Introduction to Autism Spectrum Disorders History and Neurobiology

1. Introduction to Autism Spectrum DisordersHistory and Neurobiology William C. Streusand, M.D. Medical Director, Texas Child Study Center Chief of Psychiatry, Dell Children’s Medical Center Co-Medical Director, Seton Healthcare Autism Research and Evaluation (S.H.A.R.E.)

2. Autism as a Schizophrenic AttributeBleuler • Eugen Bleuler(1857-1939)-dementia praecox changed to schizophrenia • Bleuler coined the word autismus (English translation autism) in 1910 • Bleuler’s 4 A’s: Autism Associations Affect Ambivalence

3. D.B. Klein, 1944 Henry Holt & Co, Inc.

4. D.B. Klein, 1944Henry Holt & Co, Inc. • P 359,”In technical language, much of our thinking is dereistic or, as it is sometimes called, “autistic”.The latter adjective stresses the part played by the self in encouraging the impulsive drift of ideas and beliefs in line with wishful fantasy.” • P 475,autistic, directed inward toward the self; in line with private longings or wishes (Contrasted with realistic; hence dereistic, q.v.)

5. DSM I-1952 • 000-x28 Schizophrenic reaction, childhood type Here will be classified those schizophrenic reactions occurring before puberty. The clinical picture may differ from schizophrenic reactions occurring in other age periods because of the immaturity and plasticity of the patient at the time of onset of the reaction. Psychotic reactions in children, manifesting primarily autism, will be classified here. Special symptomatology may be added to the diagnosis as manifestations.

6. DSM II-1968 • 295.8* Schizophrenia, childhood type* This category is for cases in which schizophrenic symptoms appear before puberty. The condition may be manifested by autistic, atypical, and withdrawn behavior; failure to develop identity separate from the mother's; and general unevenness, gross immaturity and inadequacy in development. These developmental defects may result in mental retardation, which should also be diagnosed. (This category is for use in the United States and does not appear in ICD-8. It is equivalent to "Schizophrenic reaction, childhood type" in DSM-I.)

7. Leo Kanner(1894-1981)

8. Kanner-1943 • The June 1943 issue of the now extinct journal The Nervous Child carried a paper entitled Autistic Disturbances of affective contact • The patients were between 2 and 8 years old when first seen at the Children's Psychiatric Clinic of the Johns Hopkins Hospital • Description of 11 children with previously undescribed syndrome • Traits these children presented with included: • Inability to relate to others • Failure to use language to convey meaning • Need for maintaining consistency

9. Kanner’s Missed Concepts • Thought that Autism was not associated with other medical conditions • Thought that Autistic children were not intellectually disabled • Thought high social class parents • Ambivalent representation about nature vs. nurture- noted both biological predisposition and “genuine lack of maternal warmth” • In interview referred to autistic parents as "just happening to defrost enough to produce a child“ but in 1969 felt he was mistakenly quoted that “it was all the parent’s fault” and asserted that condition was innate

10. Hans Asperger(1906-1980)

11. Asperger-1944 • Originally called the condition Autistic Psychopathy implying stability over time • Poor non-verbal communication and appreciation • Odd verbal communication-tone and content, “little professors” • Special obsessional interests that would lead to high level adult accomplishments • Clumsiness and poor body awareness • Conduct problems • Familial condition • Male predominance, not recognizable before 3

12. Refrigerator Mom • Popular 50’s through 70’s • Bruno Bettelheim (1903 –1990) , University of Chicago wrote in1967 The Empty Fortress: Infantile Autism and the Birth of the Self • Took autistic children out of their home long term to correct the problem

13. Spectrum? • Autism and Asperger’s not proposed as a spectrum until Lorna Wing in 1981 • DSM III(1980)-infantile autism & PDD, residual autism • DSM III-R(1987)-autistic disorder (broader spectrum criteria), PDD-NOS, Asperger’s as a mild variant of Autism • Is Asperger’s a linearly less severe variant of autism or is it (and possibly some other conditions) a side branch on the severity line? • What are the distinctions between high functioning autism and Asperger’s?

