{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T17:47:01Z","timestamp":1792086421391,"version":"4.4.0"},"reference-count":61,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"1","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Circ: Cardiovascular Imaging"],"published-print":{"date-parts":[[2026,1]]},"abstract":"<jats:sec>\n                    <jats:title>BACKGROUND:<\/jats:title>\n                    <jats:p>Depression is linked to major adverse cardiac events (MACE), yet the role of stress-related neural activity\u2013previously implicated in stress and anxiety in mediating this association remains unclear. Because anxiety and depression frequently co-occur and share neurobiological pathways, we hypothesized that the relationship between depression, anxiety, and their co-occurrence with MACE is partially mediated by increased stress-related neural activity and related autonomic-immune mechanisms.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>METHODS:<\/jats:title>\n                    <jats:p>\n                      Data were obtained from participants enrolled in the Mass General Brigham Biobank (2010\u20132020). A subset underwent\n                      <jats:sup>18<\/jats:sup>\n                      F-fluorodeoxyglucose positron emission tomography\/computed tomography imaging to assess stress-related neural activity, defined as the ratio of amygdala to background prefrontal cortical activity. Heart rate variability and CRP (C-reactive protein) served as indicators of autonomic activity and systemic inflammation. Depression and anxiety were determined at enrollment, and MACE was identified during follow-up using International Classification of Diseases codes. Each exposure (depression, anxiety, or concurrent anxiety plus depression) was modeled separately against study outcomes using linear and Cox regressions.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS:<\/jats:title>\n                    <jats:p>\n                      Of 85\u2009551 study subjects, 3078 (3.6%) participants developed MACE, over a median 3.4 years follow-up (interquartile range, 1.9\u20134.8). Depression was associated with higher MACE risk (hazard ratio, 1.24 [95% CI, 1.14\u20131.34];\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      &lt;0.001), with stronger associations for concurrent anxiety plus depression (hazard ratio, 1.35 [1.23\u20131.49];\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      &lt;0.001) and remained significant after adjustment for demographics, lifestyle, cardiovascular, and socioeconomic factors. In subsamples with available imaging (N=1123) or biomarkers (heart rate variability, N=7862; CRP, N=12\u2009906), depression was linked to higher amygdala-to-cortex activity ratio (\u03b2=0.16;\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      =0.006), lower heart rate variability (\u03b2=\u22120.20;\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      &lt;0.001), and higher CRP (\u03b2=0.14;\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      &lt;0.001). Mediation analyses showed indirect effects of amygdala-to-cortex activity ratio, heart rate variability, and CRP on the depression\u2013MACE relationship (log odds ratios, 0.04, 0.04, and 0.02, respectively; all\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      &lt;0.05). Similar associations were observed for anxiety or concurrent anxiety plus depression.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>CONCLUSIONS:<\/jats:title>\n                    <jats:p>Depression and anxiety independently associate with increased MACE risk, partly mediated by heightened stress-related neural activity and autonomic-immune dysregulation. The risk is greatest among those with both conditions, underscoring shared stress-related pathophysiology.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1161\/circimaging.124.017706","type":"journal-article","created":{"date-parts":[[2025,12,17]],"date-time":"2025-12-17T10:00:11Z","timestamp":1765965611000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":13,"title":["Depression and Anxiety Associate With Adverse Cardiovascular Events via Neural, Autonomic, and Inflammatory Pathways"],"prefix":"10.1161","volume":"19","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5033-8881","authenticated-orcid":true,"given":"Shady","family":"Abohashem","sequence":"first","affiliation":[{"name":"Cardiology Division (S.A., I.Q., S.S.G., M.T.O., A.T.), Massachusetts General Hospital and Harvard Medical School, Boston."},{"name":"Cardiovascular Imaging Research Center (S.A., I.Q., S.S.G., G.C., S.I., W.A., A.V.S., M.T.O., A.T.), Massachusetts General Hospital and Harvard Medical School, Boston."},{"name":"Cardiovascular Research Center, Massachusetts General Hospital, Boston (S.A., S.B., A.A.A., A.T.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Iqra","family":"Qamar","sequence":"additional","affiliation":[{"name":"Cardiology Division (S.A., I.Q., S.S.G., M.T.O., A.T.), Massachusetts General Hospital and Harvard Medical School, Boston."},{"name":"Cardiovascular Imaging Research Center (S.A., I.Q., S.S.G., G.C., S.I., W.A., A.V.S., M.T.O., A.T.), Massachusetts General Hospital and Harvard Medical School, Boston."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0675-1951","authenticated-orcid":true,"given":"Simran S.","family":"Grewal","sequence":"additional","affiliation":[{"name":"Cardiology Division (S.A., I.Q., S.S.G., M.T.O., A.T.), Massachusetts General Hospital and Harvard Medical School, Boston."},{"name":"Cardiovascular Imaging Research 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Research Center (S.A., I.Q., S.S.G., G.C., S.I., W.A., A.V.S., M.T.O., A.T.), Massachusetts General Hospital and Harvard Medical School, Boston."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sandeep","family":"Bollepalli","sequence":"additional","affiliation":[{"name":"Cardiovascular Research Center, Massachusetts General Hospital, Boston (S.A., S.B., A.A.A., A.T.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2392-7365","authenticated-orcid":true,"given":"Rachel P.","family":"Rosovsky","sequence":"additional","affiliation":[{"name":"Department of Medicine (R.P.R.), Massachusetts General Hospital and Harvard Medical School, Boston."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonia V.","family":"Seligowski","sequence":"additional","affiliation":[{"name":"Cardiovascular Imaging Research Center (S.A., I.Q., S.S.G., G.C., S.I., W.A., A.V.S., M.T.O., A.T.), Massachusetts General Hospital and Harvard 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