Neurodevelopmental disorders like autism, dyslexia, and language impairment often co-occur. This document discusses several possible explanations for why this is the case, including shared genetic risk factors, correlated environmental risks, and gene-gene interactions. It also notes evidence that for some children, their language problems may be a "phenomimic" of autism rather than sharing the same root cause. The document advocates classifying children based on their profile of difficulties rather than diagnostic labels, to best address their needs.

1. Neurodevelopmental disorders:
Why do they co-occur?
Dorothy Bishop
Wellcome Principal Research Fellow
Department of Experimental Psychology
University of Oxford

2. 2
Meanings of ‘neurodevelopmental
disorder’
 Neurological disorders with known prenatal
cause (genetic or acquired)
• e.g. Williams syndrome, fetal alcohol syndrome
 Disorders where abnormal neurodevelopment is
inferred: actual cause is complex or unknown
• e.g. developmental dyslexia, autistic disorder, specific
language impairment (SLI), developmental
coordination disorder (DCD), developmental
dyscalculia, ADHD

3. 3
Common characteristics of
neurodevelopmental disorders
 Defined in terms of behaviour
 Often use medical terminology, drawing parallel
with acquired disorders
 Tend to run in families
 No single biological cause
 Male preponderance in most

4. Distinct disorders?

5. Kaplan et al, 2001
Developmental co-ordination
disorder, 17%
ADHD, 65%
Dyslexia, 70%
“Comorbidity is the rule, not the exception” (Gilger & Kaplan, 2001)
• Sample of 179 children
and families recruited from
clinics, special schools
• All had dyslexia and/or
ADHD
• Comprehensive
assessment for ADHD,
dyslexia, DCD, and
psychiatric disorders
Kaplan, B. J., et al (2001). The term comorbidity is of questionable value in reference to
developmental disorders: data and theory. Journal of Learning Disabilities, 34, 555-565.

6. Dyck, M. J., et al. (2011). The validity of psychiatric diagnoses: The case of 'specific'
developmental disorders. Research in Developmental Disabilities, 32(6), 2704-2713.
608 children aged 3 – 14 years
 449 Typically-developing
 30 Autism spectrum disorder (ASD)
 24 Mental retardation (MR)
 30 Receptive-expressive language disorder (SLI)
 22 Developmental co-ordination disorder (DCD)
 53 Attention deficit hyperactivity disorder (ADHD)
 Assessments of IQ, language, motor, attention,
social cognition, executive function
Western Australian study
Murray Dyck

7. Typical
Autism
MR
SLI
DCD
ADHD
Dyck et al: Discriminant function analysis

8. A non-causal explanation:
Ascertainment bias
Language
Motor
Population
sample
needed to
test if
association
is true
Likelihood
of referral

9. Genuine association:
Needs causal explanation
Reading
Motor
r = .25
e.g., Brookman, A., et al (2013). Fine motor deficits in reading disability and language
impairment: same or different? PeerJ. doi: 10.7717/peerj.217

10. Motor
impairment
Reading
impairment
Motor
impairment
Reading
impairment
Q1: Why are disorders associated?
• Generally, simple causal model doesn’t work
• Too many cases of dissociation
• Also, in this case, implausible

11. Motor
impairment
Reading
impairment
Motor
impairment
Reading
impairment
Factor
X
Motor
impairment
Reading
impairment
Q1: Why are disorders associated?

12. 12
Q2: At what level is the overlap?
Bishop, D., & Rutter, M. (2008). Neurodevelopmental disorders: conceptual issues. In M.
Rutter et al (Eds.), Rutter's Child and Adolescent Psychiatry (pp. 32-41).Blackwell.

