Biochemical research in 'schizophrenia' — I have stated that the results of biological psychosis research have so far been unimpressive, and that the lack of a proper research strategy has substantially contributed to this situation. I have also stated that neuroleptics can fill the gap: that they can serve as point of crystallization of working hypotheses, playing the same role as the antidepressants play in biological depression research. I have presented the following arguments in support of this statement.
Neuroleptics are chemically heterogeneous, but have two characteristics in common. In psychopathological terms: they have a therapeutic effect on psychotic disorders. In biochemical terms: they reduce CA-ergic transmission in the brain. This raises at least three questions:
1 is CA-ergic transmission in the human brain likewise blocked by neuroleptics;
2 does the psychotic patient show signs of CA-ergic hyperactivity;
3 is there a correlation between the biochemical and the psychopathological action profile of neuroleptics.
Together, these questions provide us with an adequate research strategy. We, at least, have used them as such. The principal results of research on these lines have so far been the following.
1. The neuroleptics studied — chlorpromazine, haloperidol and oxypertine — influence human central CA metabolism also, and in a manner to be expected on the basis of results obtained in animal experiments.
2. An increased central DA turnover does occur in psychotic disorders, but this phenomenon is linked not so much to such 'genuine' psychotic symptoms as delusions and hallucinations as to the factor motor agitation.
3. A comparative study of chlorpromazine and oxypertine was undertaken as the first of a planned series of studies. Chlorpromazine was selected because it is believed to reduce both DA-ergic and NA-ergic transmission, and oxypertine was selected because it is a more selective blocker of NAergic transmission. On the basis of this biochemical difference we formulated three hypotheses predicting clinical differences. These hypotheses were generally confirmed. In view of this it seems likely that the biochemical action profile of neuroleptics is a more reliable indicator of their clinical action profile than their chemical structure.
We are now in quest of arguments which can reinforce the foundation of this theory.