The n-3 polyunsaturated fatty acid/dopamine hypothesis of schizophrenia.

The dopamine hypothesis of schizophrenia has been the most influential since the 1970s. Normally, the prefrontal dopamine system suppressively controls the limbic dopamine system. Since the activities of prefrontal dopaminergic neurons are reduced in schizophrenia, the suppressive effect of the prefrontal area on the limbic system is reduced, and activities of the limbic dopamine system are enhanced. Reduced activities of the prefrontal dopamine system contribute to negative symptoms and cognitive disorders, and increased activities of the limbic dopamine system induce positive symptoms. While the dopamine hypothesis explains the relationship between dopamine kinetics and psychiatric symptoms in schizophrenia, it is not a direct explanation of its etiology. The cause of the abnormal activities of dopaminergic neurons in schizophrenia and its resultant symptoms are unknown. Since the late 1980s, it has been revealed that the n-3 fatty acid concentration is reduced in the plasma and erythrocyte membranes of schizophrenic patients and that the administration of n-3 fatty acids may be effective for the treatment of schizophrenia. Whether or not n-3 fatty acid deficiency plays a direct role in schizophrenia etiology, and the mechanisms underlying their therapeutic effect have yet to be clarified. Recently, the dopamine hypothesis and n-3 fatty acid hypothesis have been suggested to represent different aspects of the same pathology of schizophrenia. In schizophrenia, the brain concentrations of certain n-3 fatty acids are decreased. In rodents, n-3 fatty acid deficiency has been shown to cause decreases in dopamine concentration, number of vesicles and D2 receptors at prefrontal presynaptic terminals. The following minireview provides a summary of findings from n-3 fatty acid deficient animal models and their relevance to schizophrenia pathology is discussed.