincing convergent evolution among rodents and primates.
Activation of the pallidum, a key area in mammalian reward circuitry, is thought
to reinforce affiliative behavior leading to conditioned partner preference, and
initiation of pair-bonding (Pitkow et al., 2001).

In male prairie voles, infusions of vasopressin directly into the brain facilitate
partner preference formation and receptor antagonists block it (Winslow et al.,
1993). Altering receptor density also makes a difference. Experimentally
increasing the vasopressin receptor (V1aR) levels in the ventral pallidum of
nonmonogamous meadow voles using the injection of a viral vector directly in
the ventral pallidum resulted in the formation of strong partner preferences.
Hammock and Young (2006) describe this experiment in the following way:
“Therefore, even though these two species diverged long ago, this simple
change in the expression of a single gene replicated a hypothetical
evolutionary event that may have ultimately led to the development of
monogamy.”

Vasopressin receptors in the lateral septum (which projects directly to the
nucleus accumbens) have been shown, by studies using site-specific
injections of a V1aR-specific antagonist, to be critical for social recognition in
male mice (Bielsky et al., 2005). Further, these authors found that a viral
vector causing reexpression of V1aR in the lateral septum of V1aR knockout
mice resulted in a complete rescue of social recognition. Knowledge of the
role of the ventral pallidum, the lateral septum and the nucleus accumbens in
this circuit offers clues as to where to look and what brain areas to target in
autism. In fact, the receptivity of these areas to vasopressin in autism remains
undefined. These findings further substantiate the importance of attaining
receptor distribution profiles in autism so that specific brain areas and their
receptors can be manipulated for therapeutic purposes.

There is also evidence for a role of the gene that codes for the human
vasopressin receptor, AVPR1A, in ASD. This evidence comes from genetic
studies of the polymorphic microsatellite repeats in the 5’ flanking region of the
gene (3,625 base pairs upstream of the transcription start site of AVPR1A). Of
these repeats, overtransmission of RS3 and undertransmission of RS1 has
been associated with ASD (Yirmiya et al., 2006; Wassink et al., 2004).
Fascinatingly, similar microsatellite repeats have also been found in avpr1a in
prairie voles and have been viewed as instrumental in regulating social
behavior. Some, but not all studies have found an association of these
repeats with social behaviors in voles (Mabry et al., 2011; Hammock & Young,
2005). King (1994) has suggested that instability of microsatellite sequences
serves as a kind of evolutionary tuning knob (King, 1994). Hammock and
Young have done extensive experimentation suggesting that the AVPR1A
locus may be such a tuning knob, while relating their findings to autism (2005).


Endogenous Opioids
Endogenous opioids are opiate-like peptides that bind to opioid receptors in
the central and peripheral nervous system and the gastrointestinal tract. In the
brain this binding has an analgesic effect due to decreased perception of pain,
decreased reaction to pain, and increased pain tolerance.  Endogenous
opioids are thought to be heavily involved in the consummatory phase of
affiliation (Depue & Morrone-Strupinsky, 2005). Their release and action
during social intercourse is thought to make social encounters pleasurable
and reinforcing. Blockade of endogenous opioid receptors by an opioid
antagonist increases the need for social attachment and therefore the
solicitation of affiliative behavior from social partners (Martel et al., 2004).
Acute treatment with nonsedative doses of morphine significantly decreases
clinging behavior and grooming solicitations in primates, as well as decreasing
grooming performed. Morphine also reduces huddling duration and social
activity in prairie voles (Shapiro et al., 1989). Because low levels of opioids
increase seeking for affiliative comfort in mammals, and high levels decrease
it, it has been suspected that high levels are associated with autism and this
seems to be the case (Machin & Dunbar, 2011). Perhaps presumed high
action of opioids in the autistic brain keeps these individuals from seeking
social contact, and the presumed absence of phasic opioid release during
affiliation keeps social encounters from being rewarding.

