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)

In the adolescent population, fatigue is associated with somatic complaints, unrefreshing sleep, cognitive disturbances and symptoms of depression and anxiety. This pattern of symptoms resembles the one described in chronic fatigue syndrome (CFS). Since immunological alterations have been reported in CFS patients, we wondered whether also severely fatigued girls from a healthy population would show comparable alterations in psychological and immunological parameters. We tested this hypothesis in a longitudinal design, allowing a reliable assessment of the participants' characteristic immune status. Groups of severely fatigued (N=67) and non-fatigued (N=61) participants were selected. Severely fatigued girls reported more depressive symptoms, anxiety, reduced sleep quality, and somatic and CFS-related symptoms than non-fatigued participants across three measurements during one year (T1: spring, T2: autumn, T3: spring). In contrast, no group differences in mitogen-induced cytokine production or T-cell proliferation in vitro or in leukocyte subset counts were observed. Although absolute cytokine production and cell counts were affected by seasonal variation, the within-subject values, relatively to the rest of the participants, were fairly stable. Data from a small group of CFS patients (N=11) showed similarities in self-reported complaints between CFS patients and fatigued participants. Interestingly, CFS patients showed a distinct immune profile when compared to the severely fatigued or non-fatigued participants, i.e. increased levels of anti-inflammatory cytokines (IL-10, decreased IFN-gamma/IL-10 ratio) and reduced levels of pro-inflammatory cytokines (IL-6, TNF-alpha) over all three time points analyzed. These results show that, although overlap in symptomatology between the general population and patients with CFS was observed, only CFS patients show a skewing of the cytokine balance towards an anti-inflammatory profile.
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PMID:Longitudinal analysis of pro- and anti-inflammatory cytokine production in severely fatigued adolescents. 1754 55

Cytokines are involved both in various immune reactions and in controlling certain events in the central nervous system (CNS). In our earlier studies, it was shown that monoamine neurotransmitters, released in stress situations, represent a tonic sympathetic control on cytokine production and on the balance of proinflammatory/anti-inflammatory cytokines. Basic and clinical studies have provided evidence that the biophase level of monoamines, determined by the balance of their release and uptake, is involved in the pathophysiology and treatment of depression, while inflammatory mediators might also have a role in its etiology. In this work, we studied the role of changes in norepinephrine (NE) level on the lipopolysaccharide (LPS) evoked tumor necrosis factor (TNF)-alpha and interleukin (IL)-10 response both in the plasma and in the hippocampus of mice. We demonstrated that the LPS induced TNF-alpha response is in direct correlation with the biophase level of NE, as it is significantly higher when the release of NE of vesicular origin was completely inhibited in an animal model of depression (reserpine treatment) and it is significantly lower in the case of increasing biophase levels of NE by genetic (NET-KO) or chemical (desipramine) disruption of NE reuptake. IL-10 was changed inversely to TNF-alpha levels only in the desipramine-treated animals. Our results showed that depression is related both to changes in peripheral and in hippocampal inflammatory cytokine production and to monoamine neurotransmitter levels. Since several anti-inflammatory drugs also have antidepressant effects, we hypothesized that antidepressants are also able to modulate the LPS-induced inflammatory response, which might contribute to their antidepressant effect.
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PMID:The catecholamine cytokine balance: interaction between the brain and the immune system. 1758 82

Synaptic plasticity underlies higher brain functions such as learning and memory. At glutamatergic synapses in the vertebrate central nervous system, plasticity usually requires changes in the number of postsynaptic AMPA receptors. Recently, several studies have revealed that glial cells play an important role in regulating postsynaptic AMPA receptor density. This is accomplished through the release of gliotransmitters such as D-serine, ATP and TNF-alpha. More specifically, the availability of D-serine, the endogenous co-agonist of N-methyl-D-aspartate receptors in many brain areas, governs the induction of long-term potentiation and long-term depression. Meanwhile, ATP and TNF-alpha trigger long-lasting increases in synaptic strength at glutamatergic hypothalamic and hippocampal inputs, respectively, through mechanisms that promote AMPA receptor insertion in the absence of coincident presynaptic and postsynaptic activity. These data clearly demonstrate a vital role for glia in plasticity and argue that their contributions to brain function extend well beyond their outdated role as cellular 'glue'.
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PMID:Glia: they make your memories stick! 1763 72

