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Research Notes: Psychiatric Disorders and Prader-Willi SyndromeSee also: J Intellect Disabil Res. 2007 Jan. BACKGROUND: 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. METHOD: 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. RESULTS: 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. CONCLUSION: 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. Int Rev Neurobiol. 2006. Prader-Willi syndrome (PWS) is the result of a lack of expression of genes on the paternally derived chromosome 15q11-q13 and can be considered as a hypothalamic disorder. Its behavioral phenotype is characterized by ritualistic, stereotyped, and compulsive behaviors as well as motor abnormalities. After adolescence, recurrent affective psychoses are relatively frequent, especially in patients with uniparental disomy. These psychotic states have a subacute onset with complete recovery and comprise an increase of psychomotor symptoms that show resemblance with catatonia. Some evidence has emerged that gamma-aminobutyric acid (GABA) dysfunctionality is involved in both PWS and catatonia. Treatment of these atypical psychoses should preferably include GABA mimetic compounds like lorazepam, valproic acid, and possibly topiramate. Am J Med Genet A. 2004 Jun 15. The Prader-Willi syndrome (PWS) is a genetically determined developmental disorder caused by abnormalities of the proximal region of chromosome 15q11-13. In a previous study, we reported that psychotic episodes, occurring in 16% of persons with PWS, had an onset in adolescence, never occurred in persons with paternal deletion, and were exclusively associated with maternal uniparental disomy (UPD) or imprinting abnormalities (IM). In order to gain a better understanding of the psychopathology and to further refine the psychiatric diagnosis, we describe in more detail the psychopathological manifestations of six adults with a history of psychotic episodes. All these individuals had a detailed psychiatric examination, including the use of the operational criteria (OPCRIT) checklist. An identifiable subtype of psychotic disorder was associated with PWS. Characteristics include early age of onset, acute onset, polymorphous, and shifting symptomatology and a need for psychiatric hospitalization. The presence of precipitating stress factors and a prodromal phase with physiological symptoms was reported in all patients. Current diagnostic categories do not allow an unequivocal psychiatric diagnosis. CNS Drugs. 2003. Although people with intellectual disabilities are at increased risk for psychiatric disorders, the type and rate of these problems differ between those with different causes for their retardation. In this paper, we review behavioural and psychiatric problems in persons with Prader-Willi syndrome, a disorder caused by a paternally derived deletion at chromosome 15(q11-q13) in about 70% of affected patients, and by maternal uniparental disomy in the majority of the remaining patients. In addition to the syndrome's characteristic hyperphagia and food seeking, individuals with Prader-Willi syndrome also have increased risks of nonfood, compulsive behaviours. These include skin picking, which is highly prevalent, as well as more variable rates of hoarding, redoing and concerns with symmetry, exactness, cleanliness, ordering and arranging. Relative to others with mental retardation, persons with Prader-Willi syndrome are at a marked increased risk for developing full-blown, obsessive-compulsive disorder. In addition, many people with Prader-Willi syndrome show increased rates of tantrums, oppositionality and aggression. Recent findings suggest that they also have an increased risk of psychotic disorder or affective illness with a psychotic component, especially young adult patients and those with the maternal uniparental disomy as opposed to paternal deletion. Dietary approaches include a reduced-calorie diet and increased physical activity, as well as close supervision around food and keeping food locked away. To date, neither CNS stimulants nor anorectic agents have been effective in treating hyperphagia, in part because hyperphagia in Prader-Willi syndrome is attributed to decreased satiation as opposed to increased hunger. Treatment for compulsivity and maladaptive behaviours include: behavioural programming; a structured, predictable routine; extra help with transitions; family support; and pharmacotherapy. Although formal drug studies have yet to be conducted, SSRIs have been effective in reducing skin picking, compulsivity and aggressive episodes in some individuals with Prader-Willi syndrome. Atypical antipsychotics have also proven helpful in persons with psychotic features or extreme aggression and impulsivity. Largely on the basis of case studies, the risks and benefits of these and other drugs in Prader-Willi syndrome are reviewed. Drug trials that move beyond case studies and that assess the relative efficacy of behavioural treatments alone or in combination with pharmacotherapy are sorely needed. Int J Neuropsychopharmacol. 