Intellectual Disability

Question 1

What are the skills we develop as newborns, children and adults as we get older?

Answer 1

• newborns: develop response to their environment to communicate their needs
• children: learn to solve problems related to daily living and more abstract problems
• adults: learn to solve abstract problems

Question 2

Which 3 normal cognitive skills are lacking in a child with intellectual disability?

Answer 2

1. language
2. activity of daily living (like taking care of yourself)
3. Learning and memory

Question 3

What are some potential broad causes of ID ?

Answer 3

genetic, environment, drugs, brain malformation

they can be inherited or sporadic (de novo) where parents dont have it but it was somewhere down the line

Question 4

How many % of the population does ID effect?

Answer 4

3%

Question 5

What are the age ranges that ID is diagnosed in typically?

Answer 5

diagnosed between 3 and 9 years old typically (the earlier the better) and is a lifetime disorder

Question 6

What are some indirect (treatable) comorbidities associated with ID? (6)

Answer 6

1. OCD
2. Sleep defecits
3. anxiety
4. sensory processing defects
5. epilepsy
6. autism

Question 7

What are some direct (non treatable) comorbidities present in all people with ID? (3)

Answer 7

1. general mental ability
2. defects in adaptive function
3. onset in developmental period

Question 8

What is used to assess the developmental milestones?

Answer 8

• scales are used and have been developed to monitor the development of children and acquisition of new skills (all doctors need to have this) it shows what time the child should be able to do certain activities

Question 9

What is the psychometric testing approach to study intellectual development?

Answer 9

includes testing intelligence

Question 10

what are the two types of intelligence?

Answer 10

theoretical (i.e. general mental capability, ability to reason, solve problems, think abstractly and plan)
and
objective (IQ)

Question 11

Who was the first person to administer the IQ exam and why?

Answer 11

Alfred Binet was a psychologist that developed the IQ exams to test various mental functions to help identify the children who are struggling in school
- his test yielded a mental age of the child (age at which their mental capacity is at) and apply necessary schooling to keep child at appropriate mental age

Question 12

What are 2 components of the IQ?

Answer 12

1. verbal

2. non verbal (aka visuospatial) [usually for kids who cant speak or understand yet]

Question 13

what is the properties of the IQ results?

Answer 13

• mean is 100
• IQ is normally distributed
• IQ is relative to the children of the same age

Question 14

How is intellectual disability classified based on IQ level?

Answer 14

ID is an IQ of 2SD below the mean so below 70

Question 15

What is the IQ of mild ID?

Answer 15

50 - 70

Question 16

what is the IQ of moderate ID?

Answer 16

less than 36-50

Question 17

What is the IQ of severe ID?

Answer 17

less than 20-35

Question 18

What is the IQ of profound ID?

Answer 18

less than 20

Question 19

What are some abnormalities that are common in ID and shown in CT scans and MRI’s

Answer 19

cerebellar hypolasia (small cerebellum/ataxia) [most commonly seen in imaging]

• schizencephaly (split or cut in brain)
• hemimegalencephaly (when one side of the brain is larger than the other
• dysmorphic brain
• cerebral atrophy (loss of neurons and connections between them)

Question 20

How can genome sequencing tell us more about the genetics behind ID?

Answer 20

• it has a single base pair resolution
• allows us to identify single base pair changes in the DNA sequence of the exons or can be applied to entire genome (only looks at exons because introns are way too complicated to look at even tho introns contain most of our unique DNA)

Question 21

How has the evolution of sequencing change over time?

Answer 21

in the earlier days before 2001, you added one BP at a time with a radio active label and putting it into the gel electropheresis to see where it travels depending on the size of the basepair (this took a very long time)

after 2001, we switched from radioactive to flourescent and automated with color coded bases (called next generation)

Question 22

describe what happens during next-generation in steps?

Answer 22

1st step: amplifying DNA (extracting DNA from blood and amplify it by taking double stranded DNA and adding adaptors (primers) to it to give it direction; then it goes into a cell and the researcher floods cell with polymerase and makes more DNA replicates)
2nd step: sequencing DNA –> adding color coding base pair, then stopping the reaction, taking a picture, and then adding another color coding base pair, stopping reaction, and taking a picture …etc… for the entire exome or genome at the time so they can find mutations

Question 23

What are the pros and cons of old method genome sequencing and the next generation?

