Serum Dopamine-beta-hydroxylase Research Articles

Effect of cold exposure on serum DBH and interscapular brown adipose tissue MAO activity in hypothyroid T3- and T4-treated rats.

As the indicators of sympathetic nervous system (SNS) function, the activity of serum dopamine-beta-hydroxylase (DBH) and interscapular brown adipose tissue (IBAT) monoamine oxidase (MAO) were examined in rats that were chemically thyroidectomized (TX), treated with thyroid hormones, and exposed to cold (4 degrees C). In TX animals, body temperature (bt) significantly decreased, and relative IBAT mass increased as compared with control, euthyroid animals, independent of the ambient temperature. The bt fall in TX cold-exposed animals was more severe, provoking hypothermia after 4 h. Under the same experimental conditions, the SNS function was enhanced as judged by the increased serum DBH and IBAT MAO activities. The treatment of TX animals with T(4) and T(3) re-established the temperature (bt was at the level of controls) and sympathetic homeostasis (DBH activity was at the level of controls) in animals maintained at room temperature but not in those kept under cold conditions. T(4) and T(3) did not affect IBAT MAO activity of TX rats: It remained significantly above the control values whether the animals were maintained at room temperature or exposed to cold. In conclusion, the IBAT of TX cold-exposed rats is incapable of responding to the enhanced thermogenic needs despite the increased SNS activity and thyroid hormone substitution.

Genetically determined low maternal serum dopamine beta-hydroxylase levels and the etiology of autism spectrum disorders.

Autism, a neurodevelopmental disability characterized by repetitive stereopathies and deficits in reciprocal social interaction and communication, has a strong genetic basis. Since previous findings showed that some families with autistic children have a low level of serum dopamine beta-hydroxylase (DbetaH), which catalyzes the conversion of dopamine to norepinephrine, we examined the DBH gene as a candidate locus in families with two or more children with autism spectrum disorder using the affected sib-pair method. DBH alleles are defined by a polymorphic AC repeat and the presence/absence (DBH+/DBH-) of a 19-bp sequence 118 bp downstream in the 5' flanking region of the gene. There was no increased concordance for DBH alleles in affected siblings, but the mothers had a higher frequency of alleles containing the 19-bp deletion (DBH-), compared to an ethnically similar Canadian comparison group (chi(2) = 4.20, df = 1, P = 0.02 for all multiplex mothers; chi(2) = 4.71, df = 1, P < 0.02 for mothers with only affected sons). Although the odds ratios suggested only a moderate relevance for the DBH- allele as a risk allele, the attributable risk was high (42%), indicating that this allele is an important factor in determining the risk for having a child with autism. DBH genotypes also differed significantly among mothers and controls, with 37% of mothers with two affected sons having two DBH- alleles, compared to 19% of controls (chi(2) = 5.81, df = 2, P = 0.03). DbetaH enzyme activity was lower in mothers of autistic children than in controls (mean was 23.20 +/- 15.35 iU/liter for mothers vs. 33.14 +/- 21.39 iU/liter for controls; t = - 1.749, df = 46, P = 0.044). The DBH- allele was associated with lower mean serum DbetaH enzyme activity (nondeletion homozygotes: 41.02 +/- 24.34 iU/liter; heterozygotes: 32.07 +/- 18.10 iU/liter; and deletion homozygotes: 22.31 +/- 13.48 iU/liter; F = 5.217, df = 2, P = 0.007) in a pooled sample of mothers and controls. Taken together, these findings suggest that lowered maternal serum DbetaH activity results in a suboptimal uterine environment (decreased norepinephrine relative to dopamine), which, in conjunction with genotypic susceptibility of the fetus, results in autism spectrum disorder in some families.

Is the polymorphic microsatellite repeat of the dopamine β-hydroxylase gene associated with biochemical variability of the catecholamine pathway in schizophrenia?

