Abstract
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.
Similar content being viewed by others
References
Prader A, Labhart A, Willi A. Ein syndrom von aidositas, kleinwuchs, kryptorchismus und oligophrenie nach myotonieartigem zustand im neugeborenenalter. Schweiz Med Wochenschr 1956; 86: 1260–1
Ledbetter DH, Riccardi VM, Airhart SD, et al. Deletion of chromosome 15 as a cause of Prader-Willi syndrome. N Engl J Med 1981; 304: 325–9
Butler MG, Meaney FJ, Palmer CG. Clinical and cytogenetic survey of 39 individuals with Prader-Labhart-Willi syndrome. Am J Med Genet 1986; 23: 793–809
Nicholls RD. Genomic imprinting and uniparental disomy in Angelman and Prader-Willi syndrome: a review. Am J Med Genet 1993; 46: 16–25
Whittington JE, Holland AJ, Webb T, et al. Population prevalence and estimated birth incidence and mortality rate for people with Prader-Willi syndrome in one UK Health Region. J Med Genet 2001; 38: 792–8
Dykens EM, Hodapp RM, Finucane BM. Genetics and mental retardation syndromes: a new look at behavior and interventions. Baltimore (MD): Brookes, 2000
Curfs LMG. Psychological profile and behavioral characteristics in Prader-Willi syndrome. In: Cassidy SB, editor. Prader-Willi syndrome and other 15q deletion disorders. Berlin: Springer-Verlag, 1992: 211–22
Dykens EM, Hodapp RM, Walsh KK, et al. Profiles, correlates, and trajectories of intelligence in Prader-Willi syndrome. J Am Acad Child Adolesc Psychiatry 1992; 31: 1125–30
Curfs LG, Wiegers AM, Sommers JR, et al. Strengths and weaknesses in the cognitive profile of youngsters with Prader-Willi syndrome. Clin Genet 1991; 40: 430–4
Dykens EM, Hodapp RM, Walsh K, et al. Adaptive and maladaptive behavior in Prader-Willi syndrome. J Am Acad Child Adolesc Psychiatry 1992; 31: 1131–6
Dykens EM. Are jigsaw puzzle skills “spared” in persons with Prader-Willi syndrome? J Child Psychol Psychiatry 2002; 43: 343–52
Dykens EM, Cassidy SB, King BH. Maladaptive behavior differences in Prader-Willi syndrome due to paternal deletion versus maternal uniparental disomy. Am J Ment Retard 1999; 104: 67–77
Roof E, Stone W, MacLean W, et al. Intellectual characteristics of Prader-Willi syndrome: comparison of genetic subtypes. J Intellect Disabil Res 2000; 44: 25–30
Dykens EM, Cassidy SB. Correlates of maladaptive behavior in children and adults with Prader-Willi syndrome. Am J Med Genet 1995; 60: 546–9
Clarke DJ, Boer H, Chung MC, et al. Maladaptive behaviour in Prader-Willi syndrome in adult life. J Intellect Disabil Res 1996; 40: 159–65
Dykens EM, Kasari C. Maladaptive behavior in children with Prader-Willi syndrome, Down syndrome, and non-specific mental retardation. Am J Ment Retard 1997; 102: 228–37
Holm VA, Cassidy SB, Butler MG, et al. Prader-Willi syndrome: consensus diagnostic criteria. Pediatrics 1993; 91: 398–402
Achenbach TM. Manual for the Child Behavior Checklist. Burlington (VA): University of Vermont, Department of Psychiatry, 1999
Dykens EM, Cassidy SB. Prader-Willi syndrome. In: Goldstein S, Reynolds CR, editors. Handbook of neurobehavioral and genetic disorders in children. New York: Guilford Press, 1999: 525–54
Dykens EM, Leckman JF, Cassidy SB. Obsessions and compulsions in Prader-Willi syndrome. J Child Psychol Psychiatry 1996; 37: 995–1002
Dykens EM. Psychopathology in children with intellectual disability. J Child Psychol Psychiatry 2001; 41: 407–17
Vitiello B, Spreat S, Behar D. Obsessive-compulsive disorder in mentally retarded patients. J Nerv Ment Dis 1989; 177: 232–6
Dimitropoulos A, Feurer I, Butler MG, et al. Emergence of compulsive behavior and tantrums in children with Prader Willi syndrome. Am J Ment Retard 2001; 106: 39–51
Symons FJ, Butler MG, Sanders MD, et al. Self-injurious behavior and Prader-Willi syndrome: behavioral forms and body locations. Am J Ment Retard 1999; 104: 260–9
Dykens EM, Smith ACM. Distinctiveness and correlates of maladaptive behavior in children and adolescents with Smith-Magenis syndrome. J Intellect Disabil Res 1998; 42: 481–9
