Risk Characteristics And Interaction Patterns For Late-onset Depression Based On Brain Neuroimaging And Genetics

Late-onset depression(LOD)is one of the most common psychiatric disorders and an important health problem in older adults.It is characterized by high recurrence,disability and suicide.The etiology of LOD is complex.However,the pathogenesis of the LOD is not clear.Thus,elucidating the pathogenesis is important to the LOD in the brain science field.Neuroimaging studies found that the LOD associated with different depressive symtoms might attribute to disturbing the dynamics and functions of different bran networks.The polymorphism of gene leads to the alteration of the brain function.The combination of the brain neuroimaging and gene would be benefit to the analyze the pathogenesis of the LOD,achieve the early identification,diagnosis and intervention of the LOD,and improve the effectiveness of the treatment.It would make a significant sense to clinical treatment and research.In order to reveal the pathgenesis of the LOD based on the brain neuroimaging data and gene data,the study investigated the risk characteristics and interaction patterns of the LOD from the aspect of brain network functional connectivity,neurofibromatosis,and the interaction between the gene,brain functional connectivity and cognitive function.Brain neuroimaging studies found that the LOD is associated with the abnormal of the brain function,however,little is known about the altered patterns of the brain networks and its interaction with the cognition.This study focused on investigating the connectivity patterns of intra-network and inter-network of the congnitive control network(CON),dorsal attention network(DAN),and sensory-motor network(SMN)based on the brain neuroimaging data from three levels,i.e.integrity level,network level and edge level.(1)For the integrity and edge level,we found the functional connecitivties of left middle temporal,dorsomedial prefrontal cortex and right primary auditory were decreased and most of the abnormal functional connectivties occurred in the DAN and SMN.The results showed that the occurrence of the LOD is related to the impairment of the cognition,emotion and sensory functions.It is suggested that the progression of the LOD might be caused by the increase of abnormal function connectivities between the seeds,distrupt the intra-network,and lead to the abnormality of inter-network.(2)For the network level,LOD showed significantly reduced connectivity strength within DAN,CON,and SMN,and reduced connectivity strength in the DAN-CON pair and DAN-SMN pair.The results suggested that the LOD utilizes an altered model of cognitive control where the altered DAN may mediate the transition stage of the information processing from bottom-up information about sensory-motor inputs to high-level cognition.Default-mode network(DMN)is a key network-based biological marker for the disease mechanism of the LOD.The anterior DMN(aDMN)and posterior DMN(pDMN)showed a dissociation pattern in the depression.Therefore,we speculated that it is sentitive for revealing the pathophysiologic progression of LOD based on DMN sub-networks.Whether the features of the DMN sub-networks could be used to predict the LOD needs further study.Thus,the purpose of the study was to investigate changes in functional connevtivity in the aDMN and pDMN so as to explore potential risk factors for the LOD.The study found:(1)Functional connectivity between the ventromedial prefrontal cortex(vmPFC)and right middle temporal gyrus(MTG),between the vmPFC and left precuneus(PCu_L),and between the PCC and left PCu were the risk factors for the LOD.(2)The functional connectivity of vmPFC-MTG_R and PCC-PCu_L positively correlates to processing speed and semantic memory,and the functional connectivity of the vmPFC-PCu_L negatively correlates to processing speed and semantic memory.In this study,the results showed that LOD patients mainly present cognitive deficits in processing speed and semantic memory.Moreover,the study suggested that FC within DMN sub-networks associated with cognitions were risk factors,which may be used for the prediction of LOD.The interaction of the gene and the brain function leads to the LOD.However,it is unclear to explain the physiological mechanism of the LOD with the cognitive impairment.The aim of the study is to explore the interaction between the gene,brain function,cognitiove function and the depression degree in the LOD patients.(1)The study found the Angiotension-converting enzyme(ACE),catechol-O-methyl transferase(COMT),Tryptophan hydroxylase(TPH2 rs 7305115),and apolipoprotein E(APOE)were the risk factors of the LOD.There were significant main interactive effect of risk genes and diagnosis on the DMN sub-networks functional connectivies,processing speed and semantic memory.(2)The study constructed an interaction model with gene,brain function and cognitiove function,and found that:(a)For the direct effect,the polymorphisms of the genes caused the decrease of the brain functional connectivity and the degree of the LOD have an impact on the processing speed and semantic memory.(b)For the indirect effect,the abnormal brain functional connectivity played a mediate effect between the gene and cognitive function,and between the gene and degree of the LOD.(c)For the total effect,the polymorphisms of the genes showed significant effect on the bran dysfunction,cognitive impairment and depression degree.Meanwhile,the depressive degree showed significant effect on the cognitive impairment.The degree of the LOD is a risk factor for the cognitive function(processing speed and semantic memory).The results showed that the genes through the brain dysfunction and cognitive impairment lead to the LOD.The interactive pattern suggested that the brain function plays a mediate role in the physiological mechanism of the LOD,and is the protective factor for the cognitive impairment.