Oxytocin & Vasopressin In Treating Autism

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    Oxytocin and Vasopressin in Treating

    Autism: Results of Comparative Research

    by Daniel M. Hitzfield


    Using animal models to understand the mechanisms underlying human social behavior

    reveals otherwise inaccessible neurophysiological processes. There are three purposes to this

    paper. First, to review the findings of prominent comparative research on oxytocin and

    vasopressin in regards to their effect on adult social bonding. Second, to summarize

    advancements made in treating autism, a social disorder. Third, to discuss the limits of

    comparing animal models to human research.

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    Long-term, healthy social affiliations (e.g., relationships) have been clinically correlated

    with the peak mental health of human individuals (Lim & Young, 2006). The latter century has

    yielded the necessary equipment for scientific studies to pinpoint the areas of the human brain

    associated with social behavior, such as the amygdala and medial prefrontal cortex (Fossati,

    2012). Unfortunately, the neuroendocrinology of human social behavior remains under research

    without a wholly consistent explanation for its effects; it is considered a critical area of

    neuroscience to explore because understanding the neurophysiological mechanisms will

    hopefully highlight possible treatments for human social disorders. This ongoing work is still

    largely in the stages of correlating specific pathways with subsets of behavior (e.g., Zink et al.,

    2011). At best, analyzing just the human brain and relevant behavior in case studies only allows

    for a superficial understanding of the adult mental and behavioral processes governing social

    interaction. Animal models, on the other hand, have been previously shown to shed light on the

    mental and behavioral processes of humans without overstepping the bounds of ethics that would

    be violated in similar experiments actually involving humans (Modi & Young, 2012). Moreover,

    animal correlates to human behavior are practically necessary to uncover the the most effective

    size, time period and method of treatment in many cases. Defining the effect of oxytocin (OT)

    and vasopressin (VP) treatments on animals' adult social affiliative behavior will be the former

    purpose of this paper. The latter will be review and summary of case studies and other

    experiments performed on humans regarding OT and VP treatment as a potential cure for autism

    spectrum disorder (ASD). ASD covers a range of dysfunctional behaviors from almost

    unnoticeable to crippling degrees of social impairment.

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    Adult Social Affiliation

    Affiliative behavior is defined as any action that fosters social relationships, or bonds.

    Regarding humans, this set of behaviors dominates life and relationships with peers of either sex

    (Lim & Young, 2006). As peer relationships are the most common, they will be the sole

    subsection of affiliate behavior discussed. The most long-lasting of these relationships are often

    those of pair-bonds (i.e., sexual partners), as evidenced by the research of Young & Wang (2004).

    Pair bonds are typically judged by recording the quantity of particular behaviors in non-human

    experiments, such as the work done by Garber & Leigh (1997) on eleven different species of

    New World primates. These can include social grooming (i.e., allogrooming), sharing resources

    and huddling together (Garbe & Leigh, 1997; Adiseshan et al., 2011). Other experiments on

    primates, particularly a study done on macaques by Adiseshan et al. (2011), demonstrated much

    longer-term social relationships on a scale beyond pair bonds; these varied by kin (i.e., extended-

    family alliances) or simple living-proximity group alliances (Adiseshan et al., 2011).

    Furthermore, maintenance of these larger-scale alliances has been observed as conciliatory

    behavior soon after aggression occurs by one or both parties involved (Cords and Aureli, 1997).

    The importance of this social activity as a whole is confirmed by the majority of time spent in

    affiliative behavior by primates in general: anywhere from 50-98% (Sussman et al., 2005). This

    behavior (ie making and maintaining friendship) is also observed alongside and blunting

    aggressive or competitive behavior in a variety of non-human species (Sussman et al., 2005).

    These studies of animals and particularly of primates correlate well with studies of equivalent

    human social affiliative behavior (Ebstein et al., 2012), making comparison the most promising

    method of determining the most efficacious treatments of ASD.

