The document discusses conceptual issues related to neurodevelopmental disorders, emphasizing their classification and commonalities despite distinct features. It critiques the broad and sometimes misleading approaches used historically, advocating for a nuanced understanding that acknowledges shared genetic and developmental factors. The authors suggest redefining neurodevelopmental disorders to better reflect their multifactorial etiology and co-occurrence among various conditions.

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Neurodevelopmental Disorders:
3 Conceptual Issues
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Dorothy Bishop and Michael Rutter
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From the beginnings of psychiatric classifications, there have a separate axis because they differed from the general run of
been attempts to establish broad overarching groups (see psychopathologic conditions in three key respects:
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chapter 2). Thus, for many years, mental disorders tended to 1 An onset that is invariably during infancy or childhood;
be put into the two broad categories of “organic” and “func- 2 An impairment or delay in the development of functions
tional” disorders. The rationale was that, with respect to that are strongly related to biologic maturation of the central
causation, the disorders within each group had more in com- nervous system; and
mon with other disorders in the same group than with those 3 A steady course that does not involve the remissions
in the alternative group. The implication was that it might and relapses that tend to be characteristic of many mental
be useful for research into causal processes to determine com- disorders.
monalities within these broad groups, rather than to assume The overall description of this group of disorders noted that
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that each diagnostic category would have a unique cause not there is impairment in some aspect of mental development,
shared by all other conditions. but the impairment tends to lessen as the children grow older;
One such broad grouping was the notion of “minimal despite this, deficits tend to continue into adult life; most
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brain dysfunction” (MBD) which was popular in the 1960s of the conditions are more common in males than females;
and 1970s (Wender, 1971). The concept has been discredited and a family history of similar or related disorders is com-
(Rutter, 1982) and is no longer in general use. The crucial flaws mon, suggesting that genetic factors have an important
were that particular behaviors could not be used to infer brain role in the etiology. The subclassification within this axis com-
pathology, and that organic brain dysfunction did not lead prised disorders involving language development, scholastic
to a homogeneous psychopathologic pattern. In addition, it skills or motor function. DSM-IV (American Psychiatric
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seemed to presuppose that all types of brain dysfunction Association, 2000) has a broadly comparable subclassifica-
would have similar consequences. It is clear that is not so. The tion but the disorders are not placed on a separate axis and
problem with this broad grouping is that it arose from a the overall conceptualization for grouping is not expressed
theoretical notion for which there was no good empirical sup- so explicitly.
port. The question that we consider in this chapter is whether An alternative usage extends the term “neurodevelopmen-
the concept of neurodevelopmental disorders fares any better tal disorders” much more broadly to include single-gene dis-
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as a guide to the future. Our focus here is on conceptual issues orders such as Williams syndrome or Prader–Willi syndrome
in the characterization and classification of disorders, rather (Tager-Flusberg, 1999) or disorders deriving from prenatal
than on aspects of clinical management, which are dealt with insults or toxins, such as fetal alcohol syndrome (Harris,
in the chapters on individual disorders. 1995). These conditions develop on the basis of neural
impairment, involve cognitive deficits of various kinds, and,
as with the specific disorders of psychologic development, are
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What Do We Mean by characterized by a steady course without remissions or
Neurodevelopmental Disorders? relapses. However, whereas the Axis 2 ICD-10 disorders are
defined in terms of a profile of specific impairment of linguistic,
Over the last two decades or so, there has been increasing scholastic or motor skills, these disorders are defined in terms
use of this concept. However, there are at least four rather of etiology. Although it can sometimes be fruitful to compare
different ways in which the term has been used. The narrowest the deficits associated with a particular known etiology and
concept is provided by the second axis of the ICD-10 classifica- those in a specific developmental disorder, it is potentially
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tion (World Health Organization, 1996), dealing with Specific confusing to classify these different types of disorder together,
Disorders of Psychological Development. They were placed on and in this chapter we restrict consideration to those dis-
orders with a putative multifactorial etiology. For similar
reasons, we would argue against adopting a definition that
Rutter’s Child and Adolescent Psychiatry, 5th edition. Edited by M.
includes mental retardation, cerebral palsy, traumatic brain
Rutter, D. Bishop, D. Pine, S. Scott, J. Stevenson, E. Taylor and A. injury and epilepsy under the rubric of neurodevelopmental
Thapar. © 2008 Blackwell Publishing, ISBN: 978-1-4051-4592-3. psychiatric disorders.
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NEURODEVELOPMENTAL DISORDERS
There are two more modest ways in which the concept origins in a neurodevelopmental abnormality rather than as
of neurodevelopmental disorder can be broadened beyond a neurodevelopmental disorder as such, and confine the term
specific disorders of psychologic development. First, many neurodevelopmental to those disorders traditionally regarded
people include both autism spectrum disorders (ASD) and atten- as specific developmental disorders, plus ASD and ADHD.
