Low Dopamine-beta-hydroxylase Activity Research Articles

Dopamine beta‐hydroxylase (DBH) activity and ‐1021C/T polymorphism of DBH gene in combat‐related post‐traumatic stress disorder

The roles of dopamine (DA) and norepinephrine (NE) in posttraumatic stress disorder (PTSD) are unclear. The aim of the study was to determine plasma dopamine beta-hydroxylase (DBH) activity and DBH-1021C/T gene polymorphism in combat veterans with (N = 133) or without (N = 34) chronic PTSD. Similar frequencies in genotype or allele distribution were found between veterans with or without PTSD. War veterans with PTSD had lower DBH activity, associated with the DBH-1021C/T variant in DBH genes, than veterans without PTSD. A significantly lower plasma DBH activity was found in combat veterans with PTSD carrying the CC genotype as compared to veterans without PTSD carrying the corresponding genotype. Since both groups were exposed to the same trauma, it is possible that a pre-existing trait difference in regulation of NE function contributed to a differential vulnerability to develop PTSD, or that the regulation of DBH expression was different in response to trauma. The results suggest that that genotype-controlled measurement of plasma DBH activity might be used as a potential biological marker of the response to trauma, and that further studies of DBH and other loci related to DA and NA in PTSD are warranted.

Advances in the pharmacotherapy of stimulant dependence: From alcohol antagonists to Xenova vaccines

Several widely varying pharmacotherapies, which help ‘re-normalize’ documented stimulant-induced brain dysfunction in DA, GABA and glutamate receptors and metabolism, are promising for stimulant dependence. Disulfiram has significantly reduced cocaine abuse in six independent clinical trials. It inhibits dopamine beta hydroxylase (DBH), which converts dopamine (DA) to norepinephrine (NE), and thereby reduces NE, which may reduce cocaine withdrawal symptoms, and increases DA, which may ‘re-normalize’ depleted DA and compensate for down-regulated DA receptors that are associated with chronic cocaine dependence. Low DBH activity, which is determined by a functional genetic polymorphism, appears critical to disulfiram's efficacy in cocaine dependence. Amantadine, which is also an indirect DA agonist, is only effective in patients with severe withdrawal symptoms, a subgroup of patients who also respond to the adrenergic blocker propranolol. The GABA enhancers including tiagabine, baclofen and topiramate have shown some efficacy in clinical trials and in reducing cue-induced cocaine craving. Glutamate enhancers like modafinil show efficacy, perhaps by enhancing learning of new relapse prevention behaviors. Finally, a cocaine vaccine, which prevents cocaine from getting out of the blood stream and into the brain, shows a dose-response in reducing cocaine use.

Dopamine beta-hydroxylase (DBH) gene and schizophrenia phenotypic variability: a genetic association study.

Recently, two polymorphisms (DBH5'-Ins/del and DBH 444 g/a) of the Dopamine Beta Hydroxylase (DBH) gene were isolated, and one haplotype (Del-a) was found to be associated with low DBH activity and cocaine-induced paranoia. The purpose of this study is to test for association between these two polymorphisms and schizophrenia or its phenotypic variability with respect to neuroleptic therapeutic response and symptom profile. Allelic and haplotype distributions of these two polymorphisms were compared between two groups of schizophrenic patients (excellent neuroleptic-responders; R, n = 42 and non-responders; NR, n = 64), and one group of healthy volunteers (n = 120). The "Del" and "a" alleles were in positive linkage disequilibrium. No allelic or genotype differences in the distribution of these two polymorphisms were observed between patients and controls. However, The Del-a haplotype was significantly more common in NR patients, and the mean total BPRS score was significantly higher in the group of patients with the Del-a compared to those without the Del-a haplotype. These results suggest that the DBH gene is not a causative factor in schizophrenia but that it may be a modulator of psychotic symptoms, severity of the disorder and therapeutic response to neuroleptic drugs.

Possible control of dopamine beta-hydroxylase via a codominant mechanism associated with the polymorphic (GT)n repeat at its gene locus in healthy individuals.

Six allelic fragments were typed by a PCR-based process with a pair of primers specific for a sequence containing the polymorphic (GT)n repeat at the human dopamine beta-hydroxylase (DBH) locus in 125 unrelated healthy individuals. Their frequencies among these individuals were 0.012 (A1), 0.08 (A2), 0.344 (A3), 0.548 (A4), 0.004 (A5) and 0.012 (A6); the two major alleles, A3 and A4, made up nearly 90% of the alleles. These individuals were divided into four groups according to the genotype they possessed, i.e. A3/A3, A4/A4, A3/A4 and others (mixed group). Kruskal-Wallis analysis revealed a significant difference in serum DBH activity among these four genetic groups (H = 32.7, P < 0.0001). The homozygotic genotypes, A3/A3 and A4/A4, were associated with low and high DBH activity, respectively, and the heterozygotic genotype, A3/A4, seemed to play a role in keeping the DBH activity at a moderate level. The present work suggests that the human DBH is likely to be controlled via a codominant mechanism associated with the dinucleotide repeat polymorphism at its gene locus.

