The History of Autism: Steps toward evidence based practice' Part III: Aetiology and management'

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The History of Autism Steps toward evidence
based practice.Part III Aetiology and
management.

• Dr. Jennifer E. Fisher M.B., B.S., MRCPsych,
  FRCP(C)
• Clinical Associate Professor
• Department of Psychiatry
• The University of Calgary
• Consultant Psychiatrist
• Developmental Clinic
• Alberta Childrens Hospital

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Learning objectives

• Participants will know the major theories
  regarding aetiology of autism.
• Knowledge about evidence based treatment and
  management strategies.
• Be familiar with outcome data.
• (summary will be available on my Web Site)

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The History of Autism Steps toward evidence
based practice.

• Part I History what have we learned?
• Part II Evidence based practice diagnosis,
  prevalence, comorbidities.
• Part III Evidence based practice aetiology,
  management and prognosis.

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Introduction in Part I we learned

• with DSM IV there seemed to be diagnostic
  consensus.
• Autistic Disorder
• Retts Disorder
• Childhood Disintegrative Disorder (CDD)
• Aspergers Disorder (AD)
• Pervasive Developmental Disorder NOS
• . But this was soon complicated by
• An explosion of new diagnoses
• A reported huge increase in the prevalence of ASD
• Confusion about whether this was an actual
  increase in numbers or due to diagnostic
  substitution (e.g. with MR)

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The new diagnoses of the 1980s 1990s

• High functioning autism
• Sensory Integration Disorder
• Regulatory Disorder of Infancy
• Non-verbal Learning Disability
• Right Hemisphere Syndrome in Children
• Hyperlexic Syndromes
• Visual Spatial Motor Disorder
• DAMP (deficits in attention, motor control,
  memory and perception)
• Multiplex Developmental Disorder
• Pragmatic Language Disorder

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In Part II we noted that the ADOS and ADI

• . were robust and valid instruments for
  Classical Autism (Kanners syndrome) and
  Aspergers Syndrome.
• . but less validity and specificity with the
  high end of the spectrum HFA, atypical autism,
  NVLD, sensory issues, pragmatic language
  disorder.
• Reliability and Accuracy of Differentiating
  Pervasive Developmental Disorder Subtypes.
  Mahoney, WJ., Szatmari, P. et al. Journal of the
  American Academy of Child Adolescent
  Psychiatry. 37(3)278-285, March 1998.
• Exploring the borderlands of autistic disorder
  and specific language impairment a study using
  standardised diagnostic instruments. Bishop, D.
  V. and C. F. Norbury (2002). Journal of Child
  Psychology Psychiatry Allied Disciplines,
  43(7), 917-29.

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Historically the search for the cause has been
impacted and slowed by

• conceptual and definitional problems
• methodological problems
• study population selection
• shifting ideas on prevalence
• the heterogeneity of the phenotype
• the absence of biological markers
• what do we do with the new diagnoses?
• The most reliable studies have been conducted
  with children with Kanners syndrome and
  Aspergers syndrome.

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Aetiology

• Most now agree there is compelling evidence for
• abnormal brain development resulting in regional
  brain abnormalities at the gross and
  microanatomical levels and at the biochemical and
  neurophysiological levels
• strong genetic influences

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Not only was there an explosion in
diagnosesbut also in theories of causation

• numerous genetic conditions with "autistic like"
  symptoms (congenital rubella, tuberous sclerosis,
  phenylketonuria, fragile X and many others)
• heavy metals toxicity lead, Hg
• abnormalities in trace elements
• environmental pollution
• infection candida albicans etc
• prenatal viral brain infection
• prenatal alcohol exposure
• immunizations (MMR)
• hypoglycaemia and malabsorption

• electromagnetic radiation
• ultrasound in pregnancy
• a seizure variant
• "starving brains" nutritional causes
• allergies to all and everything
• a variant of attachment disorder
• psychodynamic causes
• GI causes gluten
• prenatal and perinatal injury / hypoxia
• etc

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Genes of Autism  Where Are The Genes? (Web link)
Dr. Francois Bernier (March 8th 2006)

• Idiopathic (95)
• essential autism 70 (Kanners Syndrome)
• complex autism 30 (with comorbidities)
• Secondary (5) (?autism or autistic like
  phenotype)
• chromosomal and single gene
• environmental influences
• (Miles, Am J Med Genet 2005)

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Evidence for the genetic influence from(Bernier)

• Twin studies (Folstein, Steffenburg, Bailey)
• MZgtDZ (90)
• Familial aggregation
• family clustering of siblings for autism, AS,
  atypical
• Other genetic strategies
• autism genome project
• molecular studies
• genome scans assesses all chromosomal regions
  for linkages, linkage studies basically a
  statistical method of determining if a region of
  the genome relates to the phenotype
• candidate gene strategies - focus on candidate
  genes for which there is functional evidence of
  aetiological involvement e.g. 5HT observations.

