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 antidepressant and biochemical effects of femoxetine, a selective serotonin uptake inhibitor, and desipramine, a selective nor-adrenaline uptake inhibitor, have been compared in a double-blind study in 42 outpatients with depressive illness. The patients were allocated at random to treatment with either 600 mg femoxetine or 150 mg desipramine daily for 6 weeks. The total depression score showed a significant decrease in both groups, indicating an overall improvement in depressive symptoms. The patients treated with femoxetine reported significantly less severe anticholinergic effects during the whole treatment period than the desipramine patients. Both drugs, decreased the level of 5-HIAA in CSF, whereas no consistent changes were found in the MHPG and HVA levels. The pretreatment level of the metabolites had no predictive value for the outcome of the treatment with either drug. No significant correlation was found between therapeutic effect and the plasma concentration of the active compounds.
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PMID:Antidepressant effect of femoxetine and desipramine and relationship to the concentration of amine metabolites in cerebrospinal fluid. A double-blind evaluation. 618 53

Untreated adult coeliac patients have previously been shown to have a high frequency of depressive symptoms as reported in a personality inventory (the MMPI). In the present study we determined the concentrations of three major monoamine metabolites in samples of lumbar cerebrospinal fluid of ten consecutive adults with newly detected coeliac disease. They showed significant reduction in levels of 5-HIAA (70.3 +/- 25.4 pmol/ml). HVA (128.2 +/- 58.3 pmol/ml), and MOPEG (27.7 +/- 7.4 pmol/ml), indicating reduced central metabolism in all three monoamine pathways. The concentrations, in particular that of MOPEG, were inversely correlated with depressive symptoms reported on the MMPI scale 2 ('depression'), which conforms with current concepts on the pathogenesis of depression.
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PMID:Psychic disturbances in adult coeliac disease. III. Reduced central monoamine metabolism and signs of depression. 618 5

As part of the National Institute of Mental Health Clinical Research Branch Collaborative Program on the Psychobiology of Depression, the authors compared concentrations of CSF monoamine metabolites (the norepinephrine metabolite 3-methoxy-4-hydroxyphenylglycol [MHPG], the dopamine metabolite homovanillic acid [HVA], and the serotonin metabolite 5-hydroxyindoleacetic acid [5-HIAA]) from 14 hospitalized manic patients with concentrations from 62 healthy comparison subjects. The manic patients had significantly higher levels of MHPG. Levels of 5-HIAA and HVA did not differ between the manic patients and the comparison male subjects, but they were elevated in the female manic patients. MHPG was the only metabolite that correlated significantly with mania symptom ratings. These data are consistent with findings that have shown abnormal, perhaps excessive, central noradrenergic activity in patients with mania, but not with those suggesting deficits in serotoninergic function.
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PMID:CSF monoamine metabolites in mania. 618 81

In the cerebrospinal fluid of 38 patients with major depressive disorders the purine metabolites hypoxanthine and xanthine were positively correlated to the monoamine metabolites HVA and 5HIAA (p less than 0.0001). Hypoxanthine was also positively linked to the noradrenaline metabolite MHPG (p less than 0.005). By the use of multiple regression analysis 70% of the variance in hypoxanthine and 51% of the variance in xanthine were explained by HVA and 5HIAA. The scored magnitude of memory disturbance during depression was positively correlated to hypoxanthine, xanthine, HVA, and 5HIAA, while the degree of somatic anxiety as well as worrying was or tended to be negatively correlated to the same biochemical markers. The conspicuous relationship observed between purine and monoamine metabolite concentrations in CSF during depressive illness might indicate a parallel purinergic and monoaminergic activation of the brain. The observation that certain isolated depressive symptoms appear to relate to hypoxanthine/xanthine in CSF is consistent with the hypothesis of a central role of purines in behaviour.
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PMID:Purine and monoamine metabolites in cerebrospinal fluid: parallel purinergic and monoaminergic activation in depressive illness? 618 5

