Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011570 (depression)
 172,036 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The responses of rabbit aortic strips superfused with noradrenaline, adrenaline and 5-HT were studied alone and in combination with ketamine (50 mug/ml). Ketamine caused a slight depression of the isolated aorta but potentiated responses to adrenaline but not to noradrenaline or 5-hydroxytryptamine. Ketamine did not potentiate aortic strips contracted to a stable level by pyrogallol and adrenaline. Experiments carried out with COMT from homogenates of rat liver showed that, in contrast to pyrogallol (10(-5) M), ketamine (10(-3) M) did not inhibit the enzyme. Other experiments with rabbits given 6-hydroxydopamine showed that aortas of these rabbits responded in a similar manner to controls when treated with ketamine and catecholamines. Results obtained with aortas contracted by adrenaline and noradrenaline with ketamine present, followed by oil immersion, showed that ketamine prolonged greatly the relaxation induced by adrenaline and to a lesser extent the relaxation induced by noradrenaline. The results of these studies indicate that ketamine prevented catecholamines from reaching the intracellular site of COMT. In this respect, ketamine can be termed an inhibitor of uptake site 2. If this hypothesis is valid then the action of ketamine on vascular tissue might explain the cardiovascular effects of the drug in man and experimental animals.
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PMID:The actions of ketamine on vascular smooth muscle. 95 82

As shown by examination in apparently healthy persons aged from 20 to 100 years and in experiments on 1--28-month-old albino rats there was a significant change with the progress of age in the content and ratio of catecholamines in the blood, various organs and the urine. The blood noradrenaline level fell considerably; Na/A coefficient also dropped sharply. Catecholamine content in the organs changed irregularly: in the kidneys it increased, in the skeletal muscles--remained unchanged, in the adrenal glands, the heart, the spleen and the liver--decreased. There was a significant reduction with the progress of age of the urinary excretion of adrenaline, noradrenaline, DOPA and vanilyl-amygdalic acid. Elemination of the intravenously injected noradrenaline from the blood of old rats was markedly delayed in comparison with that in the young animals. Depression of the COMT activity did not alter the noradrenaline level in the heart of adult and old rats. Administration of ipraside caused an increase in noradrenaline content in the heart of old rats, but failed to alter it in adult animals. It is suggested that in the catecholamine metabolism of old animals prevalence is given to the processes of oxidative desamination.
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PMID:[Catecholamine concentration and metabolism in old age]. 116 5

This review of the literature concerning the biochemical factors of resistance to antidepressants is essentially based on the anomalies of neurotransmitters and the enzymes which regulate them. In the case of 5HIAA, because of the bimodal distribution in depressed patients, it appears to be generally accepted that when a low level of this catabolite is found in the cerebrospinal fluid, this may represent a factor of resistance to noradrenergic antidepressants, or even to all antidepressants. In contrast, a high level of this catabolite represents a factor of poor response to serotoninergic antidepressants. Low levels of urinary MHPG predict a poor response to serotoninergic antidepressants, while high levels are observed in cases of depression resistant to noradrenergic antidepressants. MAO activity, evaluated after two weeks' treatment with MAOI, is considered to be a biochemical factor of resistance when it is inhibited by less than 80%. High levels of COMT (related to the degree of anxiety and agitation) reflect a poor response to noradrenergic antidepressants. Finally, a number of strategies designed to control resistant depression (reserpine, lithium carbonate, ...) could, in certain cases, suggest the existence of a functional defect in the serotoninergic systems.
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PMID:[Biochemical factors of resistance to antidepressants]. 354 87

The biochemical features of depressions able to guide the prescription of antidepressants are seen through a review of the literature. The papers were mainly focused on the peripheral catabolites of brain monoamines. Depressions characterized by low levels of 5 HIAA in the C.S.F. would predict a better efficacy of the antidepressants acting on the re-uptake of serotonin. The dosage of urinary MHPG seems to be a valuable index for the choice of the drug. Subjects with low levels response better to IMI, DE-IMI and NT, and those with normal levels to AMI. COMT activity and platelet MAO activity are may be a valuable index for the predictivity of the therapeutic results. Finally, the dexamethasone suppression test can be useful in order to guide the length of the treatment.
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PMID:[Therapeutic implications of the biochemical features about depressive illness (author's transl)]. 617 68

