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The Effects of Prenatal Alcohol Exposure on Brain and Behavior
Edward Riley
Center for Behavioral Teratology and Department of Psychology
San Diego State UniversitySan Diego, CA
Alcohol and Pregnancy: An Overview of Fetal Alcohol Spectrum Disorders A Congressional Briefing Sponsored by
The FRIENDS OF NIAAAWednesday, May 20, 2009
Fetal Alcohol Syndrome In the early 1970’s case reports
began appearing describing the consequences of heavy maternal alcohol use during pregnancy.
The offspring were noted to have distinctive facial characteristics.
They were also small for gestation age and had poor postnatal growth.
Also evidenced disorders of the central nervous system.
Photo courtesy of T. Kellerman
Facies in Fetal Alcohol Syndrome
Discriminating Features Associated Features
Epicanthal folds
Low nasal bridge
Minor ear anomalies
Micrognathia
Short palpebral fissure
Indistinct philtrum
Thin upper lip
In the young child Streissguth, 1994
Examples of Children with FAS
Short palpebral fissure
Indistinct philtrum
Thin upper lip
*
CNS anomalies
Example of extreme brain damage resulting from prenatal alcohol exposure
Soon after the identification of FAS researchers confirmed that alcohol was a teratogen in animal models ranging from mice and rats to dogs, miniature swine, and primates.These models were important
because case reports were confounded by numerous variables that could not be well controlled.
smoking, SES, poor prenatal care
Small headSmall head
Small noseSmall nose
Small midfaceSmall midface
Long philtrum; Long philtrum; Thin upper lipThin upper lip
normalnormalalcohol-exposedalcohol-exposed
Mouse fetusesMouse fetuses
Comparison: Child with FAS and mouse fetus Comparison: Child with FAS and mouse fetus with fetal alcohol exposurewith fetal alcohol exposure
Child with FASChild with FAS
Short palpebral fissuresShort palpebral fissures
*Photos courtesy of K. Sulik
Critical Periods of Development
FAS – Only the tip of the iceberg
Fetal alcohol effects ARND/ARBD
Appear normal but clinical suspect
Fetal alcohol syndrome
Fetal alcohol spectrum disorder(s)
Alcohol Consumption Prevalence Among Non-Pregnant Women 18-44 years
Binge: ≥ 5 drinks on one occasion in past month Any Use: 1 or more drinks in past month
Source: Behavioral Risk Factor Surveillance System 2001-2005, CDC.
0
10
20
30
40
50
60
2001 2002 2003 2004 2005
BingeAny Use
Alcohol Consumption Prevalence Among Pregnant Women 18-44 years
Binge: ≥ 5 drinks on one occasion in past month Any Use: 1 or more drinks in past month
Source: Behavioral Risk Factor Surveillance System 2001-2005, CDC.
0
2
4
6
8
10
12
14
2001 2002 2003 2004 2005
Binge
Any use
Estimates about costs FAS costs US $5.4 billion in direct and indirect costs in 2003
$3.9 billion in direct costs (Actual use of goods and services) $1.5 billion in indirect costs (Lost potential productivity)
An FAS birth carries lifetime health costs of just under a million dollars, although it can be as high as 4.2 million.
Even “expensive” FAS prevention may have a large cost/benefit ratio.
Take Home Message 1
Prenatal exposure to alcohol, at least high doses of alcohol, can cause permanent changes in the brain
Alcohol can act as a behavioral teratogenPrenatal exposure to alcohol can result in a variety
of behavioral dysfunctions, even in the absence of obvious physical effects.
Take Home Message 2
MRI Investigation of Children with FASD
Image Analysis
T1-Weighted Skull stripped tissue segmented Surface rendering
*
Diagnostic Groups
Fetal Alcohol Syndrome (FAS) - Dysmorphic FASD Children with all of the required diagnostic criteria and a confirmed
history of heavy prenatal alcohol exposure
Prenatal Exposure to Alcohol (PEA) - Non Dysmorphic FASD Children with a known history of significant alcohol exposure, but without
the physical features necessary for a diagnosis of FAS
Non-exposed Control (CON) Children who have no history of exposure to alcohol or other known
teratogens
Given overall changes in brain size, we would expect to see global deficits
Given changes in cerebellum, we would expect to see changes in balance, motor skills,
timing, attention, and classical conditioning
General Intellectual Performance
NDFASD* * *
IQ scale
FSIQ VIQ PIQ40
55
70
85
100
115S
tan
dar
d s
core
NC
FAS
****
Mattson, S.N., 1997.
FAS is the leadingknown cause ofmental retardation in the western world, but the majority are not retarded
*
Language Test Performance
PPVT-R BNT
30
70
Sta
nd
ard
sco
re
0
10
20
40
50
60
Raw
score
Language Measure
115
130
40
55
85
100
NC
FAS
NDFASD
*
Fine-Motor Skill:Grooved Pegboard Test
Dominant Nondominant
150
Hand
NC
FAS
NDFASD
60
75
90
105
120
135T
ime
(sec
.)