2002 Jun. Self-injurious behaviour (SIB), most notably skin picking, has been described by various terms in the literature ranging from neurotic/psychogenic excoriations to compulsive/pathological skin picking. Prader-Willi Syndrome (PWS) is a neurogenetic multisystem disorder characterized by infantile hypotonia, mental retardation, short stature, hypogonadism, dysmorphic features, and hyperphagia with a high risk of obesity. Psychiatric manifestations include SIBs in the form of skin picking, nail biting and rectal gouging. Topiramate is a novel anti-epileptic medication without significant liability of weight gain. There are no published reports of topiramate being utilized in PWS or SIB. We report attenuation of SIB with resultant lesion healing in three PWS adults treated with topiramate in an 8-wk open-label trial. Although our findings should be treated with caution, they suggest that double-blind or cross-over studies with topiramate are warranted to establish the possible role of topiramate in attenuating SIB in PWS and other disorders that involve SIB. Br J Psychiatry. 2002 Apr. BACKGROUND: Obsessive-compulsive disorder has been reported in association with Prader-Willi syndrome. AIMS: To report the nature and prevalence of compulsive and similar symptoms associated with Prader-Willi syndrome in a population ascertained as completely as possible. METHOD: Attempted complete ascertainment of people with Prader-Willi syndrome in eight English counties. Administration of standardised rating scales and a structured interview. Comparison with people with learning disability and high body mass indices. RESULTS: Prader-Willi syndrome was associated with high rates of ritualistic behaviours, such as the need to ask or to tell something, insistence on routines, hoarding and ordering objects and repetitive actions and speech, compared with the control group, and was negatively correlated with IQ and socialisation age. Typical obsessive-compulsive symptoms, such as checking, counting and cleaning compulsions or obsessional thoughts, were not found. CONCLUSIONS: Ritualistic and compulsive behaviours occur more frequently in association with Prader-Willi syndrome than among people with intellectual disability and significant obesity. Lancet. 2002 Jan 12. In a population-based study of Prader Willi syndrome (PWS), we investigated the relation between genetic subtypes of the syndrome and psychiatric morbidity. Of 25 patients aged 18 years or older, seven (28%) had severe affective disorder with psychotic features, with a mean age of onset of 26 years (SD 5.9). The seven people affected, all aged 28 years or older, included all five with disomies of chromosome 15, one with a deletion in this chromosome, and one with an imprinting centre mutation in the same chromosome. We postulate that in PWS, an abnormal pattern of expression of a sex-specific imprinted gene on chromosome 15 is associated with psychotic illness in early adult life. J Intellect Disabil Res. 2002 Jan. Prader-Willi syndrome (PWS) is a genetic disorder caused by the loss of the paternal contribution of the proximal part (15q11-q13) of the long arm of chromosome 15 (i.e. deletion, disomy and imprinting mutation). The syndrome is associated with distinct physical dysmorphism, as well as with specific behavioural and psychopathological characteristics. Psychiatric symptoms in adolescence and adulthood have been described, including acute cycloid psychosis, and obsessive compulsive, bipolar and pervasive developmental disorders. At the Centre for Human Genetics in Leuven, Belgium, 53 individuals (31 children and adolescents, and 22 adults) have been followed up for 15 years by a special multidisciplinary team. Attention was given to their medical, cognitive, behavioural and emotional development, and the evolution of psychiatric disorders in adolescence and adulthood. This study describes the psychiatric problems in four patients diagnosed with acute cycloid psychosis and traces their development from infancy to adolescence. Four other individuals needed psychiatric evaluation and treatment, and could be diagnosed as having unspecified bipolar disorder, also termed unstable mood disorder. Both groups were compared, and significant differences in early development and later evolution into adulthood were noted. The individuals with PWS who later developed psychotic episodes were described as active and extrovert toddlers, and showed autistic behaviour during their primary school education. Their intellectual functioning was in the moderate to severely retarded range. The individuals with PWS who later developed an unstable mood disorder were described as rather passive and introvert toddlers, and they presented less disturbed behaviour during their primary school education. The intellectual functioning of these subjects was in the normal to borderline range. Genet Couns. 