P s y c h i a t r i c C o m o r b i d i t y w i t h ASD Attention-Deficit/Hyperactivity Disorder

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1 P s y c h i a t r i c C o m o r b i d i t y w i t h ASD Attention-Deficit/Hyperactivity Disorder GAGAN JOSHI, MD Assistant Professor of Psychiatry Director, Autism Spectrum Disorder Program Clinical & Research Program in Pediatric Psychopharmacology Massachusetts General Hospital, Harvard Medical School

2 Disclosures My spouse/partner and I have the following relevant financial relationship with a commercial interest to disclose: Research Support: PI for Investigator-Initiated Studies: -National Institute of Mental Health (NIMH) grant Award #K23MH145 -Pfizer pharmaceuticals Site PI for Multi-Site Studies: -Simons Center for the Social Brain -Duke University -Forest Research Laboratories -Sunovion pharmaceuticals Co-Investrigator for Clinical Trials: -U.S. Department of Defense -Merck Schering Plough Corporation -Pamlab LLC. Honoraria: -Governor s Council for Medical Research and Treatment of Autism in New Jersey -American Academy of Child and Adolescent Psychiatry -Medical Society of Delaware -Simons Foundation

3 N e u r o d e v e l o p m e n t a l D i s o r d e r s ASD a n d A D H D Shared Characteristics ASD Prevalence in Children 6-8% 2% Heritability Estimates 75% >9% Male:Female Ratio 2.5:1 4:1 Manifest early in life Yes Yes Lifelong Disorders Yes Yes

4 C o r e D i a g n o s t i c F e a t u r e s o f A S D a n d A D H D ASD Symptom Triad Impaired social interaction Impaired social communication Restricted Repetitive Behaviors Inattention Hyperactivity Impulsivity

5 Historical Perspective: Co-occurrence of and ASD Majority of ASD recognized in populations with Intellectual Disability Considered as an associated feature of ASD Ability to hyper-focus on preferred activities rules out Poor response to anti- medications

6 I m p l i c a t i o n s o f U n r e c o g n i z e d R e c i p r o c a l C o m o r b i d i t y Impairs intellectual/school performance Further worsens already compromised social functioning Interferes with ASD specific behavioral interventions Leads to attempts to treat with ASD specific interventions Fails to receive disorder specific treatment Increases risk for developing other psychiatric conditions (disruptive behaviors & substance abuse) ASD Risk of receiving inappropriately aggressive treatment for psychopathology Failure to recognize atypical precipitants negatively affecting psychopathology Failure to receive treatment specific for ASD Miss opportunity to implement early interventions for ASD 1/17/217 6

7 Prevalence of Significant ASD Traits/Dx in Referred Populations with ASD Traits ASD Diagnosis Clark et al., 1999 *Kochhar et al., 211 *Cooper et al., 214 *Grzadzinski et al., 211 *Mulligan et al., 29 Reirsen et al., 27 *Kotte et al., 213 Joshi et al., 213 Jensen & Steinhausen, 214 Faber et al., 21 18% - 63% Larson et al % - 15% Smalley et al. 27 Percentage * Youth with no prior diagnosis of ASD Percentage

8 A u t i s t i c Tr a i t s i n R e f e r r e d Yo u t h Research Participants Total N: 242 Age Range: 6-18 years IQ: >7 18% Significant Autistic Traits CBCL-ASD Profile + for ASD: 18% (N=44)

9 % Endorsed % Endorsed A D H D S y m p t o m P r o f i l e i n t h e P r e s e n c e o f A u t i s t i c T r a i t s DSM-III-R Symptoms (N=198) +CBCL-AT (N=44) Difficulty remaining seated Fidgety Difficulty playing quietly Talks excessively Shifts activities Difficulty sustaining attention Difficulty following instruction Easily Interrupts or Blurts out distracted intrudes answers Difficulty waiting turn Acts before thinking DRS F DPQ TE SA DSA DFI ED IOI BOA DWT ABT LT DL Additional Symptoms (N=15) +CBCL-AT (N=26) a* a* a** a** a* a vs. ; Statistical Significance: *p.5, **p.5 Accidents Accidents Messy Messy or or Sloppy Sloppy Clumsy Clumsy Hyperactive Hyperactive Equally Equally Inattentive & Onset Onset Before Before Age Age 5 5 Fighting Fighting with with Other Other Rejection by Other Rejection by Other Inattentive Hyperactive& Peers Peers Peers Peers Hyperactive Loses things Doesn t listen

