Promoting social behavior with oxytocin in high-functioning autism spectrum disorders

Andari, Elissar; Duhamel, Jean‐René; Zalla, Tiziana; Herbrecht, Evelyn; Leboyer, Marion; Sirigu, Angela

doi:10.1073/pnas.0910249107

Cited by 813 publications

(640 citation statements)

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“…Interestingly, the AVPR1a receptor of the closely related nonapeptide vasopressin has also been associated with ASD [40][41][42]. This provisional role of OT in ASD, is further supported by two linkage studies [43,44], clinical evidence by several groups demonstrating clinical improvement in ASD following OT administration [45][46][47][48][49][50][51] (also see [52,53]) and studies showing that ASD is also associated with alterations in OT plasma levels [54].…”

Section: Oxytocin and Autism Spectrum Disorders (Asd)mentioning

confidence: 91%

Are retinoids potential therapeutic agents in disorders of social cognition including autism?

et al. 2011

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Edited by Sergio Papa, Gianfranco Gilardi and Wilhelm JustKeywords: Autism spectrum disorder (ASD) All-trans retinoic acid (ATRA) CD38 Oxytocin Polymorphism a b s t r a c t Increasing evidence suggests that the nonapeptide, oxytocin (OT), helps shape social and affiliative behaviors not only in lower mammals but also in humans. Recently, an essential mediator of brain OT release has been discovered, ADP-ribosyl cyclase and/or CD38. We have subsequently shown that polymorphisms across the CD38 gene are associated with autism spectrum disorders (ASD). Notably, CD38 expression in lymphoblastoid cells (LBC) is reduced in cell lines derived from ASD subjects compared to parental cell lines. Intriguingly, a correlation was observed between CD38 expression and measures of social function in ASD. Finally, we have shown that all-trans retinoic acid (ATRA), a known inducer of CD38 transcription, can rescue low CD38 expressing LBC lines derived from ASD subjects and restore normal levels of transcription of this ectoenzyme providing 'proof of principle' in a peripheral model that retinoids are potential therapeutic agents in ASD. Ó 2011 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved. OxytocinClassically, the nonapeptide oxytocin (OT) has been viewed as a hypothalamic neuropeptide that is released into the general circulation from the neural lobe of the pituitary, inducing uterine contractions during parturition and milk ejection during lactation. OT is derived from a pre-prohormone precursor that is synthesized in the hypothalamus and stored in vesicles at the posterior pituitary for storage and subsequent release into the bloodstream (see [1] for comprehensive review of the oxytocin receptor system). OT and social behaviorBeyond the long-known peripheral effects of OT, a wealth of animal studies have elaborated the role of OT, or their analogues such as isotocin and vasotocin [2], in molding social behavior from fish to mammals [3]. In the past few years the role of OT has also been examined in our own species, and similar to what has been learned from animal studies, it appears that this nonapeptides also influence social behaviors in humans [4,5]. Indeed, OT has been suggested as the 'great facilitator of life' in a recent review [6].In humans, intranasal administration of OT has been shown to increase trust [7], facilitate mind-reading [8], enhance human memory for social identity [9], increase positive communication between couples [10], increase gaze to the eye region [11] and increase generosity [12]. Intriguingly, OT plasma levels have been linked to individual patterns of maternal-fetal attachment [13] and salivary OT levels were associated with bonding to own parents and inversely related to psychological distress, particularly depressive symptoms [14]. Social anxiety symptom severity, adjusted for age and gender in a healthy group of subjects, was associated with higher plasma oxytocin levels [15]. Imaging studies reinforce the role of OT in influencing human social ...

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Section: Oxytocin and Autism Spectrum Disorders (Asd)mentioning

confidence: 91%

Are retinoids potential therapeutic agents in disorders of social cognition including autism?

et al. 2011

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“…Human studies have focused on pharmacological administration and the measurement of plasma neuropeptides, mainly of OXT. It has been suggested that intranasal OXT is beneficial for the remission of autistic symptoms by improving cooperation and sense of trust [15] as well as by enhancing social responsiveness [16] and social reciprocity [17].…”

Section: Introductionmentioning

confidence: 99%

“…Four studies have shown lower plasma OXT levels in children with ASD than in control individuals [15,[18][19][20], two studies have reported higher OXT levels [21,22], and one has reported no overall group difference [23]. Relationships between plasma OXT levels and social behaviors were either not investigated [15,21] or were analyzed in subsets or subtypes of ASD [22,23].…”

Section: Introductionmentioning

confidence: 99%

Plasma Oxytocin and Arginine-Vasopressin Levels in Children with Autism Spectrum Disorder in China: Associations with Symptoms

Zhang

Dai

et al. 2016

Neurosci. Bull.

