5. Etiology: Genetic & Environmental Causes

Question 1

How do twin studies demonstrate that genetics play a huge role in autism.

Answer 1

if one identical twin has autism, the other twin has an 80% chance of also having autism.

Question 2

How might mutations be involved in contributing to autism?

Answer 2

Most mutations are harmless but a few may work together to cause autism.

Question 3

What are environmental risk factors?

Answer 3

Anything a person can encounter before or after birth that is NOT genetic. (eg. chemical exposures, womb environment, birth complications, parental age, SES etc.)

Question 4

What are some environmental factors known to be associated with autism?

Answer 4

• mothers’ use of valproic acid (an anti seizure medicine during pregnancy)
• advanced paternal age
• pregnancy complications

Question 5

Explain the consistent finding of early brain overgrowth in kids with autism.

Answer 5

Early brain overgrowth is a consistent finding in kids with autism. The brain has excessive neurons and tissue at the frontal lobe. The frontal lobe is important for social, emotional, communication, and reasoning functions. The excess number of neurons can create substantial and excess miswiring. Too many incorrect connections can impair a child’s ability to learn social and communication functions well.

Question 6

Current estimates that there are ___ genes that are implicated in autism.

Answer 6

200-400 (this explains a huge spectrum!)

Question 7

Are the genes implicated in autism random?

Answer 7

These genes are not random genes but they cluster together in a network that is starting to make sense

Question 8

Explain a multilevel understanding of ASD.

Answer 8

1) Genotype - biological/genetic factors
2) Endophenotype - altering brain development, function, structure, connectivity
3) Phenotype - presenting in development, functioning, behavior

Question 9

Explain one possible ethical controversy pertaining to understanding the causes of autism

Answer 9

wanting to eliminate this group of people through genetic modification or abortion. Autism is not the same as measles! autism has positive and negative aspects, we need such people around and it is unethical to “eliminate” them altogether. Purpose of research should be to serve the autistic community, not be to eliminate them.

Question 10

Why might it be important to know the causes of ASD? (6)

Answer 10

1) to understand developmental course, trajectory, and progression of ASD over the lifespan
2) to reduce severity and negative impact of difficulties
3) to strengthen competencies and skills/improve QOL
4) to reduce severity of distress and associated impairments
5) to target modifiable environmental factors
6) to have individualized treatments for different “subgroups” within ASD. subgroups have different genetic loads and combinations. treatment should match their profile so they can benefit more from such specialist support.

Question 11

Why is it so challenging to investigate and identify the causes of ASD?

Answer 11

1) ASD is a very heterogeneous condition between individuals and within individuals across development
2) hard to identify “cause-and-effect” or directionality.
3) ethical consideration - how will the findings be used (controversial)

Question 12

When researching the causes for ASD, what are we currently focusing on?

Answer 12

On explaining:
- social communication impairments
- restricted, repetitive behaviors (RRBs)
- associated ID and verbal impairments
at all levels (genetic, neurobiology, neuropsychology, behavioral)

Question 13

DNA can have mutations. What are the 2 types of mutations?

Answer 13

• De novo (spontaneous)

- Inherited

Question 14

Why do we think ASD is genetic? (5)

Answer 14

1) prevalence - occurs everywhere in the world, across SES levels, ethnic groups, and age groups
2) high heritability - twin studies, family studies (increased prevalence in siblings, relatives)
3) higher association with other genetic disorders (eg. Fragile X syndrome FXS, Rett’s, Prader-Willi)
4) High rates of associated conditions (ID, Epilepsy, ADHD, OCD, Depression, Anxiety)
5) Higher Male to Female ratio (but could be a diagnostic problem)

Question 15

Why is it interesting that even for identical twins, ASD is not 100% genetically determined?

Answer 15

Because it shows that environmental factors still play a small role

Question 16

What is the Fragile X Syndrome?

Answer 16

• no. 1 inherited cause of intellectual disability
• mutation of FMR1 gene on X chromosome
• also “spectrum” of severity
• about 20% of individuals with FXS also have ASD
• most common genetic cause of ASD

Question 17

How do we study genetics in ASD using family studies?

Answer 17

Compare non-affected, simplex families, and multiplex families.
Simplex - only 1 person affected
Multiplex - more than 1 person affected

Question 18

How do we study genetics in ASD using twin studies?

Answer 18

Compare identical vs non-identical twins.
Identical twins have the same DNA so any differences in symptoms come from environment. Non-identical twins are like siblings basically. Share some DNA but not all.

Question 19

How do we study genetics in ASD using animal studies?

Answer 19

Can manipulate the genes. Eg. Knock out certain genes in mice and observe their behavior. Can also test out pharmacological treatment and see how it changes symptoms.

Question 20

What are the limitations of epidemiological, twin, and family studies?

Answer 20

Do not tell us about the genes involved or the frequency of copy-number variants.

