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)

Records of 908 patients of 10 Parisian gynecologists are included in these preliminary results of an ongoing 3-year survey of patient characteristics and consequences of contraception in France. The population averaged 26.8 years, parity 1.1; 39% were single, 21% not working, 15% students, the rest working. These characteristics, and the methods chosen, differed widely among patients of different physicians. 55.5% first chose pills, 26% IUDs, 18.5% chose diaphragm; of these, 28 pill patients, 11 IUD patients and 13 diaphragm patients then chose another method. The second choices were pills by 17, IUDs by 15, and diaphragms by 20. Those who chose pills tended to be single, working, nulliparas, and without previous contraceptive history. IUD and diaphragm users were similar in these characteristics. 7 types of IUDs (61% Corolle, 25% Saf-T-Coil, 16% Omega, 11% Trefle, 10% Sterilem, 6% Lippes loop, 1% Canel) resulted in 23 (9.7%) patients with bleeding side effects and 17 (7.1%) expulsions. 75% of pill patients took Stediril, 25% took 12 other types. Chief complications were weight gain in 11 (1%), nervousness or depression in 11, bleeding in 7, and nausea in 7. There were 7 accidental pregnancies, 2 with IUDs in place, 1 after expulsion (3.5% Pearl index), 4 pregnancies with diaphragm (11.06% Pearl index), and 2 unplanned pregnancies after the women stopped their pill and diaphragm because of their partner's objections.
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PMID:[Follow-up survey of women under contraception]. 1225 83

The effectiveness and side effects of Marvelon (0.150 mg desogestrel and 30 mcg ethinyl estradiol) were evaluated in a multicenter study of 1570 women for a total of 22,158 menstrual cycles. Half the women in the study were under age 25. Only 1 pregnancy was reported, and this was due to patient failure. The frequency of spotting and breakthrough bleeding decreased steadily from 22.3% in the 1st treatment cycle, 14.9% in the 2nd, 8.4% in the 6th, 5.6% in the 12th, to 2.8% in the 21st and then rose slightly from 3.6% in the 24th cycle. This pattern of irregular bleeding during the early cycles is common to all oral contraceptive preparations. Changes in body weight were almost negligible and restricted to women under age 20. There was no change in average blood pressure when compared with pretreatment values. Superficial thrombophlebitis occurred in 7 women. Side effects, including nausea, headache, nervousness, depression, and breast tenderness, declined to negligible levels as treatment progressed. Levels of plasma protein sex-hormone-binding globulin (SHBG) appear to be higher with Marvelon than with a similar preparation containing levonorgestrel and ethinyl estradiol. Other studies have noted significantly higher serum high density lipoprotein (HDL) cholesterol levels with Marvelon than with combined levonorgestrel and ethinyl estradiol. This is attributed to the lack of androgenicity of desogestrel in the clinical dosage used in this study. SHBG and serum HDL levels are increased by estrogens and decreased by androgens.
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PMID:Desogestrel and ethinyloestradiol. 1227 90

Preliminary results of side effects are reported by 66 physicians of the M.F.P.F. (Mouvement Francais de Planning Familial) on 2026 women taking Stediril, 610 taking Aconcept, and 824 taking Ov 28 for at least 6 months (less for dropouts) since 1969. There were no pregnancies or severe complications except 1 case of jaundice and 2 of thrombosed hemorrhoids. Blood pressure was unchanged in 60-70% of cases, and the graph of these changes, except for a slight increase at "up to 10 mm Hg," was a symmetrical bell curve. Stediril and Ov 28 had identical effects on blood pressure, but the curve for Aconcept was flatter. Weight gain of 1 kg or more was reported in 37% of Stediril users and 42% of Ov 28 users (p less than .05). Other side effects showing significant differences between products were: nausea greater with Ov 28, depression greater with Aconcept, metrorragia greater with Stediril, pelvic pain less with Stediril, headaches less with Ov 28, amenorrhea less with Stediril. This absence of serious side effects was considered the most significant French statisitc published to date on oral contraceptives.
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PMID:[Statistical study of side effects in 3460 women taking combined estrogen-progestagens: preliminary results]. 1230 13

