Membrane lipid metabolism and redox regulation may be disturbed in schizophrenia. We examined the clinical effect of adding an omega-3 fatty acid and/or vitamins E+C to antipsychotics. It was hypothesized that lower baseline levels of polyunsaturated fatty acids (PUFAs) would predict more benefit from the add-on treatment. The trial had a multicenter, randomized, double-blind, placebo-controlled 2 × 2 factorial design. Patients aged 18–39 years with schizophrenia or related psychoses were consecutively included at admission to psychiatric departments in Norway. They received active or placebo ethyl-eicosapentaenoate (EPA) 2 g day−1 and active or placebo vitamin E 364 mg day−1+vitamin C 1000 mg day−1 (vitamins) for 16 weeks. The main outcome measures were Positive and Negative Syndrome Scale (PANSS) total and subscales scores, analyzed by linear mixed models. Ninety-nine patients were included. At baseline, erythrocyte PUFA were measured in 97 subjects. Given separately, EPA and vitamins increased drop-out rates, whereas when combined they did not differ from placebo. In low PUFA patients, EPA alone impaired the course of total PANSS (Cohen's d=0.29; P=0.03) and psychotic symptoms (d=0.40; P=0.003), especially persecutory delusions (d=0.48; P=0.0004). Vitamins alone impaired the course of psychotic symptoms (d= 0.37; P=0.005), especially persecutory delusions (d=0.47; P=0.0005). Adding vitamins to EPA neutralized the detrimental effect on psychosis (interaction d=0.31; P=0.02). In high PUFA patients, there were no significant effects of trial drugs on PANSS scales. In conclusion, given separately during an acute episode, EPA and vitamins E+C induce psychotic symptoms in patients with low levels of PUFA. Combined, these agents seem safe.

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BackgroundAlterations in serum and membrane lipids may be involved in schizophrenia pathophysiology. It is not known whether lipid profiles are associated with disease severity or current symptom level.MethodsClinical and lipid data were gathered from 55 patients with schizophrenia admitted to psychiatric emergency wards in an acute stage of the disease (T1). The patients were re-examined after 5 years at a stable phase (T2). The clinical assessments included Positive and Negative Syndrome Scale (PANSS total, positive, negative) and Global Assessment of Functioning (GAF S, symptom and F, function). Serum lipids (cholesterol and triglyceride) and membrane polyunsaturated fatty acids (PUFA, LCPUFA) were measured. Healthy controls were recruited among hospital workers.ResultsSerum triglyceride was significantly higher in patients with schizophrenia compared to healthy controls both at T1 and T2 (p < 0.001), while serum cholesterol did not differ significantly. The levels of serum lipids in patients remained stable over time. At T1, serum lipids and symptoms were not significantly correlated. At T2, higher serum lipids were associated with more severe symptoms and poorer functioning. Higher serum lipid levels at T1 were associated with more severe symptoms and poorer functioning at T2; cholesterol with GAF-S (p < 0.05), triglyceride with PANSS total (p < 0.05), GAF-S (p < 0.01) and GAF-F (p < 0.01). Membrane lipids were significantly lower in the patient group compared to healthy controls at T1 (PUFA p < 0.001, LCPUFA p < 0.001), but not at T2. Membrane lipids were not significantly correlated with symptoms at T1, but significantly associated with negative symptoms and functioning at T2 as previously reported.ConclusionsThe present findings suggest different roles of membrane and serum lipids in schizophrenia pathophysiology. To further elucidate the relation of lipid biology to disease traits, replication in independent studies of longitudinal samples are warranted.

Inpatients in long term psychosis treatment wards have alarmingly high cardiometabolic risk. Level of physical activity was associated with both psychiatric and somatic health. Focus on lifestyle and somatic health should be an integral part of the treatment for hospitalized SMI patients.