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)

Temporary suppression of rats' bar pressing, activity, and feeding by the dopamine beta-hydroxylase inhibitor FLA-63 was synergistically potentiated by triiodothyronine (T3) treatment. The increased severity of duration of behavioral depression from the combination of mildly-depressing doses of FLA-63 (10 mg/kg, SC) and T3 (200 mug/kg, SC, 4X) was most marked 36-72 hr after FLA-63 and closely resembled the depressive syndrome produced by higher (30-90 mg/kg) doses of FLA-63 alone in timing and specific behavioral features; these depressions were more likely due to toxicity than to depletion of brain norepinephrine. T3 did not potentiate behavioral depression induced by diethyldithiocarbamate (25 mg/kg, SC). This pattern of findings suggested an interpretation of the T3-FLA-63 synergism in terms of increased FLA-63 toxicity in hyperthyroidism.
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PMID:Behavioral depression: thyroid interactions with norepinephrine-depleting drugs. 18 17

Antibodies against tyrosine hydroxylase (TH, the rate-limiting enzyme in norepinephrine synthesis) and dopamine beta-hydroxylase (DBH, the last enzyme in the synthesis) were used for immunohistochemical staining of human brain locus coeruleus sections, obtained postmortem from suicide victims and matched controls. Stain density over individual cells was quantified by a computerized, video-camera-based image analysis system. Mean stain density for TH was significantly lower (by about 30%) in the locus coeruleus of suicide victims. There was no difference between suicides and controls in DBH immunoreactivity or in the number of TH immunoreactive cells. Reduced TH availability, either genetically or environmentally determined, may contribute to the noradrenergic insufficiency postulated to occur in depression and the increased beta-adrenergic receptor concentrations observed in prefrontal cortex of suicide victims.
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PMID:Reduced tyrosine hydroxylase immunoreactivity in locus coeruleus of suicide victims. 134 45

Regulation of catecholamine biosynthesis is crucial in the adaptation to various physiological conditions, such as stress, and in several disorders, including hypertension and depression. In this study we have found that in PC12 cells, the mRNA levels of dopamine beta-hydroxylase (DBH), the enzyme that catalyzes the formation of norepinephrine from dopamine, can be regulated by glucocorticoids and cyclic AMP (cAMP) analogues. Treatment with dexamethasone increased DBH mRNA levels by 6 h. with maximal elevation (four- to fivefold) obtained after 1 day of exposure, and these levels were maintained for up to 4 days. DBH mRNA levels were also elevated on treatment of PC12 cells with 8-bromo cAMP for 8 h to 1 day. The response to 8-bromo cAMP, however, was bimodal, because DBH mRNA levels declined below control values on treatment for > 1 day. In combined treatments with 8-bromo cAMP and dexamethasone, the cAMP effect was dominant. To begin to characterize the regulation of DBH mRNA, genomic clones for rat DBH were isolated, and 1 kb of the 5' flanking region was sequenced. Several putative regulatory elements, which may be involved in cAMP and glucocorticoid regulation, were identified, including two adjacent cAMP response elements, another element that can also bind members of the ATF/CREB family of transcription factors, a NF-kappa B-like sequence, several AP-2 sites, and three core glucocorticoid receptor binding sequences.
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PMID:Regulation of expression of dopamine beta-hydroxylase in PC12 cells by glucocorticoids and cyclic AMP analogues. 135 11

To review data supporting or not supporting the designation of unipolar psychotic major depression as a distinct syndrome in DSM-IV, the authors used computerized literature searches to identify reports of studies that have directly compared the characteristics, biology, familial transmission, course/outcome, and response to treatment of psychotic and nonpsychotic major depression. The review showed that statistically significant differences between the two types of depression have been found on each of these dimensions. There are greater guilt feelings and psychomotor disturbance, among other features, in psychotic depression. Studies have found significant differences between patients with psychotic and nonpsychotic depression in glucocorticoid activity, dopamine beta-hydroxylase activity, levels of dopamine and serotonin metabolites, sleep measures, and ventricle-to-brain ratios. Family studies show higher rates of bipolar disorder in first-degree relatives of probands with psychotic major depression than of probands with nonpsychotic major depression. Greater morbidity and residual impairment have also been reported in patients with psychotic major depression, and they respond more poorly to placebo and to tricyclic antidepressants. Differences between patients with psychotic and nonpsychotic major depression on many of these measures were not due to differences in severity or endogenicity. Since the data indicate that psychotic and nonpsychotic major depression can be separated, the frequency with which the diagnosis of psychotic major depression is missed and its unique course and response to treatment point to the practical importance of a separate diagnosis for this disorder. However, further studies are needed to resolve important methodological issues and to develop an optimal set of operational criteria.
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PMID:Psychotic (delusional) major depression: should it be included as a distinct syndrome in DSM-IV? 831 97

