ASD (Autism Spectrum Disorders)

Question 1

What are some basic characteristics of ASD?

Answer 1

1. neurodevelopmental disorder with complex etiology (cause)
2. genetic factors play a central role and so does interaction with non-genetic factors
3. clinical and etiologic diversity
4. characterized by impairments in reciprocal social interaction, verbal and non verbal communication and a preference for repetitive activity
5. it is on a spectrum

Question 2

what is the prevalence of ASD?

Answer 2

1 in 68 and a recurrence risk estimated at 8-18%

Question 3

How common is ASD in Canada?

Answer 3

1 in 135 kids in K to grade 11 in montreal

1 in 150 in 3 to 10 yo in alberta

1 in 95 across 6 regions

1 in 94 in gr 1 to 12 in calgary

Question 4

What is the epidemiololgy of ASD?

Answer 4

• more common in boys than girls (4:1 sex ratio)
• genetic and environmental factors play a big role in biological vulnerability
• rates of ASD are consistant across international studies and ethnic and socioeconomic groups (except in the US diagnosis is less in minorities because theres not much access to healthcare)
• prevalence estimates steadily increasing over past 40 years

Question 5

What is ASD?

Answer 5

it is a developmental disorder like autism
- it changes with development in terms of clinical expression and it affects development like affects social experience, learning/cognition..etc..

it is heterogenous (clinically and etiologically diverse in terms of clinical and biological ways)

Question 6

According to the DSM-5 what are the requirements to be diagnosed with ASD? copy in notes

Answer 6

1. persistent deficits in social communication and interactions (need 3 out of 3 on that list)
2. restricted, repetitive patterns of behavior, interests and activities (need 2/4 on the list)

therefore a total of 5/7 and higher is needed to be diagnosed with ASD

Question 7

How do people with ASD show deficits in social-emotional reciprocity?

Answer 7

• One of the deficits in social communication and interaction across multiple contexts in DSM-5
  it ranges from abnormal social approach to failure of normal back and forth conversation, to reduced sharing interestes, emotions or affect; to failure to initiate or respond to social interactions

difficulty reading people and their motivations and intentions in a conversation and show either disengagement or TOO much engagement in their own topics and ideas

Question 8

How do individuals with ASD show nonverbal communicative behaviors?

Answer 8

• One of the deficits in social communication and interaction across multiple contexts in DSM-5
• used for social interaction ranging for example:
• from poorly integrated verbal and nonverbal communication; to abnormalities making eye contact and body language; to deficits in understanding and use of gestures; to a total lack of facial expressions and nonverbal communications

in little kids it shows as lacking joint attention skills like looking at something when they want it and then looking at the adult and then looking back at the object

Question 9

How do individuals with ASD show deficits in developing, maintaining and understanding relationships?

Answer 9

• One of the deficits in social communication and interaction across multiple contexts in DSM-5
• ranges from:
• difficulties adjusting behavior to suit various social contexts; to difficulties in sharing imaginative play or making friends; to absence of interest in peers
• ranges bascially from completely disengaged to somewhat having friends but in a very small circle

Question 10

How are restricted, repetitive patterns of behavior, interests, or activities shown in ASD according to DSM-5?

Answer 10

1. sterotyped or repetitive motor movements, use of objects or speech shown in ASD –> for example: simple motor stereoypes include lining up toys or flipping objects, echolalia (echoing what u say) and idisyncratic phases (innapropriate word use)
2. insistence on sameness, inflexible adherence to routines, or ritualized patterns of verbal/nonverbal behavior (i.e. showing extreme distress at small changes, difficulty transitioning, ridgid thinking patterns, greeting rituals, need to take same route or eat same food everyday) do not feel comfortable with unpredictability
3. highly restricted and fixated interests that are abnormal in intensity or focus (i.e. strong attachment to or preoccupation with unusual objects, excessively circumscribed or preservative interest) [i.e. public transportation]
4. Hyper- or hypo-sensitivity to sensory input or unusual interests in sensory aspects of the environment (i.e. apparent indifference to pain/temperature, adverse response to specific sounds or textures, excessive smelling or touching of objects, visual fascination with lights or movement)

Question 11

What are 6 major differences between DSM-5 and DSM-4 in defining ASD?

Answer 11

1. in DSM-5 theres two rather than 3 symptom domains
2. fewer permutations of symptoms for diagnosis (fewer ordering of the symptoms) therefore more on a spectrum
3. diagnostic qualifiers rather than subtypes
4. severity in each symptom domain relates to level of support required
5. age of onset is early but may not be evident until demands overwhelm capacity (in adult diagnosis)
6. boundaries are recast –> if you are diagnosed w ASD in DSM - 4 then u for sure are in DSM-5)

Question 12

What is the early signs of ASD findings in high risk infants?

Answer 12

1. social communication
2. play interests and behavior
3. motor skills and behavior

Question 13

How does social communication deficits manifest in high-risk infants?

Answer 13

manifests through:

1. delayed words and gestures
2. atypical eye gaze
3. reduced social smiling
4. reduced joint attention behaviors
5. reduced expression of positive affect (lack of ability to enagage even with familiar people) and lack of showing positive emotions

Question 14

How does Play deficit manifest in high risk infants?