One hundred and ten patients with Research Diagnostic Criteria (RDC) diagnoses of major depressive disorders were assessed for present or recent suicidal ideation and behavior and for suicidal acts earlier in life before current depression using the Schedule for Affective Disorders and Schizophrenia (SADS). Suicidal scores were correlated uni- and bivariately with levels of CSF monoamine metabolites (HVA, 5HIAA, MHPG), urinary MHPG, the proportion post-/predexamethasone plasma cortisol at 1100 h, and platelet MAO activity (all standardized to same sex, age, height and weight). Results indicate that all 3 monoamine metabolites and their interactions are involved in various aspects of suicidality, at least in unipolar patients. MHPG and 5HIAA (both low or both high) were involved in current or recent suicidal ideation, and low HVA was mainly associated with past potential lethality of suicidal acts. Current hypercortisolism was found in patients that earlier in life had tried to commit dangerous suicides. Bipolar patients (depressives with a history of manic or hypomanic episodes) had earlier in life significantly more, and more dangerous, suicidal attempts than the unipolars.
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PMID:Life at risk: markers of suicidality in depression. 620 42

Acute, uncontrollable stress increases norepinephrine (NE) turnover in the rat's brain (thereby depleting NE) and diminishes the animal's subsequent tendency to explore a novel environment. We determined whether supplemental dietary tyrosine could prevent some of these changes. Rats given a control diet or diets enriched with tyrosine or tyrosine plus valine were exposed to tail-shock stress or to no stress over a 60-min period. Exposure to the stress caused an increase in NE turnover, decreasing NE and increasing 3-methoxy-4-hydroxy-phenylethylene glycol sulfate (MHPG-SO4) concentrations within the locus coeruleus, hypothalamus and hippocampus. No changes were detected in serotonin (5-HT) levels or turnover. Behavioral deficits following the stress were observed using measures of locomotion and of exploration in a novel open-field environment: stressed animals displayed much less spontaneous motor activity, hole-poking or frequency of standing on their hind legs than control animals. Animals receiving the tyrosine-enriched diet displayed neither the stress-induced depletion of NE nor the behavioral depression. These preventive effects of tyrosine were abolished by co-administration of valine, a large neutral amino acid that competes with tyrosine for transport across the blood-brain barrier. Since tyrosine alone, in animals not subjected to stress, did not change NE turnover nor the behaviors studied, our observations affirm that catecholaminergic neurons respond to the precursor amino acid only when they are physiologically active. Supplementary tyrosine may be useful therapeutically in people exposed chronically to stress.
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PMID:Neurochemical and behavioral consequences of acute, uncontrollable stress: effects of dietary tyrosine. 620 15

Relationships between pretreatment neurotransmitter metabolite levels and response to imipramine and amitriptyline were studied in 104 depressed patients. Normal values for urinary norepinephrine and low values for urinary MHPG were associated with greater incidence of drug response in bipolar, but not unipolar, patients. For unipolar, but not bipolar, patients low CSF 5-HIAA and high urinary metanephrine values were associated with a greater incidence of drug response. These data indicate that the pretreatment functional state of catecholamine and serotonin systems is associated with type of response to drug treatment. The authors present hypotheses about the association of alterations in serotonin and norepinephrine systems and definable subtypes of depression.
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PMID:Pretreatment neurotransmitter metabolite levels and response to tricyclic antidepressant drugs. 620 36

The diagnosis of depression has traditionally been based on clinical history and behavioral observations. While objective laboratory tests will further our understanding of the pathophysiology and perhaps aid in the management of depression, a critical examination of the application of these techniques in clinical psychiatry is warranted by their increasing use. The utility for clinicians of the dexamethasone suppression test (DST), urinary MHPG assay, and tricyclic antidepressant plasma level assay is reviewed.
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PMID:Possible clinical applications of laboratory tests in depression. 637 Sep 77

