Hostname: page-component-f554764f5-c4bhq Total loading time: 0 Render date: 2025-04-11T07:37:05.169Z Has data issue: false hasContentIssue false
  • English
  • Français

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

Published online by Cambridge University Press:  04 January 2008

S. Soni ,
J. Whittington ,
A. J. Holland ,
T. Webb ,
E. N. Maina ,
H. Boer  and
D. Clarke
S. Soni*
Affiliation:
Section of Developmental Psychiatry, Department of Psychiatry, University of Cambridge, UK
J. Whittington
Affiliation:
Section of Developmental Psychiatry, Department of Psychiatry, University of Cambridge, UK
A. J. Holland
Affiliation:
Section of Developmental Psychiatry, Department of Psychiatry, University of Cambridge, UK
T. Webb
Affiliation:
Medical and Molecular Genetics, Birmingham Women's Hospital, Edgbaston, Birmingham, UK
E. N. Maina
Affiliation:
Medical and Molecular Genetics, Birmingham Women's Hospital, Edgbaston, Birmingham, UK
H. Boer
Affiliation:
Janet Shaw Clinic, Marston, Birmingham, UK
D. Clarke
Affiliation:
Lea Castle Centre, Birmingham, UK
*
*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: [email protected])
Get access Rights & Permissions [Opens in a new window]

Abstract

Background

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.

Method

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.

Results

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.

Conclusions

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.

Keywords

Affective psychosisbehavioural phenotypePrader–Willi syndromepsychiatric illnesspsychotic illness
Type
Original Articles
Information
Psychological Medicine , Volume 38 , Issue 10 , October 2008 , pp. 1505 - 1514
Copyright
Copyright © 2008 Cambridge University Press

