Lipid correlates of antidepressant response to omega-3 polyunsaturated fatty acid supplementation: A pilot study

Abstract

Low omega-3 polyunsaturated fatty acid (PUFA) levels are seen in major depression. We examined effects of six weeks of fish oil supplementation on clinical characteristics in 16 patients with symptomatic major depressive disorder, and tested plasma phospholipid levels of docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) as correlates of clinical response. Depression symptoms improved after supplementation (p=0.007). The reduction in depression severity was not predicted by baseline PUFA levels but did exhibit a relationship with endpoint PUFAs, correlating negatively with DHA as a percentage of plasma phospholipids (DHA%; R2=0.60, p=0.004), adjusting for endpoint EPA%; and correlating positively with endpoint EPA% (R2=0.58, p=0.007), adjusting for endpoint DHA%. Thus, the higher the proportion of DHA to EPA, the greater the reduction in depression severity (r=−0.43, p=0.097). Five patients showed a decrease of > 50% on the 17-item Hamilton Depression Rating Scale and a final score < 7 and were thus not only responders but met standard criteria for remission, and were distinguished from non-responders by higher levels of DHA% (p=0.03). This pilot study suggests that post-supplementation DHA% levels may be a necessary target for antidepressant response to fish oil, and that this may depend to some extent on the efficacy of EPA conversion to DHA.

Docosahexaenoic acid regulates the formation of lipid rafts: A unified view from experiment and simulation

“…The results from this study also have consequences for other immune cells such as helper T cells and the formation of the immunological synapse, which is a key regulator of inflammatory signaling [65]. Finally, we speculate that DHA-induced modification to raft size could have an effect on neurotransmission, which has implications for a variety of mental health disorders such as depression [66].…”

Food for Mood: Relevance of Nutritional Omega-3 Fatty Acids for Depression and Anxiety

“…The beneficial effect of EPA has been recently corroborated by a new meta-analysis ( Mocking et al, 2016 ). EPA efficiency could be linked to its conversion into DHA by elongase leading to increased DHA brain bioavailability and decreased LC ω6 PUFAs production ( Ganança et al, 2017 ). Indeed, as the conversion of EPA into DHA compete with the production of n-6 DPA from AA by using the same enzymatic pathway (i.e., FADS and elongases), the supplementation of EPA can simultaneously lead to an increase in DHA and a decrease in n-6 DPA levels that can subsequently improve mood.…”

Long-Term Fluoxetine Administration Causes Substantial Lipidome Alteration of the Juvenile Macaque Brain

“…In blood, patients suffering from depression displayed reduced omega-3 fatty acids levels, including DHA [45,46]. Moreover, omega-3 supplementation was suggested to improve depressive symptoms [47,48], while dietary omega-3 PUFA deprivation induced depressive-like behaviors in rodents [49][50][51] coupled with a decrease in prefrontal cortex DHA levels [49]. While brain PUFAs levels are relatively stable in adulthood, the brain undergoes major changes in fatty acid content in childhood, including accretion of DHA [52,53], highlighting the risk of brain PUFAs metabolism abnormalities during this period.…”