State M, Dykens EM, Rosner B, et al. Obsessive-compulsive symptoms in Prader-Willi and “Prader-Willi—like” patients. J Am Acad Child Adolesc Psychiatry 1999; 38: 329–34
Cassidy SB, Devi A, Mukaida C. Aging in Prader-Willi syndrome: 22 patients over age 30 years. Proc Greenwood Genet Cent 1994; 13: 102–3
Holland AJ, Treasure J, Coskeran P, et al. Characteristics of the eating disorder in Prader-Willi syndrome: implications for treatment. J Intellect Disabil Res 1995; 39: 373–81
Swaab DF, Purba JS, Hofman MA. Alterations in the hypothalamic paraventricular nucleus and its oxytocin neurons (putative satiety cells) in Prader-Willi syndrome: a study of 5 cases. J Clin Endocrinol Metab 1995; 80: 573–9
Caldwell ML, Taylor RL. A clinical note on the food preference of individuals with Prader-Willi syndrome: the need for empirical research. J Ment Defic Res 1983; 27: 45–9
Taylor RL, Caldwell ML. Type and strength of food preferences of individuals with Prader-Willi syndrome. Am J Ment Defic 1985; 29: 109–12
Fieldstone A, Zipf WB, Schwartz HC, et al. Food preferences in Prader-Willi syndrome, normal weight, and obese controls. Int J Obes Relat Metab Disord 1997; 21: 1–7
Dykens EM. Contaminated and unusual food combinations: what do people with Prader-Willi syndrome choose? Ment Retard 2000; 38: 163–71
Beardsmore A, Dorman T, Cooper SA, et al. Affective psychosis and Prader-Willi syndrome. J Intellect Disabil Res 1998; 42: 463–71
Clarke DJ. Prader-Willi syndrome and psychoses. Br J Psychiatry 1993; 163: 680–4
Clarke DJ, Boer H, Webb T, et al. Prader-Willi syndrome and psychotic symptoms. 1: case descriptions and genetic studies. J Intellect Disabil Res 1998; 42: 440–50
Clarke DJ, Webb T, Bachmann-Clarke JP. Prader-Willi syndrome and psychotic symptoms: report of a further case. Ir J Psychol Med 1995; 12: 27
Verhoeven WMA, Curfs LMG, Tuinier S. Prader-Willi syndrome and cycloid psychoses. J Intellect Disabil Res 1998; 42: 455–62
Clarke DJ. Prader-Willi syndrome and psychotic symptoms. 2: a preliminary study of prevalence using the psychopathology assessment schedule for adults with developmental disability checklist. J Intellect Disabil Res 1998; 42: 451–4
Stein DJ, Keating K, Zar HJ, et al. A survey of the phenomenology and pharmacotherapy of compulsive and impulsive-aggressive symptoms in Prader-Willi syndrome. J Neuropsychiatry Clin Neurosci 1994; 6: 23–9
Bregman JD. Current developments in the understanding of mental retardation. Part II: psychopathology. J Am Acad Child Adolesc Psychiatry 1991; 30: 861–72
Whitman BY, Accardo P. Emotional problems in Prader-Willi adolescents. Am J Med Genet 1987; 28: 897–905
Holland T, Whittington J, Webb T, et al. Findings from a population-based study of Prader-Willi syndrome. The 4th Prader-Willi Syndrome International Scientific Workshop and Conference; 2001 Jun 27–Jul 1; St. Paul
Vogels A, Descheemaeker M, Govers V, et al. Long-term follow-up of children with Prader-Willi syndrome: are some Prader-Willi syndrome children more vulnerable for developing psychotic problems than others? The 4th Prader-Willi Syndrome International Scientific Workshop and Conference; 2001 Jun 27–Jul 1; St. Paul
Huffa BP. One year results of growth hormone treatment of short stature in Prader-Willi syndrome. Acta Paediatr Suppl 1997; 423: 63–5
Lindgren AC, Hagenas L, Muller J, et al. Effects of growth hormone treatment on growth and body composition in Prader-Willi syndrome: a preliminary report. Acta Paediatr Suppl 1997; 423: 423–62
Hodapp RM, Freeman SFN, Kasari C. Parental educational preferences for students with metal retardation: effects of etiology and current placement. Educ Train Ment Retard Develop Disabil 1998; 33: 342–9
Lindgren AC, Barkeling B, Hagg A, et al. Eating behavior in Prader-Willi syndrome, normal weight, and obese control groups. J Pediatr 2000; 137: 50–5
Itoh M, Koeda T, Ohno K, et al. Effects of mazindol in two patients with Prader-Willi syndrome. Pediatr Neurol 1995; 13(4): 349–51
