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However, few studies have investigated the relationship between depression and social interaction anxiety using a dimensional approach. The current study aimed to explore the associations between depression and social interaction anxiety with a multivariate approach in a comparably large dataset (<jats:italic>n<\/jats:italic>\u00a0=\u00a0194, 95 males). All participants completed a structural and a resting\u2010state functional magnetic resonance imaging (fMRI) scan and self\u2010report measures of depression via Beck's Depression Inventory II and social interaction anxiety by social interaction anxiety scale. Voxel\u2010based morphometry (VBM) results first identified grey matter volumes of insula were positively correlated with depression dimension scores. Next, whole brain seed\u2010to\u2010voxel analyses were conducted using a VBM\u2010identified insula as a seed region to examine associations between depression\/social anxiety and functional connectivity. The results suggested that a significant positive effect of depression\/social anxiety was found on the connectivity between insula and dorsal lateral prefrontal cortex (dlPFC). Moreover, variations in depression meditated the association between insula\u2010dlPFC connectivity and social interaction anxiety. Overall, the results indicate that individual differences in depression relate more to insula\u2010dlPFC coupling compared to social interaction anxiety.<\/jats:p>","DOI":"10.1002\/hbm.25952","type":"journal-article","created":{"date-parts":[[2022,5,21]],"date-time":"2022-05-21T08:19:39Z","timestamp":1653121179000},"page":"4266-4273","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":23,"title":["Depression mediates the association between insula\u2010frontal functional connectivity and social interaction anxiety"],"prefix":"10.1002","volume":"43","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1780-4606","authenticated-orcid":false,"given":"Weihua","family":"Zhao","sequence":"first","affiliation":[{"name":"The Clinical Hospital of Chengdu Brain Science Institute MOE Key Laboratory for NeuroInformation of Ministry of Education, Center for Information in Medicine, University of Electronic Science and Technology of China  Chengdu China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiaolu","family":"Zhang","sequence":"additional","affiliation":[{"name":"The Clinical Hospital of Chengdu Brain Science Institute MOE Key Laboratory for NeuroInformation of Ministry of Education, Center for Information in Medicine, University of Electronic Science and Technology of China  Chengdu China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5032-9141","authenticated-orcid":false,"given":"Xinqi","family":"Zhou","sequence":"additional","affiliation":[{"name":"Institute of Brain and Psychological Sciences Sichuan Normal University  Chengdu China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xinwei","family":"Song","sequence":"additional","affiliation":[{"name":"The Clinical Hospital of Chengdu Brain Science Institute MOE Key Laboratory for NeuroInformation of Ministry of Education, Center for Information in Medicine, University of Electronic Science and Technology of China  Chengdu China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhao","family":"Zhang","sequence":"additional","affiliation":[{"name":"The Clinical Hospital of Chengdu Brain Science Institute MOE Key Laboratory for NeuroInformation of Ministry of Education, Center for Information in Medicine, University of Electronic Science and Technology of China  Chengdu China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lei","family":"Xu","sequence":"additional","affiliation":[{"name":"Institute of Brain and Psychological Sciences Sichuan Normal University  Chengdu China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4509-4026","authenticated-orcid":false,"given":"Feng","family":"Zhou","sequence":"additional","affiliation":[{"name":"Faculty of Psychology Southwest University  Chongqing China"},{"name":"Key Laboratory of Cognition and Personality Ministry of Education  China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0371-5904","authenticated-orcid":false,"given":"Keith M.","family":"Kendrick","sequence":"additional","affiliation":[{"name":"The Clinical Hospital of Chengdu Brain Science Institute MOE Key Laboratory for NeuroInformation of Ministry of Education, Center for Information in Medicine, University of Electronic Science and Technology of China  Chengdu China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2022,5,21]]},"reference":[{"issue":"983","key":"e_1_2_9_2_1","article-title":"Proportion mediated in a causal mediation analysis: How useful is this measure?","volume":"126","author":"Ananth C. 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