2000. Prader-Willi psychiatric syndrome and Velo-Cardio-Facial psychiatric syndrome: Similar to the studies on behavioural phenotypes, it is suggested to more rigorously promote the investigation of psychopathological phenotypes. The psychopathological profile in patients with Prader-Willi Syndrome (PWS) or Velo-Cardio-Facial Syndrome (VCFS) appears to be not classifiable within the current nosological systems. On a descriptive level, PWS-psychotic states show similarities with the cycloid psychoses, but VCFS psychosis does not. It is therefore advocated to adopt the notion of a brain-structure phenotype as well as that of a syndrome-specific psychiatric disorder. J Intellect Disabil Res. 1998 Dec. The psychiatric symptomatology of people with Prader-Willi syndrome (PWS) has mainly been described in case reports and some large-scale descriptive studies. Unfortunately, there is still no systematic description of all the psychiatric symptoms which accompany this chromosomal error. Symptoms of mood disorder and anxiety dominate the picture of PWS, although some reports also mention psychotic symptoms with variations in prevalence of between 15% and 60%. The present paper presents six case reports of adult male subjects with a diagnosis of PWS and psychiatric symptoms who fulfill the criteria for cycloid psychosis (ICD-10 F.23.0). This psychotic disorder requires a specific psychopharmacological approach with mood stabilizing agents, particularly Lithium. It is concluded that subjects with PWS may be especially vulnerable to the development of cycloid psychosis, which suggests the existence of a specific 'psychopathological phenotype'. J Intellect Disabil Res. 1998 Dec. Previous studies have demonstrated that maladaptive behaviours are common amongst adults with Prader-Willi syndrome (PWS). Case reports have also previously demonstrated that psychosis can occur amongst adults with PWS. The present study was undertaken in order to gain a better understanding of the psychopathology of the psychosis of PWS. Twenty-three out of 25 adults identified with PWS living in Northamptonshire, UK, agreed to participate. Comprehensive psychiatric assessments (using the PPS-LD), and measures of adaptive and maladaptive behaviours (using the AAMR-ABS) were completed. Comparisons were made for the prevalence of psychiatric disorders against those from a previous epidemiological study of adults with intellectual disability of other aetiologies from a neighbouring county. The PWS group was found to have higher rates of affective disorders (a point prevalence of 17.4%), in which psychotic symptoms were common, but similar rates of schizophrenia/delusional disorders (4.3%) compared with the comparison group. Behaviour disorders were also common. Surprisingly, none of the PWS group was found to have generalized anxiety or phobic disorders. The diagnostic criteria for the episodes including psychotic symptoms are explored. The high rates of affective disorders is of clinical (i.e. treatment) importance as well as being of academic interest with regard to the genetics of psychiatric disorders. J Intellect Disabil Res. 1998 Dec. Six people with Prader-Willi syndrome (PWS) who developed psychoses are described. Along with other literature reviewed in the present paper, the results imply an association between PWS and psychotic symptoms. Genetic studies were possible in five cases and SNRPN expression was examined in three cases. Maternal uniparental disomy and 15q11q13 deletions were found, demonstrating that psychotic symptoms are not associated with a single type of genetic abnormality. J Intellect Disabil Res. 1998 Dec. The Psychopathology Assessment Schedule for Adults with Developmental Disability (PAS-ADD) checklist was used to screen for psychotic symptoms among people with Prader-Willi syndrome (PWS) aged 16 years and over. The scoring instructions for the PAS-ADD checklist were modified to take account of knowledge about the behavioural phenotype of PWS. Using modified scoring, 6.3% of the 95 people for whom checklists were completed had a possible psychotic disorder in the month before the assessment was made. The results should be treated as a crude estimate of the prevalence of psychotic symptoms associated with PWS in adult life in view of potential biases in the sample reported. These findings lend some support to the hypothesis that PWS has a non-chance association with psychotic symptoms and that the association is not entirely accounted for by the increased prevalence of psychosis associated with intellectual disability. Eat Weight Disord. 