Skip to main content
    • Aa
    • Aa
  • Get access
    Check if you have access via personal or institutional login
  • Cited by 36
  • Cited by
    This article has been cited by the following publications. This list is generated based on data provided by CrossRef.

    Burack, Jacob A. Russo, Natalie Green, Cathryn Gordon Landry, Oriane and Iarocci, Grace 2016. Developmental Psychopathology.

    Crespi, Bernard J. 2016. Evolutionary Thinking in Medicine.

    Walton, Catherine and Kerr, Mike 2016. Prader Willi syndrome: systematic review of the prevalence and nature of presentation of unipolar depression. Advances in Mental Health and Intellectual Disabilities, Vol. 10, Issue. 3, p. 172.

    Avrahamy, Hamutal Pollak, Yehuda Shriki-Tal, Liron Genstil, Larry Hirsch, Harry J. Gross-Tsur, Varda and Benarroch, Fortu 2015. A disease specific questionnaire for assessing behavior in individuals with Prader–Willi syndrome. Comprehensive Psychiatry, Vol. 58, p. 189.

    Laurier, V. Lapeyrade, A. Copet, P. Demeer, G. Silvie, M. Bieth, E. Coupaye, M. Poitou, C. Lorenzini, F. Labrousse, F. Molinas, C. Tauber, M. Thuilleaux, D. and Jauregi, J. 2015. Medical, psychological and social features in a large cohort of adults with Prader-Willi syndrome: experience from a dedicated centre in France. Journal of Intellectual Disability Research, Vol. 59, Issue. 5, p. 411.

    Mokkonen, Mikael and Crespi, Bernard J. 2015. Genomic conflicts and sexual antagonism in human health: insights from oxytocin and testosterone. Evolutionary Applications, Vol. 8, Issue. 4, p. 307.

    Noor, Abdul Dupuis, Lucie Mittal, Kirti Lionel, Anath C. Marshall, Christian R. Scherer, Stephen W. Stockley, Tracy Vincent, John B. Mendoza-Londono, Roberto and Stavropoulos, Dimitri J. 2015. 15q11.2 Duplication Encompassing Only theUBE3AGene Is Associated with Developmental Delay and Neuropsychiatric Phenotypes. Human Mutation, Vol. 36, Issue. 7, p. 689.

    Crespi, B. Foster, K. and Ubeda, F. 2014. First principles of Hamiltonian medicine. Philosophical Transactions of the Royal Society B: Biological Sciences, Vol. 369, Issue. 1642, p. 20130366.

    Krefft, Maja Frydecka, Dorota Adamowski, Tomasz and Misiak, Blazej 2014. From Prader–Willi syndrome to psychosis: translating parent-of-origin effects into schizophrenia research. Epigenomics, Vol. 6, Issue. 6, p. 677.

    Craddock, Nick and Sklar, Pamela 2013. Genetics of bipolar disorder. The Lancet, Vol. 381, Issue. 9878, p. 1654.

    Dykens, Elisabeth M. 2013. Aging in rare intellectual disability syndromes. Developmental Disabilities Research Reviews, Vol. 18, Issue. 1, p. 75.

    Millan, Mark J. 2013. An epigenetic framework for neurodevelopmental disorders: From pathogenesis to potential therapy. Neuropharmacology, Vol. 68, p. 2.

    Pignatti, Riccardo Mori, Ileana Bertella, Laura Grugni, Graziano Giardino, Daniela and Molinari, Enrico 2013. Exploring Patterns of Unwanted Behaviours in Adults with Prader-Willi Syndrome. Journal of Applied Research in Intellectual Disabilities, p. n/a.

    Relkovic, Dinko and Isles, Anthony R. 2013. Behavioural and cognitive profiles of mouse models for Prader–Willi syndrome. Brain Research Bulletin, Vol. 92, p. 41.

    Sinnema, Margje Maaskant, Marian A. van Schrojenstein Lantman-de Valk, Henny M.J. Boer, Harm Curfs, Leopold M.G. and Schrander-Stumpel, Constance T.R.M. 2013. The use of medical care and the prevalence of serious illness in an adult Prader–Willi syndrome cohort. European Journal of Medical Genetics, Vol. 56, Issue. 8, p. 397.

    Matson, Johnny L. Belva, Brian C. Hattier, Megan A. and Matson, Michael L. 2012. Scaling methods to measure psychopathology in persons with intellectual disabilities. Research in Developmental Disabilities, Vol. 33, Issue. 2, p. 549.

