The treatment of ASD in young adults'

1
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.
2
Take Home Message(s)

• 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.

3
Autistic Disorders

• Autism H.F.A. Aspergers
• 
  
  

Difficulties with reciprocal interaction
behaviour
Ritualistic stereotyped behaviour
Language delay
Learning disability
4
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.

5
Co-Morbid

• Commonly present
• 1. Depression.
• 2. ADHD.
• 3. Anxiety, social phobia, agoraphobia.
• 4. OCD (?).
• 5. Psychosis ?
• Dont 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.

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Assessment takes one day. Approx 120 with ASD
seen last year.
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Eventual Diagnosis
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Co-morbid diagnosis within ASD ()
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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User/Carer Satisfaction
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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).

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Obsessionality/Repetitive Behaviour
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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
  Mar28(2)385-95.
• Micali N, Chakrabati S, Fombonne E. Autism. 2004
  Mar8(1)21-37.

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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 ?.

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OCD vs Autism.McDougle et al Am. J. Psych.
1995
Obsessions
Behaviours

• Autism
• Hoarding
• Need to know

• OCD
• Aggression
• Sex
• Religion
• Contamination
• Symmetry
• Somatic

OCD Cleaning Checking Counting
Autism Repeat Order Hoard Touch Self damage
15
Baron-Cohen WheelwrightBr. J. Psych. 1999

• Folk Physics
• Numerical information
• Dates
• Timetables
• Diaries
• Maths
• Measuring counting

16
High prevalence of obsessions and compulsions in
Aspergers syndrome (Russell et al, Br J
Psychiatry, 2005,186525-8 )
Table 1. Frequency () of participants reporting
symptoms from the Yale Brown Obsessive Compulsive
Symptom Checklist (YBOCS-SCL) by group.  
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 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)

18
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.

19
Preliminary results of CBT pilot
study.Proportions of improved/unimproved
patients (gt25 drop on the YBOCS) in the CBT
(n12) and no-treatment (n7) groups.
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Individual responses
21
OCD in ASD

• More common than we thought.
• Preliminary evidence for CBT, and SSRIs as
  effective.
• Why the increase in OCD/obsessional symptoms ?

22
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
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Fronto-striatal circuits Implicated in OCD
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Gray Matter
McAlonan et al 1) Brain, 2002, Vol 127,
1594-1606, and 2) Brain. 2005 Feb128(Pt 2)268-76
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So.pretty straightforward

• Abnormalities in the function and anatomy of
  fronto-striatal circuits may help explain OCD in
  ASD

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I Wish !

• 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.

27
Gray Matter
McAlonan et al 1) Brain, 2002, Vol 127,
1594-1606, and 2) Brain. 2005 Feb128(Pt 2)268-76
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Putamen vs caudate and repetitive behaviour in
ASD
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Magnetic Resonance Spectroscopy
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a)
b)
Murphy et al Arch Gen Psych 2002.
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Communication deficits (ADI-C)
Obsessionality (Y-BOCS score)
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32
White Matter Association Tracts
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VIRTUAL IN VIVO DISSECTIONS OF THE CEREBELLAR
WHITE MATTER FIBRES (RIGHT HEMISPHERE)
Superior CP P lt 0.003
Short Cerebellar Fibres P lt0.0001
Middle CP (cortical afferents)
Inferior CP
Middle CP (commissural fibres)
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Social Berhaviour and challenging behaviour
35
                                   
 
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

36
0 vs 25 vs 100 Emotion (disgust)
Controls
Asperger Subjects
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Magnetic Resonance Spectroscopy
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Amygdala-Hippocampal complexNAA Kids vs adults
NS

Preliminary data. Replication required.
39
So what is causing neuronal death to be different
? Is it Glutamate ?
Page et al. Am J Psychiatry. Jan 2007
40
Genetic variation in the serotonin transporter
modulates system-wide activation to emotion
short allele of a polymorphism in the promoter
region of the serotonin transporter gene, SLC6A4
41
5-HT 2 A receptor binding in ASD.
Murphy et al, Am J Psychiatry, 2005
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Take Home Message(s)

• 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.

43
MRC UK Autism Imaging Multicentre Study(MRC UK
AIMS PROGRAM)
CAMBRIDGE
IOP
OXFORD