Erythrocyte COMT activity was determined in 31 healthy persons (16 men, 15 women) and in 34 persons with endogenous depressive syndrome (12 men, 22 women). It was found that enzyme activity is significantly higher in healthy men than in healthy women. In the group of women with endogenous depressive syndrome COMT activity is elevated as compared with the group of healthy women (P less than 0.05). This is true of all forms of affective disease: bipolar, unipolar, and undifferentiated. High COMT activity in women with depression is apparent mainly in patients whose first and second degree relatives revealed psychiatric disturbances, particularly affective disorders. This supports the significance of the sex factor in the genetic transmission of affective disorders, and a possible involvement of COMT activity changes in the pathogenesis of such disorders in women. No correlation was found between the changes in COMT activity and the psychopathological picture of depression or the severity of endogenous depressive syndrome.
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PMID:Studies on biogenic amine metabolizing enzymes (DBH, COMT, MAO) and pathogenesis of affective illness. II. Erythrocyte catechol-O-methyltransferase activity in endogenous depression. 684 43

COMT enzyme characteristics (Km, V, ratio of meta/paramethylation) were determined in the red blood cells of 20 patients with endogenous depression, in 20 healthy controls matched as to age and sex, as well as in 10 patients with mania, and 10 patients with neurotic depression. Assessment was done twice, i.e. before and after remission in patients with endogenous depression and in the manic patients. If male and female patients are considered together there was no statistical difference between the COMT characteristics of these patient groups, either before or after remission. Only the bipolar patients showed a higher COMT-activity (V) than their individually matched controls. If however, only the female patients are taken into consideration, COMT-activity of the patients with endogenous depression vs. controls is significantly increased by 60%. This difference can be demonstrated also after remission ("free interval") though statistical significance is reached only for the unipolar group. Further in vitro experiments indicate that antidepressant drugs do not possess a relevant influence on COMT-activity. Ranking the mean COMT-values leads to the following order: matched controls (< neurotic depression < unipolar depression < bipolar depression, which would be in good agreement with theoretical expectations based on the amine hypothesis of depression. Compared with normal male subjects COMT-activity of female controls is significantly lower. On the other hand, the female patients with endogenous depression show a significantly higher enzyme activity than the corresponding male patients.
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PMID:Erythrocyte COMT-activity in patients with affective disorders. 740 11

Anxiety, a common accompaniment of depression, can be a source of confusion in affective disorder research. The present study examined the effect of anxiety on platelet monoamine oxidase, RBC catechol-0-methyltransferase, and serum dopamine-beta-hydroxylase-enzymes frequently implicated in affective disorders. Levels of anxiety, plasma catecholamines and the enzymes mentioned above were quantified in groups of anxious subjects and mentally and physically healthy controls. Anxious subjects were found to have significantly higher levels of blood plasma catecholamines and platelet monoamine oxidase. significant positive correlations were demonstrated between plasma catecholamines and platelet monoamine oxidase, while significant inverse correlations were found between trait anxiety and COMT, norepinephrine and DBH, and COMT and DBH
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PMID:MAO, DBH and COMT: the effect of anxiety. 744 May 22