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Genetics

• Veenstra-Vanderweele, J., Cook, EH.
• Genetics of Childhood Disorders, XLVI, Part 5
  Genetics of Autism.
• J. AM. Acad. Child Adolesc. Psychiatry. 421,
  January 2003.
• MZ twin of patient with autism 60 chance of
  autism
• 90 chance of ASD
• DZ twin of patient with autism 4.5 of autism
• (about the same as a sibling)
• General population risk 0.2

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A wider familial phenotype?

• Heritability for ASD 90
• After one affected sib recurrence 5 8
  (Bernier)
• 10 15 for broader familial phenotype
• Family clustering of
• Obsessive compulsive disorder
• Anxiety disorders
• Social avoidance
• Motor problems
• Particular occupations
• Never married

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Genetics conclusions

• There is no doubt there is a substantial genetic
  component
• Molecular genetics are promising but limited
  success so far
• Interest in chromosome 15
• .. and interest in chromosome 7 and language
  disorders
• Genetics of a wider familial phenotype???
• Two most informative papers I have read
• GENETICS OF AUTISM COMPLEX AETIOLOGY FOR A
  HETEROGENEOUS DISORDER
• Folstein, SE., Rosen-Sheildley, B. Nature Reviews
  Genetics 2, 943-955. 2001
• The Genetics of Autism(Web Link)
• Muhle, R., Trentacoste, SV., Rapin, I.PEDIATRICS
  Vol. 113 No. 5 May 2004, pp. 472-486

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A question?

• Is it categorically defined disorders (e.g.
  autism, Aspergers syndrome) that are inherited
  .
• or
• Dimensionally defined traits, such as
  obsessions, shyness,
• anxiety, 5HT transporter gene abnormalities,
  facial recognition or facial affect processing,
  that are inherited?
• with
• Differing doses of each resulting in the
  spectrum of disorder
• (functional psychopathology)

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Genetics
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Early findings

• Increase in MPAs
• Brain size increased by 5 10
• (Kanner, 1943. Enlarged head circumference in 5
  of the 11 children - "rediscovered" in 1998!
  Bailey A., Palferman S, Heavy L, Le Couter A.
  Autism the phenotype in relatives. J Autism
  Develop Dis 19 19-31
• Reduced size of corpus callosum
• Post mortem studies fewer Purkinjie and granule
  cells in the cerebellum
• Increased incidence of seizures
• Abnormal EEGs often nonspecific
• Studies were inconsistent with numerous
  non-replicated reports
• No biological markers were identified

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More questions than answers

• Nearly every neural system has been proposed
• The social, language and behavioural problems
  suggest the syndrome effects functionally diverse
  and widely distributed sets of neural systems
• At the same time, the effected systems must be
  discrete because autism spares many perceptual
  and cognitive systems for example autistic
  children can have normal intellect and superior
  visual perceptual skills

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More questions than answers

• It is not known whether all brain systems are
  equally involved or specific areas or whether
  this is prenatal or postnatal (e.g. if prenatal
  ?glial cell disturbances, ?cell proliferation,
  ?neuronal migration, ?apoptosis)
• It is that the initial insult is localized
  branching off into more pervasive impairments
  because of the highly interdependent nature of
  early developmental processes and unknown
  interactions with the environment?

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More questions than answers

• Given that 70 of children with Kanners
  syndrome have MR it is a considerable challenge
  to disentangle the causative processes specific
  to autism from the
• ubiquitous confound of cognitive disability
• Genetics of Childhood Disorders XLIII
• Autism, Part 2 Neural Foundations
• Schultz, RT., Klin, A
• J. Am. Acad. Child Psychiatry, 4110, October 2002

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Tantalizing hints?

