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)

Corticotropin-releasing factor (CRF), the hormone responsible for adrenocorticotropin release during stress, is thought to be hypersecreted in depression. Because recent studies suggest that CRF may serve as a neurotransmitter in the major noradrenergic nucleus, locus coeruleus (LC), it was hypothesized that antidepressants interfere with the putative neurotransmitter role of CRF in the LC by either: 1) decreasing release of CRF; 2) pharmacologically antagonizing CRF; or 3) functionally antagonizing CRF by producing effects on LC cells that oppose these of CRF. In order to test this hypothesis, the effects of acute and chronic administration of two antidepressants, a norepinephrine re-uptake inhibitor (desmethylimipramine, DMI) and a serotonin re-uptake inhibitor (sertraline, SER), on LC spontaneous discharge, LC sensory evoked discharge, LC activation by a stressor and LC activation by CRF, were compared in halothane-anesthetized rats. Acute i.v. administration of DMI decreased both LC spontaneous discharge and discharge evoked by repeated sciatic nerve stimulation. In contrast, acute i.v. SER administration decreased only evoked LC discharge rate. Chronic DMI administration (10.0 mg/kg/day, i.p., 21 days) resulted in tolerance to its effects on spontaneous and sensory-evoked LC discharge. However, chronic DMI administration attenuated LC activation by hemodynamic stress, which is thought to require CRF release. LC activation by intracerebroventricular CRF was not altered in the chronic DMI rats. In contrast to DMI, chronic SER (10 mg/kg/day, i.p., 21 days) did not alter LC activation by either stress of CRF. However, the response of LC cells to repeated sciatic nerve stimulation was somewhat enhanced in chronic SER rats. This is an effect that is opposite that produced by CRF.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Antidepressant actions on brain noradrenergic neurons. 233 58

The response to lithium prophylaxis was assessed in a sample of bipolar patients subdivided into the following groups on the basis of the previous pattern of course of their illness: MDI (sequence mania-depression-free interval), DMI (sequence depression-mania-free interval), CC-LC (continuous circular course with long cycles), CC-RC (continuous circular course with rapid cycles), IRR (irregular course). A significant reduction of the mean number of morbid episodes and of the mean total morbidity during lithium treatment was observed only in patients with a previous MDI or IRR course. The percentage of responders to prophylaxis was significantly different among the five groups, and the difference could be mainly ascribed to the high response rate in the MDI group and the low response rate in the DMI and CC-RC groups. These results suggest that the classification of bipolar patients according to the previous pattern of course of their illness may be useful for the prediction of lithium response.
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PMID:Previous pattern of course of the illness as a predictor of response to lithium prophylaxis in bipolar patients. 252 91

Subcutaneous chronic desipramine (DMI, 5 mg/kg once daily for 18 consecutive days) prevented subcutaneous THIP (20 mg/kg) reduction in body temperature but did not affect THIP behavioral depressant effect (open-field behavior). Repeated DMI treatment did not affect subcutaneous baclofen (2.5-10 mg/kg) reduction in body temperature and behavioral depression (open-field behavior).
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PMID:Functional responses to baclofen and 4,5,6,7-tetrahydroisoxazolo (5,4-c) pyridin-3-ol (THIP) in rats repeatedly treated with desipramine. 335 25

As an alternative to the bipolar I/II distinction, a subtyping of bipolar affective disorders according to the sequence of polarity (mania or depression) has been proposed. In a study of 93 patients with bipolar affective and bipolar schizoaffective disorders we tested the stability of a subtyping using the sequence of polarity. Furthermore we investigated its relationship to bipolar I/II subtypes and to response to stabilizing therapy with lithium. In the individual patient the first sequence of polarity significantly predicted the same sequence of polarity of further manifestations. However, only half of the patients could be classified as either MDI (mania-depression-interval) or DMI (depression-mania-interval). Subtyping according to the sequence of polarity was not significantly related to the bipolar I/II subgroups. MDI patients showed a significantly better response to stabilizing therapy with lithium than DMI patients. Our findings lend support to the notion that the polarity sequence is of clinical relevance. The observed association between polarity sequence and effectiveness of lithium prophylaxis could be linked to direct consequences of a MDI or DMI sequence (e.g.: different treatment approaches). On the other hand, a difference in polarity sequence might be the clinical expression of a difference in the underlying mechanisms of dysregulation, which in turn might be more or less prone to respond to lithium therapy.
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PMID:Sequence of affective polarity and lithium response: preliminary report on Munich sample. 362 28

