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Prader–Willi syndrome (PWS) is a genomic imprinting disorder characterized by infantile hypotonia with a poor suck and failure to thrive, hypogenitalism/hypogonadism, behavior and cognitive problems, hormone deficiencies, hyperphagia, and obesity. The Stanford Binet and Wechsler (WAIS-R; WISC-III) intelligence (IQ) tests were administered on 103 individuals with PWS from two separate cohorts [University of California, Irvine (UCI) (N = 56) and Vanderbilt University (N = 47)] and clinical information obtained including growth hormone (GH) treatment, PWS molecular classes, weight and height. Significantly higher IQ scores (p < .02) were found representing the vocabulary section of the Stanford Binet test in the growth hormone (GH) treated group when compared with non-GH treatment in the pediatric-based UCI PWS cohort with a trend for stabilization of vocabulary IQ scores with age in the GH treated maternal disomy (UPD) 15 subject group. Significant differences (p = .05) were also found in the adult-based Vanderbilt PWS cohort with 15q11-q13 deletion subjects having lower Verbal IQ scores compared with UPD 15. No difference in body mass index was identified based on the PWS molecular class or genetic subtype. Medical care and response to treatment with growth hormone may influence intelligence impacted by PWS genetic subtypes and possibly age, but more studies are needed.

A series of 26 different antioxidants and commercial antioxidant packages designed for petroleum-based materials, containing both natural and synthetic-based materials, were evaluated with dimeric coconut-oleic estolide 2-ethylhexyl ester (2-EH), a bio-based material. The different antioxidants were categorized into different classes of phenolic, aminic, and blended/others materials. The oxidation onset temperatures (OT) using non-isothermal pressurized differential scanning calorimetry (PDSC) were measured and recorded under previously reported standard conditions. The aminic series gave the best resistance to oxidation as defined by the PDSC method with OT of 246.6 and 244.7 °C for the best two performers, which was a 38 °C improvement over the uninhibited or unformulated dimer estolide material. The phenolic series, containing most of the naturally occurring antioxidants, was the least successful formulation package for the dimer estolide. The blended/other materials, which were specifically designed for petroleum-based lubricants, did not have the best OT, since the estolides and other bio-based materials interact differently than their petroleum counterparts. A number of potential antioxidants have been identified as useful additives for the estolides esters. The OT of the estolide and formulated materials correlated well with other bio-based materials such as biodiesel.

For three decades after Leo Kanner's first clinical description, research progress in understanding and treating autism was minimal but since the late 1960s the growth of autism discoveries has been exponential, with a remarkable number of new findings published over the past two decades, in particular. These advances were made possible first by the discovery and dissemination of early intensive behavioural intervention (EIBI) for young children with autism that created the impetus for earlier accurate diagnosis. Other factors influencing the rapid growth in autism research were the first accepted diagnostic test for autism, the Autism Diagnostic Interview and Observation Schedule (ADI and ADOS). Developments in brain imaging and genetic technology combined to create a fuller understanding of the heterogeneity of autism, its multiple aetiologies, very early onset and course, and strategies for treatment. For a significant proportion of children with autism, it appears EIBI may be capable of promoting brain connectivity in specific cerebral areas, which is one of autism's underlying challenges. Disagreements about the most appropriate early intervention approach between developmental and behavioural psychologists have been unproductive and not contributed to advancing the field. Naturalistic behavioural and structured discrete trial methods are being integrated with developmental strategies with promising outcomes. Over these past 30 years, young people with autism have gone from receiving essentially no proactive treatment, resulting in lives languishing in institutions, to today, when half of children receiving EIBI treatment subsequently participate in regular classrooms alongside their peers. The future has entirely changed for young people with autism. Autism has become an eminently treatable condition. The time is overdue to set aside philosophical quarrels regarding theories of child development and apply what we know for the benefit of children with autism and their families.

Purpose The mean length of children’s utterances is a valuable estimate of their early language acquisition. The available normative data lack documentation of language and nonverbal intelligence levels of the samples. This study reports age-referenced mean length of utterance (MLU) data from children with specific language impairment (SLI) and children without language impairments. Method Of the 306 child participants drawn from a data archive, ages 2;6–9;0 (years;months), 170 were in the SLI group and 136 were in the control group. There were 1,564 spontaneous language samples collected, and these were transcribed and analyzed for sample size and MLU in words and morphemes. Means, standard deviations, and effect sizes for group differences are reported for MLUs, along with concurrent language and nonverbal intelligence assessments, per 6-month intervals. Results The results document an age progression in MLU words and morphemes and a persistent lower level of performance for children with SLI. Conclusion The results support the reliability and validity of MLU as an index of normative language acquisition and a marker of language impairment. The findings can be used for clinical benchmarking of deficits and language intervention outcomes as well as for comparisons across research samples.

Background Differences in behavioral phenotypes between the two most common subtypes of Prader-Willi syndrome (PWS) [chromosome 15q deletions and maternal uniparental disomy 15 (UPD)] indicate that distinct neural networks may be affected. Though both subtypes display hyperphagia, the deletion subgroup demonstrates reduced behavioral inhibition around food, whereas those with UPD are generally more able to maintain cognitive control over food intake impulses. Objective To examine the neural basis of phenotypic differences to better understand relationships between genetic subtypes and behavioral outcomes. We predicted greater food motivation circuitry activity in the deletion subtype and greater activity in higher order cognitive regions in the UPD group, especially after eating. Design and Subjects Nine individuals with PWS due to UPD and 9 individuals with PWS due to (type 2) deletion, matched for age, gender, and BMI, underwent fMRI scanning while viewing food images during two food motivation states: one before (pre-meal) and one after (post-meal) eating a standardized 500 kcal meal. Results Both PWS subgroups demonstrated greater activity in response to food pre- and post-meal compared to the healthy-weight group. Compared to UPD, the deletion subtype showed increased food motivation network activation both pre- and post-meal, especially in the medial prefrontal cortex and amygdala. In contrast, the UPD group demonstrated greater activation than the deletion subtype post-meal in the dorsolateral prefrontal cortex and parahippocampal gyrus. Conclusion These preliminary findings are the first functional neuroimaging findings to support divergent neural mechanisms associated with behavioral phenotypes in genetic subtypes of PWS. Results are discussed within the framework of genetic mechanisms such as haploinsufficiency and gene dosage effects and their differential influence on deletion and UPD subtypes, respectively.