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

Article purchase

Temporarily unavailable

References

Andreasen, NC, Endicott, J, Spitzer, RL, Winokur, G (1977). The family history method using diagnostic criteria. Reliability and validity. Archives of General Psychiatry 34, 1229–1235.CrossRefGoogle ScholarPubMed
Beardsmore, A, Dorman, T, Cooper, S-A, Webb, T (1998). Affective psychosis and Prader–Willi syndrome. Journal of Intellectual Disability Research 42, 463–471.Google ScholarPubMed
Boer, H, Holland, A, Whittington, J, Butler, J, Webb, T, Clarke, D (2002). Psychotic illness in people with Prader Willi syndrome due to chromosome 15 maternal uniparental disomy. Lancet 359, 135–136.CrossRefGoogle ScholarPubMed
Buiting, K, Saitoh, S, Gross, S, Dittrich, B, Schwartz, S, Nicholls, RD, Horsthemke, B (1995). Inherited microdeletions in the Angelman and Prader–Willi syndromes define an imprinting centre on human chromosome 15. Nature Genetics 9, 395–400.CrossRefGoogle ScholarPubMed
Clarke, DJ (1993). Prader–Willi syndrome and psychoses. British Journal of Psychiatry 163, 680–684.CrossRefGoogle ScholarPubMed
Clarke, DJ, Boer, H, Whittington, J, Holland, A, Butler, J, Webb, T (2002). Prader–Willi syndrome, compulsive and ritualistic behaviours: the first population-based survey. British Journal of Psychiatry 180, 358–362.CrossRefGoogle ScholarPubMed
Holland, AJ, Whittington, JE, Butler, J, Webb, T, Boer, H, Clarke, D (2003). Behavioural phenotypes associated with specific genetic disorders: evidence from a population-based study of people with Prader–Willi syndrome. Psychological Medicine 33, 141–153.CrossRefGoogle ScholarPubMed
Horsthemke, B, Maat-Kievit, A, Sleegers, E, van den Ouweland, A, Buiting, K, Lich, C, Mollevanger, P, Beverstock, G, Gillessen-Kaesbach, G, Schwanitz, G (1996). Familial translocations involving 15q11–q13 can give rise to interstitial deletions causing Prader–Willi or Angelman syndrome. Journal of Medical Genetics 33, 848–851.CrossRefGoogle ScholarPubMed
Klein, OD, Cotter, PD, Albertson, DG, Pinkel, D, Tidyman, WE, Moore, MW, Rauen, KA (2004). Prader–Willi syndrome resulting from an unbalanced translocation: characterization by array comparative genomic hybridization. Clinical Genetics 65, 477–482.CrossRefGoogle ScholarPubMed
McGuffin, P, Farmer, A, Harvey, I (1991). A polydiagnostic application of operational criteria in studies of psychotic illness. Development and reliability of the OPCRIT system. Archives of General Psychiatry 48, 764–770.CrossRefGoogle ScholarPubMed
Moss, S, Goldberg, D, Patel, P, Prosser, H, Ibbotson, B, Simpson, N, Rowe, S (1996). The Psychiatric Assessment Schedule for Adults with Developmental Disability (ICD 10 Version). Hester Adrian Research Centre, University of Manchester: Manchester.Google Scholar
Moss, S, Prosser, H, Costello, H, Simpson, N, Patel, P, Rowe, S, Turner, S, Hatton, C (1998). Reliability and validity of the PAS–ADD Checklist for detecting psychiatric disorders in adults with intellectual disability. Journal of Intellectual Disability Research 42, 173–183.CrossRefGoogle ScholarPubMed
Murphy, KC, Jones, LA, Owen, MJ (1999). High rates of schizophrenia in adults with velo-cardio-facial syndrome. Archives of General Psychiatry 56, 940–945.CrossRefGoogle ScholarPubMed
Olsson, MB, Hwang, CP (2001). Depression in mothers and fathers of children with intellectual disability. Journal of Intellectual Disability Research 45, 535–543.CrossRefGoogle ScholarPubMed
Paykel, ES (1996). The Interview for Recent Life Events. Psychological Medicine 27, 301–310.CrossRefGoogle Scholar
Perneger, TV (1998). What's wrong with Bonferroni adjustments. British Medical Journal 316, 1236–1238.CrossRefGoogle ScholarPubMed
Perris, C, Brockington, IF (1981). Cycloid Psychoses and their Relation to the Major Psychoses. Elsevier: Amsterdam.Google Scholar
Regier, DA, Boyd, JH, Burke, Jr. JD, Rae, DS, Myers, JK, Kramer, M, Robins, LN, George, LK, Karno, M, Locke, BZ (1988). One-month prevalence of mental disorders in the United States. Based on five Epidemiologic Catchment Area sites. Archives of General Psychiatry 45, 977–986.CrossRefGoogle ScholarPubMed
Roof, E, Stone, W, MacLean, W, Feurer, ID, Thompson, T, Butler, MG (2000). Intellectual characteristics of Prader–Willi syndrome: comparison of genetic subtypes. Journal of Intellectual Disability Research 44, 25–30.CrossRefGoogle ScholarPubMed
Russell, JA, Douglas, AJ, Ingram, CD (2001). Brain preparations for maternity – adaptive changes in behavioral and neuroendocrine systems during pregnancy and lactation. An overview. Progress in Brain Research 133, 1–38.CrossRefGoogle ScholarPubMed
Smith, A, Lindeman, R, Volpato, F, Kearney, A, White, S, Haan, E, Trent, RJ (1991). A de novo unbalanced reciprocal translocation identified as paternal in origin in the Prader–Willi syndrome. Human Genetics 86, 534–536.CrossRefGoogle Scholar
Soni, S, Whittington, J, Holland, AJ, Webb, T, Maina, EN, Boer, H, Clarke, D (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, 32–42.CrossRefGoogle ScholarPubMed
Sturmey, P (1995). DSM-III-R and persons with dual diagnoses: conceptual issues and strategies for future research. Journal of Intellectual Disability Research 39, 357–364.CrossRefGoogle ScholarPubMed
Swaab, DF (1997). Prader–Willi syndrome and the hypothalamus. Acta Paediatrica Scandinavica Supplement 423, 50–54.CrossRefGoogle ScholarPubMed
Veltman, MW, Thompson, RJ, Roberts, SE, Thomas, NS, Whittington, J, Bolton, PF (2004). Prader–Willi syndrome – a study comparing deletion and uniparental disomy cases with reference to autism spectrum disorders. European Child and Adolescent Psychiatry 13, 42–50.CrossRefGoogle ScholarPubMed
Verhoeven, WM, Curfs, LM, Tuinier, S (1998). Prader–Willi syndrome and cycloid psychoses. Journal of Intellectual Disability Research 42, 455–462.Google ScholarPubMed
Verhoeven, WM, Tuinier, S, Curfs, LM (2003). Prader–Willi syndrome: the psychopathological phenotype in uniparental disomy. Journal of Medical Genetics 40, e112.CrossRefGoogle ScholarPubMed
Vogels, A, De Hert, M, Descheemaeker, MJ, Govers, V, Devriendt, K, Legius, E, Prinzie, P, Fryns, JP (2004). Psychotic disorders in Prader–Willi syndrome. American Journal of Medical Genetics 127A, 238–243.CrossRefGoogle ScholarPubMed
Vogels, A, Matthijs, G, Legius, E, Devriendt, K, Fryns, JP (2003). Chromosome 15 maternal uniparental disomy and psychosis in Prader–Willi syndrome. Journal of Medical Genetics 40, 72–73.CrossRefGoogle ScholarPubMed
Webb, T, Clarke, D, Hardy, CA, Kilpatrick, MW, Corbett, J, Dahlitz, M (1995). A clinical, cytogenetic, and molecular study of 40 adults with the Prader–Willi syndrome. Journal of Medical Genetics 32, 181–185.CrossRefGoogle ScholarPubMed
Wechsler, D (1997). Wechsler Adult Intelligence Scale – Third Edition (WAIS-III). The Psychological Corporation: San Antonio, TX.Google Scholar
Wechsler, D (1999). Wechsler Abbreviated Scale of Intelligence. The Psychological Corporation: San Antonio, TX.Google Scholar
Whittington, JE, Holland, AJ, Webb, T, Butler, J, Clarke, D, Boer, H (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, 792–798.CrossRefGoogle ScholarPubMed
Whittington, J, Holland, A (2004). Prader–Willi Syndrome: Development and Manifestations. Cambridge University Press: Cambridge.CrossRefGoogle Scholar
WHO (1992). International Statistical Classification of Diseases and Related Health Problems, 1989 Revision. World Health Organisation: Geneva.Google Scholar
Williams, J, Farmer, AE, Ackenheil, M, Kaufmann, CA, McGuffin, P (1996). A multicentre inter-rater reliability study using the OPCRIT computerized diagnostic system. Psychological Medicine 26, 775–783.CrossRefGoogle ScholarPubMed