Genetic propensity for higher levels of arachidonic acid is linked to a lower risk of bipolar disorder

A genetic propensity for higher circulating levels of lipids containing arachidonic acid, an omega-6 polyunsaturated fatty acid found in eggs, poultry and seafood, has been found to be linked to a lower risk of bipolar disorder , according to a new study a Biological Psychiatry, published by Elsevier. This new evidence paves the way for potential lifestyle or dietary interventions.

Bipolar disorder is a debilitating mood disorder characterized by recurrent episodes of mania and depression. Although its etiology is still unclear, previous studies have shown that bipolar illness is highly hereditary. The results of this study indicate a link between bipolar disorder and altered metabolite levels, supporting the idea that circulating metabolites play an important etiological role in bipolar illness and other psychiatric disorders.

Principal Investigator David Stacey, PhD, Australian Center for Precision Health, University of South Australia; UniSA Clinical and Health Sciences; and the South Australian Health and Medical Research Institute, Adelaide, Australia, explains: “Accumulating evidence indicates a role for metabolites in bipolar disorder and other psychiatric disorders. By identifying metabolites that play a causal role in bipolar disorder, we hoped to highlight potential lifestyle or dietary interventions.”

By applying Mendelian randomization, a powerful method of causal inference, the researchers identified 33 of the 913 studied metabolites present in the blood that were associated with bipolar disorder, most of them lipids.

The researchers also found that a group of bipolar disorder risk genes (FADS1/2/3), which encodes enzymes associated with lipid metabolism, mediated the association between bipolar disorder and levels of arachidonic acid and other metabolites.

Commenting on the findings, John Krystal, MD, editor of Biological Psychiatrysays, ARachidonic acid is an omega-6 fatty acid commonly found in the body and brain that contributes to the health of cell membranes. This study provides a fascinating step forward in the effort to develop blood biomarkers of risk for bipolar disorder, particularly in those patients with bipolar disorder and risk gene variations in the FADS1/2/3 gene cluster”.

Dr. Stacey points out, “Interestingly, we observed a pattern whereby a genetic propensity for higher levels of lipids containing an arachidonic acid side chain fatty acid was associated with a lower risk of bipolar disorder, while the reverse was true for lipids which contained a linoleic acid side chain. The acid is synthesized from linoleic acid in the liver, suggesting that arachidonic acid synthesis pathways are important for bipolar disorder.”

Given its presence in human milk, arachidonic acid is considered essential for infant brain development and is added to infant formula in many countries. Thus, it may exert an effect on bipolar disorder risk by affecting neurodevelopmental pathways, which would be consistent with contemporary views of bipolar disorder as a neurodevelopmental disorder. Arachidonic acid can be obtained directly from meats and seafood or synthesized from dietary linoleic acid (eg nuts, seeds and oils).

Dr. Stacey concludes: “To our knowledge, ours is the first study to highlight a possible causal role between arachidonic acid and bipolar disorder. Preclinical studies and randomized controlled trials will be needed to determine the preventive or therapeutic value of arachidonic acid supplements, perhaps with a particular focus on people with a compromised arachidonic acid synthesis pathway or with poor natural dietary sources. arachidonic acid and other polyunsaturated fatty acids to support optimal brain development, which may also reduce the risk of bipolar disorder.”


Journal reference:

Stacey, D., et al. (2024). A metabolome-wide Mendelian randomization study identifies dysregulated arachidonic acid synthesis as a potential causal risk factor for bipolar disorder. Biological Psychiatry.

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