RECENT RESEARCH ON FASD
Edward P. Riley, Ph.D.
SDSU/UCSD Joint Doctoral Program in Clinical Psychology
Center for Behavioral Teratology
San Diego State University
Alcohol and Pregnancy: An Over view of Fetal Alcohol Spectrum Disorders
A Congressional Briefing Sponsored by
The FRIENDS OF NIAAA
April 13, 2015
CIFASD CONCEPTUAL FRAMEWORK
Alcohol Consumption
During
Pregnancy
Embryonic and
Fetal
Development
Dose
Timing
Pattern
Genetics
Age
Nutrition
Brain
Environment
Genetics
Face
Behavior
RESEARCH CHALLENGES
Improve Diagnostic Capabilities
 Develop simple, reliable methods to make these
diagnosis across the whole spectrum
Adapted from talk by K. Warren
MISSED AND MISDIAGNOSIS OF FASD
Examined 547 adopted and foster children with
behavioral problems for a comprehensive evaluation,
including an assessment of FASD
28.52% of the children were ultimately identified with
a diagnosis related to prenatal alcohol exposure.
80.13% of the children diagnosed with an FASD had
no previous diagnosis or were missed diagnosed.
* This is a high risk group for FASD, and these data do not represent the prevalence of
FASD in the general population.
Chasnoff, Wells, and King, Pediatrics, January, 2015
*
FACIAL FEATURES OF FETAL ALCOHOL
SYNDROME
Discriminating Features
Associated Features
Epicanthal folds
Short palpebral fissure
Low nasal bridge
Minor ear anomalies
Indistinct philtrum
Micrognathia
Thin upper lip
In the child
Streissguth, 1994
Ways to Improve Diagnosis
3 D Facial Imaging and Analysis
Peter Hammond and Tatiana Foroud
3D Photograph
Appearance and Shape
3D photograph shape
28,000 3D pts on male
adult face
LOOKING AT THE SIMILARITIES BETWEEN
FACES
Mapping 3D images
FAS - MALE
FACE
SIGNATURE
red-contracted
blue-expanded
SIGNATURE
GRAPH
IS THE COMPUTER CAPABLE OF
DIAGNOSING FAS?
clinical
categorization
(FAS/PFAS/HE)
face shape
DSM
PCA modes
agreement?
(ROC analysis)
HC vs FAS
SVM
face
100
periorbit
96.7
perioral
88.4
perinasal
93.4
profile
91.7
classification
algorithm
support vector machines (SVM)
(Suttie et al, 2012)
Able to diagnose FAS - but what about the affected,
alcohol-exposed child without the facial signature
FAS-Like
Control-Like
Similar in performance on IQ,
Similar in performance on IQ,
learning and memory to those with
learning and memory to those with
no exposure
FAS/pFAS
The Face Predicted the Behavioral and Cognitive Effects
(Suttie et al, Pediatrics, 2013)
THE MAJOR ISSUE IN FASD IS THE IMPACT OF
ALCOHOL ON THE BRAIN:
THE FACE IS A WINDOW INTO THE BRAIN
Most severe face
Most reduced volume
Adapted from Roussotte et al., 2011, CIFASD
VALUE OF THIS FACIAL RECOGNITION
TECHNOLOGY
Pediatricians were asked about their knowledge and experience
in the care of children with FAS.
 Almost all knew about the teratology and clinical presentation
of FASD
 But only 50% felt prepared to diagnose
 Pediatricians are knowledgeable about FAS, but do not feel
competent enough to deal with it in their everyday practice.
Gahagan et al. Pediatrics, 2006, 118, 657-68
HOW ELSE CAN WE USE THIS TECHNOLOGY?
AUTOMATED FACE SCREENING - TELEMEDICINE
Referral or
not
RESEARCH CHALLENGES
Better understand the alterations in brain
that underlie the neurobehavioral
problems that occur in these individuals
This is a brain/behavior disorder
Total change in attitude when one understands
that this is a brain-based problem
Courtesy of K. Warren
CNS PROBLEMS
BRAIN ABNORMALITIES
 Central nervous system dysfunction may be:
 Physical changes in the brain
 Behavioral and cognitive problems
 Alcohol causes changes in overall brain structure as well
as damage to specific brain regions and brain functioning
WHAT DO FAS BRAINS LOOK LIKE
S O M E A N O M A L I E S A R E FA I R LY O B V I O U S - B U T R A R E
U S U A L LY Q U I T E U N R E M A R K A B L E B Y V I S U A L I N S P E C T I O N
A. Agenesis of the corpus
callosum.
B. Schizencephaly.
C. Lissencephaly.
D. Heterotopias.
Image courtesy of D. Atkinson, MD.
CHANGE IN CEREBRAL SIZE
Cerebrum
100
95
90
85
p < 0.010
80
ARND
FAS
75
Mattson et al., 1994
BRAIN SIZE AND SHAPE
• Overall brain size is reduced in volume, but
some areas are more affected than others
• Area in red indicate where the cerebrum is
especially small
REDUCED VOLUME AND INTEGRIT Y IN
VARIOUS SUBCORTICAL AREAS
hippocampus: formation of new
memories
Slide courtesy of E. Sowell.
basal ganglia: motor control, cognitive
and emotional functions
DIFFERENT BRAIN AREAS NEED TO
COMMUNICATE WITH EACH OTHER
THE CORPUS CALLOSUM – A LARGE
ROADWAY CONNECTING THE HEMISPHERES
Cerebrum
Cerebellum

