Prader–Willi syndrome (PWS) is a complex neurobehavioral condition which has been classically described as having two nutritional stages: poor feeding, frequently with failure to thrive (FTT) in infancy (Stage 1), followed by hyperphagia leading to obesity in later childhood (Stage 2). We have longitudinally followed the feeding behaviors of individuals with PWS and found a much more gradual and complex progression of the nutritional phases than the traditional two stages described in the literature. Therefore, this study characterizes the growth, metabolic, and laboratory changes associated with the various nutritional phases of PWS in a large cohort of subjects. We have identified a total of seven different nutritional phases, with five main phases and sub-phases in phases 1 and 2. Phase 0 occurs in utero, with decreased fetal movements and growth restriction compared to unaffected siblings. In phase 1 the infant is hypotonic and not obese, with sub-phase 1a characterized by difficulty feeding with or without FTT (ages birth—15 months; median age at completion: 9 months). This phase is followed by sub-phase 1b when the infant grows steadily along a growth curve and weight is increasing at a normal rate (median age of onset: 9 months; age quartiles 5–15 months). Phase 2 is associated with weight gain—in sub-phase 2a the weight increases without a significant change in appetite or caloric intake (median age of onset 2.08 years; age quartiles 20–31 months;), while in sub-phase 2b the weight gain is associated with a concomitant increased interest in food (median age of onset: 4.5 years; quartiles 3–5.25 years). Phase 3 is characterized by hyperphagia, typically accompanied by food-seeking and lack of satiety (median age of onset: 8 years; quartiles 5–13 years). Some adults progress to phase 4 which is when an individual who was previously in phase 3 no longer has an insatiable appetite and is able to feel full. Therefore, the progression of the nutritional phases in PWS is much more complex than previously recognized. Awareness of the various phases will aid researchers in unraveling the pathophysiology of each phase and provide a foundation for developing rational therapies. Counseling parents of newly diagnosed infants with PWS as to what to expect with regard to these nutritional phases may help prevent or slow the early-onset of obesity in this syndrome.

Fragile X syndrome (FXS) is the most common single gene (FMR1) disorder affecting cognitive and behavioral function in humans. This syndrome is characterized by a cluster of abnormalities including lower IQ, attention deficits, impairments in adaptive behavior and increased incidence of autism. Here, we show that young males with FXS have profound deficits in prepulse inhibition (PPI), a basic marker of sensorimotor gating that has been extensively studied in rodents. Importantly, the magnitude of the PPI impairments in the fragile X children predicted the severity of their IQ, attention, adaptive behavior and autistic phenotypes. Additionally, these measures were highly correlated with each other, suggesting that a shared mechanism underlies this complex phenotypic cluster. Studies in Fmr1-knockout mice also revealed sensorimotor gating and learning abnormalities. However, PPI and learning were enhanced rather than reduced in the mutants. Therefore, these data show that mutations of the FMR1 gene impact equivalent processes in both humans and mice. However, since these phenotypic changes are opposite in direction, they also suggest that murine compensatory mechanisms following loss of FMR1 function differ from those in humans.

BACKGROUND: Compared with other parents, mothers of children with autism spectrum disorder or other neurodevelopmental disabilities experience more stress, illness, and psychiatric problems. Although the cumulative stress and disease burden of these mothers is exceptionally high, and associated with poorer outcomes in children, policies and practices primarily serve the identified child with disabilities. METHODS: A total of 243 mothers of children with disabilities were consented and randomized into either Mindfulness-Based Stress Reduction (mindfulness practice) or Positive Adult Development (positive psychology practice). Well-trained, supervised peer mentors led 6 weeks of group treatments in 1.5-hour weekly sessions, assessing mothers 6 times before, during, and up to 6 months after treatment. Mothers had children with autism (65%) or other disabilities (35%). At baseline, 85% of this community sample had significantly elevated stress, 48% were clinically depressed, and 41% had anxiety disorders. RESULTS: Using slopes-as-outcomes, mixed random effects models, both treatments led to significant reductions in stress, depression, and anxiety, and improved sleep and life satisfaction, with large effects in depression and anxiety. Mothers in Mindfulness-Based Stress Reduction versus Positive Adult Development had greater improvements in anxiety, depression, sleep, and well-being. Mothers of children with autism spectrum disorder improved less in anxiety, but did not otherwise differ from their counterparts. CONCLUSIONS: Future studies are warranted on how trained mentors and professionals can address the unmet mental health needs of mothers of children with developmental disabilities. Doing so improves maternal well-being and furthers their long-term caregiving of children with complex developmental, physical, and behavioral needs.

Although some genetic, mental retardation syndromes have well-described behavioral features, comparative studies have not yet assessed the relative uniqueness of these so-called phenotypes. Maladaptive behavior of 43 children with Prader-Willi syndrome was compared to age- and gender-matched children with Down syndrome and with nonspecific mental retardation. The Prader-Willi group showed more frequent and severe internalizing, externalizing, and total problem behaviors on the Child Behavior Checklist. Some problems were elevated in all groups, and 12 behaviors were significantly elevated in Prader-Willi subjects relative to both comparison groups. Seven behaviors predicted membership into the Prader-Willi group with 91% accuracy. Implications were discussed for research on behavioral phenotypes in general and for dual diagnosis in particular.

