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- W35213071 abstract "JUSTIFY Autism is currently viewed as a largely genetically determined neurodevelopmental disorder. Over the last decades, an increasing number of studies have been performed, trying to establish the underlying biological causes of autism. However, its exact etiology still remains unclear. In this thesis, we have tried to list the existing literature on and enhance the knowledge of structural brain abnormalities as applied to autism. First, we have written two reviews, one on the existing structural MRI literature and one on the available neuropathological literature. Second, we have performed 4 structural MRI studies, 3 investigating which brain structures are abnormal in volume in high-functioning medication-naive subjects with autism and one investigating to what extent the brain abnormalities, as found in autistic subjects, show genetic susceptibility. Third, we have investigated brains of autistic and control subjects by using design-based stereological techniques, to explore the underlying cellular causes of differences in brain volumes.We investigated brain volumes in two groups of autistic subjects (children and adolescents) and in closely matched control groups. Both high-functioning medication-naive autistic children and adolescents displayed brain enlargements of ~ 5%. The enlargement could be ascribed to a global enlargement of the cortical gray matter volume and the cerebellum, but not of the subcortical white matter volume. The hippocampus was enlarged as well, proportional to the increase in brain volume, whereas the amygdala did not show an increase in volume. In addition, the ventricular volumes were excessively enlarged; in childhood, the increase encompassed 45%, whereas in adolescence this increase ran up to more than 70%. As to the underlying mechanisms of increased gray matter volume one can only speculate, but either increased neurogenesis or decreased pruning processes, such as apoptosis seem likely, which would result in an increase in neuronal number.As both autism and brain volume are highly genetically determined we wanted to examine the possible genetic component of brain enlargement in autism. Therefore we set out to investigate brain volumes of biological non-affected parents of autistic probands (19 couples) and of closely matched control couples (n = 20 couples). No significant difference in any of the brain volumes was found between the parents of autistic probands –either fathers or mothers- and healthy control couples. Thus, most likely, increased brain volume in autism is caused by the interaction of paternal and maternal genes, possibly with an additional effect of environmental factors. Finally, after reviewing the existing neuropathological literature on autism, we used the last part of this thesis, to describe the first quantitative stereological study on autism, which we performed last year. Increased neuronal number (and density) was found in the hemispheres of 6 autistic cases compared to 6 age-matched control cases (4-25 years), which seems to be in accordance with the increase in gray matter volume, found with MRI.In conclusion, we have reached the goal of this thesis: list the existing literature on structural brain abnormalities in autism and better define the anatomical abnormalities found in autism. However, although we posed a theory of disrupted pruning processes, which might explain the findings reported in the present thesis, no definitive answers can be given yet." @default.
- W35213071 created "2016-06-24" @default.
- W35213071 creator A5038066448 @default.
- W35213071 date "2005-03-22" @default.
- W35213071 modified "2023-09-26" @default.
- W35213071 title "Structural brain abnormalities in autism : neuroimaging and neuropathology studies" @default.
- W35213071 hasPublicationYear "2005" @default.
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