Low activity allele of catechol-O-methyltransferase gene associated with rapid cycling bipolar disorder
George Kirov,Kieran C. Murphy,Maria Arranz,Ian Jones,F McCandles,Hiroshi Kunugi,R.M. Murray,Peter McGuffin,D. A. Collier,Michael John Owen,Nicholas John Craddock,Nicholas John Craddock +11 more
TLDR
The hypothesis that variation in the COMT gene modifies the course of bipolar disorder is supported, and a sample of British Caucasian DSM-IV bipolar patients studied showed a dose-dependent increased risk of lifetime occurrence of rapid cycling.Abstract:
Catechol-O-methyltransferase (COMT) plays a major role in the breakdown of catecholamines. An amino acid polymorphism (val-108-met) determines high and low activity of the enzyme. A recent study in a small sample of patients with velo-cardio-facial syndrome who had bipolar affective disorder suggested that the Met (low activity) COMT allele might be associated with rapid-cycling in this population. We therefore tested the hypothesis that the Met allele might be associated with rapid cycling bipolar disorder in the wider population. We studied a sample of British Caucasian DSM-IV bipolar patients, of whom 55 met criteria for rapid cycling at some time during the illness and 110 met stringent criteria for a definite non-rapid cycling course. The COMT genotype was determined using a PCR assay. The low activity allele was more frequent in the group of rapid cyclers: 0.55 vs 0.42 (one-tailed chi 2 = 5.12, d.f. = 1, P = 0.012), and bearers of low activity alleles showed a dose-dependent increased risk of lifetime occurrence of rapid cycling: chi 2 test of linear association = 4.84, d.f. = 1, P = 0.014. Our data support the hypothesis that variation in the COMT gene modifies the course of bipolar disorder.read more
Citations
More filters
Journal Article
Catechol-O-methyltransferase (COMT): biochemistry, molecular biology, pharmacology, and clinical efficacy of the new selective COMT inhibitors.
Pekka T. Männistö,Seppo Kaakkola +1 more
TL;DR: The enzyme responsible for the O- methylation, catechol- O -methyltransferase (COMT) was partly purified and characterized by the same group as EC, which first described the enzyme-catalyzed O-methylation of catechlamines and other catechols in the late 1950s.
Journal ArticleDOI
Genetics of bipolar disorder
TL;DR: It is almost certain that over the next few years bipolar susceptibility genes will be identified, which will have a major impact on the understanding of disease pathophysiology and will provide important opportunities to investigate the interaction between genetic and environmental factors involved in pathogenesis.
Journal ArticleDOI
The genetics of schizophrenia and bipolar disorder: dissecting psychosis
TL;DR: Increasing evidence suggests an overlap in genetic susceptibility across the traditional classification systems that dichotomised psychotic disorders into schizophrenia or bipolar disorder, most notably with association findings at DAOA(G72), DISC1, and NRG1.
Journal ArticleDOI
A developmental model for similarities and dissimilarities between schizophrenia and bipolar disorder.
TL;DR: A model is suggested to explain the similarities and differences between the disorders and it is proposed that, on a background of shared genetic predisposition to psychosis, schizophrenia, but not bipolar disorder, is subject to additional genes or early insults, which impair neurodevelopment, especially of the medial temporal lobe.
Journal ArticleDOI
Genetics of bipolar disorder
Nicholas John Craddock,Ian Jones +1 more
TL;DR: It is almost certain that over the next few years bipolar susceptibility genes will be identified, which will have a major impact on the understanding of disease pathophysiology and will provide important opportunities to investigate the interaction between genetic and environmental factors involved in pathogenesis.
References
More filters
Journal ArticleDOI
A Diagnostic Interview: The Schedule for Affective Disorders and Schizophrenia
Jean Endicott,Robert L. Spitzer +1 more
TL;DR: Initial scale development and reliability studies of the items and the scale scores are reported on.
Book
Manic-Depressive Illness
TL;DR: In this paper, psychodynamic features of families with multigenerational bipolar manic-depressive illness are described, including avoidance of affect, unrealistic standards of conformity, absence of intimate relationships apart from family, displaced parental low self-esteem, and fears related to illness heritability.
Journal ArticleDOI
SCAN. Schedules for Clinical Assessment in Neuropsychiatry.
J. K. Wing,Thomas F. Babor,T. Brugha,J. D. Burke,John E. Cooper,R. Giel,A. Jablenski,Darrel A. Regier,Norman Sartorius +8 more
TL;DR: The new system, known as SCAN (Schedules for Clinical Assessment in Neuropsychiatry), includes the 10th edition of the PSE as one of its core schedules, preliminary tests of which have suggested that reliability is similar to that of PSE-9.
Journal ArticleDOI
Human catechol-O-methyltransferase pharmacogenetics: description of a functional polymorphism and its potential application to neuropsychiatric disorders.
Herbert M. Lachman,Demitri F. Papolos,Takuya Saito,Yue Min Yu,Carol L. Szumlanski,Richard M. Weinshilboum +5 more
TL;DR: The identification of a gentic marker associated with significant alterations in enzyme activity will facilitate the analysis of a possible role for the COMT gene in neuropsychiatric conditions in which abnormalities in catecholamine neurotransmission are believed to occur.
Journal ArticleDOI
Enzymatic O-methylation of epinephrine and other catechols.
Julius Axelrod,Robert Tomchick +1 more
TL;DR: The properties of an enzyme that transfers the methyl group of S-adenosylmethionine to the hydroxyl group in position 3 of epinephrine and other catechols are described.