Adolescents with or at ultra‐high risk for bipolar disorder exhibit erythrocyte docosahexaenoic acid and eicosapentaenoic acid deficits: a candidate prodromal risk biomarker

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Abstract

Abstract Aim Mood disorders are associated with low levels of the long‐chain omega‐3 ( LC n ‐3) fatty acids eicosapentaenoic acid ( EPA ) and docosahexaenoic acid ( DHA ). This study investigated LC n ‐3 fatty acid biostatus in youth with or at varying risk for developing mania to assess its utility as a prodromal risk biomarker. Method Erythrocyte fatty acid composition was determined in healthy adolescents ( n = 28, HC ), asymptomatic adolescents with a biological parent with bipolar I disorder ( n = 30; ‘high risk’, HR ), adolescents with a biological parent with bipolar I disorder and major depressive disorder, or depressive disorder not otherwise specified ( n = 36; ‘ultra‐high risk’, UHR ), and first‐episode adolescent bipolar manic patients ( n = 35, BP ). Results Group differences were observed for DHA ( P ≤ 0.0001) and EPA ( P = 0.03). Compared with HC , erythrocyte EPA + DHA (‘omega‐3 index’) was significantly lower in BP (−24%, P ≤ 0.0001) and UHR (−19%, P = 0.0006) groups, and there was a trend in the HR group (−11%, P = 0.06). Compared with HC (61%), a greater percentage of HR (77%, P = 0.02), UHR (80%, P = 0.005) and BP (97%, P = 0.001) subjects exhibited EPA + DHA levels of ≤4.0%. Among all subjects ( n = 130), EPA + DHA was inversely correlated with manic ( r = −0.29, P = 0.0008) and depressive ( r = −0.28, P = 0.003) symptom severity. The AA / EPA + DHA ratio was significantly greater in BP (+22%, P = 0.0002) and UHR (+16%, P = 0.001) groups. Conclusions Low EPA + DHA levels coincide with the initial onset of mania, and increasing risk for developing bipolar disorder is associated with graded erythrocyte EPA + DHA deficits. Low erythrocyte EPA + DHA biostatus may represent a promising prodromal risk biomarker warranting additional evaluation in future prospective studies.

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