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tion deficit/hyperactivity disorders (ADHD) in the overall
grouping of neurodevelopmental disorders. At first sight,
it might be objected that there are several ways in which Are the Neurodevelopmental Disorders
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both of these are rather different. Thus, neither reflects a Distinct Conditions?
straightforward impairment in a development-based skill that
is closely related to biologic maturation. Also, both involve Both traditional medical, and traditional psychologic, appro-
deviant functioning (i.e., that which is not normal at any age) aches have tended to operate with discrete diagnostic categories.
as much as impaired functioning (i.e., that which is normal Thus, reading disability continues to be conceptualized as
in form but impaired in level). Nevertheless, the reason why “developmental dyslexia,” with the implication that it is a
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they have come to be grouped with neurodevelopmental dis- discrete neurologic condition (Démonet, Taylor, & Chaix,
orders is that they share with the other disorders the facts that 2004). For many years, specific language impairment was
they are multifactorial in origin; are present from early life; termed developmental dysphasia (Zangwill, 1978) with the
tend to improve with increasing age but are also associated same kind of implication. This terminology has now gone
with disordered functioning that extends right into adult life; out of fashion because of the recognition that impairments in
they involve a strong genetic influence; and both show a marked language development differed in important ways from
male preponderance. Furthermore, they are characterized by acquired disorders of language. In psychiatric classifications,
neuropsychologic impairments, in aspects of executive func- both ASD and ADHD are treated as if they were conditions
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tion in ADHD (see chapter 34), and in social cognition, that were entirely separate from other disorders of psychologic
central coherence and executive function in ASD (see chap- development. In line with this conceptualization, cognitive
ter 46). Strikingly, epidemiologic and clinical studies have shown psychologists have looked for a single specific underlying
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that these two disorders often co-occur with the ICD-10 Axis deficit that is responsible for each disorder, the nature of the
! 2 disorders of psychologic development, and genetic findings
have similarly begun to point to a possible shared genetic
deficit differing for each one (Morton & Frith, 1995).
There are two main reasons for challenging this view of neuro-
liability (as well as a liability that is more syndrome specific; developmental disorders as a set of independent conditions.
@ Grigorenko, submitted). In addition, although autism may be
associated with other forms of psychopathology that do show
First, there is substantial co-occurrence among them. Second,
both etiologic and psychologic studies indicate that multiple
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# remission and relapses (Hutton, Goode, Murphy et al., in press)
the basic disorder is persistent rather than recurrent. Much
deficit models are more consistent with the multifactorial and
probabilistic etiology of such disorders (Pennington, 2006),
the same applies to ADHD (see chapter 34). and that significant developmental impairment may arise only
A further possible broadening of the concept of neurode- when there is more than one risk factor present (Bishop, 2006).
velopmental disorders brings in life-course-persistent anti- As in internal medicine, the same pathologic endpoint can
social behavior (Moffitt, 1993) and schizophrenia (Rapoport, arise through multiple, rather different, causal pathways (cf.
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Addington, & Frangou, 2005). At one time, both of these would Rutter, 1997). In the following sections, we present evidence
have been regarded as acquired disorders but there is now an to support the case that rather than looking for the cause
abundance of evidence that schizophrenia is often associated of each type of neurodevelopmental disorder, we need to take
with impairments in the development of both language and account of the commonalities among them, and develop more
motor function and with cognitive impairments that precede complex models that can explain the patterns of association
the development of overt schizophrenia (see chapter 45). and dissociation among deficits.
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Similarly, unlike adolescence-limited antisocial behavior, the
life-course-persistent variety of antisocial behavior begins in
the preschool years and is associated with hyperactivity and Commonalities Among Developmental
impairments in information processing and social cognition (see Disorders
chapter 35). For the purposes of this chapter we have not
included either of these disorders under the rubric of neuro- Research findings across the whole of psychopathology, both
developmental disorders for two main reasons. First, both in childhood and adult life, have been consistent in showing
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antisocial behavior and schizophrenia do show fluctuations the high frequency with which individuals have multiple, sup-
in their manifestations that are more akin to the remissions posedly separate, disorders (Angold, Costello, & Erkanli, 1999;
and relapses associated with the broad run of mental dis- Caron & Rutter, 1991). This is strikingly apparent for the
orders than with the relatively steady state of the specific neurodevelopmental disorders – indeed, it has been argued that
disorders of psychologic functions. Second, there is not the a pure disorder is the exception rather than the rule (Gilger
same evidence of a shared genetic liability. For these reasons, & Kaplan, 2001; Kaplan, Dewey, Crawford et al., 2001) –
we prefer to conceptualize these as disorders that have their and is reflected in the ICD-10 category of mixed developmental
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disorders. Thus, there is considerable overlap between specific A “Syndrome” of Neurodevelopmental
reading disability (SRD) and specific language impairment Disorder?
