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Defining a Neurobehavioural Phenotype in Fetal Alcohol Spectrum Disorder. Nash, K., Greenbaum R., Fantus, E., Rovet, J., & Koren, G. What is Fetal Alcohol Spectrum Disorder (FASD)?. FASD is a neurodevelopmental disorder caused by exposure to alcohol in utero - PowerPoint PPT Presentation
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Defining a Neurobehavioural Phenotype in Fetal Alcohol
Spectrum DisorderNash, K., Greenbaum R., Fantus,
E., Rovet, J., & Koren, G.
What is Fetal Alcohol Spectrum Disorder (FASD)?
• FASD is a neurodevelopmental disorder caused by exposure to alcohol in utero
• Has effects on both brain and behaviour
Diagnostic Criteria
Based on a triad of features Pre and postnatal growth
retardation CNS damage Characteristic facial
dysmorphology
Only a minority of children meet criteria for the full blown syndrome
How do we diagnose without visible signs?
The Motherisk Follow-up Clinic
Began in 1996• Provides a specialized diagnosis in a
central location
Many obstacles exist• Not every child has physical symptoms• Misdiagnosis of ADHD - 70% of children 70% of children
with FASD are diagnosed with with FASD are diagnosed with ADHDADHD
• Long wait lists
The Issue of ADHD
• Children with FASD present with a unique and specific behavioural profile compared to children with ADHD (Greenbaum (2004); Fantus et al., (2004))
0
10
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30
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OPP HYP PS EM GLB
FASD
ADHD
The Issue of Access
• The majority of children with FASD reside in communities with limited access to a specialized diagnosis
• How do we address this issue?
Aims of the current research
• To identify whether the diagnosis of FASD can be predicted by individual items from a validated questionnaire
• To compare children with FASD to children with ADHD and controls on this questionnaire
• To develop an empirically derived screening tool (Streissguth, 1998)
MethodsParticipants: children between the ages of 6-16
years. FASD (dx; n=30)ADHD (dx; n=30): No exposure historyControls (n= 30): No exposure history, LD, ADHD
Exposure History (FASD): Confirmed by(a) Verbal report of biological parent or relative(b) Knowledge that the child suffered alcohol
withdrawal at birth(c) The child having been place in care because of
maternal alcohol abuse
The Child Behaviour Checklist (CBCL; Achenbach, 1991)
• 113 item parent questionnaire
• T-scores yield:» Competence Scales» 3 Broadband scales» 8 Narrowband scales» DSM Oriented Scales
Item selection
• Selected only 12 based on the work of Greenbaum (2000)
CBCL: 12 Items
• #1 acts to young for his/her age• #3 argues• #8 can’t concentrate/poor attention• # 10 can’t sit still/restless/hyperactive• #16 cruelty/bullying/meanness to others• #22 disobedient at home• #26 no guilt after misbehaving• #41 impulsive/acts without thinking• #43 lying or cheating• #74 showing off/clowning• #81 steals from home• #82 steals outside
Analyses of Data
• Frequency Counts
• Proportions endorsed per group (chi square)
• Endorsement totals per item/group: Discriminant Function Analysis (DFA)
• Sensitivity and Specificity: Receiver Operating Curves (ROC)
Receiver Operating CurvesROC Curve
Diagonal segments are produced by ties.
1 - Specificity
1.00.75.50.250.00
Se
ns
itiv
ity
1.00
.75
.50
.25
0.00
CBCL items involving significant group differences
(Controls & FASD)
0
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40
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80
100
120
CBCL Items
% E
nd
ors
ed
FASD
CON
Seven items most strongly differentiating FASD from
control• #1 acts to young for his/her age• #8 can’t concentrate/poor attention• #9 can’t sit still/restless/hyperactive• #22 disobedient at home• #26 no guilt after misbehaving• #41 impulsive/acts without thinking• #43 lying or cheating
ROC Analysis:FASD and Controls
0.0 0.2 0.4 0.6 0.8 1.0
1 - Specificity
0.0
0.2
0.4
0.6
0.8
1.0
Sen
sit
ivit
y
Source of the Curve
discrim
ayimngd
Diagonal segments are produced by ties.
ROC Curve
CBCL items involving significant group differences
(FASD and ADHD)
0
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100
ActsYoung
Cruelty No Guilt Lying StealsH StealsO
FASD
ADHD
Six items most strongly differentiating FASD from
ADHD• #1 Acts to young for his/her
age• #16 cruelty/bullying/meanness
to others• #26 no guilt after misbehaving• #43 lying or cheating• #81 steals from home• #82 steals outside
ROC Analysis:FASD and ADHD
0.0 0.2 0.4 0.6 0.8 1.0
1 - Specificity
0.0
0.2
0.4
0.6
0.8
1.0
Se
ns
itiv
ity
Source of the Curve
discrim
noguilt&creul&actsyoung
Diagonal segments are produced by ties.
ROC Curve
Screening checklist for FASD
Step 1: Identifying behaviour suggestive of FASD
The following questions should be asked of the child’s parent/guardian to determine whether the child’s behaviour is suggestive of FASD
Screening Checklist Continued
1. Does your child act too young for his/her age?2. Does your child have difficulty concentrating
and can’t pay attention for long?3. Is your child disobedient at home?4. Does your child lie or cheat?5. Does your child lack guilt after misbehaving?6. Does your child act impulsively and without
thinking?7. Does your child have difficulty sitting still/is
restless/hyperactive?
• If the parent answers YES to at least 6 out of 7 items this is suggestive of FASD with comorbid ADHD
• If the child does NOT exhibit behaviour consistent with ADHD then they must receive a score of 3 out of 4 on the conduct related items
Step 2: Differentiating FASD from ADHD
i). The child needs to exhibit 2 of the following 31. Does your child lack guilt after misbehaving?2. Does your child act cruel, bully or is mean to others?3. Does your child act young for his/her age?
ORii). 3 of the following 61. Does your child lack guilt after misbehaving?2. Does you child act cruel, bully or is mean to others?3. Does your child act young for his/her age?4. Does your child steal from outside the home?5. Does your child steal from home?6. Does your child lie and cheat?
Clinical Implications
• Address the issue of access
• Spare the long wait times for a diagnosis
• Misdiagnosis of ADHD
Limitations
• Dose and timing of alcohol exposure
• Confounders
• Small sample size
• Clinic referred
Future Directions
• Compare to children diagnosed with conduct disorder
• Replicate and empirically validate
• Neuroimaging and mapping
Acknowledgments
• Rovet Lab: Meagan Williamson, Dina Lafoyannis, Sarah Borokowski, Erin Sheard, Dr. Mary Desrocher, Darlene Walker
• Canadian Institute of Health Research (CIHR)