AUTISM THE GLUTAMATE HYPOTHESIS

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AUTISM THE GLUTAMATE HYPOTHESIS

• PSY346H
• Elizabeth Vanatoru
• Std. no. 991560271

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OVERVIEW

• Autism
• Glutamate
• Brain regions - Areas of Interest
• Glutamate and Serotonin
• Glutamate receptor agonists, Transmission,
  Serotonin antagonist
• Autism and Schizophrenia
• Hypoglutamatergic Theory of Autism Why is it
  attractive?
• Future Research Directions - Treatment

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AUTISM

• Pervasive Developmental Disorder
• Wings triad impaired sociability, communication
  and imagination
• Kanner echolalia, difficulties with pronouns,
  repetitious behaviour
• Aspergers syndrome high functioning autism

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Differences between Autism and Aspergers

• Individuals with autism live in a world of their
  own (Happe Frith, 1996)
• Individuals with Aspergers live in our world in
  their own way (Kugler, 1998)

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ContdTHE DOMINO EFFECT IN AUTISM

• From
• Heightened perception of stimuli sensory
  overstimulation reactive withdrawal social
  isolation sensory deprivation
• To
• defective social skills, language skills and
  stereotyped behaviour

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GLUTAMATE

• Main excitatory NT in CNS
• Role in cognitive and Pathological processes
• Glutamate Receptors Metabotropic and ionotropic
  (NMDA, AMPA, kainate)
• Excitotoxin damage

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EXCITATORY AMINO ACID PATHWAYS
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BRAIN REGIONS- AREAS OF INTEREST

• Limbic System Amygdala and Hippocampus
• Cerebellum
• Cortical Areas Frontal, Prefrontal and Parietal
  Cortex

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GLUTAMATE AND SEROTONIN

• Glutamate receptor antagonist
• increased 5-HT receptor mediated transmission
• 5-HT receptor stimulation
• decreased glutamatergic transmission

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AUTISM AND SCHIZOPHRENIA

• Both display frontal and temporal brain areas
  abnormalities
• Both distorted perception of stimuli
• Time frame factor differences
• Hallucinations and paranoid delusions in
  schizophrenia
• No production of hallucinations in autism
• Social interaction experience (schizophrenia)

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IN SUPPORT OF THE HYPOGLUTAMATERGIC THEORY OF
AUTISM

• Heritability
• IQ and seizures
• Evidence from neuroanatomical studies
• and symptoms produced by glutamate antagonists
  in healthy subjects
• Animal models

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More on the Hypoglutamatergic Theory of Autism

• Susceptibility loci in autism
• Evidence from genome scans
• GluR6 Linkage Disequilibrium Autism
• Post mortem brain abnormalities

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Glutamate Receptor Autoradiography
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WHY IS GLUTAMATE HYPOTHESIS ATTRACTIVE?

• Glutamate involved in brain development
• Glutamate high concentrations in cerebellum and
  hippocampus
• Abnormalities in glutamate transmission
• Glutamate receptor antagonists
• Blocking glutamate receptors
• Role of glutamate work in progress

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FUTURE DIRECTIONS TREATMENT

• Glutamate agonist treatment ?
• Ketamine Anesthesia
• Ampakines
• 5-HT Receptor antagonists
• Further neurochemical research
• Animal models
• Behaviour Therapy

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END OF PRESENTATION