This article can be found at http://www.ncbi.nlm.nih.gov/pubmed/22284793

There are multiple causes of autism, and we have to rely on behavioral definitions because we can’t define biomarkers

Possible causes:

  • Alteration in common signaling pathways
  • Alteration of neurotransmitters, implications during brain development - if we can understand what goes wrong with NT, can develop pharmacological intervention

PET and SPECT

used to study serotonin and dopamine and GABA systems

Dopamine:

Together these studies suggest altered dopaminergic function in frontal cortical regions but not in striatum in children and adults with autism

  • Ernst et.al reported a 39% reduction of the anterior medial prefrontal cortex/occipital cortex ratio in the autistic group. suggest that decreased dopaminergic function in prefrontal cortex may contribute to the cognitive impairment seen in autism.
  • (Transporter) study reported a whole brain increase in dopamine transporter binding in the autism (child) group
  • Nakamura and colleagues17 measured dopamine transporter binding in adults with autism, significantly higher in orbital frontal cortex in the autism group compared with 20 age-matched and IQ-matched control subjects

Serotonin:

  • Schain and Freedman, increased blood serotonin in 1/3 autistic patients (1961)
  • Chugani et al found two serotonin abnormalities: 1) difference in whole brain serotonin synthesis, greater, suggested that humans undego period of high brain serotonin synthesis during childhood and this process is disrupted in autistic children
  • Assymetries of AMT uptake in frontal cortex, thalamus, and cerebellum, suggesting a role of the dentatothalamocortical pathway in autism.
  • Decreased serotonin transporter binding has been reported in both children and adults with autism.
  • Reduction in binding in anterior and posterior cingulate cortices was correlated with impairment in social cognition, whereas the reduction in serotonin transporter binding in the thalamus was correlated with repetitive or obsessive behavior.
  • Measured 5HT2A receptors in 8 men with Asperger syndrome, had significantly reduced serotonin receptor binding in total, anterior, and posterior cingulate cortex, bilateral in frontal and superior temporal lobes and in the left parietal lobe. significant correlations with qualitative abnormalities in social interaction with binding reductions in anterior and posterior cortices, as well as right frontal cortex.
  • (5-HT2) receptor binding was significantly lower in autism parents, 5HT2 binding potential was inversely correlated with platelet serotonin levels in the parent group

GABA

  • Cytogenetic studies reported the abnormalities in chromosome 15 in autism, specifically 15q11 to 15q13, the region encoding several GABAA receptor subunit genes
  • Symptoms of autism can be associated with both Prader-Willi and Angelman syndromes, both of which involve alterations in the chromosome 15q11 to 15q13 region (deletion maternal chromosome –> Angelman, paternal –> Prader William) (GABRB3, GABRA5, and GABRG3

NAA

  • Most studies report decreased NAA throughout autistic brain
  • A study of Asperger syndrome showed higher NAA in the medial prefrontal lobe of the Asperger group (14 adults) compared with 18 age-matched, gender-matched, and IQ-matched adults. The increase in NAA was significantly correlated with obsessional behavior in the Asperger group
  • Changes in serotonin synthesis, NAA decreases, and fMRI activation all point to dysfunction of the corticothalamocortical pathway