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Psychiatric aspects in PWSPsychiatric aspects in PWS

Tony HollandTony HollandCambridge Intellectual and Developmental Disabilities Research GroupCambridge Intellectual and Developmental Disabilities Research Group

www.CIDDRG.orgwww.CIDDRG.org


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OutlineOutline

The risk of behavioural and psychiatric disorderThe risk of behavioural and psychiatric disorderin people with PWS;in people with PWS;

The importance of assessment and formulationThe importance of assessment and formulation --

integrating knowledge about the individual andintegrating knowledge about the individual andabout PWS;about PWS;

Interventions to prevent, manage and to treatInterventions to prevent, manage and to treat

behavioural and psychiatric problems;behavioural and psychiatric problems;

ResearchResearch from genotype to phenotype andfrom genotype to phenotype andunderstanding mechanismsunderstanding mechanisms


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PWS over the lifespanPWS over the lifespan

InfancyInfancy Extreme hypotoniaExtreme hypotonia

Failure to thriveFailure to thrive

ChildhoodChildhood

Developmental delayDevelopmental delay intellectual disabilitiesintellectual disabilities Short statuteShort statute relative growth hormone deficiencyrelative growth hormone deficiency

Sexual immaturitySexual immaturity sex hormone deficienciessex hormone deficiencies

OverOver--eatingeating -- risk of severe obesity and its complicationsrisk of severe obesity and its complications

Scoliosis, respiratory disorders, maladaptive behavioursScoliosis, respiratory disorders, maladaptive behaviours

AdulthoodAdulthood

Increased risk of obesity (with greater independence)Increased risk of obesity (with greater independence)

AgeAge--related physical and psychiatric morbidityrelated physical and psychiatric morbidity


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Behaviour in PWSBehaviour in PWS

PopulationPopulation--based studybased studyInformant reportedInformant reported

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

Definite sometime noneDefinite sometime none

Excessive eating 78Excessive eating 78 2121 11

Repetitive/ritualistic 70Repetitive/ritualistic 70 2323 77

TempersTempers 6767 27 627 6

Skin pickingSkin picking 59 2259 22 1919

Mood swingsMood swings 3838 1919 4343

Holland et al, 2003 Psych. Med. 33:141-153


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Behavioural Phenotype of PWSBehavioural Phenotype of PWS

Research questionsResearch questions

Why do such problems occur in excess inWhy do such problems occur in excess inPWS?PWS?

What separate or shared mechanismsWhat separate or shared mechanismsdirectly or indirectly link genotype todirectly or indirectly link genotype tophenotype?phenotype?

How are they best managed/treated?How are they best managed/treated?


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Eating disorderEating disorder

E

ating behaviourE

ating behaviour Hunger and satietyHunger and satiety

Brain responses to food intakeBrain responses to food intake

MechanismsMechanisms


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Weight chart of young adult with PWS


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Satiety Cascade

Blundell, 1991


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FastingFasting -- High Cal MealHigh Cal Meal

Fasting (in comparison to high cal meal) in those withFasting (in comparison to high cal meal) in those with

PWS resulted in greater activation in a similar network ofPWS resulted in greater activation in a similar network of

areas as fasting in those without PWSareas as fasting in those without PWS

Brain Re ion Lef Right t value

H pothalamus L 6.5

Am gdala R 4.46

Insula

rain Stem

asal Ganglia R 4.84

Thalamus R 6. 4

Anterior ingulate R 3.57

H pothalamus

asal Ganglia


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High Cal MealHigh Cal Meal -- FastingFasting

TheThe highhigh caloriecalorie mealmeal (in(in comparisoncomparison toto fasting)fasting) diddid

notnot resultresult inin thethe samesame patternpattern ofof brainbrain activationactivation

thatthat waswas foundfound followingfollowing foodfood intakeintake inin thosethosewithoutwithout PWSPWS

NoNo activationsactivations survivedsurvived thethe analysisanalysis onceonce thethe

correctioncorrection forfor multiplemultiple comparisonscomparisons waswas appliedapplied


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Summary of eating disorderSummary of eating disorderImplications for managementImplications for management

Transition in early childhood;Transition in early childhood;

OverOver--eating a consequence of a failure ofeating a consequence of a failure of

satiation and increased reward of food;satiation and increased reward of food; Reasons for the above unknownReasons for the above unknown

presumed hypothalamic in originpresumed hypothalamic in origin

Management:Management: KnowledgeKnowledge

Supervised access to foodSupervised access to food

Diet and exerciseDiet and exercise


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Repetitive and ritualistic behavioursRepetitive and ritualistic behaviours

