精神分裂症是一种严重的慢性疾病，妄想作为典型的精神分裂症症状之一受到了许多研究者的关注。由于妄想的复杂性，有关妄想的成因和神经生物学机制并未得到一致的解释。多方面研究表明，妄想涉及多个认知功能缺损，神经环路异常，以及广泛的脑结构和功能损伤。以往有关精神分裂症妄想的研究多将精神分裂症患者在量表上的妄想得分与异常脑区数值(如灰质体积/脑区激活)做相关，而较少关注精神分裂症伴有妄想患者和不伴有妄想患者脑结构的差异。同时，探索妄想相关的白质微结构和功能连接的研究也相对较少。另一方面，从谱系角度出发，较少有研究关注亚临床高妄想倾向群体的白质微结构和功能连接。因此，本论文主要对伴有妄想症状的临床患者和高妄想倾向的亚临床群体脑结构(灰质体积和白质微结构)以及功能连接进行探讨。
本论文包括两个研究：研究一，探讨首发精神分裂症伴有妄想和不伴有妄想患者，以及健康对照组在脑结构和功能连接上的差异；研究二，探讨亚临床高/低妄想倾向群体的脑结构和功能连接差异。
研究一共招募45名精神分裂症患者(16名伴有妄想患者，29名不伴有妄想患者)，以及25名健康对照被试参与研究并完成脑结构和静息态磁共振扫描。结果表明：在脑结构方面，伴有妄想患者右侧枕叶和左侧脑岛的灰质体积显著低于健康对照组；左侧颞上回和中央后回的灰质体积显著高于不伴有妄想患者，而右侧额叶灰质体积则显著低于不伴有妄想患者；在白质微结构上，三组被试差异不显著；在静息态功能连接方面，2名伴有妄想患者因头动较大未纳入分析。在默认网络上，相比于健康对照组，伴有妄想患者表现出显著的功能连接降低，分别是右侧海马和左侧颞上回的功能连接，左侧额中回和左侧中央前回的功能连接；相比于不伴有妄想患者，伴有妄想患者在右侧海马和左侧额上回的功能连接显著增高，但在左侧颞中回和右侧顶下小叶的功能连接显著降低。在突显网络中，相比于健康对照组和不伴有妄想患者，伴有妄想患者与左侧额中回相关的功能连接均显著增高。
研究二共招募25名高妄想倾向个体和25名低妄想倾向个体参与研究并完成脑结构和静息态磁共振扫描。结果表明：在脑结构方面，高妄想倾向群体右侧枕叶和右侧额中回的灰质体积存在降低趋势；此外，高妄想倾向群体左侧颞叶下纵束各向异性(FA)值出现降低趋势；在静息态功能连接方面，剔除3名头动过大被试，24名高妄想倾向个体和23名低妄想倾向个体被纳入分析。结果表明，两组人群在默认网络和突显网络上均存在显著差异。在默认网络中，高妄想倾向群体既存在功能连接异常增高 (如，扣带回中部和左侧颞横回、右侧屏状体的功能连接等)；也存在功能连接异常降低(如，额内回和左侧楔前叶的功能连接；右侧额上回和右侧额中回的功能连接等)。在突显网络中，高妄想倾向群体同样存在功能连接异常增高(如，左侧脑岛与左侧前扣带回的功能连接等)和功能连接异常降低(如，辅助运动区和左侧中央前回的功能连接；左侧小脑与左侧额上回的功能连接等)。该结果表明高妄想倾向群体在脑功能连接上存在显著改变。
总体来看，本研究结果表明，精神分裂症伴有妄想患者和亚临床高妄想倾向群体在一定程度上均存在脑结构和脑功能连接异常。其中，两类群体在灰质体积上存在相似的异常(临床伴有妄想患者枕叶灰质体积显著降低；亚临床高妄想倾向群体枕叶体积轻微降低)。但功能连接结果并不一致，相比于健康被试，伴有妄想患者主要表现为默认网络的功能连接降低，突显网络的功能连接增高；亚临床高妄想倾向群体在两个网络上既存在功能连接增高，也存在降低。该结果提示，灰质体积的异常可能可以作为妄想的生物学标记。本研究通过对妄想的针对性探讨，加深了对其神经病理学机制的理解。

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.