Linking oxytocin and arginine vasopressin signaling abnormalities to social behavior impairments in Prader-Willi syndrome.

Prader-Willi syndrome (PWS) is a genetic neurodevelopmental disorder. Global hypothalamic dysfunction is a core feature of PWS and has been implicated as a driver of many of PWS's phenotypic characteristics (e.g., hyperphagia-induced obesity, hypogonadism, short stature). Although the two neuropeptides (i.e., oxytocin [OXT] and arginine vasopressin [AVP]) most implicated in mammalian prosocial functioning are of hypothalamic origin, and social functioning is markedly impaired in PWS, there has been little consideration of how dysregulation of these neuropeptide signaling pathways may contribute to PWS's social behavior impairments. The present article addresses this gap in knowledge by providing a comprehensive review of the preclinical and clinical PWS literature-spanning endogenous neuropeptide measurement to exogenous neuropeptide administration studies-to better understand the roles of OXT and AVP signaling in this population. The preponderance of evidence indicates that OXT and AVP signaling are indeed dysregulated in PWS, and that these neuropeptide pathways may provide promising targets for therapeutic intervention in a patient population that currently lacks a pharmacological strategy for its debilitating social behavior symptoms.

Intervention Response by Genetic Subtype: PRETEND-Preschool Program for Children with Prader-Willi Syndrome via Remote Parent Training.

Prader-Willi Syndrome (PWS) is a rare neurodevelopmental disorder associated with social cognitive challenges, and pretend play has been demonstrated as a tool to achieve developmental goals. Following previous report on feasibility and acceptability of a remote, play-based parent-training program (Zyga, Russ, & Dimitropoulos, 2018), we now report on preliminary efficacy of this program to enhance pretend play skills and social cognitive skills in preschoolers with PWS. Results across two studies demonstrated efficacy when live-coaching play sessions incorporated children into the intervention. Increases in play skills were observed for children with the mUPD subtype of PWS who underwent intervention, compared with children with mUPD who were waitlisted. Children with DEL subtype were less likely to respond to intervention. Implications for results are discussed.

Socio-behavioral dysfunction in disorders of hypothalamic-pituitary involvement: The potential role of disease-induced oxytocin and vasopressin signaling deficits.

Disorders involving hypothalamic and pituitary (HPIT) structures-including craniopharyngioma, Langerhans cell histiocytosis, and intracranial germ cell tumors-can disrupt brain and endocrine function. An area of emerging clinical concern in patients with these disorders is the co-occurring socio-behavioral dysfunction that persists after standard hormone replacement therapy. Although the two neuropeptides most implicated in mammalian social functioning (oxytocin and arginine vasopressin) are of hypothalamic origin, little is known about how disease-induced damage to HPIT structures may disrupt neuropeptide signaling and, in turn, impact patients' socio-behavioral functioning. Here we provide a clinical primer on disorders of HPIT involvement and a review of neuropeptide signaling and socio-behavioral functioning in relevant animal models and patient populations. This collective evidence suggests that neuropeptide signaling disruptions contribute to socio-behavioral deficits experienced by patients with disorders of HPIT involvement. A better understanding of the biological underpinnings of patients' socio-behavioral symptoms is now needed to enable the development of the first targeted pharmacological strategies by which to manage patients' socio-behavioral dysfunction.

A comparison of curricula: Examining the efficacy of a school-based musical theater intervention.

Students qualifying for services under the Individuals with Disabilities Education Act may experience challenges meeting the socioemotional demands of the school environment, creating a need for targeted interventions that can be delivered within school settings. The current study used a mixed-methods approach to examine the efficacy of a 4-week school-based musical theater intervention delivered to 121 elementary students with intellectual and developmental disabilities. Quantitative analyses of teacher-reported changes in student engagement pre- and post-intervention were conducted to compare student gains made across two intervention curricula, followed by qualitative content analyses of teachers' responses to open-ended survey questions. Results indicated an overall benefit of the musical theater intervention, with increases found in composite scores on the teacher-report Student Engagement Survey measure after completion of both intervention curricula; however, gains in individual survey item scores differed by curricula. Additionally, qualitative analyses provided positive insight into several aspects of the intervention.

Show me what happens next: Preliminary efficacy of a remote play-based intervention for children with Prader-Willi syndrome.

