Deficiency in long-chain omega-3 (LCn ？ 3) fatty acids, eicosapentaenoic acid (EPA, 20:5n ？ 3) and docosahexaenoic acid (DHA, 22:6n ？ 3), has been implicated in the pathoetiology of cardiovascular disease, a primary cause of excess premature mortality in patients with schizophrenia (SZ). In the present study, we determined erythrocyte EPA + DHA levels in adult medication-free patients SZ ( ) and age-matched healthy controls ( ). Erythrocyte EPA + DHA composition exhibited by SZ patients (3.5%) was significantly lower than healthy controls (4.5%, ？22%, ). The majority of SZ patients (72%) exhibited EPA+DHA levels ≤4.0% compared with 37% of controls (Chi-square, ). In contrast, the omega-6 fatty acid arachidonic acid (AA, 20:4 ) (+9%, ) and the AA:EPA + DHA ratio (+28%, ) were significantly greater in SZ patients. Linoleic acid (18:2 ) was significantly lower (？12%, ) and the erythrocyte 20:3/18:2 ratio (an index of delta6-desaturase activity) was significantly elevated in SZ patients. Compared with same-gender controls, EPA + DHA composition was significantly lower in male (？19%, ) but not female (？13%, ) SZ patients, whereas the 20:3/18:2 ratio was significantly elevated in both male (+22%, ) and female (+22%, ) SZ patients. These results suggest that the majority of SZ patients exhibit low LCn ？ 3 fatty acid levels which may place them at increased risk for cardiovascular morbidity and mortality. 1. Introduction Patients with schizophrenia (SZ) have two- to three-fold higher mortality rates compared with the general population, corresponding to an average 15-year reduction in life expectancy, and cross-sectional epidemiological studies have found that cardiovascular disease is a primary cause of excess premature mortality in SZ patients [1–6]. The etiology of elevated cardiovascular risk in SZ is likely multifactorial, potentially involving excessive smoking and alcohol use, lack of exercise, and poor diets [7, 8]. Moreover, second generation antipsychotic (SGA) medications are associated with cardiovascular risk factors including dyslipidemia, metabolic syndrome, and weight gain [9–13], though these risk factors have also been reported in SGA-na？ve first-episode SZ patients [14–16]. Together, these data highlight an urgent need to identify risk and resilience factors associated with elevated cardiovascular disease risk in SZ. An emerging body of evidence suggests that low levels of long-chain omega-3 (LCn ？ 3) fatty acids, principally eicosapentaenoic acid (EPA, 20:5n ？ 3) and docosahexaenoic acid (DHA, 22:6n ？ 3), are a modifiable risk factor for
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