Abstract: Background: Several studies have found widespread structural changes affecting the grey matter at various stages of schizophrenia (the prodrome, first-episode, and the chronic stage). It is unclear which of these neuroanatomical changes are associated with a predisposition or vulnerability to develop schizophrenia rather than the appearance of the clinical features of the illness.Methods: 16 voxel-based morphometry (VBM) analyses involving 733 genetically high-risk relatives (HRR) of patients with schizophrenia, 563 healthy controls and 474 patients were meta-analysed using the Signed Differential Mapping (SDM) technique. Two meta-analyses were conducted, with one comparing HRR group with healthy controls and the other comparing HRR group with the patients.Results: A significant grey matter reduction in the lentiform nucleus, amygdala/parahippocampal gyrus and medial prefrontal cortex was seen in association with the genetic diathesis. Grey matter reduction in bilateral insula, inferior frontal gyrus, superior temporal gyrus and the anterior cingulate was seen in association with the disease expression.Conclusions: The neuroanatomical changes associated with the genetic diathesis to develop schizophrenia appear to be different from those that contribute to the clinical expression of the illness. Grey matter abnormalities in multimodal brain regions that have a supervisory function are likely to be central to the expression of the clinical symptoms of schizophrenia.
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