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

Abstract

We have shown that bipolar individuals have reduced quality diets, including lower intake of polyunsaturated fatty acids (PUFA). We have also reported reduced plasma levels of the n-6 PUFA, linoleic acid (LA), and the n-3 PUFA, eicosapentaenoic acid (EPA) in bipolar subjects. In the current analysis we hypothesized that LA and EPA plasma levels would mediate lower self-reported mental health and life functioning scores in bipolar subjects. In a cross-sectional study, we collected a 7-day diet record in bipolar (n=56) and control subjects (n=46) followed by a fasted blood draw. We used structured equation modeling path analysis to test for mediating effects of dietary intake and plasma levels of LA and EPA on self-reported mental health questionnaire scores, including the Life Functioning Questionnaire (LFQ), the Patient Health Questionnaire (PHQ9), and the Short Form Health Survey (SF12), extracting the mental health component summary score (SF12-MH). We adjusted for age, gender, psychiatric medication use, body mass index (BMI), and total caloric intake as covariates with bipolar disorder as the primary predictor. We found a significant path association from bipolar disorder to lower plasma LA levels (p=0.03) and significant paths from plasma LA to PHQ9 (p=0.05), LFQ (p=0.01) and SF12-MH (p=0.05) scores, such that lower plasma LA predicted worse outcomes. We found no significant paths from plasma EPA levels to any of the outcome measures. These findings suggest that plasma LA levels partially mediate the effect of bipolar disorder on self-reported measures of mental health and life functioning.

Plasma phospholipid profiling of a mouse model of anxiety disorder by hydrophilic interaction liquid chromatography coupled to high‐resolution mass spectrometry

“…In the present report we have focused on the lipid content of plasma, which might indicate anxiety pathogenesis. The plasma level of certain n‐6 fatty acids, phospho‐ and sphingolipids shows correlation with depressive disorder states (Demirkan et al, ; Evans et al, ), suggesting that profiling the plasma lipidome may yield a useful biomarker in mood disorders. In our study, the developed HILIC‐ESI‐MS method and applied bioinformatics software provided a fast and comprehensive tool for the qualitative and quantitative analysis of plasma PLs.…”

Depressive symptoms predict antibody titers after a second dose of the SARS-CoV-2 BNT162b2 vaccine among hospital workers in Japan

“…This result is consistent with recent reports of studies conducted among hospital healthcare workers ( Kanizsai et al, 2022 , Tani et al, 2022 ). A review article suggested that febrile temperatures boosted the effectiveness of the immune response by stimulating both the innate and adaptive arms of the immune system ( Evans et al, 2015 ). Among demographic factors, older age has frequently been reported to be associated with reduced antibody responses following COVID-19 vaccination ( Kanizsai et al, 2022 , Tani et al, 2022 , Terpos et al, 2021 ).…”

Bipolar disorder moderates associations between linoleic acid and markers of inflammation

“…This is based on our previous studies suggesting dysregulated LA metabolism in bipolar disorder by metabolomics analysis following dietary monitoring (Evans et al, 2014), and association with with burden of disease measures (Evans et al, 2015). …”

“…Results from plasma and erythrocyte phospholipid in patients with severe depression showed significant and positive correlation between the ratio of AA to EPA, and severity of depression (Adams, Lawson, Sanigorski, & Sinclair, 1996) and suicidal behavior (Evans et al, 2012b). However, plasma LA inversely associates with burden of disease measures in bipolar patients, including severity of depression and self-reported life functioning (Evans et al, 2015; Evans et al, 2012a; Evans et al, 2014). Other studies of bipolar disorder found higher n-3 and n-6 PUFA levels in the human postmortem superior temporal gyrus, a cortical area related to emotion (McNamara, Rider, Jandacek, & Tso, 2014), but no association in the postmortem entorhinal cortex (Hamazaki, Hamazaki, & Inadera, 2013).…”