ESSENTIAL FATTY-ACIDS IN THE TREATMENT OF SCHIZOPHRENIA

Neuroleptics have been used to treat psychosis in schizophrenia for ov er 40 years. Unfortunately, this treatment has consistently been found to have severe side effects, becomes less effective in later years, a nd overall cognitive performance of the majority of patients continues to decline over time. Since the etiology of schizophrenia is unknown, and its pathophysiology is heterogeneous and psychopathology is varia ble, there is no standard treatment. This has made it necessary to dev elop alternative ways of treatment that will improve the course and ou tcome of the illness without serious side effects. It is generally acc epted that the abnormal neurodevelopment as well as the multitransmitt er dysfunctions are associated with the psychopathophysiology of schiz ophrenia. Since several etiopathogenetic theories have been proposed f or schizophrenia, the biochemical basis of abnormal neurodevelopment m ay be complex. Based on the dopamine receptor blocking activity of neu roleptics, dopamine dysfunction has been implicated in the pathophysio logy of schizophrenia. However, a large number of psychopharmacologica l studies indicate a multitransmitter dysfunction. Recently, a common defect in neurotransmitter signal transduction, particularly the gener ation of second messengers derived from membrane phospholipids (e.g., inositol polyphosphates, IPs; diacyl glycerol, DAG; arachidonic acid, AA), has been suggested in schizophrenia. Since the phospholipid metab olism is altered in schizophrenia, even at or before the onset of psyc hosis, it may contribute to the proposed abnormal neurodevelopment as well as altered signal transduction. Evidence is increasing to support this hypothesis. Neuronal plasma membrane phospholipids are preferent ially enriched in essential polyunsaturated fatty acids (EPUFAs). EPUF As are synthesized from dietary essential fatty acids (EFAs) and there fore the availability of EFAs determines the quality and quantity of b rain phospholipids. This makes the brain selectively dependent on the availability of EFAs throughout life. Dietary EFA supplementation has been shown to correct the alterations in membrane phospholipids as wel l as the defective brain development and neurotransmitter receptor-med iated signal transduction in animals. Initial clinical studies and epi demiological evidence suggest that treatment with appropriate EFAs fro m the onset of psychosis or even earlier in high risk subjects may cor rect neurodevelopmental as well as neurotransmitter functions and thus improve the course and outcome of schizophrenia. This treatment at th erapeutic doses has no side effects. However, since neuroleptics are s till the drugs of choice for the control of psychosis, EFA supplementa tion can only be done as an adjunctive treatment. The improved outcome of schizophrenia may help to substantially reduce the costs of lifeti me treatment and management and also improve the quality of lives of p atients and their family.