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)

Gynecologists use either oral or parenteral progestogens either alone or in combination with estrogens to treat various conditions. Parenteral routes of progestogen delivery are intramuscular injections, intravaginal pessaries, subcutaneous implants, and vaginal rings. Progestogens treat dysfunctional uterine bleeding by first controlling the acute bleeding episode and then by establishing normal ovulatory cycles. 1-2 tablets of medroxyprogesterone acetate (MPA)/day or 1-3 tablets of norethindrone/day should stop uterine bleeding in 72 hours. If not, 25 mg intravenous premarin should control it in 6-24 hours. Cyclical progestational (e.g., MPA) therapy for 3-6 cycles should establish normal ovulatory cycles. After appropriate laparoscopic staging by double puncture technique, progestogens can be used to treat mild-moderate endometriosis. Gynecologists should consider the following criteria when selecting the ideal progestin for hormone replacement therapy: adjustment of dosage of progestin and estrogen over 3-6 months to maintain the beneficial effects of the estrogen and to minimize the adverse effects of the progestin, progestin dosage sufficient to protect against endometrial hyperplasia and cancer, economical progestin, and minimization of weight gain, depression, oral intolerance, and androgenic action. Hydrogesterone and MPA meet these criteria. Oral contraceptives with a progestin and the smallest possible dose of estrogen are well-tolerated, cause no break-through bleeding, produce minimal side effects, and protect against pregnancy (99% contraceptive effectiveness rate). They also protect against endometrial cancer, endometriosis, premenstrual tension, dysmenorrhea, and irregular cycles. Intramuscular injections of progestins (MPA, NET-EN), subcutaneous levonorgestrel implant, and the levonorgestrel IUD are new contraceptive developments and provide a high degree of contraceptive efficacy. MPA at very high doses cause remission of breast endometrial lesions.
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PMID:Progestogens in gynaecological practice. 1217 92

The results of 2 validation studies for an assessment tool designed specifically for quality improvement and outcomes assessment efforts in mental healthcare are presented in this paper. The studies evaluated a new tool to assess the patient outcomes for major depressive disorder following treatment in routine clinical settings called the Depression-Arkansas Scale (D-ARK). Study 1 included 54 patients recruited from 3 hospital-based clinics (2 mental health clinics and 1 primary care clinic). Study 2 includes 827 patients from 5 clinical settings including a university based outpatient clinic, a VA based mental health clinic, and a managed-care program. These 2 very different studies provide preliminary evidence that the D-ARK may be a useful tool for quality improvement efforts in the mental healthcare setting. Specifically, they indicate that the D-ARK has strong validity when compared to 2 different research assessments, the Structured Clinical Interview for DSM-III-R, Patient Edition (SCID-P) and the Inventory to Diagnose Depression (IDD), and compared to clinical assessments using both the clinical diagnosis and a clinician checklist.
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PMID:Validity of the Depression-Arkansas (D-ARK) Scale: a tool for measuring major depressive disorder. 1238 69

The genetically selected long attack latency (LAL) and short attack latency (SAL) mice differ in a wide variety of behavioural traits and display differences in the serotonergic system and the hypothalamus-pituitary-adrenocortical (HPA)-axis. Serial analysis of gene expression (SAGE) was used to generate a hippocampal expression profile of almost 30 000 genes in LAL and SAL mice. Using SAGE, we found differential expression of 191 genes. Among these were genes involved in growth, signal transduction, and cell metabolism. The SAGE study was supported by GeneChip analysis (Affymetrix). Strikingly, both SAGE and GeneChips showed a higher expression of numerous cytoskeleton genes, such as cofilin and several tubulin isotypes in LAL mice. LAL mice also showed a higher expression of several calmodulin-related genes and genes encoding components of a MAPK cascade, namely raf-related oncogene and ERK2. The findings were confirmed by in situ hybridization. Our results of differential expression of cytoskeleton and signal transduction genes therefore suggest differential regulation of the raf/ERK pathway that may be related to structural differences in the hippocampus of LAL and SAL mice. As stress-related disorders, such as depression, are also linked to differential regulation of the HPA-axis and the serotonergic system and are associated with altered hippocampal morphology, differential regulation of these genes may be involved in the pathogenesis of these diseases.
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PMID:Serial analysis of gene expression predicts structural differences in hippocampus of long attack latency and short attack latency mice. 1254 75

