the treatment of asd in young adults. declan murphy, professor of psychiatry and brain maturation,...
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The treatment of ASD in The treatment of ASD in young adults. young adults.
Declan Murphy, Professor of Psychiatry and Brain Maturation,Declan Murphy, Professor of Psychiatry and Brain Maturation,Institute of Psychiatry, London, UKInstitute of Psychiatry, London, UK
Work Funded by the MRC U.K. A.I.M.S network, the Wellcome Trust, National Institutes of Health (USA), Cure Autism Now, Autism Speaks, Dept of Health (NIHR program UK), SLAM.
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Take Home Message(s)Take Home Message(s)1.1. Most people with ASD do not need a psychiatrist.Most people with ASD do not need a psychiatrist.2.2. But, many young adults with ASD do have significant co-But, many young adults with ASD do have significant co-
morbidity in mental health. That needs to be treated.morbidity in mental health. That needs to be treated.3.3. The (RCT) evidence base for treatments The (RCT) evidence base for treatments specificallyspecifically in in
young adults is missing.young adults is missing.4.4. Avoid the use of antipsychotics for ‘challenging behaviour’ Avoid the use of antipsychotics for ‘challenging behaviour’
if at all possible.if at all possible.5.5. Use clinical ‘best practice’ and treat co-morbidity as in any Use clinical ‘best practice’ and treat co-morbidity as in any
other person, but take ASD into account.other person, but take ASD into account.6.6. ASD has life-long consequences. You need close working ASD has life-long consequences. You need close working
with colleagues in CAMHS and other services. with colleagues in CAMHS and other services. 7.7. There is Increasing understanding of the neurobiology.There is Increasing understanding of the neurobiology.8.8. Glutamate/Glutamine and 5-HT may be especially Glutamate/Glutamine and 5-HT may be especially
implicated.implicated.
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Autistic DisordersAutistic Disorders
AutismAutism H.F.A. H.F.A. AspergersAspergers
Difficulties with reciprocal interaction & behaviour
Learning disability
Ritualistic & stereotyped behaviour
Language delay
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Services for adults with ASD.Services for adults with ASD.
1.1. Very few that cover whole IQ/age spectrum.Very few that cover whole IQ/age spectrum.
2.2. National. Approximately 3 outpatient services. National. Approximately 3 outpatient services. Approx 3 private inpatient services opened in Approx 3 private inpatient services opened in the last year. Mainly for CBs. Many out-of-area the last year. Mainly for CBs. Many out-of-area care homes opening.care homes opening.
3.3. Services addressing life-long problems. Nil.Services addressing life-long problems. Nil.
4.4. Formal handover of child-to-adult. Often nil Formal handover of child-to-adult. Often nil when no LD.when no LD.
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Co-MorbidCo-MorbidCommonly presentCommonly present
1. Depression.1. Depression.2. ADHD.2. ADHD.3. Anxiety, social phobia, agoraphobia.3. Anxiety, social phobia, agoraphobia.4. OCD (?).4. OCD (?).5. Psychosis ?5. Psychosis ?
Don’t forgetDon’t forget..6. Modifies symptom presentation of other disorders (e.g. 6. Modifies symptom presentation of other disorders (e.g.
Schizophrenia and OCD).Schizophrenia and OCD).
Always think of ASD in those who are not ‘getting better’Always think of ASD in those who are not ‘getting better’8. Social Phobia +/- OCD.8. Social Phobia +/- OCD.9. Schizophrenia. 9. Schizophrenia.
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Assessment – takes one day. Assessment – takes one day. Approx 120 with ASD seen last Approx 120 with ASD seen last
year.year.
Family/clinical Interview Formal rating scales
Social and Biological measures – neuropsych, EEG, ECG, sMRI/MRS, karyotyping
Person with disorder
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Eventual DiagnosisEventual Diagnosis
0
5
10
15
20
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35
40
45
Person Profile
no ASD and no needfor ANY MH serviceASD
Other
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Co-morbid diagnosis within ASD Co-morbid diagnosis within ASD (%)(%)
0
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40
Diagnostic groups
'Only ASD'+ OCD+ anxiety disorder+ depression+ Psychosis+ PD'Risk to others'
NB – the screening out of ‘nothing needing Murphy’ and ‘only ASD’ removes a significant burden of care. Social Phobia and Drugs and alcohol increased across all groups.
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0
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40
50
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wait assessment feeback treatment
Not satisfiedSatisfiedVery Satisfied
User/Carer Satisfaction
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HOW DO I TREAT ?HOW DO I TREAT ?
CO-MORBIDITYCO-MORBIDITY As if it were the primary disorder, but As if it were the primary disorder, but
modify explanation and approach.modify explanation and approach. Core disorderCore disorder
Depending upon severity. Mostly Depending upon severity. Mostly behavioural/social/education/advice, behavioural/social/education/advice, occasional pharmacological occasional pharmacological (risperidone, and/or SSRIs).(risperidone, and/or SSRIs).
