Manic symptom severity correlates with COMT activity in the striatum: A post-mortem study.

Objectives:The enzyme catechol-O-methyltransferase (COMT), which catalyses the degradation of dopamine and norepinephrine, is posited to participate in the pathophysiology of bipolar disorder (BD) and schizophrenia. In support of this notion, rich evidence has documented that the severity of various BD and schizophrenia symptoms is moderated byrs4680, a single nucleotide polymorphism of theCOMTgene featuring a valine (Val)-to-methionine (Met) substitution that results in lower catalytic activity. Nevertheless, the specific relevance of COMT enzymatic activity in the pathophysiology of BD and schizophrenia dimensions remains elusive. Methods:We measured COMT catalytic activity in post-mortem prefrontal cortices, striata and cerebella of schizophrenia and BD patients, as well as non-affected controls. These values were then correlated withrs4680genotypes and psychopathology scores in the last week of life. Results:No direct correlation between COMT activity andrs4680genotypes was found; however, the severity of manic symptoms was highly correlated with COMT activity in the striatum, irrespective of the diagnostic group. Conclusions:These results suggest that COMT striatal activity, but notrs4680genotype, may serve as a biomarker for manic symptoms. Future studies are warranted to confirm these findings and assess the neurobiological links between COMT striatal activity and manic symptoms. [ABSTRACT FROM AUTHOR]