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A defective capability of cultured rat glioma cells to reutilize purine bases (hypoxanthine-guanine phosphoribosyltransferase deficiency) was associated with a reduced capacity to oxidatively deaminate serotonin and tryptamine. The mutant glioma cells were also more sensitive to the cytotoxic effects of serotonin than were normal cells

Two statements are presented here: 1) antidepressants increase the amount of MA at the central receptors, and 2) antidepressants are effective in some, but quite ineffective in other patients, even if they belong to the same diagnostic category. Three questions result from these statements: 1) Does a central MA deficiency occur in depressive patients? 2) If so, is this disorder present in only a proportion of the patients? 3) If so, can this explain the apparent selectivity of antidepressants in the sense that particularly MA-deficient patients benefit from this type of therapy? A tentative answer is given to these three questions. In depressive patients the cerebral MA turnover can be diminished. These disorders do not occur in all patients but seem to be confined to certain categories of depression. Diminution or non-diminution of the central MA turnover is a (not the) factor which determines whether antidepressant medication will succeed or fail. The theoretical and practical implications of these answers are discussed.

A highly significant decrease in platelet monoamine-oxidase activity has been observed in migrainous subjects during a migraine attack compared with activity outside an attack. The effect did not derive from drugs commonly used in migraine therapy.

Platelet-monoamine-oxidase activity predicts treatment response to lithium in manic-depressive illness. In the treatment-responsive group enzyme activity is similar to that in normal controls, whereas in the treatment-refractory group enzyme activity is significantly less than both control and treatment-responsive groups.

Mapping of the human MAOA gene to chromosomal region Xp21-p11 prompted our study of two affected males in a family previously reported to have Norrie disease resulting from a submicroscopic deletion in this chromosomal region. In this investigation we demonstrate in these cousins deletion of the MAOA gene, undetectable levels of MAO-A and MAO-B activities in their fibroblasts and platelets, respectively, loss of mRNA for MAO-A in fibroblasts, and substantial alterations in urinary catecholamine metabolites. The present study documents that a marked deficiency of MAO activity is compatible with life and that genes for MAO-A and MAO-B are near each other in this Xp chromosomal region. Some of the clinical features of these MAO deletion patients may help to identify X-linked MAO deficiency diseases in humans.