Brain Connectivity Study Of Depressive Disorder And Neuroticism Personality

Major depressive disorder(MDD),known simply as depression,is a mental disorder with the main clinical symptoms of depressed mood and cognitive impairment.With the increasing social burden and sub-optimal clinical treatment of depression,the early diagnosis and prevention to reduce the prevalence of depression has become an urgent scientific problem.It is of great significance for the early diagnosis and prevention of depression to explore the pathogenesis and identify biomarkers that can predict the development of depression.Studies have shown that impaired information processing in the brain neural network in MDD patients.The technology of brain network connectivity analysis based on magnetic resonance imaging can characterize the information transmission and communication between brain regions at different levels,which has the potential to reveal the pathogenesis of depression and guide the early diagnosis and prevention.Although preliminary progress has been made in the study of the brain connection mechanism of depression,the ability of its clinical transformation is limited.In addition,previous researches mainly focus on clinical patients,which lead to the limitation of disentangling effects that arise as a result of depression from the predictors of depression.Neuroticism and extraversion are closely related to depression.In particular,neuroticism is associated with negatively biased emotion and cognition.Neuroticism is a risk factor for depression and shares genetic basis with depression,which impacts on the aetiology of depression.Accordingly,this dissertation will employ multimodal brain network connectivity methods to explore the mechanism of key neural circuits in the developmental trajectory of depression,so as to isolate biomarkers for prevention and treatment strategies of depression.This dissertation has three aspects,including depressive disorder(content: 1-2),neuroticism and extroversion(content: 3-4),as well as the combination of neuroticism and depressive disorder(content: 5).The main research contents are shown as follows:1.Right anterior insula(AI)is responsible for integrating cognitive and emotional processes.The dynamic functional connectivity(FC)analysis was employed to investigate the abnormal dynamic functional connectivity of the dorsal and ventral AI in MDD patients.We further explored the biomarkers that can differentiate MDD from bipolar depression(BD)which has similar clinical symptoms with MDD.Results showed decreased dynamic FC between ventral AI and ventrolateral prefrontal cortex(PFC)in MDD and BD,which indicated that this change might be the state characteristic of depressive episode.In addition,MDD patients showed increased dynamic FC between the ventral AI and default mode network and executive control network,while BD patients exhibited increased dynamic FC between dorsal AI and sensory cortical regions.The specific expression of the abnormal dynamic FC of the dorsal and ventral anterior insula in MDD and BD demonstrated that the different pathological mechanisms of MDD and BD,which was helpful to distinguish these two mental disorders clinically.2.The brain connection patterns of MDD were investigated in the whole brain by combining static and dynamic FC strength(FCS)methods.Furthermore,the clinical classification and clinical symptom prediction models of MDD and BD were established.We found that MDD patients showed increased static FCS in the default mode network and dynamic FCS in the sensorimotor network.Whereas BD patients showed decreased static FCS in the medial orbital frontal cortex,increased static FCS in the caudate,and increased static and dynamic FCS in the thalamus.In addition,the combination of static and dynamic FCS contributed to improve the classification accuracy of diseases,and to predict the negative emotion in MDD and anhedonia in BD.This study indicated that the altered FC within the default mode network/sensorimotor network of MDD patients and within frontal–striatal–thalamic circuits of BD patients might serve as biomarkers for differential diagnosis and provide clues to the pathogenesis of mood disorders.3.Focusing on the prefrontal cortex(PFC),which plays a central role in the cognitive-emotional impairment of depression,the relationships between brain connectivity of the PFC and individual differences in neuroticism and extroversion in healthy subjects were investigated using FC and structural covariance connectivity based on cortical thickness.Results showed that neuroticism and extraversion had different neural network mechanisms.Neuroticism was related to the network subserving emotion regulation,which might explain the individual differences of emotional stability in neuroticism.Extraversion was related to the network subserving social cognition,which perhaps explained the social characteristic of extroversion.These findings provided new evidence for elucidating the relationship between neuroticism and extroversion and depression,and the change of PFC connectivity might be associated with the onset of depression.4.To explore the role of brain connections of the amygdala,the core of emotional processing,in the development of depression.Focusing on vulnerability factors of depression,the relationships between amygdala connections and neuroticism and extroversion were investigated in healthy subjects using effective connectivity and white matter fiber connectivity.Results showed compared to individuals with low levels of neuroticism,those with high levels of neuroticism had an increased influence from amygdala to dorsolateral PFC and a decreased influence from precuneus to amygdala.These perhaps reflected the suboptimal ability to regulate emotions and the negatively biased cognitive processing in individuals with high neuroticism.Compared to introverts,the increased influence from inferior occipital gyrus to amygdala might be helpful to explain the flexible social interaction in extroverts.The fiber connectivity of amygdala showed no significantly correlated with neuroticism and extraversion.This study suggested that the alterations in the amygdala connectivity might be an important neurobiological mechanism that increased the risk of depression.5.Based on the study findings of MDD and vulnerability factor,the resting-state FC analysis was employed to explore the change in the connectivity of the cognitive emotion regulation system composed of the PFC and limbic system in individuals at high risk for depression(i.e.,subjects with high levels of neuroticism)and MDD patients.MDD patients showed increased default mode network connectivity,and decreased medial orbifrontal cortex-hippocampus,and precuneus-temporal pole connectivity that related to emotional regulation.And these abnormal connections already happened in individuals at high risk for depression,implying the importance of these connections in the development of depression.Furthermore,the FCs between precuneus and inferior frontal gyrus and hippocampus subserving memory progress were decreased in MDD patients,whereas there was an increased tendency in the subjects at high risk for depression.This indicated that the abnormal connections might be caused by the onset of depression,meanwhile,it also might reflect a neural adaptation against the development of depression.The findings of this study went beyond previous behavioral indexes and provided an important reference basis for clinically effective screening individuals at high risk for depression,as well as the early prevention and intervention of depression.