AUTISM - GLUTAMATE HYPOTHESIS by T8QqX451

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									AUTISM – THE GLUTAMATE
      HYPOTHESIS
          PSY346H

      Elizabeth Vanatoru
      Std. no. 991560271
                      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
               AUTISM
• Pervasive Developmental Disorder
• Wing’s triad: impaired sociability,
  communication and imagination
• Kanner – echolalia, difficulties with
  pronouns, repetitious behaviour
• Asperger’s syndrome – high functioning
  autism
  Differences between Autism and
             Asperger’s
• “Individuals with autism live in a world of
  their own” (Happe & Frith, 1996)

• “Individuals with Asperger’s live in our
  world in their own way” (Kugler, 1998)
Cont’d…THE 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
           GLUTAMATE
• Main excitatory NT in CNS
• Role in cognitive and Pathological
  processes
• Glutamate Receptors: Metabotropic and
  ionotropic (NMDA, AMPA, kainate)
• Excitotoxin damage
EXCITATORY AMINO ACID
      PATHWAYS
         BRAIN REGIONS-
        AREAS OF INTEREST
• Limbic System – Amygdala and
  Hippocampus
• Cerebellum
• Cortical Areas – Frontal, Prefrontal and
  Parietal Cortex
 GLUTAMATE AND SEROTONIN
• Glutamate receptor antagonist
  increased 5-HT receptor mediated
  transmission

• 5-HT receptor stimulation
  decreased glutamatergic transmission
 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)
       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
 More …on the Hypoglutamatergic
       Theory of Autism
• Susceptibility loci in autism

• Evidence from genome scans

• GluR6 & Linkage Disequilibrium & Autism

• Post mortem brain abnormalities
Glutamate Receptor
 Autoradiography
      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
         FUTURE DIRECTIONS
            TREATMENT
•   Glutamate agonist treatment ?
•   Ketamine Anesthesia
•   Ampakines
•   5-HT Receptor antagonists
•   Further neurochemical research
•   Animal models
•   Behaviour Therapy
END OF PRESENTATION

								
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