Omega-3 fatty acid deficiency: a preventable risk factor for schizophrenia?

Epidemiological and monozygotic twin studies indicate that the risk for developing schizophrenia is conferred equally by genetic and environmental factors. While the search for genes that increase susceptibility for schizophrenia has been a focus of recent researchefforts, similar efforts need tobemade to identify environmental risk factors, particularly those that are amenable to modification. A body of evidence has emerged over the past 30 years that has implicated a dysregulation in polyunsaturated fatty acid (PUFA) homeostasis in the pathophysiology and treatment of schizophrenia (McNamara, 2009). PUFAs are lipid family comprised of both omega-3 and omega-6 fatty acids, and PUFA status is governed by both genetic (fatty acid desaturase and elongase genes) and environmental (dietary intake) factors. Long-chain PUFAs, including docosahexaenoic acid (22:6n−3) and arachidonic acid (20:4n−6), are both essential for normal brain development (McNamara and Carlson, 2006), and longchainPUFAdeficiencies are frequentlyobserved in schizophrenic patients. While these and other data suggest that ‘PUFA deficiency’ is a risk marker for schizophrenia, its status as a risk factor has remaineduncertain. A risk factor, unlike a riskmarker, implies a causal link with the disease/disorder, correction of which reduces the risk of developing the disease/disorder. Multiple criteria, including prediction, consistency, response to treatment, dose–response, specificity, and biological plausibility, have been established to evaluate the validity of a risk factor (Hill, 1965). The recent findings of Amminger et al. (2010) provide three critical, previously missing, pieces of evidence that are directly relevant to the evaluationof omega-3 fatty acid deficiency as a ‘risk factor’ for schizophrenia. First, this study demonstrates that adolescents at ultrahigh risk for developing psychosis (i.e., subsyndromal symptoms and having a biological parent with schizophrenia) exhibit low erythrocyte levels of two principal long-chain omega-3 fatty acids, eicosapentaenoic acid (EPA, 20:5n−3) and DHA (22:6n−3), prior to psychosis onset. Specifically, mean erythrocyte EPA+DHA composition (termed the ‘omega-3 index’) was 3.1%, a value that is approximately 40% lower than that observed in healthy adolescents (Jakobik