Six allelic fragments were typed by a polymerase chain reaction process with a pair of primers specific for a sequence containing the polymorphic (GT)n repeat, a microsatellite repeat, in the human dopamine beta-hydroxylase (DBH) gene. Their frequencies in unrelated patients with schizophrenia were 0.003 (A1), 0.114 (A2), 0.343 (A3), 0.526 (A4), 0.006 (A5), and 0.009 (A6), and in unrelated control subjects, 0.012 (A1), 0.086 (A2), 0.309 (A3), 0.574 (A4), 0.006 (A5), and 0.012 (A6). Kruskal-Wallis analysis revealed significant differences among the three groups, the drug-free and drug-treated patients, and the control subjects, in serum DBH activity of the subjects whose genotype was A2/A3 (H = 6.0, p < .05) or A3/A3 (H = 9.8, p < .01), in serum homovanillic acid concentration of those whose genotype was A3/A4 (H = 7.7, p < .025), and in serum tyrosine concentration of those whose genotype was A4/A4 (H = 8.3, p < .02). Mann-Whitney U test showed that in the subjects carrying the A3/A4 genotype, serum noradrenaline concentration of drug-treated patients was significantly higher than that of control subjects (N = 58, p < .02). These results suggest that genotypic polymorphism of the human DBH is likely to be associated with biochemical variability of the catecholamine pathway in schizophrenia.

Maltreatment, conscience functioning and dopamine β hydroxylase in emotionally disturbed boys

Objective: Identify associations among early maltreatment, sufficiencies, and psychopathological interferences in the domains of conscience functioning and low serum dopamine beta hydroxylase activity. Method: Nineteen emotionally disturbed boys screened for maltreatment experiences were compared according to age at onset of maltreatment, enzyme activity, and their conscience functioning in the domain of moral valuation. They were also compared in conscience functions to 19 age and sex matched normal counterparts. Results: Subjects who endured maltreatment prior to 36 months had developmental delays and interferences with functioning in more conscience domains than those who were either spared such experiences or who endured maltreatment later in life. Subjects with low enzyme activity had significantly more interference with authority and peer valuation than subjects with high enzyme activity. Greater interference with valuation was associated with lower enzyme activity and more frequent abuse prior to 36 months. Conclusions: Psychosocial sequelae of early maltreatment have been identified in the domains of conscience. An association has been established between pathological interference in the domain of moral valuation and a putative neurobiologic sequelae of early maltreatment. Implications for future research in the psychobiology of maltreatment are discussed.

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.

Serum dopamine beta hydroxylase and maltreatment in psychiatrically hospitalized boys

Fifty boys, hospitalized on a school-age and an adolescent unit in an intermediate length psychiatric hospital, were studied while off psychoactive medication to determine how serum dopamine beta hydroxylase (DBH) activity varies with different childhood maltreatment experiences. Childhood maltreatment was categorized according to onset (before 36 months old, between 36–72 months old and over 72 months old). Childhood maltreatment groups were compared with a group of psychiatrically hospitalized boys who had neither been abused nor neglected. Boys who were younger than 72 months at age of onset of maltreatment had significantly lower DBH activity than those who had experienced maltreatment later in childhood and those who had not been subjected to abuse or neglect. This difference appeared attributable to the DBH activity of school age (but not adolescent) boys who had been abused/neglected before 72 months. Boys with a principal diagnosis of conduct disorder solitary aggressive type had lower DBH activity than boys without this diagnosis regardless of whether or not they had been maltreated. Low serum DBH may be a biological sequela of maltreatment early in life that correlates with the development of conduct disorder solitary aggressive type in boys.

Molecular studies in patients with serum dopamine beta hydroxylase deficiency

Molecular studies in patients with serum dopamine beta hydroxylase deficiency

Serum dopamine-beta-hydroxylase activity in clinical subtypes of depression.

Serum dopamine-beta-hydroxylase (DBH) activity was determined in male adult psychiatric patients (n = 280) and age-matched male healthy controls (n = 100). Patients included in the study had no history of previous or current exposure to psychoactive drugs and were diagnosed according to Research Diagnostic Criteria. A significant decrease in serum DBH activity was noted in patients with psychotic major depressive disorder (n = 50) as compared with controls. In acute schizophrenics (n = 100), nonpsychotic major depressives (n = 45) and patients with manic disorder (n = 85), mean DBH activity did not differ significantly from the control values.