    Mizen, Lindsay and Cooper, Sally-Ann 2012. Learning disabilities. Medicine, Vol. 40, Issue. 11, p. 619.

    Reus, Linda van Vlimmeren, Leo A. Staal, J. Bart Otten, Barto J. and Nijhuis-van der Sanden, Maria W.G. 2012. The effect of growth hormone treatment or physical training on motor performance in Prader–Willi syndrome: A systematic review. Neuroscience & Biobehavioral Reviews, Vol. 36, Issue. 8, p. 1817.

    2012. A Handbook for the Assessment of Children's Behaviours.

    McAllister, C. J. and Whittington, J. E. 2011. A short clinical overview of Prader-Willi syndrome. Clinical Obesity, Vol. 1, Issue. 4-6, p. 184.


The phenomenology and diagnosis of psychiatric illness in people with Prader–Willi syndrome

  • S. Soni (a1), J. Whittington (a1), A. J. Holland (a1), T. Webb (a2), E. N. Maina (a2), H. Boer (a3) and D. Clarke (a4)
  • DOI:
  • Published online: 01 January 2008

Psychotic illness is strongly associated with the maternal uniparental disomy (mUPD) genetic subtype of Prader–Willi syndrome (PWS), but not the deletion subtype (delPWS). This study investigates the clinical features of psychiatric illness associated with PWS. We consider possible genetic and other mechanisms that may be responsible for the development of psychotic illness, predominantly in those with mUPD.


The study sample comprised 119 individuals with genetically confirmed PWS, of whom 46 had a history of psychiatric illness. A detailed clinical and family psychiatric history was obtained from these 46 using the PAS-ADD, OPCRIT, Family History and Life Events Questionnaires.


Individuals with mUPD had a higher rate of psychiatric illness than those with delPWS (22/34 v. 24/85, p<0.001). The profile of psychiatric illness in both genetic subtypes resembled an atypical affective disorder with or without psychotic symptoms. Those with delPWS were more likely to have developed a non-psychotic depressive illness (p=0.005) and those with mUPD a bipolar disorder with psychotic symptoms (p=0.00005). Individuals with delPWS and psychotic illness had an increased family history of affective disorder. This was confined exclusively to their mothers.


Psychiatric illness in PWS is predominately affective with atypical features. The prevalence and possibly the severity of illness are greater in those with mUPD. We present a ‘two-hit’ hypothesis, involving imprinted genes on chromosome 15, for the development of affective psychosis in people with PWS, regardless of genetic subtype.

Corresponding author
*Address for correspondence: Dr S. Soni, Section of Developmental Psychiatry, Department of Psychiatry, University of Cambridge, Douglas House, 18B Trumpington Road, Cambridge CB2 8AY, UK. (Email:
Linked references
Hide All

This list contains references from the content that can be linked to their source. For a full set of references and notes please see the PDF or HTML where available.

NC Andreasen , J Endicott , RL Spitzer , G Winokur (1977). The family history method using diagnostic criteria. Reliability and validity. Archives of General Psychiatry 34, 12291235.

A Beardsmore , T Dorman , S-A Cooper , T Webb (1998). Affective psychosis and Prader–Willi syndrome. Journal of Intellectual Disability Research 42, 463471.

H Boer , A Holland , J Whittington , J Butler , T Webb , D Clarke (2002). Psychotic illness in people with Prader Willi syndrome due to chromosome 15 maternal uniparental disomy. Lancet 359, 135136.

K Buiting , S Saitoh , S Gross , B Dittrich , S Schwartz , RD Nicholls , B Horsthemke (1995). Inherited microdeletions in the Angelman and Prader–Willi syndromes define an imprinting centre on human chromosome 15. Nature Genetics 9, 395400.

DJ Clarke (1993). Prader–Willi syndrome and psychoses. British Journal of Psychiatry 163, 680684.

DJ Clarke , H Boer , J Whittington , A Holland , J Butler , T Webb (2002). Prader–Willi syndrome, compulsive and ritualistic behaviours: the first population-based survey. British Journal of Psychiatry 180, 358362.

B Horsthemke , A Maat-Kievit , E Sleegers , A van den Ouweland , K Buiting , C Lich , P Mollevanger , G Beverstock , G Gillessen-Kaesbach , G Schwanitz (1996). Familial translocations involving 15q11–q13 can give rise to interstitial deletions causing Prader–Willi or Angelman syndrome. Journal of Medical Genetics 33, 848851.