In a review on this topic, Sahley and Panksepp (1987) point out that a growing
body of evidence points out that: (1) autistic-like symptoms can be induced in
animals with the administration of exogenous opioids, (2) human individuals
addicted to opiates exhibit autistic-like symptoms, (3) autistic-like symptoms in
the severely mentally retarded can be attenuated by opioid blockade, and (4)
the many brain areas that have been suggested to be dysfunctional in autism
have high concentrations of opioids. The following quote from Panksepp
(1994) illustrates that the role of opioids in autism is complicated but
potentially informative: “Thus opioid blockade with naltrexone can reduce
maternal competence in animals, while at the same time increasing maternal
motivation. Opioid blockade likewise appears to increase the social motivation
of rat pups, but reduces the reinforcing quality of interaction with the mother,
suggesting that opioids provide feedback concerning the pleasurable qualities
of social interaction in both mothers and infants. The clinical implications of
this knowledge are not straightforward, but they generally suggest that
clinically deficient social bonding might be capable of being strengthened via
manipulation of brain opioid systems.”

Autistic children lack the normal motivation to engage others socially, as
indicated by their poor social skills and lack of spontaneous communication.
They seem to lack emotional interest in other people, leading to a decreased
initiative to affiliate (Sahley & Panksepp, 1986). Autism has been speculated
to be associated with higher opioid levels and higher opioid receptor activation
which may underlie the reluctance to engage (Gilberg, 1995), although this
has not been clearly demonstrated and many details remain unclear. Further
research into the effects of opioids in social behavior and their role in autism
should prove informative. Specific pathways stand out as having promise.
Studies in animals indicate that of the different families of opiate receptors, the
µ-opiate receptor family seems to be the most directly implicated in the
regulation of social behavior, and that the β-endorphin has high affinity for
those receptors. It is generally thought that interactions between µ-opiate
receptors and dopamine neurons in the ventral tegmental area of the
hypothalamus produce the experience of reward associated with the
appetitive and consummatory phases of social contact (Gilberg, 1995). This
pathway should be interrogated by future autism research. Oxytocin and
vasopressin also facilitate the effects of endogenous opioids. In rodents,
oxytocin neurons in the paraventricular nucleus of the hypothalamus project to
the neurons in the arcuate nucleus and phasically increase the release of
opioids there (Csiffary et al., 1992). Endogenous opioids have been shown to
play a role in diminishing the release of oxytocin and vasopressin as well as a
role in regulating the hypothalamic pituitary adrenal axis. The details about
how these systems interact remain to be described.

There is a close functional relationship between endogenous opioid and
serotonergic systems in the brain. In fact, serotonin pathways modulate both
enkephalin and morphine analgesia. Serotonergic input to the hypothalamus
via the raphe nuclei may result in reduced arousal and facilitation of opioid-
mediated feelings of affiliative gratification (Depue & Morrone-Strupinsky,
2005). Thus high and dysregulated levels of serotonin observed in autism may
also play a role in dampening the need for certain forms of social contact
(Anderson, 2005). In fact, administration of the anorexigenic drug fenfluramine
has been shown to lower elevated serotonin levels and partially ameliorate
several symptoms in autism (Clineschmidt et al., 1978). Social network
analysis has shown that patterns of grooming and aggressive behavior in
rhesus macaques can be partially explained by repeat polymorphisms
associated with the serotonin system (Brent et al., 2011).  Rhesus macaques
that carry a copy of the short allele in the serotonin transporter linked repeat
polymorphism direct less attention to the eyes and are less likely to look at a
face than a non-face image (Watson et al., 2009). Allelic heterogeneity at the
serotonin transporter locus has been similarly implicated in autism as well
(Sutcliffe et al., 2005).


Alterations in Amygdalar, Vagus and Parasympathetic Responses

Highly social animals share with humans the capacity to form long-lasting
social relationships and thus provide an opportunity to examine the
physiological effects of social isolation. In prairie voles isolation from a partner
for a few days produces behavioral responses that significantly mimic
depression and anxiety in humans. The prairie vole for instance has an
autonomic nervous system that is relatively human-like, with high levels of
parasympathetic-vagal activity (Grippo et al., 2007). These animals exhibit
increases in heart rate, decreases in parasympathetic function, and increased
behavioral reactivity to social isolation and social stressors. Socially isolated
prairie voles explore less, show increases in anhedonia and are more likely to
display immobility in response to a stressor (Grippo et al., 2008), whereas
montane voles are relatively inured. Also like solitary mammals, individuals
with autism are less sympathetically responsive to social separation and
isolation (Buitelaar, 1995; Naber et al., 2008).

