Sex differences in oxytocin and vasopressin: implications for autism spectrum disorders?

The Brain Body Center, Department of Psychiatry, University of Illinois at Chicago, Chicago 60612, USA.
Behavioural Brain Research (Impact Factor: 3.39). 02/2007; 176(1):170-86. DOI: 10.1016/j.bbr.2006.08.025
Source: PubMed

ABSTRACT Autism spectrum disorders (ASD) are male-biased and characterized by deficits in social behavior and social communication, excessive anxiety or hyperreactivity to stressful experiences, and a tendency toward repetitiveness. The purpose of this review is to consider evidence for a role for two sexually dimorphic neuropeptides, oxytocin (OT) and arginine vasopressin (VP), in these features of ASD. Both VP and OT play a role in normal development. VP is androgen-dependent and of particular importance to male behavior. Excess VP or disruptions in the VP system could contribute to the male vulnerability to ASD. Alternatively, protective processes mediated via OT or the OT receptor might help to explain the relatively rare occurrence of ASD in females. Disruptions in either OT or VP or their receptors could result from genetic variation or epigenetic modifications of gene expression, especially during early development. Deficits in other developmental growth factors, such as reelin, which may in turn regulate or be regulated by OT or VP, are additional candidates for a role in ASD.

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    ABSTRACT: The neuropeptides oxytocin (OT) and arginine vasopressin (AVP) are involved in social bonding in attachment relationships, but their role in friendship is poorly understood. We investigated whether rhesus macaques' (Macaca mulatta) friendships at age one predicted plasma OT and AVP at two later time points. Subjects were 54 rhesus macaques at the California National Primate Research Center (CNPRC). Blood was drawn during a brief capture-and-release in the home cage, and plasma assayed for OT and AVP using an enzyme immunoassay (EIA). Separate linear mixed models for each sex tested the effects of dominance rank, age, sampling time point, housing condition, parturition status, two blood draw timing measures, and five friendship types: proximity friendships, play friendships, reciprocal friendships (a preference for a peer that also preferred the subject), multiplex friendships (friendships displayed in more than one behavioral domain), and total number of friendships. Females' number of reciprocal and play friendships at age one significantly predicted later OT; additionally, these two friendship types interacted with rank, such that high-ranking females with the fewest friendships had the highest OT concentrations. Friendship did not predict later OT levels in males, however proximity, play, reciprocal, and total number of friendships predicted males' plasma AVP. Play and total number of friendships also tended to predict AVP in females. Our results show that peripheral measures of neuroendocrine functioning in juvenile rhesus monkeys are influenced by early involvement in friendships. Friendships have an especially strong impact on an individual's psychosocial development, and our data suggest OT and AVP as potential underlying mechanisms. Moreover, sex differences in the functioning of the OT and AVP systems, and their relation to friendship, may have important clinical implications for the use of OT as a therapeutic, as well as informing the social context in which it is administered.
    Frontiers in Behavioral Neuroscience 08/2014; 8:295. DOI:10.3389/fnbeh.2014.00295 · 4.16 Impact Factor
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    ABSTRACT: Parental behavior is commonly displayed by progenitors. However, other individuals, genetically related (e.g. siblings, aunts, uncles) or not with the newborns, also display parental behavior (commonly called alloparental, or adoptive behavior). I hypothesize that species that live in family or social groups where other non-reproductive members (males and females) take care of infants, have brain adaptations to promote or facilitate that behavioral response. The present work revises the evidence supporting the hypothesis that high density of oxytocin receptors (OXTR) in the nucleus accumbens (NA) is one of those adaptations. All species known to have high NA OXTR show not only female, but also male alloparental care. Therefore, I predict that high NA OXTR could be present in all species in which juvenile and adult male alloparental behavior have been observed. Strategies to test this and other alternative working hypothesis and its predictions are presented.
    Journal of Physiology-Paris 10/2014; 108(2-3). DOI:10.1016/j.jphysparis.2014.10.002 · 2.35 Impact Factor
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    ABSTRACT: Oxytocin (OT) is a neuropeptide involved in mammalian social behavior. It is currently in clinical trials for the treatment of autism spectrum disorder (ASD). Previous studies in healthy rodents (prairie voles and C57BL/6J mice) have shown that there may be detrimental effects of long-term intranasal administration, raising the questions about safety and efficacy. To investigate the effects of OT on the aspects of ASD phenotype, we conducted the first study of chronic intranasal OT in a well-validated mouse model of autism, the BTBR T+ Itpr3tf/J inbred strain (BTBR), which displays low sociability and high repetitive behaviors. BTBR and C57BL/6J (B6) mice (N=94) were administered 0.8 IU/kg of OT intranasally, daily for 30 days, starting on day 21. We ran a well-characterized set of behavioral tasks relevant to diagnostic and associated symptoms of autism, including juvenile reciprocal social interactions, three-chambered social approach, open-field exploratory activity, repetitive self-grooming and fear-conditioned learning and memory, some during and some post treatment. Intranasal OT did not improve autism-relevant behaviors in BTBR, except for female sniffing in the three-chambered social interaction test. Male saline-treated BTBR mice showed increased interest in a novel mouse, both in chamber time and sniffing time, whereas OT-treated male BTBR mice showed a preference for the novel mouse in sniffing time only. No deleterious effects of OT were detected in either B6 or BTBR mice, except possibly for the lack of a preference for the novel mouse's chamber in OT-treated male BTBR mice. These results highlight the complexity inherent in understanding the effects of OT on behavior. Future investigations of chronic intranasal OT should include a wider dose range and early developmental time points in both healthy rodents and ASD models to affirm the efficacy and safety of OT.
    Translational Psychiatry 11/2014; 4:e480. DOI:10.1038/tp.2014.117 · 4.36 Impact Factor

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