Abstract
Polyunsaturated fatty acids (PUFA) have shown efficacy in the treatment of bipolar disorder, however their specific role in treating the illness is unclear. Serum PUFA and dietary intakes of PUFA associate with suicidal behavior in epidemiological studies. The objective of this study was to assess serum n-3 and n-6 PUFA levels in bipolar subjects and determine possible associations with suicidal risk, including suicidal history and relevant personality factors that have been associated with suicidality. We studied 27 bipolar subjects using the NEO-PI to assess the big five personality factors, structured interviews to verify diagnosis and assess suicidal history, and lipomics to quantify n-3 and n-6 PUFA in serum. We found positive associations between personality factors and ratios of n-3 PUFA, suggesting that conversion of short chain to long chain n-3s and the activity of enzymes in this pathway may associate with measures of personality. Thus, ratios of docosahexaenoic acid (DHA) to alpha linolenic acid (ALA) and the activity of fatty acid desaturase 2 (FADS2) involved in the conversion of ALA to DHA were positively associated with openness factor scores. Ratios of eicosapentaenoic acid (EPA) to ALA and ratios of EPA to DHA were positively associated with agreeableness factor scores. Finally, serum concentrations of the n-6, arachidonic acid (AA), were significantly lower in subjects with a history of suicide attempt compared to non-attempters. The data suggest that specific lipid profiles, which are controlled by an interaction between diet and genetics, correlate with suicidal history and personality factors related to suicidal risk. This study provides preliminary data for future studies to determine whether manipulation of PUFA profiles (through diet or supplementation) can affect personality measures and disease outcome in bipolar subjects and supports the need for further investigations into individualized specific modulations of lipid profiles to add adjunctive value to treatment paradigms.
Highlights
Bipolar Illness strikes approximately 5.7 million adults in the United States, or about 1–2% of the adult population in any given year [1]
In assessing the relationship between the five personality factor scores and n-3, n-6 fatty acids, we found that the relative plasma concentrations of several lipid species or physiologically relevant ratios between lipid species significantly correlated with various personality factors
An effect of n-3 fatty acid supplementation has shown inconsistent association with improvements in bipolar symptomology ([7]) and we suggest that this may be due to variable concentrations of other lipid species, either n-6 fatty acids that tend to compete with n-3 fatty acids in a variety of signaling, inflammatory and other pathways; or genetically variant enzyme activities that favor pooling one fatty acid over another
Summary
Bipolar Illness strikes approximately 5.7 million adults in the United States, or about 1–2% of the adult population in any given year [1]. The lifetime prevalence of suicide attempts in bipolar patients is over 30% [2], making uncontrolled bipolar disorder a large risk factor for suicidal behavior. In spite of the plethora of medications used to manage bipolar disease, including 60 years of clinical use of lithium, the majority of treated bipolar patients have ‘‘less than a satisfactory outcome’’ [3]. Several potential risk factors have been linked to suicidal behavior. Two of these include personality factors and PUFA serum levels. It is unknown whether PUFA serum levels are associated with personality factors and if these may interact to affect suicidal behavior. Several studies suggest that low serum n-3 PUFA associate with aggressive and violent behavior. Serum n-3 PUFA levels predict serotonin and dopamine metabolites in cerebrospinal fluid that differ between violent and non-violent subjects [6]
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