Transmethylation Processes in Schizophrenia

It is generally agreed today that the etiology of schizophrenia is compounded of a genetically determined predisposition, in the form of some vulnerable enzyme system or systems in the brain possibly concerned with reactions to stress, together with various environmental factors that determine whether the genotype is actually expressed as the phenotype. There is very little information, however, on what the biochemical lesion is, and only a handful of hypotheses about what the lesion could be. The so-called transmethylation hypothesis is based on the observation made in 1950 by Harley-Mason, Osmond, and Smythies that mescaline is an O-methyl derivative of dopamine. Many other psychotomimetic drugs have been discovered since then, and most of these are either O-methyl, or N-methyl (or both) derivatives of the central neurotransmitters, noradrenaline, dopamine and serotonin.