Leptin inhibits appetite by activating several neuroendocrine systems, including the hypothalamo-pituitary-adrenal cortical (HPA) axis. In turn, chronically elevated glucocorticoids increase circulating leptin. HPA axis hyperactivity occurs in 30-50% of patients with major depression, but the few prior reports of leptin measurements in this illness have shown inconsistent results. We, therefore, measured plasma leptin in 12 female and 8 male unipolar major depressives and 12 female and 8 male individually matched normal controls administered low-dose physostigmine (PHYSO) and arginine vasopressin (AVP) to stimulate the HPA axis. The subjects underwent four test sessions 5-7 days apart: PHYSO (8 microg/kg IV); AVP (0-08 U/kg IM); PHYSO+AVP; and saline control. Serial blood samples were taken before and after pharmacologic challenge and analyzed for leptin, ACTH(1-39), cortisol and AVP. Estradiol and testosterone also were measured at each test session. PHYSO and AVP produced no side effects in approximately half the subjects and predominantly mild side effects in the other half, with no significant patient-control differences. Correlations between side effects (absent or present) after PHYSO or AVP and the corresponding leptin responses were non-significant in all groups. Baseline plasma leptin concentrations (mean+/-S.D.) were significantly higher in the female patients compared to the female controls (22.5+/-13.9 ng/ml vs. 12.3+/-9.7 ng/ml), whereas they were similar in the male patients and the male controls (3.9+/-1.4 ng/ml vs. 3.6+/-2.0 ng/ml). Leptin concentrations following PHYSO remained unchanged from baseline, indicating that the short-lived ACTH and cortisol increases produced by PHYSO did not affect leptin secretion. In contrast, AVP administration, while also increasing ACTH and cortisol, significantly suppressed leptin, more so in the women than in the men. Baseline leptin and the leptin decrease after AVP were moderately positively correlated with the Hamilton Depression Scale 'somatization' factor in the female patients (r=0.50) and more strongly correlated with the 'mood-depression' factor in the male patients (r=0.81). These findings indicate a sexual diergism (functional sex difference) in plasma leptin measures between major depressives and matched normal controls.
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PMID:Sexual diergism of baseline plasma leptin and leptin suppression by arginine vasopressin in major depressives and matched controls. 1255 82

We have developed a short-term gonadal recrudescence test with the estuarine mummichog (Fundulus heteroclitus) and determined endocrine end points sensitive to a strong estrogen agonist (ethynylestradiol; EE2) and an antiestrogen (ZM 189,154; ZM) at concentrations of 0 to 1,000 ng/L in three separate experiments. A protocol was developed to ensure a year-round supply of recrudescing fish. A protocol for determining steroid production (testosterone and 11-ketotestosterone [11-KT] in incubated testes tissue and testosterone and 17-estradiol [E2] in incubated prematurational follicles) was optimized. Recrudescing fish (males, gonadosomatic index = 2%; females = 10%) were exposed to graded doses of EE2 or ZM for 7 to 15 d using a static daily-renewal protocol. At high EE2 (>250 ng/L), the effect on males was depression of androgen steroidogenesis and plasma steroid levels. In females, high EE2 depressed gonadal production and circulating E2 levels; however, EE2 concentrations <100 ng/L caused increased gonadal production and plasma E2. Low ZM (<100 ng/L) had little effect on male and female fish, while higher concentrations (>250 ng/L) increased E2 and 11-KT production while decreasing plasma 11-KT and E2 (1,000 ng/L only). Male and female plasma vitellogenin responded in a concentration-dependent fashion to EE2 with no effect by ZM. The low observable effect concentrations for the endocrine parameters were 1 ng/L for EE2 and 250 ng/L for ZM. The bioassay and results encompassing the environmentally relevant exposure range (1-100 ng/L) will be useful for assessing effects of endocrine-active contaminants in estuarine environments.
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PMID:Development of a short-term reproductive endocrine bioassay using steroid hormone and vitellogenin end points in the estuarine mummichog (Fundulus heteroclitus). 1272 9

