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The treatment of ASD in young
adults.
Declan Murphy, Professor of Psychiatry and Brain Maturation,
Institute 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.
Take Home Message(s)
1.
2.
3.
4.
5.
6.
7.
8.
Most people with ASD do not need a psychiatrist.
But, many young adults with ASD do have significant co-morbidity
in mental health. That needs to be treated.
The (RCT) evidence base for treatments specifically in young adults
is missing.
Avoid the use of antipsychotics for ‘challenging behaviour’ if at all
possible.
Use clinical ‘best practice’ and treat co-morbidity as in any other
person, but take ASD into account.
ASD has life-long consequences. You need close working with
colleagues in CAMHS and other services.
There is Increasing understanding of the neurobiology.
Glutamate/Glutamine and 5-HT may be especially implicated.
Autistic Disorders
Autism
H.F.A.
Aspergers
Difficulties with reciprocal interaction & behaviour
Ritualistic & stereotyped behaviour
Language delay
Learning disability
Services for adults with ASD.
1. Very few that cover whole IQ/age spectrum.
2. National. Approximately 3 outpatient services.
Approx 3 private inpatient services opened in
the last year. Mainly for CBs. Many out-of-area
care homes opening.
3. Services addressing life-long problems. Nil.
4. Formal handover of child-to-adult. Often nil
when no LD.
Co-Morbid
Commonly present
1. Depression.
2. ADHD.
3. Anxiety, social phobia, agoraphobia.
4. OCD (?).
5. Psychosis ?
Don’t forget.
6. Modifies symptom presentation of other disorders (e.g. Schizophrenia
and OCD).
Always think of ASD in those who are not ‘getting better’
8. Social Phobia +/- OCD.
9. Schizophrenia.
Assessment – takes one day.
Approx 120 with ASD seen last year.
Social and Biological measures – neuropsych, EEG, ECG, sMRI/MRS, karyotyping
Person with disorder
Family/clinical Interview
Formal rating scales
Eventual Diagnosis
45
40
35
no ASD and no need
for ANY MH service
ASD
30
25
20
15
10
5
0
Other
Person Profile
Co-morbid diagnosis within ASD (%)
40
35
'Only ASD'
+ OCD
+ anxiety disorder
+ depression
+ Psychosis
+ PD
'Risk to others'
30
25
20
15
10
5
0
Diagnostic groups
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.
User/Carer Satisfaction
90
80
70
60
50
Not satisfied
Satisfied
Very Satisfied
40
30
20
10
0
wait
assessment
feeback
treatment
HOW DO I TREAT ?
CO-MORBIDITY
As if it were the primary disorder, but modify
explanation and approach.
Core disorder
Depending upon severity. Mostly
behavioural/social/education/advice,
occasional pharmacological (risperidone,
and/or SSRIs).
Obsessionality/Repetitive
Behaviour
Familial aggregation of OCD in ASD
Motor tics, obsessive-compulsive (OCD) and affective
disorders significantly more common in relatives of autistic
probands.
Individuals with OCD more likely to exhibit autistic-like social
and communication impairments.
OCD may index an underlying liability to autism.
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.
Summary 1.
OCD is probably part of the genetic
landscape for ASD.
BUT.
Are the obsessional/repetitive behaviours in
ASD similar or different to OCD ?
How common is OCD – and other symptoms
?.
OCD vs Autism.
McDougle et al; Am. J. Psych. 1995
Obsessions
OCD
Aggression
Sex
Religion
Contamination
Symmetry
Somatic
Behaviours
Autism
OCD
Autism
Hoarding
Need to
know
Cleaning
Checking
Counting
Repeat
Order
Hoard
Touch
Self damage
Baron-Cohen & Wheelwright
Br. J. Psych. 1999
Folk Physics
Numerical information
Dates
Timetables
Diaries
Maths
Measuring & counting
High prevalence of obsessions and compulsions in Asperger’s syndrome
(Russell et al, Br J Psychiatry, 2005,186:525-8
ASD Group
(n=35)
OCD Group
(n=38)
2
(df=1)
p
17 (48.6)
22 (57.9)
.636
ns
21 (60)
25 (65.8)
.262
ns
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
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
Contamination
Sexual
Interference/Distress
38% at least 1-3 hours/day
Obsessions:
Aggressive
)
Compulsions:
56% at least moderate levels
of interference
47% at least moderate anxiety
if ritual prevented
Treatment. Evidence base for SSRIs
Few treatment studies of OCD in people with Autism
Spectrum Disorders, all have focused on pharmacology
targeting generic symptom ‘classes’.
Several studies of pharmacological interventions have
reported that repetitive thoughts and behaviors in
individuals with ASD are significantly reduced by
treatment with a variety of serotonin reuptake inhibitors
(Brodkin et al, 1997; Hollander et al,. 2005; McDougle et
al, 1998), and risperidone (McDougle et al, 2000, 2005)
Evidence base for CBT
Single-case reports.
A child with Asperger Syndrome (Reaven and Hepburn, 2003).
An adult with autism (Lindley et al, 1977).
RCTs
Nil specifically of OCD in ASD.
However…….CBT intervention for anxiety disorders in children with
Asperger Syndrome which included young people with OCD
(Sofronoff, Atwood & Hinton (2005). Pediatric OCD cases in this
study who were in the wait list control group did not improve on
parental ratings; whereas those who received CBT did.
Preliminary results of CBT pilot study.