It is thought that social mammals uniquely have the ability to regulate an
autonomic state of calmness while regulating communicative functions
including the musculature of the face and neck necessary to produce
prosocial facial expressions, vocalizations and head gestures (Porges &
Carter, 2010). These capacities are limited in autism suggesting that
parasympathetic function may be involved. The primary nerve of the
parasympathetic branch of the autonomic nervous system exits the brainstem
as the vagus or 10th cranial nerve. This nerve has both motor-efferent and
sensory-afferent components. Many of these afferent sensory fibers carry
information from the viscera to a brainstem region known as the nucleus
tractus solitarius. Stephen Porges (2005) has documented alterations in
vagus morphology and parasympathetic tone in autism that are consonant
with phenotypes seen in nonsocial species. He points out that social contact
in autism leads to sympathetic activation and fight-flight arousal states that
induce a drive to diminish contact or withdraw. Individuals with autism have
been widely reported to have increased fear activity in the amygdala and high
levels of sympathetic function during social interaction (Baron-Cohen et al.,
2000). Autonomic arousal is linked to social stimuli for solitary animals
because it is important that solitary animals protect their foraging space, and
actively avoid threatening conspecifics. Animals that are solitary are often
territorial and find the presence of another animal in their territory aversive,
especially an animal of their own species (Harcourt, 1989).



Alterations in Social Processing Cortical Regions
The brain abnormalities in autism do not seem to constitute indiscriminate
pathological abnormalities as one might expect if autism were simply a
disease. The most conspicuous brain abnormalities seem to consistently
affect the areas of the brain that have been associated with social cognition
(Adolfs, 2001). The amygdala, the anterior cingulate cortex, the orbito and
medial frontal cortex, and the mirror neuron system have all been strongly
associated with social cognition (Dapretto et al., 2006), and also have been
shown to be the same areas that exhibit the prominent anomalies in autism
(Williams et al., 2001). Unfortunately, despite some hopeful research (i.e., Bell
et. al., 2010; Pellis et. al., 2006) little is known about the social cortex in
mammals, especially solitary ones.

The brain in autism has shown underactivity in nearly every brain region
associated with the empathy circuit (Di Martino, 2009). When individuals with
autism attempt to make judgments about the intentions, motives or state of
mind of another they show reduced activity in the dorsomedial prefrontal
cortex (dmPFC) (Happe et al., 1996; Wang et al., 2007). When asked to infer
emotional state from pictures of people’s faces they demonstrate underactivity
in the frontal operculum (FO), amygdala and anterior insula (Baron-Cohen &
Hammer, 1997; Baron-Cohen et al., 2001). When individuals with autism are
asked to rate how they feel after viewing emotionally charged pictures, they
show less activity within a number of regions in the empathy circuit including
the dmPFC, the posterior cingulate cortex and the temporal pole (Silani,
2008). Not only are areas involved in empathy underactive during empathy
tasks, but the dmPFC and ventromedial prefrontal cortex (vmPFC) show
atypical baseline activity, during rest (Kennedy et al., 2008; Kennedy et al.,
2006). In fact, social impairment in autism is correlated positively with degree
of atypical vmPFC response (Lombardo et al., 2007; 2010). The
corresponding studies in nonhuman animals have not been performed, but it
might be expected that solitary or nonmonogamous species exhibit the same
neuroanatomical irregularities in homologous cortical areas and the motor
neuron system. Analogues of the relevant prefrontal areas may not be present
in rodents but are in other primates. Existent, yet limited empathic abilities
have been documented in apes and cortical regions that correspond to human
social cortical regions are thought to be instrumental (Dunbar, 2008; Joffe &
Dunbar, 1997; Povinelli, 1994).

It has been suggested that empathizing and systemizing of physical systems
are contingent on separate brain modules (Baron-Cohen, 1995), but both may
in fact be made possible by the same architecture for systemizing, namely the
pathways involved in immediate and working memory. In other words,
empathy may involve systemizing another’s perceived mental state using
mirror neurons and social schemas derived from social learning experiences.
Perhaps social mammals naturally find stimuli coming from conspecifics
captivating and will automatically attempt to systemize this information unless
fear sets in first. Phasic increases in dopamine neurotransmission in the PFC
are thought to underlie the ability to internally represent, maintain, and update
contextual information about salient external and internal stimuli (Braver and
Cohen, 1999). Stimuli that are deemed novel, surprising, or appetitive are
given priority. Seamans and Robbins (2010) have proposed that this
dopaminergic process regulates the access of salient contextual
representations and maintains them online in active memory so that
systemization and modeling of these representations can take place. Perhaps
the brains of solitary mammals are fine-tuned to perceive incoming social
stimuli as fearful and not appetitive or novel in order to keep these stimuli from
entering working memory. Aberrations in the receptivity of subcortical
motivational areas to neurochemicals such as oxytocin and vasopressin are
likely to be the prior or proximate causes of altered cognition in autism. These
low-level aberrations likely influence and give rise to the emergent aberrations
in cortical areas, which should be considered the high-level targets for
cognitive/behavioral interventions.