Coakley JH, Moorcraft J, Hipkin LJ, et al. The effect of mazindol on growth hormone secretion in boys with Duchenne muscular dystrophy. J Neurol Neurosurg Psychiatry 1988; 51: 1551–7
Weiss GF, Rogacki N, Fueg A, et al. Impact of hypothalamic d-norfenfluramine and peripheral d-fenfluramine injection on macronutrient intake in the rat. Brain Res Bull 1990; 25(6): 849–59
Selikowitz M, Sunman J, Pendergast A, et al. Fenfluramine in Prader-Willi syndrome: a double-blind, placebo-controlled trial. Arch Dis Child 1990; 65: 112–4
Fowles RE, Cloward TV, Yowell RL. Endocardial fibrosis associated with fenfluramine-phentermine [letter]. N Engl J Med 1998; 338(18): 1316
Kimmel SE, Keane MG, Crary JL, et al. Detailed examination of fenfluramine-phentermine users with valve abnormalities identified in Fargo, North Dakota. Am J Cardiol 1999; 84(3): 324–6
Baumann MH, Ayestas MA, Dersch CM, et al. Serotonin transporters, serotonin release, and the mechanism of fen-fluramine neurotoxicity. Ann N Y Acad Sci 2000; 914:172–86
Akefeldt A, Ekman R, Gillberg L, et al. Cerebrospinal fluid monoamines in Prader-Willi syndrome. Biol Psychiatry 1998; 44(12): 1321–8
Dech B, Budow L. The use of fluoxetine in an adolescent with Prader-Willi syndrome. J Am Acad Child Adolesc Psychiatry 1991; 30: 298–302
Hellings JA, Warnock JK. Self-injurious behavior and serotonin in Prader-Willi syndrome. Psychopharmacol Bull 1994; 30(2): 245–50
Benjamin E, Buot-Smith T. Naltrexone and fluoxetine in Prader-Willi syndrome. J Am Acad Child Adolesc Psychiatry 1993; 32: 870–3
Kohn Y, Weizman A, Apter A. Aggravation of food-related behavior in an adolescent with Prader-Willi syndrome treated with fluvoxamine and fluoxetine. Int J Eat Disord 2001; 30: 113–7
Berendsen HH. The role of serotonin in hot flashes. Maturitas 2000; 36: 155–64
Warnock JK, Clayton AH, Shaw HA, et al. Onset of menses in two adult patients with Prader-Willi syndrome treated with fluoxetine. Psychopharmacol Bull 1995; 31(2): 239–42
Akefeldt A, Tornhage CJ, Gillberg C. A woman with Prader-Willi syndrome gives birth to a healthy baby girl [letter]. Dev Med Child Neurol 1999; 41: 789–90
Jerome L. Prader-Willi and bipolar illness. J Am Acad Child Adolesc Psychiatry 1993; 32(4): 876–7
Tu J-B, Hartridge C, Izawa J. Psychopharmacogenetic aspects of Prader-Willi syndrome. J Am Acad Child Adolesc Psychiatry 1992; 31: 1137–40
Gupta BK, Fish DN, Yerevanian BI. Carbamazepine for intermittent explosive disorder in a Prader-Willi syndrome patient [letter]. J Clin Psychiatry 1987; 10: 423
Shapira NA, Lessig MC, Goodman WK, et al. Open label pilot study of topiramate in adults with Prader-Willi syndrome. The 4th Prader-Willi Syndrome International Scientific Workshop and Conference; 2001 Jun 27–Jul 1; St. Paul
Ebert MH, Schmidt DE, Thompson T, et al. Elevated plasma gamma-amino butyric acid (GABA) levels in individuals with either Prader-Willi syndrome or Angelman syndrome. J Neuropsychiatry Clin Neurosci 1997; 9(1): 75–80
Pereda Bikandi M, Antizar Moro I, Querejeta Ayerdi I, et al. Psychotic disorder in Prader-Willi syndrome: a case report. Actas Esp Psiquiatr 2001; 29(3): 208–12
Frankenburg FR. Choices in antipsychotic therapy in schizophrenia. Harv Rev Psychiatry 1999; 5: 241–9
Durst R, Rubin-Jabotinski K, Raskin S, et al. Risperidone in Prader-Willi syndrome [letter]. J Am Acad Child Adolesc Psychiatry 2000; 39: 545–6
Acknowledgements
This work was supported in part by a grant from the National Institute of Child Health and Human Development (NICHD), Rol HD 35684. The authors are grateful for the support of the National Prader-Willi Syndrome Association and Prader-Willi California Foundation for their support of our research in general. The authors have no conflicts of interest that are directly relevant to the contents of this review.
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Dykens, E., Shah, B. Psychiatric Disorders in Prader-Willi Syndrome. CNS Drugs 17, 167–178 (2003). https://doi.org/10.2165/00023210-200317030-00003
Published:
Issue Date:
DOI: https://doi.org/10.2165/00023210-200317030-00003