Recent trends in mental-health care have increased the need for practical depression instruments. The Depression-Arkansas (D-ARK), a brief, economical, multipurpose instrument, has been validated for assessing major depressive disorder (MDD) and depressive-symptom severity. Psychometric properties of the D-ARK were compared with standard depression scales (Beck Depression Inventory and Geriatric Depression Scale) among 294 adult and 193 senior primary-care patients, respectively, and 163 patients enrolled in cognitive-behavioral depression classes. The severity scale displayed adequate internal reliability (coefficient alpha =.81-.86), high correlation with the BDI-2 (r =.78-.83) and GDS (r =.75), and similar factor structure to the BDI-2. The D-ARK was calibrated against the BDI-2 and GDS, providing familiar severity category cutpoints with the new instrument. This study yields further data supporting the reliability, validity, and practical utility of the D-ARK.
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PMID:The Depression-Arkansas scale: A validation study of a new brief depression scale in an HMO. 1265 38

Multiple genetic alterations such as in Ras or EGFR can result in sustained signaling through PI3K. Our previous experiments have shown that resistance to radiation results from PI3K activity in cells in culture. Here we examined whether inhibition of PI3K in vivo would sensitize tumors to radiation. The human bladder cancer cell line T24 has amplified and mutated H-Ras resulting in sustained PI3K activity and phosphorylation of the downstream target of PI3K, Akt. Nude mice bearing T24 tumor cell xenografts were randomly assigned to one of four groups: control, radiation alone, the PI3K inhibitor LY294002 alone, or combined LY294002 and radiation. The LY294002 was delivered intraperitoneally to the mice. Downregulation of Akt was documented by Western blot analysis of tumor lysates. In vivo sensitization was measured using clonogenic assays or regrowth assays.A dose of 100 mg/kg of LY294002, but not 50 mg/kg, consistently eliminated the phosphorylation of Akt. This inhibition was transient, and Akt activity returned after 30 min. This dose resulted in severe respiratory depression and lethargy resolving without lethality. It is not possible to tell whether these side effects of LY294002 were mechanism-based or idiosyncratic. The PI3K inhibitor LY294002 by itself had minimal antitumor effect. The combination of LY294002 and radiation resulted in significant and synergistic reduction in clonogenicity and growth delay. Inhibition of PI3K by LY294002 can synergistically enhance radiation efficacy. This acts as a proof of principle that inhibition of the Ras to PI3K pathway could be useful clinically.
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PMID:Radiation sensitization of human cancer cells in vivo by inhibiting the activity of PI3K using LY294002. 1278 94

We describe two signaling events downstream of ERK-MAP kinase contributing to cell motility in colon carcinoma cells. The Fos family member Fra-1 is expressed in an ERK-dependent manner. Silencing of Fra-1 expression with short interfering RNAs leads to losses of cell polarization, motility, and invasiveness in vitro. These effects of ablating Fra-1 are a consequence of activation of a RhoA-ROCK pathway by beta1-integrin, leading to an increase in the amount of stress fibers and stabilization of focal adhesions. We propose that Fra-1 promotes cell motility by inactivating beta1-integrin and keeping RhoA activity low. This depression of RhoA activity is necessary to permit a second ERK-dependent signaling event via uPAR, the receptor for urokinase-type plasminogen activator, to activate Rac and to drive motility through polarized lamellipodia extension.
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PMID:ERK-MAPK signaling coordinately regulates activity of Rac1 and RhoA for tumor cell motility. 1289 14

The association between psychotic symptoms and violence is unclear, due in part to methodological features of investigations that have examined this question, and in part to the fact that the association likely differs by disorder and treatment conditions. Using data from The Comparative Study of the Prevention of Crime and Violence by Mentally Ill Persons, we examined 128 men with schizophrenia or schizoaffective disorder discharged from general and forensic psychiatric hospitals in Canada, Finland, Germany, and Sweden. The association between symptoms and aggressive behavior was studied during two 6 month periods when the patients lived in the community. Severe positive and negative symptoms of psychosis, depression, and anxiety were measured at the beginning of each of the 6 month periods. In addition, at the beginning of the second 6 month period changes in symptoms in the previous period were indexed. Aggressive behavior was measured in each 6 month period by reports from patients and from collaterals. During the first 6 months post-discharge, after controlling for the presence of antisocial personality disorder or PCL score and past diagnoses of alcohol/drug abuse/dependence, the presence of a severe positive symptom significantly increased the risk of aggressive behavior. During the second 6 month period, after controlling for antisocial personality disorder or PCL score and self-reported alcohol/drug use, the presence of a severe positive symptom, a TCO symptom, and an increase in TCO symptoms significantly increased the risk of aggressive behavior. Neither depot medications nor obligatory community treatment reduced the risk of aggressive behavior after controlling for the presence of a severe positive symptom and/or TCO symptoms. These findings suggest that, among men with schizophrenia being treated in the community, the presence of severe psychotic symptoms and the development of TCO symptoms are antecedents of aggressive behavior.
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PMID:The antecedents of aggressive behavior among men with schizophrenia: a prospective investigation of patients in community treatment. 1289 6

