Transcript The physical and psychological issues affecting

Understanding the eating disorder and mental
health needs of people with PWS
Behaviour and mental health in PWS
Bewleys Hotel, Dublin
Tuesday 19th April 2013
Tony Holland
Cambridge Intellectual and Developmental Disabilities Research Group
Department of Psychiatry
www.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 lifespan
Intra-uterine (placental)
• Poor growth
• Limited foetal movement
• High rates atypical births
Gender specific genomic imprinting
C/D box snoRNA SNORD 116 (HBII-85)
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
Display of normal human chromosome complement
Pairs 1 to 23
Chr 15 pair
Y chromosome
X chromosome
Schematic of chromosome abnormalities
resulting in PWS
Chromosome 15
70%
25%
<5%
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 infancy
Deletions only
Mean difference between wt & ht centiles
By age- Deletions (wt-ht)
Mean no centiles +- 2 SE
6
3
0
-3
N=
9
19
birth
20
16
6m
3m
14
1yr
9m
14
13
11
18m
15m
21m
11
2y
9
10
9
30m
27m
33m
9
3y
9
8
6
42m
39m
6
4
4y w t
45m
4
2
54m
51m
57m
Weight and height in infancy
Non-deletions only (UPD)
Mean difference between wt & ht centiles
By age - non deletions
Mean no centiles +- 2 SE
6
3
0
-3
N=
10
20
birth
23
22
6m
3m
21
1y
9m
17
14
14
18m
15m
21m
9
2y
8
8
8
30m
27m
33m
7
3y
7
7
8
42m
39m
45m
6
4y
6
5
4
54m
51m
57m
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
PET functional brain imaging study
Hunger condition
Post meal condition
Controls
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
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.
Farooqi, Oxford Textbook of Medicine
Signals from fat
cells
Signals from the gut
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
Diabetes (type II) 0
Respiratory
18/34 (53%)
Scoliosis
9/34 (26%)
Fractures
7/34 (21%)
Butler et al 2002
>17years
8/32 (25%)
12/32 (38%)
10/31 (32%)
12/32 (38%)
Morbidity in PWS
Sleep disorders:
•
•
•
•
Noisy or disturbed sleep
Exc. daytime sleepiness
Diagnosis of sleep apnoea
Diagnosis of narcolepsy
40/63 (64%)
47/64 (73%)
13/64 (20%)
1/64
Mean BMI of those with diagnosis of sleep
disorder 36kg/m2 vs 29.6kg/m2 (p>0.05)
MENTAL HEALTH
Behaviour in PWS
Population-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 PWS
Psychotic Illness (Boer et al, Lancet, 2002)
Number with psychotic illness (7/25 28%)
Age 18-27
Del (15q11-13)
0/4
UPD
0/3
Other
0/3
Total
0/10
*Imprinting centre defect
age 28+
1/9 (11%)
5/5 (100%)
1/1*
7/15 (49%)
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)
Soni et al 2008, Psychological Medicine, 38, 1505
Prevalence of psychiatric illness
Genetic subtype
Psychotic illness more common in mUPD than deletion
p<0.001, effect size 0.45
Deletion
(n=85)
71.8
11.8 16.5
No psychopathology
History of non-psychotic
illness
History of psychotic symptoms
UPD (n=34)
35.3
0%
20%
2.9
40%
61.8
60%
80%
Percentage of participants
100%
Psychiatric Diagnosis
Non-psychotic depressive illness more common in deletion than
mUPD p=0.005, effect size 0.43
Genetic subtype
Deletion (n=24)
10
9
0
Non-psychotic depression
5
Depressive psychosis
UPD (n=22) 1
6
Comparison
0 3
(n=15)
2
0
11
4
Bipolar illness w ith psychotic
symptoms
Psychotic illness
10
5
10
15
Count
20
25
30
90
80
70
60
50
40
30
20
10
0
Deletion (n=12)
Hypersomnia
Disturbed
sleep
Decreased
appetite
Increase in
food seeking
behaviour
Agitation*
Poor
concentration
Loss of
confidence
Disomy (n=19)
Loss of
energy
Percentage of people
Graph to show symptoms in participants with
psychotic symptoms (n=31)
Symptoms
*Difference between genetic subtypes on scores of “agitation”: Fishers Exact test 2 sided; p<0.05
9
8
7
6
5
4
3
2
1
0
Symptoms
Exaggerated self
esteem
Overactivity
Distractibility
Overtalkativeness
Pressing, racing
thoughts
Expansive mood
Number of people
Symptoms of hypomania in people with psychotic
symptoms (n=31)
Deletion (n=12)
Disomy (n=19)
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An iso
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ni
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In mp n
sig to
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pr
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Number of people
Frequency of psychotic symptoms
16
14
12
10
8
6
4
2
0
Deletion (n=12)
Disomy (n=19)
Symptom
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