Prader-Willi Syndrome (PWS) is characterized by decreased social and emotional functioning. Due to the low base-rate of children with PWS, developing behavioral interventions for individuals with PWS is faced with the challenge of enrolling enough local participants for adequate study of behavioral intervention efficacy. However, these types of studies are greatly needed in PWS and telehealth methodology may be useful in addressing this challenge. This article is a follow-up to a previous feasibility study (Dimitropoulos et al., 2017) and reports on the preliminary efficacy of a telehealth intervention delivered to 15 children, ages 6-12, with PWS. Overall, children demonstrated significantly improved cognitive and affective processes in pretend play and general cognitive flexibility following the 6-week remote intervention. These findings are limited by the lack of control group and small sample size which should be considered when interpreting results. Overall, these preliminary findings point to the potential role pretend play can serve as a means of enacting cognitive and behavioral change via telehealth.

Complex Interplay Between Cognitive Ability and Social Motivation in Predicting Social Skill: A Unique Role for Social Motivation in Children With Autism.

Impairment in social interaction is a core feature of autism spectrum disorder (ASD), but the factors which contribute to this social skill deficiency are poorly understood. Previous research has shown that cognitive ability can impact social skill development in ASD. Yet, children with ASD whose cognitive abilities are in the normal range nevertheless demonstrate deficits in social skill. More recently, the social motivation theory of ASD has emerged as a framework by which to understand how failure to seek social experiences may lead to social skill deficits. This study was designed to better understand the relationships between cognitive ability, social motivation, and social skill in a well-characterized cohort of children with ASD (n = 79), their unaffected siblings (n = 50), and unrelated neurotypical controls (n = 60). The following instruments were used: The Stanford-Binet intelligence quotient (IQ), the Social Responsiveness Scale's Social Motivation Subscale, and the Vineland Adaptive Behavior Scales' Socialization Standard Score. We found that lower cognitive ability contributed to diminished social skill, but did so universally in all children. In contrast, social motivation strongly predicted social skill only in children with ASD, such that those with the lowest social motivation exhibited the greatest social skill impairment. Notably, this relationship was observed across a large range of intellectual ability but was most pronounced in those with IQs ≥ 80. These findings establish a unique link between social motivation and social skill in ASD and support the hypothesis that low social motivation may impair social skill acquisition in this disorder, particularly in children without intellectual disability. LAY SUMMARY: The relationships between cognitive ability, social motivation, and social skill are poorly understood. Here we report that cognitive ability predicts social skill in all children, whereas social motivation predicts social skill only in children with autism. These results establish a unique link between social motivation and social skill in autism, and suggest that low social motivation may impair social skill acquisition in this disorder, particularly in those without intellectual disability.

Pretend Play as an Intervention for Children With Cancer: A Feasibility Study.

Children with cancer suffer from symptoms and burdensome treatments that often cause distress to children and their families. Mortality is one aspect of cancer diagnosis, while another is the quality of life and well-being during and after the treatment. By supporting children's communication, self-efficacy and coping ability in the care situation, children are given the possibilities for increased independence and participation and are allowed to develop an influence over their care. The aim of this study was to develop and evaluate the feasibility and acceptability of an adult-facilitated pretend play intervention for children with cancer. Five children with ongoing treatment for cancer were invited to a play intervention that consisted of six to eight sessions of structured pretend play aimed at increasing participation, independence, and well-being. A mixed method design was used to evaluate the feasibility and acceptability of the play intervention. Measures were collected before and after interventions, and in conjunction with every play session. Results suggest that the children enjoyed the play intervention. Findings indicate small improvements regarding self-efficacy in care situations and equal or increased quality of life for participants. A main finding was that no adverse events or increased worrying was reported in conjunction with play sessions. Therefore, the intervention is regarded as safe, feasible, and acceptable as reported by participants and their primary caregivers and a possible means of increasing participation and independence in children with a cancer diagnosis.

Preliminary Characterization of Parent-Child Interaction in Preschoolers With Prader-Willi Syndrome: The Relationship Between Engagement and Parental Stress.

Early parent-child interactions (PCI) impact social cognitive development. Relatedly, children with various developmental disorders exhibit abnormal parental attachment relationships. Parental characteristics and behaviors can impact PCI and socioemotional development as well. No research has examined the parent-child dynamic in Prader-Willi syndrome (PWS), a neurodevelopmental disorder that presents with social cognitive deficits. This article provides a preliminary characterization of PCI quality and parenting stress in 17 PWS parent-child dyads, children ages 3-5 years, in comparison to 20 typically developing children and their parent. Results suggest early PCI disruption in preschoolers with PWS and their parents report increased levels of stress in various domains. These findings have important implications not only on parent well-being in PWS but its impact on child development.