Norethindrone 2 mg. with mestranol 0.1 mg. (Ortho-Novum 2 mg.) was taken in cyclic fashion for fertility control by 62 private patients through 312 cycles. Each patient was interviewed every month during the trial period. No pregnancies occurred. The most common side effects noted were breakthrough bleeding, headache, fatigue and tension, nausea and depression. Five patients left the study because of depression and one because of nausea. It is suggested that the use of norethindrone 2 mg. with mestranol 0.1 mg. be reserved for the following situations: (1) those patients who have used other methods without success and in whom a further pregnancy would, in the opinion of the family physician, create hardship; (2) those patients in whom fear of pregnancy is part of the cause of marital problems; and (3) those patients in whom the product is primarily used for the treatment of menstrual disorders.
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PMID:The use of norethindrone (2 Mg.) with mestranol (0.1 Mg.) in fertility control; a preliminary report. 1399 1

Compelling evidence now exists for estrogen's involvement in the regulation of mood and cognitive functions. Serum estrogen levels have been shown to play an important role in the expression of psychiatric disorders such as depression and schizophrenia. We have characterized the distribution of the estrogen receptors, ERalpha and ERbeta, in the human brain and showed a preferential limbic-related expression pattern for these transcripts. The ERalpha mRNA dominates in the amygdala and hypothalamus, suggesting estrogen modulation of autonomic and neuroendocrine as well as emotional functions. In contrast, the hippocampal formation, entorhinal cortex, and thalamus appear to be ERbeta-dominant areas, suggesting a role for ERbeta in cognition, non-emotional memory, and motor functions. The role of estradiol can also be examined in regard to its relationship to other neurotransmitter systems known to be linked to specific psychiatric disorders. Estradiol has been shown to regulate the serotonin (5-HT) system, which has been strongly implicated in affective disorders. We have studied a genetic animal model of depression, and found altered 5-HT receptor mRNA levels in discrete brain regions; many of the abnormalities are reversed by estradiol treatment, especially for the 5-HT(2A) receptor subtype. The norepinephrine (NE) system is, similar to serotonin, a target for antidepressant drugs, and projects to mesocorticolimbic structures implicated in mood disorders. We have recently observed that NE neurons in the human locus coeruleus (LC) express moderate levels of both ER transcripts. The possibility of estrogen's regulating LC function has been documented in animal studies. Results from our preliminary experiments have revealed that the ERbeta mRNA is decreased in persons committing suicide, a cause of death that is highly linked to affective disorder. Follow-up studies are currently under way with a much larger population to validate these results. Overall, the discrete anatomical organization of the ER mRNAs in the human brain provide evidence as to the specific neuronal populations in which the actions of ERs could modulate mood and thus underlie the neuropathology of psychiatric disorders such as depression.
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PMID:Estrogen receptor gene expression in relation to neuropsychiatric disorders. 1499 40

Estradiol (E2) may influence depressive symptomology of women and decrease depressive behavior among rodents. The mechanism(s) for E2's antidepressant effects are not well understood. To determine whether antidepressant effects of E2 may involve actions at intracellular estrogen receptor (ER) alpha or beta isoforms, selective ER modulators (SERMs) were administered (10 microg sc) to ovariectomized rats 48 h before testing in the forced swim test, an animal model of depression, and the horizontal crossing task. Rats received sesame oil vehicle, 17beta-E2, which has a high affinity for ERalpha and ERbeta, SERMs that vary in their activity at ERalpha and beta, or a tricyclic antidepressant (desipramine; 30 mg/kg ip), as a positive control. ERalpha-selective SERMs were propyl pyrazole triol (PPT) and 17alpha-E2. PPT has more selective effects at ERalpha than does 17alpha-E2, which also binds ERbeta. ERbeta-selective SERMs were diarylpropionitrile (DPN) and 7,12-dihydrocoumestan (coumestrol). DPN is more selective at ERbeta than coumestrol, which also binds ERalpha. 17beta-E2, ERbeta-selective SERMs (DPN, coumestrol), and desipramine administration produced antidepressive behavior (decreased immobility, increased struggling and swimming). ERalpha-selective SERMs (PPT, 17alpha-E2) were not different from vehicle. There were no differences among groups in the number of beam breaks made in the horizontal crossing task. These data suggest that E2's antidepressive effects may involve actions at ERbeta.
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PMID:Antidepressant effects of ERbeta-selective estrogen receptor modulators in the forced swim test. 1525 Dec 61