14. DSM IV • Meeting Criteria For Autism: • Individual must show at least 6 of the 12 symptoms • At least 2 symptoms from the social domain • At least 1 symptom from the communication domain • At least 1 symptom from the restricted behaviors/interest domain • Delays or abnormal functioning in at least one of the following areas, with onset prior to age 3 years: (1) social interaction, (2) language as used in social communication, or (3) symbolic or imaginative play • The disturbance is not better accounted for by Rett's Disorder or Childhood Disintegrative Disorder • American Psychiatric Association. (2000).Autism. Diagnostic and statistical manual of mental disorders (4th ed. text revision, pp. 59 – 61). Washington, D.C.

15. Social Interaction • (1) qualitative impairment in social interaction, as manifested by at least two of the following: • (a) marked impairment in the use of multiple nonverbal behaviors such as eye-to-eye gaze, facial expression, body postures, and gestures to regulate social interaction(b) failure to develop peer relationships appropriate to developmental level(c) a lack of spontaneous seeking to share enjoyment, interests, or achievements with other people (e.g., by a lack of showing, bringing, or pointing out objects of interest)(d) lack of social or emotional reciprocity • American Psychiatric Association. (2000).Autism. Diagnostic and statistical manual of mental disorders (4th ed. text revision, pp. 59 – 61). Washington, D.C.

16. Communication • (2) qualitative impairments in communication as manifested by at least one of the following: • (a) delay in, or total lack of, the development of spoken language (not accompanied by an attempt to compensate through alternative modes of communication such as gesture or mime)(b) in individuals with adequate speech, marked impairment in the ability to initiate or sustain a conversation with others(c) stereotyped and repetitive use of language or idiosyncratic language(d) lack of varied, spontaneous make-believe play or social imitative play appropriate to developmental level • American Psychiatric Association. (2000).Autism. Diagnostic and statistical manual of mental disorders (4th ed. text revision, pp. 59 – 61). Washington, D.C.

17. Narrow Interests/Repetitive Behaviors • (3) restricted repetitive and stereotyped patterns of behavior, interests and activities, as manifested by at least two of the following: • (a) encompassing preoccupation with one or more stereotyped and restricted patterns of interest that is abnormal either in intensity or focus(b) apparently inflexible adherence to specific, nonfunctional routines or rituals(c) stereotyped and repetitive motor mannerisms (e.g., hand or finger flapping or twisting, or complex whole-body movements)(d) persistent preoccupation with parts of objects • American Psychiatric Association. (2000).Autism. Diagnostic and statistical manual of mental disorders (4th ed. text revision, pp. 59 – 61). Washington, D.C.

18. Other Diagnoses Where You Are Doing Great-Then You’re Not • Childhood Disintegrative Disorder • Rett’s Disorder • Very Early Onset Schizophrenia • Some Genetic/Metabolic Diseases

19. DSM V Autistic Disorder(299) • Must meet criteria 1, 2, and 3: • 1.  Clinically significant, persistent deficits in social communication and interactions, as manifest by all of the following: • a.  Marked deficits in nonverbal and verbal communication used for social interaction: • b.  Lack of social reciprocity; • c.  Failure to develop and maintain peer relationships appropriate to developmental level • 2.  Restricted, repetitive patterns of behavior, interests, and activities, as manifested by at least TWO of the following: • a.  Stereotyped motor or verbal behaviors, or unusual sensory behaviors • b.  Excessive adherence to routines and ritualized patterns of behavior • c.  Restricted, fixated interests • 3.  Symptoms must be present in early childhood (but may not become fully manifest until social demands exceed limited capacities)

20. DSM V Autistic Disorder(299) Replaces • PDD-NOS • Aperger’s • Childhood Disintegrative Disorder • Old Autistic Disorder Criteria • Gone- Rett’s