Corpus Callosum
 Connects the left and
right halves of the
brain
 Allows them to work
together and put
information together
CORPUS CALLOSUM ANOMALIES
*
REDUCTIONS IN CORPUS CALLOSUM AREA
CON
NDFASD
FAS
Riley EP, et al, Am J Med Genet C Semin Med Genet,
WHITE VERSUS GRAY MATTER
THE CORPUS CALLOSUM IS A LARGE WHITE MATTER
TRACT
Myelin - The white
matter coating our
nerves.
 Make nerve
conduction faster.
DIFFUSION TENSOR IMAGING IN FASD
 Dif fusion Tensor
Imaging (DTI)
CONTROL
FASD
Corpus Callosum
 Decreased
integrity of white
matter
 Malformed,
underdeveloped
(Wozniak & Meutzel, 2011)
FUNCTIONAL MAGNETIC RESONANCE IMAGING
HOW THE BRAIN WORKS
Primary visual cortex
Not what your brain looks like (size, cortical thickness
etc.), but, what it is doing, and where.
From Fox and Raichle, 2007
HOW WELL ARE BRAIN AREAS
COMMUNICATING?
FUNCTIONAL CONNECTIVITY
fMRI time-series from one control subject
illustrating high correlation between brain
activity in right and left medial orbital frontal
cortex.
fMRI time-series from one FASD subject
illustrating low correlation between brain
activity in right and left medial orbital frontal
cortex.
Courtesy of Jeff Wozniak
RESEARCH CHALLENGES
 Refine our understanding of the complexities in
the neurobehavioral phenotype associated with
FASD
 To achieve better recognition of these disorders, as
many of the individuals without the facial features
go unrecognized
Courtesy of K. Warren
BEHAVIORAL DYSFUNCTION
Brain changes
Cognition & behavior
 Global brain
 Intellectual development
 Cerebral cortex
 Executive function
 Corpus callosum
 Learning & memory
 Cerebellum
 Visuospatial processing
 Hippocampus
 Language
 Basal ganglia
 Motor function
 White & gray matter
development
 Attention & hyperactivity
 Emotional regulation
 Social cognition
GENERAL INTELLECTUAL PERFORMANCE
Standard score
115
NC
100
85
*
**
*
*
*
FAS
NDFASD
70
55
40
FSIQ
VIQ
IQ scale
*
*
PIQ
FAS is the leading
known cause of
Intellectual disability
in the western world,
but the majority have
IQs over 70
Mattson, S.N., 1997.
LEARNING & MEMORY
 Children with and without the facial features of FAS are
impaired in both learning and memory of verbal and
visual information.
 Problems learning information
 Greater difficulty recalling and recognizing information after
a delay
MOTOR FUNCTION
 Children prenatally exposed to alcohol experience a
number of motor impairments in both gross and fine
motor skills:
 Poor hand-eye coordination
 Unstable balance
 Delayed reaction time
 Gait difficulties
 Slowed motor speed
 Poor force control
FINE-MOTOR SKILL:
GROOVED PEGBOARD TEST
150
∗
Time (sec.)
135
120
∗
∗
NC
FAS
NDFASD
∗
105
90
75
60
Dominant
Nondominant
Hand

Mattson et al., Neuropsychology, 1998
INTERHEMISPHERIC DEFICITS
Corpus Callosum
We expect changes in
behavior where
information has to cross
the corpus callosum
CON NDFASD
FAS
LEFT BRAIN/RIGHT BRAIN
THE CORPUS CALLOSUM
Left Brain
Right Brain
•Spatial abilities
•Language
•Face recognition
•Math
•Visual imagery
•Logic
•Music
WHAT EACH HALF OF THE BRAIN SEES
Stimuli
Controls
Alcohol-exposed
YY
YY
YY
YY
YY
YY
D
Alcohol-exposed
EXECUTIVE FUNCTIONS
“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.”
-Hilar y O’Loughlin Iceberg, 1995)
EXECUTIVE FUNCTIONS
 Executive function is an
umbrella term for cognitive
processes that regulate,
control, and manage other
processes.







planning
problem solving
concept formation
working memory
reasoning
inhibition
multi-tasking
 Children with FASD show
deficit in all of these areas.
 Performance is characterized by
increased errors and more
difficulty adhering to rules.
EXECUTIVE FUNCTIONING
TOWER OF CALIFORNIA TEST
3
1
2
Starting position
Items passed
10
NC
8
PEA
FAS
6
4
2
0
Ending position
Move only one piece at a time
using one hand and never place
a big piece on top of a little piece
*
6
Rule Violations
1
2
3
Group
NC
5
PEA
4
FAS
3
2
1
0
Group
VARIABILIT Y OF OUTCOMES
 Not every woman who drinks heavily during pregnancy will
give birth to a child with an FASD
 Not all children with an FASD have exactly the same defects
or deficits
 Many biological and environmental factors influence the
ef fects of alcohol on the developing fetus
GENETIC SUSCEPTIBILIT Y TO FASD
+/+
+/X
½
+/-
½
+/+
GENOT YPE X ALCOHOL EXPOSURE
Fyn
CC
CT/TT
micrognathia, flatter face
OTHER IMPORTANT ISSUES
A LIFELONG CONDITION
But we know very little about the long-term
effects
•
Long-term health consequences
•
How the behavioral issues change
OTHER IMPORTANT ISSUES
Interventions
 Nutritional, pharmacological, behavioral
Biomarkers of exposure and/or effect
Interaction with other drugs
Factors of resiliency
THANK YOU
Edward Riley
6330 Alvarado Ct. #100
San Diego, CA 92120
[email protected]