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Past research has been limited by a reliance on cross\u2010sectional designs, which does not allow for identification of within\u2010person changes due to lithium and has not examined communication between brain regions (ie, networks). In the present study, we prospectively investigated the lithium monotherapy associated effects in vivo on the brain connectome in medication\u2010free BP patients. In particular, we examined the within\u2010person impact of lithium treatment on connectome indices previously linked to mania and depression in bipolar disorder.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Thirty\u2010nine medication\u2010free subjects \u2013 26 BP (13 (hypo)manic and 13 depressed) and 13 closely matched healthy controls (HC) \u2013 were included. fMRI data were obtained at 3 timepoints: baseline, after 2\u00a0weeks, and after 8\u00a0weeks (total of 117 scans: 78 BP and 39 HC scans). BP subjects were clinically treated with lithium for 8\u00a0weeks while HC were scanned at the same time points but not treated. Graph theory metrics and repeated measures GLM were used to analyze lithium treatment associated effects.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Consistent with hypotheses, lithium treatment was associated with a normalizing effect on mania\u2010related connectome indices. Furthermore, shifts in both mania\u2010 and depression\u2010related connectome indices were proportional to symptom change. Finally, lithium treatment\u2010associated impact on amygdala function differed depending on baseline mood.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Present findings provide deeper insight into the therapeutic neural mechanisms associated with lithium treatment.<\/jats:p><\/jats:sec>","DOI":"10.1111\/bdi.12718","type":"journal-article","created":{"date-parts":[[2018,11,13]],"date-time":"2018-11-13T05:14:15Z","timestamp":1542086055000},"page":"361-371","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":29,"title":["Lithium monotherapy associated longitudinal effects on resting state brain networks in clinical treatment of bipolar disorder"],"prefix":"10.1111","volume":"21","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8348-7157","authenticated-orcid":false,"given":"Jeffrey M","family":"Spielberg","sequence":"first","affiliation":[{"name":"Department of Psychological and Brain Sciences 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