Summary: Researchers discovered a link between higher levels of arachidonic acid, an omega-6 fatty acid found in foods like eggs and seafood, and a reduced risk of bipolar disorder. Utilizing Mendelian randomization, the study identified 33 metabolites associated with bipolar disorder, suggesting that lipid levels play a significant role in its etiology.
This connection opens the door to potential dietary interventions aimed at managing or preventing this mood disorder. The findings also hint at the importance of arachidonic acid in early brain development, aligning with views of bipolar disorder as a neurodevelopmental condition.
Key Facts:
- Metabolite Association: The study identified a specific cluster of risk genes related to lipid metabolism that are linked to bipolar disorder, emphasizing the role of metabolic pathways in the disorder.
- Dietary Implications: Higher levels of lipids containing arachidonic acid are associated with a lower risk of bipolar disorder, suggesting that dietary choices may influence the onset and progression of psychiatric conditions.
- Neurodevelopmental Impact: Arachidonic acid is crucial for infant brain development and its adequate intake might influence neurodevelopmental pathways that could affect bipolar disorder risk later in life.
Source: Elsevier
A genetic propensity to 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 with a lower risk for bipolar disorder, according to a new study in Biological Psychiatry. This new evidence paves the way for potential lifestyle or dietary interventions.
Bipolar disorder is a debilitating mood disorder characterized by recurring episodes of mania and depression. Although its etiology is still unclear, previous studies have shown that bipolar disease is highly heritable.
The findings of this study indicate a link between bipolar disorder and altered metabolite levels, supporting the notion that circulating metabolites play an important etiological role in bipolar disease and other psychiatric disorders.
Lead investigator David Stacey, PhD, Australian Centre for Precision Health, University of South Australia; UniSA Clinical and Health Sciences; and 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 causal roles in bipolar disorder, we hoped to be able to highlight potential lifestyle or dietary interventions.”
By applying Mendelian randomization, a powerful causal inference method, the researchers identified 33 out of 913 metabolites studied present in the blood that were associated with bipolar disorder, most of them lipids.
Researchers also found that a bipolar disorder risk gene cluster (FADS1/2/3), which encodes enzymes associated with lipid metabolism, mediated the association between bipolar disorder and the levels of arachidonic acid and other metabolites.
Commenting on the findings, John Krystal, MD, Editor of Biological Psychiatry, says, “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.”
Given its presence in human milk, arachidonic acid is considered essential for infant brain development and is added to infant formula in many countries.
Therefore, 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 sourced directly from meat and seafood products or synthesized from dietary linoleic acid (e.g., nuts, seeds, and oils).
Dr. Stacey concludes, “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.”
About this bipolar disorder research news
Author: Eileen Leahy
Source: Elsevier
Contact: Eileen Leahy – Elsevier
Image: The image is credited to Neuroscience News
Original Research: Open access.
“A Metabolome-Wide Mendelian Randomization Study Identifies Dysregulated Arachidonic Acid Synthesis as a Potential Causal Risk Factor for Bipolar Disorder” by David Stacey et al. Biological Psychiatry
Abstract
A Metabolome-Wide Mendelian Randomization Study Identifies Dysregulated Arachidonic Acid Synthesis as a Potential Causal Risk Factor for Bipolar Disorder
Background
Bipolar disorder (BPD) is a debilitating mood disorder with an unclear etiology. A better understanding of the underlying pathophysiological mechanisms will help to identify novel targets for improved treatment options and prevention strategies. In this metabolome-wide Mendelian randomization study, we screened for metabolites that may have a causal role in BPD.
Methods
We tested a total of 913 circulating metabolite exposures assessed in 14,296 Europeans using a mass spectrometry-based platform. For the BPD outcome, we used summary data from the largest and most recent genome-wide association study reported to date, including 41,917 BPD cases.
Results
We identified 33 metabolites associated with BPD (padjusted < 5.48 × 10−5). Most of them were lipids, including arachidonic acid (β = −0.154, SE = 0.023, p = 3.30 × 10−11), a polyunsaturated omega-6 fatty acid, along with several complex lipids containing either an arachidonic or a linoleic fatty acid side chain.
These associations did not extend to other closely related psychiatric disorders like schizophrenia or depression, although they may be involved in the regulation of lithium response. These lipid associations were driven by genetic variants within the FADS1/2/3 gene cluster, which is a robust BPD risk locus encoding a family of fatty acid desaturase enzymes that are responsible for catalyzing the conversion of linoleic acid into arachidonic acid.
Statistical colocalization analyses indicated that 27 of the 33 metabolites shared the same genetic etiology with BPD at the FADS1/2/3 cluster, demonstrating that our findings are not confounded by linkage disequilibrium.
Conclusions
Overall, our findings support the notion that arachidonic acid and other polyunsaturated fatty acids may represent potential targets for BPD.