(SLI) (Bishop & Snowling, 2004; Eisenmajer, Ross, & Pratt,
2005), between SRD and ADHD (Dykman & Ackerman, 1991; One might start to wonder if, rather than differentiating
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Willcutt & Pennington, 2000) and between SLI and ADHD between neurodevelopmental disorders, it would make more
(Beitchman et al., 1996). Less work has been carried out on sense to group them all together into an overarching category,
developmental coordination disorders (DCD), but there is treating them as variant forms of a common underlying
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evidence for an overlap between motor impairment and both disorder. However, there are sufficient differences among the
SLI (Hill, 2001) and ADHD (Kadesjö & Gillberg, 1998). As neurodevelopmental disorders to preclude such a conceptual-
far as autistic disorder is concerned, the defining criteria ization. First, molecular genetic studies have been successful
disallow a diagnosis of SLI in a child meeting criteria for in identifying chromosomal regions associated with risk for
autistic disorder, but it is clear that at the symptomatic level reading disability, SLI, ADHD and ASD, but there has been
there is considerable overlap, with many affected children little or no overlap between the linkages reported for these
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showing the kinds of structural language deficits that charac- different disorders. For instance, Fisher (2006) noted that
terize SLI (Tager-Flusberg & Joseph, 2003). Furthermore, whereas linkages to dyslexia have been found on chromosomes
many children with SLI or ADHD show in milder form the 1, 2, 3, 6, 15 and 18, those to SLI have been found on chro-
kinds of social/pragmatic impairments that are characteristic mosomes 13, 16 and 19. Fisher pointed out that we need to
of autistic disorder (Bishop & Norbury, 2002; Clark, Feehan, be careful in interpreting such findings: it would be danger-
Tinline et al., 1999; Farmer, 2000; Geurts et al., 2004). SRD ous to assume that there are highly specific pathways from
co-occurs with mathematical difficulties at a higher level than genotype to phenotype, especially because few studies have
predicted from the prevalence of either disorder on its own used multivariate methods to look at more than one disorder
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(Lewis, Hitch, & Walker, 1994). at a time. Undoubtedly there are some genes whose effects
It has become accepted to refer to these patterns of co- are common to more than one neurodevelopmental disorder
occurrence as “comorbidity,” but this is misleading because (e.g., Willcutt et al., 2002), but behavior genetic studies also
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it ignores the possibility that much of the supposed com- usually find evidence for specific as well as common genetic
orbidity is simply a function of the invalid, and artificial, influences on co-occurring disorders (e.g., Martin, Piek, & Hay,
diagnostic subdivisions in classification systems (see chap- 2006). Second, there are differences among disorders in drug
ter 2). Thus, for example, it seems likely that much of the response. It is striking, for example, that whereas ADHD shows
co-occurrence of supposedly different anxiety disorders is a marked beneficial response to stimulant medication (see
simply a consequence of these disorders being slightly differ- chapter 34), no drugs have other than a slight inconsistent effect
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ent manifestations of the same underlying condition (see on the basic problems associated with ASD (see chapter 46).
chapter 39). Might the same apply to neurodevelopmental Similarly, although medication may provide some symp-
disorders? Clearly it could. tomatic improvement with the other neurodevelopmental
Thus, SLI and reading disability both comprise disorders disorders, there are not the marked benefits that are seen with
of language – the former with respect to spoken language ADHD. Third, although it is difficult to compare across
and the latter with respect to written language. It would be imaging studies because of variations in the ways in which they
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rather surprising if there was no co-occurrence between the have been conducted (Peterson, 2003), patterns in the vari-
two. That is not to argue that all cases of reading disability ous neurodevelopmental disorders do not seem at all closely
derive from oral language impairment, because manifestly similar: for instance, fronto-striatal systems are implicated in
they do not (Bishop & Snowling, 2004); but it is to suggest ADHD (see chapter 34), whereas in dyslexia there is reduced
that co-occurrence of some degree is to be expected. activation in left temporo-parietal cortex (see chapter 48).
