Abstract
The overall aim of this thesis is to study MR spectroscopic, radiologic, and volumetric brain correlates in very young children with severe developmental disorders; ASD, mental retardation, and language disorder. We wished to examine brain – behaviour relationships in children with ASD at a very young age. The studies reported
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in this thesis were closely linked to the SOSO project. The SOSO project (ScreeningsOnderzoek Sociale Ontwikkeling, Screening Study on Social Development) was aimed at identifying children with ASD at the very early age of 14 months in the general population. Children suspected of ASD or other developmental disorders were asked to participate in an extensive state of the art laboratory work-up. This included spectroscopy and MRI, the results of which are described in this thesis. In chapter 2 we describe the examination of the MR images of the participating children for the prevalence of brain abnormalities, such as cortical migration disorders, ventricular dilations, and disturbed myeliniation patterns. In almost half of the population, abnormalities were reported. In chapter 3, neuronal integrity in frontal subcortical white matter and the amygdala-hippocampal complex is addressed with magnetic resonance spectroscopy (MRS). No differences in metabolite concentrations were found between children with ASD and children with developmental delay. However, this study does not permit any final conclusions on the presence of aberrant levels of metabolite concentrations in children with ASD, as well as in children with mental retardation and language disorder, given methodological limitations such as small sample size and the absence of a control group of normally developing children. Chapter 4 takes a closer look at the participants diagnosed with mental retardation or language disorder. The relationship between brain volumes and intellectual functioning is investigated. We report a correlation of 0.74 between intellectual functioning and total brain volume after correction for intracranial volume, meaning that brain size relative to head size accounted for 56% of the variance in intellectual functioning at this age in developmentally delayed children. Chapter 5 compares brain volumes between the ASD group and the developmentally delayed control group, and examines whether brain volumes are increased in children with ASD compared to brain volumes of children without ASD but with developmental delay. This chapter also addresses the relationship of brain volumes and intellectual functioning in children with ASD. We did not find volumetric differences for any of the brain measures in ASD as compared to developmentally delayed children. Unfortunately, we were not able to include a control group of typically developing children, as these would have been below the age permitted for MR studies in the Netherlands.The positive correlation between intellectual functioning and total brain volume after controlling for intracranial volume in the developmentally delayed group was not replicated in the ASD group. Finally, chapter 6 gives a summary of the previous chapters and discusses the results in more detail.
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