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Obsessionality/Repetitive Obsessionality/Repetitive BehaviourBehaviour
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Familial aggregation of OCD in Familial aggregation of OCD in ASD ASD
Motor tics, obsessive-compulsive (OCD) and affective Motor tics, obsessive-compulsive (OCD) and affective disorders significantly more common in relatives of disorders significantly more common in relatives of autistic probands.autistic probands.
Individuals with OCD more likely to exhibit autistic-Individuals with OCD more likely to exhibit autistic-like social and communication impairments. like social and communication impairments.
OCD may index an underlying liability to autism.OCD may index an underlying liability to autism.
Bolton PF et al Psychol Med. 1998 Mar;28(2):385-95.Bolton PF et al Psychol Med. 1998 Mar;28(2):385-95.
Micali N, Chakrabati S, Fombonne E. Autism. 2004 Mar;8(1):21-37.Micali N, Chakrabati S, Fombonne E. Autism. 2004 Mar;8(1):21-37.
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Summary 1.Summary 1.
OCD is probably part of the genetic OCD is probably part of the genetic landscape for ASD.landscape for ASD.
BUT.BUT.Are the obsessional/repetitive behaviours Are the obsessional/repetitive behaviours
in ASD similar or different to OCD ?in ASD similar or different to OCD ?How common is OCD – and other How common is OCD – and other
symptoms ?.symptoms ?.
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OCD vs Autism.OCD vs Autism.McDougle et al; Am. J. Psych. 1995McDougle et al; Am. J. Psych. 1995
OCDOCDAggressionAggression
SexSex
ReligionReligion
ContaminationContamination
SymmetrySymmetry
SomaticSomatic
AutismAutism
HoardingHoarding
Need to Need to knowknow
ObsessionsObsessions
OCDOCD
CleaningCleaningChecking Checking CountingCounting
AutismAutism
RepeatRepeatOrderOrderHoardHoardTouchTouchSelf damageSelf damage
Behaviours
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Baron-Cohen & WheelwrightBaron-Cohen & WheelwrightBr. J. Psych. 1999Br. J. Psych. 1999
Folk PhysicsFolk Physics
Numerical informationNumerical information
DatesDates
TimetablesTimetables
DiariesDiaries
MathsMaths
Measuring & countingMeasuring & counting
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High prevalence of obsessions and compulsions in Asperger’s High prevalence of obsessions and compulsions in Asperger’s
syndrome (Russell et al, Br J Psychiatry, 2005,186:525-8syndrome (Russell et al, Br J Psychiatry, 2005,186:525-8 ))
ASD Group (n=35)
OCD Group(n=38)
2
(df=1)p
Obsessions:
Aggressive 17 (48.6) 22 (57.9) .636 ns
Contamination 21 (60) 25 (65.8) .262 ns
Sexual 10 (28.6) 11 (28.9) .001 ns
Hoarding 14 (40) 20 (52.6) 1.16 ns
Religious 10 (28.6) 10 (26.3) .047 ns
Symmetry 18 (51.4) 24 (63.2) 1.02 ns
Somatic 6 (17.1) 19 (50.0) 8.73 p=.003
Compulsions:
Cleaning 20 (57.1) 25 (65.8) .576 ns
Checking 22 (62.9) 31 (81.6) 3.21 ns
Repeating 14 (40) 25 (65.8) 4.87 p=.024
Counting 3 (8.65) 9 (23.7) 3.02 ns
Arranging 8 (22.9) 14 (36.8) 1.69 ns
Hoarding 11 (31.4) 17 (44.7) 1.36 ns
Interference/Distress
38% at least 1-3 hours/day
56% at least moderate levels of interference
47% at least moderate anxiety if ritual prevented
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Treatment. Evidence base for Treatment. Evidence base for SSRIsSSRIs
Few treatment studies of OCD in people with Autism Few treatment studies of OCD in people with Autism Spectrum Disorders, all have focused on Spectrum Disorders, all have focused on pharmacology targeting generic symptom pharmacology targeting generic symptom ‘classes’. ‘classes’.
Several studies of pharmacological interventions Several studies of pharmacological interventions have reported that repetitive thoughts and have reported that repetitive thoughts and behaviors in individuals with ASD are significantly behaviors in individuals with ASD are significantly reduced by treatment with a variety of serotonin reduced by treatment with a variety of serotonin reuptake inhibitors (Brodkin reuptake inhibitors (Brodkin et alet al, 1997; Hollander , 1997; Hollander et al,.et al,. 2005; McDougle 2005; McDougle et alet al, 1998), and , 1998), and risperidone (McDougle risperidone (McDougle et alet al, 2000, 2005), 2000, 2005)
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Evidence base for CBTEvidence base for CBTSingle-case reports.
