Autism: Comorbid Conditions and Implications for Treatment

1
AutismCo-morbid Conditions and Implications for
Treatment

• Dr. Jennifer E. Fisher M.B., B.S., MRCPsych,
  FRCP(C)
• Clinical Associate Professor
• Department of Psychiatry
• The University of Calgary

2
Definition

• The Pervasive Developmental Disorders (PDD) are
  a group of neurodevelopmental / neuropsychiatric
  disorders characterized by specific delays and
  deviance in social, communicative and cognitive
  development with an early onset, typically in the
  first years of life. Although commonly
  associated with mental retardation, these
  disorders differ from other developmental
  disorders in that their developmental and
  behavioural features are distinctive and do not
  simply reflect developmental level
• (Rutter, 1978)

3
History

• Eugene Bleuler 1911 First use of the word
  autism
• The three As of schizophrenia
• - altered association
• - altered affectivity
• - ambivalence and autism
• (- Autism meaning undirected fantasy
  thinking)
• Kretschmer 1924 Schizoid Character
• Schizothymia in Average People Detached
  Idealism
• Ssucharewa 1926 Boys with Schizoid personality
  disorder
• Leo Kanner 1943 Autistic disturbances of
  affective contact
• Hans Asperger 1944 High Functioning autism

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History

• The term autistic psychopathywas used by
• Van Krevelen and Kuipes 1962
• Van Krevelen 1971
• Wurst 1974
• Dauner and Martin 1978
• Newson 1970 More able autistic people
• DeMeyer et al 1981 High functioning Autism
• Wing 1981 coined the term Aspergers
  Syndrome (AS)

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History

• Aspergers Syndrome rapidly accepted in UK,
  Scandinavia and Canada
• PDD used in the USA, widely accepted by the
  1970s
• The term Aspergers Syndrome was adopted by the
  WHO in 1992 and by the American Psychiatric
  Association in 1994

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Autism and Schizophrenia
(Web Link) Israel Issy Kolvin (1929 2002)
There was long standing confusion between
infantile autism, childhood psychosis and
schizophrenia. The seminal work of Kolvin and
his group (part of the Newcastle Group) in the
early 1970s separated schizophrenia from autism.
It was thought, prior to Kolvin that many adult
schizophrenics had childhood histories of autism
and a high proportion of childhood autists became
schizophrenic. Studies in the childhood
psychoses. I. Diagnostic criteria and
classification Kolvin, Br. J. Psychiatry. 1971
Apr 118(545)381-4 Studies in the childhood
psychoses. II. The phenomenology of childhood
psychoses. I Kolvin, C Ounsted, M Humphrey, A
McNay. Br. J. Psychiatry. 1971 Apr,
118(545)385-95
7
DSM III 1980

• Autism (as we know the concept today) did not
  become a diagnostic entity until 1980 when
  operational criteria for infantile autism
  were established.
• - onset before 30 months of age
• - lack of responsiveness to other human beings
• - gross impairment in communication and
  language
• - bizarre responses to the environment
• (American Psychiatric Association. Diagnostic and
  Statistical Manual of Mental Disorders, 3rd
  edition. Washington (DC)
• American Psychiatric Association 1980)

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DSM-IV (1994)

• These definitional issues are a major part of
  the substantial problems in establishing accurate
  epidemiology, understanding the natural history
  of the condition, comparing studies, replicating
  research findings and speculating on prognosis
• .. never mind trying to understand the medical
• and psychiatric co-morbidities.

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The DSM-IV Pervasive Developmental Disorders

• Autistic Disorder
• Retts Disorder
• Childhood Disintegrative Disorder (CDD)
• Aspergers Disorder (AD)
• Pervasive Developmental Disorder Not Otherwise
  Specified
• (PDD-NOS)

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• Clarity?

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Not in the least!

