Dietary intake and plasma metabolomic analysis of polyunsaturated fatty acids in bipolar subjects reveal dysregulation of linoleic acid metabolism

Abstract

Polyunsaturated fatty acids (PUFA) profiles associate with risk for mood disorders. This poses the hypothesis of metabolic differences between patients and unaffected healthy controls that relate to the primary illness or are secondary to medication use or dietary intake. However, dietary manipulation or supplementation studies show equivocal results improving mental health outcomes. This study investigates dietary patterns and metabolic profiles relevant to PUFA metabolism, in bipolar I individuals compared to non-psychiatric controls. We collected seven-day diet records and performed metabolomic analysis of fasted plasma collected immediately after diet recording. Regression analyses adjusted for age, gender and energy intake found that bipolar individuals had significantly lower intake of selenium and PUFAs, including eicosapentaenoic acid (EPA) (n-3), docosahexaenoic acid (DHA) (n-3), arachidonic acid (AA) (n-6) and docosapentaenoic acid (DPA) (n-3/n-6 mix); and significantly increased intake of the saturated fats, eicosanoic and docosanoic acid. Regression analysis of metabolomic data derived from plasma samples, correcting for age, gender, BMI, psychiatric medication use and dietary PUFA intake, revealed that bipolar individuals had reduced 13S-HpODE, a major peroxidation product of the n-6, linoleic acid (LA), reduced eicosadienoic acid (EDA), an elongation product of LA; reduced prostaglandins G2, F2 alpha and E1, synthesized from n-6 PUFA; and reduced EPA. These observations remained significant or near significant after Bonferroni correction and are consistent with metabolic variances between bipolar and control individuals with regard to PUFA metabolism. These findings suggest that specific dietary interventions aimed towards correcting these metabolic disparities may impact health outcomes for individuals with bipolar disorder.

Plasma linoleic acid partially mediates the association of bipolar disorder on self-reported mental health scales

“…We found significantly reduced dietary intake of EPA, DHA and AA in bipolar individuals. Furthermore, we found reduced levels of EPA and LA, as well as several LA metabolites in plasma from bipolar individuals after correcting for age, gender, dietary intake, BMI, and psychiatric medication use; suggesting potential dysregulation of LA metabolism in bipolar disorder (Evans et al, 2014). Taken together the literature on the role of PUFA in regulating mood disorders suggests that dietary intake as well as factors regulating PUFA metabolism may independently associate with mood disorders and interact to yield their effects.…”

“…Mechanistic studies in rodents show inhibition of AA turnover and processing in brain phospholipids by the AAP, olanzapine and clozapine, (Cheon et al, 2011; Kim, Cheon, Modi, Rapoport, & Rao, 2012; Modi et al, 2013) and common mood stabilizer medications (Rapoport, Basselin, Kim, & Rao, 2009); and the AAP, risperidone and paliperidone, increase liver biosynthesis and erythrocyte membrane composition of PUFA (McNamara et al, 2011a). In humans, AAP and mood stabilizer use by bipolar subjects associates with n-3 and n-6 metabolite levels in plasma (Evans et al, 2014)…”

“…We have recently reported reduced n-6 and n-3 PUFA intake in a cross-sectional study of individuals with bipolar disorder (Evans et al, 2014). We found significantly reduced dietary intake of EPA, DHA and AA in bipolar individuals.…”

Metabolic Comorbidity and Physical Health Implications for Bipolar Disorder: An Update

“…Epidemiological data indicates that individuals with BD, on average, have an excessive caloric intake and high glycemic load (94,95). Moreover, reduced intake of polyunsaturated fatty acids, including, but not limited to, eicosapentaenoic acid and docosahexaenoic acid, has been reported among BD patients (96,97). Nonetheless, there are contradictory reports to suggest that BD patients consume fewer total calories from carbohydrates and fats when compared with healthy controls (98).…”

On the possible quantum role of serotonin in consciousness

“…Extensive literature published in this area reports that psychopathologies are correlated with an unbalanced pro¯le or with a dysregulation of polyunsaturated FAs such as arachidonic acid and linoleic acid, with respect to normal subject FA pro¯les (Rapoport et al, 2009;Demisch et al, 1987Demisch et al, , 1992De Vriese et al, 2004;Du Bois et al, 2006;Engelberg, 1992;Evans et al, 2014). Consequently, considering a psychopathologic state as a somehow altered state of consciousness, FAs could be seen as correlates or perhaps even active molecular agents leading to the development of the di®erent states of consciousness .…”