A new study published in Biological Psychiatry reveals a potential link between higher levels of arachidonic acid, an omega-6 polyunsaturated fatty acid, and reduced risk of bipolar disorder. The findings suggest that dietary or lifestyle interventions targeting arachidonic acid levels could help mitigate the risk of developing this debilitating mood disorder.
Bipolar disorder is characterized by recurrent episodes of mania and depression, which have serious consequences on the lives of those affected. The exact causes of bipolar disorder remain unclear, but it is known to have a strong genetic component. Previous studies have highlighted the potential role of metabolites (small molecules involved in metabolism) in psychiatric disorders. The researchers aimed to identify specific metabolites that could causally influence the risk of bipolar disorder, potentially opening new avenues for prevention and treatment.
The researchers used a method called Mendelian randomization, which uses genetic variants as tools to infer causal relationships between exposures (in this case, metabolite levels) and outcomes (bipolar disorder). They analyzed genetic data from large genome-wide association studies (GWAS) covering 913 metabolites in more than 14,000 European individuals and bipolar disorder data from more than 413,000 participants, including 41,917 diagnosed with bipolar disorder.
Focusing on genetic variants associated with lipid metabolism, the researchers identified a group of genes (FADS1/2/3) encoding enzymes involved in the synthesis of arachidonic acid from linoleic acid, another omega-6 fatty acid. They looked at the levels of various metabolites in the blood and their genetic associations with bipolar disorder risk.
The study discovered 33 metabolites associated with bipolar disorder, most of which were lipids. A key finding was that a genetic predisposition to higher levels of arachidonic acid-containing lipids was linked to a lower risk of bipolar disorder. Conversely, higher levels of linoleic acid-containing lipids were associated with higher risk. This pattern suggests that the pathway converting linoleic acid to arachidonic acid is crucial in modulating the risk of bipolar disorder.
Arachidonic acid, widely found in the body and brain, contributes to healthy cell membranes and is essential for infant brain development. It can be obtained directly from foods such as meat and seafood or synthesized from linoleic acid found in nuts, seeds and oils.
The researchers also noted that the FADS1/2/3 gene cluster plays a mediating role in the relationship between bipolar disorder and lipid levels. This group is crucial for lipid metabolism, highlighting a genetic mechanism by which arachidonic acid levels could influence the risk of bipolar disorder.
“Intriguingly, we observed a pattern whereby a genetic propensity for higher levels of lipids containing an arachidonic acid fatty acid side chain was associated with lower risk of bipolar disorder, while the opposite was true for lipids containing a linoleic acid side chain. Since arachidonic acid is synthesized from linoleic acid in the liver, this suggests that arachidonic acid synthesis pathways are important for bipolar disorder,” said study author David Stacey of the University of South Australia and the South Australian Institute of Medical and Health Research.
“To our knowledge, our study is the first to highlight a potential 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 particular emphasis on individuals whose arachidonic acid synthesis pathway is compromised or whose Natural food sources are poor.
“Our findings also support potential avenues for precision health interventions focused on young children’s nutrition to ensure that infants and children receive sufficient arachidonic acid and other polyunsaturated fatty acids to support optimal brain development , which may also reduce the risk of bipolar disorder.”
Although the results are promising, the study has several limitations. First, the results are based on genetic data from individuals of European ancestry, so their applicability to other populations is uncertain. Second, the study relies on genetic associations that, while robust, do not account for all potential environmental and lifestyle factors influencing bipolar disorder.
Future research should focus on replication in diverse populations and further exploration of the mechanisms by which arachidonic acid influences bipolar disorder. Preclinical studies and randomized controlled trials are needed to determine the potential preventative or therapeutic value of arachidonic acid supplements, particularly for individuals with genetic variations affecting their ability to synthesize arachidonic acid.
Additionally, research on the impact of early nutrition on brain development could provide information on how adequate intake of arachidonic acid and other polyunsaturated fatty acids in infants and children could reduce the risk of bipolar disorder. This could lead to precision health interventions tailored to individual genetic profiles, improving mental health outcomes from an early age.
Despite its limitations, the study marks a significant advance in understanding the complex interplay between genetics, metabolism and mental health.
“Arachidonic acid is generally an omega-6 fatty acid widely found in the body and brain that contributes to the health of cell membranes. This study represents a fascinating advance in efforts to develop blood-based biomarkers of bipolar disorder risk, particularly in bipolar disorder patients with risk genetic variations in the FADS1/2/3 gene cluster. said John Krystal, editor-in-chief of Biological Psychiatry.
The study titled “A Metabolism-Wide Mendelian Randomization Study Identifies Dysregulated Arachidonic Acid Synthesis as a Potential Causal Risk Factor for Bipolar Disorder” was authored by David Stacey, Beben Benyamin, S. Hong Lee and Elina Hyppönen.
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