On the Spectrum

General discussion
RATIONALE
Phenotypic studies point to a dimensional structure of child psychiatry (Insel, Cuthbert, Garvey,
Heinssen, Pine et al. 2010). However, neuroimaging studies are still primarily designed as casecontrol
studies. In this thesis, we explored the neurobiology of various dimensions of child
psychopathology, primarily focusing on autistic traits. In addition, we studied internalizing and
externalizing symptoms in children. Instead of using the traditional case-control framework,
we used alternative approaches to define the phenotypes of interest. In the context of ASD,
we utilized the fact that the social impairment in autism can be conceptualized as part of a
continuum, at which ASD represents the severe end. Further, we studied internalizing and
externalizing symptoms in children, using both continuous and categorical approaches. Here,
we will describe the main findings of this thesis and discuss them in the context of the most
recent literature. Moreover, we will address some methodological considerations that are of
interest for this field of research. Finally, we will discuss the implications for future research
and clinical practice.
Social responsiveness on a continuum as endophenotypes of ASD
Unaffected relatives of people with ASD often show milder expressions of the same traits.
Observations of this phenomenon date back to Kanner’s first case descriptions, where he
observed that that some parents of children with autistic impairment were ‘late talkers’
and seemed ‘uninterested in people’ (Kanner 1968). The existence of a spectrum for ASD
was initially studied by assessing the severity distribution within affected individuals. Later,
the observation that there are people that do not quite meet criteria for a DSM-disorder,
but do have traits, broadened that spectrum to the so called ‘Broader Autism Phenotype’
(Sucksmith, Roth and Hoekstra 2011). Finally, the spectrum was extended even further by the
observation that people in the general population showed traits as well (Constantino 2011).
Instruments were developed to measure traits of ASD, including the Social Responsiveness
Scale (Constantino 2002) and the Autism Quotient (Baron-Cohen, Wheelwright, Skinner,
Martin and Clubley 2001) and it was found that these traits are continuously distributed
in the population. Such scales, representing the full spectrum of subclinical to severe traits
can be used an endophenotype of ASD (Gottesman and Gould 2003). Endophenotypes
are “components” of psychiatric disorders that can be helpful in the identification of the
underlying neurobiology. Initially, they were mostly used in the context of genetics. However,
this approach can be applied in neuroimaging as well. The use of continuous trait phenotypes
in the general population is especially beneficial, as they increase the power of the analyses
and findings can be more broadly extrapolated. In terms of symptom severity, the majority
of people in the general population with such traits clearly do not meet criteria for a clinical
diagnosis of ASD. However, their symptoms can still be disabling, can hamper the building of
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