ABSTRACT
Adenosine is an important modulator of the nervous system that has been implicated in the pathophysiology of schizophrenia. We studied peripheral adenosine metabolism by determining the activity of serum adenosine deaminase, which converts adenosine into inosine, and 5'-nucleotidase, which converts AMP into adenosine, in 26 DSM-IV male schizophrenic patients under antipsychotic monotherapy and 26 healthy volunteers balanced for age and race. Schizophrenic patients treated either with typical antipsychotics or clozapine showed increased serum adenosine deaminase activity compared to controls (controls=18.96+/-4.61 U/l; typical=25.09+/-10.98 U/l; clozapine=30.32+/-10.83 U/l; p<0.05, ANOVA) and 5'-nucleotidase activity was also increased in patients on clozapine. After adjusting for confounding factors, adenosine deaminase, but not 5'-nucleotidase, alterations remained significant particularly in the clozapine group. This result suggests that either altered adenosine metabolism is present in schizophrenic patients or is influenced by treatment with antipsychotics, particularly clozapine.
Subject(s)
Adenosine Deaminase/blood , Adenosine/metabolism , Brain/drug effects , Brain/enzymology , Schizophrenia/drug therapy , Schizophrenia/enzymology , 5'-Nucleotidase/blood , 5'-Nucleotidase/drug effects , Adenosine Deaminase/drug effects , Adolescent , Adult , Antipsychotic Agents/pharmacology , Biomarkers/analysis , Biomarkers/blood , Brain/physiopathology , Clozapine/pharmacology , Drug Resistance/drug effects , Drug Resistance/physiology , Humans , Male , Middle Aged , Schizophrenia/blood , Up-Regulation/drug effects , Up-Regulation/physiologyABSTRACT
Adenosine has been proposed to contribute to the pathophysiology of schizoprenia and as a target for therapeutic intervention. In the lack of direct adenosine agonists, allopurinol may indirectly elevate adenosine levels by inhibiting degradation of purines. We report two cases of poorly responsive schizophrenic patients who improved considerably with add-on allopurinol 300 mg/day. Their clear clinical improvement warrant further investigation of allopurinol, as well as other purinergic strategies, for the treatment of schizophrenia.