Multivariate analysis of monoamine indices in patients with chronic schizophrenia

Levels of dopamine (DA), dihydroxyphenylacetic acid (DOPAC), homovanillic acid (HVA), noradrenaline (NA), 5-hydroxyindoleacetic acid (5-HIAA) in cerebrospinal fluid and serum levels of prolactin (PRL) and dopamine-beta-hydroxylase (DBH) were measured in 42 chronic schizophrenic inpatients grouped according to their scores on the Brief Psychiatric Rating Scale (BPRS) and the Abnormal Involuntary Movement Scale (AIMS). Factor analysis was carried out on various combinations of variables. In patients with tardive dyskinesia (TD), cerebrospinal fluid DA, DOPAC, HVA, NA, and serum DBH were distributed into three factors; in patients without TD, these substances were assembled in only one factor. Cerebrospinal fluid DA, DOPAC, and HVA were dispersed in two factors in patients with severe positive symptoms versus one factor in subjects with mild productive signs. Factor structures diverged only when the variables listed above were included in the analysis. These findings support the hypothesis that both the dopaminergic and the noradrenergic system contribute to TD and that positive schizophrenic symptoms are associated with dopaminergic dysregulation.

Heart rate variation and serum dopamine-beta-hydroxylase activity in workers exposed to vibration.

Tests of autonomic nervous function were conducted on 38 workers who had been exposed to vibration [16: VWF(+) group, 22: VWF(-) group, VWF: vibration-induced white finger] and 17 workers who had not been exposed to vibration (control group). Measurements were made of R-R interval variation of the electrocardiogram at rest and during deep breathing, and serum dopamine-beta-hydroxylase (DBH) activity during an immersion test of the hand in 10 degrees C water. Heart-rate variation related to respiratory arrhythmia indicates parasympathetic activity, and serum DBH activity is regarded as an indicator of sympathetic activity. The variations in the R-R interval during deep breathing were smallest in the VWF(+) group, followed by the VWF(-) group (P less than 0.05 and P less than 0.01, compared with the control group). The DBH activity of the VWF(+) group was larger than those of the VWF(-) group and the control group, however, the differences were small and not statistically significant. The reduced R-R interval variations in the VWF(+) and the VWF(-) groups support the hypothesis that autonomic nervous function can be affected by exposure to vibration. The change of DBH activity induced by cold exposure may be an unsuitable index of sympathetic tone. Further study of the autonomic nervous function in workers with vibration syndrome is recommended.

Comparative effects of carbohydrate restriction vs starvation on biochemical parameters related to neurotransmitters in rat.

Adult rats were submitted to a 4-day starvation period or maintained on a 50% carbohydrate-restricted diet for 8 consecutive days to obtain a body weight loss of 20-30%. Serum dopamine-beta-hydroxylase (DBH) activity and amino acids content were measured as well as brain tryptophan and tyrosine levels. Moreover, brain serotonin (5-HT), 5-hydroxyindoleacetic acid (5-HIAA), noradrenaline (NA), and dopamine (DA) contents were assayed in five brain areas. In 4-day starved and 8-day carbohydrate-restricted rats, the serum tyrosine and total tryptophan contents as well as tyrosine to the sum of six neutral amino acids ratios were lowered. Moreover, in these groups, free tryptophan to the sum of six neutral amino acids ratio remained normal and serum DBH activity increased. In the brain, to a decreased tyrosine content observed in 4-day starved and 8-day carbohydrate-restricted rats corresponded a high DA to NA ratio in the hypothalamus, thalamus, and raphe nuclei, thus suggesting a low DA utilization whereas a low DA to NA ratio was found in the neostriatum. On the other hand, brain tryptophan content was decreased in 4-day starved rats and increased in 8-day carbohydrate-restricted rats. In the former group, a high 5-HT to 5-HIAA ratio characteristic of a low 5-HT utilization was found in the hypothalamus and neostriatum whereas in the latter group a significant decrease in this ratio was only observed in the thalamus. These results suggest that the biochemical response to starvation vs carbohydrate restriction can be differentiated on neurochemical and neuroanatomical bases.

Localization of the human dopamine beta hydroxylase (DBH) gene to chromosome 9q34.