Thirty-four adolescents with mean age 14.25 years who met RDC criteria for major depressive disorder as assessed with the K-SADS, were treated for 6 weeks on a fixed schedule of imipramine hydrochloride titrated to a dosage of 5.0 mg/kg/day except as limited by side effects. Mean dose was 246 mg/day (4.5 mg/kg/day). In spite of good indications of compliance with treatment only 44% of the adolescents improved to the level of no or only slight depressed mood or anhedonia, though most had less depressive symptomatology at the end of treatment. There was neither a linear nor curvilinear relationship between total plasma level of IMI plus DMI and clinical response, despite a wide range of both plasma level (77 ng/ml to 986 ng/ml) and outcome. Adolescents with associated separation anxiety had significantly poorer response to treatment of their depressive disorder than those with major depression alone. Poor response was also weakly associated with being female, having endogenous subtype of depression, and having higher plasma IMI (but not DMI) level. In the context of similar studies of IMI on depression in other age groups, it is hypothesized that high levels of sex hormones during adolescence and young adulthood may interfere with IMI's antidepressant effects. It is concluded that other types of antidepressants should be tested in adolescents with major depression.
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PMID:Imipramine in adolescent major depression: plasma level and clinical response. 371 45

Despite their widespread use, there are few data concerning the effects of tricyclic antidepressants on EEG sleep in depression. The present study documented the effects of desipramine (DMI, n = 17) and amitriptyline (AT, n = 16) upon EEG sleep in hospitalized depressed patients as part of a double-blind protocol involving 28 days of active treatment. Compared to placebo, patients receiving DMI showed somewhat worsened sleep continuity, particularly after 1 week of administration when the dose was 150 mg/day. On the other hand, sleep architecture and REM measures showed a rapid suppression of REM sleep, and then partial tolerance for this effect was observed with continued administration of DMI for 3 weeks. DMI was a more potent suppressor of REM sleep, while AT was more sedative. Based on these differences in effects upon EEG sleep, a discriminant function was derived and resulted in a correct classification of 87.5% of AT cases and 76.5% of DMI cases. These results are discussed in terms of the differences in pharmacological profiles for uptake blockade and anticholinergic potency for these two compounds.
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PMID:Comparison of effects of desipramine and amitriptyline on EEG sleep of depressed patients. 392 Jun 95

EEG sleep recordings and two provocative neuroendocrinological tests (the DST and the GH stimulation test after desipramine) were investigated in two depressed pubertal monozygotic twin boys with Major Depressive Disorder and compared with results from one normal pubertal control boy and an adolescent girl suffering from major depression. REM latency was reduced in the adolescent depressed girl but not in the pubertal depressed twin children when compared to the normal control. Sleep continuity and sleep architecture were, however, disturbed in pubertal and adolescent depression as a function of severity of the depressive state. The results of the DST showed abnormal cortisol values in the most severely depressed twin and in the depressed adolescent. GH secretion after DMI showed a clear GH response in the less depressed twin and in the normal subject while in the depressed adolescent, the GH response was blunted. The findings suggest that REM latency disturbances in our depressed patients do not appear before adolescence, while neuroendocrine dysfunction can already be present in pubertal depression.
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PMID:Electroencephalogram and neuroendocrine parameters in pubertal and adolescent depressed children. A case report study. 623 57

