Understanding the eating disorder and mental health needs of people with PWS

Behaviour and mental health in PWSBewleys Hotel, Dublin

Tuesday 19th April 2013

Tony HollandCambridge Intellectual and Developmental Disabilities Research Group

Department of Psychiatrywww.ciddrg.org.uk

Outline• Introduction to PWS

– Characteristics over the lifespan (phenotype)– Genetics (genotype)

• Eating behaviour and risk of obesity• Physical ill-health

– Obesity related co-morbidities– Other physical illnesses

• Mental ill-health and problem behaviours• Implications for services and support

– Importance of the environment

PWS over the lifespanIntra-uterine (placental)

• Poor growth• Limited foetal movement• High rates atypical births

Infancy• Extreme hypotonia• Failure to thrive

Childhood• Developmental delay – intellectual disabilities• Short statute – relative growth hormone deficiency• Sexual immaturity – sex hormone deficiencies• Over-eating - risk of severe obesity and its complications• Scoliosis, respiratory disorders, maladaptive behaviours

Adulthood• Increased risk of obesity (with greater independence)• Age-related physical and psychiatric morbidity

McAllister et al, International Journal of Obesity 2011

Gender specific genomic imprinting

C/D box snoRNA SNORD 116 (HBII-85)

Display of normal human chromosome complement Pairs 1 to 23

Chr 15 pair

X chromosome

Y chromosome

Schematic of chromosome abnormalities resulting in PWS

70% 25% <5%

Chromosome 15

Cambridge PWS Study

Assuming no age-specific ascertainment bias

Estimated birth incidence 1:29,000

Estimated population prevalence 1:52,000

Estimated mortality rate: 3% across the age-range

or

7% per year over age 30

Whittington et al, 2001

Eating disorder in PWS

• Initial presentation– Failure to thrive– Development of over-eating

• Mechanisms– Abnormality of satiety– Increased reward value of food

• Implications– Childhood– Adult life

Intra-uterine and peri-natal problems

• Abnormal foetal growth (small for dates at gestation) (imprinted genes and placental function)

• Reduced foetal movement

• Increased rates of caesarean section

• Polyhydramnios (excess intra-uterine fluid)

Dudley et al 2007 Early Human Development 83: 471

Whittington et al (2008). Early Human Development, 84: 331-336.

Characteristics that predicts +genetics

•Hypotonia at birth and failure to thrive

•Developmental delay and learning disabilities

•Undescended testes at birth

•Over-eating behaviour

Whittington et al 2003 J Med Genet, 39, 926

Weight and height in infancyDeletions only

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Mean difference between wt & ht centiles

By age- Deletions (wt-ht)

57m

54m

51m

4y w t

45m

42m

39m

3y

33m

30m

27m

2y

21m

18m

15m

1yr

9m

6m

3m

birth

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- 2

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6

3

0

-3

Weight and height in infancyNon-deletions only (UPD)

4566877788891414172122232010N =

Mean difference between wt & ht centiles

By age - non deletions

57m

54m

51m

4y

45m

42m

39m

3y

33m

30m

27m

2y

21m

18m

15m

1y

9m

6m

3m

birth

Me

an

no

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ntil

es

+-

2 S

E

6

3

0

-3

Weight chart of young adult with PWS

Holland et al. (1993). Measurement of excessive appetite and metabolic changes in Prader-Willi Syndrome. International Journal of Obesity: 17:527-532.

PWS

The high calorie meal (in comparison to fasting) did not result in the same pattern of brain activation that was found following food intake in those without PWS

No activations survived the analysis once the correction for multiple comparisons was applied

Hunger condition Post meal condition

Controls

PWS

PET functional brain imaging study

Hinton et al (2006). Neural Representations of hunger and satiety in Prader-Willi syndrome. International Journal of Obesity 30:313-321

Satiety Cascade

Blundell, 1991

Brain control of food intake

Regulation of food intake is controlled by a combination of signals to and from the brain.

People with PWS have delayed and impaired satiety and may be lacking or insensitive to peripheral signals to the brain.

Signals from fat cells Signals from the gut

Farooqi, Oxford Textbook of Medicine

Why the eating disorder?

