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)

Antidepressant drugs are thought to counteract effects of hypercortisolemia, frequently associated with depression, by lowering cortisol level and by modifying the function of glucocorticoid receptors (GR). Indeed, classical antidepressants inhibit corticosteroid-induced gene transcription in cell cultures. The aim of the present study was to investigate effects of new generation antidepressant drugs on GR function in mouse fibroblast cells (L929), stably transfected with mouse mammary tumor virus-chloramphenicol acetyltransferase (MMTV-CAT) plasmid (LMCAT cells). It has been found that reboxetine (at 10 and 30 microM), venlafaxine, citalopram and mirtazapine (at 30 microM), but not milnacipran, in statistically significant manner inhibited corticosterone-induced gene transcription. However, the effects of new generation antidepressant drugs were weaker than those evoked by imipramine, which was active already at 3 microM concentration. Further studies on the mechanism of antidepressant action on GR function revealed that protein kinase C, but not mitogen-activated protein kinases (MAPK), glycogen synthase kinase (GSK-3) and protein kinase B (PKB, Akt) play a role in this phenomenon.
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PMID:Effects of some new antidepressant drugs on the glucocorticoid receptor-mediated gene transcription in fibroblast cells. 1638 95

The persistent sexual arousal syndrome (PSAS) is a newly described entity where women become involuntarily aroused genitally for extended periods in time in the absence of sexual desire. Genital vasoengorgement and oedema have been observed. These women are found to be usually very distressed. The cause of the syndrome in the majority of cases is unknown, although a number of women report symptoms after withdrawal from selective serotonin reuptake inhibitors (SSRI) antidepressants. There is no specific therapy at present, although electroconvulsive therapy (ECT) has resulted in clinical improvement in cases where there was concomitant severe depression.
Int J STD AIDS 2006 Apr
PMID:Persistent genital arousal in women -- a new syndrome entity. 1659 40

We used qualitative methods to explore factors, which might explain increased anxiety in patients attending a sexually transmitted infection (STI) clinic. Twenty patients, who scored significantly for anxiety on the Hospital Anxiety and Depression Scale (HADS) attended a 20-minute interview. This explored factors contributing to their current psychological symptoms. Transcripts revealed three main themes. First were factors related to possible STIs and the clinic visit. These included health anxieties about HIV or fertility and clinic factors, including staff attitudes and clinic location. Second were factors unrelated to the clinic, including previous emotional difficulties or substance misuse. Third were issues concerning stigma, embarrassment and shame. The origins of anxiety in STI patients are multifactorial and difficult to identify during brief appointments. Despite modern clinics and attitudes, stigma and embarrassment remain prominent. Interventions to address these factors could improve psychological health in this patient group.
Int J STD AIDS 2006 May
PMID:Factors associated with anxiety in patients attending a sexually transmitted infection clinic: qualitative survey. 1664 78

The Future Events Scale (FES; S. M. Andersen, 1990) is an expectancy-based measure of optimism and pessimism, grounded in cognitive theories of depression, with implications for clinical practice. Although ample research has documented the utility of the FES in predicting important cognitive and behavioral outcomes, psychometric data on the scale are lacking. The current article presents multisample analyses to show that the FES has clear factor structure, good reliability, and a theoretically meaningful nomological network. The FES is shown to be distinct from the best known measure of optimism and pessimism, the Life Orientation Test (M. F. Scheier & C. S. Carver, 1985). Applications are discussed.
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PMID:Perceived likelihood as a measure of optimism and pessimism: support for the Future Events Scale. 1676 98

