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The article discusses a study on the biological phenomenology of schizophrenia with the use of molecular analysis. The results indicate the involvement of altered mitochondrial function in the symptomatology and etiology of schizophrenia. The subunits of cytochrome oxidase are the mitochondrial components that are significant because of their expression to dopaminergic blockade and upregulation by estrogen.

Ethylcholine mustard aziridinium (ECMA) inhibits choline transport in synaptosomes at a half-maximal concentration of about 20 microM. The rate of inhibition falls off rapidly after 10 min and the concentration dependency reaches a plateau at about 100 microM. The inhibition is not removed by washing the synaptosomes, and choline and hemicholinium-3 protect the carrier against attack by the mustard. Choline efflux, particularly that stimulated by choline in the medium (transactivation) is also inhibited by the aziridinium compound. Similarly choline influx activated by preloaded internal choline is inhibited by ECMA. The mustard can enter the synaptosomes in an active form but most of the carrier is alkylated when facing the outside. Prior depolarization of the synaptosomes causes an increase in the rate of inhibition by ECMA which is proportionally about the same as the increase in choline influx also caused by depolarization. At low ECMA concentrations the rate of inhibition is that of a first-order reaction with the carrier but at high ECMA concentrations the translocation of the carrier to the outward-facing conformation controls the rate of inhibition. Using a model of choline transport with some simplifying assumptions it is possible to estimate the amount of carrier; cholinergic synaptosomes carry about six times the concentration of carrier found in noncholinergic ones. In noncholinergic synaptosomes the carrier faces predominately out, the reverse in cholinergic ones. The rate constant of carrier translocation is increased by combination with choline some six- to sevenfold to about 3.5 min-1. The rate constant of ECMA attack on the carrier is about 440 M-1 sec-1. [ABSTRACT FROM AUTHOR]

Messenger RNA, obtained from post-mortem brain of 10 schizophrenics, five depressed patients and 10 control subjects, was characterised with respect to a number of parameters. It was found that post-mortem delay was not the major factor in determining RNA yield, size (as determined by cDNA synthesis) and biological activity. Biological activity, as determined by in vitro translation in a reticulocyte-lysate system, could be observed using messenger RNA from periods of 0 to 84 hours post-mortem. Two-dimensional gel analysis of the newly-synthesised radiolabelled products obtained from this material revealed several hundred individual species but no consistent degradation of any particular species with post-mortem delay. It is suggested, therefore, that premortem changes are as important as post-mortem changes in determining RNA yield, size and biological activity. Although no consistent difference could be found between patients and controls using any of these parameters, this study confirms that, by isolating messenger RNA from post-mortem human brain, valuable information can be gained on gene expression in psychiatric disorders. [ABSTRACT FROM AUTHOR]

Erythrocytes from lithium treated patients were separated according to the time they had been circulating in the plasma. Choline transport and choline content were measured in the erythrocyte fractions separated according to age, in order to investigate the relationship between decreased choline transport and increased choline content seen in lithium treated patients. The most recently formed erythrocytes of normal subjects had the greatest choline content and the most active choline carrier. The erythrocytes of lithium treated patients had reduced choline carrier activity and increased choline content in all age bands. However the greatest accumulation of choline and least inhibited choline carrier activity was seen in the most recently formed cells. The alteration in phospholipid concentrations measured could not of themselves account for elevated erythrocyte choline levels seen in lithium treated patients. It is concluded that the increase in choline content levels in lithiated erythrocytes does not have a simple inverse relationship with the deficiency in choline transport. The inhibition of the choline carrier is caused by modification due to circulation in lithiated plasma rather than a lack of its synthesis in reticulocytes. [ABSTRACT FROM AUTHOR]