Omega-3 fatty acids reduce cardiometabolic risk in first-episode schizophrenia patients treated with antipsychotics: Findings from the OFFER randomized controlled study.

Metabolic syndrome (MetS) increases the risk of premature mortality observed in schizophrenia (SCZ). N-3 polyunsaturated fatty acid (PUFA) deficiency has been reported in different stages of schizophrenia. N-3 PUFA supplementation was found to be beneficial in both chronic SCZ and MetS. No intervention studies based on n-3 PUFA as add-on therapy to antipsychotics have examined the changes in MetS risk in first-episode schizophrenia. AIM: This randomized placebo-controlled trial assesses the effect of a 26-week intervention composed of either 2.2 g/day of n-3 PUFA or olive oil placebo on the frequency of MetS and the changes in its constituents as a secondary outcome measure. METHODS: Seventy-one adult inpatients diagnosed with first-episode schizophrenia were randomly assigned to study groups. The active intervention used a 3:2 mixture of eicosapentaenoic (EPA) and docosahexaenoic (DHA) acids. Metabolic syndrome components were monitored throughout the study. RESULTS: A significant reduction in the frequency of MetS was observed in the EPA + DHA group (p = 0.0408); as well as some specific MetS components: e.g., a decrease in fasting blood glucose (p = 0.045). The beneficial effects of EPA + DHA were even more pronounced in patients treated mainly with olanzapine, e.g. significant reductions of total cholesterol (p = 0.037) and blood glucose levels (p = 0.034). Significant positive correlations were found between the general psychopathology subscale of PANSS (primary outcome) and triglyceride level changes. CONCLUSION: N-3 PUFA supplementation in early SCZ may constitute a safe and affordable intervention that can reduce the risk of MetS and its lethal complications.

An increase in plasma brain derived neurotrophic factor levels is related to n-3 polyunsaturated fatty acid efficacy in first episode schizophrenia: secondary outcome analysis of the OFFER randomized clinical trial.

RATIONALE: N-3 polyunsaturated fatty acids (n-3 PUFA) influence multiple biochemical mechanisms postulated in the pathogenesis of schizophrenia that may influence BDNF synthesis. OBJECTIVES: A randomized placebo-controlled study was designed to compare the efficacy of a 26-week intervention composed of either 2.2 g/day of n-3 PUFA or olive oil placebo, with regard to symptom severity in first-episode schizophrenia patients. The secondary outcome measure of the study was to describe the association between n-3 PUFA clinical effect and changes in peripheral BDNF levels. METHODS: Seventy-one patients aged 16-35 were enrolled in the study and randomly assigned to the following study arms: 36 to the EPA + DHA group and 35 to the placebo group. Plasma BDNF levels were assessed three times, at baseline and at weeks 8 and 26 of the intervention. BDNF levels were determined in plasma samples using Quantikine Human BDNF ELISA kit. Plasma BDNF level changes were further correlated with changes in the severity of symptoms in different clinical domains. RESULTS: A significantly greater increase in plasma BDNF levels was observed in the intervention compared to the placebo group (Cohen's d = 1.54). Changes of BDNF levels inversely correlated with change in depressive symptoms assessed using the Calgary Depression Rating Scale in Schizophrenia (Pearson's r = - 0.195; p = 0.018). CONCLUSIONS: The efficacy of a six-month intervention with n-3 PUFA observed in first-episode schizophrenia may be related to an increase in BDNF levels, which may be triggered by the activation of intracellular signaling pathways including transcription factors such as cAMP-reactive element binding protein.

Telomerase level increase is related to n-3 polyunsaturated fatty acid efficacy in first episode schizophrenia: Secondary outcome analysis of the OFFER randomized clinical trial.

Schizophrenia is associated with shortening of the lifespan mainly due to cardiovascular events, cancer and chronic obstructive pulmonary disease. Both telomere attrition and decrease of telomerase levels were observed in schizophrenia. Polyunsaturated fatty acids (PUFA) influence multiple biochemical mechanisms which are postulated to accelerate telomere shortening and limit the longevity of patients with schizophrenia. Intervention studies based on add-on therapy with n-3 polyunsaturated fatty acids (n-3 PUFA) in patients with schizophrenia did not assess the changes in telomerase levels. A randomized placebo-controlled trial named OFFER was designed to compare the efficacy of a 26-week intervention composed of either 2.2g/day of n-3 PUFA or olive oil placebo with regard to symptom severity in first-episode schizophrenia patients. The secondary outcome measure of the study was to describe the association between the clinical effect of n-3 PUFA and changes in telomerase levels. Seventy-one patients aged 16-35 were enrolled in the study and randomly assigned to the study arms. The Positive and Negative Syndrome Scale (PANSS) was used to assess the change in symptom severity. Telomerase levels of peripheral blood mononuclear cells (PBMC) were assessed at three points: at baseline and at weeks 8 and 26 of the intervention. A significantly greater increase in PBMC telomerase levels in the intervention group compared to placebo was observed (p<0.001). Changes in telomerase levels significantly and inversely correlated with improvement in depressive symptoms and severity of the illness. The efficacy of a six-month intervention with n-3 PUFA observed in first-episode schizophrenia may be related to an increase in telomerase levels.