This study examines the nature, severity and correlates of non-food obsessions and compulsions in 91 people with Prader-Willi syndrome (PWS) aged 5-47 years (mean age = 19 years). Prominent symptoms, seen in 37-58% of the sample, included hoarding; ordering and arranging; concerns with symmetry and exactness; rewriting; and needs to tell, know or ask. A remarkably high proportion of participants had moderate to severe symptom severity ratings; 64% showed symptom-related distress, and 80% showed symptom-related adaptive impairment. The study also compared obsessive-compulsive symptoms in 43 adults with PWS to age- and sex-matched non-retarded adults with obsessive-compulsive disorder (OCD). The PWS and OCD groups showed similar levels of symptom severity and numbers of compulsions; they also showed more areas of symptom similarity than difference. Increased risks of OCD in persons with PWS are strongly indicated. Implications are discussed for pharmacotherapy, behavioral therapy and family support.

Similar to the state of the broader intellectual disabilities field, many gaps exist in the research and treatment of mental health concerns in people with Down syndrome. This review summarizes key findings on the type and prevalence of behavior and emotional problems in children, adolescents, and adults with Down syndrome. Such findings include relatively low rates of severe problems in children, and well-documented risks of depression and Alzheimer's disease in older adults. The review also considers emerging data on autism, and the paucity of studies on adolescents. Three next steps for research are highlighted, including a need to: (1) connect research on psychiatric status and diagnoses across developmental periods, including adolescence, and to examine such associated processes as sociability, anxiety and attention; (2) unravel complicated biopsycho-social risk and protective factors that serve to increase or diminish psychopathology; and (3) identify evidence-based treatments that both reduce distressful symptoms and enhance well-being in individuals with Down syndrome.

Prader-Willi syndrome (PWS) and Angelman syndrome (AS) are clinically distinct complex disorders mapped to chromosome 15q11-q13. They both have characteristic neurologic, developmental, and behavioral phenotypes plus other structural and functional abnormalities. However, the cognitive and neurologic impairment is more severe in AS, including seizures and ataxia. The behavioral and endocrine disorders are more severe in PWS, including obsessive-compulsive symptoms and hypothalamic insufficiency. Both disorders can result from microdeletion, uniparental disomy, or an imprinting center defect in 15q11-q13, although the abnormality is on the paternally derived chromosome 15 for PWS and the maternally derived 15 for AS because of genomic imprinting. Although the same gene may control imprinting for both disorders, the gene(s) causing their phenotypes differ. AS results from underexpression of a single gene, UBE3A, which codes for E6-AP, a protein that functions to transfer small ubiquitin molecules to certain target proteins, to enable their degradation. The genes responsible for PWS are not determined, although several maternally imprinted genes in 15q11-q13 are known. The most likely candidate is SNRPN, which codes for a small nuclear ribonucleoprotein, a ribosome-associated protein that controls gene splicing and thus synthesis of critical proteins in the brain. Animal models exist for both disorders. The genetic relationship between PWS and AS makes them unique and potentially highly instructive disorders that contribute substantially to the population burden of cognitive impairment.

Objective: Prader-Willi syndrome (PWS), the leading known genetic cause of obesity, is characterized by intellectual disabilities, maladaptive and compulsive behaviors, and hyperphagia. Although complications of obesity resulting from hyperphagia are the leading cause of death in PWS, quantifying this drive for food has long been an unmet research need. This study provides factor-analytic and within-syndrome analyses of a new measure of hyperphagia in PWS. Research Methods and Procedure: A 13-item informant measure, the Hyperphagia Questionnaire, was developed and administered to the parents of 153 persons with PWS, 4 to 51 years of age. The intelligence quotients, genetic subtypes of PWS, and BMIs of offspring were obtained, as were measures of their non-food problem behaviors. Results: Factor analyses with varimax rotation produced three statistically and conceptually robust factors that accounted for 59% of the variance: Hyperphagic Behaviors, Drive, and Severity. Hyperphagic Behavior increased with age, whereas Drive remained stable, and Severity dipped in older adults. Hyperphagic Drive and Severity were positively correlated with non-food behavior problems, and Hyperphagic Drive differentiated the 36% of participants with extreme obesity from those who had overweight/obese (48%) or healthy (16%) BMI classifications. Discussion:The Hyperphagia Questionnaire is a robust tool for relating breakthroughs in the neurobiology of hyperphagia to in vivo food-seeking behavior and for examining the psychological and developmental correlates of hyperphagia in PWS. The Hyperphagia Questionnaire also offers a nuanced, real-life outcome measure for future clinical trials aimed at curbing the life-threatening drive for food in PWS.