10 Social Disability on SAICA (%) S o c i a l D i s a b i l i t y A s s o c i a t e d w i t h A D H D + AT Social Disability in Youth with ±AT per Social Adjustment Inventory for Children & Adolescents [SAICA] % ** 68% +AT Statistical Significance: *p.5, **p.1, ***p.1

11 Prevalence of ED (%) E m o t i o n a l D y s r e g u l a t i o n A s s o c i a t e d w i t h A D H D + A T Emotional Dysregulation [ED] in Youth with ±AT per CBCL-ED Profile* *[composite T-scores of the Attention, Aggression, & Anxious/Depressed subscales] % ** 93% CBCL-ED [ 18] 39% 2% CBCL-Moderate ED [ 18 - <21] 6% *** 73% CBCL-Severe ED [ 21] Statistical Significance: *p.5, **p.1, ***p.1

12 P s y c h i a t r i c D i s o r d e r s A s s o c i a t e d w i t h A D H D + A T Lifetime Psychiatric Comorbidity Disruptive Behavior Disorders ** Mood Disorders Multiple Anxiety Disorders ** * ** * +A T Substance Use Disorders * Percentage Statistical Significance: *p.5, **p.1, ***p.1

13 Prevalence of Significant Symptoms/ Dx in Populations with ASD Symptoms Diagnosis Sverd et al., 1995 Lee & Ousley, 26 Sturm, et al., 24 Tani et al., 26 Yoshida & Uchiyama, 24 Holtmann et al., 25 Goldstein & Schwebach, 24 Gadow et al., 24 49% - 88% Frazier et al., 21 Joshi et al., 21 Wozniak et al., 1997 Sinzig et al., 29 DeBruin et al., 27 Mattila et al., 21 Leyfer et al., 26 Gjevik et al., 211 Simonoff et al., 28 28% - 83% Percentage Percentage

14 C o m o r b i d i t y a s s o c i a t e d w i t h ASD Comorbidity in US population-based sample of ASD 25 (Medical records of children 8 years old reviewed by trained clinicians) 21% 21% % 16% 15 % 1 6.5% 5 4% Medical Diagnosis Neurologic Diagnosis Intellectual Disability Learning Disorder Other Psychiatric Disorders

15 Psychiatric Comorbidity with ASD in Youth Attending Specialty & General Psychiatry Clinics Lifetime Psychiatric Comorbidity Attention-deficit/Hyperactivity Disorder Oppositional Defiant Disorder Conduct Disorder *** Multiple ( 2) Anxiety Disorders Major Depressive Disorder Bipolar I Disorder Psychosis Substance Use Disorders Cigarette Smoking *** *** Psychiatry Clinic Referred ASD Specialty Clinic Referred ASD Percentage Statistical Significance: *p.5, **p.1, ***p.1

16 Psychopathology Associated with ASD in Psychiatrically Referred Populations Lifetime Psychiatric Comorbidity Youth Attention-deficit/Hyperactivity Disorder Oppositional Defiant Disorder Conduct Disorder Adults *** Multiple ( 2) Anxiety Disorders *** Major Depression Bipolar I Disorder *** Psychosis *** 2 1 Substance Use Disorders % ASD NON-ASD Statistical Significance: ***p.1 Joshi et al., 21, 213

17 Clinical Correlates of in Youth with ASD Demographic Characterization Demographics ASD+ p-value Total (N) Age (years) 11 ± ±3.2.5 Gender (Male) 94 (88%) 57 (77%).5 Race (Caucasian) 88 (83%) 67 (91%).2 Socioeconomic status 2 ± ±.62 <.1 Full scale IQ Mean 97 ±14 12 ±16.3 IQ range >85 85 (79%) 62 (84%).5 Values expressed as N (%) or Mean ±Standard Deviation; IQ=Intelligence Quotient Subtypes of ASD (N = 17) 24% 14% 62% Autistic Disorder Asperger's Disorder PDD-NOS