Self-awareness is a specific type of autoclitic discriminative behavior and inferential generalization to similar performances exhibited by other people. Brain imaging findings take on special importance within behavior analysis when they indicate that dysfunctions in these areas are related to differential effects of our interventions, with some acquiring substantially typical self-awareness skills and others failing to do so. It appears that those individuals whose brain dysfunctions are limited to these areas, and are not part of more generalized brain abnormalities, are amenable to substantial acquisition of those most basic of human skills called self-awareness, whereas individuals with more generalized brain dysfunction are not so disposed. Through a combination of less or more effective teaching contingencies during childhood, and degrees of dysfunction of those brain structures, some children grow up lacking self-reflective abilities and self-insight, whereas others are extraordinarily astute at those capacities. Among children with autism spectrum disorders who lack those skills due to abnormal brain development, approximately half of them can acquire those skills, at least to some degree through the use of effective, intensive, early behavior therapy methods.

OBJECTIVES To assess the prognostic effect of perineural invasion (PNI) for patients undergoing external beam radiotherapy for prostate cancer. METHODS We evaluated 657 consecutive patients who had undergone external beam radiotherapy for clinically localized prostate cancer. The clinical/treatment parameters used for analysis included PNI, clinical stage, biopsy Gleason score, pretreatment prostate-specific antigen, radiation dose, and androgen deprivation. The primary endpoint was biochemical recurrence defined by the Radiation Therapy Oncology Group-American Society for Therapeutic Radiology Oncology Phoenix consensus; the secondary endpoint was prostate cancer death. RESULTS Of 586 men with a minimum of 24 months of follow-up, 112 (19.1%) had PNI present in the biopsy specimen. When patients were stratified into risk groups using the National Comprehensive Cancer Network criteria, PNI was more prevalent in patients within higher risk groups (6.8% in low-risk versus 18.3% in intermediate-risk versus 30.1% in high-risk groups; P

Background Prader–Willi syndrome (PWS) is a genetic syndrome associated with several physical, cognitive and behavioural characteristics. For many individuals with this syndrome, compulsive behaviour is often noted in both food and non-food situations. The focus of this paper is on the non-food-related compulsions in individuals with PWS and comparing differences across the three genetic subtypes of the syndrome. Methods Compulsive behaviours in 73 people with PWS were assessed using the Yale-Brown Obsessive Compulsive Scale and the Compulsive Behavior Checklist. Compulsive behaviour and its relation to IQ and academic achievement also were evaluated. Phenotypic differences were characterized for the three most common genetic subtypes of the disorder: 16 individuals with the long Type I (TI) 15q deletion, 26 individuals with the short Type II (TII) 15q deletion and 31 individuals with maternal disomy 15. Results There appeared to be important differences between the two deletion subtypes. Specifically, individuals with the TI deletion had more compulsions regarding personal cleanliness (i.e. excessive bathing/grooming), and their compulsions were more difficult to interrupt and interfered with social activities more than the other subtypes. Individuals with the TII deletion were more likely to have compulsions related to specific academic areas (i.e. rereading, erasing answers and counting objects or numbers). Conclusions These findings may help clinicians and researchers identify possible intervention strategies and supports based on the behavioural phenotype associated with genetic subtype in individuals with PWS.

This paper proposes that an organism's integrated repertoire of operant behavior has the status of a biological system, similar to other biological systems, like the nervous, cardiovascular, or immune systems. Evidence from a number of sources indicates that the distinctions between biological and behavioral events is often misleading, engendering counterproductive explanatory controversy. A good deal of what is viewed as biological (often thought to be inaccessible or hypothetical) can become publicly measurable variables using currently available and developing technologies. Moreover, such endogenous variables can serve as establishing operations, discriminative stimuli, conjoint mediating events, and maintaining consequences within a functional analysis of behavior and need not lead to reductionistic explanation. I suggest that explanatory misunderstandings often arise from conflating different levels of analysis and that behavior analysis can extend its reach by identifying variables operating within a functional analysis that also serve functions in other biological systems.

Objective: Prader-Willi syndrome (PWS) is a genetic disorder associated with developmental delay, obesity, and obsessive behavior related to food consumption. The most striking symptom of PWS is hyperphagia; as such, PWS may provide important insights into factors leading to overeating and obesity in the general population. We used functional magnetic resonance imaging to study the neural mechanisms underlying responses to visual food stimuli, before and after eating, in individuals with PWS and a healthy weight control (HWC) group. Research Methods and Procedures: Participants were scanned once before (pre-meal) and once after (post-meal) eating a standardized meal. Pictures of food, animals, and blurred control images were presented in a block design format during acquisition of functional magnetic resonance imaging data. Results: Statistical contrasts in the HWC group showed greater activation to food pictures in the pre-meal condition compared with the post-meal condition in the amygdala, orbitofrontal cortex, medial prefrontal cortex (medial PFC), and frontal operculum. In comparison, the PWS group exhibited greater activation to food pictures in the post-meal condition compared with the pre-meal condition in the orbitofrontal cortex, medial PFC, insula, hippocampus, and parahippocampal gyrus. Between-group contrasts in the pre- and post-meal conditions confirmed group differences, with the PWS group showing greater activation than the HWC group after the meal in food motivation networks. Discussion: Results point to distinct neural mechanisms associated with hyperphagia in PWS. After eating a meal, the PWS group showed hyperfunction in limbic and paralimbic regions that drive eating behavior (e.g., the amygdala) and in regions that suppress food intake (e.g., the medial PFC).