Dopamine-beta-hydroxylase in behaviorally disturbed youth: Relationship between teacher and parent ratings

A series of neurotransmitters, metabolites, and enzymes considered relevant to emotional and behavioral disorders was studied in blood samples obtained from boys admitted to a residential setting because of disruptive or unmanageable behavior in their home environments. The youth were categorized into mainly prepubertal (under 12.0 years) and pubertal/post pubertal (12.0 years and over) groups. Behavior ratings of the younger group completed by parents revealed significant inverse correlations between several behavioral factors and dopamine-beta-hydroxylase (DBH) activity levels, notably in the agressive behavior and antisocial domains. Teacher ratings completed after about 1 month of living in the residential setting also showed numerous significant, but positive, correlations between several behavior factors and DBH activity levels. Furthermore, teacher and parent ratings themselves often were significantly and inversely correlated. The findings related to DBH activity levels were strongest in the younger group of boys. The results are discussed in terms of the possibility that low DBH activity in boys reflects a vulnerability towards behavioral disorder, which in certain environments becomes manifested by conduct problems and antisocial behavior.

Developmental change of dopamine ?-hydroxylase activity in cerebrospinal fluid of epileptic and non-epileptic children

The developmental change of dopamine beta-hydroxylase (DBH) activity in cerebrospinal fluid (CSF) of epileptic children was studied. Non-epileptic children showed lower DBH activity in CSF than adult, and its activity increased with age. In contrast, epileptic children showed no increase in DBH activity with age. DBH in CSF may be a good index of noradrenergic function in child brain. The results on developmental change in DBH in CSF suggest that refractory epilepsy with long term medication has decreased activity in central noradrenergic neurons.

Dopamine-beta-hydroxylase activity of the cat carotid body under different arterial O2 and CO2 conditions.

To determine the importance of dopamine and noradrenaline as neurotransmitters during chemoreception in the cat carotid body we investigated the contents of both compounds as well as the activity of dopamine-beta-hydroxylase (DBH) under different arterial PO2 and PCO2 conditions. The superior cervical ganglion was used as a control organ. In the carotid body and the ganglion an inverse relationship exists between the catecholamine content and the DBH activity. The carotid body has a high catecholamine content with a low DBH activity whereas the superior cervical ganglion has a low catecholamine content and high DBH activity. Hypercapnia did not produce any significant change in the catecholamine content or in the DBH content of the carotid body. However, in comparison with hyperoxia, hypoxia produced a significant change (p less than 0.05) in the noradrenaline content without changing the DBH activity. The dopamine content under these conditions did not change significantly. The results may indicate that the high catecholamine content of the carotid body is the result of a high retention and/or low rate of degradation rather than of a high rate of synthesis.

Studies on biogenic amine metabolizing enzymes (DBH, COMT, MAO) and pathogenesis of affective illness. I. Plasma dopamine-beta-hydroxylase activity in endogenous depression.

On the basis of studies carried out with a group of 47 patients with endogenous depressive illness, lower plasma activity of dopamine-beta-hydroxylase (DBH) was found as compared with a control group (31 healthy persons). Lower DBH activity particularly characterized bipolar patients. Lowest DBH activity was found in patients with a family history of psychiatric disorders, in particular, affective illness (in comparison with the control group the difference was statistically significant, P less than 0.05). It was noticed, that in a period of remission or significant improvement the enzymatic activity increases, although in some cases the level of activity is still lower than in the control group. There was a correlation between activity of the enzyme and clinical course of the illness and susceptibility to antidepressive drugs. Most of the observed phenomena are related to male patients. On the basis of these studies and data supplied by corresponding literature, concerning in particular the effects of DBH inhibitors (fusaric acid, disulfiram), the authors consider that changes in DBH activity may play a role in the pathogenesis of depression and that DBH deserves further studies, also of genetic nature.