A topographic map of the substance P and monoamine neurons in the ventrolateral medulla of the cat has been constructed from peroxidase anti-peroxidase immunohistochemically stained sections. The coordinates of this map use the foramen cecum of the medulla oblongata (i.e. the triangular depression at the junction between the caudal boundary of the pons and the rostral limit of the median fissure between the pyramidal tracts) as the zero point. Two distinct groups of substance P neurons have been found: a rostral group lies ventral to the facial nucleus and a caudal one is found ventrolateral to the inferior olivary nucleus. Two dopamine beta-hydroxylase-containing cell groups were identified that correspond to the A1 and A5 cell groups. The A5 cell group lies dorsal, lateral and caudal to superior olivary nucleus. The A1 cell group lies approximately 4.0-5.0 mm lateral to the midline at the level of the inferior olive; these cells lie mainly dorsolateral to the region of the magnocellular division of the lateral reticular nucleus. The B1 and B3 serotonin (5-hydroxytryptamine) cell groups of the ventrolateral medulla appear to form a continuous column with a rostral and a caudal swelling. The rostral group begins at the level of the facial nucleus (approximately 4 mm caudal to the foramen cecum) and is concentrated in the area just lateral to the pyramidal tract. It becomes reduced in size approximately 8.0 mm caudal to the foramen cecum, and then enlarges to form a caudal group (approximately 10 mm caudal to foramen cecum). Portions of this column overlap with the caudal substance P cell group. The C1 cell group lies in a restricted zone approximately 4.0 mm lateral to the midline at the level of the rostral part of the inferior olivary nucleus.
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PMID:Topographic organization of substance P and monoamine cells in the ventral medulla of the cat. 241 70

RS-Goitrin can be conveniently prepared by a simplification of the Ettlinger procedure. Goitrin is a moderate inhibitor of purified bovine adrenal dopamine beta-hydroxylase. The administration of goitrin leads to a depression of brain norepinephrine and to an elevation of heart and adrenal dopamine.
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PMID:Inhibition of dopamine beta-hydroxylase by goitrin, a natural antithyroid compound. 246 16

The preovulatory surge of luteinizing hormone reaches a maximum at 18.00 h on the day of pro-oestrus in female rats maintained with regular lighting from 06.00 to 20.00 h. This surge is initiated by a discharge of luteinizing hormone-releasing hormone into hypophysial portal blood. In this study, drugs which affect catecholamine-mediated neurotransmission were administered on the day of pro-oestrus and the effects on serum concentrations of luteinizing hormone and on subsequent ovulation were observed. alpha-Methyl-p-tyrosine, diethyldithiocarbamate and SKF 64139 inhibit catecholamine synthesis at the level of tyrosine hydroxylase, dopamine beta-hydroxylase and phenylethanolamine N-methyltransferase, respectively. Although alpha-methyl-p-tyrosine suppressed ovulation, it had a negligible effect on the incidence of the preovulatory surge. In contrast, the various treatments with diethyldithiocarbamate and SKF 64139 resulted in a minimal occurrence of the 18.00 h surge; at relatively low doses, however, these drugs frequently elicited a surge at 22.00 or 24.00 h which invariably resulted in ovulation. The failure of the surge after diethyldithiocarbamate or SKF 64139 was not associated with a loss of pituitary sensitivity to luteinizing hormone-releasing hormone. In terms of the hypothalamic concentration of dopamine, noradrenaline, adrenaline and 5-hydroxytryptamine at 18.00 h on pro-oestrus, the only common effect of diethyldithiocarbamate and SKF 64139, given in a dose which blocks the surge, was a severe depletion of adrenaline; alpha-methyl-p-tyrosine failed to produce this effect despite inducing a marked depression of dopamine and a moderate loss of noradrenaline. Neither the increase in hypothalamic dopamine after diethyldithiocarbamate, nor the alpha 2 receptor blocking properties of SKF 64139 appear to be relevant in this context since injections of L-dopa or piperoxane, an alpha 2 receptor antagonist, were without effect on the surge or ovulation. The failure of the surge after prazosin, an alpha 1 receptor antagonist, indicates that the function of adrenaline may be mediated postsynaptically by alpha 1 receptors. Clonidine, an alpha 2 receptor agonist which reduces the turnover rate of hypothalamic adrenaline, had effects of the surge and ovulation which were comparable to those of diethyldithiocarbamate and SKF 64139, the relatively low doses causing some of the surges to occur at 24.00 instead of 18.00 h and higher doses suppressing the surge at both times and thus preventing ovulation.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Effects of manipulating catecholamines on the incidence of the preovulatory surge of of luteinizing hormone and ovulation in the rat: evidence for a necessary involvement of hypothalamic adrenaline in the normal or 'midnight' surge. 635 42