Natural selection cannot act on behavior directly but instead acts on the
neural substrates that generate the psychological mechanisms that create the
behavior (Buss, 1995). These brain modules were naturally selected to be
sensitive to a narrow range of perceptual information, preparing the organism
to learn about or solve particular adaptive problems. Tuning differences in
domain-specific mechanisms or modules may underlie the differences in
autistic cognition and, like other differences seen in nature, may have been
created by natural selection to help solitary foragers face their particular set of
recurrent or ecologically relevant threats and opportunities. High level
behaviors affected by these processes may include eye contact, facial
expressiveness and facial recognition.

Averted gaze and poor eye contact are very common in autism (Hutt &
Ounsted, 1966). Autistic individuals describe eye contact as uncomfortable
and even threatening. Interestingly, eye contact is also very rare in the vast
majority of solitary species, including orangutans, who actively avoid both
direct gazing and even facing (Yamagiwa, 1992). Chimpanzees and gorillas
share gazes and use the eyes for communication frequently, just like most
humans (Gomez, 1996). Staring between unfamiliar apes is often interpreted
as a threat signal; therefore, it is best for the solitary orangutan to avoid both
eye contact and direct gazing in order to forestall an attack (Gomez, 1996).
Solitary orangutans actively avoid gazing and eye contact and this tendency,
very common among solitary animals, has been explicitly interpreted as
adaptive for their solitary foraging niche (Yamagiwa, 1992). Instead of face-to-
face direct viewing, orangutans, like individuals with autism, glance
momentarily at others sideways with the head turned away (Kaplan & Rogers,
1996). The neurological substrates (including amygdalar sensitivity) that
underlie this very specific and prominent tendency may have evolved for the
same adaptive, defensive reasons in both autism and orangutan.
Studies have shown that autistic individuals are less expressive especially
with respect to facial communication. They make fewer facial expressions and
are rated as more flat or neutral in affect by observers (Yirmija et al., 1989).
This absence of facial responsiveness is probably due to underlying neuronal
mechanisms and there is evidence that the facial motor nucleus is significantly
reduced in size in autism (Rodier et al., 1996). Fascinatingly, the size of the
facial motor nucleus is thought to vary predictably in total volume as a function
of group size in monkeys and apes. The larger the average group size, the
more important facial expressiveness is and the larger the facial motor nucleus
must be (Sherwood, 2005). It should be informative to analyze the anatomical
organization of the autistic facial motor nucleus taking note of the general size,
the placement of motor neurons, distribution of neuron types and the general
topography of muscle representation.

Face processing, a key factor in the development of social perception, is
severely impaired in autism (Dalton et al., 2005). The area responsible for
face recognition, the fusiform face area, in particular has demonstrated
reduced activation in autism during facial discrimination tasks (Pierce &
Redcay, 2008) indicating that in autism, like in many solitary animal species
(Cosmides & Tooby, 1992), identity recognition may not be as valuable.


Epigenetics and Phenotypic Plasticity
Research in the field of phenotypic plasticity and epigenetics has shown that
many organisms, from plants to flies to people demonstrate predictive
adaptive responses to particular environmental stressors (Auld et al., 2010).
There are many examples of predictive adaptive responses in nature and they
allow organisms to use specific, early, environmental cues to influence their
developmental trajectory (Via & Lande, 1985). Study of these “predictive,
adaptive responses” have shown that virtually all species can be
reprogrammed by portending environmental cues, that the morphological
changes are brought about by alterations in gene expression and that this
potential for change allows members of a species to conform to occasional but
regularly recurring environmental pressures (DeWitt & Scheiner, 2004). It may
be possible that some social mammals are receptive to certain foreboding
environmental cues that give them information about the social environment
that they can expect after birth. Cues indicative of social attenuation might be
used by developing mammals to alter their social neurochemistry. It is already
known that rats and humans respond in a similar way to cues about stress in a
behavioral response referred to as “social referencing.” Researchers like
Michael Meaney at McGill University have documented that stress
responsiveness can be largely programmed in young rats. The frequency of
early cues indicative of maternal care (such as the extent of early maternal
stress, arched back nursing, licking and grooming) modulate the expression of
genes that regulate behavioral and neuroendocrine responses to stressors
(Zhang et al., 2006). In other words, mammals stressed in utero and beyond
genetically modify themselves to ensure that they are better prepared for a
threatening environment (Reser 2006; 2007).