21. Rationale • Three domains become two: 1)     Social/communication deficits 2)     Fixated interests and repetitive behaviors • Deficits in communication and social behaviors are inseparable and more accurately considered as a single set of symptoms with contextual and environmental specificities • Delays in language are not unique nor universal in ASD and are more accurately considered as a factor that influences the clinical symptoms of ASD, rather than defining the ASD diagnosis • Requiring both criteria to be completely fulfilled improves specificity of diagnosis without impairing sensitivity • Providing examples for subdomains for a range of chronological ages and language levels increases sensitivity across severity levels from mild to more severe, while maintaining specificity with just two domains • Decision based on literature review, expert consultations, and workgroup discussions; confirmed by the results of secondary analyses of data from CPEA and STAART, University of Michigan, Simons Simplex Collection databases

22. Understanding Autism-Eye Tracking Studies • Klin, Jones, Schultz, Volkmar, & Cohen(2002) defining and quantifying the social phenotype in autism. American Journal of Psychiatry, 159(6), 895-908 • Controls vs. High Functioning Autistic Young Adults • Scenes from emotionally evocative movie • Focus of gaze on eyes vs mouth

23. Understanding Asperger’s-Case Study • Speech • Concreteness • Special Interests • Socialization

24. Neurobiology-Many Questions, Too Many Partial Answers • Increased head Circumference/Brain Size • Temporal Lobe-excessive methylation of oxytocin receptors • Amygdala- small size, damaged can show problems with: recognizing facial expressions, detecting social faux pas, judging trustworthiness, attributing social intention • Cerebellum-reduced Purkinje cell complexity, some areas with smaller size • Mitochondrial Dysfunction

25. Neurobiology-Many Questions, Too Many Partial Answers-2 • Frontal Lobe-Connectivity problems from epigenetic factors changes in factors that influence gene expression • Orbitomedial and Ventromedial Prefrontal Cortex-lesions produce social inappropriateness • Fusiform (gyrus) Facial Area (FFA)-decreased activity in autism in fMRI studies

26. Genetics-NIMH Sponsored Studies From Pooled Genetic Database • Mutation-one percent of autism was traced to a conspicuous "hot spot" of missing or duplicated genes on Chromosome 16 • Inherited-people with autism were more prone than healthy controls to have certain versions of a gene on Chromosome 7 , 1% of ASD • Chromosome 15 abnormalities in higher incidence

27. Proposed Environmental Etiologies • MMR Vaccines-multiple studies dispute this assertion statistically “It may be concluded that it is quite implausible that MMR is generally associated with a substantially increased risk of autism. It is not possible to rule out the possibility that there may be occasional idiosyncratic responses to MMR that involve autism, but there is no good evidence that this happens.” Michael Rudder( Volkmar, et. al., 2005)

28. Proposed Environmental Etiologies • Thimersol (contains ethyl mercury, vaccine preservative)- Large demographic study from Denmark showed discontinuation of this substance was followed by an increase incidence in autism in 1992 • Food allergies-Gluten-free/Casein-free diet; no clear scientific support for benefit, anecdotal only, ? of possible vitamin deficiency if not supplemented • Leaky Gut Syndrome/Autistic Enterocolitis- Andrew Wakefield suggested, generally not currently thought to be credible

29. Meanwhile……. • According to the Center for Disease Control 1 in 110 children have an Autism Spectrum Disorder • Boys-1 in 80 • Girls- 1 in 315 • Percent of ASD Children with intellectual disability is 44% • Average age of diagnosis is 4.6 years

30. ASD Mission It Is Not A Choice of Whether In Central Texas We Will Address the Problems of Autism Spectrum Children and Their Families It Is Only a Choice of Whether We Will Do It Excellently or Poorly

31. Thank You For Attending Our First Autism Spectrum Disorders Conference...........Enjoy!!!

32. Interesting Links • http://psych.rice.edu/mmtbn/autism/autismTheory.html • http://www.autismspeaks.org/ • http://www.nimh.nih.gov/health/topics/autism-spectrum-disorders-pervasive-developmental-disorders/index.shtml • http://www.cdc.gov/ncbddd/features/counting-autism.html