[The n-3 fatty acid/dopamine hypothesis in schizophrenia].
The dopamine hypothesis of schizophrenia has been 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 cause negative symptoms and cognitive disorders, and the increased activity of the limbic dopamine system induces positive symptoms. While the dopamine hypothesis explains the relationship between intracranial dopamine kinetics and psychiatric symptoms in schizophrenia, it is not a direct explanation of its etiology. The cause of the activities of dopaminergic neurons in schizophrenia and the resultant symptoms are unknown. n-3 Fatty acids are not synthesized in the human body and are called "essential fatty acids". 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 is effective for the treatment of schizophrenia. However, how n-3 fatty acid deficiency induces psychiatric symptoms remains unclear, and the mechanism of the therapeutic effect of n-3 fatty acids has not been 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 inactivation of phospholipase A2 causes an excessive depletion of essential fatty acids from the Sn2 position of cell membrane phospholipids, and the brain concentrations of essential fatty acids decrease. This causes decreases in dopamine vesicles, dopamine concentration, and D2-receptors at prefrontal presynaptic terminals. The reduced activity of dopaminergic neurons in the prefrontal area induce negative symptoms and cognitive disorders. Furthermore, as the suppression of activities in the limbic dopamine system by the prefrontal area is reduced, the dopamine concentration and D2-receptors increase in the striate body. As a result, the hyperactivity of the limbic dopamine system induces positive symptoms. The administration of antipsychotics and n-3 fatty acids act on different points in this etiological cascade.
Ohara
Koichi
K
Department of Psychiatry, National Hospital Organization, Nagoya Medical Center, Japan. kohara@nnh.hosp.go.jp
D004298:Dopamine / Q000378:metabolism*; D015525:Fatty Acids, Omega-3 / Q000378:metabolism* / Q000494:pharmacology; D010741:Phospholipases A / Q000378:metabolism; D054467:Phospholipases A2; D017397:Prefrontal Cortex / Q000378:metabolism; D012559:Schizophrenia / Q000209:etiology* / Q000378:metabolism
D015525:Fatty Acids, Omega-3; D010741:Phospholipases A; D054467:Phospholipases A2; D004298:Dopamine