Home > Causes, Librarianship, Mental Illnesses and Disorders > The Neuroscience of Autism and Learning Disabilities (Science Librarian Boot Camp 2012 Tufts University)

The Neuroscience of Autism and Learning Disabilities (Science Librarian Boot Camp 2012 Tufts University)

Instead of inundating you with my notes from yet another professional development session, I decided to select out my favorite part to share with you all.  Out of everything I did in the Science Librarian Boot Camp, I enjoyed the Neuroscience presentations the most.  So, here they are. Enjoy!

“Genetics of Neurodevelopmental Disorders,” Dr. Anthony Moncao, Tufts University

  • Genetics studies Genes. Neurodevelopment studies Proteins and Regulatory DNA. Imagining studies the Brain.  Psychiatry studies Behavior.
  • Genes aren’t determinative.  They interact with the environment.
  • There is very strong evidence that genetic factors increase risk.
  • Susceptibility genes–genes that with environmental factors increase risk for these diseases
  • How do we find susceptibility genes?
  • Identify a chromosomal translocator and neurodevelopmental disorder.
  • Copy number variants –> Deletion or addition/duplication of material.  We all have these in some variation but in some instances they hit important areas.  They are inherited or de novo (neither parent had it).
  • What is “strict” Autism?
  • Impairment in: verbal and nonverbal communication, reciprocal social interaction, repetitive and stereotyped patterns of interest (don’t ilke change)
  • Onset before 3 years
  • male to female ratio: 4 to 1
  • Autism Spectrum includes Asperger Syndrome, PDD-NOS (removed from DSM5)
  • Autism Spectrum has a combined incidence of about 1%
  • 5% of Autism Spectrum disorders are comorbid with Fragile X, Tuberous Sclerosis, Down’s, muscular dystrophy, and other Mandelian disorders.
  • What are the genetic factors in Autism?
  • heritability is about 85 to 92%
  • rate among siblings is 3 to 9%
  • It is one of the most strongly genetic of childhood-onset psychiatric disorders.
  • No evidence yet for genes with variants in all forms of Autism.
  • Hardly any two autistic kids are gonna be the same (genetically).
  • Many of these genes are important in synapses.
  • Cadherin 8 (CDH8) is probably the culprit in these microdeletions.
  • Variable expressivity –> a deleted gene can cause multiple different outcomes (autsim, learning disorder, etc…) so evidence is strong environment is a factor
  • Future prospects include: Cohorts, sequencing, translation, use of rare CNVs diagnostically, genetic counseling, early intervention for sibs, CNVs may help us predict the outcome.
  • Projected future difficulties include: CNVs are common, so we have to be sure the one we’re calling Autism really is.  Ethical issues of testing children before they have any symptoms.
  • Autism has very complex etiology.
  • Collaboration is important to make progress.
  • Specific Language Impairment.
  • Just as frequent as dyslexia/autism.
  • It is a difficulty acquiring expressive and/or receptive language despite adequate intelligence and no physical problems (ie deafness).  Problems in producing and comprehending speech, problems reading, normal nonverbal IQs.
  • It has an almost 100% heritability.
  • Inheritance is simple but complex phenotype.
  • The damaged gene –> FOXP2
  • A transcription factor.
  • Important in how the rest of the gene is regulated.  Kind of like a master switch.
  • Not the gene for speech (found in nonverbal species but important in vocalizations.  Mice won’t squeak properly.  Songbirds can’t learn songs if it is damaged.)
  • FOXP2 inhibits CNTNAP2 from being expressed (Sitting on it and not letting it make RNA).
  • Where is FOXP2 expressed in the brain? In the basal ganglia, phallus, cerebellum (motor centers).
  • Chimps are more similar to mice than humans in this gene.
  • FOXP2 is a regulatory gene.  Its downstream targets offer entrypoints into neural pathways involved in speech and language.
  • Developmental Dyslexia.
  • It is a diagnosis of exclusion.
  • 5% of schoolchildren have it.
  • Males are 3 to 4 times more effected than females.
  • Gene variant is two times as frequent in dyslexics as in controls.
  • Variants in KIAA0319 repress the expression of the gene.
  • These variants increase risk in reading problems in the general population.
  • May inhibit migration of neurons to the right are of the cortex.
  • ectopia–small bundles of neurons in the wrong area of the cortex
  • 4 dyslexia susceptibility genes have been found so far.
  • All 4 play a role in neuronal migration and/or axonal growth.
  • DNA is not determinative.  There are many other factors involved.

“Neuroimaging of Children’s Brains,” Dr. Jean Frazier, UMass Med

  • Goal: To explore how neuroimaging techniques provide insight into potential biomarkers for childhood onset neuropsychiatric disorders.
  • Basic principles of brain development: structures start small, get big, then get small again
  • 8 to 14 is an important age range.
  • They exuberate then prune, and it is the pruning that is important.
  • The more complicated a process is the more potential it could go awry.
  • Pruning is guided by “use it or lose it.”
  • The exact timing varies by structure.
  • birth to 3–time of rapid intellectual, emotional, and physical growth of brain and brain wiring
  • by age 6–95% of brain development completed
  • 8 to 13–2nd major brain growth spurt
  • 13 to 20s–pruning to organizing, especially in frontal cortex.
  • We can measure things that require energy using: PET, SPECT, fMRI, EEG, MEG
  • What MRI can tell us: structure, metabolites, blood flow, connectivity
  • MRS–noninvasive, analytic method to measure chemicals within body parts
  • If we are going to fully appreciate what is going wrong in brains, we have to fully understand what is going right in brains.
  • Whereas gray matter gets pruned, white matter increases.
  • Less gray matter, brain becomes more efficient.
  • But what happens in atypical development?
  • More blood flow in amygdala of depressed and anxious.
  • amygdala–governs ability to modulate our affect
  • Bipolars have abnormal connectivity in brain, especially in areas dealing with affect regulation and attentional capacity.
  • Application to Autism?
  • Recommends “Localization of white matter volume increase in autism and developmental language disorder” in Annals of Neurology by Herbert et al
  • Children with autism have more white matter.
  • Tracks most severely affected in Autism are growing/changing just after birth.
  • Biomarkers are a distinct characteristic that is an indicator of a particular biological condition or process.
  • Maybe the genetic risk factors are indicators of the dysfunction not the disorder.
  • Both schizophrenia and autism symptom is social withdrawal.
  • 1 in 54 boys and 1 in 252 girls (1 in 88 children) have Autism Spectrum, according to study from 2008
  • Inhibition of GABA and excitation of Glutamate are associated with autism.
  • Tuberous make too little of a certain protein. Fragile X makes too much.
  • Glutamate levels are higher in Autism.
  • Biomarkers could be used as predictors for treatment response.
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