Bipolar disorder moderates associations between linoleic acid and markers of inflammation.
Dietary polyunsaturated fatty acids (PUFA) and inflammatory proteins associate with immune activation and have been implicated in the pathophysiology of mood disorders. We have previously reported that individuals with bipolar disorder (BPD) have decreased PUFA intake, including eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), and arachidonic acid (AA); and decreased PUFA concentration of plasma EPA and linoleic acid (LA). We have also reported an association between plasma LA and its metabolites and burden of disease measures in BPD. In the current cross-sectional study we collected blood samples and diet records from both bipolar (n = 91) and control subjects (n = 75) to quantify plasma cytokine concentrations and dietary LA intake, respectively. Using multiple linear regression techniques, we tested for case control differences in plasma cytokine levels and associations between cytokines and dietary LA intake, adjusting for sex, age, BMI, and total energy intake. We found significantly higher plasma levels of interleukin 18 (IL-18) (p = 0.036), IL-18 binding protein (IL-18BP) (p = 0.001), soluble tumor necrosis factor receptor (sTNFR) 1 (p = 0.006), and sTNFR2 (p = 0.007) in BPD compared with controls. Moreover, BPD significantly moderated the associations of dietary LA intake with plasma levels of IL-18, sTNFR1 and sTNFR2, which were inverse associations in bipolar individuals and positive associations in controls (p for dietary LA x BPD diagnosis interaction < 0.05 for all three). These findings suggest potential dysregulation of LA metabolism in BPD, which may extend to a modified influence of dietary LA on specific inflammatory pathways in individuals with BPD compared to healthy controls.
Department of Nutritional Sciences, School of Public Health, University of Michigan, Ann Arbor, MI, United States.
Ya-Wen
YW
Chang
Department of Psychiatry, University of Michigan, Ann Arbor, MI, United States.
Shervin
S
Assari
Department of Psychiatry and Behavioral Sciences, University of Texas Health Science Center, Houston, TX, United States.
Alan R
AR
Prossin
Department of Psychiatry and Behavioral Sciences, University of Texas Health Science Center, Houston, TX, United States.
Laura
L
Stertz
Department of Psychiatry, University of Michigan, Ann Arbor, MI, United States.
Melvin G
MG
McInnis
Department of Psychiatry, University of Michigan, Ann Arbor, MI, United States. Electronic address: evanssi@umich.edu.
Simon J
SJ
Evans
D000328:Adult; D000367:Age Factors; D015415:Biomarkers / Q000097:blood; D001714:Bipolar Disorder / Q000097:blood* / Q000276:immunology*; D015992:Body Mass Index; D016022:Case-Control Studies; D003430:Cross-Sectional Studies; D004032:Diet; D004435:Eating; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D020382:Interleukin-18 / Q000097:blood*; D007406:Interview, Psychological; D016014:Linear Models; D019787:Linoleic Acid / Q000097:blood*; D008297:Male; D008499:Medical Records; D047888:Receptors, Tumor Necrosis Factor, Type I / Q000097:blood*; D047889:Receptors, Tumor Necrosis Factor, Type II / Q000097:blood*; D012737:Sex Factors
D015415:Biomarkers; C000589760:IL18 protein, human; D020382:Interleukin-18; D047888:Receptors, Tumor Necrosis Factor, Type I; D047889:Receptors, Tumor Necrosis Factor, Type II; D019787:Linoleic Acid
Bipolar disorder; Interleukin; Linoleic acid; Tumor necrosis factor receptor