13. How to distinguish causal accounts?
 Better measures of phenotype – get at
common underlying cognitive processes
 Use family data: can test whether disorders
“breed true”
 Training study
Example: Autistic spectrum disorder and Specific
Language Impairment

14. Autism spectrum disorder (ASD)
Autistic disorder: impairments in:
 Communication
 Social interaction
 Behavioural repertoire
14

15. Specific language impairment (SLI)
 Diagnosed in children when language
does not follow normal developmental
course
 Not due to hearing loss, physical
abnormality, acquired brain damage
 Normal development in other areas
 Problems with language structure
(phonology and syntax) common

16. Good ‘markers’ of SLI
Measures which are sensitive to SLI, and heritable
• Nonword repetition
Child listens to spoken nonwords and repeats, e.g.
2 syllables: hampent
3 syllables: dopelate
4 syllables: confrantually
5 syllables: pristoractional
• Verb inflectional morphology
“Here’s a farmer. Tell me what a
farmer does”
Measures of language form, rather than content/use

17. Evidence that aetiology is complex and
multifactorial in autism and SLI
i.e. Combined effect of many genes and
environmental risks
 Disorders aggregate but do not segregate in
families
 Unaffected relatives of affected individuals may
show mild or partial symptoms
 High heritability in twin studies, yet genome
scans have revealed few single gene causes
 Relatively common disorders affecting
reproductive success, yet persist in population
17

18. Traditional view: two separate disorders
risk
factors
Y
ASDSLI
-liability X
risk
factors
X
-liability Y
18

19. Predictions: independent disorders model
• Children with ASD and SLI together
should be vanishingly rare:
• SLI prevalence 7%
• ASD prevalence 1%
• Predicts comorbid 7 per 10,000
19
ASD
SLI

20. • Many children with ASD have language problems similar to SLI:
Kjelgaard & Tager-Flusberg (2003): poor nonword repetition and
use of verb inflections;
76% ASD with LI
Loucas et al (2008): epidemiological sample, cases with ASD and
normal nonverbal IQ & impaired performance on a language
battery:
57% (41 of 72) ASD with LI
High comorbidity between ASD and
language impairment (LI)
20
Kjelgaard, M. M., & Tager-Flusberg, H. (2001). An investigation of language impairment in autism:
Implications for genetic subgroups. Language and Cognitive Processes, 16, 287-308.
Loucas, T. et al. (2008). Autistic symptomatology and language ability in autism spectrum disorder
and specific language impairment. [Article]. Journal of Child Psychology and Psychiatry, 49(11),
1184-1192. doi: 10.1111/j.1469-7610.2008.01951.x

21. Key question
ASD and LI can be dissociated
Yet they co-occur far more often than by chance
Conventional wisdom of independent disorders
seems wrong
How to explain?
21?

22. Correlated risk factors
Some possible reasons for correlation:
• Same gene influences both liabilities (pleiotropy)
• Genes close together on same chromosome (linkage)
• Correlated environmental factors (e.g. poverty)
• Non-random (assortative) mating
risk
factors
Y
ASDSLI
-liability X
risk
factors
X
-liability Y
r
22

23. But nonword repetition shows
different pattern in relatives
• In SLI, nonword repetition deficit is
clearly familial (e.g. Barry et al, 2007)
• In autism, where child is poor at nonword
repetition, parents and sibs are not
23
Barry, J. G., Yasin, I., & Bishop, D. V. M. (2007). Heritable risk factors associated with language
impairments. Genes, Brain and Behavior, 6, 66-76.
Bishop, D. V. M., et al (2004). Are phonological processing deficits part of the broad autism
phenotype? American Journal of Medical Genetics: Neuropsychiatric Genetics, 128B(54-60).
Whitehouse, A. J. O., et al (2008). Further defining the language impairment of autism: Is there a
specific language impairment subtype? Journal of Communication Disorders, 41, 319-336.
Lindgren, K. A.,et al (2009). Language and reading abilities of children with autism spectrum
disorders and specific language impairment and their first-degree relatives. Autism Research, 2(1),

24. Shared genetic risk? CNTNAP2
CNTNAP2 gene; polymorphic gene, neurexin, regulated
by FOXP2.
Common variant associated with risk of
neurodevelopmental problems
• Alarcon et al, 2008; assoc with late language in ASD
• Vernes et al, 2008: assoc with nonword repetition in children with SLI
• Li et al, 2010: autism association in Chinese Han
• Steer et al, 2010; assoc with late lang acquisition
• Whitehouse et al, 2011; assoc with delayed language milestones in gen
pop. sample
but NB very small effect sizes!
24Graham, S. A., & Fisher, S. E. (2013). Decoding the genetics of speech and language.
Current Opinion in Neurobiology(0). doi: http://dx.doi.org/10.1016/j.conb.2012.11.006

25. Alternative genetic
explanation
G x G interaction (epistasis)
25
25
Bishop, D. V. M. (2010). Overlaps between autism and language impairment:
phenomimicry or shared etiology. Behavior Genetics, 40, 618-629.

