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Conversely, anti-Tumor Necrosis Factor (TNF) therapies improve depression providing key empirical support for the \u201cinflammatory theory\u201d of depression. Heightened amygdala reactivity (particularly to negatively valanced stimuli) is a consistent finding within MDD; can predict treatment efficacy and reverses following successful treatment. However, whether IFN-\u03b1 and anti-TNF enhance\/attenuate depressive symptoms through modulation of amygdala emotional reactivity is unknown. Utilizing a prospective study design, we recruited 30 patients (mean 48.0\u2009\u00b1\u200910.5 years, 21 male) initiating IFN-\u03b1 treatment for Hepatitis-C and 30 (mean 50.4\u2009\u00b1\u200915.7 years, 10 male) anti-TNF therapy for inflammatory arthritis. All completed an emotional face-processing task during fMRI and blood sampling before and after their first IFN-\u03b1 (4-h) or anti-TNF (24-h) injection and follow-up psychiatric assessments for 3 months of treatment. IFN-\u03b1 significantly increased depression symptoms (Hamilton Depression Rating Scale HAM-D) at 4 weeks (\n                    <jats:italic>p<\/jats:italic>\n                    \u2009&lt;\u20090.001) but not 4-h after first dose (\n                    <jats:italic>p<\/jats:italic>\n                    \u2009&gt;\u20090.1). Conversely, anti-TNF significantly improved depressive symptoms (Hospital Anxiety and Depression Rating Scale HADS) at both 24-h (\n                    <jats:italic>P<\/jats:italic>\n                    \u2009=\u20090.015) and 12 weeks (\n                    <jats:italic>p<\/jats:italic>\n                    \u2009=\u20090.018). In support of our a-priori hypothesis, both IFN-\u03b1 and anti-TNF significantly modulated amygdala reactivity with IFN-\u03b1 acutely\n                    <jats:italic>enhancing<\/jats:italic>\n                    right amygdala responses to sad (compared with neutral) faces (\n                    <jats:italic>p<\/jats:italic>\n                    \u2009=\u20090.032) and anti-TNF conversely\n                    <jats:italic>decreasing<\/jats:italic>\n                    right amygdala reactivity (across emotional valence) (\n                    <jats:italic>p<\/jats:italic>\n                    \u2009=\u20090.033). Furthermore, these changes predicted IFN-induced increases in HAM-D 4 weeks later (\n                    <jats:italic>R<\/jats:italic>\n                    <jats:sup>2<\/jats:sup>\n                    \u2009=\u20090.17,\n                    <jats:italic>p<\/jats:italic>\n                    \u2009=\u20090.022) and anti-TNF-associated decreases in HADS at 24-h (\n                    <jats:italic>R<\/jats:italic>\n                    <jats:sup>2<\/jats:sup>\n                    \u2009=\u20090.23,\n                    <jats:italic>p<\/jats:italic>\n                    \u2009=\u20090.01) suggesting that actions of systemic inflammation on amygdala emotional reactivity play a mechanistic role in inflammation-associated depressive symptoms.\n                  <\/jats:p>","DOI":"10.1038\/s41380-020-0790-9","type":"journal-article","created":{"date-parts":[[2020,5,26]],"date-time":"2020-05-26T11:03:57Z","timestamp":1590491037000},"page":"5150-5160","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":56,"title":["Interferon and anti-TNF therapies differentially modulate amygdala reactivity which predicts associated bidirectional changes in depressive symptoms"],"prefix":"10.1038","volume":"26","author":[{"given":"Kevin A.","family":"Davies","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ella","family":"Cooper","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Valerie","family":"Voon","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeremy","family":"Tibble","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4550-2456","authenticated-orcid":false,"given":"Mara","family":"Cercignani","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Neil A.","family":"Harrison","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2020,5,26]]},"reference":[{"key":"790_CR1","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1038\/nri.2015.5","volume":"16","author":"AH Miller","year":"2016","unstructured":"Miller AH, Raison CL. 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