• While over the last 15 years the phenotypic and
  etiologic complexities have contributed to
  numerous non-replicated reports, important and
  consistent findings in the MRI literature are now
  beginning to emerge which elucidate the
  neurodevelopmental underpinnings and brain
  behaviour relationships in this disorder
• Structural and functional magnetic resonance
  imaging of autism
• Cody, H., Pelphrey, K., Pivin, J.
• Int. J. Devl Neuroscience 20 (2002) 421-438
• Synonyms for tantalizing
• enticing, tempting, tormenting,
• alluring, teasing, beguiling

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• Neuroimaging techniques (MRI, fMRI, MRS, PET and
  MEG) are beginning to suggest something about
  the neural systems that may be involved.
• These include brain areas responsible for
• Emotional and social function
• Perceptual systems specific to face and affect
  recognition
• Social-cognitive systems involved in social
  reciprocity

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• The current working hypothesis
• A limbic system abnormality, involving
  especially the amygdala and its functional
  partners the temporal and frontal cortices

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Areas of interest

• Limbic system
• Amygdala
• Hippocampus
• Septum
• Anterior cingulate
• Mamillary bodies
• Temporal Lobe
• Fusiform gyrus
• Pre-frontal cortex

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Amygdala

• Has a critical role in
• Emotional arousal
• Assigns significance to environmental stimuli
• Mediates formation of visual-reward associations
• (emotional learning)
• Numerous afferent and efferent connections to
  temporal lobes

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AMYGDALA

• Japanese band, heavily Zeuhl-influenced - a
  landmark of the greatest Japanese bands of these
  last few years. Almost all instrumental, the
  line-up features drums, bass, synths, piano,
  guitar occasional other instruments.
• Dark, pulsating and complex, their music
  combines powerful rock energy and the complex
  rythmical patterns of Magma.

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Temporal lobes

• Deficits in
• Facial recognition
• Discrimination of faces
• Understanding facial expression
• fMRI and lesion data reveal consistent evidence
  of hypoactivation of the fusiform gyrus
  (replicated).
• Emotional Attribution in High Functioning
  Individuals with Autistic Spectrum Disorder A
  Functional Imaging Study. Piggot, J et al. J. Am.
  Acad. Child Adolesc. Psychiatry, 434, April 2004
• Neural Correlates of Facial Affect processing in
  Children and Adolescents with Autism Spectrum
  Disorder. Ting Wang, A et al. J. Am. Acad. Child
  Adolesc. Psychiatry. 434, April 2004

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Frontal lobes

• Older studies (neuropsychological) suggested
  general hypoactivation
• In the last 10 years data is converging to show
  that sub-regions of the prefrontal cortex (the
  orbital and medial prefrontal cortices) have
  especially rich reciprocal connections with the
  limbic system (especially the amygdala) and are
  critical for social cognition that is,
  thinking about thoughts, feelings and
  intentions.
• Genetics of Childhood Disorders XLIII
• Autism, Part 2 Neural Foundations
• Schultz, RT., Klin, A
• J. Am. Acad. Child Psychiatry, 4110, October 2002

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Theory of MindBaron-Cohen (and others)

• Being able to infer the full range of mental
  states (such as desires, intentions, imagination,
  emotions, etc.) that cause action.
• Once an individual is able to reflect on the
  contents of ones own mind and the minds of
  others, that individual has developed a theory of
  mind.
• Understanding the mental states of others allows
  individuals to make sense of past behaviour,
  allows influence on present behaviour and permits
  prediction of future behaviour.
• This ability to predict the behaviour of others
  is a crucial component of social skill
  development.
• Does the autistic child have a "theory of
  mind"?Baron-Cohen S, Leslie AM, Frith U.
  Cognition. 1985 Oct21(1)37-46.

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Post mortem studies (few studies)

• Findings are widespread
• Changes in size, density and dendritic
  arborization in amygdala, hippocampus, septum,
  anterior cingulate, mamillary bodies. Neurons are
  densely packed and unusually small suggesting a
  curtailing of normal development
• Frontal lobe cortex volume is increased and
  correlates with the degree of cerebellar
  abnormality.
• Reduced size of corpus callosum
• Fewer Purkinjie /granule cells in the cerebellum
• Cerebellar gliosis.
• Megalencephaly.
• Inverse correlation between frontal lobe and
  cerebellum sizes in children with autism. Ruth A.
  Carper, RA., Courchesne, E. Brain, Vol. 123, No.
  4, 836-844, April 2000
• A clinicopathological study of autism. Bailey et
  al. MRC Child Psychiatry Unit, Institute of
  Psychiatry, London, UK Brain. 1998 May121 ( Pt
  5)889-905.

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• Lesions placed in the amygdala of less than one
  year old monkeys results in symptoms very close
  to human autism. Lesions in adult monkeys fail
  to do this.
• Neuropathology of infantile autism. Kemper TL,
  Bauman ML.
• Mol Psychiatry. 20027 Suppl 2S12-3.