OD Klein , PD Cotter , DG Albertson , D Pinkel , WE Tidyman , MW Moore , KA Rauen (2004). Prader–Willi syndrome resulting from an unbalanced translocation: characterization by array comparative genomic hybridization. Clinical Genetics 65, 477482.

P McGuffin , A Farmer , I Harvey (1991). A polydiagnostic application of operational criteria in studies of psychotic illness. Development and reliability of the OPCRIT system. Archives of General Psychiatry 48, 764770.

S Moss , H Prosser , H Costello , N Simpson , P Patel , S Rowe , S Turner , C Hatton (1998). Reliability and validity of the PAS–ADD Checklist for detecting psychiatric disorders in adults with intellectual disability. Journal of Intellectual Disability Research 42, 173183.

KC Murphy , LA Jones , MJ Owen (1999). High rates of schizophrenia in adults with velo-cardio-facial syndrome. Archives of General Psychiatry 56, 940945.

MB Olsson , CP Hwang (2001). Depression in mothers and fathers of children with intellectual disability. Journal of Intellectual Disability Research 45, 535543.

ES Paykel (1996). The Interview for Recent Life Events. Psychological Medicine 27, 301310.

TV Perneger (1998). What's wrong with Bonferroni adjustments. British Medical Journal 316, 12361238.

DA Regier , JH Boyd , Jr. JD Burke , DS Rae , JK Myers , M Kramer , LN Robins , LK George , M Karno , BZ Locke (1988). One-month prevalence of mental disorders in the United States. Based on five Epidemiologic Catchment Area sites. Archives of General Psychiatry 45, 977986.

E Roof , W Stone , W MacLean , ID Feurer , T Thompson , MG Butler (2000). Intellectual characteristics of Prader–Willi syndrome: comparison of genetic subtypes. Journal of Intellectual Disability Research 44, 2530.

JA Russell , AJ Douglas , CD Ingram (2001). Brain preparations for maternity – adaptive changes in behavioral and neuroendocrine systems during pregnancy and lactation. An overview. Progress in Brain Research 133, 138.

A Smith , R Lindeman , F Volpato , A Kearney , S White , E Haan , RJ Trent (1991). A de novo unbalanced reciprocal translocation identified as paternal in origin in the Prader–Willi syndrome. Human Genetics 86, 534536.

S Soni , J Whittington , AJ Holland , T Webb , EN Maina , H Boer , D Clarke (2007). The course and outcome of psychiatric illness in people with Prader–Willi syndrome: implications for management and treatment. Journal of Intellectual Disability Research 51, 3242.

P Sturmey (1995). DSM-III-R and persons with dual diagnoses: conceptual issues and strategies for future research. Journal of Intellectual Disability Research 39, 357364.

MW Veltman , RJ Thompson , SE Roberts , NS Thomas , J Whittington , PF Bolton (2004). Prader–Willi syndrome – a study comparing deletion and uniparental disomy cases with reference to autism spectrum disorders. European Child and Adolescent Psychiatry 13, 4250.

WM Verhoeven , LM Curfs , S Tuinier (1998). Prader–Willi syndrome and cycloid psychoses. Journal of Intellectual Disability Research 42, 455462.

WM Verhoeven , S Tuinier , LM Curfs (2003). Prader–Willi syndrome: the psychopathological phenotype in uniparental disomy. Journal of Medical Genetics 40, e112.

A Vogels , M De Hert , MJ Descheemaeker , V Govers , K Devriendt , E Legius , P Prinzie , JP Fryns (2004). Psychotic disorders in Prader–Willi syndrome. American Journal of Medical Genetics 127A, 238243.

A Vogels , G Matthijs , E Legius , K Devriendt , JP Fryns (2003). Chromosome 15 maternal uniparental disomy and psychosis in Prader–Willi syndrome. Journal of Medical Genetics 40, 7273.

T Webb , D Clarke , CA Hardy , MW Kilpatrick , J Corbett , M Dahlitz (1995). A clinical, cytogenetic, and molecular study of 40 adults with the Prader–Willi syndrome. Journal of Medical Genetics 32, 181185.

JE Whittington , AJ Holland , T Webb , J Butler , D Clarke , H Boer (2001). Population prevalence and estimated birth incidence and mortality rate for people with Prader–Willi syndrome in one UK Health Region. Journal of Medical Genetics 38, 792798.

Recommend this journal

Email your librarian or administrator to recommend adding this journal to your organisation's collection.

Psychological Medicine
  • ISSN: 0033-2917
  • EISSN: 1469-8978
  • URL: /core/journals/psychological-medicine
Please enter your name
Please enter a valid email address
Who would you like to send this to? *