A long-term epidemiological genetic study was conducted in which all new patients were evaluated prospectively at the Foundation for Depression and Manic Depression and two Lithium/Affective Disorders clinics at the Columbia-Presbyterian Medical Center between the years of 1972 and 1978. All patients met Feighner, RDC and DSM III criteria for Major Depressive Disorder after initial clinical screening interviews and were further subtyped using the Fieve-Dunner 7-point criteria. All 604 probands and 90% of 2711 first-degree relatives were interviewed blindly by diagnosticians trained in the use of the SADS structured interview. Cumulative morbid risk in parents, siblings and children of 490 bipolar probands was 15.6 +/- 3% and 14.0 +/- 1.7% in the first-degree relatives of 114 unipolar probands. A number of biological and genetic marker studies were simultaneously performed on samples of the overall population. The enzymes catechol O-methyltransferase and dopamine beta-hydroxylase, and the dexamethasone suppression test (SDT) did not show any biological marker value for outpatients even though both enzymes were determined to have hereditability. The HLA system, monoamine oxidase and acetylcholinesterase segregated differently from normal controls in samples of the patient population. The positive association findings with monoamine oxidase and the HLA system conflicted with the positive findings of other investigators, leaving doubtful their biological marker value. Red cell acetylcholinesterase was found to be significantly lower in affective disorder patients than in controls. This positive association finding was recently replicated by Mathews et al. (1982) but needs further confirmation. Using 28 blood group markers, a prior association study between the trait defining susceptibility to affective disorder and the genetic marker was positive for haptoglobin GC, and properdinfactor B, confirming earlier findings. Using the sib-pair method on the remaining 25 blood groups revealed that none other than peptidase A showed significant linkage with affective disorder since one significant finding is expected by chance. We conclude from the overall morbid risk data and segregation analyses that bipolar manic-depressive illness is a spectrum disease inherited through a multifactorial mode of genetic transmission (which is not synonymous with polygenetic inheritance) with possible genetic heterogeneity and find no evidence for X-linkage. Additional studies with acetylcholinesterase, haptoglobin, GC, and properdin-factor B are needed to confirm their positive biological/genetic marker value suggested by our long-term epidemiological study.
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PMID:Search for biological/genetic markers in a long-term epidemiological and morbid risk study of affective disorders. 651 12

Pretreatment of guinea pigs with paragyline (100 mg/kg i.p., 18 hr before sacrifice) resulted in a significant depression in the overflow of endogenous norepinephrine (NE), total 3H, [3H]NE and dopamine beta-hydroxylase associated with stimulation of the sympathetic nerves to the isolated heart. The depression was pronounced at 5 Hz. At 10 Hz, pargyline pretreatment was without effect. The effect on dopamine beta-hydroxylase output was not as great as that on total 3H, [3H]NE or endogenous NE release, suggesting the possibility that more than one mechanism is responsible for the depressant effect of monoamine oxidase (MAO) inhibition on sympathetic neurotransmission. A benzoquinolizine compound with reserpine-like properties, 2-hydroxy-2-ethyl-3-isobutyl-9, 10-dimethoxy,1,2,3,4,6,7-hexahydro-11b-H-benzo[alpha]quinolizine (RO 4-1284), increased the nerve stimulation-mediated overflow of all the measured indices of neurotransmitter release, in addition to producing a significant increase in the spontaneous overflow of 3H from hearts of untreated guinea pigs. The augmentation of nerve-stimulated NE release by RO 4-1284 was even greater in hearts from pargyline pretreated guinea pigs. These results would tend to eliminate a causal role for a deaminated metabolite of NE in the augmenting effect on release seen with RO 4-1284. Conversely, the inhibition of neurotransmitter release associated with MAO inhibition is not mediated by the blockade in the formation of deaminated catecholamine metabolites. Enhancement in the negative feedback mechanism on release and the accumulation of false transmitter probably account for the local effects of MAO inhibitors on neurally mediated norepinephrine release.
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PMID:The effect of pargyline pretreatment on the enhancement of the exocytotic release of norepinephrine during nerve stimulation which is induced by a benzoquinolizine compound with reserpine-like properties. 690 14

A 72 year-old female patient is presented in whom delusional depression, a possible distinct subtype of depressive illness characterized by a selective decrease of cerebrospinal fluid (CSF) norepinephrine (NE) metabolism, preceded the onset of Parkinsonism by several years. The report suggests that delusional depression may be a particular manifestation of depressive illness in Parkinsonian patients. In addition, since the activity of plasma and cerebrospinal fluid (CSF) dopamine beta-hydroxylase (DBH) is genetically determined, the co-occurrence of delusional depression and Parkinsonism in this patient may be related to a common underlying genetic defect that expresses itself biochemically by reduced cerebral NE metabolism.
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PMID:Delusional depression in Parkinson's disease. 808 26


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