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Web link

• Neurofunctional Models of Autistic Disorder and
  Asperger Syndrome Clues from Neuroimaging
• RT. Shultz, Ph.D. , LM. Romanski, Ph.D. , and K
  Tsatsanis, Ph.D.
• Child Study Center, Yale University, New Haven,
  CT , Section of Neurobiology, Yale University
  School of Medicine, New Haven, CT
• In A. Klin, F.R Volkmar S.S Sparrow (Eds.)
  Asperger Syndrome.
• New York Guilford Press, 2000, 172-209

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Aetiology

• Attachment Disorder and Maternal deprivation
• (Bowlby J. The making and breaking of
  affectional bonds. I. Aetiology and
  psychopathology in the light of attachment
  theory. An expanded version of the Fiftieth
  Maudsley Lecture, delivered before the Royal
  College of Psychiatrists, 19 November 1976. The
  British Journal of Psychiatry 130 201-210
  (1977)
• Psychosocial dwarfism
• (Money J, Anneselle C. IQ changes following
  changes in domicile in the syndrome of reversible
  hyposomatotropinism (psychosocial dwarfism).
  Psychoneuroendocrinology 1 427-429, 1976)
• Refrigerator mothers
• (Bruno Bettelhiem The Empty Fortress. Infantile
  Autism and the Birth of the Self 1967)
• (Web link)
• Article on non-maternal care and autism and early
  narcissistic injury

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Is there evidence to implicate environmental
factors and brain anatomy / function?

• The feral child
• Child maltreatment
• Post Traumatic Stress Disorder
• Obsessive Compulsive Disorder and Cognitive
  Behavioural Therapy

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The Feral Child

• Reared by wolves or other wild animals.
• Mute, walk on all fours, insensitive to cold and
  eat only raw food.
• Numerous cases described in the 18th and 19th
  centuries, especially in India.
• Ireland (1875) described them as idiots who had
  been abandoned by impoverished parents and that
  idea that cruel animals would spare the
  innocents was an agreeable myth
• Tredgold felt these children had isolation
  dementia
• (Tredgold AF. A Textbook of Mental Deficiency
  (Amentia). Bailliere, Tindall and Cox. London
  1947.)

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Dr. Bruce Perry Senior Fellow, Child Trauma
Academy, Houston, Texas

• The Neuroarcheology of Childhood Maltreatment
  The Neurodevelopmental Costs of Adverse Childhood
  Events
• (Web Link)
• Childhood maltreatment has profound impact on
  the emotional, behavioral, cognitive, social and
  physical functioning of children. Developmental
  experiences determine the organizational and
  functional status of the mature brain and,
  therefore, adverse events can have a tremendous
  negative impact on the development of the brain.

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Perry The Neurodevelopmental Costs of Adverse
Childhood Events

• Events described global neglect, profound
  neglect, sensory deprivation, natural disasters
  (e.g., tornadoes, floods, hurricanes), motor
  vehicle accidents, life threatening illness and
  associated painful medical procedures (e.g.,
  severe burns, cancer), physical abuse, sexual
  assault, witnessing domestic or community
  violence, kidnapping and sudden death of a
  parent, adoptions from impoverished areas etc.
• Changes in
• Frontal occipital circumference
• CT / MRI ventricular enlargement, cortical
  atrophy, indistinct gyri
• Cognitive abnormalities (not just IQ changes)
• Delayed or absent language development
• Gross and fine motor delays

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• Heidenreich, 1834.
• Reported on a child raised in a dungeon from
  about age two to 17 years. At autopsy smooth
  brain (cortical atrophy) and few cerebral gyri.

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Post Traumatic Stress Disorder

• Chronic disorders
• Anxiety symptoms, panic, flash-backs etc
• Respond to SSRIs and CBT
• Microarchitectural and physiological changes at
  the receptor level are postulated
• Neuropsychological and fMRI studies changes in
  anterior cingulate, frontal, and thalamic
  involvement, fusiform gyrus, hippocampus
• A Functional Magnetic Resonance Imaging Study of
  Amygdala and Medial Prefrontal Cortex Responses
  to Overtly Presented Fearful Faces in
  Posttraumatic Stress Disorder. LM Shin et al.
  Arch Gen Psychiatry, 62 273-281. 2005
• Disturbance in the neural circuitry underlying
  positive emotional processing in post-traumatic
  stress disorder (PTSD) An fMRI study. Jatzko A
  et al. Eur Arch Psychiatry Clin Neurosci 256, 2
  112. 2005
• Neural Correlates of Traumatic Memories in
  Posttraumatic Stress Disorder A Functional MRI
  Investigation. Ruth A. Lanius et al. Am J
  Psychiatry 1581920-1922, November 2001