• The late 1980s and 1990s exploded with a host of
• new diagnoses
• High functioning autism
• Sensory Integration Dysfunction
• 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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Autistic symptoms

• also associated with some cases of
• Gilles de la Tourettes Syndrome
• Obsessive Compulsive Disorder
• Social Anxiety Disorder
• Disorders of Written Expression
• Developmental Coordination Disorder

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

• Vaccination
• Diet
• Electromagnetic waves (power cables)
• Infection
• Pollutants
• Abnormal trace elements
• Allergies
• etc, etc ,etc

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(No Transcript)
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An occupational hazard of academics attempting to
classify and understand the autistic spectrum
Ha! Websters blown his cerebral cortex
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Autistic Spectrum Disorders

• A spectrum of related diagnostic categories
• Within the spectrum of categories researchers
  have attempted to identify stable dimensions of
  symptom presentation that manifest across all of
  the categories.

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Szatmari et al (2002)

• 129 children with autism and other forms of PDD
  from two samples with different inclusion
  criteria were assessed using the Vineland
  Adaptive Behaviour Scales (VAB) to measure level
  of functioning and the Autism Diagnostic
  Interview (ADI) to measure the severity of
  autistic symptoms. Two relatively robust
  dimensions were identified
• Dimension I representing autistic symptoms
• (ADI measures of reciprocal social
  interaction, repetitive movements and
  communication)
• Dimension II representing level of functioning
• (VAB measures of socialization,
  communication, motor skills, daily living
  skills)
• (Szatmari et al Quantifying Dimensions in
  Autism A Factor-Analytic Study.
• J. Am. Acad. Child Adolesc. Psychiatry, 414,
  April 2002)

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Why is it important to identify robust domains of
symptoms?

• Szatmari, 2002
• If it were true that autism / PDD is composed
  of more than one dimension, this would have
  important implications for research into
  neurobiological mechanisms. Separate dimensions
  may be influenced by separate etiological
  mechanisms, a model that has also been suggested
  for schizophrenia (Andreason and Carpenter, 1993)
  and could be equally applied to autism

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"Monoamines and Abnormal Behaviour. A
Multi-Aminergic Perspective"

• H. M. VAN PRAAG, G. M. ASNIS, R. S. KAHN, S. L.
  BROWN, M. KORN, J. M. HARKAVY FRIEDMAN and S.
  WETZLER. British Journal of Psychiatry (1990),
  157, 723-734.

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"Functional psychopathology.

• From the very beginning, biological psychiatry
  has orientated itself towards nosology, a way of
  looking at behavioral disorders as distinct,
  separable entities, each with their own symptoms,
  causation, outcome and treatment.
• (van Praag)

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van Praag the concepts - 1

• The basic units of classification in
  psycho-pathology are not syndromes or nosological
  entities, but psychological dysfunctions,
  (Szatmaris dimensions) such as disturbances in
  perception, cognition, memory and information
  processing. They are the elementary constituents
  of psychiatric syndromes.

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van Praag the concepts - 2

• Functional psychopathology is dimensional in
  orientation, viewing a given psychiatric disorder
  as a conglomerate of psychological dysfunctions,
  most of them nosologically non-specific and
  occurring in different severities and in
  different combinations in the various psychiatric
  syndromes.
• Psychiatric symptoms are the behavioral
  expression of a psychological dysfunction, not
  the dysfunction itself.
• For example a visual hallucination is a symptom
  (and visual hallucinations occur in numerous
  nosological conditions).
• Perceptual disturbance the underlying
  dysfunction.

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van Praag the concepts - 3

• Within a functional framework, psychological
  dysfunctions are the targets of biological
  research and treatment interventions.

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van Praag - for example in an autistic child

• A stereotypic movement is the observed symptom, a
  disturbance in neurotransmitter motor function is
  the underlying dysfunction.
• A repetitive compulsion is an observed symptom,
  a particular problem with the persistence of a
  thought (obsession) is the underlying
  dysfunction.
• A rage episode is a symptom, a particular problem
  with mood regulation is the underlying
  dysfunction.
• Short attention span and distractibility are the
  observed symptoms, the underlying dysfunction is
  being unable to filter out stimuli from the
  environment.

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Functional neuroimaging techniques

• Positron Emission Tomography (PET)
• functional Magnetic Resonance Imaging (fMRI)
• Magnetic Resonance Spectroscopy (MRS)
• Magnetoencephalogram (MEG)
• are beginning to correlate and map observed
  symptom complexes (as measured by standardized
  instruments, such as the ADI and ADOS)
  Szatmaris dimensions and van Praags
  psychological dysfunctions with disturbances
  in regional brain functioning and
  neurotransmitter abnormalities.

