POLYAMINES AND THEIR METABOLIZING ENZYMES IN HUMAN FRONTAL-CORTEX ANDHIPPOCAMPUS - PRELIMINARY MEASUREMENTS IN AFFECTIVE-DISORDERS

Affective disorders are associated with maladaptive response to stress ful life events, Based on the observation that a transient increase in brain polyamine metabolism is a common response to stressful stimuli, our hypothesis is that a maladaptive polyamine stress response may be involved in the pathophysiology of affective disorders, Our current r esearch efforts, therefore, concentrate on the characterization of thi s PA response, and on its pharmacological regulation. The present prel iminary study is the first to measure the polyamines, putrescine, sper midine, and spermine, and their metabolizing enzymes, ornithine decarb oxylase, S-adenosylmethionine decarboxylase, and spermidine/spermine N -1 acetyltransferase, in brain autopsy samples from people who suffere d from depressive disorders or schizophrenia, or from those who commit ted suicide. The data of affected individuals did not reveal significa nt differences when compared to those of suicide cases, or to those of people with no known neurologic or psychiatric abnormalities. The fol lowing regional differences were observed: spermidine concentrations a nd ornithine decarboxylase activity were higher, but S-adenosylmethion ine decarboxylase activity was lower in the hippocampus as compared to the frontal cortex Preliminary studies with rat brain indicate that a n increase in polyamine metabolizing enzyme activities occurs within s everal hours after death and persists for at least 48 hours, These obs ervations, in turn, indicate that earlier autopsies are crucial for de tection of changes in polyamine metabolism, We conclude that further s tudies to test the polyamine hypothesis are warranted.