Summary: Researchers have found 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. Using Mendelian randomization, the study identified 33 metabolites associated with bipolar disorder, suggesting that lipid levels play an important role in its etiology.
This connection opens the door to possible dietary interventions aimed at managing or preventing this mood disorder. The findings also hint at the importance of arachidonic acid in early brain development, consistent with the view of bipolar disorder as a neurodevelopmental disorder.
Highlights:
- Association of metabolites: The study identified a specific group of risk genes related to lipid metabolism that are linked to bipolar disorder, highlighting the role of metabolic pathways in the disorder.
- Dietary implications: Higher levels of arachidonic acid-containing lipids are associated with a lower risk of bipolar disorder, suggesting that dietary choices may influence the onset and progression of psychiatric disorders.
- Neurodevelopmental impact: Arachidonic acid is crucial for infant brain development and its adequate intake could influence neurodevelopmental pathways that could affect the risk of bipolar disorder later in life.
Source: Elsevier
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 shown to be linked to a lower risk of bipolar disorder, according to a new study published in Biological Psychiatry. This new evidence paves the way for possible lifestyle or dietary interventions.
Bipolar disorder is a debilitating mood disorder characterized by recurrent episodes of mania and depression. Although its etiology is still uncertain, 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 Institute of Medical and Health Research, Adelaide, Australia, explains: “Increasing evidence indicates the role of metabolites in bipolar disorder and other psychiatric disorders.
“By identifying metabolites that play a causal role in bipolar disorder, we hoped to be able to highlight possible 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 blood and associated with bipolar disorder, most of them lipids.
Researchers also found that a group of genes at risk for bipolar disorder (FAD1/2/3), which encodes enzymes associated with lipid metabolism, mediates the association between bipolar disorder and levels of arachidonic acid and other metabolites.
Commenting on the findings, John Krystal, MD, editor-in-chief of Biological Psychiatrysaid, “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. »
Dr Stacey notes: “Intriguingly, we observed a trend where a genetic propensity for higher levels of arachidonic acid fatty acid side chain-containing lipids was associated with lower risk of bipolar disorder, whereas the opposite was true for lipids containing 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.”
Given its presence in breast milk, arachidonic acid is considered essential for infant brain development and is added to infant formula in many countries.
Therefore, it could exert an effect on the risk of bipolar disorder by affecting neurodevelopmental pathways, which would be consistent with contemporary views of bipolar disorder as a neurodevelopmental disorder.
Arachidonic acid can come directly from meat and seafood or be synthesized from dietary linoleic acid (e.g., nuts, seeds, and oils).
Dr Stacey concludes: “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.”
About this bipolar disorder research news
Author: Eileen Leahy
Source: Elsevier
Contact: Eileen Leahy – Elsevier
Picture: Image is credited to Neuroscience News
Original research: Free access.
“A metabolism-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
Metabolism-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 unclear etiology. A better understanding of the underlying pathophysiological mechanisms will help identify new targets to improve treatment options and prevention strategies. In this metabolome-wide Mendelian randomization study, we investigated metabolites that may play 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, as well as several complex lipids containing an arachidonic or linoleic fatty acid side chain.
These associations do not extend to other closely related psychiatric disorders such as schizophrenia or depression, although they may be involved in regulating the response to lithium. These lipid associations were driven by genetic variants within the FAD1/2/3 gene cluster, which is a robust BPD risk locus encoding a family of fatty acid desaturases enzymes responsible for catalyzing the conversion of linoleic acid to arachidonic acid.
Statistical colocalization analyzes indicated that 27 of the 33 metabolites shared the same genetic etiology with BPD. FAD1/2/3 cluster, demonstrating that our results are not perturbed by linkage disequilibrium.
Conclusions
Overall, our results support the idea that arachidonic acid and other polyunsaturated fatty acids may represent potential targets for BPD.
News Source : neurosciencenews.com
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