Pervasive Developmental Disorders

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Pervasive Developmental Disorders
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Autistic Disorder

• A total of six or more items from 1, 2 and 3 with
  a t least two from 1 and one from 2 and 3
• 1) qualitative impairment in social interaction
• Nonverbal behaviours (eye to eye gaze, facial
  expression, body postures, gestures
• Failure to develop peer interactions appropriate
  to developmental level
• Lack of spontaneous seeking of sharing enjoyment
  interests or achievements with other people

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Autistic Disorder

• 2) Qualitative impairments in communication
• Delay in or total lack of development of spoken
  language without attempts to compensate
• Inability to start a conversation or sustain a
  conversation once language has been developed
• Stereotyped or repetitive use of language or
  idiosyncratic language
• Lack of varied spontaneous make believe play or
  social imitative play according to developmental
  stage

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Autistic Disorder

• 3) Restricted repetitive and stereotyped patterns
  of behaviour, interests and activities
• Encompassing preoccupation with one or more
  stereotyped and restricted patterns of interest
  abnormal in intensity and focus
• Inflexible adherence to specific, nonfunctional
  routines and rituals
• Repetitive and stereotyped motor mannerisms
• Preoccupations with part of objects

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Autistic Disorder

• Delays or abnormal functioning in
• Social interaction
• Language as used in social communication
• Symbolic or imaginative play
• .. have started prior to age 3
• Disturbance not accounted for by Retts Sx or
  disintegrative disorder

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Autistic Disorder

• Frequency of 2 to 5/ 10,000 under age 12
• Up to 20/10,000 if including MR
• Starts before age 36 months
• More common in boys than girls
• Girls more seriously affected
• Associated with neurological conditions (PKU,
  tuberous sclerosis, congenital rubella, Retts
  syndrome, grand mal seizures, ventricular
  enlargement, cerebellar vermal hypoplasia,
  polymacrogyria, abnormal cell migration, etc)

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Autistic Disorder

• Perinatal complications maternal bleeding after
  1st. trimester, meconium, respiratory distress
  syndrome, neonatal anemia, medication use
• Temporal lobe damage autistic like symptoms
• Hyperserotoninemia, and high dopamine metabolites
• Severity is proportional to 5HIAA/HVA or
  inversely proportional to 5HT

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Autistic DisorderGenetics

• Risk of siblings only 3 to 6 percent
• Risk to siblings is 100 times greater than that
  of the general population 0.0003
• Twin concordances are 60 in MZ twins
• Linkage to 7q31-33 and chromosomes 13 and 15

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Attention Deficit Hyperactivity Disorder

• Inattention six or more persisted for at least
  6months causing malfunctioning
• Fails to give attention to details, careless
  mistakes in schoolwork, work or other activities
• Difficulty in sustaining attention
• Does not seem to listen
• Does not follow instructions, fails to finish
  without being oppositional
• Difficulties organizing tasks
• Avoids or dislikes activities that require
  sustained mental effort
• Looses things necessary for work
• Easily distracted
• Forgetful in daily activities

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Attention Deficit Hyperactivity Disorder

• Hyperactivity
• Fidgets with hands or squirms in seat
• Can not remain seated
• Runs around or climbs inappropriately
  (restlessness)
• Difficulty playing or engaging in leisure
  activities quietly
• Often on the go or driven by a motor
• Talks excessively

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Attention Deficit Hyperactivity Disorder

• Impulsivity
• Blurts out answers before the question is
  finished
• Difficulty awaiting turns
• Interrupts or intrudes others
• Symptoms have been present before age 7
• Impairment in two or more settings
• Clinically significant impairment in social,
  academic or occupational environments
• Not present only when a pervasive disorder is
  occurring

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Attention Deficit Hyperactivity Disorder

• No anatomical findings consistent with disorder
• No environmental factors associated to causes
• Dopaminergic and NE disorders?
• 15-20 persist after childhood
• Persistent ADHD gt high risk CD
• 50 CD adolescent onset ASPD

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Attention Deficit Hyperactivity
DisorderBiological adversity

• Do certain food additives cause ADHD?
• Feingold diet
• Study by Conners (1980) demonstrated that food
  additives do not cause ADHD
• Toxins? Lead
• Lead intoxication cause distractibility,
  hyperactivity and restlessness and lower
  intellectual functioning
• Yet it does not account for the bulk of the
  disease

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Attention Deficit Hyperactivity
DisorderBiological adversity

• Pregnancy and delivery complications seem to be
  associated with higher incidence of ADHD
• Toxemia, poor maternal health, fetal
  postmaturity, duration of labour, fetal distress,
  low birthweight and antepartum hemorrhage
• May be due to hypoxia in a chronic fashion

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Attention Deficit Hyperactivity
DisorderBiological adversity

• Smoking
• Nicotine exposed pups (mice and rats) are
  hyperactive
• Pups are nicotine tolerant and increase numebr of
  nicotinic receptors
• Nicotinic receptors regulate dopaminergic
  activity and dopamine is involved in ADHD
  physiopathology..
• Increases chances of antepartum hemorrhage, low
  birthweight and abruptio placentae.

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Attention Deficit Hyperactivity
DisorderNeurobiology

• ADHD is caused by a fronto-limbic dysfunction
• Idea supported by ADHD pharmacotherapy, brain
  lesions ADHD like, animal models of dopaminergic
  damage
• Pattern of neuropsychological deficits is similar
  to that of frontal lobe damage
• It appears to be specifically related to
  prefrontal damage involving its connections to
  subcortical structures
• Orbito frontal damage disinhibition and
  impulsivity
• Dorso-lateral deficits in organization,
  planning, working memory and attention
• Deficits better described as fronto-subcortical

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Attention Deficit Hyperactivity
DisorderNeurobiology

• Neuroimaging
• Abnormalities in frontal cortex on the right side
• Smaller subcortical structures
• Functional studies found dysfunctions
  particularly in ADHD girls
• Location is the same
• These areas are rich in catecholamines
• Stimulants block recapture and increase release
  of DA and NE

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Attention Deficit Hyperactivity DisorderGenetics

• Prevalence amongst 1st degree relatives higher
  than 2 to 10 (gral pop)
• Family studies
• 2 to 8 fold increase of presence of ADHD in
  parents of probands
• Rates of hyperactivity amongst siblings or
  hyperactive probands go from 15 to 41 including
  a study of hyperactive adults
• Twin studies (6) show heritability estimations as
  high as 100 ! (Gillis, 1992) and as low as 60

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Attention Deficit Hyperactivity DisorderGenetics

• Adoption studies Couple of studies showing that
  consanguineous relatives have higher prevalence
  of ADHD and do worst in attention tests in
  general
• Segregation analysis renders two hypothesis
• More than one single gene with major effects with
  weak evidence for one mode of transmission
• Several genes of modest effect that interact
  (high prevalence in pop, high concordance in
  twins but modest risk to close relatives
• Non genetic forms of ADHD may exist

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Attention Deficit Hyperactivity DisorderGenetics

• Association studies
• Rare form of the disease associated to thyroid
  resistance mutation in thyroid b-receptor gene
• Other associations with dopamine D2 and D4
  receptors, dopamine transporter, dopamine
  b-hydroxylase
• D4 associated with novelty seeking
• Transgenic mouse for DAT genes is hyperactive