However, the co-occurrence of neurodevelopmental dis- Fourth, at a behavioral level, there are differences among
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orders does not apply only to language-related disorders; as neurodevelopmental disorders in short and long-term course
noted above, there are also overlaps between language and (Rutter, Kim-Cohen, & Maughan, 2006a). Finally, although
motor impairments, attention deficit and social deficits, and most neurodevelopmental disorders are characterized by a
these cannot readily be explained as different manifestations preponderance of males, sex ratios vary across disorders,
of a common cognitive disability. To some extent, overlaps with the male excess being far more striking for ASD than
could reflect referral bias in clinical samples: for instance, a for other neurodevelopmental disorders (Rutter, Caspi, &
child whose reading or language disability is accompanied by Moffitt, 2003). Arithmetic difficulties stand out from the
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social impairment or attentional deficit would be more likely rest, with boys and girls equally likely to be affected (Lewis
to referred to a psychiatrist than one who had an isolated et al., 1994; Rourke, 1989; Shalev, Auerbach, Manor, & Gross-
impairment. However, this cannot be the whole explanation, Tsur, 2000).
because overlaps are seen in epidemiologic samples (e.g., Clearly, it is not feasible to treat the whole gamut of
Beitchman et al., 1996), and second, the rates of co-occurrence neurodevelopmental disorders as a single condition, but
are higher than would be predicted from knowledge of the can we nevertheless identify distinct syndromes within this
frequency of individual disorders. category, in which a pattern of deficits arises from a common
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NEURODEVELOPMENTAL DISORDERS
neurobiologic cause? Rourke’s (1989) account of “non-verbal gene gene gene env env env
etiology
learning disability” (NLD) is such a model: a distinctive 1 2 3 1 2 3
pattern of strengths and weaknesses in sensorimotor skill,
scholastic achievement, and socioemotional development are
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seen as all originating from destruction or dysfunction of white
matter in the right cerebral hemisphere. The deficits seen
neurobiology
as characterizing NLD encompass specific arithmetical dis-
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order, DCD and Asperger syndrome. The construct of NLD
explains the co-occurrence of these deficits in terms of a
specific neurobiologic basis. However, the validity of the
category is questionable. The different deficits certainly can cognition cog 1 cog 2 cog 3 cog 4
and do co-occur, and the association of the symptomatology
of Asperger syndrome with the neuropsychologic manifesta-
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tions of NLD has been empirically demonstrated (Klin, beh beh beh beh
Volkmar, Sparrow, et al., 1995). However, the association behavior 1 2 3 4
appears too weak to justify treating it as a syndrome: this
Fig. 3.1. Levels of causation for developmental disorders. The
is demonstrated in studies showing that a high proportion of
dashed line emphasizes that children’s behavior (beh) can affect
children with a clinical picture of NLD do not show specific
the environment (env) they experience. [From Bishop, D. V. M.,
deficits thought to characterize this disorder (Drummond,
& Snowling, M. J. (2004). Developmental dyslexia and specific
Ahmad, & Rourke, 2005; Pelletier, Ahmad, & Rourke, language impairment: Same or different? Psychological Bulletin,
2001). If we embrace the construct of NLD, we end up in 130, 858–886 with permission.]
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excluding numerous cases because they do not show the
anticipated combination of deficits, meaning that we either have
to dilute the “syndrome” to be too general to be useful, or
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we have to devise additional categories to encompass the cases Causal Models of Neurodevelopmental
that do not fit. Similar problems arise if we try to fit language, Disorders
literacy and speech disorders into a broader syndrome; we can
find many children who show this constellation of impairments, Cognitive Deficits
but there are also many who do not (Bishop & Snowling, 2004; One goal of developmental neuropsychology is to uncover
Pennington, 2006). the underlying nature of deficits seen in neurodevelopmental
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Neurodevelopmental disorders thus pose a considerable disorders. As shown in Fig. 3.1, the same behavioral deficit
challenge for a classification system. On the one hand, we need may arise for different reasons, and one would hope that as
to explain why there is common co-occurrence of different our conceptual understanding advances, we might be able to
deficits, while at the same time allowing for dissociations categorize disorders not in terms of surface behavior, but
between different types of deficit, and variable patterns of asso- in terms of underlying cognitive deficits. For instance, most
ciated features. The causal model shown in Fig. 3.1 provides children with reading disability have difficulties with phono-
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a framework for conceptualizing these questions. In this logic analysis which are evident even when they are tested using
model, first put forward in the context of SLI and dyslexia, methods that do not require any reading or writing (see chap-
a neurodevelopmental disorder is identified on the basis of a ter 48). Other poor readers have visual difficulties, problems
constellation of behaviors; these result from specific cognitive learning specific spellings of irregular words or poor com-
deficits, which have particular neurobiologic bases, which are prehension of written texts. A focus on underlying cognitive
in turn affected by genetic or environmental factors. When deficits thus could help identify new subgroups. It also sug-
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extending the model to cover the whole gamut of neurode- gests that some of the existing distinctions among disorders
velopmental disorder, the “cognitive” level is taken to include may be unrealistic; for instance, increasingly speech, language
a wide range of underlying mental operations that cannot be and literacy problems are regarded as different manifestations
directly observed, but are inferred from behavior, including of a common phonologic impairment, whose behavioral
perceptual-motor skills, language, memory, social cognition, correlates would vary depending on the age at which the child
reasoning and executive functions. Relationships among the was observed and the severity of the impairment (Bishop
different levels of functioning are not one-to-one, but involve & Snowling, 2004). Nevertheless, if we try to categorize
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complex multifactorial influences going from etiology to neu- disorders in terms of underlying deficit rather than observed
robiology, from neurobiology to cognition, and from cogni- behavior, this does not necessarily simplify our nosology,
tion to behavior. Viewed from this perspective, it is clear that because multiple deficits are the rule rather than the excep-
overlaps between observed behavioral impairments may arise tion, at the cognitive as well as the behavioral level. Thus,
from shared cognitive deficits, shared neurobiologic origins although one can identify children who fit the picture of
and/or shared etiology. We now turn to consider evidence for “phonologic dyslexia” or “surface dyslexia,” most poor
these different causal mechanisms. readers present a mixed picture (Snowling & Nation, 1997).