A human cDNA clone for dopamine beta hydroxylase (DBH) has been isolated from a phaeochromocytoma library. In situ hybridization of this probe to replication-banded chromosomes has localized the gene to chromosome 9q34. The structural gene for the enzyme is therefore close to the ABO blood group locus. This suggests that the previously described activity variation in levels of serum DBH may reflect alterations in either the structure or regulation of the DBH coding sequences. Both biochemical and genetic evidence therefore indicate independence of DBH from the pterin-dependent aromatic amino acid hydroxylases of the neurotransmitter pathways.

Serum dopamine beta hydroxylase activity and tardive dyskinesia

A case-control study was done to test the effect of serum dopamine-beta-hydroxylase (DBH) activity on tardive dyskinesia (TD) among 85 schizophrenic outpatients treated with neuroleptics. In contrast to the results of several previous studies, we found no significant association between serum DBH activity and the occurrence or severity of TD, controlling for other TD predictors.

A comprehensive study of chronic schizophrenic patients. II: Biological, neuropsychological, and clinical correlates of CT abnormality.

There are numerous reports of lateral cerebral ventricle enlargement on computed tomography (CT) in schizophrenics, but the significance and its relationship to traditional notions of organicity remain unclear. Therefore we studied a subgroup of chronic schizophrenics who had lateral ventriculomegaly (and also cortical hyperdensity) on a battery of relevant biological, neuro-psychological, and clinical parameters such as electroencephalogram (EEG), platelet monoamine oxidase (MAO) and serum dopamine-beta-hydroxylase (DBH) activity, the Halstead Reitan Neuropsychological Battery (HRB), premorbid personality adjustment, drug response, positive and negative symptoms, employment history, and family history. Our findings support the notion that there is an "organic" subgroup of schizophrenia that has 1) CT structural abnormalities such as lateral ventricle enlargement and cortical hyperdensity; and cerebral dysfunction or deficits as evidenced by 2) an increased incidence of abnormal EEGs and also 3) greater impairment on neuropsychological tests. The biochemical measures, platelet MAO and serum DBH activity, nor any of the clinical measures could differentiate between the subgroups. The implications of these findings for the subtyping of schizophrenia are discussed.

Serum dopamine beta-hydroxylase activity in menstrual migraine.

Migraine has been considered a manifestation of sympathetic dysfunction. Serum dopamine beta-hydroxylase (D beta H) has been shown to be an index of peripheral sympathetic activity by some workers and there are two reports of elevated activity of the enzyme during the migraine headache as well as in the headache-free interval. We studied the enzyme in seven women complaining of regular attacks of menstrual migraine and eleven controls during the mid-follicular (days 10 +/- 2) and premenstrual (days 28 +/- 2) phases of the menstrual cycle. Although levels were on average 26% and 10% higher respectively than in control subjects, the difference failed to reach statistical significance because of the large normal range for enzyme activity. However, the premenstrual results were significantly lower (p less than 0.001) than the mid-follicular measurements in the migraine group, little difference being found in controls. This finding, and the effects of successful therapy with anovulatory doses of oestradiol implants in not only significantly lowering serum D beta H but also significantly reducing the difference in enzymic activity between the early and late phases of the menstrual cycle, suggest that if this enzyme is an index of sympathetic activity, it is excessive fluctuations of the sympathetic nervous system that may be relevant in menstrual migraine.

Study on the mechanism of the appearance of noise effects

This study was undertaken to investigate the dose-response relationship between the biological effect and noise exposure, and to consider the mechanism of the appearance of noise effects. Rats were exposed to noise at intensities of 60 dB (A), 80 dB (A) and 100 dB (A) for 240 min and examined for the change of activities of dopamine-beta-hydroxylase (DBH) in serum and adrenal glands. Plasma cyclic adenosine 3',5'-monophosphate (c-AMP) levels were also measured. Some rats were given 6-hydroxydopamine (6-OHDA) as a chemical sympathectomyzing agent 20 h before noise exposure in order to consider the mechanism of the appearance of noise effects. By noise exposure, serum DBH activity was significantly (P less than 0.01) increased at each intensity compared with the control group, but there were no remarkable changes in adrenal DBH activity. Plasma c-AMP level was also significantly elevated in response to the noise stress. When the rats, which had been pretreated with 6-OHDA, were exposed to noise with an intensity of 100 dB (A), the response of serum DBH activity was no longer observed. Therefore it is suggested that the effect due to noise exposure appears through the post-ganglionic sympathetic nerve fiber.

