Abstract.

Schizophrenia is a psychiatric disease with devastating effects for both patient, relatives and society. The cause of the disease is still not known. Medical treatment is usually aimed on reducing the effects of dopamine. This is only a symptomatic treatment, the disease process itself is not influenced. In schizophrenia a hyperactive dopamine system has been found. In healthy people glutamate plays a role as regulator of dopamine; if there are enough NMDA-glutamate receptors there will not be a hyperactive dopamine system. The NR1 protein is an essential component of this receptor. In patients with schizophrenia there is a shortage in the mRNA that codes for this protein. The reason thereof is not known. Among the possible causes of schizophrenia three factors can be mentioned that surely play a role. These are: infection with the herpes simplex virus, hormonal influences, and abnormalities in the metabolism of fatty acids. In this study we will show how this three factors are interrelated in a process-chain in which things go wrong. These together might explain the pathophysiology of schizophrenia. The first step is in the metabolism of the omega 3 and -6 fatty acids. These are not transported on the proper way to the brain, due to a low level of the apolipoprotein A-IV. This causes the level of these fatty acids in the blood and neurons to be decreased. Second step: the tiny amount of fatty acids that nevertheless is transported in the blood arrives at the brain, where they have to pass the blood-brain-barrier, and this passage is hampered by a shortage of caveolin-1. This will lead to a low level of both free cholesterol and cholesteryl esters inside the neuron, and thus the permeability of the membranes of the neuron increases. Third step: this increased permeability enables the microglia to attack the herpes simplex virus that lies ‘dormant’ within the neuron. A part of the virus resembles a component of the DNA of the neuron. This leads to the hypothesis that antibodies of the microglia not only attack the virus, but also the own DNA of the neuron, thus hampering the production of the mRNA needed for the production of the NR1 protein of the glutamate receptor. 

Key words: Schizophrenia, glutamate, omega 3 and - 6 fatty acids, apolipoproteins, caveolin, herpes simplex virus.  Nieuwe alinea