Omega-3 and omega-6 polyunsaturated fatty acids (PUFAs) are molecular modulators of neurotransmission and inflammation. Researchers hypothesized that plasma concentrations of omega-3 PUFAs would be lower and those of omega-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 omega-3 but lower omega-6 PUFA levels. Additionally, they explored clinical correlations and group differences in plasma levels of saturated and monounsaturated fatty acids. Their study was published in the journal Bipolar Disorders.

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 omega-3 PUFAs (DHA:ALA, EPA:ALA and EPA:DHA), and the ratio of omega-6:omega-3 AA:EPA.

UE EPA was lower in subjects with BD than in HCs, with a large effect size (Cohen’s d=0.86, p < 0.002); however, it was not statistically significant after correction for multiple comparisons. No statistically significant difference was seen in any plasma PUFA concentration between the BD and HC groups after Bonferroni correction for 40 comparisons, at p < 0.001. Neither depressive severity nor mania severity was correlated significantly with any PUFA concentration. Exploratory comparison showed lower UE:E EPA in the BD than the HC group (p < 0.0001). At follow-up in the BD group, UE, E DHA:ALA, and UE EPA:ALA were decreased (p < 0.002). Exploratory correlations of clinical variables revealed that mania severity and suicidality were positively correlated with UE:E EPA ratio, and that several plasma levels and ratios correlated with panic disorder and psychosis. Depressive severity was not correlated with any ratio. No plasma fatty acid level or ratio correlated with self-reported omega-3 PUFA intake or use of medication by class.

A large effect size of reduced UE EPA, and a lower plasma UE:E concentration ratio of EPA in the symptomatic BD state may be important factors in vulnerability to a mood state, according to researchers. Altered omega-3 PUFA ratios could indicate changes in PUFA metabolism concurrent with symptom improvement. The findings were consistent with preclinical and postmortem data and suggested testing interventions that increase omega-3 and decrease omega-6 dietary PUFA intake.