Prader-Willi syndrome (PWS) is a genetic disorder characterized by hyperphagia and food preoccupations. Researchers indicate that individuals with PWS, including young children, exhibit food and non-food-related compulsions. Normative rituals are also often present among typically developing preschoolers. However, it is unclear how these behaviors affect the child. Although preschoolers with PWS exhibit more types of rituals than other populations, it is uncertain if the severity of these behaviors differs from the rituals experienced during normative development. Thus, the purpose of this research was to determine whether the ritualistic behaviors exhibited by preschoolers with PWS differ in severity from those exhibited during normative development. We also sought to identify whether non-food ritualistic behavior was related to the hyperphagia in PWS. Parents of 68 children with PWS, 86 typically developing children, and 57 children with developmental delays completed questionnaires on rituals and eating behavior. Children with PWS exhibited more severe ritualistic behavior than typically developing children but not other children with developmental delays. However, the severity of non-food-related rituals was related to the severity of eating behavior in PWS. We hypothesize that this link between hyperphagia and non-food-related compulsivity may share a common underlying neurobiological mechanism.

Background Individuals with Prader–Willi syndrome (PWS), a chromosome 15 genetic disorder, often have a significant preoccupation with food and problem behaviour related to food seeking is often prevalent. Methods In the present study, we compared how individuals with PWS responded on a survey regarding the acceptability of food in various locations that varied according to degree of appropriateness for human consumption (e.g. food on a plate, food in a garbage can). For a subgroup of participants, we observed how they actually responded when placed in a room with food items placed in the same locations depicted in the survey. In the first part of the study, three groups (25 typically developing individuals, 7 individuals with intellectual disability (ID), and 19 individuals with PWS) responded to a visual survey to determine the degree of acceptability of food items in various locations (e.g. on a table near a hairbrush, on the floor behind a toy box, in a trash can). In the second part of the study, these food items (popcorn, jelly beans) were placed in the 12 locations described above. Nine individuals diagnosed with PWS (deletion type) and three individuals with ID were given some break time in the room for 15 min. The amount of food consumed, the time spent food seeking, and time spent interacting with materials were measured. Results Results of the survey indicated that the PWS group differed significantly with regard to how they responded on the survey from the typically developing group, but did not differ significantly from the ID group. Results of the food seeking observations indicated that only three individuals with PWS ate a significant number of items. The three individuals did not differ from the rest of the group according to IQ or compulsivity score; however, they had significantly lower body mass index (BMI) scores and were younger than the other participants. Conclusions The findings from the survey indicate that individuals with PWS are able to discriminate the appropriateness of eating items in more or less contaminated areas; however, the amount of time spent seeking food and the amount of food covertly consumed appeared to depend more directly on age and BMI.

Objective. To determine whether phenotypic differences exist among individuals with Prader-Willi syndrome with either type I or type II deletions of chromosome 15 or maternal disomy 15 leading to a better understanding of cause and pathophysiology of this classical genetic syndrome. Methods. We analyzed clinical, anthropometric, and behavioral data in 12 individuals (5 men, 7 women; mean age: 25.9 ± 8.8 years) with PWS and a type I (TI) deletion, 14 individuals (6 men, 8 women; mean age: 19.6 ± 6.5 years) with PWS and a type II (TII) deletion, and 21 individuals (10 men, 11 women; mean age: 23.6 ± 9.2 years) with PWS and maternal disomy 15 (UPD). The deletion type was determined by genotyping of DNA markers between proximal chromosome 15 breakpoints BP1 and BP2. TI deletions are ∼500 kb larger than TII deletions. Several validated psychological and behavioral tests were used to assess phenotypic characteristics of individuals with PWS representing the 3 genetic subtypes. Results. Significant differences were found between the 2 deletion groups and those with UPD in multiple psychological and behavorial tests, but no differences were observed in other clinical or anthropometric data studied. Adaptive behavior scores were generally worse in individuals with PWS and the TI deletion, and specific obsessive-compulsive behaviors were more evident in the TI individuals compared with those with UPD. Individuals with PWS with TI deletions also had poorer reading and math skills as well as visual-motor integration. Conclusions. Our study indicates that individuals with TI deletion generally have more behavioral and psychological problems than individuals with the TII deletion or UPD. Four recently identified genes have been identified in the chromosome region between BP1 and BP2 with 1 of the genes (NIPA-1) expressed in mouse brain tissue but not thought to be imprinted. It may be important for brain development or function. These genes are deleted in individuals with TI deletion and are implicated in compulsive behavior and lower intellectual ability in individuals with TI versus TII.

We have paid little attention to gender differences in developmental disabilities aside from the purpose of establishing prevalence. Yet, studying sex differences in the incidence and presentation of developmental disability and mental health disorders may contribute to our understanding of the neural circuitry and neurochemistry of both the normal and the abnormal brain. Furthermore, investigation into gender difference may have practical implications, as we may need to design sex-specific interventions for persons with developmental disability. In this article, we first review sex differences in typically developing children as well as some of the literature on the biology proposed to explain those differences. We then explore differences in prevalence and presentation of several developmental and mental health disorders as they may relate to biological mechanisms–with special attention to autism. Finally, we look at research needs as they relate to sex in developmental disability.