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Even if one looks at impairments in very different domains, Furthermore, the notion that “birth injury” was the main
associated disorders are common. risk factor fell into disrepute in view of the evidence that many
Pennington (2006) conducted a series of studies comparing of the risks supposedly associated with obstetric complica-
children with pure dyslexia, pure ADHD, and comorbid tions actually derived from prenatal problems. A genetically
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dyslexia and ADHD. He was interested in the possibility that abnormal fetus is more likely to have a low birth weight
comorbidity among these disorders might reflect the influence and to be born following premature gestation. That pro-
of one behavior on another (e.g., attentional difficulties might bably accounts for the somewhat inconsistent association
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arise because the child who could not read well became bored between obstetric complications and ASD (Bolton et al.,
and distractible; or conversely, the child’s difficulty in attend- 1997). Undoubtedly, extremely low birth weight does lead to
ing could lead to scholastic deficits). If the first account were an increased rate of motor, language, scholastic and attentional
true, then the comorbid children should resemble the pure difficulties (Marlow, 2004; Marlow et al., 2005). However,
dyslexic cases in terms of underlying impairment. If the the association is not strong when assessed in the opposite
second account applied, then the comorbid children should direction (i.e., by starting with children with neurodevelop-
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resemble the pure ADHD cases. In fact, the pure dyslexia group mental disorders and studying their perinatal history). With
had phonologic deficits, the ADHD group had inhibition the possible exception of developmental co-ordination dis-
deficits, but the comorbid group had evidence of both phono- order (for review see Cermak, Gubbay, & Larkin, 2002),
logic and inhibition deficits. These results are consistent with obstetric complications do not have a particularly important
conventional wisdom that links dyslexia to poor phonology association with any of the neurodevelopmental disorders. It
and ADHD to weak inhibition, but it leaves unexplained the is family history that provides the key differentiator.
co-occurrence of these two impairments.
We can summarize by saying that it was hoped that, by The Concept of Maturational Lag
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studying underlying impairments, we would obtain clearer dis- Given that neurodevelopmental disorders are, on the one
tinctions between disorders and find that apparent comorbidity hand, familial, and on the other hand, not caused by acquired
was a consequence of poor specification of disorders. In fact, brain lesions, we need to seek another causal mechanism at
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studies such as this show that comorbidity is just as apparent the neurobiologic level. There is often an implicit assumption
at the level of cognitive impairment as it was at the level of that genetic or other prenatal influences have led to some
observed behavior. This suggests we need to seek an explana- failure of neurodevelopment that leads to abnormality that is
tion for the associations among neurodevelopmental disorders functionally equivalent to a focal brain lesion – hence the anal-
at a different causal level. ogous syndromes seen in neurodevelopmental disorders and
adult acquired disorders (Temple, 1997). According to this view,
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Neurobiologic Bases the brain of a child with a neurodevelopmental disorder has
Neuropsychologic studies of adults highlight how fairly an underlying abnormality that persists through childhood. An
specific impairments in functions such as language, reading, alternative possibility is that these disorders are no more than
arithmetic or motor programming can arise as a consequence an extreme of the normal variation in the timing of develop-
of a focal brain lesion (McCarthy & Warrington, 1990). ment. We know that there are huge differences in the timing
When one sees analogous impairments in children, it is of puberty in both males and females, and marked differences,
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tempting to assume a similar etiology via underlying brain too, in the timing of the eruption of teeth. In similar fashion,
damage, with the precise pattern of observed impairment there is marked individual variation in the timing of speech
depending on the extent, location and severity of the damage. acquisition. When such a delay is followed by later normal
This kind of model was put forward in the 1950s by functioning it may be regarded as a maturational lag of some
Pasamanick and colleagues, who proposed a “continuum of kind. The implication is that the problem involves a normal
reproductive casualty,” suggesting that whereas major neuro- variation in the development of certain brain systems respons-
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logic insult resulting from birth trauma, intracranial hemor- ible for cognitive functioning, rather than in some abnormal
rhage or anoxia can lead to clear signs of neurologic damage difference in brain systems, and that there can be a highly
such as cerebral palsy or epilepsy, milder damage may lead selective delay in the maturation of just one brain system.