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Epidemiology

• Prevalence rates have increased over the last
  decade
• ? a true increase
• ? related to shifting diagnostic criteria and
  categories
• ? due to international differences (DSM vs
  ICD-10)
• ? a fashionable diagnosis
• ? better education of teachers, psychologists and
  physicians
• Rates of classical autism have increased, but
  modestly
• Rates of Retts disorder and CDD have not
  increased
• Rates of Aspergers syndrome and PDD-NOS have
  risen a great deal
• Then we have all of the other associated
  diagnoses (described above) that have become
  fashionable in the last 10 to 15 years - and
  these are often inappropriately used
  interchangeably with Aspergers and PDD-NOS

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Associations Cognitive Function

• Frombonne (2003) 40 severe retardation
• 30 mild to moderate retardation
• 30 normal intellect
• Includes all subtypes classical, Aspergers
  syndrome and PDD-NOS
• Classical autism
• 75 severe to profound mental retardation

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Associations with Medical Disorders

• In general the proportion of cases attributable
  to specific medical conditions is low and
  identifying clear causal relationships is complex
• Speculations of such associations were usually
  based on case reports
• For example it was established clinical
  impression that there was a strong relationship
  between autism and congenital rubella this
  idea had to be revised because it became
  apparent that cases became less autistic with
  the passage of time.

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Associations with Medical Disorders

• Frombonne (2003)
• reported on 15 studies
• rates from 0 16.7
• mean 6
• Gillberg and Coleman (1996) about 25
• Rutter et al (1994) I think more accurate at 10

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Associations with Medical Disorders

• Data does not suggest more than chance
  associations between autism and
• Downs syndrome
• Congenital rubella
• Cerebral palsy
• Phenylketonuria
• Neurofibromatosis

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Associations with Medical Disorders

• However
• 4 of autistic children have fragile X syndrome
• (Dykens and Volkmar 1997)
• Rates of autism are increased in tuberous
  sclerosis
• (Smalley et al 1992)
• Infants with sensory handicaps may present with
  autistic like symptoms because of unusual
  movements and / or language difficulties, but
  usually the criteria for DSM Autistic disorder
  are not met.

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Associations with Medical Disorders

• Epilepsy
• In various studies rates from 5 38.3
• Mental retardation in autism is predictive for
  the development of seizures
• Rates are highest in adolescents and adults up
  to 1/3 may have seizures
• (However in 1 study (Rutter et al 1994) 39 of
  children under age 3 years had seizures. A UK
  study using narrow diagnostic criteria i.e.
  severe classical cases)

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Associations with Psychiatric Disorders

• Numerous reports of associations with
  behavioural disorders
• Are such associations greater than would be
  expected by chance alone?
• Are such symptoms and behavioural manifestations
  part of the primary autistic condition or the
  manifestation of other comorbid conditions? (Tsai
  1996)

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Associations with Psychiatric Disorders

• Associations include
• Oppositional behaviour
• Anxiety
• Depression
• Hyperactivity
• Poor attention
• Tics
• Obsessive and compulsive behaviour
• Volkmar et al Practice Parameters for the
  Assessment and Treatment of Children,
  Adolescents and Adults with Autism and Other
  pervasive Developmental Disorders. J. AM. ACAD.
  CHILD ADOLESC PSYCHIATRY. 3812 Supplement,
  December 1999

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Associations with Psychiatric Disorders

• Diagnosis of these disorders is particularly
  difficult in individuals who are largely or
  entirely mute or function in the severely or
  profoundly mentally retarded range
• Diagnosis of these associated problems in higher
  functioning individuals (e.g. the gifted,
  Aspergers disorder, high functioning autism etc)
  may result in functional diagnoses of
• Generalized anxiety disorder
• Social anxiety disorder
• Obsessive compulsive disorder
• Schizoid, schizotypal, avoidant or other
  personality disorders
• And these may be assumed to be primary diagnoses
  standing alone and mask exploration of underlying
  autistic spectrum disorders. This can be
  particular problem in adult psychiatry

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Associations with Psychiatric Disorders

