Fish Oil to Fend Off Psychosis: New Evidence
Dietary Supplementation and Psychosis
Mental healthcare providers continue to struggle with an inadequacy of treatment options for the most serious psychiatric illnesses, including schizophrenia and related psychotic disorders. Although diverse psychosocial treatments (eg, assertive community treatment, cognitive-behavioral therapy, cognitive remediation, family interventions, integrated substance abuse treatment, psychoeducation, social skills training, supported employment) are clearly beneficial in key outcome domains, diverse symptoms, and disabling psychosocial impairment continue to stand in the way of adequate remission and recovery for many affected individuals. While the armamentarium of antipsychotic agents is expanding, pharmacologic treatments for symptom clusters outside of the positive symptom domain (eg, negative symptoms, disorganization or formal thought disorder, neurocognitive deficits) remain largely elusive. Given the need for more effective treatments, the potential for symptom amelioration through dietary modification or dietary supplements represents an enticing possible treatment modality.
Along these lines, recent years have witnessed a growing interest in the possibility that polyunsaturated fatty acids, some of which feature prominently in fish oils, may be beneficial for psychiatric disorders. Attention has focused primarily on omega-3 fatty acids; these include eicosapentaenoic acid and docosahexaenoic acid (both thought to be beneficial in terms of reductions in risk for cardiovascular disease in addition to having other health benefits), which are most widely available in cold water oily fish such as salmon, herring, and mackerel. Omega-6 polyunsaturated fatty acids (found in plant oils including palm, soybean, rapeseed, and sunflower oils) have also been studied, although with perhaps less evidence in terms of health benefits. In fact, excesses of omega-6 fatty acids are believed to potentially interfere with the health-promoting effects of omega-3 fatty acids.
Polyunsaturated Fatty Acids: The Evidence
Although an exhaustive summary of the research on polyunsaturated fatty acids in the context of schizophrenia and related psychotic disorders is beyond the scope of this brief column, a summary of 3 recent studies, each published in 2010, provides a glimpse into the ongoing research in this area, and foreshadows future research that will come about in upcoming years. This column gives brief summaries of: (1) an epidemiologic study involving more than 33,000 women in the general population in Sweden; (2) a randomized, controlled trial of the administration of omega-3 fatty acids among individuals at apparent ultra-high risk of developing a psychotic disorder in Austria; and (3) a laboratory study in which endogenous levels of omega-3 fatty acids were measured in relation to hostility among patients diagnosed with schizophrenia or schizoaffective disorder in Japan.
Is There a Correlation?
At the general population level, Hedelin and colleagues conducted a large-scale epidemiologic study among women in the Uppsala Health Care Region in Sweden to evaluate the association of dietary intake of different fish species and specific polyunsaturated fatty acids with the prevalence of positive psychotic-like symptoms. Data were available from more than 33,000 women who reported on dietary habits in 1991/1992 and then reported their experiences of having any psychotic-like symptoms in 2002/2003. Women were divided into a "low-level symptoms group" (55%), a "middle-level symptoms group" (43%), and a "high-level symptoms group" (2.4%) based on their responses in 2002/2003. Among many of their findings, Hedelin and colleagues reported that the intake of omega-3 and omega-6 fatty acids was associated with a decreased relative risk for psychotic-like symptoms, after adjusting for multiple other potentially confounding variables. Interpretation of the findings is limited given that dietary intake and self-reported psychotic-like symptoms were measured only once, and men were not included. Nonetheless, the results provide an interesting hint into possible correlations between dietary intake and psychosis-continuum experiences in the population at large.