Some mammals have been documented to exhibit adaptive, social flexibility or
plasticity to changing social environments. Both sexes of African striped
mouse (Rhabdomys pumilio) have been shown to exhibit such resilience by
changing their reproductive tactics facultatively (Schradin et al., 2011).  In
mammals, high population density favors philopatry and group-living, while
reproductive competition, absence of surviving female relatives, high
predation pressure, infanticide, and low food availability favor dispersal and
solitary-living (Schradin et al., 2011; Randall et al., 2005). Ecological
constraints in the prevailing environment determine which strategy will
contribute the most to evolutionary fitness. Phenotypic flexibility, in the form of
endocrine adjustments have been documented in the African striped mouse
and the phenotypic flexibility is attributed to epigenetic changes and a broad
reaction norm, not to polymorphism. Ongoing research has shown that
specific endocrine changes underlie these proclivities including higher
testosterone, lower prolactin and lower glucocorticoid levels (Schradin et al.,
2011). Interestingly, there is also evidence of aberrations in each of these
three hormones in humans with autism. Similar plasticity has been
documented in adult male primates. First-time and experienced father
marmosets who had spent a considerable amount of time carrying infants had
a greater number of vasopressin V1a receptors in the prefrontal cortex than
adult male nonfathers living in similar social conditions (Kozorovitskiy et al.,
2006).

Recent research has underscored the large environmental influences in
autism. These studies have confirmed that autism is not only driven by
genetics but can be strongly associated with particular environmental
scenarios. Research has even revealed that autism may be associated with
aberrant epigenetic methylation of the oxytocin receptor (Gregory et al., 2009).
Autism may be linked with specific environmental cues that are predictive of
the quality of the social environment that the fetus is “expecting” to be born
into. The questions to ask are: 1) “Could epidemiological factors that
predispose to autism, or some facet related to them, offer information to a
fetus about the condition of the social environment that its mother is
experiencing? 2) Are there other cues that the fetus could intercept and
respond to that indicate how valuable social cognition has proven to be to its
parents?” This perspective could influence geneticists and epidemiologists to
reinterpret the epigenetic contributions to autism, change how they look for
environmental effects and cause them to hone in on specific molecular
pathways responsible for changes in gene expression.

The Social/Solitary Dichotomy in Nonhuman Primates
Non-human primate models can be preferable to rodent models because
primates are more closely related to humans, have complex social structures,
rely on vision for social signaling, and have deep homology in brain circuitry
mediating the computation of reward sensitivity and social value. On the other
hand, they have only infrequently been used to model autism because
primates are more expensive to manage than rodents, are not appropriate for
invasive studies due to ethical concerns, are “low-throughput” due to much
longer gestation times, and are not ideal for knock-in, knock-out or
optogenetic studies. Primates, and especially apes, are relatively social
mammals but each species can be shown to lie on a spectrum. Nocturnal
prosimians, such as mouse lemurs, dwarf lemurs, bushbabies, and lorises are
solitary foragers, do not live in groups, but do exhibit some social networking
faculties (Bearder, 1987). Interestingly, these “stem primates” are thought to
represent the ancestral pattern of primate social organization (Muller &
Thalmann, 2000; Shultz et. al., 2011).

Orangutans, socially cautious and introverted, are known to eat, sleep, hunt,
and forage on their own, and are thought to spend around 95% of their time in
the wild alone (Delgado & Van Schaik, 2000; Van Schaik, 1999). Orangutans
have low interaction and association rates, and only infrequently meet up with
conspecifics, often only to mate (Van Schaik & Van Hoof, 1996). Chimpanzees
are gregarious yet have fluid, fission-fusion societies, in which group members
split up into small groups during daily excursions, and later reconvene in
response to changes in food distribution. Chimps usually forage in groups but
are known to forage solitarily when food becomes scarce (de Waal, 1982).
Bonobos and savanna baboons tend to form significantly larger, more socially
cohesive groups and both primarily forage together. Despite these dramatic
differences in the behavior of these primates, it has not yet been made clear if
these discrepancies are attributable to ecological factors, neurological factors
or both.

