Adult medication-free schizophrenic patients exhibit long-chain omega-3 Fatty Acid deficiency: implications for cardiovascular disease risk

Abstract

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 (n = 20) and age-matched healthy controls (n = 24). Erythrocyte EPA + DHA composition exhibited by SZ patients (3.5%) was significantly lower than healthy controls (4.5%, -22%, P = 0.007). The majority of SZ patients (72%) exhibited EPA+DHA levels ≤4.0% compared with 37% of controls (Chi-square, P = 0.001). In contrast, the omega-6 fatty acid arachidonic acid (AA, 20:4n - 6) (+9%, P = 0.02) and the AA:EPA + DHA ratio (+28%, P = 0.0004) were significantly greater in SZ patients. Linoleic acid (18:2n - 6) was significantly lower (-12%, P = 0.009) 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%, P = 0.04) but not female (-13%, P = 0.33) SZ patients, whereas the 20:3/18:2 ratio was significantly elevated in both male (+22%, P = 0.008) and female (+22%, P = 0.04) 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.

Figure 1

Comparison of the 20:63/18:2 ratio, an index of delta6-desaturase activity (a), the 20:4/20:3 ratio, an index of delta5-desaturase activity (b), and the 16:1/16:0 (c) and 18:1/18:0 (d) ratios, indices of delta9-desaturase activity, in healthy controls (HC, n = 24) and SZ patients (n = 18). Values are group mean ± SEM. **P ≤ 0.001 versus healthy controls.

Figure 2

The erythrocyte Omega-3 Index (EPA + DHA) (a), the ratio of arachidonic acid (20:4n − 6) to the Omega-3 Index (EPA + DHA) (b), and the 20:3/18 ratio, an index of delta6-desaturase activity (c), in female and male and healthy controls (HC) and SZ patients. Values are group means ± SEM. *P ≤ 0.05, **P ≤ 0.01 versus same-gender healthy controls.

Figure 3

(a) The percentage of healthy controls (37%) and SZ patients (72%) with an omega-3 index (EPA + DHA) of ≤4.0%. (b) Comparison of the omega-3 index in adult SZ patients residing in the USA (present study), adult US patients with acute coronary syndrome (ACS, n = 768, from [26]), healthy adults (HA) residing in the USA (n = 163, from [23]), and healthy adults residing in Japan (n = 456; from [24]). Proposed risk zones for sudden cardiac death (SCD) derived from prior prospective longitudinal evidence [25] are indicated **P = 0.001 (Chi-Square).