The Transmethylation Hypothesis Jan Trnka 2nd February 2009 Once these investigations have been done our hypothesis will either join the large number of plausible theories which have failed to stand up to the test of experiment and are now to be found on the scrap-heap of psychiatry in the pages of old journals, or the cause of schizophrenia will be known. O smond and S mythies , 1952 1 Introduction In the 20th century our understanding of mental illness and psychosis in particular underwent major developments: description of schizophrenia as a separate disorder, advent of first effective therapies (insulin shocks, electroconvulsive therapy, neuroleptics, antidepressants) and formulation of a multitude of scientific hypothesis of their causes and pathogenesis. The 20th century also witnessed the penetration of psychiatry from hidden asylums into everyday cultural and political life: creation of psy- choanalysis, abuses of psychiatry by the Nazi and communist regimes, ‘psychedelic revolution’ of the 1960s and the Prozac phenomenon are among the most important events in this respect. The topic of this paper is a hypothesis of the pathogenesis of schizo- phrenia suggested in the early 1950s, the first to propose a specific biochem- ical disorder as the cause of the disease. The transmethylation hypothesis ( tmh), as it was called, is now mostly forgotten and has lost most of its scientific support. At the same time it was never shown to be wrong, only superseded by rival, more assertive or more interesting hypotheses. 1