26. Overview of G x G model
• Common variant of gene such as CNTNAP2
creates mild risk for poor nonword repetition
• Other genes have risk variants that contribute
to autism
• If CNTNAP risk variant occurs together with
certain ASD risk genes, effect on language
much more severe
26

27. Evaluation of G x G model
• Predicts high frequency of comorbid ASD + LI
• Predicts lower rate of LI symptoms in relatives
of ASD+LI than relatives of SLI
• Fits with current move to look at gene networks
rather than individual genes
• Predicts molecular genetic overlaps
27

28. risk
factors
Y
-liability Y
ASDSLI
-liability X
risk
factors
X
Phenomimicry model
• Primary form of disorder, each with own cause, but also secondary
form that mimics the other disorder.
• Crucially, does NOT predict  SLI in relatives of those with ASD+LI
28
LI

29. Evidence for phenomimicry
Different error patterns for ASD+LI cf. SLI on tests
of nonword repetition and verb inflection
29
Williams, D., Botting, N., & Boucher, J. (2008). Language in autism and
specific language impairment: Where are the links? Psychological Bulletin,
134(6), 944-963. doi: 10.1037/a0013743
From Whitehouse
et al (2008)

30. Remaining puzzle:
Why do only a subset of ASD have LI?
30
Not down to severity
Lindgren et al found language in ASD cases was not correlated
with ASD symptoms measured by ADI-R
communication social repetitive
normal language
language impaired
Lindgren, K. A., et al
(2009). Language and
reading abilities of
children with autism
spectrum disorders and
specific language
impairment and their first-
degree relatives. Autism
Research, 2(1), 22-38.

31. The terminological jungle

32. Overlap in neurodevelopmental disorders
Clinical implications
ASD
SLI
Dyslexia
DCD ADHD

33. Same child, different diagnosis
 Educational psychologist: Dyslexia
 Speech and language therapist: SLI
 Psychiatrist: Autism spectrum
disorder (ASD)
 Neurologist: Developmental
co-ordination disorder (DCD)
 Paediatrician: ADHD

34. Implications of terminological confusion
• Children’s needs may go unmet
• Arbitrary and unfair decisions about access to
services
• Lack of recognition of some conditions
34

35. 35
Amount of research (1985-2009) and
prevalence of neurodevelopmental disorders
Condition
papers
/year
freq.
%
Tourette syndrome 83 0.5
Autistic spectrum disorder 643 0.7
Developmental dyscalculia 9 3.0
Attention deficit hyperactivity disorder 505 5.0
Developmental dyslexia 152 6.0
Developmental coordination disorder 16 6.5
Specific language impairment 46 7.4
Data from: Bishop, D. V. M. (2010). Which neurodevelopmental
disorders get researched and why? PLOS One, 5(11), e15112. doi:
10.1371/journal.pone.0015112

36. 36
NIH funding over time for
neurodevelopmental disorders
$K
0
100000
200000
300000
400000
500000
600000
700000
800000
900000
2000-
2001
2002-
2003
2004-
2005
2006-
2007
2008-
2009
Attention deficit
hyperactivity
disorder
Autistic spectrum
disorder
Dyslexia/SLI/speech
/dyscalc/DCD
Data from: Bishop, D. V. M. (2010). Which neurodevelopmental
disorders get researched and why? PLOS One, 5(11), e15112. doi:
10.1371/journal.pone.0015112

37. One alternative
 Broad category of ‘neurodevelopmental disability’ to
establish need for services
 ‘Disability’ emphasises impact on individual
 ‘Neurodevelopmental’ emphasises biological basis: not
just poor teaching
 Supplemented with assessment to establish profile of
difficulties/strengths on different dimensions, and
determine which services to prioritise
http://deevybee.blogspot.com.au/2010/12/whats-in-name.html

38. Raising Awareness of Language Learning Impairments
http://www.youtube.com/RALLIcampaign

39. Dorothy Bishop
Oxford Study of Children’s
Communication Impairments,
Department of Experimental
Psychology,
South Parks Road,
Oxford,
OX1 3UD,
England.
dorothy.bishop@psy.ox.ac.uk
@deevybee