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The vaccination controversy

• The issues of regression in autism came to the
  forefront as part of the measles, mumps, rubella
  (MMR) vaccine controversy
• Wakefield (1998) described a small group of
  children with autism who had diarrhea and who
  lost previously acquired developmental skills
  after receiving MMR vaccination at 15 months.
• Taylor et al (2002) found no association
• Numerous studies since then have not confirmed an
  association
• Wakefield A. Ilial-lymphoid-nodular hyperplasia,
  non-specific colitis and pervasive developmental
  disorder in children. Lancet 1998 351637-41
• Taylor B et al. Measles, mumps and rubella
  vaccination and bowel problems or developmental
  regression in children with Autism population
  study. BMJ 2002 324393-6

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Vaccines and mercury

• There has also been controversy about the
  relation between high mercury levels in children
  with autism and the use of thimerosal in
  vaccines.
• The hypothesis is that vulnerable children will
  develop neurodevelopmental problems secondary to
  the neurotoxic effect of mercury.
• There is no evidence supporting this.
• Thimerosal has not been present in Canadian
  vaccines since 1992, except in one preparation of
  the hepatitis B vaccine that children receive at
  birth. This vaccine contains mercury levels well
  below safety estimates (12.5 mcgm Hg)
• Nelson K, Bauman M. Thimerosal and autism.
  Paediatrics 2003 111674-9

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Is autism an autoimmune disease? Ashwood P, Van
de Water. Autoimmunity Review 3 (2004), 557-562

• There is no proven cause-effect relationship
  between immune dysfunction and the development of
  Autism Spectrum Disorders.
• The results of the studies conducted so far
  remain highly speculative and theoretical.
• The findings are not consistent and there is no
  consensus among researchers about an underlying
  immune disorder in people with autism.

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Relation of childhood gastrointestinal disorders
to autism Nested case-control study using data
from the UK General Practice Research
Database.Black C., Kaye, JA., Jick, H. BMJ, 325
419-21. 2002

• Case-control study. 96 children from UK GP
  Research Database (211,480 children) who were
  later diagnosed with autism matched with 449
  controls
• Outcome Measures Documented history of
  inflammatory gastrointestinal tract disease,
  celiac disease, any food intolerance, or
  recurrent GI symptoms.
• Conclusions No evidence children with autism
  were more likely to have had a GI disorder prior
  to their diagnosis of autism.
• 9 of children with autism were found to have had
  a history of mild GI problems.
• There was no association between the time when
  the GI symptoms started and when the child
  received MMR vaccine.

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A Typical Management Plan

• Office detection / screening family doctors and
  paediatricians
• Specialist assessment / some referred on to
  Developmental Services
• Creating a multidisciplinary team
• Establishing funding for resources
• Establishing goals for language/communication
  interventions
• Establishing goals for educational intervention
• Specific behavioral approaches
• Prioritizing target symptoms/comorbid conditions
• Monitoring multiple domains of functioning
• Social intervention with family members and peers
• Monitoring target symptoms and comorbid disorders
• Monitoring medications
• FOLLOW UP

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Local Calgary Resources

• Web Links
• The Society for the Treatment of Autism
• Autism Calgary
• Both Sites contain excellent information and
  links.

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Early Intervention Programs

• Recent explosion in the development of intensive
  early intervention programs in the community, at
  school, and in the home for young children with
  autism.
• 1961
• Ferster and De Myer were among the first to
  report on the effects of behavioural intervention
  in the treatment of autism.
• Classical and operant conditioning methods
• The development of performance in autistic
  children in an automatically controlled
  environment
• Ferster, C. B., De Myer, M. K. (1961). Journal
  of Chronic Diseases, 13, 312-345

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Early intervention programs Lovaas

• Lovaas IO. Behavioral treatment and normal
  educational
• and intellectual functioning in young autistic
  children
• J Consult Clinics Psychol 1987 55 3-9
• 1987, Controlled study
• Intensive and comprehensive approach
• 40 hrs a week for 2 years during early preschool
  period.
• remarkable gains in language and IQ
• Claimed 50 of children no longer symptomatic
  (recovered)
• The gains were found to be preserved in a
  follow-up study in 1993
• Long-term outcome for children with autism who
  received early intensive behavioral treatment.
• McEachin, J. J., Smith, T., Lovaas, O. I.
  (1993). American Journal on Mental Retardation,
  97(4), 359-372 discussion 373-391.