18 % % P r e v a l e n c e o f A D H D C o m o r b i d i t y w i t h A S D 1 Lifetime 1 Current (Last month) 8 *** 79% 8 ** 76% 66% 65% ASD Psychopharmacology Clinic Population (N = 271) GENERAL Psychopharmacology Clinic Population (N = 264) ASD Psychopharmacology Clinic Population (N = 253) GENERAL Psychopharmacology Clinic Population (N = 231) Statistical Significance: *p.5, **p.1, ***p.1

19 Percent with Symptom A D H D S y m p t o m P r o f i l e i n A S D 1 8 ** +ASD ** ** * ** * Careless/ Sloppy Doesn't listen Difficulty organizing tasks/ activities Loses things Forgetful in daily activities Fidgets/ Squirms Physically restless On the go/ Driven by a motor Blurts out answers Interrupts/ Intrudes Inattentive Symptoms Statistical Significance: *p.5, **p.1, ***p.1 Hyperactive/Impulsive Symptoms

20 Percentage Mean # of Symptoms P r o f i l e o f A D H D i n A S D 75 6 Subtypes of ** 57% * 59% # of Symptoms % 41% * % 2% 4 2 ASD+ ASD+

21 Rates of (%) Distribution of by ASD Subtype % 77% 76% Autistic Disorder Asperger's Disorder PDD-NOS (N=185) (N=44) (N=42)

22 Percentage SRS Severity Mean Score Severity Profile of Comorbid & ASD ASD 6 ASD+ 1 ASD+ ASD 5 4 5% 47% 45% 42% % 8% 2 Mild Moderate Severe

23 Percentage GAF Mean Score L e v e l of Functioning School Functioning 19% 11% 77% 8% *** 51% 23% Global Functioning * 46±5 48±8 * 51±5 53±6 Repeated Grades Extra Tutoring Special Classes 2 GAF-Lifetime GAF-Current ASD+ ASD+ Statistical Significance: *p.5, **p.1, ***p.1

24 Percentage A D H D Tr e a t m e n t H i s t o r y i n A S D 5 4 * 41% 43% 3 24% 27% * 26% 2 * 15% 18% 1 Treatment Naïve 5% Counseling Only ASD+ Pharmacotherapy Only Counseling + Pharmacotherapy Statistical Significance: *p.5, **p.1, ***p.1 undertreated in youth with ASD

25 Mean Score Mean Score 1/17/ Neuropsychological Correlates of HF -ASD Processing Speed Wechsler Adult Intelligence Scale (WAIS-III) *** AB [VALUE ] HC [N=52] [N=52] Cognitive Flexibility Delis Kaplan Executive Function System 11 (D-KEFS) *** 1 *** *** AB AB AB [VALUE] [VALUE] [VALUE] Processing Speed Index Number-Letter Switching Trail Making Subtest Inhibition Colour-Word Interference Subtest Switching Colour-Word Interference Subtest A=Versus HC, B=Versus ; Statistical Significance: *p.5, **p.1, ***p.1 HC=Healthy Controls

26 I n Summary.. ASD+: Prevalence & Presentation Greater than expected rates of in youth with ASD is the most common psychopathology associated with ASD The clinical presentation of in youth with ASD is typical of the disorder ASD youth with are significantly more impaired in their various indices of psychosocial functioning Significantly fewer ASD youth receive targeted treatment for

27 A c k n o w l e d g m e n t s T h e A l a n a n d L o r r a i n e B r e s s l e r C l i n i c a l a n d R e s e a r c h P r o g r a m f or Autism Spectrum Disorder Massachusetts General Hospital Boston MA Joseph Biederman, MD Janet Wozniak, MD Atilla Ceranoglu, MD Lynn Grush, MD Amy Yule, MD Carrie Vaudreuil, MD Robert Doyle, MD Sheeba A. Anteraper, PhD Kaustubh R. Patil, PhD Stephen Faraone, PhD Ronna Fried, EdD Maribel Galdo, LCSW Maura Fitzgerald, MA Yvonne Woodworth, BA Daniel Kaufman, BS Ryan Kilcullen, BA Abigail Belser, BA Philia Henderson, BA Stefani Callinan, BS Melissa De Leon Phone: (617) MGHASDprogram@Partners.org Facebook: Facebook.com/BresslerMGH Web Link: