The occurrence of Β-carbolines in man and rat, putative biochemical substrates responsible for psychosis

Many research groups have been putting effort in finding biochemical aberrations related to the etiology of psychoses, as discussed in Chapter I (Gillin, 1978; Smythies, 1982; Bruinvels and Peppinkhuizen, 1984). It has been suggested that excessive activity of methylation processes could result in the formation of abnormally methylated biogenic amines with hallucinogenic or even "psychotogenic" properties (Osmond and Smythies, 1952). Until now, these compounds have not been found in significant amounts, although some enzymatic abnormalities are present in different subgroups (Chapter I). In 1980 Pepplinkhuizen et al. published on a group of acute psychotic patients of the manicpsychedelic type, who showed a disturbance in serine- and glycine metabolism. These findings were used as a starting-point for this thesis. As described in Chapter I, an animal model was developed, based on an enhanced conversion of serine into glycine, in order to study the putative formation of beta-carbolines. The presence of these compounds was correlated with behavioural disturbances in these animals. Moreover, beta-carbolines were measured in plasma, prepared from blood from episodic psychotic patients. In the following paragraph, results from these studies are discussed.