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However

• Significant methodological issues
• No one has replicated results as dramatic as
  these other researchers using the Lovaas
  approach
• Other studies have documented improvement but not
  recovery
• UK Group
• Progress and outcomes for children with autism
  receiving parent-managed intensive interventions.
  Bibby, P., Eikeseth, S., Martin, N. T., Mudford,
  O. C., Reeves, D.
• Research in Developmental Disabilities, 23(1),
  81-104. 2002
• Parent-managed behavioral treatment for preschool
  children with autism Some characteristics of UK
  programs. Mudford, O.C., Martin, N.T., Eikeseth,
  S., Bibby, P
• Research in Developmental Disabilities, 22(3),
  173-182. 2001
• Web link
• Lovaas Institute for Early Intervention

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Reasons for lack of replication

• Poor methodology
• Poor case selection
• Many studies do not include exclusion and
  inclusion criteria
• Mixed study populations (not always
  representative)
• Treatment study protocols are difficult maintain
  in family homes
• Stressed families
• Effort after meaning
• Expensive
• Intensive 20 to 40 hours per week

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Psychosocial interventions can change the
disorders course Early intervention programs

• Involve highly focused and individualized
  teaching activities targeting all areas of
  development
• Several different programs eg
• TEACCH (Treatment and Education of Autism and
  related communications handicapped children), The
  Denver model, LEAP (learning experiences and
  alternative program for preschoolers and
  parents), Princeton etc
• Common to all
• Intensive and expensive
• 1 to 1
• All based on learning theory in one way or
  another condition a behaviour and then work on
  generalization of the behaviour
• Family involvement

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Early intervention programs unanswered questions

• How many hours needed to get optimum effects?
• Is one method better than another?
• If recovery is not expected what are the most
  important outcomes? (social skills, language, IQ,
  adaptive skills, decrease in autistic symptoms?)
• To what extent are these independent outcome
  variables?
• Which is the best indicator of adult outcome?

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Early intervention programs

• The literature supports
• delivering interventions for more than 20 hours
  weekly that are individualized, well planned and
  target language development and other areas of
  skill development significantly increase
  childrens developmental rates- especially in
  language compared to no or minimal treatment
• Bryson et al 2003

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Sensory Integration

• Sensory integration is the neurological process
  of organizing the information we get from our
  bodies and from the world around us for use in
  daily life
• Sensory integration provides a crucial foundation
  for later more complex learning and behavior
• The organization of behavior, learning and
  performance is a natural outcome of the process,
  as is the ability to adapt to incoming sensations

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A. Jean Ayres, PhD, OTR1920 - 1989

• Professor, University of Southern California.
  Developed the concepts of SI theory a quiet
  genius
• just the right challenge the adaptive
  response
• . when she passed away, it was so hard to
  convince the Los Angeles Times to print an
  obituary. If she had been a silent movie star in
  just one film....

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Sensory Integration Dysfunction

• Sensory integration dysfunction is a complex
  neurological disorder, manifested by difficulty
  detecting, modulating, discriminating or
  integrating sensation adaptively.
• This causes children to process sensation from
  the environment or from their bodies in an
  inaccurate way, resulting in "sensory seeking" or
  "sensory avoiding" patterns or "dyspraxia", a
  motor planning problem

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Signs of Sensory Integrative Dysfunction

• Overly sensitive to touch, movements, sights, or
  sounds.
• Behavior issues distractible, withdrawal when
  touched, avoidance of textures, certain clothes,
  and foods. Fearful reactions to ordinary movement
  activities such as playground play. Sensitive to
  loud noises. May act out aggressively with
  unexpected sensory input.
• Under reactive to sensory stimulation. Seeks out
  intense sensory experiences such as body
  whirling, falling and crashing into objects. May
  appear oblivious to pain or to body position. May
  fluctuate between under and over-responsiveness.
• Unusually high/low activity level. Constantly on
  the move or may be slow to get going, and fatigue
  easily.

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Signs of Sensory Integrative Dysfunction

• Coordination problems. May have poor balance, may
  have great difficulty learning a new task that
  requires motor coordination, appears awkward,
  stiff, or clumsy.
• Delays in academic achievement or activities of
  daily living. May have problems in academic
  areas, despite normal or above normal
  intelligence. Problems with handwriting, scissors
  use, tying shoes, buttoning and zipping clothes.
• Poor organization of behavior. May be impulsive,
  distractible, lack of planning in approach to
  tasks, does not anticipate result of actions. May
  have difficulty adjusting to a new situation or
  following directions. May get frustrated,
  aggressive, or withdraw when they encounter
  failure.
• Poor self concept. May appear lazy, bored, or
  unmotivated. May avoid tasks and appear stubborn
  or troublesome

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Sensory Integration Strategies

• Some examples of treatment approaches
• Oral sensory motor development can be aided by
  whistles, blowers and bubble blowing kits.
• Fine motor A number of toys like cone and ball
  catch, puppets etc
• Gross motor Bean bags, Therabands
• Vestibular and Proprioception Swings,
  trampoline.
• Tactile Fabrics, brushes
• High arousal / anxiety weighted jackets,
  squishes