The next study summarized here pertains to the goal of prevention of psychosis among those who appear to be at imminent risk of developing a psychotic disorder. Because the few available intervention studies to date involving adolescents and young adults who appear to be in a prodromal state for a psychotic disorder have relied on cognitive-behavioral therapy and low-dose antipsychotics, Amminger and colleagues conducted a study to test whether omega-3 polyunsaturated fatty acids would reduce the rate of transition to first-episode psychosis in an ultra-high risk cohort. In this sentinel study, they randomized, in a double-blind fashion, 81 individuals aged 13 to 25 years to 12 weeks of either 1.2 g/day of omega-3 polyunsaturated fatty acids (which included eicosapentaenoic acid, docosahexaenoic acid, and vitamin E) or placebo, followed by a 40-week monitoring period. Two of 41 (4.9%) of those receiving the active agent transitioned to psychosis, compared to 11 of 40 (27.5%) in the placebo group, which represented a statistically significant difference. Omega-3 polyunsaturated fatty acids also reduced the severity of positive, negative, and general symptoms, and improved functioning compared to the placebo condition. This study provided the first, early evidence that fish oils may be useful as a preventive intervention in those at particularly high risk, although further study is clearly warranted.
A Look at Concentration
Some studies have examined the relationship between levels of specific polyunsaturated fatty acids (either through observational studies examining diet or concentrations in blood or through experimental studies that administer supplements) and specific symptom domains in diverse psychiatric disorders, including schizophrenia. In Japan, Watari and colleagues assessed 75 inpatients with acute schizophrenia or schizoaffective disorder (48% male, mean age of 36.3 ± 9.9 years) who were drug-free at the time of hospital admission. They determined the red blood cell composition of key polyunsaturated fatty acids and rated hostility using the Positive and Negative Syndrome Scale. They found that the concentrations of eicosapentaenoic acid and docosahexaenoic acid in red blood cells were negatively correlated with hostility scores (the higher the level of those omega-3 fatty acids, the lower the severity of hostility), after adjusting for age, gender, smoking status, and other covariates. On the other hand, the concentration of arachidonic acid was positively correlated with hostility scores. This and related studies may have clinical implications in terms of either dietary modifications that could be beneficial to people with schizophrenia, or the use of specific polyunsaturated fatty acid supplements among such patients.
Putting It all Together
These 3 studies, each published this year, provide initial evidence that: (1) dietary habits within the general population could potentially influence the manifestation of subclinical, psychotic-like symptoms that are thought to be markers of elevated risk of developing diagnosable psychotic disorders; (2) dietary modification or supplementation could have a role to play as the field continues to pursue preventive interventions aimed at reducing the risk of developing a psychotic disorder among those at especially high risk; and (3) similar dietary modification or supplementation may serve as an adjunctive treatment modality to reduce specific domains of symptoms, such as hostility, among patients diagnosed with schizophrenia and related psychotic disorders. Thus, in these 3 studies alone, there appears to be a convergence of epidemiological findings, "prodromal" research, and clinical studies with individuals with schizophrenia that indicates a beneficial effect of omega-3 polyunsaturated fatty acids, or fish oils.
What do these studies tell us about the state of dietary supplementation for schizophrenia and related psychotic disorders? First, we should be cognizant that the research is still in a relatively nascent state; recommendations for clinical practice are likely premature until additional studies can be conducted. Second, the exact nature of the associations found in these studies requires further research in terms of which polyunsaturated fatty acids are most beneficial, the optimal amount of intake, and the ways in which genetic factors may interact with dietary patterns in the manifestation of psychiatric symptoms. Third, the relations among the effects produced by fish oils and other polyunsaturated fatty acids and antipsychotic medicines remain to be determined; it is unknown whether such supplements will ever serve as replacements for pharmacologic agents, or if they are better thought of as adjunctive to mainstay treatments.
Hedelin M, Löf M, Olsson M, et al. Dietary intake of fish, omega-3, omega-6 polyunsaturated fatty acids and vitamin D and the prevalence of psychotic-like symptoms in a cohort of 33000 women from the general population. BMC Psychiatry. 2010;10:38.
Amminger GP, Schäfer MR, Papageorgiou K, et al. Long-chain w-3 fatty acids for indicated prevention of psychotic disorders: a randomized, placebo-controlled trial. Arch Gen Psychiatry. 2010;67:146-154. Abstract
Watari M, Hamazaki K, Hirata T, Hamazaki T, Okubo Y. Hostility of drug-free patients with schizophrenia and n-3 polyunsaturated fatty acid levels in red blood cells. Psychiatry Res. 2010;177:22-26. Abstract