1998 Dec. This study focused in the treatment of two major Prader-Willi symptoms: hyperphagia and self-injurious behavior (SIB). Four patients participated in a four-year study with monthly follow-ups. Patients lived in a behaviorally structured environment, and were treated with selective serotonin reuptake blockers and phenothiazines. Psychopharmacological intervention improved SIB symptoms, but was ineffective to control appetite satiation. J Neuropsychiatry Clin Neurosci. 1994 Winter. Prader-Willi Syndrome (PWS) is a congenital disorder characterized by hyperphagia as well as by other behavioral disturbances such as self-mutilation and temper outbursts. Some of these symptoms have been reported to respond to psychotropic medications. A systematic survey was conducted to gather information on the phenomenology and pharmacotherapy of compulsive and impulsive-aggressive symptoms in PWS. Both compulsive and impulsive-aggressive symptoms are frequent in this population. Pharmacotherapeutic intervention may have a role in the management of these symptoms. Rigorous diagnostic and treatment studies should be undertaken in this population. Psychopharmacol Bull. 1994. Low central nervous system (CNS) serotonin levels have been associated with impulsive, aggressive and self-injurious behavior (SIB). Persons with Prader-Willi Syndrome (PWS) often engage in self-injury by severe compulsive skin picking and gouging and often manifest compulsive eating, hoarding, and explosive outbursts. Some of the compulsive behaviors seen in patients with obsessive-compulsive disorder (OCD) bear similarity to behaviors associated with PWS: Skin picking, trichotillomania, and onychophagia (nail biting). There is abundant evidence that selective serotonin reuptake inhibitors (SSRIs) are effective in treating OCD. Three cases are described in which persons with PWS responded favorably to SSRI treatment. Two persons showed a significant decrease in skin picking. The third case showed a significant decrease in hoarding and explosive outbursts. Strategies are discussed for investigating the possibility of a shared neurochemical basis for the self-injurious, aggressive, and compulsive behaviors in persons with PWS. PWS may provide a relatively homogenous model for the study of skin picking and explosive outbursts among other populations. Br J Psychiatry. 1993 Nov. Prader-Willi syndrome (PWS) is associated with an insatiable appetite and (often) other maladaptive behaviours (self-injury, sleep disorders, insistence on routines, and temper tantrums). Psychoses are not a recognised feature. Most affected people have a chromosome 15 abnormality (deletion, disomy, structural rearrangement, etc.). Three people with PWS who developed psychotic disorders in early adult life are described. The nature of the psychoses and the significance of the association are discussed. J Am Acad Child Adolesc Psychiatry. 1993 Jul. The case discussed is of a 9-year-old boy with a diagnosis of Prader-Willi, compulsive eating, severe skin picking, mild mental retardation, and behavioral problems. Prehospital, hospital, and posthospital course is reviewed. An approach using fluoxetine and naltrexone shows a marked improvement in weight control, skin picking, and behavior. Obesity and self-mutilation are discussed with regard to the use of fluoxetine and naltrexone. Arch Dermatol. 1992 Dec. BACKGROUND. Prader-Willi syndrome (PWS) is characterized by hypotonia at birth, hypogonadism, early childhood obesity, and mental deficiency. Other behavioral symptoms that become prominent during adolescence and adulthood include temper outbursts, stealing and hoarding food, and skin picking. The self-excoriating skin picking behavior observed in individuals with PWS is quite common and can lead to persistent sores and infections, even requiring hospitalization. OBSERVATION. Two patients with PWS who displayed repetitive, self-mutilatory behavior of skin picking are described. They were both treated successfully with different doses of fluoxetine, a selective serotonin reuptake inhibitor. CONCLUSIONS. The skin-picking behavior in patients with PWS may be a variant of the spectrum of obsessive-compulsive disorders. Obsessive-compulsive disorders have been successfully treated with serotonin reuptake inhibitors such as fluoxetine. Thus, fluoxetine may be considered an option in the management of skin-picking behavior in patients with PWS. |