Increasing evidence suggests that two nonapeptides, arginine vasopressin and oxytocin, shape human social behavior in both nonclinical and clinical subjects. Evidence is discussed that in autism spectrum disorders genetic polymorphisms in the vasopressin–oxytocin pathway, notably the arginine vasopressin receptor 1a (AVPR1a), the oxytocin receptor (OXTR), neurophysin I and II, and CD38 (recently shown to be critical for social behavior by mediating oxytocin secretion) contribute to deficits in socialization skills in this group of patients. We also present first evidence that CD38 expression in lymphoblastoid cells derived from subjects diagnosed with autism is correlated with social skill phenotype inventoried by the Vineland Adaptive Behavioral Scales. Additionally, we discuss molecular genetic evidence that in nonclinical subjects both AVPR1a and OXTR genes contribute to prosocial or altruistic behavior inventoried by two experimental paradigms, the dictator game and social values orientation. The role of the AVPR1a is also analyzed in prepulse inhibition. Prepulse inhibition of the startle response to auditory stimuli is a largely autonomic response that resonates with social cognition in both animal models and humans. First results are presented showing that intranasal administration of arginine vasopressin increases salivary cortisol levels in the Trier Social Stress test. To summarize, accumulating studies employing a broad array of cutting-edge tools in psychology, neuroeconomics, molecular genetics, pharmacology, electrophysiology, and brain imaging are beginning to elaborate the intriguing role of oxytocin and arginine vasopressin in human social behavior. We expect that future studies will continue this advance and deepen our understanding of these complex events.
"However, small variations in the genes coding for vasopressin and oxytocin receptors cause species-specific behavioral variation (Hammock and Young, 2005), likely through differences in the brain distribution patterns of these receptors (Donaldson and Young, 2013; Insel and Shapiro, 1992). In humans, genotype variation, for both Avpr1a and OXTR, is linked with prosociality (Israel et al., 2009; Knafo et al., 2008), social cognition (Ebstein et al., 2009) and partner bonding (Walum et al., 2008, 2012). Similar effects have been described in voles (Microtus sp.), where genotype differences for Avpr1a and OXTR are associated with levels of parental care, social engagement and partner bonding (Hammock et al., 2005; Hammock and Young, 2005). "
"The interpretation of this finding remains challenging , but it points toward a possible role of CS in ASDs, not necessarily linked to perinatal complications. Some authors have also investigated the possibility that the administration of OT intrapartum may be involved in the pathogenesis of ASDs  . In one study, out of 54 autistic patients, 33 had a history of labor induction using OT, corresponding to 61%, while the national average was only 20–25% . "
[Show abstract][Hide abstract] ABSTRACT: The etiology of Autism Spectrum Disorders (ASDs) continues to be elusive. While ASDs have been shown to be heritable, several environmental co-factors, such as, e.g. pre- or perinatal adverse events, could play a role in the pathogenesis of the disorder as well. Prevalence of ASDs appears to have increased in the last three decades, but the causes of this surge are not fully understood. As perinatal adverse events have increased as well, they have been regarded as logical contributors to the risen prevalence of ASDs. Over the last three decades there has been also a considerable increase in the rates of induced labor and caesarean sections (CS). However, even if a causal association between CS and ASDs increase has been suggested, it has not yet been proven. Nevertheless, we hypothesize here that such an association is actual and that it might help to explain a part of the increase in ASD diagnoses. Our assumption is based on the wider epidemiological picture of ASDs and CS, as well as on the possible biological plausibility of this correlation, by postulating potential epigenetic and neurobiological mechanisms underpinning this relationship. Today, several observations point toward the existence of epigenetic dysregulation in ASDs and this raises the issue of the role of environmental factors in bringing about epigenetic modifications. Epigenetic dysregulations in some brain neuropeptide systems could play a role in the behavioral dysfunctions of ASDs. Particularly, some evidence suggests a dysregulation of the oxytocinergic system in autistic brains. Perinatal alterations of oxytocin (OT) can also have life-long lasting effects on the development of social behaviors. Within the perinatal period, various processes, like pitocin infusion or CS, can alter the OT balance in the newborn; OT dysregulation could then interact with genetic factors, leading ultimately to the development of ASDs. Large long-term prospective studies are needed to identify causal pathways for ASDs and examine whether and how (epi-)genetic susceptibility interacts with obstetric risk factors in the development of ASDs. A better understanding of such a potential interplay could become paradigmatic for a wide range of genetic-environmental interactions in ASDs.
Medical Hypotheses 03/2014; 82(6). DOI:10.1016/j.mehy.2014.03.011 · 1.07 Impact Factor
"Arginine vasopressin is a peptide hormone with both peripheral and central effects in vertebrates (Caldwell et al. 2008). It has important effects on affiliative, agonistic, and sexual behaviors in animals as diverse as fish (Godwin and Thompson 2012), rodents (Winslow et al. 1993), and humans (Ebstein et al. 2009; Heinrichs et al. 2009; Prichard et al. 2007; Walum et al. 2008). Variation in the regulation and distribution of central vasopressin receptors —particularly receptor 1a, the product of AVPR1A— may help explain inter-and intraspecific variation in social behavior in mammals (Young and Hammock 2007; cf. "
[Show abstract][Hide abstract] ABSTRACT: Primates and other mammals show measurable, heritable variation in behav-ioral traits such as gregariousness, timidity, and aggression. Connections among be-havior, environment, neuroanatomy, and genetics are complex, but small genetic differences can have large effects on behavioral phenotypes. One of the best examples of a single gene with large effects on natural variation in social behavior is AVPR1A, which codes for a receptor of the peptide hormone arginine vasopressin. Work on rodents shows a likely causal association between AVPR1A regulatory polymorphisms and social behavior. Chimpanzees also show variation in the AVPR1A regulatory region, with some individuals lacking a ca. 350-bp segment corresponding to a putative functional element. Thus, chimpanzees have a "short" allele (segment deletion) and a "long" allele (no deletion) at this locus. Here we compare AVPR1A variation in two chimpanzee populations, and we examine behavioral and hormonal data in relation to AVPR1A genotypes. We genotyped AVPR1A in a captive population of western chimpanzees (Pan troglodytes verus, New Iberia Research Center; N = 64) for which
International Journal of Primatology 02/2014; 35(1). DOI:10.1007/s10764-013-9747-z · 1.99 Impact Factor
Data provided are for informational purposes only. Although carefully collected, accuracy cannot be guaranteed. The impact factor represents a rough estimation of the journal's impact factor and does not reflect the actual current impact factor. Publisher conditions are provided by RoMEO. Differing provisions from the publisher's actual policy or licence agreement may be applicable.