Essential fatty acids, lipid membrane abnormalities, and the diagnosis and treatment of schizophrenia

Recent research suggests that deficient uptake or excessive breakdown of membrane phospholipids may be associated with schizophrenia. We review available clinical research on abnormalities in membrane fatty acid composition and metabolism in schizophrenia, and therapeutic trials of fatty acid in this disorder. All potentially relevant English-language articles were identified from the medical and psychiatric literature with the aid of computer searches using key words such as lipids, phospholipids, prostaglandins and schizophrenia. All studies which include human subjects are reviewed. Empirical studies related to membrane hypotheses of schizophrenia focus on: 1) assessment of prostaglandins (PG) and their essential fatty acid (EFA) precursors in the tissues of patients with schizophrenia; 2) evaluation of the niacin flush test as a possible diagnostic marker; 3) evaluation of phospholipase enzyme activity; 4) NMR spectroscopy studies of brain phospholipid metabolism; and 5) therapeutic trials of PG precursors for the treatment of schizophrenia. The most consistent clinical findings include red blood cell fatty acid membrane abnormalities, NMR spectroscopy evidence of increased phospholipid turnover and a therapeutic effect of omega-3 fatty acid supplementation of neuroleptic treatment in some schizophrenia patients. Studies of EFA metabolism have proved fruitful for generating and testing novel etiologic hypotheses and new therapeutic agents for schizophrenia. Greater attention to factors that influence tissue EFA levels such as diet, tobacco and alcohol are required to reconcile inconsistent findings. Treatment studies, although promising, require independent replication.