We tested the influence of (1) the homelike appearance of residences, (2) residential staff-members' attitudes about people with mental retardation and (3) Client IQ on the number of activities adults clients with mental retardation conducted in their community. We tested the hypothesis these three variables exerted their influence by promoting positive staff-member interactions with clients. This was assessed by measuring the duration of Staff-initiated Social Interactions with residential clients. In our initial path model, Residential Homelikeness, Positive Staff Attitudes and Client IQ had no significant direct effect on Community Activities. In the final model, however, Residential Homelikeness and Positive Staff Attitudes exerted a statistically significant influence on Staff-initiated Social Interactions with clients, which in turn, exerted a statistically significant influence on Community Activities. This model illustrated: (1) the nearly equal influence of Staff Attitudes and architectural characteristics on Staff-initiated Interactions; and (2) the role of Staff-initiated Interactions in mediating the influence of Residential Homelikeness on community participation by adults with developmental disabilities.

The fields of genetics and neuroscience are yielding findings useful in understanding complex behavior-environment relations. We believe that these developments in interdisciplinary basic research are of interest to applied behavior analysts because of the long history of basic findings being used by the readership of the Journal of Applied Behavior Analysis to improve everyday human activities. An awareness of contemporary developments in a range of basic research disciplines may facilitate the systematic replication of those functional relations in applied settings. In this context, we selectively review papers published in the Journal of the Experimental Analysis of Behavior and other basic research journals that relate to gene-brain-behavior relations.

The cardinal feature of individuals with Prader-Willi syndrome (PWS) is severe hyperphagia-mediated obesity resulting from a faulty satiety mechanism. PWS is the most common genetic cause of marked obesity. Cholecystokinin (CCK) is a 33-amino-acid peptide found in high levels in the gut and brain involved in mediating the satiety response to meals. Free fatty acids (FFA) are responsible for the stimulation of CCK release after a fatty meal, and CCK and plasma FFA levels rise in tandem in normal individuals. Fasting plasma CCK levels were measured by radio-immunoassay in 33 PWS subjects with a mean age of 22.2 years +/- 8.1 years and 24 obese control subjects without a known cause of their obesity with a mean age of 28.7 years +/- 12.9 years. Consistent with previous findings, neither fasting plasma FFA levels (617.5 versus 486.8 microm/mL) or CCK levels (21.0 versus 19.1 pg/mL) were significantly different in PWS or control subjects, respectively. However, there was a significant correlation between fasting plasma FFA and CCK levels in obese subjects (r = 0. 64, P < 0.01), this correlation was completely lacking in PWS subjects (r = -0.06, P = 0.79). This difference in correlation coefficients constitutes a large effect. There were no significant effects observed for genetic subtypes (15q11-q13 deletion or maternal disomy 15), body mass index, percentage of fat, plasma levels of insulin, C-peptide, glucagon or leptin, age, or gender on CCK levels in our PWS subjects. These results suggest that differences in the peripheral CCK response to FFA levels may be a factor contributing to the altered satiety response in PWS subjects.

Among the most significant trendsin science over the past decade is onetoward translational research—workthat spans the continuum from labo-ratory science to practical applica-tion. The translational model, some-times also known as ‘‘bench tobedside,’’ seeks to build bridges acrossresearch areas and disciplines, promot-ingcross-fertilizationofideas.Muchofthe best work in behavior analysis is ofthis translational character. To high-light this research in behavior analysis,a special program track at the 2009Association for Behavior AnalysisInternational (ABAI) convention wascreated. Cosponsored by the ABAIPractice and Science Boards, the key-note events in this special track weretwo sessions—one on stimulus controlin autism and one on behavioralmomentum—withthecontributingau-thors invited to submit papers forpublication in The Behavior Analyst.The result is the present collection ofpapers.Stimulus Control in AutismIn the early days of autism researchand practice, consequence strategiesfor increasing skills and decreasingbehavioral challenges were empha-sized (Ferster, 1961). Lovaas’s earli-est autism work employed simplediscrimination procedures drawn di-rectly from the laboratory (Lovaas,1967). However, even in the earlyyears it was recognized that autism isdistinguished by unusual responses toantecedentstimuli(Lovaas&Schreib-man, 1971). It is widely recognizedtoday that lack of control by, andinappropriate responses to, anteced-ent stimuli are important distinguish-ing features of autism (AmericanPsychiatric Association, 1994, p. 72).Specifically, children and youth withautism may exhibit no spoken lan-guageinresponsetosocialorlanguagestimuliemanatingfromothers,ormayfailtorespondtosymbolicmeaningofwords or other symbols (AmericanPsychiatric Association, 1994, p. 75).McIlvane’s paper examines trans-lational behavior analysis, linkingnonhuman laboratory research oncomplex stimulus control proceduresto studies with individuals with au-tism and other developmental dis-abilities. Based on matching-to-sam-ple methodology originally developedby Sidman and Tailby (1982), McIl-vane, Dube, and colleagues haveconducted extensive research demon-strating that many individuals whohad heretofore been believed to beincapable of developing symboliclanguage skills, could be taught suchskills (McIlvane et al., in press). Theirmethods derived directly from non-human laboratory research and lab-oratory research with individualswith developmental disabilities. McIl-vane argues that translational behav-ior analysis is a two-way street, withknowledge generated by applied re-search feeding back and enrichingsubsequent laboratory investigations.Koegel, Shirotova, and Koegelexamine a problem practitioners inschools and home-based therapysettings often encounter when work-ing with young children with autism

The self-injurious behaviour of people with intellectual disabilities, autism, and related developmental disabilities remains one of the most difficult behaviour problems to treat clinically. Two promising approaches to effective treatment involve teaching the person communication skills that are functionally equivalent to the self-injury or administering opiate antagonist medication. Here an experimental case study, in which naltrexone was combined with functional communication training, is reported. Using a within-subject ABCDC experimental design, reductions in rate of self-injury were observed during the naltrexone alone phase as well as during combined treatment phases. The implications of conducting a functional assessment prior to behavioural and pharmacological intervention are discussed.