The objectives were to determine the effects of rate of BW gain and type of silage fed before puberty on the partitioning of excess dietary energy between synthesis of milk and BW gain in second or third lactation. Accordingly, 41 Holstein heifers weighing 175 kg were fed diets containing either alfalfa silage or corn silage to gain either 725 or 950 g/d until BW was 325 kg and two estrous cycles were observed. Puberty occurred near 281 kg of BW. During second (n = 36) or third (n = 5) lactation, the cows were fed a control diet (60% forage and 40% concentrate) and a high energy diet (20% forage and 80% concentrate) in a double-reversal experimental design with three 6-wk periods. The rate of BW gain before puberty did not affect the magnitude of changes in DMI, milk yield, milk composition, or concentrations of thyroid hormones, insulin, bST, glucose, or lipids in serum when cows were switched from a control to a high energy diet during second or third lactation. However, compared with cows fed a corn silage diet, cows fed alfalfa silage between 175 and 325 kg of BW had more depressed yields of fat, total solids, and FCM when fed the high energy diet than when fed the control diet during second or third lactation. Increased deposition of fat in adipose and mammary tissues of cows with mean BW gain in excess of 950 g/d or fed a corn silage diet between 175 and 325 kg of BW did not result in more pronounced depression of milk fat percentage when cows were switched from a control to a high energy diet during second or third lactation. Overall, neither rate of BW gain nor type of silage fed between 175 and 325 kg of BW had a major influence on partitioning of excess dietary energy between synthesis of milk and BW gain during second or third lactation.
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PMID:Effects of prepubertal growth rate and diet on lipid metabolism in lactating Holstein cows. 759 46

Data were pooled from 11 studies evaluating supplemental fat sources differing primarily in degree of saturation (tallow, animal-vegetable fat, vegetable oil, and hydrogenated fats). Data were standardized as proportions of the respective controls to reduce variation among individual studies and were subjected to stepwise multiple regression against the iodine value of fats, the percentage increases of total fatty acids in diets above the respective controls, or the ratio of total C16 to C18 fatty acids in fats (only for hydrogenated fats). Increased iodine value (increasing unsaturation) of fats increased apparent fatty acid digestibility, especially as iodine value increased from 11 to 27. For partially hydrogenated fat sources, as the ratio of C16 to C18 fatty acids increased, digestibility also increased, especially with increasing iodine value (positive interaction). Beneficial effects of higher C16:C18 ratio were reduced as amount of added fat increased (negative interaction). Dry matter intake and FCM production decreased as iodine value increased, perhaps because of inhibition of fiber digestion or metabolic regulation of DMI. Milk protein percentage depression averaged .2 percentage units for most fats. However, as partially hydrogenated fat sources became more saturated, milk protein depression appeared to be less evident; increased ratio of C16:C18 of fatty acids appeared to increase milk protein percentage. Despite the lower apparent digestibility of fatty acids of hydrogenated fats, increased milk production and percentages of fat and protein appeared to make them more economical than more unsaturated fats.
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PMID:Assessment of the effects of iodine value on fatty acid digestibility, feed intake, and milk production. 796 57

Nine pregnant, nonlactating cows were used to monitor liver triglycerides before and after parturition. Estimates were made of the contribution of depressed feed intake and parturition to plasma NEFA concentrations and development of fatty liver. Liver biopsies and plasma samples were obtained on d 19, 10, 5, 3, and 1 prior to calving and on d 1, 7, 14, and 21 after calving. Depression of DMI started on d 2 prior to calving and was 40% of DMI on d 3 prior to depression of feed intake. Elevation of plasma NEFA concentrations started prior to DMI depression, on d 5 before parturition. Liver triglyceride infiltration did not occur until the concentration of plasma NEFA was maximized on d 1 after calving. This result implicated the acute rise in NEFA at calving as a contributing factor to triglyceride accumulation in the liver. The increasing plasma glucose and decreasing plasma BHBA prior to calving may have reflected metabolic changes toward gluconeogenesis. Liver glycogen decreased 70% during the final 19 d prior to calving. Hepatic triglyceride infiltration (7.7% DM basis) on d 1 post-partum and duration of DMI depression prepartum were less severe than those observed in previous studies. Frequent liver biopsies did not affect DMI.
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PMID:Peripartum liver triglyceride and plasma metabolites in dairy cows. 808 10


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