to more subtle learning difficulties. However, this conceptu- Associations between neurodevelopmental disorders would
alization of the etiology of neurodevelopmental disorders has then arise in cases where the maturational lag extended to
not received much empirical support. There is good evidence encompass several brain regions, or where there is pluripo-
that such damage often gives rise to behavioral and cognitive tentiality (i.e., a given brain structure is involved in a range
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sequelae (Pasamanick & Knobloch, 1966), but the suggestion of cognitive functions; Noppeney, Friston, & Price, 2004).
that neurodevelopmental disorders often arise from damage A key prediction from the “lag” hypothesis is that not only
during the obstetric process has not proved to be the case. should the pattern of functioning resemble that of a normal
Nichols and Chen (1980) found only weak associations younger child but also, as the children with a neurodevelop-
among neurologic soft signs, hyperactivity and learning dis- mental disorder get older, the main difference from normal
orders, and even weaker associations between these variables functioning should be found for later-maturing functions
and perinatal complications. and not for early-maturing functions (Bishop & Edmondson,
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1987; Bishop & McArthur, 2004, 2005). The limited avail- it is difficult to become fully competent in the phonology
able evidence is in keeping with that expectation and runs and syntax of a second language acquired after puberty
against the outmoded static lesion notion. However, for most (Mayberry & Lock, 2003; Oyama, 1976). However, critical
neurodevelopmental disorders, although there is a general periods for auditory development have not been demon-
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tendency for gains in function with increasing age, delayed early strated, and there is electrophysiologic evidence that devel-
development is not followed by later normal functioning opment of the auditory system (Albrecht, von Suchodoletz,
(Rutter et al., 2006a). Can a maturational lag account have & Uwer, 2000) as well as of some other cortical systems con-
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any explanatory value in such cases? tinues right up into adulthood (see chapter 12). Longitudinal
Two main possible explanations, both speculative, have studies using magnetic resonance imaging (MRI) have con-
been proposed for why children with a neurodevelopmental firmed that brain development continues well after the onset
disorder do not ultimately catch up. First, the persistence could of puberty, with higher-order association areas maturing only
derive from what Stanovich (1986) termed a “Matthew after lower-order somatosensory and visual areas (Gogtay
effect,” whereby the poor (poor readers) get poorer (make slow et al., 2004; see also chapter 12), and that such changes – espe-
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progress), while the rich (good readers) get richer (make good cially in the frontal cortex – are associated with intellectual
progress) as a result of literacy experience boosting further functions (Shaw et al., 2006a). There is considerable vari-
language and literacy development. Furthermore, a poor ation from one cortical region to another, with some showing
reader may lack the necessary experiences later (i.e., reading radical changes at puberty and others unaffected (Nelson
is not usually taught in secondary schools, and such books as et al., 2002). Clearly, further research is required in order to
are available are likely to be too advanced to be intelligible). provide an understanding of both brain development (and
There could also be more indirect effects whereby early impair- its functional consequences) in typically developing indi-
ments create a negative spiral affecting other skills (e.g., the viduals and in those with neurodevelopmental disorders. As
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effects on intimate social relationships of communication the evidence currently stands, the postulate that the relevant
difficulties in early childhood). Because of the importance brain systems lose plasticity around the time of puberty remains
of experiences in the development of psychologic functions, highly speculative, and to test it we would need studies that
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there is little doubt that something of this kind could have compare the impact of training on brain and behavior in
a contributory role. What is much less certain is whether pre- and postpubertal individuals. The trajectory findings of
it could account for the severe problems in intimate social Francis et al. (1996) are compatible with the suggestion of a
relationships in adult life found for many individuals with a change in brain plasticity in adolescence but they provide no
severe receptive SLI in adult life reported by Clegg, Hollis, direct support.
Mawhood et al. (2005) – because the relationship deficits We may sum up by concluding that there is little hard
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were not a function of the severity of the earlier language evidence in support of a maturational lag account. We need
deficits (at least in terms of those measured), and because more longitudinal and neurobiologic studies to evaluate this
the nature of the deficits appeared so different from those idea. In its favor, this kind of explanation has the potential
usually associated with social rejection. It is also noteworthy to highlight parallels between causal mechanisms in normal
that persistence of disorder is often seen in young people with and impaired development, and to account for changing
SLI who have been enrolled in special education throughout profiles seen in neurodevelopmental disorders. It provides the
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the secondary as well as primary school years (Conti-Ramsden, impetus for studies that track neurodevelopment over time:
Botting, Simkin, et al., 2001; Haynes & Naidoo, 1991). for instance, Shaw et al. (2006b) documented changes in
Perhaps the key empirical finding is provided by Francis, cortical thickness over time in children with ADHD, with evid-
Shaywitz, Stuebing, Shaywitz et al.’s (1996) individual growth ence of normalization in children who had a good outcome.
