Convergent Findings Of Functional And Structural Alterations Within The Frontal-limbic System In Adolescents With Social Anxiety Disorder:A Multimodal MRI Study

OBJECTIVE:To investigate the differences in the brain mechanism of frontal-limbic system and brain structural in social anxiety disorder(SAD)and healthy controls at different age period.So that we can explore different trend of pathological social anxiety and normal development.METHODS:A total of 38 social anxiety patients and 40 healthy controls were included in the study.The two groups were divided into two age groups,10-14 years old for the younger group and 15-17 years old for the older group.Age and gender were matched in each age group.We use emotional face matching tasks to trigger the subjects’ processing of negative emotional stimuli,including matching emotional(angry and fearful)faces and matching graphics.Symptom severity was measured through a series of scales.By adopting multi-modal brain imaging technique,we analyze brain function from three aspects including activation patterns,functional connections,and network attributes,while analyzing brain structure from three aspects including gray matter volume,cortical thickness and structural covariation network.A two-factor analysis of variance between group and age was used to investigate the differences in brain function and structure between social anxiety patients and healthy controls at different age period.RESULTS:(1)The social anxiety level of all subjects increased with age.The older SAD patients showed significantly higher overall anxiety than the control group,showing the characteristics of anxiety generalization and somatization.(2)In terms of gray matter volume,compared with the control group,gray matter volume in the left central anterior and left frontal gyrus of the SAD patients increased significantly,but the significance did not remain after multiple comparison correction.(3)In terms of cortical thickness,there was no significant difference between SAD patients and control group,nor interaction with age.(4)In terms of structural covariation network,subject loadings of SAD patients in a frontopariental network were significantly higher than control group.(5)In terms of activation mode,there were interactions between different groups and age in dorsolateral prefrontal cortex,precentral cortex,parahippocampus,insula and anterior cingulate cortex.Older SAD patients showed hyperactivation in these areas when processing angry and fearful faces.In SAD patients,activation in these areas increased with age.(6)In terms of psychophysiological interactions,the functional connectivity between amygdala and hippocampus when processing angry and fearful faces in control group decreased with age while SAD patients did not show such trend;the functional connectivity between amygdala and orbital frontal cortex when processing angry and fearful faces in control group increased with age while SAD patients did not show such trend.(7)In terms of the network attribute,the degree of centrality and node Efficiency of posterior cingulate gyrus and global efficiency of frontal-limbic system were reduced in older SAD patients.Symptom severity was positively associated with abnormal frontal-limbic functional results.CONCLUSION:In adolescents with SAD,brain function in frontal-limbic system exhibits complex interaction with different age period,which is correlated with symptom severity.In addition,gray matter in frontoparietal network shows stronger covariation in patients.This study provides new evidence for brain mechanism in social anxiety disorder.The specific role of functional and structural alterations within the frontal-limbic system in the pathological mechanisms of SAD remains to be further investigated.