Traumatic brain injury (TBI) is a triggering event for a set of pathophysiological changes and concomitant depressive behavior. Glycogen synthase kinase-3 (GSK-3) is a potent in vivo regulator of cell apoptosis and, in addition, is implicated in depressive behavior. In this study, we investigated the role of GSK-3 in the physiological model of mild TBI (mTBI) at both the cellular and behavior levels. mTBI resulted in increased phosphorylation of inhibitory site serine(9) of GSK-3beta, which coincided with increased serine(473) phosphorylation of its upstream kinase PKB and accumulation of its downstream target beta-catenin in the hippocampus. mTBI induced a depressive behavior which was evident as early as 24 h post-injury. Pretreatment with GSK-3 inhibitors, lithium, or L803-mts prevented mTBI-induced depression. We suggest that mTBI elicits a pro-survival cascade of PKB/GSK-3beta/beta-catenin as part of a rehabilitation program. Furthermore, the use of selective GSK-3 inhibitors may have therapeutic benefits in treatment conditions associated with brain injury.
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PMID:Role of glycogen synthase kinase-3beta in early depressive behavior induced by mild traumatic brain injury. 1728 99

Sigma-1 receptors are widely expressed in the mammalian brain and also in organs of the immune, endocrine and reproductive systems. Based on behavioral and pharmacological assessments, sigma-1 receptors are important in memory and cognitive processes, and are thought to be involved in specific psychiatric illnesses, including schizophrenia, depression, and drug addiction. It is thought that specific neuroactive steroids are endogenous ligands for these sites. In addition, several sigma-1 receptor binding steroids including progesterone, dihydroepiandrosterone (DHEA), and testosterone are being examined clinically for specific therapeutic purposes; however, their mechanisms of action have not been clearly defined. We previously described the high affinity sigma-1 receptor selective PET tracer [(18)F]FPS. This study examines the effect of neuroactive steroids on [(18)F]FPS binding in vitro and in vivo. Inhibition constants were determined in vitro for progesterone, testosterone, DHEA, estradiol, and estriol binding to the [(18)F]FPS labeled receptor. The affinity order (K(i) values) for these steroids ranged from 36 nM for progesterone to >10,000 nM for estrodiol and estriol. Biodistribution studies revealed that i.v. coadministration of progesterone (10 mg/kg), testosterone (20 mg/kg), or DHEA (20 mg/kg) significantly decreased [(18)F]FPS uptake (%ID/g) by up to 50% in nearly all of eight brain regions examined. [(18)F]FPS uptake in several peripheral organs that express sigma-1 receptors (heart, spleen, muscle, lung) was also reduced (54-85%). These studies clearly demonstrate that exogenously administered steroids can occupy sigma-1 receptors in vivo, and that [(18)F]FPS may provide an effective tool for monitoring sigma-1 receptor occupancy of specific therapeutic steroids during clinical trials.
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PMID:In vitro and in vivo binding of neuroactive steroids to the sigma-1 receptor as measured with the positron emission tomography radioligand [18F]FPS. 1744 54

Although anal intercourse carries great risk for HIV transmission, little research has focused on it among the general population, particularly pre- and early adolescents. This study describes the prevalence of anal and vaginal intercourse among Bahamian pre- and early adolescents and associations with other risk behaviours, family interactions and intrapersonal correlates. Data were from 1274 sixth-grade students aged 9-14 years who completed self-administered questionnaires at baseline of a larger school-based behavioural intervention study. Youth who reported having had anal intercourse engaged in significantly higher rates of several risk behaviours and were significantly more likely to engage in risk behaviours over the next six months, compared with youth with a history of vaginal intercourse only, who in turn were more likely than virgin adolescents. Youth indulging in anal intercourse also perceived significantly lower levels of parental monitoring. Multivariate analyses revealed that anal intercourse, vaginal intercourse, reduced parental monitoring, depression and perceived friend high-risk involvement were associated with both past involvement and future intention to engage in other risk behaviours. Anal intercourse poses a direct threat to the health of these children and is a flag for a constellation of other risks.
Int J STD AIDS 2007 Jun
PMID:At greatest risk: pre- and early adolescent Bahamian youth experiencing anal intercourse. 1760 29

