Autism in 12 Minutes

1. Autism in 12 Minutes Paul H. Patterson Caltech California Science Center May 5, 2012

2. Autism Sensory sensitivity Seizures Self-injurious behavior Communication & language deficit Repetitive & stereotyped behaviors Mental retardation Sleep disturbance Social interaction deficits GI problems Immune problems

3. ASD symptoms cluster into 4 discrete groups Immune abnormalities Sleep disturbance Repetitive & stereotyped behaviors Repetitive & stereotyped behaviors Sensory sensitivity Immune abnormalities Sensory sensitivity Sensory sensitivity Sleep disturbance Sleep disturbance Sacco et al., 2012

4. Treatment • Severity and specific nature of symptoms is heterogeneous • There is no fully effective treatment, although intensive behavioral therapy can be extremely helpful, and expensive ($40,000 to $60,000 per year!) • Early intervention is important

5. Autism diagnosis is increasing dramatically www.cdc.gov/ncbddd/autism/data.html Does this reflect a growing problem, or does it reflect an improvement in the ability to diagnose and serve affected children?

6. Explanations for the rise in autism • Increase in diagnosis, not actual incidence: better ascertainment; financial and scholastic support is linked to this diagnosis; changing or broadening of criteria of diagnosis • Increase in maternal auto-immune disease (diabetes) and obesity: These disorders are increasing and are associated with increased risk for ASD in the offspring • Hygiene hypothesis: cleaner environment leads to deficiency in educating the immune system as well as increased asthma, allergies and autoimmune disorders; over-use of antibiotics and anti-fever medications may also contribute • Environmental toxins: • Lead • PCBs (polychlorinated bi-phenyls) • Organophosphate pesticides • Endocrine disruptors • Automotive exhaust • Polycyclic aromatic hydrocarbons • Brominated flame retardants • Perfluorinated compounds

7. Time window of vulnerability in fetal brain development – thalidomide example First trimester is also the vulnerable time for the maternal viral infection risk factor Rodier, 2000

8. Genetics and environmental risk factors in autism • Genes: monozygotic twin concordance is 50-88% • Dizygotic twin concordance is 31-36%, much higher than in siblings (3-14%) • Danish study of >10,000 ASD cases found an association between first trimester maternal viral infection and risk for ASD in the offspring • The presence of an inflammatory marker in amniotic fluid is associated with ASD outcome, as are inflammatory markers in maternal serum

9. Immune involvement in autism • The rate of autoimmune disease or allergies is higher in families with autism, particularly in the mother • Auto-antibodies directed against CNS antigens have been detected in sera of autistic subjects, as well as in the sera of mothers of autistic children • Immune-related genes are dysregulated in autism brains; microglia and astrocytes are activated; cytokines are elevated in brain and cerebral spinal fluid

10. Cytokines are elevated in autistic brains Vargas et al., 2005

11. Planned changes in autism diagnostic criteria • Published by the American Psychiatric Association, the Diagnostic and Statistical Manual of Mental Disorders (DSM) is used to diagnose mental and behavioral disorders. It thus influences the choice and availability of treatments as well as insurance coverage. • Revisions to the current DSM-IV are being finalized in 2012, with DSM-V due for publication in May, 2013. • Reason for proposed changes: attempt to establish more reproducibility and homogeneity in diagnosis

12. Planned changes in autism diagnostic criteria Proposed changes: • Eliminate subcategories including Asperger’s syndrome, PDD-NOS, Rett syndrome, and childhood disintegrative disorder. All of these would be subsumed under the umbrella term, autism spectrum disorder (ASD). • Instead of 3 domains of autism symptoms (repetitive behaviors and deficits in social interaction and language), 2 categories would be used: impairment in social communication and interaction, and restricted interests/repetitive behaviors. No mention of verbal language – it will be considered a co-morbidity. • A new symptom would be included in the second category: hyper- or hypo-reactivity to sensory input, or unusual interest in sensory aspects of the environment. • Each person will also be evaluated in terms of known genetic causes, level of language and IQ, and presence of seizures and/or GI problems. • A new category of Social Communication Disorder will be added to the DSM (people without repetitive behaviors).

13. Planned changes in autism diagnostic criteria • Positives: The subtypes that will be eliminated cannot be reliably distinguished by expert clinicians; more information will be required in the diagnosis (genetics, IQ, GI issues, seizures, regression history, nature of language impairment), so subtyping will be more straightforward.

14. Planned changes in autism diagnostic criteria • Negatives: There is some concern that the criteria will exclude some people who currently have the diagnosis, particularly the higher functioning, milder cases, that do not display repetitive behaviors, for instance. This may result in denying medical treatment and social services to some people on the autism spectrum. • Three published studies suggest that 25-78% of Aspergers or high functioning autism will be excluded from the autism diagnosis in DSM-V. Two other, small studies did not support these conclusions, however. • The Autism Speaks foundation is currently funding studies to determine how many people might be excluded and what the healthcare consequences might be. • A significant change in diagnostic criteria in 2013 would complicate future longitudinal studies of prevalence.

15. NOW, for all the answers… from MIT Press Book blog: http://infectiousbehavior.wordpress.com Children withautism - M.I.N.D. Institute, U.C. Davis