On the Spectrum

Summary
SUMMARY
Despite evidence from genetic and phenotypic studies that points to a dimensional structure
of child psychiatry, where traits of disorders extend to the general population, most
neuroimaging studies are still designed as clinical case-control 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 applied alternative approaches
to define the phenotypes of interest. Two approaches of quantifying psychiatric symptoms
were applied. In the context of Autism Spectrum Disorder (ASD), we utilized the fact that
the social impairment in autism can be conceptualized along a continuum, at which ASD
represents the severe end. Second, using a latent class approach of dimensional data, we
evaluated categorical constructs of internalizing and externalizing problems in the general
population. The studies in this thesis were performed in the Generation R cohort, a large
prospective population-based cohort study in Rotterdam, the Netherlands. In this cohort,
children are followed from prenatal life onwards. A large subgroup of children participated in
a neuroimaging component of the study, which included structural and functional MRI scans,
as well as a thorough neuropsychological assessment. The first aim of this thesis was to study
various characteristics of the underlying neurobiology of ASD, using the continuum of traits
in the general population. The second aim of this thesis was to study cognitive deficits and
neurobiological correlates of internalizing and externalizing problems. Part I of this thesis
addresses the first aim and focuses on various aspects of the neurobiology of autism, utilizing
continuous trait measures.
In chapter 2, we studied the association between autistic traits and several characteristics
of cortical morphology, including gyrification; the pattern of folding of the cerebral cortex.
Children with more autistic traits showed widespread areas of decreased gyrification of the
cortex. We found that this association was present along a continuum of autistic traits: after
excluding children with the highest levels of autistic traits and confirmed ASD, the association
remained in cortical areas involving the left temporal lobe and left precuneus. In addition,
we found similar effects when comparing a small sample of children with confirmed ASD to
age and gender-matched controls. Taken together, our findings in cortical morphology lend
support to an extension of the neurobiology of autistic traits to the general population.
In chapter 3, we focused on prenatal brain growth using ultrasound measurements.
Altered postnatal trajectories of brain growth are often reported in ASD, particularly in the
first year of life, but much less is known about prenatal head growth trajectories. Evaluating
prenatal growth trajectories of head circumference measured with ultrasound, we showed an
inverse relationship between prenatal head growth and autistic traits later in life; a lower rate
of growth in prenatal head circumference was associated with more autistic traits. However,
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