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Autism spectrum disorder (ASD) is defined by impairments of social interaction and the presence of obsessive behaviors. The ''twin'' nonapeptides oxytocin (OXT) and arginine-vasopressin (AVP) are known to play regulatory roles in social behaviors. However, the plasma levels and behavioral relevance of OXT and AVP in children with ASD have seldom been investigated. It is also unknown whether their mothers have abnormal plasma peptide levels. Here, using well-established methods of neuropeptide measurement and a relatively large sample size, we determined the plasma levels of the two neuropeptides in 85 normal children, 84 children with ASD, and 31 mothers from each group of children. As expected, children with ASD had lower plasma OXT levels than gender-matched controls (P = 0.028). No such difference was found for plasma AVP concentrations. Correlation analysis showed that ASD children with higher plasma OXT concentrations tended to have less impairment of verbal communication (Rho = -0.22, P = 0.076), while those with higher plasma AVP levels tended to have lower levels of repetitive use of objects (Rho = -0.231, P = 0.079). Unlike the findings in children, maternal plasma OXT levels showed no group difference. However, plasma AVP levels in the mothers of ASD children tended to be lower than in the mothers of normal children (P = 0.072). In conclusion, our results suggest that the OXT system is dysregulated in children with ASD, and that OXT and AVP levels in plasma seem to be associated with specific autistic symptoms. The plasma levels of OXT or AVP in mothers and their ASD children did not seem to change in the same direction.

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“…Moreover, several studies have shown that administering oxytocin improves symptoms of autism. Intranasal oxytocin improves the ability of young autistics to recognize emotions in the ''Reading the Mind in the Eyes'' task (Guastella et al, 2010) and increases the positive feelings of interacting socially in a simulated ball toss game and increases preference for reciprocal relationships (Andari et al, 2010).…”

Section: Neuroendocrine Hypothesismentioning

confidence: 99%

Sexual Differentiation and the Neuroendocrine Hypothesis of Autism

Aiello

Whitaker‐Azmitia

2011

The Anatomical Record

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The phenotypic expression of autism spectrum disorders varies widely in severity and characteristics and it is, therefore, likely that a number of etiological factors are involved. However, one finding which has been found consistently is that there is a greater incidence of autism in boys than girls. Recently, attention has been given to the extreme male hypothesis-that is that autism behaviors are an extreme form of typical male behaviors, including lack of empathy and language deficits but an increase in so-called systemizing behaviors, such as attention to detail and collecting. This points to the possibility that an alteration during sexual differentiation of the brain may occur in autism. During sexual differentiation of the brain, two brain regions are highly sexually dimorphicthe amygdala and the hypothalamus. Both of these regions are also implicated in the neuroendocrine hypothesis of autism, wherein a balance between oxytocin and cortisol may contribute to the disorder. We are thus proposing that the extreme male hypothesis and the neuroendocrine hypothesis are in fact compatible in that sexual differentiation of the brain towards an extreme male phenotype would result in the neuroendocrine changes proposed in autism. We have preliminary data, treating developing rat pups with the differentiating hormone 17-b estradiol during a critical time and showing changes in social behaviors and oxytocin, to support this hypothesis. Further studies should be undertaken to confirm the role of extremes of normal sexual differentiation in producing the neuroendocrine changes associated with autism. Anat Rec, 294:1663-1670, 2011. V V C 2011 Wiley-Liss, Inc.Key words: autism; oxytocin; cortisol; sexual differentiation; extreme male TWO HYPOTHESESSimply stated, the hypothesis which we are proposing in this article, and the work currently ongoing in our lab, is that enhanced sexual differentiation of the brain, towards the male phenotype, leads to changes in the neuroendocrine factors, oxytocin and cortisol. These factors are involved in the processing and evaluation of social bonding experiences and any disruption in their typical function can lead to the primary defining characteristic of the autism phenotype-inadequate social bonding. The Extreme Male Hypothesis of AutismAutism is a disorder of brain development and thus any factors which regulate brain development and are known to be altered in autism should be considered as possibly contributing to the phenotype. For example, much of our previous work and work of others, has focused on the known role of serotonin in brain development as well as the well known hyperserotonemia which occurs in autism (Whitaker-Azmitia, 2005). More recently, researchers have proposed a role for sexual differentiation of the brain in the phenotypic behaviors of

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Promoting social behavior with oxytocin in high-functioning autism spectrum disorders

Cited by 813 publications

References 33 publications

Are retinoids potential therapeutic agents in disorders of social cognition including autism?

Are retinoids potential therapeutic agents in disorders of social cognition including autism?

Plasma Oxytocin and Arginine-Vasopressin Levels in Children with Autism Spectrum Disorder in China: Associations with Symptoms

Sexual Differentiation and the Neuroendocrine Hypothesis of Autism

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