Autism
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description
Autism. Laura Wong [email protected]. Take Home Points. Autism (and ASD) is genetically and phenotypically diverse The unifying feature of the genetic data is that genes involved frequently relate to the synapse which can affect neuronal networks. Overview of the clinical features - PowerPoint PPT Presentation
Transcript of Autism
Take Home Points
• Autism (and ASD) is genetically and phenotypically diverse
• The unifying feature of the genetic data is that genes involved frequently relate to the synapse which can affect neuronal networks
I. Overview of the clinical featuresII. Current researchIII. Some theoriesIV. Possible treatments
I. Overview of the clinical featuresII. Current researchIII. Some theoriesIV. Possible treatments
A little history
• 1943, Leo Kanner– Observed 11 boys– Used term “autism” to describe
the progressive loss of contact with outside world
• Hans Asperger– Concurrently, and
independently wrote thesis on same type of child
– Also used “autism”
A 7-year-old boy has significant impairment in social interaction, lectures rather than converses, and is obsessed with dinosaurs. His cognitive and language development are age appropriate. The most likely diagnosis is: .
a. autism.b. Asperger's disorder.c. social anxiety disorder.d. oppositional defiant disorder.e. Rett' s disorder
A 7-year-old boy has significant impairment in social interaction, lectures rather than converses, and is obsessed with dinosaurs. His cognitive and language development are age appropriate. The most likely diagnosis is: .
a. autism.b. Asperger's disorder.c. social anxiety disorder.d. oppositional defiant disorder.e. Rett' s disorder
A 7-year-old child is brought in for an evaluation. The child began using phrase speech at 48 months of age, has poor self-help skills, and has an inability or unwillingness to follow instructions in class. The child does not engage in appropriate eye contact, respond to the social signals of others, nor engage in imaginative play. The child's language is still moderately delayed. The most likely diagnosis is:
a. childhood schizophrenia.b. oppositional deviant disorder.c. Asperger's disorder.d. Rett syndrome.e. autism.
A 7-year-old child is brought in for an evaluation. The child began using phrase speech at 48 months of age, has poor self-help skills, and has an inability or unwillingness to follow instructions in class. The child does not engage in appropriate eye contact, respond to the social signals of others, nor engage in imaginative play. The child's language is still moderately delayed. The most likely diagnosis is:
a. childhood schizophrenia.b. oppositional deviant disorder.c. Asperger's disorder.d. Rett syndrome.e. autism.
Autism most commonly occurs as a comorbid with which of the following?
a. Mental retardationb. Bipolar affective disorderc. Substance use disorderd. Obsessive-compulsive disordere. Attention-deficit hyperactivity disorder (ADHD)
Autism most commonly occurs as a comorbid with which of the following?
a. Mental retardationb. Bipolar affective disorderc. Substance use disorderd. Obsessive-compulsive disordere. Attention-deficit hyperactivity disorder (ADHD)
From dsm5.org
I. Overview of the clinical featuresII. Current researchIII. Some theoriesIV. Possible treatments
From Holt and Monaco, 2011
Causes: Genetics at the Synapse• Neural migration
– Reelin– Neurotrophin family
• Synaptogenesis– Neuroligins– Neurexin– Shank3
• Neurotransmission– Serotonin transporter– GABA and glutamate
receptors– Voltage-gated ion
channels
• Each responsible for less then 1% of autism cases
Gepner et al 2009
Penzes et al 2010
Testing Mouse Models of Autism
DiCicco et al 2006
Autistic Mouse Model: NLGN4 KO
Mouse Socialization
Mouse Ultrasonic Communication
Jamain et al 2005
Autistic Mouse Model: NLGN4 KO
Jamain et al 2005
Shank3 KO
Shank3 KO
Shank3 KO mouse
Problem
These mutations account for only a small percentage of autism!!
Copy Number Variations
• Alterations of genomic DNA structure resulting in the cell having an abnormal number of copies of one or more sections of DNA
Duplication of Ube3a
Smith et al. 2011
I. Overview of the clinical featuresII. Current researchIII. Some theoriesIV. Possible treatments
Neuronal Homeostasis
From Ramocki and Zoghbi, 2008
From Holt and Monaco, 2011
Transcriptional StudiesNeuronal genes
Inflammatory/Immune
I. Overview of the clinical featuresII. Current researchIII. Some theoriesIV. Possible treatments
Chelation
Trial to test use of DMSA (a common chelator) failed to pass IRB due to concerns regarding safety in those without detectable heavy metal poisoning.
Minocycline
Bilousova et al, 2009
Rotschafer S.E, 2012
Ultrasonic Vocalizations
Dendritic spines
Take Home Points
• Autism (and ASD) is genetically and phenotypically diverse
• The unifying feature of the genetic data is that genes involved frequently relate to the synapse which can affect neuronal networks
Common Traits of Autism
• Preference for aloneness• Insistence on sameness• Liking elaborate routines• Some abilities that seemed remarkable
compared to deficits
Core Domains• Socialization
– Impaired use of non-verbal behaviors – Delayed peer interactions– Absence of seeking to share enjoyment and interests– Delayed initiation of interactions– Little or no social reciprocity and absence of social judgment
• Communication– Delay in verbal language without non-verbal compensation– Impairment in expressive language and conversation, and disturbance in
pragmatic language use– Stereotyped, repetitive, or idiosyncratic language– Delayed imaginative and social imitative play
• Behavior– Preoccupation with stereotyped or restricted interests or topics– Adherence to routines and rigidity behavior– Stereotyped, repetitive motor mannerisms– Preoccupation or fascination with parts of items and unusual visual exploration
