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 ? 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.

6. Assessment – takes one day. Approx 120 with ASD seen last year.

7. Eventual Diagnosis

8. 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.

9. User/Carer Satisfaction

10. 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).

11. Obsessionality/Repetitive Behaviour

12. 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.

13. 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 ?.

14. OCD Aggression Sex Religion Contamination Symmetry Somatic Autism Hoarding Need to know OCD vs Autism.McDougle et al; Am. J. Psych. 1995 Obsessions Behaviours 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. Table 1. Frequency (%) of participants reporting symptoms from the Yale Brown Obsessive Compulsive Symptom Checklist (YBOCS-SCL) by group. 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 High prevalence of obsessions and compulsions in Asperger’s syndrome (Russell et al, Br J Psychiatry, 2005,186:525-8) Interference/Distress 38% at least 1-3 hours/day 56% at least moderate levels of interference 47% at least moderate anxiety if ritual prevented

17. 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 (>25% drop on the YBOCS) in the CBT (n=12) and no-treatment (n=7) groups.

20. 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

23. Fronto-striatal circuits Implicated in OCD

24. Gray Matter McAlonan et al; 1) Brain, 2002, Vol 127, 1594-1606, and 2) Brain. 2005 Feb;128(Pt 2):268-76

25. So…….pretty straightforward Abnormalities in the function and anatomy of fronto-striatal circuits may help explain OCD in ASD

26. 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 Feb;128(Pt 2):268-76

28. Putamen vs caudate and repetitive behaviour in ASD

29. Magnetic Resonance Spectroscopy

30. Medial prefrontal voxel Parietal voxel 15 15 14 14 13 NAA NAA 13 Prefrontal metabolite concentration mM Parietal metabolite concentration mM 12 12 11 11 10 10 autistic disorder autistic disorder controls controls 12 12 11 11 Cr+PCr Cr+PCr 10 10 9 9 8 8 7 7 6 6 autistic disorder autistic disorder controls controls 4 4 3 Cho Cho 3 2 2 1 1 autistic disorder controls autistic disorder controls a) b) Murphy et al; Arch Gen Psych 2002.

31. a ) b ) 2 5 3 0 2 0 2 0 1 5 Communication deficits (ADI-C) Obsessionality (Y-BOCS score) 1 0 1 0 5 0 0 7 8 9 1 0 1 1 1 2 1 3 1 4 1 1 1 2 1 3 1 4 1 5 1 6 P r e f r o n t a l N A A c o n c e n t r a t i o n ( m M ) P r e f r o n t a l C r + P C r c o n c e n t r a t i o n ( m M )

32. White Matter Association Tracts

33. 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

34. 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

37. Magnetic Resonance Spectroscopy

38. 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 transportergene, SLC6A4

41. 5-HT 2 A receptor binding in ASD. Murphy et al, Am J Psychiatry, 2005

42. 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