1. Anxiety in Autism Spectrum Disorders Todd Levine MD, FAAP Assistant Professor in Psychiatry and Human Behavior Brown Center for the Study of Children at Risk Warren Alpert Medical School of Brown University, Providence, RI

2. Disclosures  No financial relationships or conflicts of interest  Many of these treatments are “off label”, non-Food and Drug Administration approved

3. Learning Objectives  Investigate the relationship between symptoms of Autism Spectrum Disorders (ASDs) and those of anxiety disorders  Understand common anxiety symptoms assessed and treated in ASDs  Understand how mechanisms of arousal and stress may differ in children with ASDs

4. Diagnostic Considerations  Connecting with one’s own feelings and those of others  Interpretation of motivations behind behaviors  Contextualizing behaviors Core deficits in socialization and communication can lead to difficulties with:

5. DSM-IV Considerations Some diagnoses exclude/modify for Pervasive Developmental Disorders:  Social Phobia (Social Anxiety Disorder)  Separation Anxiety Disorder  Selective Mutism  Generalized Anxiety Disorder  ADHD  Pica  Rumination Disorder  Schizophrenia (Delusions/Hallucinations present)  Schizoid Personality Disorder  Schizotypal Personality Disorder

6. With this in Mind…  Children and adults with Autism Spectrum Disorders (ASDs) are at higher risk for anxiety 1, depression 2, and ADHD 3  Psychiatric medications are likely to be prescribed to those with ASDs 4  Psychotherapies have been adapted for children with ASDs and anxiety 5 1 Gillot et al. Autism (2001), 2 Mandell et al. Pediatrics. 2008, 1 Gillot et al. Autism (2001), 2 Ghaziuddin et al. J Autism Dev Disord. (2002), 3 Ghaziuddin et al. J Intellect Disabil Res (1998), 4 Mandell et al. Pediatrics. 2008, 5 Chalfant et al. 5 Chalfant et al. J Autism Dev Disord (2007)

7. Possible Explanations  Some children with ASD may be overstimulated due to a hyperactive nervous system 1  Children with ASD may have difficulty with emotional processing 2  Deficits in socialization and communication may cause vulnerability to anxiety and depressive symptoms 1 Hirstein et al. Proc Biol Sci (2001) 2 Losh and Capps. Dev Psyc (2006)

8. Other Factors in Anxiety in ASDs  Intelligence?  Social Functioning Difficulties: May be worsened by higher anxiety  Sensory sensitivities  Changes in routine  Avoidance of non-preferred tasks  Lack of expressive language Eussen et al. Autism Eussen et al. Autism (2012), Lane et al. Am J Occup Ther (2012), Ozsuvadjian et al. Autism (2012)

9. Psychotropic Prescribing in ASD Martin et al. JAACAP. 1999

10. Psychotropic Prescribing in ASD In a sample of 60,641 children with ASDs, 56% used at least 1 psychotropic medication In a sample of 60,641 children with ASDs, 56% used at least 1 psychotropic medication 20% were prescribed 3 medications concurrently 20% were prescribed 3 medications concurrently Use was common even in children aged 0 to 2 years (18%) and 3 to 5 years (32%) Use was common even in children aged 0 to 2 years (18%) and 3 to 5 years (32%) Neuroleptic drugs were the most common psychotropic class (31%), followed by antidepressants (25%) and stimulants (22%) Neuroleptic drugs were the most common psychotropic class (31%), followed by antidepressants (25%) and stimulants (22%) Mandell et al. Pediatrics. 2008

11. Taking a Different Perspective

12. Obsessive Compulsive Disorder vs. Repetitive Interests in ASDs  Obsessions are “recurrent and persistent thoughts, impulses, or images that…cause marked anxiety or distress” (DSM-IV)  Compulsions are acts designed to counteract those thoughts, impulses, or images  Are either consistent with “restricted repetitive and stereotyped patterns of behavior, interests, and activities” in ASDs?  “Insistence on Sameness” different from anxiety in study. Gotham et al. Autism Research (2013)