Plasma gamma-aminobutyric acid (GABA) levels were measured in 14 subjects with Prader-Willi syndrome, 9 subjects with Angelman syndrome, and matched control subjects. Mean levels in both patient groups were 2 to 3 times higher than in nonretarded moderately obese or retarded nonobese control subjects. Levels in each patient group differed significantly from both control groups. Neither the two patient groups nor the two control groups differed. GABA levels seemed unrelated to genetic status (chromosome 15 deletion or disomy). These preliminary findings of elevated plasma GABA levels possibly represent a compensatory increase in presynaptic GABA release in response to hyposensitivity of a subset of GABA receptors and could produce increased postsynaptic activation of other normal GABA receptor subtypes, resulting in complex alterations of GABAergic function throughout the brain.

Pigeons were taught to interact communicatively (i.e., exchange discriminative stimuli) based on 1 pigeon’s internal state, which varied as a function of cocaine, pentobarbital, and saline administration. These performances generalized to untrained pharmacological agents (d-amphetamine and chlordiazepoxide) and were observed in the absence of aversive stimulation, deprivation, and unconditioned reinforcement. The training procedure used in this study appears similar to that by which humans learn to report on (tact) their internal environments and may be construed as a rudimentary animalmodel of the interpersonal communication of private events.Keywords: private events, tacts, interanimal communication, emotion, pigeons., Pombos foram ensinados a interagir comunicativamente (i.e., trocar estímulos discriminativos) baseados no estado interno de um deles, que variava em função da administração de cocaína, pentobarbital e salina. Esses desempenhos foram generalizados para agentes farmacológicos não treinados (d-anfetamina e clorodiazepoxina) e foram observados na ausência de estimulação aversiva, privação e reforçamento incondicionado. O procedimento de treino utilizado neste estudo parece similar àquele pelo qual humanos aprendem a relatar (tatear) seus ambientes internos e talvez se constitua em um modelo animal rudimentar da comunicação interpessoal de eventos privados.Palavras-chave: eventos privados, tatos, comunicação interanimal, emoção, pombos.

Since its inception, the John F. Kennedy Center has attempted to overcome developmental problems, which create restrictive barriers to the participation of individuals with specific disabilities in our broader society. Some of Nicholas Hobbs's earliest efforts involved developing strategies for preventing children's emotional and behavior problems, which interfered with their later full participation in society. Other investigators in the Kennedy Center explored ways of reducing dysfunctional repetitive movement problems and self-injury commonly associated with autism and severe mental retardation. We have become concerned about a group of people who have the potential to live largely independently (or semi-independently), to work at meaningful jobs in the community, and to make full use of the same recreational and leisure opportunities as other members of society but who are prevented from doing so because of a life-threatening behavior problem. Prader-Willi syndrome (PWS) is a genetic developmental disability characterized by a group of specific behavioral features of which an insatiable appetite is the most striking. PWS is the most commonly known genetic cause of obesity. The eating disorder associated with PWS can be so severe as to be life threatening, including eating to the point of stomach rupture and death. Though a cluster of commonly covarying clinical features are exhibited by people with this syndrome, only the eating disorder is common to all affected individuals. PWS shares behavioral features with other disorders and disabilities, such as obsessive compulsive disorder and autism, but only PWS includes the unique combination of characteristics that distinguish this syndrome. Because eating disorders such as bulimia and anorexia nervosa also share features with PWS, any light that could be shed on the causes and treatment of the eating disorder in PWS could potentially have far-reaching implications for other eating disorders as well. In this article, we review the behavioral, cognitive, and other psychological features of PWS and explore their relationships to known genetic mechanisms.

The current study demonstrates the ability of neuropeptide Y (NPY) to increase break points under a progressive ratio 1 (PR1) reinforcement schedule. An initial response resulted in delivery of a food reinforcer (45 mg pellet) under the PR1, and an additional response was required for each successive reinforcer. The break point, the number of responses emitted to obtain the last reinforcer, is considered a measure of reinforcing efficacy or motivational strength of the food reinforcer. NPY (0.3-10 micrograms) significantly increased break point to levels comparable to those produced by 36-48 h of food deprivation. Although insulin (3-8 U/kg) and 2-deoxyglucose (150-250 mg/kg) also increased food intake, neither increased break points to levels produced by NPY or food deprivation. These data suggest that NPY may change the value of food in ways that cannot be accounted for by changes in insulin, glucose levels or intracellular glucoprivation. These results emphasize that simply measuring the amount of freely available food eaten is not a fully adequate measure of the strength of the feeding behavior.

The compulsive and deeply disturbing character of self-injurious behavior (SIB) makes it one of the most difficult behavior problems to understand scientifically and treat clinically. We review evidence implicating endogenous opioid peptides and the neurotransmitter dopamine in SIB. Next, we describe similarities between the self-administration of cocaine and morphine by laboratory animals and self-injury by people with mental retardation. We discuss shared behavioral and neurochemical properties that suggest common mechanisms that may be responsible for both the persistent, damaging behavior patterns characteristic of some forms of SIB and the addictive self-administration of cocaine and morphine. Multifaceted treatment approaches are explored, based on a better understanding of underlying mechanisms. © 1995 Wiley-Liss, Inc.