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The Evidence very likely an effective treatment

• A growing body of empirical support .. however
  research has been hampered by
• Lack of funding
• A paucity of doctorate trained OT clinicians and
  researchers
• Sceptical research committees
• What do we know about sensory dysfunction in
  autism? A critical review of the empirical
  evidence. Rogers, SJ., Ozonoff, S. Journal of
  Child Psychology and Psychiatry Volume 46 Page
  1255  - December 2005
• Occupational therapy using a sensory integrative
  approach for children with developmental
  disabilities. Schaaf RC, Miller LJ. Ment Retard
  Dev Disabil Res Rev. 200511(2)143-8

63
Web Link Sensory Integration

• Sensory Integration International
• The Ayres Clinic

64
Social skills training, social scripts and social
stories

• A method for teaching verbal individuals
  (including high functioning autism and
  Asperger's) the unwritten social rules and body
  language signals that people use in social
  interaction and conversation.
• Carol Gray uses a technique called "social
  stories" to help illustrate these social rules in
  a variety of situations and appropriate
  responses. Social stories and "scripting" are
  also used with nonverbal individuals to teach
  appropriate responses and prepare the individual
  for transitions.
• In very young child, they may be in the form of
  photographs or pictures.
• For an excellent Web Site on this treatment
  intervention, go here
• The Gray Center for Social Learning and
  Understanding
• (I have been unable to find any sound articles)

65
Alternative treatments

• No other group seems drawn to exposing their
  children to unproven and sometimes dangerous
  treatments more than the parents of autistic
  children
• 1/3 to 1/2 of all families use them
• Vitamins (high dose B6 and magnesium especially
  popular)
• Minerals
• Herbs
• Diets gluten free, sugar free, anti-yeast
  (fungal), casein free etc
• Dimenthylglycine (DMG)
• Secretin
• Cranio-sacral-therapy
• Trans cranial magnetic fields
• Chelation
• Auditory integration training
• Irlen lens system
• Homeopathy etc, etc

66
Alternative treatments Web links

• Cure Autism Now
• The official site of the Autism Research
  Institute founded by Dr. Bernard Rimland, PhD.
  A controversial figure who has, many have said,
  given much false hope to families of autistic
  children.

67
Psychopharmacological management

• Medications usually used sparingly and mostly in
  children with troubling comorbid conditions or
  maladaptive behaviours
• Much of the information available regarding
  psychotropic use has been gathered in adults and
  transposed down
• Many single case reports and open studies
• Few double blind, placebo controlled studies
• Off label
• Interactions with natural treatments always
  ask

68
Psychopharmacological management neuroleptics

• Although there is no strong evidence of dopamine
  involvement neuroleptics have been used for many
  years to control aggression, stereotypic
  behaviours, tics and impulsivity considerable
  evidence of their value as mood stabilzers
• Atypical neuroleptics risperidone, olanzepine,
  quetiapine
• Before starting CBC, ALT, fasting BS, lipids,
  cholesterol, prolactin, ECG
• Side effects appetite and weight increase, type
  II diabetes, lipid changes, cardiac arrhythmias
  (QTc interval), EPS, TD
• Monitoring repeat blood work and ECG at 3 and 6
  month, then annually, 6 monthly AIMS, physical
  examination for EPS and TD. Height / weight /
  growth chart each 3 months

69
Psychopharmacological management SSRIs

• Uncertain, but suggestive evidence of abnormal
  brain 5-HT functioning
• Abnormal platelet serotonin levels first
  described in 1961 (Schain and Freeman)
• Interest in the serotonin transporter gene
  (abnormalities have been described in substance
  abuse, depression, OCD, anxiety disorders and
  romantic love!)
• Magnetic resonance spectroscopy tantalizing
  suggestions very rich serotinergic innervation
  in limbic system
• 5-HT has a key role in sensory gating, appetite,
  behavioural inhibition, aggression, sleep, mood,
  neuroendocrine secretion
• Very strong evidence of 5-HT abnormalities in
  depression, OCD, anxiety disorders and solid
  evidence of the value of SSRIs in these disorders

70
Psychopharmacological management SSRIs

• ? ?
• When an autistic child presents with numerous
  obsessive behaviours and anxiety are these part
  of the primary disorder or is the mechanism
  similar to that in OCD and anxiety disorders and
  therefore SSRIs are worth a try?
• Is it really anxiety in autism or high sensory
  arousal?
• Is our traditional understanding of the
  phenomenology (Jaspers) of obsessive and anxiety
  symptoms valid in autism?