curves comparison of 69 children with a reading disability and However, a maturational account seems more plausible as an
334 children with no reading problem. Nine yearly longitud- explanation for transient delays early in development than for
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inal assessments showed that both groups tended to plateau severe and persistent neurodevelopmental disorders.
at about 13 years of age, with no narrowing or expansion of A final point to note is that it is important not to confuse
the gap between the group. They differed in level but not in the hypothesis of a developmental delay with the entirely
trajectory. The finding rather runs counter to the Stanovich different hypothesis that the causation of disorders of psy-
(1986) proposition. chologic development, together with ASD and ADHD (as well
A second kind of explanation for persistence of disorder was as numerous forms of other psychopathology), are based on
proposed in the context of language and literacy deficits by dimensional genetic and environmental risk factors (Rutter,
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Wright and Zecker (2004). They invoked a decline in neuro- Moffitt, & Caspi, 2006b). With multifactorial disorders,
plasticity as a limiting factor, and suggested that neurobiologic dimensional liability is the rule rather than the exception. The
events at age 10 years associated with the onset of puberty question of whether or not the dimensional risks are the same
halted auditory development at whatever level it has reached, ones that apply within the normal distribution is a separate
so that the adolescent was left with a lasting residue of issue and it is one that has been very little investigated up
deficit. This viewpoint is consistent with evidence that there to now, although there has been some relevant research in
are sensitive periods for aspects of language acquisition, so that relation to ADHD (see chapters 23 and 34).
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CHAPTER 3
The Neuroconstructivist Approach increased risk for the single disorders A and B, as well as for
The “maturational lag” account is not the only alternative the A + B combination. Note that these predictions are not
to a “static lesion” model of neurodevelopmental disorders. made by other models of comorbidity: for instance, if the A
We have become increasingly aware that the brain changes + B combination represented a separate subtype of disorder
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in the course of development, restructuring itself to form new with distinct causes, then it should “breed true,” and there
neural systems, both in response to interactions between should be no increase in rates of disorder A in relatives of those
functional neuronal networks and in response to environmental with disorder B (or vice versa). Furthermore, the predictions
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input (see chapter 12). Karmiloff-Smith (1998) argued that hold up for any disorder that shows familiality, regardless
one needs to take such evidence into account when devising of whether genes or shared environmental factors are more
explanations for neurodevelopmental disorders, and that an important.
apparently specific deficit in a child may be the endpoint of If the disorders are significantly heritable, it is possible to
a process that started with a relatively non-specific disruption go further using either quantitative genetic methodologies
to brain development. This “neuroconstructivist” approach (such as twin studies) or molecular genetic studies (focusing
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emphasizes interactions between different neural systems, and on individual identified genes) to determine how far there
to that extent would predict the existence of disorders affect- is a shared genetic influence between the two disorders. Few
ing more than one domain of functioning. However, this the- researchers to date have adopted this approach; an exception
oretical perspective is still very young; its main contribution is work by Pennington (2006), who studied comorbidity of
to date has been to question the simple parallels that are some- SRD and ADHD in a twin sample and concluded that there
times drawn between developmental and acquired disorders, was evidence for shared genetic influence on the two dis-
and to emphasize the need to put development centre-stage. orders. In a similar vein, Bishop (2002) found evidence for
In order to make more specific predictions about neuro- overlapping genetic influences on language impairment and
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developmental disorders and their co-occurrence, we need to motor immaturity in a sample selected for SLI. Molecular
develop specific computational models of normal development, genetic findings also suggest that susceptibility extends beyond
which then allow us to identify which perturbations could traditional diagnostic boundaries (Rutter et al., 2006b).
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result in a particular profile of deficit (Thomas & Karmiloff-
Smith, 2003).