Answer 14

• reduced imitation of actions
• reduced interest in social play
• repetititive actions with toys like spinning and rolling
• prolonged/intense visual examination of toys and other objects

Question 15

How does atypical motor skills and behavior manifest in high risk infants?

Answer 15

• delayed fine and gross motor skills
• reduced motor control
• repetitive/atypical motor behaviors and postures (waving arms up and down)

Question 16

What are 3 methods of assessment in order for clinical settings of ASD?

Answer 16

1. structured developmental and medical history (know their history) like initial concerns, developmental course, ASD symptoms, medical ROS (sleep, feeding and other med problems), and family + psychological history
2. structured observation of social, communication, and play-related behaviors
3. Developmental context –> assessment of language, cognitive and adaptive skills (developmental delays etc..)

Question 17

What are some signs of atypical brain development in ASD? (6)

Answer 17

1. abnormal acceleration in brain growth to age 2-3
2. abnormal neural connectivity
3. neuropahtologic abnormalities
4. abnormal brain activation with social perceptual tasks (decreased activation of FFA during face recgonition, and less amygdala activation and poorer preformance on tasks requiring subjects w ASD to judge facial emotion)
5. increased head circumference and brain volume among the most consistently replicated findings in ASD (20-30% macrocephaly) related to larger surface area rather than more thickness in cortical membrane
6. recent studies indicate post-natal onset of macrocephaly (average or below head size at birth)

Question 18

How is white matter abnormal in ASD?

Answer 18

white matter is disproportionately enlarged relative to gray matter

• white matter volume increase is found in subcortical areas and in origins and terminatios of projection and sensory fibers
• corpus callosum is abnormally small relative to brain volume
• structural and functional neuroimagining studies are consistence with the increased local and reduced distal connectivity (i.e. thats why they’re better at focusing on more detail oriented tasks rather than ones that require u to see the larger picture due to lack of distal connections)

their local connectivity is good for example between the same areas
distal: between larger areas and hemispheres

Question 19

What do neuropathological studies show in terms of ASD?

Answer 19

1. limbic system abnormalities: reduced number of cerebellar purkinje cells, small and densely packed neurons in limbic regions like amygdala, hippocampus and entorhinal cortex
2. abnormalities in brain stem, cranial nerve nucleii suggesting even earlier prenatal orgin
3. neuroinflammation –> micgroglia (role in synaptic pruning releases pro inflam. cytokines when activated; evidence of microglial activation in ASD in selected brain regions like dosolateral prefrontal cortex; cortical minicolumns are narrower and more numerous (immature) with greater cell dispersion; note associations between ASD and autoimmune disorders in family members like MS, diabetes..etc..

Question 20

What is the genetics of ASD?

Answer 20

• ASD is a strongly genetic disorder (90% heritibility) with MZ rates of 36-95%
• recent processes of genetics include: central role of rare de novo and inherited rare genetic varients like CNV’s
• atypical synaptic plasticity as a common functional mechanism

Question 21

What is the relation between ASD genes and synaptic plasticity?

Answer 21

ASD genes are ‘meeting at the synapse’
- meaning that many asd genes identified make proteins involved in regulating and maintaining neuronal synapse development and plasticity

Question 22

What has whole genome sequencing (WGS) show in terms of ASD?

Answer 22

shows that 16/32 families with deletrious genetic variants tat may have implications for clinical management and counseling
- de novo mutations identified in 19% and x-linked or autosomal inherited alterations linked in 30% of asd probands

Question 23

What was the significant finding in multiplex study?

Answer 23

that siblings with ASD may carry different pathogenic mutations; one sibling may have autism or ASD and the other kid might have another ID

therefore theres no single gene that accounts for autism/ASD

Question 24

What are the 3 routine recommended investigations of ASD patients?

Answer 24

1. audiology (to see if hearing isnt an issue in social understanding and response)
2. clinical microarray (array CGH) genetics testing
3. molecular testing for FraX (particularily for boys)

Question 25

what are other selective recommended invesitgations for ASD?

Answer 25

1. ferritin, TSH, CK, lead (iron levels testing)
2. metabolic testing for things like PKU
3. EEG
4. neuroimaging

Question 26

What do the EEG’s indicate in ASD?

Answer 26

EEG is not justified in children with ASD and ‘regression’ and does not predict subclinical epilepsy and does not alter management

Question 27

What does neuroimaging indicate for ASD?

Answer 27

some studies indicated relatively high rates of mostly minor CNS structural abnormalities in ASD
- other studies found low rates

summary: only indicated with specific comorbid diagnosis like TS or localizing findings

Question 28

What are some novel therapeutics for ASD?

Answer 28

• moving to an era of pharmacogenomics and tailored intervention
• identification of gene defects is the first step towards understanding the molecular pathophysiology and has yielded new treatments like for fragX and rett’s syndrome
• oxytocin has also been shown to increase levels of social interactions in individuals with ASD

Question 29

How is autism described as neurodiversity among the individuals who have it?

Answer 29

neurodiversity movement looks at ASD as a way of being

autistic adults view autisic as being a part of that person and a different way seeing the world (view it as being unique)