Lauren J. Rice

A double-blind randomized controlled trial of oxytocin nasal spray in Prader Willi syndrome.

Individuals with Prader–Willi syndrome (PWS) have a significant reduction in the number of oxytocin‐producing neurons (42%) in the hypothalamic paraventricular nucleus. A number of animal studies and observations of humans show that lesions in this region can produce PWS‐like symptoms. Given the evidence for potential oxytocin deficiency, we tested the effects of a course of intranasal oxytocin on PWS symptoms. Thirty individuals with PWS aged 12–30 years participated in an 18‐week randomized double‐blind placebo‐controlled crossover trial. Participants received 8 weeks of oxytocin and 8 weeks of placebo with a minimum 2‐week washout period. The first 11 participants received the following oxytocin doses: 24 IU (twice daily) B.I.D for participants 16 years and over and 18 IU B.I.D for participants 13–15 years. The dose was increased for the remaining 18 participants to 40 IU B.I.D for participants 16 years and over and 32 IU B.I.D for 13–15 years. Measures used to assess changes were standardized well‐accepted measures, including the Developmental Behavior Checklist—Monitor, Parent, Teacher, and Adult; The Yale‐Brown Obsessive Compulsive Scale; The Dykens Hyperphagia questionnaire; Reading The Mind in the Eyes Test; Epworth Sleepiness Scale and the Movie Stills. Oxytocin had little impact on any measure. The only significant difference found between the baseline, oxytocin, and placebo measures was an increase in temper outbursts (P = 0.023) with higher dose oxytocin. The lack of effect of oxytocin nasal spray may reflect the importance of endogenous release of oxytocin in response to exogenous oxytocin.

Cognitive and behavioural aspects of Prader-Willi syndrome.

Purpose of review To provide a review of the recent advances in the diagnosis and treatment of psychiatric disorders in Prader–Willi syndrome (PWS). Recent findings Research in the last 12 months has provided a descriptive prognosis of psychosis in PWS and highlighted the possible genes associated with the increased risk of psychosis for those with maternal uniparental disomy (mUPD). Several studies investigating social and communication skills have shown people with PWS to have difficulty with core, receptive and expressive language skills, interpreting emotional valence in faces, playing with children of their own age, understanding personal space and a developmental delay in the theory of mind. These social and communication deficits are often more pronounced in those with mUPD. Two recent clinical trials of oxytocin provide mixed results and highlight the need for an improved understanding of the neurobiological characteristics of the PWS brain. A recent pilot study suggests N-acetylcysteine may be a viable treatment for skin picking. Summary Recent advances have contributed to our understanding of the emotional and behavioural problems associated with PWS, and provided directions for further research.

The developmental trajectory of disruptive behavior in Down syndrome, fragile X syndrome, Prader–Willi syndrome and Williams syndrome

The aim of this study was to investigate the developmental trajectories of verbal aggression, physical aggression, and temper tantrums in four genetic syndrome groups. Participants were part of the Australian Child to Adult Development Study (ACAD), which collected information from a cohort of individuals with an intellectual disability at five time points over 18 years. Data were examined from a total of 248 people with one of the four following syndromes: Down syndrome, Fragile X syndrome, Prader–Willi syndrome, or Williams syndrome. Changes in behaviors were measured using validated items from the Developmental Behavior Checklist (DBC). The results indicate that, while verbal aggression shows no evidence of diminishing with age, physical aggression, and temper tantrums decline with age before 19 years for people with Down syndrome, Fragile X syndrome, and William syndrome; and after 19 years for people with Prader–Willi syndrome. These findings offer a somewhat more optimistic outlook for people with an intellectual disability than has previously been suggested. Research is needed to investigate the mechanisms predisposing people with PWS to persistence of temper tantrums and physical aggression into adulthood.

Research on adults with autism spectrum disorder: Roundtable report

The prevalence of autism spectrum disorder (ASD) in adults is estimated to be at least 1% (Brugha et al., 2011), yet almost all ASD research focuses on children. Adult intervention studies, in part...

The Developmental Trajectory of Self-Injurious Behaviours in Individuals with Prader Willi Syndrome, Autism Spectrum Disorder and Intellectual Disability

In the present study we examined the nature and developmental trajectory of self-injurious behaviour in Prader Willi syndrome (PWS) and autism spectrum disorder (ASD). The development of interventions is greatly aided by understanding gene to behaviour pathways, and this requires an accurate description of the behaviour phenotype, that is, which types and natural history of self-injurious behaviour are more common in PWS and ASD and which are shared with other forms of developmental disability. Self-injury displayed by individuals with PWS and individuals with ASD was compared with that reported in a group of individuals with intellectual disability due to mixed aetiology (ID group). Three self-injurious behaviours (head banging, skin-picking and hitting and/or biting self) were measured on five occasions over 18 years using the Developmental Behaviour Checklist (DBC) a well-validated caregiver report measure. Rates of skin picking were higher in individuals with PWS and hitting and/or biting self was higher in individuals with ASD compared to the ID group. Rates of head banging were similar across the three groups. Over time, skin-picking and head banging increased with age for individuals with ASD and hitting and/or biting self increased for the PWS group. In the PWS and mixed ID groups head banging decreased with age. These findings suggest that the typology and developmental trajectories of self-injurious behaviours differ between those with PWS and ASD.

