Neurodevelopmental Disorders

Question 1

Neurodevelopmental disorders

Answer 1

A group of disorders that affect the development of the nervous system leading to abnormal brain function which may affect emotion, learning, ability, self-control, and memory

Question 2

ASD

Answer 2

are a group of developmental disabilities that cause significant social, communication, and behavioral challenges.

Question 3

Three core deficits of ASD

Answer 3

1. Impaired social interaction
2. Impaired language and communication
3. Repetitive and stereotypical behaviors and severely restricted interests

Question 4

ASD treatment options

Answer 4

-focuses on reducing symptoms
-behavioral interventions: undertaken early in life, intensive delivery format, gold-standard treatment for behavioral symptoms associated with ASDs
-Medications: Risperidone: adult antipsychotic treatment of irritability and aripiprazole

Question 5

Mind blind hypothesis

Answer 5

Inability of mentalizing in ASDs is associated with impaired neural circuits underlying social cognition

Question 6

Anatomy of ASD

Answer 6

• social: fronto-temporal and frontoparietal regions, amygdala
  -communication: basal ganglia, cerebellum, thalamus, motor area
  Repetitive behavior: basal ganglia, thalamus

Question 7

Early brain overgrowth in ASD during early childhood

Answer 7

The brain of ASD patients is larger in volume than the brain of typically developing children, suggesting an atypical trajectory of maturation

Question 8

Dendritic Spine pathology in ASF

Answer 8

In ASD, exaggerated spine formation or incomplete pruning may occur in childhood leading to increased spine numbers

Question 9

What is some evidence of defects in synaptic pruning in ASD brains

Answer 9

Increased dendritic spine density in pyramidal neurons of the temporal lobe

Question 10

Twin studies in ASD

Answer 10

Establish the importance if genetics in autism

Question 11

Fragile X syndrome

Answer 11

Leading monogenjc cause of intellectual disability and autism

Question 12

Cause of fragile X syndrome

Answer 12

Mutations in the fragile X mental retardation 1 gene that is located in the X chromosome

Question 13

Abnormality in FMR1 Gene

Answer 13

-A trinucleotide repeat expansion (>200 CGG) within the 5’ untranslated region if the FMR1 gene causes hypermethylation and transcriptional silencing

Question 14

FMRP protein

Answer 14

-RNA binding protein that shuttles between the nucleus and cytoplasm of neuronal cells
-involved in the transport of mRNAs and their translation to synapses
-FMRP can also be involved in the nuclear RNA interference pathway that is associated with non-coding RNAs to suppress gene expression

Question 15

Altered synaptic pruning without FMRP

Answer 15

FMRP regulates the synthesis of structural proteins or signaling proteins that are important for stabilizing and maturing developing synapses

Question 16

Hyper-excitability in FXS

Answer 16

-FXS hyperexcitability is apparent in elevated neuronal firing frequency
-FMRP can indirectly regulate neurotransmitter release by controlling the action potential peak and duration, which in turn determine the amplitude and duration or presynaptic calcium influx through voltage-gated calcium channels
-Dendritic excitability is governed mainly by ion channels, a number of which are dysregulated in the absence of FMRP

Question 17

More than just neurons

Answer 17

-Altered NSC proliferation, fate specification , and maintenance
-Stunted dendritic morphogenesis and altered axon targeting -> reduced synaptogenesis and altered circuit integration
-altered astrocyte-neuron interactions
-impaired white matter development and myelination