Research ReportOxytocin and vasopressin systems in genetic syndromes and neurodevelopmental disorders
Section snippets
Introduction to OT and AVP neuropeptide hormones
Oxytocin (OT) and arginine vasopressin (AVP) are small mammalian neuropeptides nine amino acids in length, which differ by only two amino acids. OT is produced primarily in hypothalamic nuclei, including the supraoptic (SON) and paraventricular nuclei (PVN). AVP is also synthesized in the PVN and SON. In males, additional brain regions including the amygdala and the bed nucleus of the stria terminalis (BNST) also produce AVP. OT and AVP of hypothalamic origins are transported from the SON and
Autism spectrum disorders
In 1943, Leo Kanner described a male patient with repetitive behaviors—“stereotyped movements [and]…repetitions carried out in exactly the same way in which they had been performed originally” and difficulties with social communication—“he always seemed to be parroting what he had heard said to him at one time or another…Words to him had a specifically literal, inflexible meaning. He seemed unable to generalize, to transfer an expression to another similar object or situation” (Kanner, 1943).
Prader–Willi syndrome and OT
Prader–Willi syndrome (PWS) is a complex disorder with multisystem effects and a distinct behavioral phenotype. It occurs in approximately 1/10,000–1/30,000 births, and is initially characterized by severe infantile hypotonia and difficulty feeding, although later in infancy and into adolescence individuals with PWS often eat excessively and develop morbid obesity. Other characteristics of PWS include hypogonadism, short stature, small hands and feet and strabismus. The cognitive phenotype is
Williams syndrome and OT
Williams syndrome (WS) was first described over 50 years ago (Williams et al., 1961). The first reported cases were focused on infants with hypercalcemia, developmental delays, cardiac malformations and dysmorphic facial features (Morris, 1993). However, better characterization of this syndrome has elucidated a distinct behavioral phenotype marked by an increased social drive paired with social fearlessness, poor judgment, difficulty forming peer relationships and high anxiety levels (Jarvinen
Fragile X syndrome
Named for the fragile site observed at Xq27.3, Fragile X Syndrome (FXS) is the most common inherited form of intellectual disability and the most common known single gene mutation associated with ASD (O׳Donnell and Warren, 2002). Prevalence estimates range from ~1 case in 1000 to 1 case in 4000 males and has settled at 1 case in 6000 world-wide for females (Brown, 1990, Morton et al., 1997, Turner et al., 1996, Webb, 2010). This rare genetic disorder is characterized by specific physical
Conclusion and next steps
Each of the disorders described here (ASD, PWS, WS and FXS) is unique and each condition is characterized by atypical social behaviors, often with 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 (Table 4) through experiments conducted by others and ourselves.
Each of these early
Acknowledgments
This work was supported in part by NIH K23MH082121 (SJ). The authors would like to acknowledge Dr. John Larson for his contribution of the Fmr1 KO mice. We would also like to thank Jeanine Leary and Jennifer Speak for their assistance in manuscript formatting and preparation.
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2022, Neuroscience and Biobehavioral ReviewsCitation Excerpt :Thus, these collective research efforts have shown that no one single gene is the cause of PWS. Instead, lack of expression of multiple genes in this locus leads to the disorder’s characteristic phenotype (Polex-Wolf et al., 2017; Francis et al., 2014). Global hypothalamic dysfunction has been identified as a core feature of PWS and as a causal factor in many of the phenotypic characteristics of the disorder (Correa-da-Silva et al., 2021; Tauber and Hoybye, 2021).