Polyunsaturated fatty acid supplementation for schizophrenia
ABSTRACT Limited evidence supports a hypothesis suggesting that schizophrenic symptoms may be the result of altered neuronal membrane structure and metabolism. The structure and metabolism is dependent on blood plasma levels of certain essential fatty acids and their metabolites.
To review the effects of polyunsaturated fatty acids for people with schizophrenia.
We have updated the initial searches of 1998 and 2002 (Cochrane Schizophrenia Group's Register, July 2005), and where necessary, we contacted authors and relevant pharmaceutical companies.
We included all randomised clinical trials of polyunsaturated fatty acid treatment for schizophrenia.
Working independently, we selected studies for quality assessment and extracted relevant data. We analysed on an intention-to-treat basis. Where possible and appropriate we calculated the Relative Risk (RR) and their 95% confidence intervals (CI) and estimated the number needed to treat (NNT). For continuous data we calculated weighted mean differences (WMD) and their 95% confidence intervals. We also inspected the data for heterogeneity.
When any dose omega-3 (E-EPA or EPA) is compared with placebo, small short trials suggest that the need for neuroleptics appears to be reduced for people allocated omega-3 supplementation (n=30, 1 RCT, RR 0.73 CI 0.54 to 1.00) and mental state may improve (n=30, 1 RCT, RR not gaining 25% change in PANSS scores 0.54 CI 0.30 to 0.96, NNT3 CI 2-29). There are no differences in the number of people leaving the study early (n=271, 4 RCTs, RR 0.91 CI 0.36 to 2.33). There are few data on the comparison of any dose omega-6 (GLA) with placebo. For movement disorder outcomes, the only small study we found does not show any difference for average short-term endpoint AIMS score (n=16, 1 RCT, MD 1.30 CI -1.96 to 4.56). When any dose omega 3 (E-EPA or EPA) is compared with any dose omega-3 (DHA) there is no clear difference for mental state outcome of not gaining 25% change in PANSS scores (n=31, 1 RCT, RR 0.66 CI 0.39 to 1.11). When different doses of omega-3 (E-EPA) are compared with placebo there are no differences in measures of global and mental state between the studies. For the outcome of 'experiencing at least one adverse effect' no differences between groups are found for any dose (1g/day E-EPA vs placebo n=63 1 RCT, RR 0.97 CI 0.60 to 1.56; 2g/day E-EPA vs placebo n=63 1 RCT, RR 0.67 CI 0.37 to 1.20; 4g/day E-EPA vs placebo n=58, 1 RCT, RR 1.15 CI 0.72 to 1.82).
Two updates of this review have resulted in more included studies but relatively little useful additional data. The results remain inconclusive. The new trials all compare the omega-3 polyunsaturated fatty acids, in particular eicosapentaenoic acid and its ester, ethyl-eicosapentaenoic acid. The use of omega-3 polyunsaturated fatty acids for schizophrenia still remains experimental and this review highlights the need for large well designed, conducted and reported studies.
SourceAvailable from: Roel J T Mocking[Show abstract] [Hide abstract]
ABSTRACT: Objective Cardiovascular disease (CVD) is the leading cause of death in severe psychiatric disorders (depression, schizophrenia). Here, we provide evidence of how the effects of oxidative stress on fatty acid (FA) and one-carbon (1-C) cycle metabolism, which may initially represent adaptive responses, might underlie comorbidity between CVD and psychiatric disorders.Method We conducted a literature search and integrated data in a narrative review.ResultsOxidative stress, mainly generated in mitochondria, is implicated in both psychiatric and cardiovascular pathophysiology. Oxidative stress affects the intrinsically linked FA and 1-C cycle metabolism: FAs decrease in chain length and unsaturation (particularly omega-3 polyunsaturated FAs), and lipid peroxidation products increase; the 1-C cycle shifts from the methylation to transsulfuration pathway (lower folate and higher homocysteine and antioxidant glutathione). Interestingly, corresponding alterations were reported in psychiatric disorders and CVD. Potential mechanisms through which FA and 1-C cycle metabolism may be involved in brain (neurocognition, mood regulation) and cardiovascular system functioning (inflammation, thrombosis) include membrane peroxidizability and fluidity, eicosanoid synthesis, neuroprotection and epigenetics.Conclusion While oxidative-stress-induced alterations in FA and 1-C metabolism may initially enhance oxidative stress resistance, persisting chronically, they may cause damage possibly underlying (co-occurrence of) psychiatric disorders and CVD. This might have implications for research into diagnosis and (preventive) treatment of (CVD in) psychiatric patients.Acta Psychiatrica Scandinavica 03/2014; DOI:10.1111/acps.12265 · 4.86 Impact Factor
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ABSTRACT: Un nuevo enfoque para comprender los trastornos mentales graves, como la esquizofrenia, consiste en adoptar un modelo de estadios clínicos. Un modelo de este tipo define el grado de la enfermedad, de tal manera que los fenómenos más tempranos y más leves se diferencian de las manifestaciones más tardías y que causan un mayor deterioro. Concretamente, un modelo de estadios clínicos hace tres predicciones clave. En primer lugar, los parámetros patológicos deben ser más anormales en los estadios más graves. En segundo lugar, los pacientes que presentan una progresión del estadio deben mostrar un cambio en esos mismos parámetros patológicos. Por último, en los estadios más tempranos el tratamiento debe ser más eficaz, así como más benigno. En este artículo revisamos la evidencia existente respecto a estas tres predicciones en los estudios de trastornos psicóticos, centrándonos en los datos de neuroimagen. En los tres casos, el conjunto de la evidencia respalda las predicciones del modelo de estadios. Sin embargo, existen diversas explicaciones alternativas para estas observaciones, entre ellas los efectos de la medicación y la heterogeneidad de los síntomas.07/2011; 18(3):117-123. DOI:10.1016/j.psiq.2011.10.003
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ABSTRACT: This study aimed to investigate polyunsaturated (PUFA) and trans isomeric fatty acid status in schizophrenia patients. Fatty acid composition of plasma phospholipids (PL) and triacylglycerols (TG) was analyzed by gas chromatography in 29 schizophrenia patients and 15 healthy controls. We found no difference in PL n-3 fatty acid status between the two groups, while the values of 22:5n-6 were significantly higher in patients with schizophrenia than in controls. In TG, values of docosatrienoic acid (20:3n-3) and docosapentaenoic acid (20:5n-3) were significantly higher in schizophrenia patients than in controls. We found no difference in the trans fatty acid status between patients and controls. In smoking schizophrenia patients significant negative correlations were detected between Wechsler adult full-scale intelligence quotients and values of total trans fatty acids in PL lipids, whereas no such correlation was seen either in non-smoking schizophrenia patients, or in healthy controls. While data obtained in the present study fail to furnish evidence for n-3 PUFA supplementation to the diet of patients with schizophrenia, they indicate that in smoking schizophrenia patients high dietary exposure to trans fatty acids is associated with lower intelligence quotients.10/2013; 215(1). DOI:10.1016/j.psychres.2013.10.011