General Discussion 237 



to ACTH or glucose, at least the same factors were present in both 

 normals and schizophrenics, and from that point of view it doesn't 

 alter our facts. 



Xicolaysen: A long time ago 1 studied these cyclic changes in the 

 urinary composition. Some years later parallel studies were reported in 

 schizophrenics. The results were the same as in normal subjects, never- 

 theless they were interpreted as being due to the schizophrenic state. 



Freeman: As a matter of fact I think that one should have a control 

 day in which one studies this diurnal variation to evaluate the effect of 

 medication. I think that sometimes the ACTH produces much less 

 response than is assimied, 



Nicolaysen: I am returning to my point about controls, because in 

 those days it was maintained that pituitrin influenced tubular re- 

 absorption of fixed bases. However, placing my curves over the curves 

 from the experiments in which pituitrin had been injected showed that 

 the two sets of observations were identical. Obviously your conclusions 

 would not necessarily be invalidated, but they might be somewhat 

 modified. 



Freeman: Yes, I think that has probably not been taken into account 

 sufficiently in all the studies on ACTH. Practically nobody in the 

 American literature has done anything on this. 



Olbrich: I would like to ask if you have any comparative studies as to 

 insulin sensitivity, say with the blood sugar? 



Freeman: None in old schizophrenics. The young schizophrenic 

 patients have on the whole shown some insulin resistance. This was also 

 noted by Meduna, that they drop down to a lesser degree in a given 

 time, if you take rapid intervals, and on the whole they don't show as 

 quick or as great a response to a given dose of insulin as normal 

 individuals do. 



Olbrich: You see the same thing in senile dementias or in any type of 

 neurological lesions with focalizing sites. 



Frec7nan: It is undoubtedly true that reduced glucose tolerance is 

 found in other types of psychosis, because we have studied manic 

 depressives and other kinds, and it may be just a reaction to a psychosis 

 rather than specific to schizophrenia. 



Olbrich: What method did you use for the creatinine tests? 



Rubin: Incubation with sodium hydroxide and determination by 

 colorimeter. It's just a simple determination of creatinine excretion in 

 the urine, as a check on accuracy of collection; we don't give them 

 creatinine. 



Freeman: This ratio is probably not so important in young individuals 

 because the creatinine doesn't vary with the ACTH or glucose, but it 

 certainly does vary in old people. 



Shock: A study is just being completed in our laboratory by Drs. 

 Silverstone and Brandfonbrener, who have been investigating the 

 response of blood sugar to insulin in normal old people. We have found 

 that older individuals uniformly show a reduced response to insulin. In 

 these experiments, a standard amount of insulin was administered 

 intravenously along with 25 g. of glucose also given intravenously. 



