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

Abstract

Objectives The enzyme catechol-O-methyl transferase (COMT), which catalyzes 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 by rs4680, a single nucleotide polymorphism of the COMT gene 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 with rs4680 genotypes and psychopathology scores in the last week of life. Results No direct correlation between COMT activity and rs4680 genotypes 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 not rs4680 genotype, 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.

Aggressive behavior in psychiatric patients in relation to hormonal imbalance (Review)

“…Also this allele was associated with violent suicidal attempts among schizophrenic patients ( 59 ). A study found a high correlation between COMT activity and severity of maniac symptoms in patients suffering from bipolar disorder ( 60 ).…”

“…Also this allele was associated with violent suicidal attempts among schizophrenic patients (59). A study found a high correlation between COMT activity and severity of maniac symptoms in patients suffering from bipolar disorder (60). Dopaminergic circuits located in the meso-corticolimbic system are involved in the executive functions that generate aggressive behavior (61).…”