Abstract
Schizophrenia is associated with structural brain abnormalities, but the timing of onset and course of these changes remains unclear. Longitudinal magnetic resonance imaging (MRI) studies have demonstrated progressive brain volume decreases in patients around and after the onset of illness, although considerable discrepancies exist regarding which brain regions are affected. The anatomical pattern of these progressive changes in schizophrenia is largely unknown. In this study, MRI scans were acquired repeatedly from 16 schizophrenia patients approximately 2 years apart following their first episode of illness, and also from 14 age-matched healthy subjects. Cortical Pattern Matching, in combination with Structural Image Evaluation, using Normalisation, of Atrophy, was applied to compare the rates of cortical surface contraction between patients and controls. Surface contraction in the dorsal surfaces of the frontal lobe was significantly greater in patients with first-episode schizophrenia (FESZ) compared with healthy controls. Overall, brain surface contraction in patients and healthy controls showed similar anatomical patterns, with that of the former group exaggerated in magnitude across the entire brain surface. That the pattern of structural change in the early course of schizophrenia corresponds so closely to that associated with normal development is consistent with the hypothesis that a schizophrenia-related factor interacts with normal adolescent brain developmental processes in the pathophysiology of schizophrenia. The exaggerated progressive changes seen in patients with schizophrenia may reflect an increased rate of synaptic pruning, resulting in excessive loss of neuronal connectivity, as predicted by the late neurodevelopmental hypothesis of the illness.
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Acknowledgements
This research was supported by project grants from the Australian National Health and Medical Research Council (NHMRC; Grant IDs: 145627, 145737, 970598, 981112, 970391), NHMRC Program Grant (ID: 350241), Victorian Health Promotion Foundation, the Stanley Foundation and Ian Potter Foundation. Drs Velakoulis and Wood were supported as Research Officers with funding from the NHMRC. Dr McGorry was supported by a NARSAD Distinguished Investigator Award. Dr Wood is currently supported by a Clinical Career Development Award from the NHMRC (ID: 359223) and a NARSAD Young Investigator Award. Dr Thompson is supported by NIH Grants AG016570, LM05639, EB01651 and RR019771. Image analysis and statistical analysis were supported by NIH Grants MH65078 to Dr Cannon and RR021813 (Center for Computational Biology) to Dr Toga.
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Sun, D., Stuart, G., Jenkinson, M. et al. Brain surface contraction mapped in first-episode schizophrenia: a longitudinal magnetic resonance imaging study. Mol Psychiatry 14, 976–986 (2009). https://doi.org/10.1038/mp.2008.34
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DOI: https://doi.org/10.1038/mp.2008.34