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Opioids and Autism

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Gluten and gliadin. Found in wheat and other cereals. give rise to gluteomorphines and ... Effects of a gluten and casein-free diet on the symptoms of autism. ... – PowerPoint PPT presentation

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Title: Opioids and Autism


1
Opioids and Autism
  • Simone Walker
  • PSY346H
  • November 13th, 2003

2
Overview
  • Introduction Opioid system
  • Opioid theory of autism
  • ? Exogenous opioids
  • ? Endogenous opioids
  • Naltrexone
  • Conclusion

3
The Opioid System
  • Group of naturally occurring peptides
  • ? met-enkephalin, leu-enkephalin and
  • beta-endorphin.
  • Act as both neurotransmitters and hormones
  • Regulation of pleasure and pain as well as
    reward.
  • Regulation of human emotional responses

Zubieta, et al., 2003
4
The Opioid Theory of Autism
  • An early, long-term overload of the CNS by
    opioids.
  • Opioid dysfunction may underlie social and
    emotional impairments, attention deficits,
    hyperactivity, self-injurious behaviour.

Reichelt, Sælid, Lindback, Bøler, 1986
Sahley Panksepp, 1987
5
Exogenous Opioids
  • Derived from diet
  • Gluten and gliadin
  • ? Found in wheat and other cereals.
  • ? give rise to gluteomorphines and
  • gliadinmorphines respectively.
  • Casein
  • ? Found in milk and milk products.
  • ? Gives rise to caseomorphines.

Whiteley Shattock, 2002
6
Exogenous Opioids Cont
  • Autism is a metabolic disorder.
  • Opioid peptides from dietary sources pass through
    an abnormally permeable intestinal membrane.
  • Abnormalities in blood-brain barrier
  • Enter CNS where they affect neurotransmission.

Whiteley Shattock, 2002
Berney, 2000
Whiteley Shattock, 2002
7
Exogenous Opioids Cont
  • Whiteley Shattock review (2002) found that
    studies consistently found urinary peptide
    abnormalities in autistic vs normal controls.
  • High levels of opioids also found in plasma and
    spinal fluid in autistic individuals.

Reichelt, Sælid, Lindback, Bøler, 1986
8
Exogenous Opioids Cont
  • Effects of a gluten and casein-free diet on the
    symptoms of autism.
  • Single-blind, randomized design.
  • 10 kids (7 years old) with autism and abnormal
    urinary peptide patterns
  • 10 age-matched control kids
  • Tested on a number of clinical and behavioural
    scales before and after treatment.

Knivsberg, Reichelt, Hølen, Nødland, 2002
9
Exogenous Opioids Cont
  • Special diet produced a significant improvement
    in aloofness, distraction, adjustment to novel
    situations, ritualistic behaviour, resistance to
    learning, inappropriate emotions and motor
    skills.
  • Improvements were small but remarkable.
  • Small sample size
  • Single-blind design

10
Endogenous Opioids
  • Mostly ß-endorphin.
  • Autism may be a failure of striatal ß-endorphin
    to diminish with maturation
  • Conflicting evidence of elevated levels of
    ß-endorphin.
  • ? Sandman, et al., 1997
  • ? Nagamitsu, et al., 1997

Panksepp, 1979
11
Endogenous Opioids Cont
  • More recently autism and POMC
  • ? Proopiomelanocortin
  • ? Mammalian endocrine precursor for
  • endorphins, ACTH, melatonin.
  • ? mostly produced in anterior pituitary.
  • In a subgroup of autistic children POMC
  • dysfunction results in abnormal levels of ACTH
  • and opioids in bloodstream.

Chamberlain Herman, 1990
Sandman, et al., 1997
12
Endogenous Opioids
  • Elevated plasma levels of ß-endorphin fragment in
    autistic children and their mothers.
  • POMC and resulting fragments involved in HPA axis
    acute stress response
  • Overreaction to acute stressors due to opioid
    excess in CNS.

Leboyer, et al., 1994
Tordjman, et al., 1997
13
Naltrexone
  • Naltrexone
  • ? Pure opioid antagonist
  • ? Modest improvements in hyperactivity
  • and self-injurious behaviour.
  • ? Sensory/pain threshold
  • ? Pleasure associated with opioid
  • release

Sandman, et al., 1997 Bouvard, et al., 1995
Sandman, et al., 2002
14
Naltrexone
  • Reduced peripheral blood levels of ß-endorphin in
    7 of 11 autistic children after 12 weeks of
    treatment
  • Correlated reduction in social withdrawal and
    other symptoms.

Cazullo, et al., 1999
15
Naltrexone Cont
  • Long-term benefits of naltrexone
  • 6 autistic children who had previously shown
    reductions in hyperactivity after 4 weeks of
    naltrexone.
  • After 6 months, scores on the Aberrant Behaviour
    Checklist were lower than baseline for 5 out of 6
    kids.

Willemsen-Swinkels, et al., 1999
16
Naltrexone Cont
  • What does Naltrexone treatment tell us?
  • ? Modest improvements
  • ? Symptom attenuation

Berney, 2000
17
Conclusion
  • Evidence supports theory that opioid
    excess/overactivity involved in autism
  • Do not know whether it is main contributor or
    part of interaction with other systems E.g.
    serotonin
  • Treatments such as a restricted diet and
    naltrexone are promising but more studies with
    larger samples are needed.

18
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