Autism

Question 1

Severe neurodevelopmental disorders with very early onset (1 – 8 years)

Three Subtypes:
Three core deficits:

Answer 1

Autism (true Autism)
Asperger’s Syndrome (high functioning Autism)
Pervasive developmental Disorder – not otherwise specified (atypical autism)

Social interaction
Social communication
Restricted, stereotyped and repetitive pattern of behaviour

Question 2

Autism is the most severe illness within…

Approximately ? per 1000 cases. Tendency increasing.
The male to female ratio of ASD is about…

Answer 2

ASD. It starts at an earlier age and invariably is accompanied by severe mental retardation

5 – 10
4 : 1

Question 3

Additional Symptoms
Up to 40 to 50% of the patients in addition to suffering from social behavior, communication and stereotypy behavior, suffer from…
Epilepsy is seen in a large number of patients with…
Gastrointestinal disorders are seen in up to…

Answer 3

anxiety disorders or depressive disorders
neurological disorders
50 – 60% patients

Question 4

Concordance rate in monozygotic twins is about…

Answer 4

60 – 80%,

Question 5

Potential Genetic Factors

1. Neurodevelopmental genes
Reelin 
Neuroligin
MET 
CNTNAP2 

2. Neurotransmitter related genes
   SERT
   GABA receptors
   Oxytocin receptor 1

Answer 5

guiding migration of neurons
synapse formation
neuronal migration
differentiation of axons

Question 6

Environmental Factors:

1. Maternal Infection
2. Maternal autoimmune disease
3. Maternal exposure to valproate
4. Maternal stress
5. Not vaccinated

Answer 6

Viral infection in the first trimester
Bacterial infection in the second trimester
Treatment of certain forms of epilepsy
Exposure to a severe hurricane during middle of pregnancy (17-24 weeks)
Incidence 1%

Question 7

Maternal infection, maternal stress and valproate leads to…
This immune response consists of…
Interleukins and cytokines penetrate through the…
Leading to an increase in…
This then sets off a further increase in….
These cytokines affect…
Leading to an increase in…
Under normal circumstances reduced by an increase in the…
In individuals with a genetically compromised SERT activity, this increased extracellular 5-HT cannot be…

Answer 7

an activation of the immune system.
an increase in interleukins and cytokines to kill the invading bacteria
blood placenta and the blood brain barrier
interleukins in the fetal brain, where it triggers the activation of microglia.
interleukins, leading to a cytokine storm
brain development
5-HT release
SERT activity
removed fast enough and will therefore affect normal brain functioning.

Question 8

Gene – Environment Interactions in Autism

maternal infection → increase in…
normally easily compensated by…
This is not possible if the SERT activity….

Environmental factors only lead to autism in…

maternal infection → cytokine storm and increase in 5-HT, it is rapidly…

maternal infection (in individuals with genetically compromised SERT activity) → cytokine storm and increase in 5-HT → not compensated for by…

Answer 8

5-HT levels
increased SERT activity.
in genetically compromised

genetically vulnerable individuals.

counteracted by increase in SERT activity.

an increase in serotonin transporter because of the genetic deletion/reduction of SERT activity.

Question 9

Morphology
No clear abnormalities
- Brains are somewhat larger
- Some decrease in white matter (connections)
--------------------------------------------------------------------------------
Neurotransmitters
- Serotonin
> Blood 5-HT 50% increased 
- Dopamine – unclear
- Oxytocin – decreased transmission

Answer 9

predominantly a disturbance of connectivity, resulting from
miscommunication between different brain structures
——————————————————————————
The serotonin cells are in the dorsal raphe, project to all the structures in both domains. 95% of serotonin is in the periphery
——————————————————————————
plays a role in social behaviour (play behavior) and reward
The dopamine cell bodies are in the midbrain, especially in the VTA. Projects predominantly to the ACC and amygdala, regulate neurotransmission/communication at those levels.

Plays an important role in communication/social bonding

Question 10

Example of miscommunication in the brain in ASD
Tower of London/Hanoi
Aim: to place the three discs one at the time on the last stick. But larger ones cannot be on top of smaller ones
Measure activity in frontal and parietal cortex

Answer 10

In patients: lack of synchrony/communication

Strong significant correlation between frontal and parietal cortex for control participants
No correlation for autism participants
Dysconnectivity between prefrontal cortex and parietal cortex

Question 11

Oxytocin is produced by the….
Cells that produce oxytocin release oxytocin in the… Enters into the bloodstream…
The hypothalamus and median eminence where the BBB is weaker, oxytocin can be released (it is a big peptide).
Oxytocin projects to other brain regions in the brain (e.g., nucleus accumbens, amygdala)

Play a role in labour
- Stimulates...
Plays a role after birth
 - Milk ejection (together with prolaction, milk production)
- Also enhances....
Plays a role in... 
- Social bonding, romantic relationships

Answer 11

hypothalamus
pituitary gland
reaches the rest of the body

uterus contraction and placenta release
maternal bonding
social behaviour

Question 12

Treatment:
Few pharmacological possiblities, mostly aimed at reducing...
SSRI
Atypical antipsychotics (Risperidone)
Oxytocin...

No clear improvement was noted in social functioning or communication.

Answer 12

stereotyped/compulsive behaviours
It is a peptide and can therefore not be taken orally, use as a nasal spray can penetrate the brain
Oxytocin has a positive effect on social responsiveness than the repetitive behavior

Question 13

Twin Concordance Rate - MZ

Answer 13

80 to 90%