Although evidence suggests that chronic elevations in immune-inflammatory signaling can precipitate mood symptoms in a subset of individuals, associated risk and resilience mechanisms remain poorly understood.
Long-chain omega-3 (LCn-3) fatty acids, including eicosapentaenic acid (EPA) and docosahexaenoic acid (DHA), have anti-inflammatory and inflammation-resolving properties that maintain immune-inflammatory signaling homeostasis. Cross-sectional evidence suggests that the mood disorders major depressive disorder and bipolar disorder are associated with low EPA and/or DHA biostatus, elevations in the LCn-6:LCn-3 fatty acid ratio, and elevated levels of pro-inflammatory eicosanoids, cytokines, and acute-phase proteins.
Medications that are effective for reducing depressive symptoms or stabilizing manic depressive oscillations may act in part by down regulating immune-inflammatory signaling and are augmented by anti-inflammatory medications. Recent prospective longitudinal evidence suggests that elevations in the LCn-6:LCn-3 fatty acid ratio are a modifiable risk factor for the development of mood symptoms, including depression and irritability, in response to immune-inflammatory signaling. Together these data suggest that increasing LCn-3 fatty acid intake and biostatus represents a feasible strategy to mitigate the negative impact of elevated immune-inflammatory signaling on mood stability.
Key teaching points:
• Long-chain omega-3 (LCn-3) fatty acids have anti-inflammatory and inflammation-resolving properties.
• Major mood disorders are associated with both LCn-3 fatty acids deficiency and elevated immune-inflammatory signaling.
• Prospective evidence suggests that low LCn-3 fatty acid biostatus increases risk for developing inflammation-induced mood dysregulation.
• Taken collectively, this evidence suggests that increasing LCn-3 fatty acid intake and biostatus represents a promising strategy to mitigate the detrimental effects of elevated immune-inflammatory signaling on mood.
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