71
Psychopharmacological management stimulants

• Mixed responses in autism
• Methylphenidate, Concerta, dexedrine ,
  Adderal atomoxifine
• Target symptoms hyperactivity, impulsivity,
  distractibility
• Side effects appetite suppression, sleep
  disturbances, worsening of tics, obsessions,
  stereotypic movements, agitation, mood lability
  ?? likely more common in children with severe
  developmental disorders / MR
• Dosage always introduce at low dose and increase
  slowly
• Stimulants can dramatically successful or
  dramatically disastrous!

72
Psychopharmacological management others

• Anticonvulsants / mood stabilizers
  carbemazepine, valproic acid, toprimate,
  gabapentin
• Anxiolytics, benzodiazepines anxiety, mood
• Buspirone anxiety, mood
• Naltrexone hydrochloride self abuse, stereotypic
  movements
• Beta blockers anxiety, aggression
• Amantadine antiparkinsonian ?improves
  development progress

73
Conclusions The evidence

• The diagnosis of classical autism (Kanners
  Syndrome) is a robust entity.
• In retrospect, Kanners choice of the name
  autism was unfortunate, because of the
  confusion with Bleulers original definition.
  Because of this the separation of autism from
  psychoses was probably delayed by many years as
  was aetiological research.

74
Classical cases have been clearly described since
the 18th century.

• The Case of Hugh Blair of Borgue
• 1708/9 1765
• John HaslamObservations on madness
• and melancholy 1809
• William Howship Dickinson
• Autistic disorder in nineteenth
• century London three case reports
• The first definite DSM like
• descriptions

75
Psychodynamic factors cannot be so simply
dismissed - if we understand them in historical
perspective (Bowlby and Attachment, Money and
Psychosocial Dwarfism and Bettelheim) and we
really dont know the reciprocal psychodynamic
impact of having an autistic child on both the
child and family
76
The feral child and cases of extreme
maltreatmentmay offer insights into aspects of
brain development and psychodynamics

• Jean Itard and the wild boy of Aveyron.
• Dr Bruce Perry.
• The Neuroarcheology of Childhood Maltreatment
  The Neurodevelopmental Costs of Adverse Childhood
  Events

77
Diagnosis conclusions

• Coordinated population surveillance and screening
  is necessary . but we still have far to go (see
  Goulden)
• Diagnosis is often delayed
• Clinical judgment should be supported by
  standardized developmental screening instruments
  and simple ones exist
• Early diagnosis of classical autism is robust
  over time
• Regression in language always needs investigation

78
Prevalence Conclusions?

• Rates of classical autism have increased, but
  modestly
• (probably related to better identification,
  training)
• Rates of Retts disorder and CDD have not
  increased
• Rates of Aspergers syndrome, HFA and PDD-NOS
  have risen a great deal (problems with ADOS
  identification at the top end)
• Then we have all of the other associated
  diagnoses that have become fashionable in the
  last 10 to 15 years - and these are often
  inappropriately used interchangeably with
  Aspergers, HFA and PDD-NOS Something is very
  wrong with the concept of categorical
  classification especially in neurobehavioural
  disorders.

79
Comorbidities conclusions

• Medical comorbidity about 10
• About 1/3 may develop seizures
• Mental retardation in autism is predictive for
  the development of seizures
• 40 severe retardation, 30 mild to moderate
  retardation, 30 normal intellect
• Highly significant psychiatric comorbidity ?50

80
Aetiology, management conclusions

• Genetic factors are by far the most important
  (90)
• Evidence is converging on regional brain
  dysfunctions with relative sparing of other areas
• Areas of interest are the amygdala, temporal and
  frontal lobes
• Emerging evidence of central 5HT abnormalities
• Early intervention programs are beneficial
• Sensory integration treatments must be examined
  further
• Social stories may be helpful but no consistent
  evidence
• Medications are useful but there are no
  guidelines
• Prognosis Ill put a summary page on my Web
  Site ?

81
And finally ..

• Why would anyone spend so much time preparing for
  and delivering three Grand Rounds on Autistic
  Spectrum Disorders?
• I used to read dictionaries as a child
• I was into astronomy in a really big way
• I have over 800 vinyl albums all organized
• I get a buzz out of watching shows on storms
• One of my favourite movies is Twister
• I love to research and talk Progressive and Art
  Rock trivia.

82
Oh well . we changed the landscape . I really
wanted to be a rock starThe International
Progressive Rock Festival, Mexicali, Mexico
March 2006
83
I cherish and lovingly take care of my 1970 Mini
Moog
84
(No Transcript)