Phorbol esters, such as tetradecanoylphorbol 13-acetate (TPA), have been used extensively in studies of cerebellar long-term depression (LTD), based on the hypothesis that activated protein kinase C (PKC) directly mediates alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor phosphorylation. Here, we show that TPA-induced depression of synaptic transmission between granule cells and Purkinje cells in culture is mediated through activation of the MEK1/2-ERK1/2 pathway. Phosphorylation of ERK1/2 induced by TPA and co-application of high potassium and glutamate was greatly attenuated by preincubating Purkinje cells with the MEK1/2 (MAPK ERK kinase 1/2) inhibitor PD98059. TPA-induced depression of synaptic transmission between granule cells and Purkinje cells was attenuated by PD98059. The MEK1/2 inhibitor also suppressed declustering of the ionotropic glutamate receptor subunit 2/3 (GluR2/3) induced by TPA and co-application of high potassium and glutamate, even though phosphorylation of Ser880 of GluR2/3 was not inhibited significantly in the presence of PD98059. These results suggest that ERK1/2 plays an essential role in TPA-induced depression via regulation of GluR2/3 declustering at the synapse.
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PMID:ERKs regulate PKC-dependent synaptic depression and declustering of glutamate receptors in cerebellar Purkinje cells. 1452 24

The purpose of this study was to investigate the influence of physical activity and other factors on the mood of former elite male athletes and controls of middle and old age. The subjects were 664 former athletes and 500 controls who answered questionnaires in 1985 and 1995. The dependent variables depressive and anxiety symptoms were assessed by the shortened anxiety and depression scales of the BSI-53. Logistic regression was used for longitudinal as well as cross-sectional analyses to estimate odds ratios for symptoms of depression and anxiety in relation to leisure physical activity adjusted for age in 1995, sports group, personality characteristics, alcohol use, smoking, marital status, life events and socio-economic status. In the longitudinal analysis, low levels of physical activity as well as neuroticism, dissatisfaction, marital status, life events and social class in 1985 increased the risk of depression in 1995. Also physical activity has a protective effect against depressiveness; an increase of one MET-unit (hour/day) statistically significantly decreased the risk of depressiveness by 8 %. In the longitudinal analysis, physical activity had no significant association with anxiety. Cross-sectional analysis for depressive symptoms in 1995, but not for anxiety found associations with sports group and physical activity as well as alcohol use and marital status. Very high physical activity has a significant protective effect against depression.
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PMID:Influence of physical activity on depression and anxiety of former elite athletes. 1459 99

The field of migraine genetics has seen an explosion of information over the last year. In a recent breakthrough, missense mutations in a chromosome 1q23 gene, ATP1A2, encoding a Na+, K+-ATPase, have been identified in four distinct pedigrees with a rare form of familial hemiplegic migraine (FHM). ATP1A2 is expressed in the brain, like the voltage gated calcium channel gene, CACNA1A, previously identified as the first hemiplegic migraine gene (FHM1). The shared hemiplegic migraine phenotype of mutations in ATP1A2 and CACNA1A raises the possibility that they coordinately regulate ion homeostasis that determines susceptibility to the initiation of both migraine aura and the pain phase of migraine. For the more common and genetically complex forms of migraine, genome-wide screens have identified several new loci on 4q24, 6p12.2-21.1, 11q24, and 14q21.2-q22.3, suggesting additional migraine genes in these regions. In addition, a recent large case-control association study has linked single nucleotide polymorphisms in the insulin receptor/INSR gene with migraine. However, these polymorphisms do not result in detectable changes in receptor function. The continuing genetic identification of key proteins involved in migraine will refine our understanding of this common and sometimes debilitating disorder, which can strike during the most productive years of a person's life. Given the co-morbidity of migraine with depression and bipolar disorder, our knowledge of the causes of migraine may also contribute to our understanding of these disorders.
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PMID:Update on the genetics of migraine. 1462 54


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