• The Paradox of PWS: a genetic model of starvation

– Holland et al, Lancet, 2003, 362, 989-991

• Disruption of the hypothalamic feeding pathways or high threshold set for satiety (Barker hypothesis)

– McAllister et al, International Journal of Obesity, 2011

Eating disorder• Feeding support after birth and in infancy

• At transition biological abnormality of satiety and/or reward mechanisms associated with food becomes apparent;

• No specific treatment as yet for the eating disorder;

• Supervised access to food prevents obesity (and associated morbidity) and may help wellbeing;

• Strategies to help manage the tension between choice and the need to control access to food

Morbidity in PWS

Rates of reported illness

<18years >17years

Diabetes (type II) 0 8/32 (25%)

Respiratory 18/34 (53%) 12/32 (38%)

Scoliosis 9/34 (26%) 10/31 (32%)

Fractures 7/34 (21%) 12/32 (38%)

Butler et al 2002

Morbidity in PWS Sleep disorders:

• Noisy or disturbed sleep 40/63 (64%)

• Exc. daytime sleepiness 47/64 (73%)

• Diagnosis of sleep apnoea 13/64 (20%)

• Diagnosis of narcolepsy 1/64Mean BMI of those with diagnosis of sleep disorder 36kg/m2 vs 29.6kg/m2 (p>0.05)

MENTAL HEALTH

Behaviour in PWSPopulation-based study

Prevalence (%) of specific behaviours (n=65)

Definite sometime none

Excessive eating 78 21 1

Obsessional 70 23 7

Tempers 67 27 6

Skin picking 59 22 19

Mood swings 38 19 43

Holland et al 2003, Psychological Medicine

The detection of mental ill-health• The prevention and management of problem behaviours

depended on your understanding of those behaviours;

• The development of a psychiatric illness may present with a change in behaviour

• The key to intervention is a good history and mental state examination and formulation

• Long standing or of recent onset• Change in nature and severity of existing

behavioural difficulties• Evidence of disturbed mood or abnormal mental

experiences

Mental illness

• Characteristics

• Prevalence

• Mechanisms

• Implications

Psychiatric illness in PWS

• Kollrack and Wolff 1966

• Since then, over 20 studies describing the association of PWS with psychiatric illness

• Most describe an affective psychosis with characteristic features

• However, some methodological problems:– Small sample size– Not genetically confirmed

Population-based Study of PWSPsychotic Illness (Boer et al, Lancet, 2002)

Number with psychotic illness (7/25 28%)

Age 18-27 age 28+

Del (15q11-13) 0/4 1/9 (11%)

UPD 0/3 5/5 (100%)

Other 0/3 1/1*

Total 0/10 7/15 (49%)

*Imprinting centre defect

Method Soni et al 2008

• 46 of 119 (38.7%) adults screened positive for psychopathology– 24 Deletion, 22 mUPD

• Further assessment included:– Psychiatric Assessment Schedule for Adults with Developmental

Disability (PAS-ADD)– Operational criteria checklist for psychotic and affective illness

(OPCRIT)– Family History Questionnaire– modified Life Events Questionnaire– Wechsler Adult Intelligence Scale (WAIS)

Prevalence of psychiatric illness

Psychotic illness more common in mUPD than deletion p<0.001, effect size 0.45

35.3

71.8

2.9

11.8

61.8

16.5

0% 20% 40% 60% 80% 100%

UPD (n=34)

Deletion(n=85)

Gen

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ub

typ

e

Percentage of participants

No psychopathology

History of non-psychoticillness

History of psychotic symptoms

Soni et al 2008, Psychological Medicine, 38, 1505

Psychiatric Diagnosis

0

1

10

3

6

9

2

11

0

10

4

5

0 5 10 15 20 25 30

Comparison(n=15)

UPD (n=22)

Deletion (n=24)

Gen

etic

su

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pe

Count

Non-psychotic depression

Depressive psychosis

Bipolar illness w ith psychoticsymptoms

Psychotic illness

Non-psychotic depressive illness more common in deletion than mUPD p=0.005, effect size 0.43

Graph to show symptoms in participants with psychotic symptoms (n=31)

*Difference between genetic subtypes on scores of “agitation”: Fishers Exact test 2 sided; p<0.05

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Deletion (n=12)

Disomy (n=19)

Symptoms of hypomania in people with psychotic symptoms (n=31)

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Frequency of psychotic symptoms

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Summary of phenomenology

• Evidence of mood related psychiatric illness;

• Hypomanic symptoms and agitation more pronounced in those with mUPD;

• Delusions predominately persecutory in both people with deletion and mUPD;

• Auditory and visual hallucinations present in both groups;

Hypothetical model for the development of psychiatric illness in PWS

• “Two-hit” model

• Hit 1: having PWS (?5HT2cR related)

• Hit 2: mUPD paternally imprinted gene on 15

• Act in synergy to lead to development of psychotic illness

• What is the normal function of the presumed paternally imprinted gene that predisposes to affective disorder when there is excess expression and how has it become imprinted during evolution?

• Might a variant of that gene predispose to affective disorder in the general population?

Prevention, understanding and intervention

• The importance of structure, rules, and supportive and informed staff – prevention

• The importance of longitudinal knowledge – understanding

• Interventions based on a sound understanding - treatment

Finally….

• Understand the specific needs of people with PWS

• Understand the individual with PWS

• Do not place people with PWS in situations that are intolerable

• Manage the environment

• Strategies to compensate for social and cognitive impairments