Bipolar spectrum disorders are recurrent illnesses characterized by episodes of depression, hypomania, mania or the appearance of mixed states. Great variability is evident in the frequency of episode recurrence and duration. In addition to regular circannual episodes, a spectrum of cycle frequencies has been observed, from the classical rapid cycling (RC) pattern of four or more episodes per year, to those with distinct shifts of mood and activity occurring within a 24-48 h period, described as ultra-ultra rapid cycling (UURC) or ultradian cycling. RC has a female preponderance, and occurs with greater frequency premenstrually, at the puerperium and at menopause. Tricyclic antidepressants and MAOIs, both of which increase functional monoamines norepinephrine, dopamine and serotonin, are known to precipitate mania or rapid-cycling in an estimated 20-30% of affectively ill patients. We have recently reported a strong association between velo-cardio-facial syndrome (VCFS) patients diagnosed with rapid-cycling bipolar disorder, and an allele encoding the low enzyme activity catechol-O-methyltransferase variant (COMT L). Between 85-90% of VCFS patients are hemizygous for COMT. Homozygosity for the low activity allele (COMT LL) is associated with a 3-4 fold reduction of COMT enzyme activity compared with homozygotes for the high activity variant (COMT HH). There is nearly an equal distribution of L and H alleles in Caucasians. Individuals with COMT LL would be expected to have higher levels of transynaptic catecholamines due to a reduced COMT degradation of norepinephrine and dopamine. We therefore hypothesized that the frequency of COMT L would be greater in RC BPD ascertained from the general population. Significantly, we found that the frequency of COMT L was higher in the UURC variant of BPD than among all other groups studied (P = 0.002). These findings indicate that COMT L could represent a modifying gene that predisposes to ultra-ultra or ultradian cycling in patients with bipolar disorder.
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PMID:Ultra-ultra rapid cycling bipolar disorder is associated with the low activity catecholamine-O-methyltransferase allele. 970 45

Catechol-O-methyltransferase (COMT, EC 2.1.1.6) is a ubiquitous enzyme that is crucial to the metabolism of carcinogenic catechols and catecholamines. Regulation of human COMT gene expression may be important in the pathophysiology of various human disorders including estrogen-induced cancers, Parkinson's disease, depression, and hypertension. The gender difference in human COMT activity and variations in rat COMT activity during the estrous cycle led us to explore whether estrogen can regulate human COMT gene transcription. Our Northern analyses showed that physiological concentrations of 17-beta-estradiol (10(-9)-10(-7) M) could decrease human 1. 3-kilobase COMT mRNA levels in MCF-7 cells in a time- and dose-dependent manner through an estrogen receptor-dependent mechanism. Two DNA fragments immediately 5' to the published human COMT gene proximal and distal promoters were cloned. Sequence analyses revealed several half-palindromic estrogen response elements and CCAAT/enhancer binding protein sites. By cotransfecting COMT promoter-chloramphenicol acetyltransferase reporter genes with human estrogen receptor cDNA and pSV-beta-galactosidase plasmids into COS-7 cells, we showed that 17-beta-estradiol could down-regulate chloramphenicol acetyltransferase activities, and COMT promoter activities dose-dependently. Functional deletion analyses of COMT promoters also showed that this estrogenic effect was mediated by a 280 base pair fragment with two putative half-palindromic estrogen response elements in the proximal promoter and a 323-base pair fragment with two putative CCAAT/enhancer binding protein sites in the distal promoter. Our findings provide the first evidence and molecular mechanism for estrogen to inhibit COMT gene transcription, which may shed new insight into the role of estrogen in the pathophysiology of different human disorders.
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PMID:Characterization and implications of estrogenic down-regulation of human catechol-O-methyltransferase gene transcription. 1038 81

In a community sample of 2,327 Caucasians, we tested the hypotheses that polymorphisms in the COMT and DRD3 genes are associated with personality traits conferring vulnerability to anxiety, depression, or alcohol misuse, or with current symptoms of these; and that the association is stronger in persons who also have been exposed to stressor experiences. To conserve resources and to allow replication, the genetic analysis was undertaken in two stages. For the COMT polymorphism, no statistically significant associations were found in the first sample of 862 persons. The remainder of the sample was therefore not analysed for that gene. For the DRD3 polymorphism, those in the first sample with at least one of the Ser(9) alleles had significantly higher scores in neuroticism (p=0.006) and behavioral inhibition (p=0.003). There was a trend, failing to meet the 1% significance criterion, for those with this genotype also to have higher depression and anxiety. The groups did not differ in alcohol use. In persons with the Ser(9) allele who were also exposed to stressors, there was a higher level of depression at the 5% level; and the depression level was higher in homozygotes. But when the remainder of the sample (1,465) was analysed, none of the associations reached statistical significance. We conclude that neither the COMT nor DRD3 polymorphisms are associated with anxiety, depression, or alcohol abuse. Am. J. Med. Genet. (Neuropsychiatr. Genet.) 96:102-107, 2000
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PMID:COMT and DRD3 polymorphisms, environmental exposures, and personality traits related to common mental disorders. 1068 61


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