TY - JOUR
T1 - Manic symptom severity correlates with COMT activity in the striatum
T2 - A post-mortem study
AU - Bortolato, Marco
AU - Walss-Bass, Consuelo
AU - Thompson, Peter M.
AU - Moskovitz, Jackob
N1 - Funding Information:
None of the institutions had any further role in study design; in the collection, analysis and interpretation of data; in the writing of the report; and in the decision to submit the paper for publication. The authors wish to thank Dr. Dianne Cruz for her technical support, as well as the Southwest Brain Bank at UTHSCSA for providing tissue for this project and to the donor families that make this research possible. This research was supported by NIH grants R01MH104603 (to M.B.), K01MH077777 (to C.W.B.), R24MH076039 (to P.M.T.), as well as the Hedwig Miller Fund for Aging Research and by an Institutional Development Award (IDeA) from the NIGMS grant P30 GM1110761 (to J.M.).
Publisher Copyright:
© 2016 Informa UK Limited, trading as Taylor & Francis Group.
PY - 2017/4/3
Y1 - 2017/4/3
N2 - 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 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.
AB - 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 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.
KW - Catechol-O-methyltransferase
KW - bipolar disorder
KW - manic symptoms
KW - schizophrenia
KW - single nucleotide polymorphism
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U2 - 10.1080/15622975.2016.1208844
DO - 10.1080/15622975.2016.1208844
M3 - Article
C2 - 27458023
AN - SCOPUS:84979683917
VL - 18
SP - 247
EP - 254
JO - World Journal of Biological Psychiatry
JF - World Journal of Biological Psychiatry
SN - 1562-2975
IS - 3
ER -