Serum dopamine beta-hydroxylase and free fatty acids in exercise-induced asthma.

Serum dopamine beta-hydroxylase activity, which is thought to reflect noradrenaline secretion, and free fatty acid level were measured in twenty atopic asthmatic children, of whom ten had exercise-induced asthma (EIA), after exercise on the treadmill. There was a significant decrease in the level of serum dopamine beta-hydroxylase activity in the asthmatics who developed EIA and this closely accompanied the onset of airflow obstruction. There was no change in the free fatty acid levels. In contrast, the asthmatics, who did not have EIA showed a significant rise in the levels of dopamine beta-hydroxylase activity and free fatty acids after the same exercise task. Our results suggest that the atopic children studied, who developed EIA, may have had an impaired noradrenaline response to exercise. It is further suggested that this impaired noradrenaline secretion may facilitate mediator release and contribute to the airflow obstruction in EIA.

Serum dopamine-beta-hydroxylase in diagnostic subgroups of depressed patients and in relation to their personality characteristics.

Serum dopamine-beta-hydroxylase (DBH) levels were assessed in 150 depressed patients of both sexes, with a mean age of 44.0 +/- 12.3 (SD) years. Patients were divided into unipolars (n = 46), bipolars (n = 25), neurotic-reactive (n = 46) and unspecified (n = 38) i.e., those who did not fit into any of the previous categories. According to their status 38 patients were psychotic and 104 clearly nonpsychotic at the time of the DBH assessment. Personality characteristics were assessed for the same patients when they had markedly improved from their depression. In line with previous findings bipolar patients were found to have slightly lower serum DBH values than unipolars, and psychotic patients slightly lower values than nonpsychotic. However, none of the differences among diagnostic groups or between psychotic and nonpsychotic patients was statistically significant. Weak negative correlations were found between serum DBH and the personality variables social desirability and indirect aggression, but an earlier finding of a positive correlation with the personality trait monotony avoidance, could not be confirmed. Owing to the large interindividual variations in serum DBH it is concluded that correlations between serum DBH and personality characteristics might be spurious and due to chance. This study does not support the assumption that significant differences in serum DBH might occur among subgroups of depressed patients.

Serum dopamine beta hydroxylase in children with neuroblastoma.

Serum dopamine-beta-hydroxylase (DBH) activity has been reported to be raised in some patients with neuoblastoma but this has been challenged. We have studied serum DBH levels on 26 children with neuroblastoma and 58 age-matched controls. Only in 2 patients were the levels higher than in the controls, and then only transiently. In both, the rise in DBH levels could be accounted for by the transfusion of adult blood. Serum DBH levels in children with neuroblastoma were unrelated to the response of this neoplasm to treatment or to urinary catecholamine output and thus are unlikely to have any value in diagnosis or as a marker of tumour activity.

Lithium: effects of short-term and chronic treatments in rats on the activity of dopamine-beta-hydroxylase (DBH) in the central versus peripheral nervous system

The therapeutic usefulness of lithium in mania is now well-established. However, the precise neurochemical mechanisms by which lithium brings about its effects remain poorly understood. This report describes the effects of lithium on the central and peripheral levels of activity of dopamine-β-hydroxylase (DBH), the enzyme that catalyzes the final step in the biosynthetic pathway to the formation of norepinephrine (NE) from dopamine. Since the neurotransmitter NE has been implicated in the mediation of lithium's action, what effects lithium may have on the activity of DBH was deemed worth investigating. Lithium chloride was administered intraperitoneally in rats on a short-term and chronic basis and the effects on DBH activities in the hypothalamus and serum were evaluated. A significant reduction in DBH activity occurred in the hypothalamus after short-term lithium butthere was no change following chronic treatment. In contrast, serum DBH activity remained unchanged after both acute and chronic lithium injection. Since increased noradrenergic activity in the brain has been implicated in the etiology of mania, the lithium-induced decrease in hypothalamic DBH is suggestive of a neurochemical mechanism by which lithium may act in psychotic patients.