Answer 23

old method:
pros –> very DETAILED, rarely wrong
cons –> TOOK A VERY LONG TIME, only could do little segments

new method:
pros —> multiple sequences at a time, faster
Cons –> more error prone

Question 24

What is the definition of a syndrome?

Answer 24

a syndrome is when theres obvious physical dysmorphic features in the patient that the doctor can tell without doing examination the type of disorder the patient has (i.e. downs syndrome) and its certain symptoms in the history of the patient and certain signs in patient examination

Question 25

What does the karyotype of a person with Downs syndrome show?

Answer 25

three copies of chromosome 21 (abnormal)

Question 26

What are some characteristics of individuals with downs syndrome?

Answer 26

- most common cause of ID - trisomy of chromosome 21 - low tone and dysmorphic features in physical exam

Question 27

What is ID mainly linked to? and where in the lifetime of the patient does severe ID get shown?

Answer 27

ID is increasingly linked to genetic defects (done by linking ID observed in patients with specific gene mutations to understand the link) - severe ID is mainly ~55% to 70% linked to prenatal factors such as chromosomal and other genetic factors, and multiple congenital abnormalities and specific syndromes

Question 28

What are some characteristics of fragile X syndrome?

Answer 28

- most common form of ID in males because its x-linked and males only have one X - dysmorphic features like large ears and large forehead but other times u cant tell - epilepsy (30%) - visuospatial memory defects like guiding maps - autism (60%) --> most common cause of autism

Question 29

Where was the fragile X gene intially found? and what does localizing the defect on the X-chromosome allow us to do?

Answer 29

it was found at the bottom of the X chromosome strand and theres a little indent at the bottom instead of being straight out - localizing the defect to the x chromosome allows us to localize the gene responsible for fragile X on the chromosome

Question 30

What is the gene responsible for fragile X syndrome on the X-chromosome?

Answer 30

called the fragile X gene

Question 31

What occurs to the fragile x gene in individuals with fragile x disorder?

Answer 31

their fragile X gene is mutated OR more frequently, there is a CGG repeat expansion before the gene, and this extra CGG causes the gene to be silenced due to methylation (adding methyl group on the gene) long way of explaining: too many CGG repeats cause non-coding which the cell detects this non-coding as a viral invasion and shuts down that area of the chromosome and therefore silences it BY METHYLATING IT (adding a methyl group) the usual number of repeats of the CGG sequence is 200 for it to be fragile x but everyone is different

Question 32

How do the synapses and dendritic spines in individuals with Fragile X syndrome look like?

Answer 32

the dendritic spines are more immature (long/thin) and this affects the synapses and communication in the brain

Question 33

When is the genome wide approach useful?

Answer 33

it is useful in cases where there is no knowledge of the genetic basis of the disorder because it allows to test all 25,000 genes of the genome

Question 34

What is Rett's Syndrome? what are the common features of a child with it?

Answer 34

- most common cause of ID in girls - apraxia (can move limbs but cant preform tasks) - breathing problems - shaky, unsteady or stiff gait - slow head growth beginning at approx 5-6 months of age (microcephaly) - loss of purposeful hand movements - loss of normal sleep patterns very distressing because they are LOSING skills as they are developing

Question 35

What is the known cause of Rett's Syndrome?

Answer 35

mutation in the MeCP2 gene

Question 36

What is the function of the MeCP2 gene?

Answer 36

it regulates epigenetics (gene expression towards environmental factors/cues) - MeCP2 naturally blocks the site of transcription by binding the DNA to a methyl group and causing silencing of the gene - this is the normal function of the MeCP2 is to block those sites from being transcribed so theres not too much transcription

Question 37

What does epigenetics refer to?

Answer 37

1. change that do not modify the sequence of dna like mutations do 2. they control the expression of DNA

Question 38

What is another gene that is thought to cause microcephaly that isnt linked to the meCP2 gene in rett's syndrome?