A child with Asperger Syndrome (Reaven and Hepburn, 2003).A child with Asperger Syndrome (Reaven and Hepburn, 2003).An adult with autism (Lindley An adult with autism (Lindley et al, et al, 1977). 1977).
RCTs
Nil specifically of OCD in ASD. Nil specifically of OCD in ASD.
However…….CBT intervention for anxiety disorders in children However…….CBT intervention for anxiety disorders in children with Asperger Syndrome which included young people with with Asperger Syndrome which included young people with OCD (Sofronoff, Atwood & Hinton (2005). Pediatric OCD OCD (Sofronoff, Atwood & Hinton (2005). Pediatric OCD cases in this study who were in the wait list control group cases in this study who were in the wait list control group did not improve on parental ratings; whereas those who did not improve on parental ratings; whereas those who received CBT did.received CBT did.
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Preliminary results of CBT pilot study.Preliminary results of CBT pilot study.Proportions of improved/unimproved patients (>25% drop on Proportions of improved/unimproved patients (>25% drop on
the YBOCS) in the CBT (n=12) and no-treatment (n=7) groupsthe YBOCS) in the CBT (n=12) and no-treatment (n=7) groups..
0
20
40
60
80
100
Perc
entag
e
CBT (n=12) No-treatment (n=7)
Improved
Unimproved
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Individual responsesIndividual responsesFigure 1: Plot of individual values of YBOCS total severity scores pre
and post treatment
0
5
10
15
20
25
30
35
40
Time 1 Time 2
No CBT
CBT
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OCD in ASDOCD in ASD
More common than we thought.More common than we thought.
Preliminary evidence for CBT, and SSRIs Preliminary evidence for CBT, and SSRIs as effective.as effective.
Why the increase in OCD/obsessional Why the increase in OCD/obsessional symptoms ?symptoms ?
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Simplistic overview of theories for Simplistic overview of theories for obsessional symptoms/restricted obsessional symptoms/restricted
interestsinterests CognitiveCognitive
1.1. Executive Function.Executive Function.
2.2. Central coherence.Central coherence.
Anatomical/neurochemicalAnatomical/neurochemical3.3. Fronto-striatal circuits.Fronto-striatal circuits.4.4. Serotonergic systemSerotonergic system
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VENTROMEDIAL CAUDATE
ORBITO –FRONTALCORTEX
MEDIAL DORSALTHALAMUS
GLOBUS PALLIDUSSUBSTANTIA NIGRA
GLOBUS PALLIDUS EXTERNA
SUBTHALAMIC NUCLEI
Fronto-striatal circuits Fronto-striatal circuits Implicated in OCDImplicated in OCD
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McAlonan et al; 1) Brain, 2002, Vol 127, 1594-1606, and 2) Brain. 2005 Feb;128(Pt 2):268-76
Gray Matter
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So…….pretty straightforwardSo…….pretty straightforward
Abnormalities in the function and Abnormalities in the function and anatomy of fronto-striatal circuits may anatomy of fronto-striatal circuits may help explain OCD in ASDhelp explain OCD in ASD
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I Wish !I Wish !
1.1. Different parts of the circuit have Different parts of the circuit have different, and multiple, functions.different, and multiple, functions.
2.2. We also need to know HOW these We also need to know HOW these differences arise.differences arise.
3.3. We also need to understand the We also need to understand the neurochemistry.neurochemistry.
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McAlonan et al; 1) Brain, 2002, Vol 127, 1594-1606, and 2) Brain. 2005 Feb;128(Pt 2):268-76
Gray Matter
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Putamen vs caudate and Putamen vs caudate and repetitive behaviour in ASD repetitive behaviour in ASD
0.550.500.450.400.350.300.25
W_rput
15.00
12.50
10.00
7.50
5.00
2.50
0.00
Rep
etit
ive
beh
avio
rs o
n A
DI-
R
R Sq Linear = 0.09
6.004.00
right caudate
15.00
12.50
10.00
7.50
5.00
2.50
0.00R
epet
itiv
e b
ehav
iors
on
AD
I-R
R Sq Linear = 0.064
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Magnetic Resonance Magnetic Resonance SpectroscopySpectroscopy
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a)
b)
Medial prefrontal voxel Parietal voxel
Prefrontalmetabolite concentration mM
6
7
8
9
10
11
12
Cr+PCr
10
11
12
13
14
15
NAA
1
2
3
4
Cho
Parietalmetabolite concentration mM
10
11
12
13
14
15
NAA
6
7
8
9
10
11
12
Cr+PCr
1
2
3
4
Cho
autisticdisorder
controls
autisticdisorder
controls
autisticdisorder
controls
autisticdisorder
controls
autisticdisorder
controls
autisticdisorder
controls
Murphy et al;Arch Gen Psych2002.