A double-blind comparison of zimelidine, a potent and fairly selective 5-hydroxytryptamine (5-HT) uptake inhibitor, and desipramine, a noradrenaline (NA) uptake inhibitor, was carried out in hospitalized patients with endogenous depression. The patients were randomized into parallel groups receiving either zimelidine 100 mg b.i.d. or desipramine 75 mg b.i.d. Forty patients completed the study, twenty in each treatment group. Patients who did not respond adequately to one drug after 4 weeks were treated with the other drug (cross-over design) after a washout period. For evaluation of the therapeutic efficacy Hamilton Rating Scale for Depression, Comprehensive Psychopathological Rating Scale for Depression, Beck's Inventory and Global Rating Scales were used. All ratings indicated greater effectiveness for zimelidine as compared with desipramine, although the differences were not generally statistically significant. Only "somatic anxiety" on the Hamilton scale was significantly (P less than 0.05) in favour of zimelidine. Although both zimelidine and desipramine were well tolerated, the zimelidine patients reported significantly less severe anticholinergic adverse reactions. Of five patients who did not improve on zimelidine, three were then given desipramine but only one recovered completely. Of 10 patients who were switched over to zimelidine, 6 recovered completely and one moderately. Zimelidine produced strong inhibition of the uptake of 5-HT in platelets and a decrease in blood 5-HT after 2 weeks or longer treatment. The uptake of 5-HT in rat hypothalamic synaptosomes was reduced by about 50% and that of NA about 20% when incubated in the patients' plasma. All these effects seem to be mainly due to norzimelidine. Desipramine produced strong inhibition of the uptake of NA in hypothalamic synaptosomes but weak effect on the 5-HT uptake. Urinary MHPG tended to decrease during desipramine treatment but was not affected or tended to increase during zimelidine treatment.
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PMID:Controlled cross-over study of a 5-HT uptake inhibiting and an NA uptake inhibiting antidepressant. 645 94

A reliable method is described using high pressure liquid chromatography to measure creatine, creatinine, and urate in human cerebrospinal fluid (CSF) and blood; albumin was analyzed by routine methods. Creatine and creatinine serve as indices of one aspect of brain energy metabolism, the creatine-creatine phosphate (CrP) shuttle. CSF levels have been adjusted to a set blood level by analysis of covariance. The ratios between CSF and blood concentrations of urate and albumin are two sensitive indices of impaired blood-brain barrier (BBB) function. Analyses were performed on 41 male and 58 female inpatients with RDC major depressive disorders, with a mean age of about 40 years. The CSF creatinine and creatine levels were highly positively age-dependent; this factor as well as possible influences of body habits were removed by way of analysis of covariance from all measures in focus. We describe positive, highly significant correlations between creatinine and monoamine metabolites (HVA and 5HIAA) and purine metabolites (hypoxanthine and xanthine) in CSF, and a strong negative correlation between both BBB permeability measures and the noradrenalin CSF metabolite MHPG. CSF creatinine was negatively linked with suicidal ideation and increased appetite. The BBB tended to be the more permeable the less melancholic the depression. No measure appeared to be dependent on depressive state. Comparisons of depressive subgroups revealed a higher CSF creatinine concentration in sporadic unipolar patients according to Winokur. A particularly wide variance in the albumin ratio was found in pure unipolars. Pure unipolars with an impaired BBB had a more protracted onset, were more suicidal, had a higher erythrocyte sedimentation rate, and lower plasma cortisol levels than those without. Impaired BBB was further linked with a slower EEG rhythm and higher systolic blood pressure. Results suggest significant contributions of brain energy metabolism and deranged BBB permeability in accounting for some aspects of neuronal transmission and modulation as well as the symptomatology of depressive illness.
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PMID:Brain energy metabolism and blood-brain barrier permeability in depressive patients: analyses of creatine, creatinine, urate, and albumin in CSF and blood. 649 42


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