Answer 38

the single gene deletion in FOXG1 (gene involved in proliferfation of brain cells), its lacking in individuals with rett's syndrome bc their head stops growing at 5-6 months of age due to microcephaly

Question 39

What is FOXG1 syndrome and what are its characteristics?

Answer 39

- post-natal microcephaly - severe developmental delay - absent language - dyskinesia (abnormality of voluntary movement) - corpus callosum hypoplasia (under development of corpus callosum)

Question 40

What model is used to study ID?

Answer 40

learning and memory models

Question 41

How has Ivan Pavlov contributed to the learning and memory model?

Answer 41

developed behavioral experiments for studying conditioning aka conditioned stimulus via classical conditioning

Question 42

how did Watson contribute to the learning and memory model?

Answer 42

he developed paradigms in animals to model normal psychological development in humans - reinforcement of a response based on timing - development of natural reflexes that can be conditoned in a child via negative experiences (like afraid of a toy because they associate it with a frightening sound)

Question 43

How was Thorndike contributed to the learning and memory model?

Answer 43

Thorndike created the animal models that watson used in experimental psychology - he studied the associative processes of learning in animals - as u increase the trials, the animals can learn fast and faster how to get out of the cage - animals can solve problems initially by trial and error and then by planning - same to be shown in children by piaget

Question 44

How has Donald Hebb contributed to the principals of memory formation?

Answer 44

he discovered LTP (long term potentiation) that occurs when two synapses fire at the same time towards the same thing (they form an association and then start to regularly fire at the same time) he used the behaviourist methods to come up with this

Question 45

What type of animal models are commonly used to look at the genetic basis of learning disability/memory and ID?

Answer 45

1. mouse and rats 2. aplysia (a sea slug) 3. tissues and neurons cultured 4. humans (dead or alive) 5. insect, fishes and worms

Question 46

How were humans used to contribute to memory research?

Answer 46

Brenda Milner used H.M to underlie the importance of the hippocampus and temporal lobes in memory

Question 47

How was the aplysia used to contribute to genetic basis of learning and memory research?

Answer 47

used by eric Kandel by forming a simple reflex of pain in Aplasia. Kandel was able to find which genes were important in the process --> habituated and caused sensitization of the aplaysia reflexes he also identified the cAMP pathway as a key in memory

Question 48

How are rats and mice used in lab settings to contribute to learning and spatial memory research?

Answer 48

experiments done with rats and mice such as the Morris Water Maze allows to study the spatial learning in mice and rats - the morris water maze is where the rat is placed in water with with a submurged platform somewhere in it, the rat has to swim to find it. After a few short trials, the rat instaneously finds the platform. They tested the same thing in rats with spatial memory defects and they could not improve in trials like the controls did

Question 49

How were rats and mice used for research of the condition called Tuberous Sclerosis?

Answer 49

TS is a mutation of TSC 1 or TSC2 gene (it is a lesion or tumour near the ventricles that results from too many cells building up) - treatment with drugs can reverse the memory defect of the mouse model of TS (therefore mice can be used for TS research)

Question 50

how have fruit flies been used in genetics of learning and memory and ID research?

Answer 50

- Kandel used fruitflies in addition to sea slug to show the importance of cAMP in memory formation - Tully used fruitflies to show the importance of CREB in long term memory formation and how CREB is the master regulator of transcription and how it transcribes genes once its activated - the memory genes discovered by kandel and tully overlap with some genes in patients with ID

Question 51

How were fruitflies used in research of fragile-x Syndrome?

Answer 51

fruitflies have the fragile X gene that is a homologue to humans! they also have 85% of the genes involved in neurological disorder - impaired protein synthesis dependent memory in fragile X mutant flies showed that flies preformed poorly in the association/classical conditioning experiment without the fragile X gene

Question 52

What does the drug CXM do in fruitflies with fragile x mutations?

Answer 52

- The drug CXM rescues the LTM in fragile x mutants in fruit flies - it is a powerful protein synthesis inhibitor that can reverse the excess protein synthesis and the memory defect in fragile x flies. It has now been shown to have an effect on seizure and memory in mammals