Omega-6 Fatty Acid Role in Bipolar Disorder

Higher concentrations of arachidonic acid, an omega-6 fatty acid present in foods like eggs and seafood, have been linked by researchers to a lower incidence of bipolar disorder. The study found 33 metabolites related to bipolar disorder using Mendelian randomization, indicating that lipid levels are critical in the etiology of the condition.

Given this link, dietary interventions that could be used to treat or prevent this mood disorder may now be possible. The results are consistent with the idea that bipolar illness is a neurodevelopmental disorder and suggest the role of arachidonic acid in early brain development.

Important Details:

1. Metabolite Association:

The study highlighted the involvement of metabolic pathways in bipolar disorder by identifying a particular cluster of risk genes associated with lipid metabolism that are linked to the illness.

2. Dietary Implications: 

Research indicates that a lower incidence of bipolar disorder is linked to higher levels of lipids, including arachidonic acid, suggesting that dietary decisions may have an impact on the development and course of mental illnesses.

3. Impact on Neurodevelopment:

Adequate intake of arachidonic acid during infancy may influence neurodevelopmental pathways that may later affect the risk of bipolar disorder. Arachidonic acid is essential for the proper development of the baby’s brain.

Source: Elsevier

A genetic predisposition to higher circulation levels of lipids, including arachidonic acid, an omega-6 polyunsaturated fatty acid present in eggs, poultry, and seafood, has been linked to a lower risk of bipolar disorder, according to a recent study published in Biological Psychiatry. This new information opens the possibility of possible dietary or lifestyle modifications.

Recurrent episodes of mania and depression typify the crippling mood disorder of bipolar disorder. Although its origin is still uncertain, earlier investigations have revealed that bipolar disorder is highly heritable.

The results of this investigation support the idea that circulating metabolites are a primary etiological factor in bipolar illness and other psychiatric illnesses by showing a connection between bipolar disorder and changed metabolite levels.

Lead researcher David Stacey, PhD, South Australian Health and Medical Research Institute, Adelaide, Australia; UniSA Clinical and Health Sciences; Australian Centre for Precision Health, University of South Australia, explains, “Accumulating evidence indicates a role for metabolites in bipolar disorder and other psychiatric disorders.

“By identifying metabolites that play causal roles in bipolar disorder, we hoped to be able to highlight potential lifestyle or dietary interventions.”

The researchers found that 33 out of 913 metabolites they examined in the blood were linked to bipolar disorder by using Mendelian randomization, a potent causal inference technique. Lipids make up a large portion of these metabolites.

Additionally, the relationship between bipolar disorder and arachidonic acid and other metabolite levels was revealed to be mediated by a bipolar disorder risk gene cluster (FADS1/2/3), which encodes enzymes related to lipid metabolism.

John Krystal, MD, Editor of Biological Psychiatry, comments on the results, saying that Arachidonic acid is typically a widely present omega-6 fatty acid 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 bipolar disorder risk, particularly in those patients with bipolar disorder and risk gene variations in the FADS1/2/3 gene cluster.”

Dr. Stacey notes, “Intriguingly, we observed a pattern whereby a genetic propensity to higher levels of lipids containing an arachidonic acid fatty acid side chain was associated with a lower risk of bipolar disorder, while the inverse was true of lipids containing a linoleic acid side chain.

“Since arachidonic acid is synthesized from linoleic acid in the liver, this suggests arachidonic acid synthesizing pathways are important for bipolar disorder.”

Since arachidonic acid is found in human milk, it is added to infant formula in many countries since it is thought to be essential for the development of the baby’s brain.

In line with current theories of bipolar disorder as a neurodevelopmental condition, it may, therefore, have an impact on the risk of bipolar disorder via altering neurodevelopmental pathways.

Foods high in linoleic acid, such as nuts, seeds, and oils, can be used to generate arachidonic acid, or it can be obtained directly from meat and marine products.

Finally, Dr. Stacey says, “To our knowledge, ours is the first study to highlight a potential causal role between arachidonic acid and bipolar disorder.

“Preclinical studies and randomized controlled trials will be necessary to determine the preventive or therapeutic value of arachidonic acid supplements, perhaps with a particular focus on people with a compromised arachidonic acid synthesizing pathway or with poor natural dietary sources.

“Our findings also support potential avenues for precision health interventions focused on early life nutrition to ensure that infants and children are receiving enough arachidonic acid and other polyunsaturated fatty acids to support optimal brain development, which may also reduce the risk of bipolar disorder.”

For more information: A Metabolome-Wide Mendelian Randomization Study Identifies Dysregulated Arachidonic Acid Synthesis as a Potential Causal Risk Factor for Bipolar Disorder,  Biological Psychiatry, DOI:https://doi.org/10.1016/j.biopsych.2024.02.1005.