Polymorphism in the repetitive microsatellite locus for the vasopressin
receptor mentioned above is present in both humans and bonobos.
Chimpanzees, which are thought to exhibit slightly lower levels of social
reciprocity, empathy, and sociosexual bonding relative to bonobos, do not
have this microsatellite locus and Hammock and Young (2005) have
suggested that this is reminiscent of the genetic differences between montane
and prairie voles at this same locus. It is thought that bonobos are more social
and easy going because their foraging territory south of the Congo River is
much richer in large fruiting trees than that of chimpanzees north of the
Congo. Thus reduced foraging competition seems to facilitate social life in
bonobos (Wrangham RW, 1986; Hare et al., 2007), and may have resulted in
a human-like AVP expression profile. Recall that autism on the other hand,
has been strongly associated with a very different AVP expression profile and
with overtransmission of specific microsatellite repeats in this same gene
(Yirmiya et al., 2006; Wassink et al., 2004).

Pair living is relatively rare in primates but group living is not. The most
common type of social organization in nonhuman primates consists of
relatively promiscuous multimale/multifemale social groups, but even though
there is no pair bonding, group members bond. There is a paucity of research
on this topic though, and the influence of social neuropeptides on primate
group structure has been largely neglected. In anthropoid primates, same-sex
relationships have much in common with sexual relationships in mammals that
form monogamous pairs. They both involve high levels of coordination,
behavioral synchronization and compromise (Machin & Dunbar, 2011), and
both involve a central role of oxytocin (Dunbar, 2008). Thus, even though
voles provide a strong foundation for social neuroscience, further research
into primate social neurochemistry should be highly informative.


Conclusions

This line of research points to four major dichotomies that might help to model
autism, listed in Table 4 below. There is a monogamous/nonmonogamous
dichotomy; a group/solitary dichotomy; and a domestic/wild dichotomy. There
may also be a relevant female/male dichotomy as well as there is evidence of
significant sexual dimorphism in many, if not all of the neurobiological systems
discussed (Hammock & Young, 2006; Baron-Cohen, 2003). The biodiversity
underlying these dichotomies should be interrogated from the perspective of
comparative psychology and biology.

An important question remains: Are the neurobiological mechanisms found in
solitary and nonmonogamous mammals sufficient to capture the nuanced
social impairments featured in the autism diagnosis? Because of the various,
genetic and environmental, etiological contributions to autism (Cantor, 2009) it
is clear that only a fraction of what is known as autism could be accurately
modeled by cognitive specializations for solitary living in other mammals. The
modern, nosological entity of autism is a mixture of phenotypes with separate
causes lumped together by clinicians, and a large proportion of it may
represent disease that cannot be reliably compared to naturally occurring
phenotypes in animals. Based on the paucity of basic research and the
absence of consensus in the literature, the present line of research
necessitates further critical examination, as well as questioning of the
methodology and even the structuring assumptions. Ultimately, understanding
ASD will probably require synthesis across several different models, which
together should offer complementary and convergent conclusions.
This model, unlike most animal models, does not detail how to alter or
program a laboratory animal to mimic aspects of autism. The pronouncements
here have not made considerations for immediate application but are much
more general and expository. Normally diseases with discrete, recognized
causes such as Rett syndrome, Down syndrome and fragile X, are best
amenable to animal modeling and immediately suggest treatment options.
Highly polygenic disorders that also involve phenotypic plasticity, and de novo
mutations, such as autism, are more difficult to model and the models are
more difficult to assess. The utility of animal models for autism is commonly
assessed using three criteria: (i) face validity (resemblance to human
symptoms); (ii) construct validity (similarity to the underlying causes of the
disease); and, (iii) predictive validity (expected similar responses to
treatments). It is currently not possible to meaningfully assess the validity or
value of the present model.

