Polyunsaturated fatty acids, schizophrenia

Finally, an intriguing possible future therapy arises from a radical idea of Horrobin (2001) that schizophrenia is a nutritional disorder linked to a decreased intake of essential polyunsaturated fatty acids. Recent 31P-MRS studies have shown changes in plasma membrane phospholipids in the neocortex of unmedicated schizophrenics, which would have deleterious consequences on synaptic neurotransmission (Fukuzako, 2001). A clinical trial with the co6 fatty acid derivative ethyleicosa-pentaenoic acid (LAX-101) in patients who had been unresponsive to clozapine, reported that a daily dose of 2g LAX-101 gave a 26% improvement in symptoms over 12 weeks compared with 6% with placebo (Peet and Horrobin, 2001). Maybe in... 

Such imbalanced antioxidant systems in schizophrenia could lead to oxidative stress- and ROS-mediated injury as supported by increased lipid peroxidation products and reduced membrane polyunsaturated fatty acids (PUFAs). Decrease in membrane phospholipids in blood cells of psychotic patients (Keshavan et al., 1993 Reddy et al., 2004) and fibroblasts from drug-naive patients (Mahadik et al., 1994) as well as in postmortem brains (Horrobin et al., 1991) have indeed been reported. It has also been suggested that peripheral membrane anomalies correlate with abnormal central phospholipid metabolism in first-episode and chronic schizophrenia patients (Pettegrewet al., 1991 Yao et al., 2002). Recently, a microarray and proteomic study on postmortem brain showed anomalies of mitochondrial function and oxidative stress pathways in schizophrenia (Prabakaran et al., 2004). Mitochondrial dysfunction in schizophrenia has also been observed by Ben-Shachar (2002) and Altar et al. (2005). As main ROS producers, mitochondria are particularly susceptible to oxidative damage. Thus, a deficit in glutathione (GSH) or immobilization stress induce greater increase in lipid peroxidation and protein oxidation in mitochondrial rather than in cytosolic fractions of cerebral cortex (Liu et al., 1996). 

Reddy RD, Keshavan MS, Yao JK. 2004. Reduced red blood cell membrane essential polyunsaturated fatty acids in first episode schizophrenia at neuroleptic-naive baseline. Schi-zophr Bull 30 901-911. 

Das UN. Can perinatal supplementation of long-chain polyunsaturated fatty acids prevents schizophrenia in adult life Med. Sci. Monit. 2004 10 HY33-HY37. 

Ranjekar PK, Hinge A, Hegde MV, Ghate M, Kale A, Sitasawad S, et al. Decreased antioxidant enzymes and membrane essential polyunsaturated fatty acids in schizophrenia and bipolar mood disorder patients. Psychiatry Res. 2003 121 109-122. 

Peet M, Mellor J. Double blind placebo controlled trial of n-3 polyunsaturated fatty acids as an adjunct to neuroleptics. 9th Schizophrenia Winter Workshop, Davos Switzerland, 1998. 

Peet M. New strategies for the treatment of schizophrenia omega-3 polyunsaturated fatty acids. In Peet M, Glen I, Horrobin DF. (eds.), Phospholipid Spectrum Disorder in Psychiatry. Marius, Camforth, UK, 1999, pp. 189-192. 

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