Question 21

What are the 2 kinds of studies we can use to find out more about the specific genes implicated? (2)

Answer 21

1) whole-genome analyses studies
- analyse all genes using whole sequencing (more exploratory)
2) candidate gene studies
- select some more possible specific gene candidates to analyse (more confirmatory)

Question 22

What are the current findings so far in studying genetic causes of ASD?

Answer 22

polygenic and synergistic

• many genes involved (hundreds of genes implicated in small ways)
• many genes interacting and working together
• each gene gives susceptibility

Question 23

What is the difference between risk and vulnerability?

Answer 23

Risk - any experience/condition that increases likelihood for psychopathology for ANY child exposed to it (eg. smoking is bad for everyone)
Vulnerability - any condition that increases the likelihood that PARTICULAR children will succumb to the risk. Intensifies a child’s response to the risk. (eg. if i have certain gene, i’ll be more vulnerable when exposed to the risk)

Question 24

What are the different stages that environmental factors can arise? (4)

Answer 24

• preconception
• prenatal (exogenous, endogenous)
• perinatal (birth process)
• postnatal

Question 25

Describe preconception factors.

Answer 25

Higher paternal and maternal age. can affect the quality of their eggs and sperms.

Question 26

Describe the 2 types of prenatal environmental factors.

Answer 26

Exogenous (from external environment) 
- valporic acid
- SSRIs 
- Toxic chemicals 
Endoneous (form internal womb environment)
- maternal metabolic conditions 
- mother's immune system 
- prenatal testosterone levels

Question 27

Describe perinatal environmental factors.

Answer 27

Birth complications

Prematurity/post-maturity

Question 28

Describe postnatal environmental factors.

Answer 28

• social environment. extreme early deprivation and “quasi-autism” (very socially deprived orphanages in romania, autism-like presentations manifested in these kids over time on a behavioral level)

Question 29

Are vaccinations a cause of autism?

Answer 29

NO. No evidence of a link despite hundreds of studies with millions of participants using different designs and methodologies.

Question 30

What are epigenetics?

Answer 30

The study of how environmental factors interact with genetic factors to increase risk

Question 31

In terms of neurobiological processes, what do we study?

Answer 31

study the structure, function, and connectivity of the brain.

Question 32

What are the 3 ways we can study the brain?

Answer 32

1) neuroimaging (Structural, Functional, Diffusion MRI), tomogrpahy (CT/CAT scans), electrocephalography
2) Lesion studies (animals where u lesion specific brain areas, in humans only if spontaneously occurring)
3) post-mortem histological studies of brain tissue

Question 33

How do we study the brain in ASD using social cognition/social emotion tasks?

Answer 33

1) face recognition/face processing – social and emotional processing of facial expressions
2) Theory of Mind – inferring others’ internal states and intentions. associating people with emotions. See meaning and make emotional attributions with everything.

Question 34

What does visual processing research findings tell us about ASD individuals?

Answer 34

Eye-tracking studies – track the gaze of ASD individuals, we realise they are focusing on other parts of the face (eg. chin, cheek) rather than the eyes where most social information is found. What they are looking at tells us what they are attending to and processing. They tend to look at non-socially charged aspects of visual processing.

Question 35

What do eye-tracking studies reveal about the strengths of ASD individuals?

Answer 35

They select and pay attention to certain details, but not the whole. We just need to find out how to capitalize their strengths!

Question 36

What are some negative aspects/challenges of current research on ASD causes?

Answer 36

• very small sample sizes
• inconsistent findings
• mostly cross-sectional studies, few longitudinal
• publication bias
• most studies focus on “global” rather than “local” specific differences

Question 37

What are some positive aspects of current research on ASD causes?

Answer 37

• focus on networks, not just regions/structure
• moving away from “cure” and drug treatments
• open, large scale databases
• increasingly more longitudinal studies

Question 38

Describe the abnormal brain activity in ASD in reaction to social cognition tasks.

Answer 38

individuals with ASD have reduced activation in anterior/posterior cingulate, amygdala, and anterior insula. greater activation in somatosensory regions.

Question 39

Describe the nature of brain connectivity of ASD individuals.

Answer 39

• Increased LOCAL frontal cortical connectivity
• Reduced LONG-DISTANCE connectivity between frontal cortex and posterior brain regions.
  (ASD individuals - “struggle to make sense of the complex social and non-social world with powerful lower-level processing potential but with a frontal cortex that is functionally disorganized”)

Question 40

“The number 8 when rotated 90degrees look like a pair of eye glasses”. How does the brain activity look like when ASD individuals do this True-False task?

Answer 40

tasks requiring integration of spatial processing and language comprehension –> decreased connectivity between frontal language regions and parietal spatial processing regions.

Question 41

“Judge if this face is the same as one previously”. How does the brain activity look like when ASD individuals do this True-False task?

Answer 41

decreased connectivity found between frontal executive regions and fusiform gyrus (face processing)