1. Development of the NS
start with a single cell that begins to divide!

2. Neurulation
Gives rise to neural tube (which gives rise to the CNS)

3. CNS development What determines what and where a neuron should be?
very complicated – numerous models; pluripotent (versatile) to begin with
role of nearby chemical factors that can influence things

4. How do neurons get to where they need to be?
cortex has multiple layers with different size/shape neurons -
radial glia in cortex

5. Other regions - growth cones and “lamellipodia”
cell attractants and repellants

6. Once neuron reaches destination; it needs to
form synaptic connections
make neurotransmitter
elongate its axon
make postsynaptic and presynaptic receptors
JUST TO NAME A FEW THINGS!!!

7. Some things that happen during CNS development
apoptosis – “programmed cell death”
what controls apoptosis
many things!
activity
drugs?
environment?

8. Amazing it all works!!!!
two disorders where brain development does not go quite as planned
autism and Fetal Alcohol Syndrome
similar in that these both involve changes in brain during developmental;
developmental disorders
differences
one is preventable!

9. Autism characteristics: Delayed or unusual speech patterns
High pitched or flat intonation
Lack of slang or "kidspeak"
Difficulty understanding tone of voice and body language as a way of expressing sarcasm, humor, irony, etc.
Lack of eye contact
Inability to take another's perspective (to imagine oneself in someone else's shoes)
hypo or hypersensitive to environmental stimuli

10. Additional personality characteristics
Engage in repetitive behaviors and ritualized activities, ranging from lining up items to following a rigid routine; OCD symptoms
Have one or a few passionate interests,
Have difficulty in making and keeping multiple friends,
Prefer activities that require relatively little verbal interaction.

11. Evidence for CNS?
possible deficits in complex or higher order cognitive abilities
evoked potentials
auditory and visual ERPs altered
processing of emotional facial expressions
- ERPs

13. Developmental Issues Following Fetal Alcohol Exposure

14. Definitions
Teratogen: a substance capable of interfering with fetal development
Teratology: the biological study of birth defects
Behavioral Teratology: the study of how agents can affect behavior (so affects brain)

15. Historical View of Alcohol as a Teratogen
“Foolish, drunken, or harebrain women most often bring forth children like unto themselves” Aristotle in Problemata
“Behold, thou shalt conceive and bear a son: And now, drink no wine or strong drink.”
Judges 13:7

16. Alcohol as a Teratogen: 20th Century
“… the idea of germ poisoning by alcohol in humans may be safely dismissed…”
Journal of Studies on Alcohol, 1, 1940
“The offspring of alcoholics have been found defective not because of alcoholism of the parents but because the parents themselves came from a defective stock.”
Journal American Medical Association, 132:419, 1946
Ethanol drip was used to treat premature labor.
1973: First scientific paper naming Fetal Alcohol Syndrome

17. Fetal Alcohol Syndrome
Fetal alcohol syndrome is the leading preventable cause of mental retardation.
What is it, how does it affect people, what can we do about it?

18. Fetal Alcohol Syndrome: Diagnostic Criteria
Pre- and/or postnatal growth deficiency
Evidence of central nervous system dysfunction
Specific pattern of facial features

19. FAS: Characteristic Facial Features
Streissguth, 1994

20. FAS – Only the tip of the iceberg
Fetal alcohol syndrome
Fetal alcohol effects
Clinical suspect but appear normal
Normal, but never reach their potential
Adapted from Streissguth

21. Fetal Alcohol Spectrum Disorders (FASD)
ARND: Alcohol-Related Neurodevelopmental Disorder
ARBD: Alcohol-Related Birth Defects

22. Statistics Approximately 1 FAS birth out of 1000 live births in the US
Approximately 3-6 FASD births out of 1000 live births in the US
Estimated costs 2.8 billion/year

23. Cause of FASD
The sole cause of FASD is women drinking alcoholic beverages during pregnancy.
Alcohol is a teratogen.
“Of all the substances of abuse (including cocaine, heroin, and marijuana), alcohol produces by far the most serious neurobehavioral effects in the fetus.”
—IOM Report to Congress, 1996 .

24. Data from recent CDC report
more than 130,000 pregnant women/yr in US drink at levels that may increase risk of FAS
rates of frequent and binge drinking in pregnant women have NOT declined in the last 8 years

26. General Intellectual Performance40 55 70 85
100
115 NC
PEA * * * *
FAS ** *
Standard score
FSIQ
VIQ
PIQ
IQ scale

27. Executive functioning deficits
Move only one piece at a time using one hand and never place a big piece on top of a little piece 1 3
Group 2 4 6
Rule Violations NC
PEA
FAS
P<0.001 2
Starting position 3 1 2
Ending position
Mattson, et al., 1999

28. Behavioral characteristics associated with Fetal Alcohol Spectrum Disorder
hyperactivity, response inhibition deficits, attentional problems, motor coordination deficits, executive function (planning) problems,

29. Clinical Implications…..
Poor judgement
Attention deficits
Arithmetic disabilities
Memory deficits
Problems with abstract thought
Impulsivity
Easily victimized
unfocused or distractible
difficulty handling $$
difficulty learning from experience
difficulty under- standing consequences
poor frustration tolerance

30. Secondary Disabilities of Persons With an FASD
Percent of Persons With FAS or FAE Who Had Secondary Disabilities
 = Age 6+  = Age 12+  = Age 21+

31. Evidence for CNS damage
plenty of data
cerebellum
cerebral cortex
corpus callosum
basal ganglia

32. Brain damage resulting from prenatal alcohol
photo: Clarren, 1986

34. Change in brain size *** ** Mattson et al., 1994 Cerebrum Cerebellum75 80 85 90 95
100
PEA
FAS
< p
0.001
< 0.010
Cerebrum
Cerebellum
Corpus Callosum
Mattson et al., 1994

35. Corpus callosum abnormalities
Mattson, et al., 1994; Mattson & Riley, 1995; Riley et al., 1995

36. Risk Factors Dose of alcohol Pattern of exposure - binge vs chronic
Genetics
Maternal characteristics
Reactions with other drugs
Nutrition
Developmental timing of exposure

37. Body and Brain Develop in Different Stages in Pregnancy

38. Animal models – Example of the comparability of effects
Growth retardation
Facial characteristics
Heart, skeletal defects
Microcephaly
Reductions in basal ganglia and cerebellar volumes
Callosal anomalies
Hyperactivity, attentional problems
Inhibitory deficits
Impaired learning
Perseveration errors
Feeding difficulties
Gait anomalies
Hearing anomalies
Driscoll, et al., 1990; Samson, 1986;

39. Alcohol-Exposed Rodent Models Show Same Behavioral Deficits
Hyperactivity Motor Deficits

40. Interventions protective factors
interventions and stable environment and guardianship (for kids as they grow up)
numerous programs exist – maybe not enough but progress is being made

41. Pharmacotherapy and/or environmental manipulations
environmental enrichment

42. EE Reduces many of the behavioral deficits reported
increases dendritic spines (in controls and drug treated)

43. Pharmacological manipulations
drugs that
increase cholinergic activity
reduce glutamate activity
just naming a few – seem to reduce some of alcohol’s effects on the developing brain