Neuropsychological Performance
FSIQ Read Spell Arith PPVT BNT ATotal VMI PegsD CCT40
50
60
70
80
90
100
110
120
Measure
NC
PEA
FAS
*
Lobe Analysis
*
Frontal Temporal Parietal Occipital0
30000
60000
90000
120000
150000
Vol
ume
Lobe
Controls
FASp = .0003*
p = .018
p = .030
p = .0002*
* Significant after controlling for overall brain size
The parietal lobe is involved in math and visual spatial domains therefore we would expect to
see deficits in these domains
Math Disabilities
Math skills more impaired than language Can be observed in preschool period and
persists through adulthood Probably related to visual/spatial
deficits Also related to executive functioning
problemsHowell, et al (2006) J Ped Psych
Kable and Coles-Fudge, MILE
Streissguth’s cohort
Jacobson and Jacobson
Virtual Water Maze - Probe Trial Paths
Controls FAS PEA*
The frontal lobes, making logical decisions
Role of frontal lobes Executive function Judgment Difficulty in interpreting feedback from the environment Risk taking Non-compliance with rules Impaired associated learning Spontaneity Memory Social and sexual behavior Some aspects of language
Frontal Subcortical Circuits
Frontal Cortex
Striatum(caudate & putamen)
Globus Pallidus(part of lenticular nucleus)
Thalamus
Caudate * Accumbens *
70
75
80
85
90
95
100
NDFASD
FAS***
*
The Basal Ganglia (Caudate) and other Subcortical Structures
Relays information to frontal lobes Organize and prioritize
information Filters information Category learning Emotional gating Working memory
“We wondered how a child could get A’s in school and not have the sense to understand that when she is rude to friends they might get mad at her.”
-Hilary O’Loughlin
(Iceberg, 1995)*
Executive Functioning
The ability to organize and plan Focus and maintain attention Be able to store memories and retrieve them Issues related to affect and inhibition, e.g. preventing anger
from getting out of control Self-awareness Initiating and ending activities
Cognitive functions involved in planning and guidingbehavior in order to achieve a goal in an efficient manner.
*
Executive FunctioningTower of California Test
Group0
1
2
3
4
5
6
Ru
le V
iola
tio
ns NC
PEA
FAS
Group
8
0
2
4
6
10
Item
s p
asse
d
NC
PEA
FAS
21
3
12
3
Starting position
Ending position
Move only one piece at a timeusing one hand and never place a big piece on top of a little piece
*
Twenty Questions (Concept Formation)
Normal responsesIs it alive?Is it on the left of the
page?Can you eat it?Is it the banana?
The Corpus Callosum
Connects the left and right halves of the brain
Allows them to work together and put information together
Cerebrum
Cerebellum
Corpus Callosum
Corpus callosum abnormalities
Mattson, et al., 1994; Mattson & Riley, 1995; Riley et al., 1995
*
Reductions in Corpus Callosum Area
CON NDFASD FAS
*
White versus gray matter
The white matter coating our nerves. Composed of a layer of proteins packed between two layers of lipids. Produced by specialized cells:
oligodendrocytes in the CNS. Myelin sheaths wrap themselves around axons, the threadlike extensions of neurons that make up nerve fibers.
Make nerve conduction faster.
DT TRACTOGRAPHYDT TRACTOGRAPHY
13 yr old male control
13 yr old male with FAS
seed volume placed in the splenium of the CC
Combining DTI data withcomputational methods of tractography, the locations and sizes of white matter pathways can be estimated
Left brain/Right brainThe Corpus Callosum
Left Brain
•Language
•Math
•Logic
Right Brain
•Spatial abilities
•Face recognition
•Visual imagery
•Music
What each half of the brain sees
DY
Y
Y
Y
Y
Y
Y
Y
Y
Y
Y
Y
What each half of the brain sees
Stimuli
Controls
Alcohol-exposed
Alcohol-exposed
*
Given changes in numerous brain areas we would expect significant differences in complex behaviors
For example, social behavior is contingent on numerous brain areas
Orbitofrontal cortex, amygdala, insula, medial prefrontal cortex and temporoparietal junction
Social Functioning in FASD
Deficits in social functioning above and beyond IQ or other behavioral problems
Difficulty meeting age-related expectations
Quality of social interactions is often poor or inappropriate
Summary of MRI Findings
Reductions in overall brain size and in certain brain structures or areas, e.g. the cerebellum (anterior vermis), basal ganglia (caudate), corpus callosum, parietal-temporal region
To much gray matter and lesser amounts of white matter in some areas (i.e. DTI). Decrease in white matter integrity.
Distortions in shape of brain (front too blunt, sides too narrow) Cortex too thick in places Changes in energy metabolism (MRS), changes in function
noted in fMRI, changes in functional connectivity Brain imaging data correlate with both physical an behavioral
outcomes
Prenatal exposure to alcohol, at least in high doses, can cause permanent
changes in the brain These changes in brain may cause or contribute
to many of the behavioral problems seen in individuals exposed to alcohol.
These changes in brain appear to be the result of prenatal alcohol exposure, although some areas may also be affected by postnatal experiences
Knowing what brain areas are involved might enable us to develop better treatment strategies.
Summary of Neuropsychological Findings
Heavy prenatal alcohol exposure is associated with a wide range of neurobehavioral deficits
Children with and without physical features of the fetal alcohol syndrome display qualitatively similar deficits
A specific pattern of relative strengths and weaknesses may exist or there may be several patterns
Identification of children with heavy prenatal alcohol exposure is critical. Research has shown that early identification leads to interventions,
services and improved outcomes.
Incidence of FAS in
subsequent births per 1,000 live
births
771
