Bipolar disorder, a debilitating mood disorder characterized by recurring episodes of mania and depression, affects approximately 2 percent — tens of millions — of the global population. While the exact causes of bipolar disorder remain unclear, recent research has begun to shed light on potential risk factors, including the role of certain metabolites in the body. Now, a study led by researchers at the University of South Australia has identified a potential link between arachidonic acid, a polyunsaturated omega-6 fatty acid found in eggs and poultry, and lowering the risk of developing bipolar disorder.
Researchers conducted a metabolome-wide Mendelian randomization study, which uses genetic variations as natural experiments to investigate the causal relationships between metabolites and diseases. By analyzing data from over 14,000 European individuals, they screened 913 circulating metabolites to identify those that may play a role in the development of bipolar disorder.
The results were striking: 33 metabolites were found to be significantly associated with bipolar disorder risk, with arachidonic acid emerging as a key player. Lower levels of arachidonic acid and several complex lipids containing arachidonic acid side chains were consistently associated with a higher risk of bipolar disorder. Conversely, higher levels of linoleic acid-containing lipids, which are precursors to arachidonic acid, were associated with a lower risk.
These findings suggest that the conversion of linoleic acid into arachidonic acid, a process catalyzed by enzymes encoded by the FADS1/2/3 gene cluster, may be crucial in the development of bipolar disorder. In fact, researchers found that genetic variants within this gene cluster were driving the observed associations between the metabolites and bipolar disorder risk.
“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,” says lead study investigator Dr. David Stacey, of the Australian Center for Precision Health at the University of South Australia, in a media release.
The identified metabolite associations were specific to bipolar disorder and did not extend to other closely related psychiatric disorders such as schizophrenia or depression. However, researchers did find evidence to suggest that these metabolites may be involved in regulating the response to lithium, a commonly used treatment for bipolar disorder.
“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,” explains Dr. Stacey. “Since arachidonic acid is synthesized from linoleic acid in the liver, this suggests arachidonic acid synthesizing pathways are important for bipolar disorder.”
What does this all mean for the average person? While more research is needed to fully understand the implications of these findings, they suggest that a simple blood test could potentially be used to determine an individual’s lifetime risk of developing bipolar disorder. By measuring the concentrations of arachidonic acid and related metabolites in the blood, doctors may be able to identify those at higher risk and implement preventive strategies or early interventions.
Furthermore, these findings highlight the importance of arachidonic acid in brain development and function. Arachidonic acid is considered essential for infant brain development and is added to infant formulas in many countries. It plays a vital role in the central nervous system, both as a major component of neuronal and glial cell membranes and as a signaling molecule.
“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,” notes Dr. Stacey. “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.”
While further research is needed to validate these findings and explore their clinical implications, they offer hope for a future where a simple blood test could predict an individual’s lifetime risk of bipolar disorder, enabling early intervention and personalized prevention strategies. Moreover, these findings underscore the importance of proper nutrition, particularly in early life, for optimal brain development and mental health.
