Research Review: Fish Oil May Reduce the Risk of Psychotic Disorders in High-Risk Individuals

I have been a fan of fish oil for depression for years, and there have been a lot of studies that support its benefits (often as good as any of the SSRI antidepressants, which we now know are not very effective for mild, moderate, or even severe depression). For an overview of the research on omega-3 fats for major depression (generally better as a preventative than as a treatment) check out this article from open access from Lipids in Health and Disease.

Fish oil also has been used successfully to treat ADHD in children, with none of the negative side effects of Ritalin or Adderall. There have also been good studies with bipolar disorder.

In the new issue (February) of Archives of General Psychiatry, there is a research article that suggests fish oil (omega-3 fats) may reduce the manifestation of psychotic disorders in high risk people.

Here is the key finding:

For 12 weeks, 41 individuals were assigned to take daily fish oil capsules containing 1.2 grams of omega-three polyunsaturated fatty acids and 40 were assigned to take placebo; a total of 76 (93.8 percent) completed the intervention. By the end of the study, two (4.9 percent) in the omega-3 group and 11 (27.5 percent) in the placebo group had transitioned to psychotic disorder. The difference between progression to psychosis was 22.6 percent.

The dosage was very low by my standards (I take 4x this amount). But the outcome is very significant. Administering omega-3 fats at the first sign of sub-clinical psychotic symptoms may delay or prevent the escalation to full-blown psychosis. Based on this protocol, only one in four people benefited from the fish oil, but my guess is that if the dosage were higher and the duration longer than 12 weeks, there might be a better outcome.

Full citation:

Long-Chain -3 Fatty Acids for Indicated Prevention of Psychotic Disorders

A Randomized, Placebo-Controlled Trial

G. Paul Amminger, MD; Miriam R. Schäfer, MD; Konstantinos Papageorgiou, MD; Claudia M. Klier, MD; Sue M. Cotton, PhD; Susan M. Harrigan, MSc; Andrew Mackinnon, PhD; Patrick D. McGorry, MD, PhD; Gregor E. Berger, MD

Arch Gen Psychiatry. 2010;67(2):146-154.

From the Introduction to the study, this brief section describes the possible mechanisms of action for the omega-3 fats in the brain:

The therapeutic effects of -3 PUFAs may result from altered membrane fluidity and receptor responses following their incorporation into cell membranes.¹⁹ -3 Polyunsaturated fatty acids may also interact with the dopaminergic and serotonergic systems, which both have been associated with the pathophysiology of schizophrenia through modulation of receptor-coupled arachidonic acid release.²⁰ Furthermore, eicosapentaenoic acid, an -3 PUFA, may increase glutathione in the temporal lobes of first-episode psychosis patients.²¹ There are data to suggest that glutathione may be low in schizophrenia²² and protects neurons from excitotoxicity²³ and oxidative stress, which is documented in schizophrenia.²⁴

If, as this study suggests, glutathione levels are low in schizophrenics, then an additional nutritional intervention may be to introduce alpha lipoic acid into the preventative protocol, as it has been shown to substantially increase glutathione levels (abstract here).

In general, this is another important article demonstrating the link between proper nutrition and decreased mental health issues. If we consumed a healthy, balanced diet from day one, the prevalence of mental illness (not to mention physical illness) might be a lot lower.

Here is the pre-publication press release outlining the study.

Fish Oil May Reduce the Risk of Psychotic Disorders in High-Risk Individuals

CHICAGO—Individuals at extremely high risk of developing psychosis appear less likely to develop psychotic disorders following a 12-week course of fish oil capsules containing long-chain omega-3 polyunsaturated fatty acids, according to a report in the February issue of Archives of General Psychiatry, one of the JAMA/Archives journals.

"Early treatment in schizophrenia and other psychoses has been linked to better outcomes," the authors write as background information in the article. "Given that subclinical psychotic symptoms may predict psychotic disorder and psychosis proneness in a population may be related to the rate of psychotic disorder, intervention in at-risk individuals holds the promise of even better outcomes, with the potential to prevent full-blown psychotic disorders."

Long-chain omega-3 polyunsaturated fatty acids are a promising intervention in individuals with schizophrenia, who may have an underlying dysfunction in fatty acid metabolism, the authors note. G. Paul Amminger, M.D., of Medical University of Vienna, Austria, and Orygen Youth Health Research Centre, Melbourne, Australia, conducted a randomized, double-blind, placebo-controlled clinical trial of their effect on the risk of progression to psychosis in 81 individuals at ultra-high risk. These individuals either had mild psychotic symptoms, transient psychosis or a family history of psychotic disorders plus a decrease in functioning. These criteria identify individuals whose risk of becoming psychotic may be as high as 40 percent in a 12-month period.

For 12 weeks, 41 individuals were assigned to take daily fish oil capsules containing 1.2 grams of omega-three polyunsaturated fatty acids and 40 were assigned to take placebo; a total of 76 (93.8 percent) completed the intervention. By the end of the study, two (4.9 percent) in the omega-3 group and 11 (27.5 percent) in the placebo group had transitioned to psychotic disorder. The difference between progression to psychosis was 22.6 percent.

Based on the results, the authors estimate that four adults would need to be treated with omega-3 fatty acids to prevent one from developing psychosis over a 12-month period. Polyunsaturated fatty acids also significantly reduced symptoms and improved functioning compared with placebo. Rates of adverse effects were minimal and similar between the two groups.

The potential effects of fatty acids on psychosis development may result from changes to cell membranes and interactions with neurotransmitter systems in the brain, the authors note. "The finding that treatment with a natural substance may prevent or at least delay the onset of psychotic disorder gives hope that there may be alternatives to antipsychotics for the prodromal [early symptomatic] phase," the authors write. "Stigmatization and adverse effects—which include metabolic changes, sexual dysfunction and weight gain—associated with the use of antipsychotics are often not acceptable for young people."

In contrast, omega-3 fatty acids may cause some digestive complications but largely "are free of clinically relevant adverse effects. They have the advantage of excellent tolerability, public acceptance, relatively low costs and benefits for general health," the authors conclude. "Long-chain omega-3 fatty polyunsaturated fatty acids reduce the risk of progression to psychotic disorder and may offer a safe and efficacious strategy for indicated prevention in young people with subthreshold psychotic states."

(Arch Gen Psychiatry. 2010;67[2]:146-154. Available to the media pre-embargo at www.jamamedia.org).

Editor's Note: This study was supported by a grant from the Stanley Medical Research Institute. Please see the article for additional information, including other authors, author contributions and affiliations, financial disclosures, funding and support, etc.

For more information, contact JAMA/Archives media relations at 312/464-JAMA (5262) or e-mail mediarelations@jama-archives.org.

Tags: Psychology, brain, nutrition, JAMA, Fish Oil May Reduce the Risk of Psychotic Disorders in High-Risk Individuals, omega-3 fats, schizophrenia, Archives of General Psychiatry, prevention, research review, health, balanced diet