The course and outcome of psychiatric illness in people with Prader-Willi syndrome: implications for management and treatment

Section of Developmental Psychiatry, Department of Psychiatry, University of Cambridge, Cambridge, UK.
Journal of Intellectual Disability Research (Impact Factor: 2.41). 02/2007; 51(Pt 1):32-42. DOI: 10.1111/j.1365-2788.2006.00895.x
Source: PubMed

ABSTRACT This study is part of a larger UK-wide study investigating psychiatric illness in people with Prader-Willi syndrome (PWS), and describes the longitudinal aspect of psychiatric illness, in particular psychotic illness, and examines the use and role of psychotropic medication.
A total of 119 individuals with genetically confirmed PWS were included in the study. An informant-based questionnaire was administered for each participant to screen for a history of psychopathology. Those who screened positive were visited at their homes to obtain further information. This assessment included a full psychiatric history and mental state examination using the Psychiatric Assessment Schedule for Adults with Developmental Disability and the Operational Criteria Checklist for psychotic and affective illness to collect information regarding phenomenology and course of illness, and a modified life events questionnaire. At the end of the study period, informant-based telephone interviews were again carried out, up to 2.5 years after the initial screening. Information regarding medication usage was collected.
The results confirm previous findings that psychiatric illness in people with PWS resembles an affective disorder. Individuals with the maternal uniparental disomy genetic subtype had a more severe course of illness than those with the deletion genetic subtype in terms of a greater risk of recurrence, more episodes, higher incidence and a possibly poorer response to medication with more side-effects. Individuals with a recurrent episode during the follow-up period had a poorer course of illness. Selective serotonin reuptake inhibitor medication is frequently used, and beneficial effects may reflect fundamental pathological processes in PWS. Mood-stabilizing medication was found to be of little benefit and reasons for this are examined.
The longitudinal course of psychiatric illness and response to medication in people with PWS is fully described. Further research is needed regarding the effect of psychotropic medications, particularly mood-stabilizing medication. These data will enable informed decisions to be made regarding management options and provide information on the possible long-term outcome of illness.

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    ABSTRACT: Background Obsessive-compulsive (O-C) traits, and excessive food intake are well known behavioural manifestations among individuals with Prader-Willi Syndrome (PWS). Other unwanted behaviours are also frequently observed, but they need a more specific investigation, especially in the adult population. Methods The behaviour of 31 PWS adults was investigated via the Symptom Checklist-90-Revised (SCL-90-R), the Yale-Brown Obsessive Compulsive Scale Symptom Checklist (Y-BOCS-SC), and the Prader-Willi Behavioural Checklist (PBC). The PBC is a quick screening questionnaire prompted specifically for the investigation on adults with PWS. ResultsStatistical clustering revealed two patterns of unwanted behaviours from the PBC. Behaviours belonging to the first cluster (e.g. Excessive food intake, Skin picking) appear to be linked to the usual phenotypic manifestation of PWS. By contrast, many other behaviours (e.g. some O-C symptoms and aggressive actions) could show a relationship also to individual psychopathologies. Conclusions Both internal (Anxiety and Depression) and external (Hostility) difficulties in managing impulses should account for individually distinct behaviours in adults with PWS.
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    ABSTRACT: Background: Prader-Willi syndrome (PWS) is a complex human genetic disease that arises from lack of expression of paternally inherited imprinted genes on chromosome 15q11-q13.Prader-Willi syndrome. Objective: To use whole genome array to investigate observed Prader-Willi phenotype by assaying differential gene expression patterns in Prader-Willi like subjects. Methodology: Combined clinical and laboratory study. Three people who participated in a large study of Prader-Willi syndrome (PWS) were found to satisfy the criteria for a firm clinical diagnosis of the syndrome using the accepted consensus scores. A score of 8 is considered to be diagnostic for PWS but despite all three scoring >8, they were genetically negative for PWS. By using Affymetrix Cytogenetics Whole-Genome 2.7M arrays which identify both loss and gain in genomic DNA and also report loss of heterozygosity regions in which all three participants showed the same genomic abnormality were determined. By comparing these regions with the UCSC human genome database, a list of potential candidate genes was compiled in which the participants had all shown the same change. Confirmation of altered gene expression was sought using qPCR to study transcription levels in each of the genes identified. Results: Three people who participated in the study showed both maternal and paternal bands after methylation-specific PCR and they all expressed SNRPN. Increase in copy number with concomitant elevated transcription levels were found in SGSM2 which had previously been associated with severe obesity and in the protein-folding gene PPIF. Conclusion: Over-expression caused by duplication may be a contributing factor to the PWS-like phenotype in these people.