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This study investigated LCn<\/jats:italic><\/jats:styled-content>\u20103 fatty acid biostatus in youth with or at varying risk for developing mania to assess its utility as a prodromal risk biomarker.<\/jats:p><\/jats:sec>Method<\/jats:title>Erythrocyte fatty acid composition was determined in healthy adolescents (n<\/jats:italic>\u2009=\u200928, HC<\/jats:styled-content>), asymptomatic adolescents with a biological parent with bipolar I<\/jats:styled-content> disorder (n<\/jats:italic>\u2009=\u200930; \u2018high risk\u2019, HR<\/jats:styled-content>), adolescents with a biological parent with bipolar I<\/jats:styled-content> disorder and major depressive disorder, or depressive disorder not otherwise specified (n<\/jats:italic>\u2009=\u200936; \u2018ultra\u2010high risk\u2019, UHR<\/jats:styled-content>), and first\u2010episode adolescent bipolar manic patients (n<\/jats:italic>\u2009=\u200935, BP<\/jats:styled-content>).<\/jats:p><\/jats:sec>Results<\/jats:title>Group differences were observed for DHA<\/jats:styled-content> (P<\/jats:italic>\u2009\u2264\u20090.0001) and EPA<\/jats:styled-content> (P<\/jats:italic>\u2009=\u20090.03). Compared with HC<\/jats:styled-content>, erythrocyte EPA<\/jats:styled-content>\u2009+\u2009DHA<\/jats:styled-content> (\u2018omega\u20103 index\u2019) was significantly lower in BP<\/jats:styled-content> (\u221224%, P<\/jats:italic>\u2009\u2264\u20090.0001) and UHR<\/jats:styled-content> (\u221219%, P<\/jats:italic>\u2009=\u20090.0006) groups, and there was a trend in the HR<\/jats:styled-content> group (\u221211%, P<\/jats:italic>\u2009=\u20090.06). Compared with HC<\/jats:styled-content> (61%), a greater percentage of HR<\/jats:styled-content> (77%, P<\/jats:italic>\u2009=\u20090.02), UHR<\/jats:styled-content> (80%, P<\/jats:italic>\u2009=\u20090.005) and BP<\/jats:styled-content> (97%, P<\/jats:italic>\u2009=\u20090.001) subjects exhibited EPA<\/jats:styled-content>\u2009+\u2009DHA<\/jats:styled-content> levels of \u22644.0%. Among all subjects (n<\/jats:italic>\u2009=\u2009130), EPA<\/jats:styled-content>\u2009+\u2009DHA<\/jats:styled-content> was inversely correlated with manic (r<\/jats:italic>\u2009=\u2009\u22120.29, P<\/jats:italic>\u2009=\u20090.0008) and depressive (r<\/jats:italic>\u2009=\u2009\u22120.28, P<\/jats:italic>\u2009=\u20090.003) symptom severity. The AA<\/jats:styled-content>\/EPA<\/jats:styled-content>\u2009+\u2009DHA<\/jats:styled-content> ratio was significantly greater in BP<\/jats:styled-content> (+22%, P<\/jats:italic>\u2009=\u20090.0002) and UHR<\/jats:styled-content> (+16%, P<\/jats:italic>\u2009=\u20090.001) groups.<\/jats:p><\/jats:sec>Conclusions<\/jats:title>Low EPA<\/jats:styled-content>\u2009+\u2009DHA<\/jats:styled-content> levels coincide with the initial onset of mania, and increasing risk for developing bipolar disorder is associated with graded erythrocyte EPA<\/jats:styled-content>\u2009+\u2009DHA<\/jats:styled-content> deficits. Low erythrocyte EPA<\/jats:styled-content>\u2009+\u2009DHA<\/jats:styled-content> biostatus may represent a promising prodromal risk biomarker warranting additional evaluation in future prospective studies.<\/jats:p><\/jats:sec>","DOI":"10.1111\/eip.12282","type":"journal-article","created":{"date-parts":[[2015,10,22]],"date-time":"2015-10-22T02:44:04Z","timestamp":1445481844000},"page":"203-211","source":"Crossref","is-referenced-by-count":49,"title":["Adolescents with or at ultra\u2010high risk for bipolar disorder exhibit erythrocyte docosahexaenoic acid and eicosapentaenoic acid deficits: a candidate prodromal risk biomarker"],"prefix":"10.1111","volume":"10","author":[{"given":"Robert K.","family":"McNamara","sequence":"first","affiliation":[{"name":"Department of Psychiatry and Behavioral Neuroscience, Division of Bipolar Disorders Research University of Cincinnati College of Medicine Cincinnati Ohio 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