Schizophrenia pink spot

The transmethylation hypothesis depended on the psychosis of mescaline as an example of how methylated compounds similar in structure to the monoamine neurotransmitters could be psychotogenic, and demonstrated how methionine, the precursor of the methyl donor S-adenosylmethionine, could exacerbate the psychotic symptoms of schizophrenia in patients. This theory was fed by studies of the now notorious pink spot, an amine found in paper chromatography of urine extracts from schizophrenics and thought to be 3,4-dimethoxyphenylethylamine (i.e., O-methylated dopamine). Subsequent studies eventually identified this as another compound or compounds, primarily of dietary origin. Another methylated derivative erroneously proposed to be found in higher quantities in schizophrenia was dimethyltryptamine. This compound is similar in structure to LSD, the hallucinogenic nature of which was the key to the serotonin deficiency hypothesis, which proposed that the known antagonism of serotonin (5-HT) by LSD indicated that psychotic disorders such as schizophrenia may result from a hypofunction of 5-HT. 

The story is really about the Pink Spot of Schizophrenia. Many years ago, an observation was made in a biochemical laboratory on the East Coast that stirred up a rolling controversy. It had been found that if the urines of schizophrenic patients (sloppily called schizophrenic urines ) were extracted in such and such a way, and the extracts chromatographed, a pink spot would develop at a particular place on the chromatogram. Well, if this proved to be true with urines of a sick population, and were this proved to be different from the urines of a healthy population, it would constitute an objective diagnosis of schizophrenia. A simple chemical test to confirm a pathology that had defied all efforts to achieve consensus amongst the psychiatrists of the world. 

The only confirmable fact that endured was that the pink spot was due to DMPEA. So a bright spotlight was directed towards its possible role in mental illness. And this expressed itself in the simple question would it produce schizophrenia in a normal subject No. And in a way I am comforted that that did... 

O-methylation of catecholamines was suggested by the reported presence of 3,4-dimethyoxyphenylethylamine (which is structurally very similar to mescaline) in schizophrenic urine [388]. The relationship between this substance, dietary factors and the so-called pink spot detected on urinary chromatograms [389] is somewhat confused. The latter is probably a complex mixture which may or may not contain 3,4-dime thoxyphenylethylamine [163, 390, 391]. Furthermore clear evidence that this substance is either a product of endogenous metabolism or that its excretion is elevated in schizophrenia is lacking [392]. 

Pink was not the only colorful spot associated with schizophrenia. Somewhere at about this same time, a research paper from Canada reported the observation of a mauve spot in the chromatographic analysis of urines of schizophrenic patients. This had nothing to do with DMPEA. I was working closely with a researcher at the psychiatric institute and we were fascinated by, again, a possible diagnostic marker. We assayed the urines of the next 10 patients being admitted as acute schizophrenics. No trace of mauve. We wrote to Canada, and verified the analytical procedure. We were told that the whatzis should have been added after, rather than before, the whosey, and that we should have heated for 30, not 10 minutes. Okay. 

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