Teratogenic Effects of Alcohol
on Brain & Behavior
국립중앙의료원
정신과
이 소 희
INTRODUCTION
Prenatal Alcohol Exposure
(PAE)
Growth Deficiency
Facial Dysmorphology
CNS Disorders
Central Nervous System Abnormalities
1. Structural
– Head circumference
– Imaging
2. Neurologic
– Neurologic problems
3. Functional
– Global cognitive or intellectual deficits
– Functional deficits
Central Nervous System Abnormalities
Structural
• Head circumference <10th percentile,
adjusted for age and sex
• Clinically meaningful brain abnormalities
observable through imaging (e.g., reduction in
size or change in shape of the corpus callosum,
cerebellum, or basal ganglia)
CDC, 2004
Central Nervous System Abnormalities
Neurologic
• Neurologic problems (e.g., motor problems or
seizures) not resulting from a postnatal insult
or fever, or other soft neurologic signs outside
normal limits
Bertrand J et al. Fetal alcohol syndrome:
guidelines for referral and diagnosis. Atlanta,
GA: US Department of Health and Human
Services, CDC; 2004
CDC, 2004
Central Nervous System Abnormalities
Functional
• Test performance substantially below that
expected for a person’s age, schooling, or
circumstances, as evidenced by either:
• Global cognitive or intellectual deficits representing multiple domains of deficit (or substantial
developmental delay in younger children) with performance
below the third percentile (i.e., two standard deviations below
the mean for standardized testing); or
CDC, 2004
Central Nervous System Abnormalities
Functional
• Functional deficits <16th percentile (i.e., one standard
deviation below the mean for standardized testing) in at least
three of the following domains:
– cognitive or developmental deficits or discrepancies,
– executive functioning deficits,
– motor functioning delays,
– problems with attention or hyperactivity,
– social skills, or
– other (e.g., sensory problems, pragmatic language problems, or
memory deficits)
CDC, 2004
RESULTS from Various Studies
• Neuropsychological studies
– Learning & memory
– Executive functioning
– Psychological deficits and problem behaviors
• Brain imaging studies
– Structural brain imaging
– Functional brain imaging (EEG, PET, SPECT,
fMRI)
Neuropsychological Studies
• Overall cognitive ability
– FAS: “IQ < 70” ~ “average”
– FAS < FAE/PEA (Streissguth et al. 1991)
• Broad range of cognitive functioning areas
significant impairments in all
neuropsychological areas with few qualitative
differences observed between the FAS and
PEA/FAE groups.
Neuropsychological Studies
• Learning & Memory
– memorizing verbal information :difficulties with
the acquisition of the information (Mattson et al.
1996b )
– learning deficits occur in both verbal and
nonverbal arenas
– used implicit memory and that prior exposure
helped them learn and memorize the words
Neuropsychological Studies
• Executive functioning
– Higher-level cognitive abilities :solving problems,
thinking abstractly, planning ahead, and being
flexible in one’s thought processes
– Deficits greater than would have been predicted
if they were related to overall IQ scores
– Real-life implications :act without first
considering the consequences of their behavior,
difficulty succeeding in school
Neuropsychological Studies
• Psychosocial Deficits and Problem Behaviors
– psychiatric disorders, trouble with the law, alcohol
and other drug abuse, and other maladaptive
behaviors (Streissguth et al. 1996)
– hyperactive, disruptive, impulsive, or
delinquent (Roebuck et al. 1999)
– poor socialization and communication skills
– maladaptive behaviors (e.g., impulsivity) and are
less likely to be living independently (Streissguth
et al. 1991)
FAS & Attention
Focus Selective attention to appropriate stimuli
WISC-R Coding
Shift Appropriate flexibility in response to new information; allocation of attentional resources
Wisconsin Card Sorting Test (WCST)
Sustain Ability to maintain alert state and attention to task
Continuous Performance Test (CPT)
Encode Ability to learn new material and manipulate material in working memory while processing into long-term memory
Paired Associate(PA) Task
FAS & Attention
Performance on attention tasks by FAS-FAE and
ADHD status.(Coles, 2001)
Brain Imaging Studies : Structural
• Over-all size of the brain↓(Roebuck et al. 1998)
Hippocampus Corpus callosum
Basal ganglia
Cerebellum
Brain Imaging Studies : Structural
• Basal ganglia↓– Caudate nucleus (Archibald et al. 2001)
– The ability to shift from one task to another,
inhibition of inappropriate behavior, and spatial
memory
– Extensive neural connections to the frontal lobes
of the brain
Brain Imaging Studies : Structural
• Corpus callosum↓– Deficits in attention, intellectual functioning,
reading, learning, verbal memory, and executive
and psychosocial functioning
– Abnormalities ranging from a thinning to
complete absence of the corpus callosum (Roebuck
et al. 1998)
– the genu & the isthmus and splenium were
disproportionately reduced in size (Riley et al.
1995)
Brain Imaging Studies : Structural
The corpus callosum of the ALC is displaced (the isthmus and
splenium) (Sowell et al. 2001)
Corpus callosum displacement was highly related to the children’s
performance on a verbal learning task.
Brain Imaging Studies : Structural
• Cerebellum↓– learning deficits as well as in balance and
coordination
– the overall reductions in the size of the cerebellum
(Archibald et al. 2001)
– the anterior portion of the cerebellar vermis is
particularly affected before or shortly after birth
(Goodlett et al. 1990)
Brain Imaging Studies : Structural
• Hippocampus↓– Consolidation of memories
– Volume asymmetries in the hippocampus Lt<Rt
(Riikonen et al. 1999)
– Less affected than some other brain regions in FAS
children (Archibald et al. 2001)
Brain Imaging Studies : Functional
• EEG
– Infants : EEG may be a sensitive measure of
changes in brain function resulting from prenatal
alcohol exposure (Ioffe and Chernick 1990)
– ↓the power or strength of the alpha frequencies in
the left hemisphere readings (Kaneko et al. 1996b)
– Delayed P300 spikes occur in the parietal cortex
(Kaneko et al. 1996a,b)
Brain Imaging Studies : Functional
• PET
– ↓metabolic activity in the caudate nucleus and in
the thalamus (Clark et al. 2000)
• SPECT
– No normal greater resting activity in the left
hemisphere (Riikonen et al. 1999)
Brain Imaging Studies : Functional
• Functional Magnetic Resonance Imaging
(fMRI)
– Activation in a dorsolateral prefrontal cortex
– More difficult in working memory task (Connor
and Mahurin 2001).
• Brain mapping technique
– Disproportionate reductions in the brain’s white
matter (Sowell et al. 2001b)
Brain Imaging Studies : Functional
Brain-mapping studies detected areas of increased gray matter density (shown
in yellow on the left) as well as areas of reduced white matter density (shown in
red on the right) in the parietal lobe.
SOURCE: Dr. Elizabeth Sowell.
FUTURE DIRECTIONS
• The effects of the alcohol exposure
– Not global in nature
– Affect certain areas more than others in both the
neuropsychological and neuroanatomical arenas
• Continuing studies
– Focusing on the relationship between
neuropsychological and neuroanatomical data
– Develop more targeted and effective
intervention approaches