While each of the disorders described here (ASD, PWS, WS and FXS) is unique, each one is characterized by atypical social behaviors and in many cases a tendency toward high levels of anxiety. Given the importance of OT and AVP to mammalian social behaviors and anxiety, the neuropeptides’ investigative value in these syndromes is not unexpected. This review summarized the possible role of OT in these NDD through experiments conducted by others and ourselves (Table 14.3). Each of these early developmental disorders displayed alterations in the OT system and may represent many molecular pathways that lead to a commonly disrupted neuropeptide hormone system. Our preliminary data suggests decreased numbers of OT-positive and AVP-positive cells in the PVN of Fmr1 KO mice, a mouse model for FXS. Individuals with PWS have shown lower levels of OT in CSF and fewer OT producing cells in the PVN. Lower plasma OT levels have also been detected in some children or a subgroup of ASD affected children. In contrast with WS, which is characterized by hypersociability, a positive correlation was found between OT levels and increased stranger approach and decreased adaptive social behavior. Knowledge of the functionality of the OXTR in WS remains to be studied. Given the rarity of these disorders and the complex animal models needed to research these disorders, many of these studies have small sample sizes. These significant studies, however, can motivate future research on these disorders and other NDD, especially those disorders with dysfunctional social behaviors as a symptom.

ASD, as described above, is the primary NDD presumed to be associated with dysregulation of the OT system. It is striking, however, that other disorders with phenotypes marked by abnormal social behavior as well as anxiety (manifested in RRB) have abnormalities in OT production as measured in blood and CSF (Table 14.3). For example, individuals with PWS, like those in ASD, have difficulty with social competence (Dimitropoulos et al. 2013), are aloof and avoid eye contact (Dimitropoulos et al. 2009). Furthermore, RRB is also evidenced in PWS (Greaves et al. 2006), although to a lesser degree than in ASD as measured using the Repetitive Behavior Scale-Revised (RBS-R; Flores et al. 2011). A subset of the chromosomal region associated with PWS is also associated with an increased risk for ASD, as maternally inherited duplications of the 15q11-13 region are associated with 1–3 % of ASD cases (Bolton et al. 2001; Cook et al. 1997; Vorstman et al. 2006).

Williams syndrome and ASD also share commonalities, namely abnormal social phenotypes and anxiety. Individuals with WS, unlike those with PWS, show a phenotype that is markedly different from ASD. Although both groups are at risk for anxiety, individuals with ASD show higher levels of social phobia and separation anxiety, as well as higher rates of RRB. However, children with WS have higher scores on measures of generalized anxiety (Rodgers et al. 2012). WS is characterized by an increase in OT levels (Dai et al., 2012), as well as a deletion of the 7q11.23 region as opposed to a de novo duplication which leads to ASD (Sanders et al., 2011). Thus, it is likely that some ASD and WS symptoms are related to genetic dosage effects. Studies of FX and ASD mechanism may also inform each other, as mutations in mGluR5 can contribute to the diagnosis of FXS or ASD, and mGluR5 antagonists have shown promise in alleviating ASD symptoms in mouse models (Silverman et al. 2012) as well as Fragile X pathology.

As summarized in this review, animal and human research to date has shown that dysregulation of the OT system is associated with marked deficits in social behavior as well as anxiety. This commonality across multiple NDD may indicate a shared OT pathway that is affected during development. The use of animal models , particularly those developed for FXS, WS and PWS, will provide insight into such a pathway, as these disorders have well characterized genetics, whereas there are over 103 disease genes and 44 genomic loci reported to be involved in ASD (Betancur 2011). However, unlike in ASD, there is a lack of human data on the pathophysiology of FXS, WS and PWS, as well as pharmacological interventions. Ideally, scientists want to identify specific molecular pathways to target distinct syndromes and disorders for treatment. However, many effective treatments modulate common neurochemical or hormone pathways that are downstream from etiologically contributing factors (e.g. drugs for hypertension). Combining the strengths of human and animal model studies across these NDD may provide important clues into the role of OT in development, in addition to elucidating the complex neurophysiology and treatment targets for FXS, PWS, WS and ASD.