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    Mechanisms Influencing Social Affiliation

    In the history of neurophysiology in relation to social disorders, research on humans in

    the past century has been limited to individuals with social impairments or pre-existing brain

    damage (as opposed to lesioning performed on non-humans); in the latter part of this century

    brain-imaging techniques possible because of developing technology have become the forefront

    methods in human studies (Kennedy & Adolphs, 2012). While such studies provide a chance to

    determine ultimate cause-and-effect, regulatory pathways and their intermediates are still not

    coherently understood to a satisfactory degree. Moreover, the subject of social relationships and

    its set of behaviors is a difficult one, because it relies upon the processing of information on

    multiple levels of consciousness. In order to make progress, one level of these processing

    pathways in the brain is examined at a time and for a particular system. In this case, that system

    is the pathway(s) by which OT and VP regulate social cognition and emotion. Fortunately, non-

    human social behaviors recorded in a lab setting correlate well with observation of natural non-

    human social behavior (Lim & Young, 2006) and with human brain-imaging results (Zink &

    Meyer Lindenberg, 2012).

    Regarding the influence of OT and VP on social affiliative behavior, researchers have

    particularly focused on the prairie vole (Microtus Ochrogaster) and experimental manipulation

    of its naturally strong monogamous traits. Earlier experiments were only performed on a

    relatively short-term basis (e.g., Carter et al., 1995; Cho et al., 1999; Young & Wang, 2004),

    while experiments in the last year or so have expanded experimental parameters to the entire

    lifetime of the prairie vole (e.g., Bales et al., 2013). Another species that has proven useful is the

    Wistar rat (Rattus Norvegicus), used to determine specific oxytonergic and vasopressinergic

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    pathways and observe multiple social behaviors (e.g., De Vries & Bujis, 1983). Similarly, mice,

    whether bred as transgenic comparisons to other species or tested as wild-types, have provided

    additional data on social behavior (e.g., Young et al., 1999).

    Neuropeptides Implicated in Regulating Social Behavior

    According to work done by De Vries & Bujis (1983) on rats, OT is originally

    manufactured by the paraventricular nuclei (PVN) or supraoptic nuclei (SON) of the

    hypothalamus in order to act on its corresponding oxytocin receptors (OTR) scattered in the

    brain; this was proven in the experiment by lesioning the PVN, which almost completely

    crippled the oxytocinergic system. In a review of OT and VP, Sofroniew (1983) supported the

    conclusions of De Vries & Bujis, adding that both the PVN and SON project toward the posterior

    pituitary (i.e., neurohypophysis) and both OT and VP are secreted from that point as peptides

    into peripheral circulation; OT in particular was associated with numerous projection sites from

    the PVN: the hippocampus, striatum, nucleus accumbens and spinal cord. Like OT, VP is

    produced in the PVN and SON; it is additionally produced in the suprachiasmatic nucleus, bed

    nucleus of the stria terminalis and medial amygdala (De Vries & Miller, 1998). Either VP or OT

    that is released centrally instead of peripherally has been determined for some time to have a

    strong influence on social behavior; evidence that has been uniform across numerous rodent and

    other mammalian experimental subjects (Lim & Young, 2006). These two have been the

    promising candidates for research in later decades because of their additional evidence for

    altering neuronal activity.

    Adult Affiliative Behavior: Oxytocin

    Rats are ordinarily social animals with several distinctive non-sexual affiliative behaviors

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    which makes them one of the more tested subjects to determine the role of OT. In a study very

    recently performed on them by Calcagnoli et al. (2013), it was determined that acute, short-term,

    centrally-injected doses of OT resulted in two distinctive behavior changes: reduced levels of

    anti-social intruder aggression, and marked increase of time spent in social contact. Note, social

    contact simply denotes exploration among and proximity with other individuals, not necessarily

    the observation of specific behaviors. In the same experiment, another experimental group was

    centrally-injected with an OT antagonist, resulting in a non-significant increase of aggression

    among naturally low-aggression rats, and almost no difference in ordinarily high-aggression rats.

    In short, observation for one hour after the intracerebr

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