Enzyme Studies in Tardive Dyskinesia. III. Noradrenergic Hyperactivity in a Subgroup of Dyskinetic Patients

This study was undertaken to test a hypothesis that tardive dyskinesia (TD) patients with high plasma dopamine-beta-hydroxylase (DBH) activity would also have other enzymatic alterations suggestive of noradrenergic hyperactivity. Plasma renin activity was chosen as a peripheral indicator of noradrenergic function. We measured plasma renin activity in three groups of female psychiatric inpatients over the age of 50: a TD group with high plasma DBH activity, a TD group with low plasma DBH activity, and a non-TD group. The high-DBH TD group had significantly greater plasma renin activity than the other two groups. Our results are consistent with the hypothesis that a subgroup of TD patients has relative noradrenergic hyperactivity.

Plasma dopamine beta-hydroxylase activity in a North Swedish isolate with a high frequency of schizophrenia.

Plasma dopamine beta-hydroxylase (DBH) activity was determined in 115 members of a North Swedish geographical isolate with a high frequency of schizophrenia, of which 30 persons had schizophrenia, and was compared with a Middle Swedish population of 185 apparently healthy persons. There was no significant difference between the schizophrenic group and their healthy relatives or between the North and Middle-Swedish populations. The number of persons with very low plasma DBH activity in the North Swedish population appeared to be less than those in the control population.

Low serum dopamine beta-hydroxylase activity. A marker of congestive heart failure.

To gain information about the nature of disturbances in sympathetic nervous system control in congestive heart failure, serum dopamine beta-hydroxylase (DBH) activity was measured in 30 patients with heart failure of diverse etiologies and 29 healthy normotensive controls. The heart failure patients had been symptomatic for at least 6 wk and had elevated filling pressures, low cardiac indices, low ejection fractions, and wide arteriovenous oxygen differences. DBH activity was 47.1+/-4.7 (mean+/-SE) for the controls and 14.4+/-2.7 IU for the heart failure patients (P < 0.001). Sera from some patients with heart failure had potent inhibitory effects on DBH activity of normal sera. The inhibitor was heat stable and dialyzable and could be demonstrated despite presence of N-ethylmaleimide or Cu(++) in the reaction mixture. However, some inhibitory activity was also present in sera of normal patients; this inhibitory property was not demonstrable in unheated normal serum, but was unmasked when DBH was heat inactivated. It is proposed that although the inhibitor may have been a factor in low serum DBH activity in some patients with heart failure, the major cause of the low activity in the heart failure group was a reduced rate of synthesis or release of the enzyme by sympathetic nerves. This may reflect a dissociation between rates of neural release of norepinephrine and release of DBH in chronic, severe heart failure. The observation of low serum DBH levels in patients with heart failure suggests that measurement of DBH levels may serve as a useful indicator of cardiac dysfunction.

Effect of dopamine-beta-hydroxylase inhibition on cerebral vasospasm in the cat.

Inhibitors of dopamine beta hydroxylase (DBH) administered intraperitoneally were shown to prevent spasm of the basilar artery caused by blood application in cats. A low or nondetectable blood DBH activity level may be related to the absence of spasm. In several instances, however, moderate spasm did occur with a low blood DBH activity level. Possible mechanisms for these findings are discussed.

Dopamine-β-Hydroxylase Activity in Serum and Cerebrospinal Fluid in Neuropsychiatric Diseases

A 24-hour rhythm in serum dopamine-beta-hydroxylase (DBH) activity in chronic schizophrenic patients showed a similar change as that in normal subjects: the highest activity during day time with a peak at 12.00 h and the lowest activity at night with a bottom at 24.00 hr, 4 h after sleep onset. Between a group of schizophrenic patients who have sleep disturbance and another group of patients who have normal sleep patterns, no significant difference was observed in the 24-hour rhythm in serum DBH activity. Very low but significant DBH activity was found in cerebrospinal fluid of neuropsychiatric patients, and the values were approximately 1/1,000 of the serum activity. A case after cerebral injury showed a high DBH activity in cerebrospinal fluid.

Plasma dopamine beta-hydroxylase: a possible aid in the study and evaluation of hypertension.

The activity of dopamine beta-hydroxylase (DBH) in plasma ranged from 2 to 100 units per liter of plasma in 82 apparently healthy subjects (ages 22 to 35 years). A nonnormal pattern of distribution was evident: 62 subjects had values below 35 units (18 +/- 1), while 13 of the remaining 20 subjects had values above 60 units (80 +/- 5). Those with low DBH activity had lower values for urinary catecholamine excretion (31 +/- 3 micrograms), with normal and stable blood pressure; those with high DBH activity had higher values for urinary catecholamine excretion (72 +/- 6 micrograms), with greater lability of arterial blood pressure. The DBH activity was significantly elevated in patients with labile (74 +/- 2 mm-Hg) or fixed (57 +/- 2 mm-Hg) essential hypertension. The results indicate that plasma DBH activity is low and that it falls within a narrow range in young adults with normal and stable blood pressure.