Studies on biogenic amine metabolizing enzymes (DBH, COMT, MAO) and pathogenesis of affective illness

Pużyński, S; Bidziński, Andrzej; Mrozek, Ségolène; Załuska, M

doi:10.1111/j.1600-0447.1983.tb06728.x

Cited by 24 publications

(8 citation statements)

References 13 publications

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“…Because of its role in catecholamine metabolism, COMT enzymatic activity has previously been measured in the peripheral blood of patients with mood disorders and schizophrenia. However, the results of these studies have been equivocal [Dunner et al, 1977;Philippu et al, 1981;Puzynski et al, 1983;Karege et al, 19871.…”

Section: Resultsmentioning

confidence: 93%

Association of codon 108/158 catechol-O-methyltransferase gene polymorphism with the psychiatric manifestations of velo-cardio-facial syndrome

et al. 1996

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Section: Resultsmentioning

confidence: 93%

Association of codon 108/158 catechol-O-methyltransferase gene polymorphism with the psychiatric manifestations of velo-cardio-facial syndrome

et al. 1996

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“…As a first step toward understanding the consequences of the absence of COMT on neurotransmission in several brain regions, steady-state levels of dopamine and norepinephrine were compared in the striatum, frontal cortex, and hypothalamus of homozygous and wild-type animals. Based on our previous observations, which suggested a sexually dimorphic contribution of COMT in psychiatric phenotypes (10), as well as on earlier observations by others (12), male and female animals were analyzed separately (Fig. 3).…”

Section: Resultsmentioning

confidence: 99%

“…Studies on the comt allele distribution, as well as extensive mutational analysis failed to reveal a major effect of low COMT activity on schizophrenia (9), although studies on case͞control samples (10) and more recently affected families (M.K., C. A. Sobin, M. L. Blundell, B. L. Galke, L. Malinova, P. Goldberg, J. Oh, and J.A.G., unpublished results) suggested that the low activity allele of this gene is significantly associated with susceptibility to OCD in a recessive and sexually dimorphic manner. In addition, earlier studies assaying enzyme activity suggested a sexually dimorphic role for this gene in affective disorder (11,12), an observation supported by more recent studies using genetic markers (13). The involvement of COMT in the monoamine metabolic pathways could explain the pleiotropic effect of this gene on susceptibility to psychiatric disorders and symptoms.…”

mentioning

confidence: 76%

Catechol- O -methyltransferase-deficient mice exhibit sexually dimorphic changes in catecholamine levels and behavior

Gogos

Morgan

Luine

et al. 1998

Proc. Natl. Acad. Sci. U.S.A.

808

556

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Catechol-O-methyltransferase (COMT) is one of the major mammalian enzymes involved in the metabolic degradation of catecholamines and is considered a candidate for several psychiatric disorders and symptoms, including the psychopathology associated with the 22q11 microdeletion syndrome. By means of homologous recombination in embryonic stem cells, a strain of mice in which the gene encoding the COMT enzyme has been disrupted was produced. The basal concentrations of brain catecholamines were measured in the striatum, frontal cortex, and hypothalamus of adult male and female mutants. Locomotor activity, anxiety-like behaviors, sensorimotor gating, and aggressive behavior also were analyzed. Mutant mice demonstrated sexually dimorphic and region-specific changes of dopamine levels, notably in the frontal cortex. In addition, homozygous COMT-deficient female (but not male) mice displayed impairment in emotional reactivity in the dark͞light exploratory model of anxiety. Furthermore, heterozygous COMT-deficient male mice exhibited increased aggressive behavior. Our results provide conclusive evidence for an important sex-and region-specific contribution of COMT in the maintenance of steady-state levels of catecholamines in the brain and suggest a role for COMT in some aspects of emotional and social behavior in mice.Catechol-O-methyltransferase (COMT) along with monoamine oxidases (MAO-A and -B) are the major mammalian enzymes involved in the metabolic degradation of dopamine, norepinephrine, and epinephrine. COMT is a Mg 2ϩ -dependent enzyme that catalyzes the transfer of methyl groups from S-adenosyl methionine to a hydroxyl group of a catecholic substrate: dopamine is converted into 3-methoxytyramine, and norepinephrine is converted into normetanephrine (1). COMT is widely distributed in the mammalian brain, although results from pharmacological studies suggest that the relative importance of methylation (by COMT) versus deamination (by MAO) in the metabolic degradation of catecholamines varies among brain regions, with methylation accounting for about 15% of released dopamine in striatum and in nucleus accumbens and for more than 60% in frontal cortex (2). The enzyme is absent from the dopaminergic terminals and is thought to be involved in the catabolism of extraneuronal dopamine in glial cells and͞or postsynaptic neurons (1). COMT activity is probably under hormonal control. Comparisons of liver COMT activity and thermostability in humans indicated an epigenetically determined significantly lower COMT activity in females (3). A limited number of studies in other species suggest that COMT activity can be reduced epigenetically by estrogens (4) and can be affected by the process of sexual differentiation of the brain (5).

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“…Monoamine oxidase, the enzyme responsible for the degradation of both catecholamines and 5‐HT, could be one of the mediating factors in the aetiology of depression associated with ageing 25 . There are two subtypes of MAO, namely MAO‐A and MAO‐B, in rat brain 26 .…”

Section: Discussionmentioning

confidence: 99%

Changes In Endogenous Monoamines In Aged Rats

Lee

Chang

Liu

et al. 2001

Clin Exp Pharma Physio

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1. It has been documented that ageing may alter endogenous neurotransmitters. However, these results are controversial. Thus, in the present study, cerebral cortex and plasma from male Wistar rats aged 8 weeks and 6, 12 or 24 months were used to investigate the changes in monoamines using electrochemical detection. 2. A marked decrease in L-dihydroxyphenylalanine (L-DOPA) was observed in aged rats. Like the decrease in dopamine (DA), levels of 5-hydroxytryptamine (5-HT) and 5-hydroxyindolacetic acid (5-HIAA), the major metabolite of 5-HT, in aged rats were decreased in the cerebral cortex and plasma. Plasma levels of noradrenaline and levels of adrenaline in the cerebral cortex were also decreased in aged rats. Moreover, levels of 3,4-dihydroxyphenylacetic acid (DOPAC), a metabolite of DA, in the cerebral cortex and plasma were reduced by ageing. The level of homovanillic acid (HVA) in all samples was markedly increased with ageing. 3. The ratio of DOPAC/DA and 5-HIAA/5-HT, being closely linked with the activity of monoamine oxidase, was increased in the cerebral cortex and plasma with ageing. The ratio of HVA/DOPAC, an index of the activity of catechol-O-methyltransferase, was also higher in the cerebral cortex and plasma of aged rats. 4. These data suggest that ageing may alter endogenous monoamines in both the brain and peripheral tissues.

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Studies on biogenic amine metabolizing enzymes (DBH, COMT, MAO) and pathogenesis of affective illness

Cited by 24 publications

References 13 publications

Association of codon 108/158 catechol-O-methyltransferase gene polymorphism with the psychiatric manifestations of velo-cardio-facial syndrome

Association of codon 108/158 catechol-O-methyltransferase gene polymorphism with the psychiatric manifestations of velo-cardio-facial syndrome

Catechol- O -methyltransferase-deficient mice exhibit sexually dimorphic changes in catecholamine levels and behavior

Changes In Endogenous Monoamines In Aged Rats

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