Early Social Cognitive Ability in Preschoolers with Prader-Willi Syndrome and Autism Spectrum Disorder.

Children with Prader-Willi syndrome (PWS) and autism spectrum disorder (ASD) present with challenges in social cognitive ability, Research comparing PWS to ASD is important given the implication of 15q11-q13 region in the biology of autism. However, recent findings question the accuracy of relying solely on parent report in behavioral characterization. Thus, this study examined social cognition in an observable pretend play task and by parent report in 50 preschool children (ages 3-5) with PWS, by subtype, compared to ASD. Behaviorally, the paternal deletion subtype expressed overall higher functioning, whereas the maternal uniparental disomy subtype performed more similarly to the ASD group. Results are the first to show deficits in social cognitive ability early in development. The severity and differences in deficits between PWS subtypes are important in informing early intervention efforts.

The PRETEND Program: Evaluating the Feasibility of a Remote Parent-Training Intervention for Children With Prader-Willi Syndrome.

Research has shown that children with Prader-Willi syndrome (PWS) have social-cognitive challenges and decreased quality parent-child interactions. However, given the low prevalence rate, developing interventions for children with PWS is faced with the significant challenge of enrolling enough participants for local studies. To better understand the feasibility and acceptability of telehealth, the current study delivered a 6-week remote parent training intervention to 15 primary caregivers of a child with PWS (ages 3-6). Behavioral Intervention Rating Scale results indicate good acceptability (5.64/6.00) and satisfaction (4.75/5.00) with the intervention. These results are one of the first to support the use of telehealth in conducting parent training in rare disorders, such as PWS.

A preliminary investigation of a school-based musical theater intervention program for children with intellectual disabilities.

The presence of an intellectual disability may cause a child to have significant deficits in social skills and emotion regulation abilities across development. A vital next step is to find interventions that can be delivered in the school environment and across disability categories that target socioemotional factors. The current study investigated the feasibility of delivering a school-based musical theater program to students with intellectual disability across a range of school settings. A within-group repeated-measures design was used to analyze pre- and post-video recordings of the intervention program, which were coded for six domains of socioemotional ability across all participants ( n = 47). Results showed that significant gains across all domains were observed. However, these gains related to school- and individual-level student factors, such as grade level, severity of disability, and baseline social skill ability.

Evaluating the Feasibility of a Play-Based Telehealth Intervention Program for Children with Prader-Willi Syndrome.

Here we report the feasibility and acceptability of telehealth for direct intervention in children with Prader-Willi syndrome (PWS). Children with PWS have social-cognitive challenges that are similar to children with ASD. However, developing behavioral interventions for individuals with PWS is faced with the significant challenge of enrolling enough participants for local studies where multiple visits per week are indicated for effective intervention. This study delivered a 6-week play-based intervention via telehealth directly to eight children with PWS (6-12 years). Participants completed the program with minimal behavioral or technological difficulty (#sessions M = 11.875/12). Behavioral Intervention Rating Scale results indicate good acceptability (M = 5.54/6.00). These findings support using telehealth in rare disorders and delivering intervention directly to children with developmental delays through this modality.

Assessment of pretend play in Prader-Willi syndrome: a direct comparison to autism spectrum disorder.

Children with Prader-Willi syndrome (PWS) are at risk for autism spectrum disorder (ASD), including pervasive social deficits. While play impairments in ASD are well documented, play abilities in PWS have not been evaluated. Fourteen children with PWS and ten children with ASD were administered the Autism Diagnostic Observation Schedule (ADOS) (Lord et al. in Autism Diagnostic Observation Schedule manual. Western Psychological Services, Los Angeles, 2006) as part of a larger project. A modified Affect in Play Scale (APS; Russ in Play in child development and psychotherapy: toward empirically supported practice. Lawrence Erlbaum Associates Publishers, Mahwah, 2004; Pretend play in childhood: foundation of adult creativity. APA Books, Washington, 2014) was used to score ADOS play activities. Results indicate both groups scored below normative data on measures of imagination, organization, and affective expression during individual play. In addition, the inclusion of a play partner in both groups increased all scaled scores on the APS. These findings suggest children with PWS show impaired pretend play abilities similar to ASD. Further research is warranted and should focus on constructing and validating programs aimed at improving symbolic and functional play abilities within these populations.