Not only could the study of solitary mammals affect the study of autism, but
research in autism could also help to elucidate phenomena in social
neuroscience and social psychology. Traits associated with autism, aside from
those listed in Tables 1 & 2, should be investigated in a variety of solitary
mammals, including: joint attention, pretend play, facial expressiveness,
communicative intent, empathy, the mirror neuron system, fusiform recognition
areas, and other social cortical areas. Also, this research should have
implications for understanding other disorders marked by alterations in related
social pathways such as borderline personality disorder, insecure attachment
disorder, psychopathy and William’s syndrome. Robert Plomin, author of the
leading textbook, Behavioral Genetics (2008), writes: “[We predict that] when
genes are found for common disorders such as mild mental retardation or
learning disabilities, the same genes will be associated with variation
throughout the normal distribution of intelligence, including the high end of the
distribution (Plomin et al., 2006).” Could something similar be true throughout
the normal distribution of sociality, including social deficits, ASDs and other
disorders of bonding, attachment and empathy?

Convergent evolution is pervasive, and the similarities between autism and
solitary animals may extend beyond superficial resemblances. An article by
Reser (2011) reviews etiological and comparative evidence supporting the
hypothesis that some genes associated with the autism spectrum were
naturally selected and represent the adaptive benefits of being cognitively
suited for solitary foraging. People on the autism spectrum are conceptualized
here as potentially ecologically competent. The article suggests that upon
independence from their mothers, young individuals on the autism spectrum
may have been psychologically predisposed toward a different life-history
strategy, common among mammals and even some primates, to hunt and
gather primarily on their own. This may have resulted from periodic or
geographic disruptions in the efficacy of group foraging in the ancestral past,
or from reduced adaptive value of sociocultural information sharing. The
resulting evolutionary pressures may have driven the selection of genes that
created social processing deficits making their bearers resistant to the
transference of units of cultural information (memes). Many of the behavioral
and cognitive tendencies that autistic individuals exhibit are viewed as
adaptations that would have complemented a solitary lifestyle. Table 5
presents some of these tendencies, their implications for modern individuals
and their implications for prehistoric, solitary foragers. The article emphasizes
that individuals on the autism spectrum may have only been partially solitary,
that natural selection may have only favored subclinical autistic traits and that
the most severe cases of autism may be due to assortative mating.

Perhaps components of the autism spectrum can be understood in terms of
behavioral ecology and evolutionary medicine, but this does not necessarily
mean that autism is an ecological anachronism. Several scientists and many
autism advocacy groups promote the idea that autism has compensatory
advantages even in modern society (Grandin & Panek 2013; Baron Cohen,
2006). Individuals on the autism spectrum have been shown to exhibit
extremely high levels of achievement in systemizing domains, such as
mathematics, physics, and computer science (Baron-Cohen et al., 1999) and
this is referred to as the “autism advantage” in popular autism advocacy.

The contemporary, postgenomic age allows molecular methods that were
practically inconceivable before genome sequencing was possible. The
emerging field of “evolutionary cognitive genetics” makes it clear that there
can now be confluence and integration between fields such as brain
genomics, human population genetics, and molecular anthropology. The
methodology of this field may be applicable here. In order to use modern
methods to study the present relationships it might be helpful to: A) perform
large-scale comparisons of genes across several strategically selected
species in a search for social dimorphisms or social genes with highly
elevated rates of evolution in mammals or primates; B) determine if the alleles
for these genes are associated with specific social phenotypes using in vitro
and in vivo lab studies; and C) subject the candidate genes to polymorphism
and association studies in humans.

The analytical tools that social neuroscientists use to study social capacity in
other vertebrates can, with appropriate caution, be used to study social
capability in humans. Other species have found myriad ways to reduce social
contact for ecological purposes, and understanding how this is accomplished
may provide insight into prosocial pharmacotherapeutics or even gene therapy
for autism. How can the present comparative, neuroethological approach help
with autism? In this author’s opinion, the way it can help the most is through
comparative neurobiology. It will be interesting to see if neuroanatomical
receptor distribution patterns of oxytocin, vasopression, endogenous opioids,
prolactin, serotonin and dopamine in the brains of solitary mammals resembles
those observed in autism. If there are significant resemblances, it will be
important for scientists to compare the distributions patterns of these
receptors in different animals to help determine which areas in the autism
brain feature a paucity of receptor expression, so that these specific areas can
be targeted. It may be possible to test drugs and even behavioral interventions
in solitary or nonmonogamous animals to determine if these have the capacity
to reverse social interaction deficits. The model may allow an alternate
vantage point into the autistic brain, which can only be studied in limited ways
because of technical limitations and ethical concerns.

For the Tables of this article please visit:

   http://www.observedimpulse.com/2013/11/solitary-mammals-provide-animal-
model.html                 

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