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However, few studies have examined regional brain responses in explicit emotion regulation during acute BD mood states, or hopelessness, a major suicide risk factor. We assessed brain responses during explicit emotion regulation, and their relationship with hopelessness, in acutely symptomatic and euthymic individuals with BD.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Functional MRI data were obtained from individuals with BD who were either in acute negative (BD\u2010A; n\u00a0=\u00a024) or euthymic (BD\u2010E; n\u00a0=\u00a024) mood states, and from healthy volunteers (HV; n\u00a0=\u00a055), while participants performed a paradigm that instructed them to downregulate their responses to fearful (EmReg\u2010Fear) and happy (EmReg\u2010Happy) facial stimuli. Emotion regulation\u2010related differences in brain responses during negative and euthymic BD states, as well as their associations with negative affective symptoms (hopelessness and depression), were examined.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Decreased responses were observed in ventral and dorsal frontal regions, including medial orbitofrontal (mOFC) and dorsal anterior cingulate cortices, during EmReg\u2010Fear across symptomatic and euthymic states in participants with BD relative to HVs. The lowest responses were observed in the BD\u2010A group. Across BD participants, negative associations were observed between mOFC responses and hopelessness, particularly due to loss of motivation. Differences were not significant during EmReg\u2010Happy.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Lesser emotion regulation\u2010related ventral and dorsal frontal engagement in BD could represent a trait abnormality that worsens during acute negative states. The reduced mOFC engagement in BD during explicit regulation of negative emotions may contribute to hopelessness particularly in the context of diminished motivation.<\/jats:p><\/jats:sec>","DOI":"10.1111\/bdi.12954","type":"journal-article","created":{"date-parts":[[2020,6,10]],"date-time":"2020-06-10T21:11:01Z","timestamp":1591823461000},"page":"152-164","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":35,"title":["Altered frontal cortex functioning in emotion regulation and hopelessness in bipolar disorder"],"prefix":"10.1111","volume":"23","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7517-9776","authenticated-orcid":false,"given":"Anjali","family":"Sankar","sequence":"first","affiliation":[{"name":"Department of Psychiatry Yale School of Medicine New Haven CT USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kirstin","family":"Purves","sequence":"additional","affiliation":[{"name":"Department of Psychiatry Yale School of Medicine New Haven CT USA"},{"name":"Social, Genetic Developmental Psychiatry Centre Institute of Psychiatry King\u2019s College London London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lejla","family":"Colic","sequence":"additional","affiliation":[{"name":"Department of Psychiatry Yale School of Medicine New Haven CT USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elizabeth T.","family":"Cox Lippard","sequence":"additional","affiliation":[{"name":"Department of Psychiatry Yale School of Medicine New Haven CT USA"},{"name":"Department of Radiology and Biomedical Imaging Yale School of Medicine New Haven CT USA"},{"name":"Department of Psychiatry Dell Medical School University of Texas Austin TX USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hun","family":"Millard","sequence":"additional","affiliation":[{"name":"Department of Psychiatry Yale School of Medicine New Haven CT USA"},{"name":"Child Study Center Yale School of Medicine New Haven CT USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Siyan","family":"Fan","sequence":"additional","affiliation":[{"name":"Department of Psychiatry Yale School of Medicine New Haven CT USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Linda","family":"Spencer","sequence":"additional","affiliation":[{"name":"Department of Psychiatry Yale School of Medicine New Haven CT USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fei","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Psychiatry Yale School of Medicine New Haven CT USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brian","family":"Pittman","sequence":"additional","affiliation":[{"name":"Department of Psychiatry Yale School of Medicine New Haven CT USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R. 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