Polyamines and their metabolizing enzymes in human frontal cortex and hippocampus: Preliminary measurements in affective disorders

Affective disorders are associated with maladaptive response to stressful 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 research efforts, therefore, concentrate on the characterization of this PA response, and on its pharmacological regulation. The present preliminary study is the first to measure the polyamines, putrescine, spermidine, and spermine, and their metabolizing enzymes, ornithine decarboxylase, S-adenosylmethionine decarboxylase, and spermidine/spermine N¹ acetyltransferase, in brain autopsy samples from people who suffered from depressive disorders or schizophrenia, or from those who committed suicide. The data of affected individuals did not reveal significant differences when compared to those of suicide cases, or to those of people with no known neurologic or psychiatric abnormalities. The following regional differences were observed: spermidine concentrations and ornithine decarboxylase activity were higher, but S-adenosylmethionine decarboxylase activity was lower in the hippocampus as compared to the frontal cortex. Preliminary studies with rat brain indicate that an increase in polyamine metabolizing enzyme activities occurs within several hours after death and persists for at least 48 hours. These observations, in turn, indicate that earlier autopsies are crucial for detection of changes in polyamine metabolism. We conclude that further studies to test the polyamine hypothesis are warranted.