Twelve pigeons key-pecked under a multiple variable interval 15-s, 150-s schedule of food reinforcement. The effects of methadone were studied alone and in combination with chronic daily administration of either imipramine (IMI) or desipramine (DMI). Chronic IMI was also given following reductions in response rates by unsignalled delay-to-reinforcement (UDR). Acute administration of methadone produced dose-dependent reductions in response rates under both schedules of reinforcement. Chronic daily administration of IMI or DMI alone did not result in lasting changes in baseline responding. When administered in combination, chronic daily IMI significantly attenuated the rate-reducing effects of methadone, whereas neither a low nor a high dose of chronic daily DMI was effective. The same dose of chronic daily IMI failed to ameliorate response rate reductions under delayed reinforcement. The behavioral and neurochemical specificity of the antidepressant effect is discussed.

Using a two-lever drug discrimination procedure, two groups of four rats each were trained to discriminate the stimulus effects of 1.0 U/kg insulin or 125 mg/kg 2-deoxy- D -glucose (2-DG) from saline. A third group was trained to discriminate food deprivation produced by feeding 23 h prior to sessions from satiation produced by feeding 2 h prior to sessions. Differential responding was a direct function of dose or deprivation level in each group. Rats trained to discriminate insulin responded as if they had received insulin when they received 2-DG and vice versa. Insulin and 2-DG produced deprivation-appropriate responding in two of four rats trained to discriminate food deprivation. Low insulin and 2-DG doses produced drug-appropriate responding in rats deprived 47 h, but not in rats deprived 23 h. Blood glucose level was altered by the training doses of insulin and 2-DG, but not by 23-h deprivation. These results indicate that operations that induced feeding produce discriminable stimuli, and that these effects overlap or interact. Thus, drug discrimination procedures can be useful in the analysis of ingestive behavior.

Objective: To study, by direct observation, physically aggressive behavior (PAB) in a cohort of older persons with dementia. Design: Cross-sectional survey. Setting: A locked special care unit for Alzheimer's Disease and an ordinary skilled unit of two suburban nursing homes. Participants: Twenty men and women with a history of PAB. Measurements and Main Results: Portable bar-code-readers and daily diaries were used to determine the frequency of PAB as well as to elucidate the antecedents and consequences of it. PAB was most often directed toward staff (23/28 episodes), usually in the context of personal care (15/23 episodes). In the majority of cases, verbal aggression or noncompliance preceded the PAB. Most often PAB was followed by a rapid return to non-aggressive behavior. Conclusions: Very little PAB was truly spontaneous, nor was it usually the participant's normal behavior. Most PAB occurred in response to intrusion into the participant's personal space by staff or other residents. The PAB is better understood as a defensive response than an expression of anger.

The way people come to report private stimulation (e.g., feeling states) arising within their own bodies is not well understood. Although the Darwinian assumption of biological continuity has been the basis of extensive animal modeling for many human biological and behavioral phenomena, few have attempted to model human communication based on private stimulation. This target article discusses such an animal model using concepts and methods derived from the study of discriminative stimulus effects of drugs and recent research on interanimal communication. We discuss how humans acquire the capacity to identify and report private stimulation and we analyze intra- and interspecies differences in neurochemical mechanisms for transducing interoceptive stimuli, enzymatic and other metabolic factors, learning ability, and discrimination learning histories and their relation to psychiatric and developmental disabilities.

Twelve pigeons key-pecked under a multiple variable interval 15-second, variable interval 150-second schedule of food reinforcement. Effects of two opioid drugs, buprenorphine and methadone, were determined alone and in combination with chronic daily administration of the antidepressants doxepin or bupropion. Methadone initially produced dose-dependent key-pecking rate reductions when administered acutely, prior to the session, while buprenorphine produced key-pecking rates that reached a plateau at 50-80% of baseline rate and were not reduced further by higher doses. Neither doxepin nor bupropion, given alone, had lasting effects on key-pecking rates. Chronic daily doxepin administration significantly attenuated methadone-induced response rate reductions. Bupropion reduced the effect of the highest methadone dose, but this effect was mitigated by the development of opioid tolerance. Unlike bupropion, doxepin interfered with the development of opioid tolerance. Neither antidepressant systematically altered effects of buprenorphine on key-pecking.

Prader-Willi syndrome (PWS) is a complex genetic condition characterized by a range of mental and physical fi ndings, with obesity being the most signifi cant health problem. PWS is considered to be the most common genetically identifi ed cause of life-threatening obesity in humans and affects an estimated 350,000–400,000 people worldwide. The Prader-Willi Syndrome Association (USA) is aware of more than 3,500 persons with this syndrome in the United States from an estimated pool of 17,000–22,000. Prader-Willi syndrome has an estimated prevalence in the range of 1 in 8,000 to 1 in 20,000 individuals. Although PWS is thought to be one of the more common disorders seen for genetic services, pediatricians may only encounter a few patients during their lifelong clinical practice. It is present in all races and ethnic groups but reported disproportionately more often in Caucasians. Most cases are sporadic; however, at least 20 families have been reported in the literature with more than one affected member, including twins. The chance for recurrence is estimated to be less than 1%. However, in some families where defective control of differentially expressed genes through errors in the process of genomic imprinting (described in detail in Chapter 3) is present in the PWS child and in the father, then the recurrence may be as high as 50% for having additional children with PWS. Prader-Willi syndrome was apparently fi rst documented in an adolescent female by J. Langdon Down in 1887, but it was not described in the medical literature until about 70 years later. This adolescent female had mental defi ciency, obesity, short stature, and hypogonadism, and the condition was referred to as polysarcia. In 1956, Prader, Labhart, and Willi reported nine individuals (fi ve males and four females between the ages of 5 and 23 years) with similar clinical fi ndings. Since the 1970s, the disorder has been referred to as the PraderWilli syndrome. In 1981, Ledbetter and others fi rst reported the cause as an interstitial deletion of the proximal long arm of chromosome 15 at region

