Tony Holland
Cambridge Intellectual and Developmental Disabilities Research Group
www.CIDDRG.org
Outline
The risk of behavioural and psychiatric disorder
in people with PWS;
The importance of assessment and formulation -
integrating knowledge about the individual and
about PWS;
Interventions to prevent, manage and to treat
behavioural and psychiatric problems;
Research – from genotype to phenotype and
understanding mechanisms
PWS over the lifespan
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
Behaviour in PWS
Population-based study
Informant reported
Prevalence (%) of specific behaviours (n=65)
Excessive eating 78 21 1
Repetitive/ritualistic 70 23 7
Tempers 67 27 6
Skin picking 59 22 19
Mood swings 38 19 43
PWS?
What separate or shared mechanisms
directly or indirectly link genotype to
phenotype?
How are they best managed/treated?
Eating disorder
Eating behaviour
Hunger and satiety
Brain responses to food intake
Mechanisms
Weight chart of young adult with PWS
Satiety Cascade
Blundell, 1991
Fasting - High Cal Meal
Basal Ganglia
High Cal Meal - Fasting
Characteristics
Mechanisms
Implications
Population-based Study of PWS
Obsessive Compulsive Symptoms
Symptom PWS contrast
(n=80) (n=36)
Ask/tell 36/80 (46%) 4/33 (14%) **
Routines 26/80 (32%) 4/33 (12%) *
Hoarding 19/80 (24%) 1/33 (3%) **
Repetitive 18/80 (23%) 3/33 (9%) NS
Ordering 11/80 (14%) 0 *
Cleaning 2/80 (2%) 0 NS
Counting 0 0
Checking 0 0
? of Birmingham, UK
Deficit in
attention
switching
UNEXPECTED
Brain functional CHANGE
abnormalities
Physiological
arousal
Temper outbursts
Repetitive questions
Implications
Biological determined deficit in set-switching
predisposes to pattern of repetitive and ritualistic
behaviours and temper outbursts
Pattern of behaviour becomes established
through reinforcement over time
Early intervention to minimise establishment of behaviours
Psychologically informed support strategies
Training to improve set-switching
Why deficit in set-switching?
Common genetic basis for relationship between
PWS and autism?
Management of temper outbursts and
repetitive behaviours
Increased propensity – it is about
management not a cure;
Psychological/behavioural approach to
prevention and management - through
observation identifying what predisposes,
precipitates and maintains such
behaviours;
Routine (predictability)
Structure
Strategy
Mental illness
Characteristics
Prevalence
Mechanisms
Implications
Method
Soni et al 2008
Deletion No psychopathology
Genetic subtype
History of non-psychotic
illness
History of psychotic symptoms
UPD (n=34) 35.3 2.9 61.8
90
Percentage of people
80
70
60
50 Deletion (n=12)
40 Disomy (n=19)
30
20
10
0
Agitation*
confidence
concentration
energy
food seeking
Disturbed
Decreased
Hypersomnia
Loss of
Increase in
behaviour
appetite
Loss of
sleep
Poor
Symptoms
*Difference between genetic subtypes on scores of “agitation”: Fishers Exact test 2 sided; p<0.05
Number of people
0
1
2
3
4
5
6
7
8
9
Expansive mood
Pressing, racing
thoughts
Overtalkativeness
Distractibility
Symptoms Overactivity
Exaggerated self
symptoms (n=31)
esteem
Disomy (n=19)
Deletion (n=12)
Symptoms of hypomania in people with psychotic
Frequency of psychotic symptoms
16
Number of people
14
12
10 Deletion (n=12)
8
6 Disomy (n=19)
4
2
0
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 deletion and mUPD;
Auditory and visual hallucinations
present in both groups
Mental health
Key messages
Persistent increase in behaviour problems
may indicate onset of affective disorder
(evaluation needed – evidence of change
in mental state);
If a mood disorder has developed consider
the following:
Medication in low doses depending on the
psychiatric diagnosis;
Environmental factors that may be important
Formulation in Clinical Practice
Reason for referral Good Clinical
Practice
Accepted
models of
understanding History
FORMULATION Examination
Investigations
Observations
Evidence-base
for different
interventions
Intervention
Final messages
The importance of assessment and observation;
Be aware of possible physical and/pr psychiatric
illnesses;
Interventions based on a formulation that
identifies the key issues;
Follow-up carefully and re-evaluate as necessary