마더세이프라운드 - 국립의료원 이소희 교수

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


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


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


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


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.


• 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


• 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


• 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


• 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


• 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)


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.


• 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)


• 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)


• 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)


• 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-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

마더세이프라운드 - 국립의료원 이소희 교수

Health & Medicine