CharacteristicsCharacteristics


ImplicationsImplications


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PopulationPopulation--based Study of PWSbased Study of PWS

Obsessive Compulsive SymptomsObsessive Compulsive SymptomsSymptom PWS contrastSymptom PWS contrast

(n=80) (n=36)(n=80) (n=36)

Ask/tell Ask/tell 36/80 (46%)36/80 (46%) 4/33 (14%) **4/33 (14%) **

Routines 26/80 (32%) 4/33 (12%) *Routines 26/80 (32%) 4/33 (12%) *

Hoarding 19/80 (24%) 1/33 (3%) **Hoarding 19/80 (24%) 1/33 (3%) **

RepetitiveRepetitive 18/80 (23%)18/80 (23%) 3/33 (9%) NS3/33 (9%) NS

Ordering 11/80 (14%)Ordering 11/80 (14%) 0 *0 *

Cleaning 2/80 (2%)Cleaning 2/80 (2%) 0 NS0 NS

CountingCounting 00 00

CheckingChecking 00 00

Clarke et al 2002 BJ Psych; 180-358


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Repetitive behaviour in PWS and autismRepetitive behaviour in PWS and autism

Childhood Routines InventoryChildhood Routines Inventory

PWS N=80; Autism N=89PWS N=80; Autism N=89

Total scoreTotal score 13.1 (5.1) 14.1 (4.2)13.1 (5.1) 14.1 (4.2)

Just right factor score 3.4 (1.6)Just right factor score 3.4 (1.6) 3.8 (1.4)3.8 (1.4)

Repetitive factor scoreRepetitive factor score 3.6 (1.6)3.6 (1.6) 3.8 (1.2)3.8 (1.2)Total freq/intensityTotal freq/intensity 52.6 (16.6) 54.3 (15.6)52.6 (16.6) 54.3 (15.6)

Just right freq/intensityJust right freq/intensity 13.1 (5.2) 14.3 (5.1)13.1 (5.2) 14.3 (5.1)

Repetitive freq/intensity 14.6 (5.8) 15.5 (4.7)Repetitive freq/intensity 14.6 (5.8) 15.5 (4.7)

Strongly significant negative association between DQStrongly significant negative association between DQand frequency/intensity scores in PWS less so in autismand frequency/intensity scores in PWS less so in autism

Greaves et al, 2006 JIDR, 50, 92-100


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Hypothesis: genes to behaviour in PWSHypothesis: genes to behaviour in PWS

Woodcock et al 2009 JIDR, 53: 493Woodcock et al 2009 JIDR, 53: 493--500500 Repetitive and ritualistic behaviours and temperRepetitive and ritualistic behaviours and temper

outbursts cluster together;outbursts cluster together;

Children with PWS reported to show a preference forChildren with PWS reported to show a preference for

predictability with negative emotional behaviour andpredictability with negative emotional behaviour andarousal following change (Woodcock et al, 2009);arousal following change (Woodcock et al, 2009);

Repetitive questions focused on the future and occurredRepetitive questions focused on the future and occurredmore frequently following change in routine;more frequently following change in routine;

Change produces high demand on cognitive resourcesChange produces high demand on cognitive resources in PWS specific deficit in task switching from onein PWS specific deficit in task switching from onecognitive set to another (cognitive endophenotype)cognitive set to another (cognitive endophenotype)(Woodcock et al Cognitive neuropsychology)(Woodcock et al Cognitive neuropsychology)


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PWS

Deficit in

attention

switching

Physiological arousal

Temper outbursts

UNEXPECTED

CHANGE

Repetitive questions

Brain functional

abnormalities

?Courtesy of Woodcock, University

ofBirmingham, UK


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ImplicationsImplications Biological determined deficit in setBiological determined deficit in set--switchingswitching

predisposes to pattern of repetitive andpredisposes to pattern of repetitive andritualistic behaviours and temper outburstsritualistic behaviours and temper outbursts

Pattern of behaviour becomes establishedPattern of behaviour becomes establishedthrough reinforcement over timethrough reinforcement over time

Early intervention to minimise establishment of behavioursEarly intervention to minimise establishment of behaviours Psychologically informed support strategiesPsychologically informed support strategies Training to improve setTraining to improve set--switchingswitching

Why deficit in setWhy deficit in set--switching?switching? Common genetic basis for relationship betweenCommon genetic basis for relationship between

PWS and autism?PWS and autism?


