Appetitive behavior, compulsivity, and neurochemistry in Prader-Willi syndrome

Abstract

Advances in genetic research have led to an increased understanding of genotype‐phenotype relationships. Excessive eating and weight gain characteristic of Prader‐Willi syndrome (PWS) have been the understandable focus of much of the research. The intense preoccupation with food, lack of satiation, and incessant food seeking are among the most striking features of PWS. It has become increasingly clear that the behavioral phenotype of PWS also includes symptoms similar to obsessive compulsive disorder, which in all probability interact with the incessant hunger and lack of satiation to engender the intense preoccupation and food seeking behavior that is characteristic of this disorder. Several lines of evidence suggest that genetic material on chromosome 15 may alter synthesis, release, metabolism, binding, intrinsic activity, or reuptake of specific neurotransmitters, or alter the receptor numbers and/or distribution involved in modulating feeding. Among the likely candidates are GABAnergic, serotonergic, and neuropeptidergic mechanisms. This review summarizes what is known about the appetitive behavior and compulsivity in PWS and discusses the possible mechanisms underlying these behaviors. MRDD Research Reviews 2000;6:125‐130. © 2000 Wiley‐Liss, Inc.

Development of the eating behaviour in Prader–Willi Syndrome: advances in our understanding

“…40 PWS is associated with a high response on the 'ritualized eating behaviour item' from the Yale-Brown Obsessive Compulsive Scale (Y-BOCS 41 ), and people with PWS switch less between food types than mental-age matched controls on a standard meal. 42 This study also found that the bite rate correlated negatively with ordering non-food items into patterns. Despite heterogeneity in some aspects of idiosyncratic eating behaviour, excessive food intake remains the key characteristic of PWS.…”

“…68 The authors of that study postulate that this may be due to the complex derangement of neurotransmitter balance involving the hypothalamic areas associated with PWS. 42 Altered gamma-aminobutyric acid A receptor function in brain areas including the insula, a region associated with awareness of bodily states, 69 which with gamma-aminobutyric acid-ergic abnormalities in other regions, may be involved in phenotypical characteristics, including altered pain sensation. 70 A delayed signal reduction 62 and significantly different responses to food before and after meal in the insula have also been shown.…”

The expression and assessment of emotions and internal states in individuals with severe or profound intellectual disabilities

“…Current estimates suggest a prevalence of approximately 1 in 25,000 births and a gender ratio of 1:1 (Whittington et al, 2001). The behavioral and cognitive phenotype has recently been reviewed (see Dimitropoulos et al, 2000) and includes low-average intelligence or a mild to moderate intellectual disability, excessive eating, repetitive and self-injurious behavior, temper outbursts, mood disturbances and underactivity. The physical phenotype includes distinctive facial features, hypotonia at birth, hypogonadism, small hands and feet and small stature (e.g.…”

Long-acting octreotide treatment causes a sustained decrease in ghrelin concentrations but does not affect weight, behaviour and appetite in subjects with Prader–Willi syndrome

“…BMI (weight (kg)/height (m) 2 ) and BMI Z-score (using the least mean squares (LMS) method) were calculated (11). Body composition was assessed in both centres by dual-energy X-ray absorptiometry (DXA) using a Hologic QDR 4500 W bone densitometer.…”

“…It is characterized by hyperphagia, persistent hunger with increased caloric intake, decreased perception of satiety and compulsive behaviour that is primarily food related (1,2). The treatment of obesity in PWS is difficult and requires a comprehensive multidisciplinary approach as well as constant involvement of the parents or caregivers with establishment of rigid structures to limit food intake and promote supervised physical activity.…”