Desensitization of post-synaptic serotonin1A (5-HT1A) receptors may underlie the clinical improvement of neuropsychiatric disorders. In the hypothalamic paraventricular nucleus, Galphaz proteins mediate the 5-HT1A receptor-stimulated increases in hormone release. Regulator of G protein signaling-Z1 (RGSZ1) is a GTPase-activating protein selective for Galphaz proteins. RGSZ1 regulates the duration of interaction between Galphaz proteins and effector systems. The present investigation determined the levels of RGSZ1 in the hypothalamic paraventricular nucleus of rats subjected to four different treatment protocols that produce desensitization of 5-HT1A receptors. These protocols include: daily administration of beta estradiol 3-benzoate (estradiol) for 2 days; daily administration of fluoxetine for 3 and 14 days; daily administration of cocaine for 7 or 14 days; and acute administration of (+/-)-1-(2,5 dimethoxy-4-iodophenyl)-2-amino-propane HCl (DOI; a 5-HT2A/2C receptor agonist). Estradiol treatment was the only protocol that increased the levels of RGSZ1 protein in the hypothalamic paraventricular nucleus in a dose-dependent manner (46%-132% over control). Interestingly, previous experiments indicate that only estradiol produces a decreased Emax of 5-HT1A receptor-stimulation of hormone release, whereas fluoxetine, cocaine and DOI produce a shift to the right (increased ED50). Thus, the desensitization of 5-HT1A receptors by estradiol might be attributable to increased levels of RGSZ1 protein. These findings may provide insight into the adaptation of 5-HT1A receptor signaling during pharmacotherapies of mood disorders in women and the well-established gender differences in the vulnerability to depression.
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PMID:Estrogen treatment increases the levels of regulator of G protein signaling-Z1 in the hypothalamic paraventricular nucleus: possible role in desensitization of 5-hydroxytryptamine1A receptors. 1526 17

We reviewed a series of 66 deaths in Washington State between 1995-2000 in which tramadol (Ultram and Ultracet, Ortho-McNeil) was detected in the decedent's blood, in order to assess the role tramadol was determined to have played. Additionally, we reviewed a series of 83 impaired driving cases in which tramadol was detected in order to establish a non-lethal blood tramadol concentration reference range. In both populations, tramadol was consistently found together with other analgesic, muscle relaxant, and CNS depressant drugs. Death was rarely attributable to tramadol alone. However, tramadol may be a significant contributor to lethal intoxication when taken in excess with other drugs, via the potential interaction with serotonergic antidepressant medications, as well as the potential for increased CNS depression. Although the incidence of tramadol detection has increased consistently over the last eight years, there is no evidence of a corresponding increase in the number of cases in which death was attributed solely to tramadol. Blood drug concentrations in many deaths exceeded the therapeutic serum range of 0.28-0.61 mg/L; however, the concentrations overlapped almost completely with the range identified in living subjects arrested for impaired driving. These findings suggest caution in the interpretation of blood tramadol concentrations outside of the recognized therapeutic range. It also suggests that the drug, even when used in moderate excess, is not a principle cause of death in suicidal or accidental deaths.
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PMID:Tramadol (Ultram) concentrations in death investigation and impaired driving cases and their significance. 1546 Nov 18


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