Almost 50 years after originally described, Prader-Willi syndrome (PWS) continues to unfold, revealing complex physiologic, genetic, and behavioral mechanisms that often seem contradictory to standard medical and clinical understandings. This is particularly true regarding the accompanying neurodevelopmental/behavioral complex (sometimes termed behavior phenotype). While still primarily noted for the distinctive food-related behavioral constellation, PWS is characterized by a far broader neurodevelopmental profi le including a distinctive cluster of behavioral features along with mental retardation or learning diffi culties. Even so, this profi le is neither universal nor uniform; considerable phenotypic variability is observed among affected individuals and in the same individual over time. Understanding this phenotypic variability is further complicated by several published series that report varying rates of major behavior features. Some of this reported variability is refl ected in studies that either predate, or postdate, both consensus diagnostic criteria (1993) and comprehensive confi rmatory genetic technology (mid to late 1990s, M.G. Butler, personal communication). Thus, part of the reported differences may result from different ascertainment and diagnostic stra tegies. Further, previously unaccounted for genetic variation (chromosome 15 deletion versus uniparental disomy [UPD]) may be the source of additional variability. Recent studies suggest that only hyperphagia, skin picking, stubbornness, and temper tantrums are common to most affected individuals, yet substantial variation is observed even among these common characteristics. A clear understanding of the genetically driven neurobehavioral profi le and the impact of environmental infl uences on the expression of this behavioral profi le is pivotal to addressing issues of intervention and remediation, yet our understanding of these aspects of the syndrome remains rudimentary and imperfect—a state of affairs that frustrates parents and caregivers alike. In this chapter we will summarize the current understandings of the neurodevelopmental/behavioral aspects of PWS. It is fi rst necessary, however, to discuss several historical and methodological factors that

Maladaptive behaviors among 65 people with Prader-Willi syndrome were assessed using the Reiss Screen for maladaptive behaviors. Young adults in their twenties were more likely to display aggressive behavior than adolescents and older adults. Differences in maladaptive behaviors between the typical deletion and uniparental disomy (UPD) subtypes were evaluated. The typical deletion subtype had higher self-injury and stealing scores than the UPD subtype. Subject characteristics were differentially related to maladaptive behavior among the typical deletion and UPD subtypes. Differences in maladaptive behavior were also examined between the typical deletion type I and type II subtypes. The type I deletion subtype had greater physical depression scores than the type II deletion subtype. The Reiss Screen cut-off scores were used to determine whether differences occurred between the subtypes at a clinically significant level. These findings offer insight into the health care needs of people with PWS.

Discrimination of the shape of motion-produced forms generated by random elements (i.e. second-order stimuli varying in element density and temporal correlation) was tested in four groups: (1) subjects with Prader-Willi syndrome (PWS), chromosome 15q deletion subtype; (2) subjects with PWS, uniparental maternal disomy (UPD) subtype; (3) equivalent non-PWS controls; and (4) normal controls. The performance of the normal controls exceeded that of all other groups (78% correct, P < 0.009). The PWS deletion (66%) and the equivalent control groups (59%) did not differ (P < 0.95). The UPD group performed significantly less well (38%, P < 0.04) than all the other groups. The performance of the PWS deletion and equivalent control groups is consistent with other data indicating that these populations encounter difficulty meeting the processing demands posed by second-order stimuli. The inferior performance of the UPD group may be attributed to receiving two active alleles of a maternally expressed gene influencing neural development. One candidate is the ubiquitin protein ligase gene (UBE 3 A), which is maternally expressed only and localized to the 15q region. Other possibilities include the requirement of a paternally expressed gene, residual mosaic trisomy 15 in the brain tissue or complex interactions including specific ratios of differentially spliced gene products.

Seventeen patients with Prader-Willi syndrome (7 with paternal deletion of chromosome 15q11-q13 and 10 with maternal uniparental disomy [UPD]), and 9 controls performed a computerized visual recognition task. A series of color digital photographs were presented; most were presented twice, but the remainder appeared only once. Photographs presented twice were separated in their presentation by either 0, 10, 30, 50 or 100 intervening photographs. Subjects indicated whether each photograph had been presented previously. This procedure was implemented twice, once using photographs of foods, and once using photographs of nonfood objects. As the number of intervening photographs between the first and second presentation increased, subjects were less likely to remember having seen the photograph before. Performance by UPD subjects was less affected by increasing the number of intervening photographs relative to the other two groups, suggesting they had superior visual recognition memory. This raises the possibility of a beneficial effect of having two copies maternally expressed genes on chromosome 15. UBE3A is suggested as a possible candidate for this effect.

Many adults with Prader-Willi syndrome are affected by behaviors such as tantrums, skin-picking, and compulsions. The nature and extent of these problems suggest more attention be directed to their emergence in childhood. Our purpose was to investigate behavior problems in children with this syndrome and identify the age at which these behaviors emerge. Parents of children with Prader-Willi syndrome, Down syndrome, and those developing typically completed questionnaires. Children with Prader-Willi syndrome exhibited more compulsions, skin-picking, and tantrums than did the other groups. A discriminant analysis of behavior variables derived two statistically significant functions that were interpreted as developmental milestones and problematic behavior. These functions correctly predicted membership for 79% of grouped cases.

