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Fluoxetine is the antidepressant with the most favourable benefit:risk ratio profile to treat adolescent depression, but the neural mechanisms underlying antidepressant drugs in the young brain are still poorly understood. Previous studies have characterised the neural effects of long-term fluoxetine treatment in depressed adolescents, but these are limited by concurrent mood changes and a lack of placebo control. There is also recent evidence suggesting that fluoxetine reduces the processing of anger in young healthy volunteers, which is consistent with its effect for the treatment of irritability in this age group, but this remains to be investigated in depressed adolescents. Here we assessed the effects of a single, first dose of 10\u2009mg fluoxetine vs. placebo on neural response to anger cues using fMRI in a sample of adolescents with Major Depressive Disorder (MDD) who had been recently prescribed fluoxetine. As predicted, adolescents receiving fluoxetine showed reduced activity in response to angry facial expressions in the amygdala-hippocampal region relative to placebo. Activity in the dorsal anterior cingulate cortex (dACC) was also increased. No changes in symptoms were observed. These results demonstrate, for the first time in depressed adolescents, that fluoxetine has immediate neural effects on core components of the cortico-limbic circuitry prior to clinical changes in mood. The effect on anger is consistent with our previous work and could represent a key mechanism through which fluoxetine may act to alleviate irritability symptoms in adolescent depression.<\/jats:p>","DOI":"10.1038\/s41398-018-0332-2","type":"journal-article","created":{"date-parts":[[2019,1,21]],"date-time":"2019-01-21T16:02:44Z","timestamp":1548086564000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":20,"title":["A single dose of fluoxetine reduces neural limbic responses to anger in depressed adolescents"],"prefix":"10.1038","volume":"9","author":[{"given":"Liliana P.","family":"Capit\u00e3o","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert","family":"Chapman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8995-2099","authenticated-orcid":false,"given":"Susannah E.","family":"Murphy","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher-James","family":"Harvey","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anthony","family":"James","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Philip J.","family":"Cowen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Catherine J.","family":"Harmer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2019,1,21]]},"reference":[{"key":"332_CR1","doi-asserted-by":"publisher","first-page":"8","DOI":"10.1097\/00004583-199301000-00003","volume":"32","author":"M Kovacs","year":"1993","unstructured":"Kovacs, M., Goldston, D. & Gatsonis, C. 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Specifically, L.C. served as a consultant to P1vital, a contract research organization that runs industry-sponsored experimental medicine studies in academic departments. S.M. has also served as a consultant to P1vital and has participated in paid speaking engagements for Eli Lilly and Co. C.H. receives consultancy fees from and has shares in P1vital. She has also received consultancy fees from Lundbeck, Johnson and Johnson (J&J) and Servier, and has received grant income from J&J and UCB. The other authors dec;are that they have no conflict of interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}}],"article-number":"30"}}