The objective of this study was to compare deliveries in women with HIV at Homerton University Hospital with those in the general antenatal hospital population. The study was a retrospective case-note review of deliveries from 1994 to 2004 at an Inner City London Hospital, UK (Homerton University Hospital). In all, 113 deliveries were studied in 98 women with HIV. Compared with the general antenatal population, women with HIV were more likely to be from African backgrounds, describe inadequate housing and be without the support of a partner or family; 79.8% of deliveries in women with HIV were by caesarean section in comparison with 22.4% in the overall hospital population. A majority of women with HIV received antiretroviral therapy in pregnancy. Intercurrent medical and antenatal complications were uncommon and in a majority the postpartum periods were uncomplicated. A significantly higher proportion of women with HIV infection described a previous history of depression than in the general hospital population. There were two instances of vertical transmission of HIV. In conclusion, our observations suggest that with appropriate monitoring and management strategies, successful pregnancy outcomes can be achieved in a complex HIV-positive patient population.
Int J STD AIDS 2007 Aug
PMID:Experience of delivering women with HIV in an inner city London hospital 1994-2004. 1768 13

Src tyrosine kinases (TKs) are signaling proteins involved in cell signaling pathways toward cytoskeletal, membrane and nuclear targets. In the present study, using a selective Src TK inhibitor, PP1, we investigated the roles of Src TKs in the key pulmonary responses, NF-kappaB activation, and integrin signaling during acute lung injury in BALB/C mice intratracheally treated with LPS. LPS resulted in c-Src phosphorylation in lung tissue and the phospho-c-Src was predominantly localized in recruited neutrophils and alveolar macrophages. PP1 inhibited LPS-induced increases in total protein content in bronchoalveolar lavage fluid, neutrophil recruitment, and increases in the production or activity of TNF-alpha and matrix metalloproteinase-9. PP1 also blocked LPS-induced NF-kappaB activation, and phosphorylation and degradation of IkappaB-alpha. The inhibition of NF-kappaB activation by PP1 correlated with a depression of LPS-induced integrin signaling, which included increases in the phosphorylations of integrin beta(3), and of the focal adhesion kinase (FAK) family members, FAK and Pyk2, in lung tissue, and reductions in the fibrinogen-binding activity of alveolar macrophages. Moreover, treatment with anti-alpha(v), anti-beta(3), or Arg-Gly-Asp-Ser (RGDS), inhibited LPS-induced NF-kappaB activation. Taken together, our findings suggest that Src TKs play a critical role in LPS-induced activations of NF-kappaB and integrin (alpha(v)beta(3)) signaling during acute lung injury. Therefore, Src TK inhibition may provide a potential means of ameliorating inflammatory cascade-associated lung injury.
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PMID:Src tyrosine kinases mediate activations of NF-kappaB and integrin signal during lipopolysaccharide-induced acute lung injury. 1798 91

Synapsins (Syns) are synaptic vesicle (SV) phosphoproteins that play a role in neurotransmitter release and synaptic plasticity by acting at multiple steps of exocytosis. Mutation of SYN genes results in an epileptic phenotype in mouse and man suggesting a role of Syns in the control of network excitability. We have studied the effects of the genetic ablation of the SYN1 gene on inhibitory synaptic transmission in primary hippocampal neurons. Inhibitory neurons lacking SynI showed reduced amplitude of IPSCs evoked by isolated action potentials. The impairment in inhibitory transmission was caused by a decrease in the size of the SV readily releasable pool, rather than by changes in release probability or quantal size. The reduction of the readily releasable pool was caused by a decrease in the number of SVs released by single synaptic boutons in response to the action potential, in the absence of variations in the number of synaptic contacts between couples of monosynaptically connected neurons. The deletion of SYN1 did not affect paired-pulse depression or post-tetanic potentiation, but was associated with a moderate increase of synaptic depression evoked by trains of action potentials, which became apparent at high stimulation frequencies and was accompanied by a slow down of recovery from depression. The decreased size of the SV readily releasable pool, coupled with a decreased SV recycling rate and refilling by the SV reserve pool, may contribute to the epileptic phenotype of SynI knock-out mice.
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PMID:Lack of synapsin I reduces the readily releasable pool of synaptic vesicles at central inhibitory synapses. 1805 10


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