Since the initial medical description by Prader, Labhart and Willi in 1956 of individuals with overlapping features, the Prader-Willi syndrome has become recognized as a classical but sporadic genetic syndrome. Prader-Willi syndrome is the most common genetic cause of life-threatening obesity in humans. It is estimated that there are 350,000-400,000 people with this syndrome worldwide. Prader-Willi Syndrome Association USA knows of more than 3,400 persons with Prader-Willi syndrome in the USA out of an approximate 17,000-22,000. Prader-Willi syndrome with an incidence of 1 in 10,000 to 25,000 individuals and Angelman syndrome, an entirely different clinical condition, were the first examples in humans of genetic imprinting. Genetic imprinting or the differential expression of genetic information depending on the parent of origin plays a significant role in other conditions including malignancies.

Sleep patterns of 30 individuals with self-injurious behavior and mental retardation were compared with those of 30 matched controls residing in the same residential facility that did not self-injure. Individuals were recorded as asleep or awake during 30 min intervals for eight hours per night. The results of a Wilcoxon signed-ranks test (p < .05) indicated that individuals with self-injury slept significantly less than individuals without self-injury. chi2 analyses (p < .01) indicated significantly greater variability in the number of intervals recorded as asleep among individuals with self-injury than their matched controls. These results are congruent with previous findings of sleep disturbance among persons with mental retardation and behavior problems. The possibility of neurochemical dysregulation in sleep disturbance among individuals with daytime self-injury is discussed.

CHEN, KONG Y., MING SUN, MERLIN G. BUTLER, TRAVIS THOMPSON, AND MICHAEL G. CARLSON. Development and validation of a measurement system for assessment of energy expenditure and physical activity in Prader—Willi syndrome. Obes Res. Objective: The morbid obesity associated with Prader—Willi syndrome (PWS) may result from either excessive energy intake or reduced energy expenditure (EE). In this report, we describe the development and validation of an Activity—Energy Measurement System (AEMS) to measure EE and physical activity components in an environment approximating free-living conditions. Research Methods and Procedures: The AEMS consists of a live-in, whole-room indirect calorimeter equipped with a novel force platform floor system to enable simultaneous measurements of EE, physical activity, and work efficiency during spontaneous activities and standardized exercises. Free-living physical activity and estimated free-living EE are measured using portable triaxial accelerometers individually calibrated in each subject during their stay in the AEMS. Results: Representative data from two PWS patients and two matched control (CTR) subjects displayed EE during their inactive lifestyles. Discussion: This combination of methods will allow the quantification of daily EE and its components, the amount and energy cost of physical activity, and the relationships between body composition and EE, in order to determine their roles in the development and maintenance of the morbid obesity in PWS.

With few exceptions (e.g., Lesch-Nyhan syndrome), the specific nature of self-injury in relation to identified genetic syndromes associated with mental retardation is poorly understood. In the present study we surveyed the families of 62 persons with Prader-Willi syndrome to determine the prevalence, topographies, and specific body locations of self-injurious behavior. Self-injury was reported for 81% of the participants. Skin-picking was the most prevalent form, with the front of the legs and head being disproportionately targeted as preferred self-injury body sites. Individuals with the 15q11-q13 deletion injured significantly more body sites than did individuals with maternal disomy 15. Results are discussed in relation to previous self-injury body site findings and implications for the relevance of syndrome-specific behavioral phenotypes.

The presence and severity of compulsive behaviours may be evaluated via the Compulsive Behaviour Checklist (CBC) and this instrument has been successfully employed in people with intellectual disability. However, the applicability of the overall CBC scoring system, which entails tallying the number of behavioural categories represented (i.e. five) as well as the number of individual behaviours endorsed (i.e. 25), is not known in the population with Prader-Willi syndrome (PWS). The present investigation examined the latent variable structure of the CBC in people with PWS in order to identify possible population-specific scoring and interpretation considerations. The 25 behaviour-specific items of the CBC were analysed for 75 people with PWS (44 females and 31 males) aged between 4 and 41 years (mean +/- SD = 11.4+/-9.4) via factor analysis with principal component extraction and equamax rotation. The most suitable solution was determined on the basis of multiple empirical criteria: (1) the scree test; (2) eigenvalues >1.00; (3) salient loadings >0.30; (4) the clarity of item assignment to a single latent dimension; (5) the internal consistency of the latent dimension(s) (coefficient alpha > or = 0.70); and (6) item-total correlations between 0.20 and 0.79. In addition, solutions were examined with respect to psychological theory and previous research. A 'general factor' (i.e. single latent dimension) solution which adhered to all a priori criteria was indicated. Twenty-four out of 25 items achieved salient loadings ranging from 0.46 to 0.80 on the general factor. The single item which failed to achieve salience, 'deviant grooming-skin picking', exhibited both substantial unique variance (0.997) and moderate reliability (r = 0.59, P

Seven rats lever pressed under a progressive ratio 3 (PR 3) schedule of food presentation; the number of responses per reinforcer systematically increased during each session. Break point (i.e., the number of responses in the last completed ratio before session termination) was measured under daily methadone (4.5 mg/kg and 3.0 mg/kg) or buprenorphine (0.3 mg/kg) administered prior to experimental sessions. Both drugs initially eliminated rats' food-maintained progressive-ratio responding. Break points during chronic methadone did not return to baseline levels after 80 drug sessions and a dose reduction. In contrast, break points during chronic buprenorphine administration were considerably above baseline control levels for two rats and returned to baseline levels for the third.