Low unesterified:esterified eicosapentaenoic acid (EPA) plasma concentration ratio is associated with bipolar disorder episodes, and omega-3 plasma concentrations are altered by treatment

• Published in: Bipolar disorders 2015-11, Vol.17 (7), p.729-742
• Main Authors: Saunders, Erika FH, Reider, Aubrey, Singh, Gagan, Gelenberg, Alan J, Rapoport, Stanley I
• Format: Article
• Language: English
• Subjects: Adult; Antidepressive Agents - pharmacology; Antimanic Agents - pharmacology; Arachidonic Acid - metabolism; Behavioral Symptoms - blood; Behavioral Symptoms - drug therapy; Biomarkers - blood; bipolar disorder; Bipolar Disorder - blood; Bipolar Disorder - drug therapy; Bipolar Disorder - psychology; eicosapentaenoic acid; Eicosapentaenoic Acid - metabolism; Eicosapentaenoic Acid - pharmacology; Fatty Acids, Monounsaturated - metabolism; Fatty Acids, Omega-3 - blood; Fatty Acids, Omega-6 - blood; Female; Humans; inflammation; Longitudinal Studies; Male; Middle Aged; omega-3; Severity of Illness Index; Statistics as Topic; Suicide - prevention & control; Synaptic Transmission - drug effects; Synaptic Transmission - physiology
• ISSN: 1398-5647; 1399-5618
• DOI: 10.1111/bdi.12337

Objectives Omega (n)‐3 and n‐6 polyunsaturated fatty acids (PUFAs) are molecular modulators of neurotransmission and inflammation. We hypothesized that plasma concentrations of n‐3 PUFAs would be lower and those of n‐6 PUFAs higher in subjects with bipolar disorder (BD) compared to healthy controls (HCs), and would correlate with symptom severity in subjects with BD, and that effective treatment would correlate with increased n‐3 but lower n‐6 PUFA levels. Additionally, we explored clinical correlations and group differences in plasma levels of saturated and monounsaturated fatty acids. Methods This observational, parallel group study compared biomarkers between HCs (n = 31) and symptomatic subjects with BD (n = 27) when ill and after symptomatic recovery (follow‐up). Plasma concentrations of five PUFAs [linoleic acid (LA), arachidonic acid (AA), alpha‐linolenic acid (ALA), docosahexaenoic acid (DHA), and eicosapentaenoic acid (EPA)], two saturated fatty acids (palmitic acid and stearic acid) and two monounsaturated fatty acids (palmitoleic acid and oleic acid) were measured in esterified (E) and unesterified (UE) forms. Calculated ratios included UE:E for the five PUFAs, ratios of n‐3 PUFAs (DHA:ALA, EPA:ALA and EPA:DHA), and the ratio of n‐6:n‐3 AA:EPA. Comparisons of plasma fatty acid levels and ratios between BD and HC groups were made with Student t‐tests, and between the BD group at baseline and follow‐up using paired t‐tests. Comparison of categorical variables was performed using chi‐square tests. Pearson's r was used for bivariate correlations with clinical variables, including depressive and manic symptoms, current panic attacks, and psychosis. Results UE EPA was lower in subjects with BD than in HCs, with a large effect size (Cohen's d = 0.86, p