Correlations Between Functional Dyspepsia And Anxiety/depression: A Brain Imaging Study

Functional dyspepsia(FD), one of the common types of functional gastrointestinal disorders(FGID), is characterized by the presence of recurrent symptoms including recurrent epigastric pain, burning, early satiety and upper abdominal fullness in the absence of associations with obvious organic abnormalities. Its incidence is about 11%-30% of the world population, which causes a seriously medical burden on families and society and has a large impact on human health and well-being. Moreover, with the development of the economy and society, the incidence of FD presents a rising trend year by year. An important cause of this phenomenon is the increased social stress and emotional disorder. In China, anxiety and depression take up 15%-58% of the FD patients, and are the common concomitant symptoms associated with FD. However, the physiological mechanisms underlying the relationship between FD and the negative emotion remain unclear.With the development of neuroimaging technology, the proposal of brain-gut interaction theory provides a new direction for studying the relationships between psychological states and FD. Recently, most studies based on brain imaging performed the visceral stimuli and showed the brain activation patterns in the healthy controls and FGID patients. Results found that the most consistent activated regions were located in the cingulate cortex, insula, prefrontal cortex, thalamus and somatosensory cortex during the visceral stimulation. Multiple subregions in the above regions are related to the emotion information processing. Therefore, we hypothesized that the information processing patterns in the brain provided a basis for the interaction effects between developing symptoms and negative emotion.To verity the hypothesis, we collected the brain information based on multimodal neuroimaging data in this study. Relying on the medical image processing techiniques such as segmentation, registration, feature extraction, multivariate pattern analysis and general linear model, the present study mainly explored the brain structure-function model associated with FD from four levels: brain structure alterations, whole-brain functional network reorganization, local functional abnormalities and glycometabolism states. In this model, anxeity and depression were considered as important factors, aiming to reveal the interactions between FD and negative emotion. According to Rome III criterion, FD patients are divided into two types: postprandial distress syndrome(PDS) and epigastric pain syndrome(EPS). PDS was proposed to be more closely linked to the negative emotion than EPS. Although this result has not been replicated, the current study mainly focused on the FD patients with PDS to avoid the unexplained results caused by different types of FD patients. The main research results and innovations are summarized into the following four parts:The first part evaluated whether or not anxity and depression influence the brain structure in FD patients. Based on image segmentation, registration, feature extraction and non-parametic statistical analysis of the structural magnetic resonance imaging and diffusion tensor imaging, the voxel-based morphometry and tract-based spatial statistics were carried out to investigate the relevant patterns of brain gray matter and white matter in FD patients. More importantly, we observed the influences of emotional factors on the brain gray matter and white microstructure in FD patients. Results found the abnormal brain structure may centre on the posterior insula. Moreover, the majority of structural abnormalities were closely related to anxiety and depression in FD patients. The results suggested anxiety and depression made a great contribution to abnormal structure in FD patients.The second part investigated the relathionship between negative emotion and the whole-brain functional network in FD patients. Based on the resting-state functional magnetic resonance imaging, the whole-brain functional network was constructed using the correlation analysis for blood oxygenation level dependant signal between different regions. Then multivariate pattern analysis was used to identify the whole-brain functional connectivity abnormalities. Next, we assessed the attributes of abnormal networks and relationships between these abnormalities and anxiety/depression. Results found anxiety and depression showed the nonlinear variation with the changes of connectivity abnormalities.The third part expored the abnormalities in the local brain function and studied the roles of anxiety and depression in the developing symptoms of FD. Based on the resting-state functional magnetic resonance imaging data, the image realignment, normalization and image denoising were performed. We integrated the regional homogeneity and correlation analysis to construct the dependency model of gradually developed FD accompanied by the brain functional alterations, which showed the crucial role of emotional factors in the development of the disease. Results found that the dyspeptic symptom aggravation was accompanied by the increase in the brain regional homogeneity abnormalities and the occurrence of anxiety and depression, indicating that emotional states such as anxiety and depression may keep pace with the worsened symptoms of FD via brain-gut interaction.The fourth part assessed whether or not negative emotion such as anxiety and depression was an important node that nudged FD into “symptom aggravation”. Based on the resting-state Fluorine-18-deoxyglucose PET-CT, this study focused on the glucose metabolism levels in FD patients with or without anxiety/depression and healthy controls. By using general linear model analysis, we attempted to claim the brain-based reciprocal relationship of psychological factors and FD. Results exhibited that the insula, ACC, middle cingulate cortex and middle frontal cortex were associated with both dyspeptic symptoms and anxity/depression. The four sites were the key to the interaction between psychological factors and FD. Our results indicated that negative emotion may not always arise secondarily to the development of FD. The anxiety/depression may be a predisposing factor, perpetuating factors and aggravating factor of dyspeptic symptoms.In conclusion, there may be a vicious circle: anxiety and depression may affect the gastrointestional functions and symptom perception, and the abnormal perception in the gastrointestinal tract would in turn have an impact on the central circuit that regulates mood and emotion, causing the increase of the negative emotion.