14. When Does Generalized Anxiety Occur in AS?  Persistent worries about scheduling can occur in those with ASDs  Generalized Anxiety (GAD) includes being “keyed up”, sleep difficulties, and muscle tension  As in OCD, dysphoric thoughts and feelings delineate problematic anxiety

15. Considering PTSD in AS  Is trauma processed differently in those with ASD?  The symptoms of hyperarousal and social withdrawl can be difficult to delineate in people with ASDs  Is there a case for chronic trauma affecting those with ASDs?  Considerations for group therapy

16. Can Someone with AS be Socially Anxious?  Excluded from Social Anxiety Disorder diagnosis  Socially anxious people are fearful of humiliation and opinions of others  People with ASDs can be aware of these factors  Many with ASDs appear dysphoric or anxious in groups of people, but is this anxiety?  Cognitive behavior strategies have been applied

17. The Elusive “Inner State”  How reliable/valid are self-reports in adults and children with ASDs?  Can parents tell us more about their kids with ASDs than the kids?  Can we look at more concrete, biological markers of emotional response to help understand psychiatric reporting?  There are few psychiatric measures for those with ASDs

18. The Study of Social Anxiety in Asperger’s Disorder  Compares children ages 8-12 years old with Asperger’s Disorder (AD, n=19) to those without (n=12) during a social stressor  Protocol involves parent and child reports of anxiety (MASC and SPAI-C), child self- report of anxiety during the events, and measurement of psychophysiology:  Salivary cortisol reactivity  Electrodermal reactivity (EDR)  Heart rate variability, “vagal tone” (VT)

19. Vagal Tone EDR

20. Participant Example #1

21. Participant Example #2

22. Who Has Asperger’s? #1#2

23. A Look at Cortisol Responses

24. The envelope, please… #1#2

25. “Gas” and “Brake” Comparison EDR Vagal Tone

26. Brief Summary of Study Results  Children with Asperger’s were twice as likely to be cortisol non-responders than controls (p=0.056)  There were no between group differences on EDR and VT across time  EDR positively correlated with parent reports of arousal on the MASC in controls, but not the Asperger’s group

27. What’s Next?

28. Trends in Medication Treatment Studies in AS/ASD  Most studies focus on specific behaviors vs. diagnostic criteria  Specific behavioral measures have been created or modified for AS patients  Successful strategies in “neurotypical” children have been applied to children and adults with AS and similar behaviors

29. Problem Behaviors Targeted by Psychotropic Medications  Hyperactivity  Lack of Attention  Agitation  Insomnia  Aggression  Self-injury  Stereotypies  Tantrums  Repetitive Behavior  Compulsive Behavior  Anxiety  Hyperarousal  Irritability  Impulsivity

30. Side Effects of Psychotropic Medications  Hyperactivity  Lack of Attention  Agitation  Insomnia  Aggression  Activation  Agitation  Repetitive Behavior  Compulsive Behavior  Hyperarousal  Irritability  Tics

31. Antidepressants  Serotonin Specific Re-uptake Inhibitors (SSRIs) have evidence for use in children and adolescents with anxiety and depression  U.S. FDA Black Box warning spurned controversy over use of SSRIs  Applicability to AS behaviors has been explored: repetitive behaviors and anxiety  Recent research has changed previous conceptions about SSRI use in ASDs

32. Sertraline for Perseverative Anxiety  Based on clinical experience  Useful for overly-repetitive concerns or “anti-Zen” states  Low doses can work very well  Don’t have to wait too long for results  Low side effect profile  Cheap

33. Citalopram for Repetitive Behaviors King et al. (2009) Arch Gen Psychiatry

34. Risperidone for Irritability McCracken et al. (2002) NEJM

35. Anxiolytics  Family includes benzodiazepines, and antihistamines  These medications can cause disinhibition and irritability  Sometimes used in conjunction with antidepressants  Sometimes used in children

36. Meds…The Ultimate Solution??

37. 10 Minute Break

38. Video Examples of Anxiety in ASDs

40. What is RI-CART? The Rhode Island Consortium for Autism Research and Treatment

41. My Home Autism Spectrum Disorders Clinic Child Psychiatry Consultation Service Brown Center for the Study of Children at Risk Women and Infants’ Hospital (401)274-1122 x 8935 tlevine@wihri.org