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a) b)
Prefrontal Cr+PCr concentration (mM)
1413121110987
Com
mun
icati
on
defi
cits
(A
DI-
C)
25
20
15
10
5
0
Prefrontal NAA concentration (mM)
161514131211
Ob
sess
ionalit
y (
Y-B
OC
S s
core
)
30
20
10
0
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White Matter Association White Matter Association TractsTracts
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Superior CP
P < 0.003
Inferior CPMiddle CP (commissural fibres)
Middle CP (cortical afferents)
Short Cerebellar Fibres P <0.0001
VIRTUAL IN VIVO DISSECTIONS OF THE CEREBELLAR WHITE MATTER FIBRES (RIGHT HEMISPHERE)
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Social Berhaviour and Social Berhaviour and ‘challenging behaviour’‘challenging behaviour’
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Implicit gender discrimination task while viewing mild (25%) and intense (100%) expressions contrasted with neutral faces and a baseline condition in an erfRMI design. Individual facial stimulus presentation 2s, ISI 3 – 8s with average interval 4.9s, with fixation cross shown in the ISI
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0 vs 25 vs 100% Emotion (disgust)
Controls Asperger Subjects
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Magnetic Resonance Magnetic Resonance SpectroscopySpectroscopy
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Amygdala-Hippocampal Amygdala-Hippocampal complexcomplex
NAA – Kids vs adultsNAA – Kids vs adults
4.4
4.6
4.8
5
5.2
5.4
5.6
NC ASP
Kids Adults
***
NS
Preliminary data. Replication required.
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So what is causing neuronal So what is causing neuronal death to be different ?death to be different ?
Is it Glutamate ? Is it Glutamate ?
Hippo_Glu/Gln
PATIENT_
2.22.01.81.61.41.21.0.8
HIP
PO
_GL
18
16
14
12
10
8
Page et al. Am J Psychiatry. Jan 2007
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Genetic variation in the serotonin Genetic variation in the serotonin transporter modulates system-wide transporter modulates system-wide
activation to emotionactivation to emotion
ll sl ssSubgroup
-0.05
0.00
0.05
0.10
0.15
0.20
BO
LD
% c
han
ge:
Mea
n +
/- 2
SE
VLPFC
IOG
MACC
Legend; VLPFC = Ventrolateral Prefrontal Cortex: IOG = Inferior Occipital
Gyrus: MACC = Dorsal/Middle Anterior Cingulate Cortex.
short allele of a polymorphism in the promoter region of the serotonin transporter gene, SLC6A4
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5-HT 2 A receptor binding in 5-HT 2 A receptor binding in ASD.ASD.
1.0000 2.0000
cont=1 asp=2
0.0000
0.5000
1.0000
1.5000
2.0000
Me
an
cing_01
f_cor_01_l
f_cor_01_r
m_temp_cor_01_l
m_temp_cor_01_r
occ_cor_01
par_cor_01_l
par_cor_01_r
sup_temp_cor_01_l
sup_temp_cor_01_r
Murphy et al, Am J Psychiatry, 2005Murphy et al, Am J Psychiatry, 2005
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Take Home Message(s)Take Home Message(s)1.1. Most people with ASD do not need a psychiatrist.Most people with ASD do not need a psychiatrist.2.2. But, many young adults with ASD do have significant co-But, many young adults with ASD do have significant co-
morbidity in mental health. That needs to be treated.morbidity in mental health. That needs to be treated.3.3. The (RCT) evidence base for treatments The (RCT) evidence base for treatments specificallyspecifically in in
young adults is missing.young adults is missing.4.4. Avoid the use of antipsychotics for ‘challenging behaviour’ Avoid the use of antipsychotics for ‘challenging behaviour’
if at all possible.if at all possible.5.5. In the meantime, use clinical common sense and treat co-In the meantime, use clinical common sense and treat co-
morbidity as in any other person, but take ASD into morbidity as in any other person, but take ASD into account.account.
6.6. ASD has life-long consequences. You need close working ASD has life-long consequences. You need close working with colleagues in CAMHS and other services. with colleagues in CAMHS and other services.
7.7. There is Increasing understanding of the neurobiology.There is Increasing understanding of the neurobiology.8.8. Glutamate/Glutamine and 5-HT may be especially Glutamate/Glutamine and 5-HT may be especially
implicated.implicated.
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MRC MRC UK Autism Imaging Multicentre UK Autism Imaging Multicentre
StudyStudy(MRC: UK AIMS PROGRAM)(MRC: UK AIMS PROGRAM)
IOP
CAMBRIDGE
OXFORD