Proportions of improved/unimproved patients (>25% drop on the
YBOCS) in the CBT (n=12) and no-treatment (n=7) groups
100
Percentage
80
60
Improved
40
Unimproved
20
0
CBT (n=12)
No-treatment (n=7)
.
Individual responses
Figure 1: Plot of individual values of YBOCS total severity scores pre
and post treatment
40
35
30
25
No CBT
20
CBT
15
10
5
0
Time 1
Time 2
OCD in ASD
More common than we thought.
Preliminary evidence for CBT, and SSRIs as
effective.
Why the increase in OCD/obsessional
symptoms ?
Simplistic overview of theories for obsessional
symptoms/restricted interests
Cognitive
1. Executive Function.
2. Central coherence.
Anatomical/neurochemical
3. Fronto-striatal circuits.
4. Serotonergic system
Fronto-striatal circuits Implicated
in OCD
ORBITO –
FRONTAL
CORTEX
VENTROMEDIAL CAUDATE
GLOBUS PALLIDUS
SUBSTANTIA NIGRA
MEDIAL DORSAL
THALAMUS
GLOBUS PALLIDUS EXTERNA
SUBTHALAMIC NUCLEI
Gray Matter
McAlonan et al; 1) Brain, 2002, Vol 127, 1594-1606, and 2) Brain. 2005 Feb;128(Pt 2):268-76
So…….pretty straightforward
Abnormalities in the function and anatomy of
fronto-striatal circuits may help explain
OCD in ASD
I Wish !
1.
2.
3.
Different parts of the circuit have
different, and multiple, functions.
We also need to know HOW these
differences arise.
We also need to understand the
neurochemistry.
Gray Matter
McAlonan et al; 1) Brain, 2002, Vol 127, 1594-1606, and 2) Brain. 2005 Feb;128(Pt 2):268-76
15.00
15.00
12.50
12.50
Repetitive behaviors on ADI-R
Repetitive behaviors on ADI-R
Putamen vs caudate and
repetitive behaviour in ASD
10.00
7.50
5.00
2.50
10.00
7.50
5.00
2.50
R Sq Linear = 0.09
0.00
R Sq Linear = 0.064
0.00
0.25
0.30
0.35
0.40
W_rput
0.45
0.50
0.55
6.00
4.00
right caudate
Magnetic Resonance
Spectroscopy
a)
b)
Medial prefrontal voxel
Prefrontal
metabolite
concentration
mM
15
15
14
14
13
NAA
12
11
10
autistic controls
disorder
12
11
Parietal
metabolite
concentration
mM
13
NAA
12
11
10
autistic controls
disorder
12
11
Cr+P
Cr
10
9
8
7
6
Murphy et al;
Arch Gen Psych
2002.
Parietal voxel
Cr+P
Cr
10
9
8
7
6
autistic controls
disorder
4
4
3
3
Cho
2
autistic controls
disorder
Cho
2
1
1
autistic controls
disorder
autistic controls
disorder
b)
Communication deficits (ADI-C)
Obsessionality (Y-BOCS score)
a)
30
20
10
0
11
25
20
15
10
5
0
12
13
14
15
Prefrontal NAA concentration (m M)
16
7
8
9
10
11
12
13
14
Prefrontal Cr+PCr concentration (mM)
White Matter Association Tracts
VIRTUAL IN VIVO DISSECTIONS OF THE CEREBELLAR WHITE MATTER
FIBRES (RIGHT HEMISPHERE)
Superior CP
P < 0.003
Short Cerebellar
Fibres P <0.0001
Middle CP
(cortical
afferents)
Middle CP (commissural
fibres)
Inferior CP
Social Berhaviour and ‘challenging
behaviour’
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
0 vs 25 vs 100%
Emotion (disgust)
Controls
Asperger Subjects
Magnetic Resonance
Spectroscopy
Amygdala-Hippocampal complex
NAA – Kids vs adults
NS
5.6
5.4
***
5.2
Kids
Adults
5
4.8
4.6
4.4
NC
ASP
Preliminary data. Replication required.
So what is causing neuronal
death to be different ?
Is it Glutamate ?
Hippo_Glu/Gln
Page et al.
Am J Psychiatry.
Jan 2007
18
16
14
HIPPO_GL
12
10
8
.8
1.0
PATIENT_
1.2
1.4
1.6
1.8
2.0
2.2
Genetic variation in the serotonin
transporter modulates system-wide
activation to emotion
VLPFC
IOG
MACC
BOLD % change: Mean +/- 2 SE
0.20
0.15
0.10
0.05
0.00
-0.05
ll
sl
Subgroup
ss
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
5-HT 2 A receptor binding in ASD.
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
2.0000
Mean
1.5000
1.0000
0.5000
0.0000
1.0000
2.0000
cont=1 asp=2
Murphy et al, Am J Psychiatry, 2005
Take Home Message(s)
1.
2.
3.
4.
5.
6.
7.
8.
Most people with ASD do not need a psychiatrist.
But, many young adults with ASD do have significant co-morbidity
in mental health. That needs to be treated.
The (RCT) evidence base for treatments specifically in young adults
is missing.
Avoid the use of antipsychotics for ‘challenging behaviour’ if at all
possible.
In the meantime, use clinical common sense and treat co-morbidity
as in any other person, but take ASD into account.
ASD has life-long consequences. You need close working with
colleagues in CAMHS and other services.
There is Increasing understanding of the neurobiology.
Glutamate/Glutamine and 5-HT may be especially implicated.
MRC
UK Autism Imaging Multicentre
Study
(MRC: UK AIMS PROGRAM)
CAMBRIDGE
IOP
OXFORD