RESUMEN
BACKGROUND: Recent work suggests that maladaptive behaviors in genetic developmental disorders may emerge from autonomic dysfunctions impacting higher order executive functions. In Prader-Willi syndrome (PWS), executive functions are not well understood and investigations of possible underlying causes at the autonomic level are lacking. AIMS: This study aimed at clarifying the status of inhibition and working memory updating functions in PWS and searched for sympathetic signatures as well as to examine their links with executive performance. METHODS AND PROCEDURES: The performance of thirty adults with PWS was compared to that of thirty healthy adults on two tasks assessing inhibition and working memory updating while electrodermal activity (EDA) was recorded. OUTCOMES AND RESULTS: PWS adults underperformed healthy adults in the inhibition and the working memory updating tasks and showed abnormal skin conductance responses. Distinct EDA have been found in PWS and healthy adults. Furthermore, while EDA reflected distinct cognitive processes, correlations between electrodermal and behavioural data were absent when examining the two groups separately. CONCLUSIONS AND IMPLICATIONS: PWS is associated with a slight impairment of inhibition and a severe impairment of working memory updating. Furthermore, there are specific sympathetic autonomic signatures in PWS that do not present straightforward links with executive dysfunctions.
Asunto(s)
Función Ejecutiva , Respuesta Galvánica de la Piel/fisiología , Inhibición Psicológica , Memoria a Corto Plazo , Síndrome de Prader-Willi/fisiopatología , Sistema Nervioso Simpático/fisiopatología , Adulto , Estudios de Casos y Controles , Femenino , Humanos , Masculino , Persona de Mediana Edad , Síndrome de Prader-Willi/psicología , Análisis y Desempeño de Tareas , Adulto JovenRESUMEN
BACKGROUND: Prader-Willi syndrome (PWS) is a developmental genetic disorder characterised by a variable expression of medical, cognitive and behavioural symptoms. In adulthood, the prevalence and severity of these symptoms determine the quality of life of the affected persons. Because of their rare disease condition, data on health and social problems in adults with PWS are scarce. In this research, we present medical, psychological and social features of a large cohort of adults admitted to a specialised PWS centre in France and analyse the differences according to genotype, gender and age. METHODS: Data from 154 patients (68 men/86 women), with a median age of 27 years (range 16-54), were collected during their stay in our centre. Clinical histories were completed using information from parents or main caregivers, and the same medical team performed the diagnosis of different clinical conditions. Statistical analyses were performed to determine the influence of factors such as genotype, age or gender. RESULTS: Paternal deletion genotype was the most frequent (65%) at all ages. Most patients had mild or moderate intellectual disability (87%). Only 30% had studied beyond primary school and 70% were in some special educational or working programme. Most of them lived in the family home (57%). The most prevalent somatic comorbidities were scoliosis (78%), respiratory problems (75%), dermatological lesions (50%), hyperlipidaemia (35%), hypothyroidism (26%), Type 2 diabetes mellitus (25%) and lymph oedema (22%). Some form of psychotropic treatment was prescribed in 58% of subjects, and sex hormones in 43%. Patients with deletion had a higher body mass index (44 vs. 38.9 kg/m(2)) and displayed higher frequency of sleep apnoeas. Non-deletion patients received insulin treatment (19% vs. 4%) and antipsychotic treatment (54.8% vs. 32.7%) more frequently. No difference was observed in the prevalence of Type 2 diabetes between the two genotype groups. Patients >27 years of age had a higher rate of comorbidities (Type 2 diabetes, hypertension, respiratory problems and lymph oedema). Gender differences were minor. CONCLUSIONS: Adult patients with PWS showed high prevalence of comorbid health problems that need to be monitored for early treatment. Some of them are influenced by genotype and age. Another salient problem concerns the lack of adapted structures for better social integration. Further data about the real life and health conditions of adults with PWS are necessary to further our knowledge of the natural history of the disease and to design appropriate care strategies.