Omega-3 fatty acid supplementation may prevent loss of gray matter thickness in the left parieto-occipital cortex in first episode schizophrenia: A secondary outcome analysis of the OFFER randomized controlled study.

The aim of the study was to assess changes in cortical thickness related to the use of n-3 polyunsaturated fatty acids (PUFA) as add-on therapy in patients with first episode schizophrenia. A double-blind randomized controlled study was conducted using a 26-week intervention composed of concentrated fish oil containing 2.2g/d of eicosapentaenoic (EPA) and docosahexaenoic acid (DHA) or placebo (olive oil). Participants underwent MRI scanning twice to assess changes in cortical thickness: at the beginning and at the end of intervention. Data of suitable quality was obtained from 29 participants. The T1-weighted images for each participant were analyzed using FreeSurfer methodology for longitudinal pipeline. Significant differences in cortical thickness loss were observed between the groups in the parieto-occipital regions of Brodmann areas 7 and 19 of the left hemisphere, dysfunctions in which may be involved in schizophrenia symptomatology. The results of the study support the previous observations carried out in older individuals and patients with mild cognitive impairment, indicating that n-3 PUFA may have neuroprotective properties, especially at early stages of neurodegenerative diseases, such as schizophrenia. If replicated, the results of the present study may encourage clinicians to consider n-3 PUFA as a promising addition to antipsychotics for long-term treatment of schizophrenia.

A randomized controlled study of the efficacy of six-month supplementation with concentrated fish oil rich in omega-3 polyunsaturated fatty acids in first episode schizophrenia.

Short-term clinical trials of omega-3 polyunsaturated fatty acids (n-3 PUFA) as add-on therapy in patients with schizophrenia revealed mixed results. The majority of these studies used an 8- to 12-week intervention based on ethyl-eicosapentaenoic acid. A randomized placebo-controlled trial was designed to compare the efficacy of 26-week intervention, composed of either 2.2 g/day of n-3 PUFA, or olive oil placebo, with regard to symptom severity in first-episode schizophrenia patients. Seventy-one patients (aged 16-35) were enrolled in the study and randomly assigned to the study arms. The primary outcome measure of the clinical evaluation was schizophrenia symptom severity change measured by the Positive and Negative Syndrome Scale (PANSS). Mixed models repeated measures analysis revealed significant differences between the study arms regarding total PANSS score change favouring n-3 PUFA (p = 0.016; effect size (ES) = 0.29). A fifty-percent improvement in symptom severity was achieved significantly more frequently in the n-3 PUFA group than in the placebo group (69.4 vs 40.0%; p = 0.017). N-3 PUFA intervention was also associated with an improvement in general psychopathology, measured by means of PANSS (p = 0.009; ES = 0.32), depressive symptoms (p = 0.006; ES = 0.34), the level of functioning (p = 0.01; ES = 0.31) and clinical global impression (p = 0.046; ES = 0.29). The findings suggest that 6-month intervention with n-3 PUFA may be a valuable add-on therapy able to decrease the intensity of symptoms and improve the level of functioning in first-episode schizophrenia patients.

Telomere length in blood cells is related to the chronicity, severity, and recurrence rate of schizophrenia.

INTRODUCTION: Telomere shortening is strongly associated with higher mortality rates and has been shown in a number of age-related diseases, such as cardiovascular disorders, diabetes mellitus, Alzheimer's disease, and psychiatric disorders. Oxidative stress is known to induce DNA breaks and genome instability. Telomeric DNA rich in guanosine is particularly sensitive to such oxidative damages. Psychosis is associated with a disequilibrium between free radical production and antioxidative defense. Although telomere attrition has been demonstrated in schizophrenia, no relationship has been reported between telomere length and severity of schizophrenia. AIM: The aim of the present study was to identify differences in telomere length in peripheral blood cells between patients with chronic schizophrenia (C-SCZ) and early schizophrenia (E-SCZ) and to identify any relationship between telomere length and disease chronicity and severity. METHODS: Relative average telomere lengths were determined using qPCR assay in patients with E-SCZ (n=42) and C-SCZ (n=44) hospitalized due to schizophrenia exacerbation. E-SCZ was diagnosed when less than 2 years had passed since the beginning of psychotic symptoms. The severity of symptoms was assessed using appropriate scales. RESULTS: The severity of schizophrenia symptoms, as well as the number of psychotic episodes and hospital admissions, correlated significantly with telomere length in univariate analyses. Regression analysis revealed that a model incorporating study group (E-SCZ or C-ECZ), sex, and age, as well as the combined number of documented psychotic episodes and hospital admissions, can significantly predict the length of telomeres in patients with schizophrenia, with over 50% of variance in telomere length explained by the model (adjusted R (2)=0.512). CONCLUSION: The results of the current study indicate that the recurrence of psychotic symptoms as well as their intensity and chronicity may be correlated with telomere attrition, which is well known to contribute to the development of premature senescence and age-related diseases.