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Management of temper outbursts andManagement of temper outbursts and

repetitive behavioursrepetitive behaviours

Increased propensityIncreased propensity it is aboutit is aboutmanagement not a cure;management not a cure;

Psychological/behavioural approach toPsychological/behavioural approach toprevention and managementprevention and management -- throughthroughobservation identifying what predisposes,observation identifying what predisposes,precipitates and maintains suchprecipitates and maintains suchbehaviours;behaviours;

Routine (predictability)Routine (predictability)

StructureStructure

StrategyStrategy


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Mental illnessMental illness

CharacteristicsCharacteristics

PrevalencePrevalence


ImplicationsImplications


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MethodMethod

Soni et al 2008Soni et al 2008

46 of 119 (38.7%) adults screened positive for46 of 119 (38.7%) adults screened positive forpsychopathologypsychopathology

24 Deletion, 22 mUPD24 Deletion, 22 mUPD

Further assessment included:Further assessment included:

Psychiatric Assessment Schedule for Adults with DevelopmentalPsychiatric Assessment Schedule for Adults with DevelopmentalDisability (PASDisability (PAS--ADD)ADD)

Operational criteria checklist for psychotic and affective illnessOperational criteria checklist for psychotic and affective illness

(OPCRIT)(OPCRIT) Family History QuestionnaireFamily History Questionnaire

modified Life Events Questionnairemodified Life Events Questionnaire

Wechsler Adult Intelligence Scale (WAIS)Wechsler Adult Intelligence Scale (WAIS)


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Prevalence of psychiatric illnessPrevalence of psychiatric illness

Psychotic illness more common in mUPD than deletionPsychotic illness more common in mUPD than deletionp


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Graph to show symptoms in participants withGraph to show symptoms in participants with

psychotic symptoms (n=31)psychotic symptoms (n=31)

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


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Symptoms of hypomania in people with psychoticSymptoms of hypomania in people with psychotic

symptoms (n=31)symptoms (n=31)

0123

456789

Expansivemood

Pre

ssing,racing

thoughts

Ove

rtalkativeness

Distractibility

Overactivity

Exa

ggeratedself

esteem

Sym m

Numb

r

Deletion (n=12)

Disomy (n=19)


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Frequency of psychotic symptomsFrequency of psychotic symptoms

02468

10121416

Audito

ryhallu

cinatio

ns

Visual

hallucin

atio

ns

Tactile

hallucinatio

ns

Olfa

tory

hallucin

atio

ns

Though

tdiso

rder

Anydelusio

n

Catato

nicsy

mptom

s

Insigh

tprese

nt

Symptom

Numbero

fpeople

Deletion (n=12)

Disomy (n=19)


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Summary of phenomenologySummary of phenomenology

Evidence of mood related psychiatricEvidence of mood related psychiatricillness;illness;

Hypomanic symptoms and agitationHypomanic symptoms and agitationmore pronounced in those with mUPD;more pronounced in those with mUPD;

Delusions predominately persecutory inDelusions predominately persecutory in

both deletion and mUPD;both deletion and mUPD;Auditory and visual hallucinationsAuditory and visual hallucinations

present in both groupspresent in both groups


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Mental healthMental healthKey messagesKey messages

Persistent increase in behaviour problemsPersistent increase in behaviour problemsmay indicate onset of affective disordermay indicate onset of affective disorder(evaluation needed(evaluation needed evidence of changeevidence of change

in mental state);in mental state);

If a mood disorder has developed considerIf a mood disorder has developed considerthe following:the following:

Medication in low doses depending on theMedication in low doses depending on thepsychiatric diagnosis;psychiatric diagnosis;

Environmental factors that may be importantEnvironmental factors that may be important


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Formulation in Clinical PracticeFormulation in Clinical Practice

Reason or re erral

Intervention

FORMUL TION

istory

Examination

Investigations

Observations

ccepted

models o

understanding

Evidence-base

or di erentinterventions

G d Clinical

Practice


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Final messagesFinal messages

The importance of assessment and observation;The importance of assessment and observation;

Be aware of possible physical and/pr psychiatricBe aware of possible physical and/pr psychiatric

illnesses;illnesses;

Interventions based on a formulation thatInterventions based on a formulation thatidentifies the key issues;identifies the key issues;

FollowFollow--up carefully and reup carefully and re--evaluate as necessaryevaluate as necessary

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