Asunto(s)
Síndrome de Prader-Willi , Adolescente , Adulto , Estudios de Cohortes , Comorbilidad , Femenino , Francia/epidemiología , Hospitales Especializados/estadística & datos numéricos , Humanos , Masculino , Persona de Mediana Edad , Síndrome de Prader-Willi/epidemiología , Síndrome de Prader-Willi/genética , Síndrome de Prader-Willi/fisiopatología , Síndrome de Prader-Willi/psicología , Adulto JovenRESUMEN
BACKGROUND: Prader-Willi syndrome (PWS) is a rare genetic disorder characterised by developmental abnormalities leading to somatic and psychological symptoms. These include dysmorphic features, impaired growth and sexual maturation, hyperphagia, intellectual delay, learning disabilities and maladaptive behaviours. PWS is caused by a lack of expression of maternally imprinted genes situated in the 15q11-13 chromosome region. The origin is a 'de novo' deletion in the paternal chromosome in 70% of the cases and a maternal uniparental disomy in 25%. The two main genotypes show differences, notably regarding cognitive and behavioural features, but the mechanisms are not clear. This study assessed cognitive impairment in a cohort of adults with genetically confirmed PWS, analysed their profiles of cognitive strengths and weaknesses, and compared the profiles in terms of genotype. METHODS: Ninety-nine male and female adults participated, all inpatients on a specialised unit for the multidisciplinary care of PWS. The Wechsler Adult Intelligence Scale (WAIS-III) was administered to all patients in identical conditions by the same psychologist. Eighty-five patients were able to cope with the test situation. Their scores were analysed with non-parametric statistical tools. The correlations with sex, age and body mass index were explored. Two genotype groups were compared: deletion (n = 57) and non-deletion (n = 27). RESULTS: The distribution of intelligence quotients in the total cohort was non-normal, with the following values (medians): Full Scale Intelligence Quotient (FSIQ): 52.0 (Q1:46.0; Q3:60.0), Verbal Intellectual Quotient (VIQ): 53.0 (Q1:48; Q3:62) and Performance Intellectual Quotient (PIQ): 52.5 (Q1:48; Q3:61). No correlation was found with sex, age or body mass index. Comparison between groups showed no significant difference in FSIQ or VIQ. PIQ scores were significantly better in the deletion group. The total cohort and the deletion group showed the VIQ = PIQ profile, whereas VIQ > PIQ was observed in the non-deletion group. The subtest scores in the two groups showed significant differences, with the deletion group scoring better in three subtests: object assembly, picture arrangement and digit symbol coding. Some relative strengths and weaknesses concerned the total cohort, but others concerned only one genotype. DISCUSSION: We documented a global impairment in the intellectual abilities of a large sample of French PWS patients. The scores were slightly lower than those reported in most other studies. Our data confirmed the previously published differences in the cognitive profiles of the two main PWS genotypes and offer new evidence to support this hypothesis. These results could guide future neuropsychological studies to determine the cognitive processing in PWS. This knowledge is essential to improve our understanding of gene-brain-behaviour relationships and to open new perspectives on therapeutic and educational programmes.
Asunto(s)
Trastornos del Conocimiento/genética , Trastornos del Conocimiento/psicología , Cognición , Genotipo , Síndrome de Prader-Willi/genética , Síndrome de Prader-Willi/psicología , Adolescente , Adulto , Trastornos del Conocimiento/complicaciones , Estudios de Cohortes , Femenino , Francia , Humanos , Masculino , Persona de Mediana Edad , Síndrome de Prader-Willi/complicaciones , Adulto JovenRESUMEN
BACKGROUND: Prader-Willi syndrome (PWS) is associated with a characteristic behavioural phenotype whose main features are, alongside compulsive hyperphagia, deficits in social behaviour: social withdrawal, temper tantrums, perseverative speech and behaviour, mental rigidity, stereotyped behaviour, impulsiveness, etc. Similar symptoms may also be found in autistic spectrum disorders and lesional pathologies of the frontal lobe. In both cases, such symptoms have been related to dysfunctions in frontal cognitive processes such as attention, working memory and executive functions. This study uses standardized neuropsychological instruments to analyse the degree to which these processes are affected in PWS. METHODS: The sample comprised 16 individuals with a genetically confirmed PWS diagnosis. Subjects' IQ (Wechsler Adult Intelligence Scale), academic level, laterality and body mass index (BMI) were calculated. Attention, memory and executive functions were analysed using standard, widely employed neuropsychological tests. We compared the results of the sample group with the general population. Correlation analyses were carried out with IQ, academic level and BMI. RESULTS: In all the neuropsychological measures focusing on attention, executive functions and visuoperceptual organization, the study sample scored significantly lower than the normative reference population. The scores of the tests used for measuring immediate memory were also significantly lower when trials required sequential processing, although not when they required simultaneous processing. In the memorization of a list of words, subjects showed an initial deficit which disappeared with repetition, enabling them to obtain scores similar to the reference population. No significant correlations were found with BMI, and a higher IQ or academic level did not improve scores in the majority of tests. CONCLUSIONS: The study shows a deficit in elementary frontal cognitive processes in PWS patients. This deficit may be involved in the social behaviour disorders that characterize such patients, as described in other development or frontal syndrome pathologies. However, we cannot affirm that the deficits found are specific to PWS; they could also occur in other causes of intellectual disability. Although in the study sample IQ did not correlate with frontal deficits, further research is needed to establish whether the neuropsychological alterations described form part of a cognitive phenotype for PWS. We believe that our understanding of the social behaviours typical of PWS may be improved by taking into consideration the cognitive functioning models of the prefrontal lobe, particularly those applied to pervasive developmental disorders.