Research Implications of the
Etiologic Influences Neurodevelopmental Disorder Concept
For those conditions where genetically informative designs have
been applied (SRD, SLI, ADHD, ASD), there is evidence of Probably the single most crucial research implication is that
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substantial genetic influences on the liability to disorder (see investigators need to consider the possibility that the causal
chapter 23). With respect to neurodevelopmental disorders influences on key features may extend across the range of
(together with other multifactorial disorders), these probably neurodevelopmental disorders, rather than being specific to
usually reflect the actions of normal variants of multiple just one. Thus, it is striking that, with the exception of arith-
genes of small effect operating together with multiple envir- metic difficulties, all the neurodevelopmental disorders show
onmental influences (Gilger & Kaplan, 2001; Rutter et al., a marked male preponderance (Rutter et al., 2004). That stands
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2006b) rather than the determinative effect of major mutant in marked contrast to the finding that disorders with a marked
genes. This view of etiology is reflected in the causal model female preponderance all concern syndromes typically begin-
in Fig. 3.1, in that there is no one-to-one relationship between ning in adolescence and that involve emotional disturbance,
genes and neurobiology. Rather, a specific neurologic system rather than neurodevelopmental impairment, as the key
is likely to be influenced by a range of etiologic influences and feature. Baron-Cohen and Hammer (1997) have hypothesized
the given etiology will impact on a range of brain regions. Such that ASDs represent an “extreme male brain.” There is a lack
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a model allows for both co-occurrence of deficits and the of good supporting evidence but, in addition, it is necessary
existence of pure disorder. Particular patterns of variation to ask whether that same explanation should be held to apply
may reflect the influence of either specific combinations of to ADHD or SRD or SLI? It does not seem particularly likely
genetic or environmental factors, or the operation of chance that the causes of the male preponderance are entirely differ-
influences (Wolf, 1997). ent in the case of each of the syndromes, although there may
This raises the question of whether patterns of co-occurrence be syndrome-specific factors as part of the explanation.
between disorders indicate a shared liability. Klein and Riso A further question for research is whether studies should
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(1993) noted that evidence for overlapping etiology of dis- continue to be focused on “pure” disorders given that they
orders can be found by looking at the familiality of disorders do not appear to be at all typical. The answer will depend on
in pure and comorbid cases. In essence, they note that if the question that is being asked. Pure groups can be useful in
shared etiology is implicated in causing disorders A and B, then identifying correlates of a specific kind of deficit without
we should see an increased risk for disorder B (with or with- additional confounds. For instance, suppose one wants to test
out A) in relatives of a person with disorder A, and vice the hypothesis that reading disability is caused by a low-level
versa. Furthermore, relatives of comorbid cases should show auditory perceptual deficit. The goal is to compare a group
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of children with SRD and a control group on a task in which receptive language disorder may subsequently merit a diagnosis
they have to listen for small differences between sounds, and of ASD (Conti-Ramsden, Simkin, & Botting, 2006). Most
make a manual response to indicate what they have heard. If parents will be thoroughly confused by such multiple diagnoses,
the sample includes children who have substantial difficulties and conclude that somebody has “got it wrong.” It essential
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with language comprehension, motor dexterity or attentional that professionals work together to ensure that the child
control, then it may be hard to disentangle the influence of receives a diagnosis that provides access to the most appro-
these impairments on task performance. Careful sample selec- priate services, while at the same time assessing the whole range
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tion to exclude such cases may give cleaner results. Having of areas of function that may be impaired. Intervention will
said that, it is worth noting that those who claim to study need to be individually tailored to take into account the
pure cases may be including large numbers of children with child’s specific strengths and weaknesses.
additional deficits which are missed because they are not It is also important that both clinicians and parents recog-
assessed. For instance, many studies of SRD fail to assess nize that diagnostic labels are shorthand descriptors that do
children’s language or attentional skills. If a sufficiently two things: they summarize the child’s major area of deficit;
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detailed assessment battery is used, covering the whole range and they indicate that the problem is neither part of another
of neurodevelopmental disorders, the numbers of pure cases syndrome nor attributable to a known organic etiology. All
available for study may become vanishingly small. If so, it may too often, those interpreting the labels assume they imply more
be better to assess associated deficits, so that one can estab- than this, and treat terms such as “developmental dyslexia”
lish how far they are associated with the dependent variable and “developmental dyspraxia” as if they referred to syndromes
of interest, rather than try to control for their effects by exclu- with distinctive features and clear boundaries that are distinct
sion of comorbid cases (cf. Breier et al., 2001). from normality and have a known biologic basis. In practice,
In many research contexts, focus on pure groups is not these diagnoses are made on the basis of quantitative differ-
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just hard to achieve, it can be seriously misguided. In etio- ence form normality. A statement such as “My child can’t read
logic studies, restricting the phenotype to those with a pure because he’s dyslexic” is not an explanation, rather it is a
disorder may be misleading, if risk factors in fact operate across circular redescription of the problem. Furthermore, use of
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a range of neurodevelopmental disorders. As noted above, inclu- a single diagnostic label can oversimplify the complex and
sion of comorbid cases can provide a rich source of evidence multifaceted nature of many neurodevelopmental disorders.
about the reasons for co-occurrence of disorders, both when
studying underlying impairments and when the focus is on
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Author Query Form
Book title: Rutter’s Child and Adolescent Psychiatry
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Chapter title: Neurodevelopmental Disorders: Conceptual Issues
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Query Query Remarks
Refs.
1 Axis II changed to Axis 2 as used earlier
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2 Update or cite as personal communication
3 Update Hutton et al. in press
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