As
ceruloplasmin and
copper abnormalities have been implicated in
schizophrenia, we investigated the role of a second
copper-containing non-
ceruloplasmin protein, the
iron oxidase ferroxidase II, in a prospective study of ten inpatients with
schizophrenia and a comparison group.
Ferroxidase II is a
protein known to reciprocally regulate with
ceruloplasmin in
Wilson's disease, an illness characterized by psychotic symptoms, decreased
ceruloplasmin, and increased
copper deposition in tissues.
Ferroxidase II plays a key role in the maintenance of near-normal
iron metabolism in
Wilson's disease, but its role in
schizophrenia has never been studied. In this study, we assayed
ceruloplasmin by two enzymatic assays, a standard clinical laboratory
p-phenylenediamine oxidation assay and a second assay based on the rate of the oxidation and incorporation of
iron (Fe3+) into
transferrin; we assayed
ferroxidase II activity using this second
iron oxidation assay. We found that
ceruloplasmin levels as measured by both enzymatic methods, but not
ferroxidase II, were elevated in
schizophrenia. The increased
ceruloplasmin also correlated with elevated serum
copper as assayed by atomic absorption spectrophotometry, which was unsurprising as the majority of
copper in blood is bound to
ceruloplasmin. It has been proposed that
copper, as a component of several
enzymes linked to
dopamine synthesis, may play a role in
schizophrenia by exacerbating or perpetuating dopaminergic dysregulation. Our study suggests that the
ceruloplasmin elevation in
schizophrenia is specific, and not simply an elevation of plasma
copper-containing oxidative
enzymes. Increases in
ceruloplasmin may result in increased levels of
copper, which ultimately proves deleterious in
schizophrenia.