Delusions are key clinical symptoms of schizophrenia and have attracted much attention from researchers. However, researchers have not come up with an agreed explanation of delusion formation and their neurobiological mechanisms. Numerous studies have shown that delusions involve multiple cognitive impairments, neurological abnormalities, and extensive brain structural and functional impairments. Most previous structural and functional imaging studies on delusions have focused on the brain regions, and correlated severity of delusions with values (grey matter volumes or brain activations) of brain regions. However, specific brain changes such as grey matter volume, microstructure of white matter and functional connectivity of patients with and without delusions have seldom been investigated. In addition, few studies have investigated the underlying neural mechanism of subclinical form of delusions using a spectrum approach. The present dissertation aimed to investigate the brain structure (grey matter volume and microstructure of white matter) and functional connectivity of patients with delusions and individuals with sub-clinical delusional thinking.
his dissertation consists of two studies: (a) Study 1 compared the difference in brain structure and functional connectivity between patients with first-episode schizophrenia with and without delusions and healthy controls; (b) Study 2 explored the differences in brain structure and functional connectivity between two groups of individuals with high and low delusion-proneness.
In Study 1, a total of 16 first episode schizophrenia patients with delusions, 29 first episode schizophrenia patients without delusion and 25 healthy controls underwent fMRI scan. Two first episode schizophrenia patients with delusions were excluded due to excessive head motion. The results showed that grey matter volume of the right occipital lobe and the left insular of delusional patients was significantly smaller than healthy controls, while grey matter volume of their left superior temporal gyrus and their central posterior gyrus was significantly larger than patients without delusions. Their right frontal lobe was significantly smaller than patients without delusions. However, there was no difference in white matter microstructure between the three groups of participants. For functional connectivity in the Default Mode Network (DMN), compared with healthy controls, first episode schizophrenia patients with delusions had significantly reduced functional connectivity between the right hippocampus and the left superior temporal gyrus, and between the left middle temporal gyrus and the left precentral gyrus. Compared with patients without delusions, patients with delusions had significantly increased functional connectivity between the right hippocampus and the left superior frontal gyrus, and significantly reduced functional connectivity between the left temporal lobe and the right inferior parietal lobule. Moreover, in the Salience Network (SaN), compared with healthy controls and patients without delusion, the functional connectivities associated with the left middle frontal gyrus were significantly increased in patients with delusions.
In Study 2, a total of 25 individuals with high-delusion proneness and 25 individuals with low-delusion proneness were recruited. One participant with high-delusion proneness and two with low-delusion proneness were excluded for excessive head motion. There was a decreasing trend in the grey matter volume of the right occipital lobe and the right middle frontal gyrus in high-delusion proneness individuals. In addition, individuals with high-delusion proneness showed a reduction trend in the left inferior longitudinal fasciculus. For functional connectivity analysis in the DMN, the high-delusion proneness group showed significantly increased functional connectivity in various connection than the low-delusion proness group, including the connectivity between the the right middle cingulate gyrus and the left transverse temporal, and betweent the right middle cingulate gyrus and the right claustrum than indiviudals with low-delusion proneness. The high-delusion proneness group also exhibited significantly decreased various connections than the low-delusion proneness group, including the connectivity between the left medial frontal and the left precuneus, and between the right superior frontal gyrus and left middle temporal gyrus. For functional connectivity analysis in the SaN, the high-delusion proneness showed hyper-connectivity than the low-delusion proneness group in the connectivity between the left insular and the left anterior cingulate gyrus. On the other hand, they also showed reduced connectivity than the low-delusion proneness group in the connectivity between the supplementary motor area and the left precentral gyrus, and betweent the left cerebellum and left superior frontal gyrus.
Taken together, our results showed that there were brain structural abnormalities and functional connectivity changes in first-episode schizophrenia patients with delusion and individuals with high-delusion proneness. Similar abnormalities in occipital grey matter volume reduction in patients with and without delusions and subclinical delusional group were observed. However, results from functional connectivity analysis were inconsistent. First-episode schizophrenia patients with delusions showed decreased functional connectivities in the DMN and increased functional connectivity in the SaN. On the other hand, individuals with high-delusion proneness showed altered functional connectivities (increased and reduced) in both the DMN and the SaN.