• It is reasonable to assume that lower
  functioning individuals and those closer to a
  diagnosis of classical autism have a greater
  frequency of
• behavioural difficulties
• hyperactivity
• mood lability
• self injury
• manneristic and stereotypic movements
• Higher functioning individuals have more
  evidence of manifest and self described
• anxiety
• social phobia
• depression

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Associations with Psychiatric Disorders

• Obsessive compulsive problems probably occur
  with equal frequency across the spectrum but
  manifest differently as a property of severity
  and degree of cognitive delay, for example
• A severely autistic person with severe to
  profound IQ delay may sit and arrange blocks or
  spin wheels in a purposeless manner
• A higher functioning person may demonstrate
  sophisticated rituals or want to count in binary
  or insist on relating all numbers to degrees
  Kelvin

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High functioning autism and Aspergers syndrome.

• Present at an older age
• Less evidence of developmental delay but more
  evidence of developmental deviations and
  psychiatric symptoms
• Fine motor skills (buttons, cutting)
• Poor printing, copying
• Anxiety
• Obsessive rituals and routines
• Over-interest in certain topics.

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Associations

• Attachment disorder
• Maternal deprivation
• Psychosocial dwarfism
• Refrigerator mothers

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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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Management

• Should address
• Establishing goals for language/communication
  interventions
• Establishing goals for educational intervention
• Prioritizing target symptoms/comorbid conditions
• Monitoring multiple domains of functioning
• Behavioral adjustment
• Adaptive skills
• Academic skills
• Social/communication skills
• Social intervention with family members and peers
• Monitoring medications

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Early intervention programs

• psychosocial interventions can change the
  disorders course
• Such 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)

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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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Psychopharmacological management

• No curative treatment
• 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

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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.
• 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
• Dosage start low 0.25 mg bid and adjust

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Psychopharmacological management SSRIs

• Clear evidence of abnormal brain 5-HT
• SSRIs target anxiety, obsessions, stereotypic
  movements, mood stability
• Fluoxetine, paroxetine, fluvoxamine, sertraline,
  citalopram, venlafaxine. Also the TCA
  clomipramine
• Side effects sedation, agitation, high arousal,
  increased risk of suicidal ideation, withdrawal
  syndrome

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Psychopharmacological management stimulants

• Mixed responses in autism
• Methylphenidate, Concerta, dexedrine (Adderal),
  atomoxifine
• Target hyperactivity, impulsivity,
  distractibility
• Side effects appetite suppression, sleep
  disturbances, worsening of tics, obsessions,
  stereotypic movements, agitation, mood lability
• Dosage always introduce at low dose and increase
  slowly
• Stimulants can dramatically successful or
  dramatically disastrous!

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Psychopharmacological management anticonvulsants

• Used mainly as mood stabilizers and to reduce
  affective lability
• Seizures
• Carbemazepine, valproic acid, toprimate,
  gabapentin
• The relationship between seizures and behaviour
  is complex
• Usually need to monitor blood levels, WBC, LFTs
• It is uncertain whether the recommended serum
  levels used for the treatment of epilepsy apply
  when these drugs are used as mood stabilizers
• No controlled study evidence

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Psychopharmacological management others

• Anxiolytics, benzodiazepines anxiety, mood
• Buspirone anxiety, mood
• Naltrexone hydrochloride self abuse, stereotypic
  movements
• Beta blockers anxiety, aggression
• Amantadine antiparkinsonian ?improves
  development progress

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DSM, n., abbrev

• Abbreviation for the "Diagnostic and Statistical
  Manual", a lengthy work of comic fiction
  published by the American Psychiatric Association
  (APA).  Currently in its fourth major edition
  (known as the DSM-IV), this volume hilariously
  attempts to classify every aspect of human
  existence as a disorder, thereby legitimating the
  involvement of its members in devising expensive
  and intrusive methods of "treatment" for every
  living person.  Having already introduced several
  delightfully whimsical categories, the ultimate
  goal of the DSM's witty and satirical writers is
  to develop so many categories that every living
  person will require the services of at least one
  psychiatrist, eventually ensuring that there will
  be more psychiatrists than people. 
• Despite its great comic potential, this
  mischievous document has been little noticed by
  the general public due to its large physical size
  and high cover price.