Article

Promoting social behavior with oxytocin in high-functioning autism spectrum disorder. Proc Natl Acad Sci U S A

Centre de Neuroscience Cognitive, Unité Mixte de Recherche 5229, Centre National de la Recherche Scientifique, 69675 Bron, France.
Proceedings of the National Academy of Sciences (Impact Factor: 9.67). 02/2010; 107(9):4389-94. DOI: 10.1073/pnas.0910249107
Source: PubMed

ABSTRACT

Social adaptation requires specific cognitive and emotional competences. Individuals with high-functioning autism or with Asperger syndrome cannot understand or engage in social situations despite preserved intellectual abilities. Recently, it has been suggested that oxytocin, a hormone known to promote mother-infant bonds, may be implicated in the social deficit of autism. We investigated the behavioral effects of oxytocin in 13 subjects with autism. In a simulated ball game where participants interacted with fictitious partners, we found that after oxytocin inhalation, patients exhibited stronger interactions with the most socially cooperative partner and reported enhanced feelings of trust and preference. Also, during free viewing of pictures of faces, oxytocin selectively increased patients' gazing time on the socially informative region of the face, namely the eyes. Thus, under oxytocin, patients respond more strongly to others and exhibit more appropriate social behavior and affect, suggesting a therapeutic potential of oxytocin through its action on a core dimension of autism.

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Available from: Tiziana Zalla, Nov 29, 2014
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    • "More recent efforts have expanded these findings by administering IN-OT to clinical populations with deficits in social function, such as individuals with autism spectrum disorder (ASD). Indeed, there are now several studies showing that IN-OT can ameliorate several aspects of social function in adults and children with ASD, including enhancing the saliency of human faces (Domes et al., 2013), improving emotion recognition (Guastella et al., 2010), and increasing feelings of social reciprocity and increasing gaze to the eyes (Andari et al., 2010). Despite the progress that has been made in the clinical application of OT, the pharmacokinetics of IN-OT within the central nervous system (CNS) remain unclear. "
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    ABSTRACT: Oxytocin (OT) is a neuropeptide that mediates a variety of complex social behaviors in animals and humans. Intranasal OT has been used as an experimental therapeutic for human conditions characterized by deficits in social functioning, especially autism spectrum disorder and schizophrenia. However, it is currently under intense debate whether intranasal delivery of OT reaches the central nervous system. In this study, four female rhesus macaques were implanted with chronic intrathecal catheters and used to investigate the pharmacokinetic profile of OT in the central nervous system and the peripheral vasculature following intravenous (IV) and intranasal (IN) administration of OT. In a randomized, crossover design, OT was given to four awake monkeys at three different doses based on body weight (0.1 IU/kg; 1 IU/kg; 5 IU/kg). A time course of concurrent cerebrospinal fluid (CSF) and plasma samples were taken following administration. We found a dose-dependent effect of IV OT treatment on plasma OT levels, which peaked at 5 min post-dose and gradually returned to baseline by 120 min. In contrast, a change in CSF OT was only observed at the highest IV dose (5 IU/kg) at 15 min post-dose and gradually returned to baseline by 120 min. After IN administration, there was no significant change in plasma OT at any of the three doses. However, at the highest dose level, we found a significant increase in CSF OT at 15 to 30 min post-dose. The results of this study in light of recent, similar publications highlight the importance of methodological consistency across studies. This study also establishes a non-human primate model that can provide a stable platform for carrying out serial sampling from the central nervous system and peripheral vasculature concurrently.
    Full-text · Article · Jan 2016 · Psychoneuroendocrinology
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    • "Oxytocin is a neuropeptide hormone with a long-recognized role in maternal responses and mother-infant bonding. Clinical studies in subjects with autism spectrum disorder (ASD) have found that acute oxytocin can improve social function and decrease motor stereotypy and other forms of repetitive behavior (Andari et al., 2010; Guastella et al., 2010; Hollander et al., 2003, 2007). Further, Hall and colleagues (2012) observed that acute oxytocin could ameliorate indicators of social anxiety in male adolescents and adults with fragile X syndrome. "
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    ABSTRACT: Social deficits are a hallmark feature of autism spectrum disorder (ASD) and related developmental syndromes. Although there is no standard treatment for social dysfunction, clinical studies have identified oxytocin as a potential therapeutic with prosocial efficacy. We have previously reported that peripheral oxytocin treatment can increase sociability and ameliorate repetitive stereotypy in adolescent mice from the C58/J model of ASD-like behavior. In the present study, we determined that prosocial oxytocin effects were not limited to the adolescent period, since C58/J mice, tested in adulthood, demonstrated significant social preference up to 2 weeks following subchronic oxytocin treatment. Oxytocin was also evaluated in adult mice with underexpression of the N-methyl-D-aspartate receptor NR1 subunit (encoded by Grin1), a genetic model of autism- and schizophrenia-like behavior. Subchronic oxytocin had striking prosocial efficacy in male Grin1 knockdown mice; in contrast, chronic regimens with clozapine (66 mg/kg/day) or risperidone (2 mg/kg/day) failed to reverse deficits in sociability. Neither the subchronic oxytocin regimen, nor chronic treatment with clozapine or risperidone, reversed impaired prepulse inhibition in the Grin1 knockdown mice. Overall, these studies demonstrate oxytocin can enhance sociability in mouse models with divergent genotypes and behavioral profiles, adding to the evidence that this neurohormone could have therapeutic prosocial efficacy across a spectrum of developmental disorders.
    Full-text · Article · Jan 2016 · Neuropharmacology
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    • "OXT interacts with the hypothalamo– pituitary–adrenal axis to attenuate the stress response, and it induces potent physiological anxiolytic effects by decreasing cortisol levels, inhibiting cardiovascular responses to stress, and attenuating amygdala responsivity to emotional stimuli (Rodrigues et al. 2009). Much attention in the human literature has been devoted to the enhancing effect of OXT on social skills in certain psychiatric conditions such as autism (Andari et al. 2010). The Krisztina Kovács and Anna Kis have contributed equally to this work and should be considered as co-first authors. "
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    ABSTRACT: Recent studies have shown that the neuropeptide oxytocin is involved in the regulation of several complex human social behaviours. There is, however, little research on the effect of oxytocin on basic mechanisms underlying human sociality, such as the perception of biological motion. In the present study, we investigated the effect of oxytocin on biological motion perception in dogs (Canis familiaris), a species adapted to the human social environment and thus widely used to model many aspects of human social behaviour. In a within-subjects design, dogs (N = 39), after having received either oxytocin or placebo treatment, were presented with 2D projection of a moving point-light human figure and the inverted and scrambled version of the same movie. Heart rate (HR) and heart rate variability (HRV) were measured as physiological responses, and behavioural response was evaluated by observing dogs' looking time. Subjects were also rated on the personality traits of Neuroticism and Agreeableness by their owners. As expected, placebo-pretreated (control) dogs showed a spontaneous preference for the biological motion pattern; however, there was no such preference after oxytocin pretreatment. Furthermore, following the oxytocin pretreatment female subjects looked more at the moving point-light figure than males. The individual variations along the dimensions of Agreeableness and Neuroticism also modulated dogs' behaviour. Furthermore, HR and HRV measures were affected by oxytocin treatment and in turn played a role in subjects' looking behaviour. We discuss how these findings contribute to our understanding of the neurohormonal regulatory mechanisms of human (and non-human) social skills.
    Full-text · Article · Jan 2016 · Animal Cognition
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