Reduced gamma-aminobutyric acid is associated with emotional and behavioral problems in Prader–Willi syndrome

Prader–Willi syndrome (PWS) is characterized by infantile hypotonia, hypogonadism, small hands and feet, distinct facial features and usually intellectual impairment. The disorder is associated with severe behavioral disturbances which include hyperphagia leading to morbid obesity, temper outbursts, skin‐picking, and compulsive behaviors. While the brain mechanisms that underpin these disturbances are unknown these behaviors suggest a lack of inhibition and thus gamma‐aminobutyric acid (GABA), the main inhibitory neurotransmitter may be implicated. In the present study, we investigated in vivo brain GABA and its relationship with emotion and behavior in individuals with PWS. Single voxel proton magnetic resonance spectroscopy (1H‐MRS) was performed on 15 individuals with PWS and 15 age‐ and gender‐matched typically developing controls. GABA levels were measured in the parieto‐occipital lobe. All other metabolite levels (N‐acetyl aspartate, myo–Inositol, glutathione, glutamate, and glutamine + glutamate) were measured in the anterior cingulate cortex (ACC). GABA levels were significantly lower in the participants with PWS who had clinically significant emotional and behavioral problems relative to typically developing control participants and participants with PWS who did not have emotional and behavioral problems within the clinically significant range. GABA levels were negatively correlated with total behavioral problem scores as well as temper outbursts, skin‐picking, depression, social relating difficulties, and a tendency to be self‐absorbed. Our data suggests that alterations of the GABAergic system may play an important role in aspects of the pathophysiology of PWS. Pathological mechanism found in PWS may be relevant to understanding the control of similar behaviors in the general population.

The characteristics of temper outbursts in Prader-Willi syndrome

The purpose of this study was to develop a comprehensive understanding of temper outbursts in Prader–Willi syndrome (PWS). A survey was developed from interviews conducted with individuals with PWS and their caregivers. The survey was completed by 101 primary caregivers. The findings suggest that outburst frequency decreases with age while duration increases. Adolescents exhibited more severe behaviors than children or adults. No differences were found across gender or genetic subtype. Provocations fit into three themes: goal blockage, social injustice, and difficulty dealing with change. Distracting the person or giving them space to calm down were the only management strategies judged effective. Risperidone, sertraline, and fluoxetine were the most common medications prescribed for outbursts, though parents reported only minor effects.

Syndrome specific modules to enhance the Stepping Stones Triple P public health intervention

Background Service responses to behaviour phenotypes include care by expert clinicians, syndrome‐specific clinics, disability‐specific mental health services and generic mental health services. While these services contribute to care, they are often of limited accessibility. Methods We describe a population‐wide public health intervention aimed at increasing the accessibility of services to the target population. Stepping Stones Triple P (SSTP) is a public health intervention of known efficacy in reducing behaviour problems when delivered to parents of children aged 0–12 with mixed developmental disabilities. Results The strategy we discuss involves enhancing SSTP with modules for specific causes of developmental disabilities including Down, Fetal Alcohol, Fragile X, Prader‐Willi and Williams syndromes. Conclusions We propose that enhancing SSTP with syndrome specific modules will increase the accessibility of support to families who have a child with a specific behaviour phenotype. We suggest that future research should confirm the public health impact of the modified SSTP programme using the RE‐AIM framework.

Microstructural white matter tract alteration in Prader-Willi syndrome: A diffusion tensor imaging study

Prader‐Willi Syndrome (PWS) is a genetic disorder characterized by infantile hypotonia, hyperphagia, hypogonadism, growth hormone deficiency, intellectual disability, and severe emotional and behavioral problems. The brain mechanisms that underpin these disturbances are unknown. Diffusion tensor imaging (DTI) enables in vivo investigation of the microstructural integrity of white matter pathways. To date, only one study has used DTI to examine white matter alterations in PWS. However, that study used selected regions of interest, rather than a whole brain analysis. In the present study, we used diffusion tensor and magnetic resonance (T 1‐weighted) imaging to examine microstructural white matter changes in 15 individuals with PWS (17–30 years) and 15 age‐and‐gender‐matched controls. Whole‐brain voxel‐wise statistical analysis of FA was carried out using tract‐based spatial statistics (TBSS). Significantly decreased fractional anisotropy was found localized to the left hemisphere in individuals with PWS within the splenium of the corpus callosum, the internal capsule including the posterior thalamic radiation and the inferior frontal occipital fasciculus (IFOF). Reduced integrity of these white matter pathways in individuals with PWS may relate to orientating attention, emotion recognition, semantic processing, and sensorimotor dysfunction.