Synergist for serotonin present in schizophrenic blood.

During an investigation of the serotonin content of normal and schizophrenic blood sera, it was observed that many sera from severely schizophrenic patients contained a substance which augmented the response (contraction) of the isolated rat uterus to serotonin. Doses of serotonin which were too small to cause a contraction of the uterus by themselves did so when dilutions of these sera were added. Dilutions of the sera as great as 1: 1,000 or even, in some cases, as great as 1: 10,000 produced the synergism to serotonin so that it was plain that the effect was not due to excessive amounts of serotonin in the schizophrenic sera (see Table 1). Furthermore, dilutions of the sera themselves caused no contraction, and dialysis of the sera or treatment with acetone effectively removed serotonin without loss of the synergist. These experiments showed again that the effects observed were not to be explained on the basis of excess serotonin in the sera from schizophrenic patients. Sera from normal human beings also contained some of the synergist but the amount present in normal tissue was much less than in sera from many schizophrenic patients. For example, the synergistic activity of most normal sera vanished at a dilution of about 1:100, whereas, as just stated, a good schizophrenic serum could be shown to contain synergist at a dilution of 1:10,000. Normal rat brain also contained the synergist, and from that tissue it could be obtained by extraction with a mixture of chloroform and methanol, and it passed into the aqueous phase when such an extract was mixed with one fifth of its volume of water as in the Folch method" 2for the isolation of gangliosides. Because it was believed that this synergist might possibly have some relationship to the symptomatology of schizophrenia, an effort was made to purify it and to learn something of its chemical nature. The present paper was designed to report some of the findings. The synergist appeared to be a ganglioside because it was soluble in a mixture of 2:1 chloroform-methanol (hence not a protein), because aqueous solutions of it were stable to boiling or to digestion with proteolytic enzymes such as trypsin and chymotrypsin, and because the substance was destroyed by digestion with neuraminidase.