Emerging epidemiological data indicates that diabetes is a potential predisposing factor for neuropsychiatric deficits as stroke, cerebrovascular diseases, diabetic encephalopathy, depression and anxiety. Diabetic encephalopathy, characterized by impaired cognitive functions and neurochemical and structural abnormalities, involves direct neuronal damage caused by intracellular glucose. Curcumin, a well-established phenolic antioxidant and anti-inflammatory molecule, is capable of playing an important role against amyloid and dendritic pathology and thus has neuroprotective properties. The aim of the present study was to explore the effect of curcumin (60 mg/kg; p.o.) on cognitive functions, oxidative stress and inflammation in diabetic rats. Learning and memory behaviors were investigated using a spatial version of the Morris water maze test. Acetylcholinesterase activity, a marker of cholinergic dysfunction, was increased by 80% in the cerebral cortex of diabetic rats. There was 107% and 121% rise in thiobarbituric acid reactive substance levels in cerebral cortex and hippocampus of diabetic rats, respectively. Reduced glutathione level and enzymatic activities of superoxide dismutase and catalase were decreased in both cerebral cortex and hippocampal regions of diabetic rat brain. Nitrite levels in cerebral cortex and hippocampus were increased by 112% and 94% respectively. Serum TNF-alpha, a marker for inflammation, was found to increase by 1100% in diabetic rats. Chronic treatment with curcumin (60 mg/kg; p.o.) significantly attenuated cognitive deficit, cholinergic dysfunction, oxidative stress and inflammation in diabetic rats. The results emphasize the involvement of cholinergic dysfunction, oxidative stress and inflammation in the development of cognitive impairment in diabetic animals and point towards the potential of curcumin as an adjuvant therapy to conventional anti-hyperglycemic regimens for the prevention and treatment of diabetic encephalopathy.
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PMID:Curcumin attenuates diabetic encephalopathy in rats: behavioral and biochemical evidences. 1782 93

Genetic factors have a variable impact on Alzheimer's Disease (AD), ranging from familial forms that are transmitted in an autosomal dominant fashion to sporadic AD, where a polygenic component is present. Most genes conferring susceptibility to AD are related to amyloid-beta deposition (APP; PS1; PS2; APOE; Cystatin-C; ubiquilin-1), oxidative stress (NOS2; NOS3) and inflammatory response (IL-1 alpha; IL-1 beta; IL-6; TNF-alpha). Genome-wide analyses, transcriptomics and proteomics approaches have pointed also to proapoptotic genes as increasing AD liability. Depression and psychotic symptoms that occur in a large proportion of AD patients have been associated with monoamine genes coding for metabolic enzymes (COMT), transporters (5-HTTLPR) and receptors (DRD1; DRD3). Genetic testing may be useful to confirm the diagnosis of AD in individuals with clinical signs of dementia, while it is generally not recommended as a predictive testing for AD in asymptomatic individuals. Drugs currently in use to treat AD are effective in only 20% of patients; their therapeutic effect is predominantly under genetic control (CYP26 gene; APOE). Environmental factors have been shown to moderate the effects of genes on psychiatric disorders such as depression, schizophrenia and ADHD. The study of gene-environment interactions in AD, that are still poorly understood, is essential to predict disease-risk in asymptomatic individuals. Genomics will provide a dynamic picture of biological processes in AD and new targets for the forthcoming anti-AD drugs.
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PMID:Genetics of Alzheimer's disease. A rapidly evolving field. 1785 Nov 96

Fatigue without coincident depression may accompany many neurological disorders, including multiple sclerosis, Parkinson's disease, motor neuron disease, stroke and post-polio syndrome, and is frequently reported by patients as a predominant complaint. The pathophysiology of fatigue is unknown. The role of various mechanisms has been suggested, including the effect of proinflammatory cytokines (TNF-alpha, IL-1beta and IL-6) on glutaminergic transmission, hypothalamo-pituitary-adrenal (HPA) axis dysfunction, disturbances of astroglia metabolism and decreased levels of the neurotransmitters noradrenaline and serotonin. The diagnosis of fatigue syndrome is based on exclusion of depression and additional organic conditions (anaemia, cardiovascular disorders, kidney diseases or hypothyroidism). The treatment of fatigue syndrome is complex. Physical activity, rehabilitation, psychotherapy and avoidance of factors which may increase fatigue, such as fever, anxiety, depression, pain, sleep disturbances, as well as some drugs like opioids and benzodiazepines, are important. Pharmacological treatment leads to slight improvement. Amantadine, modafinil and pemoline are administered to such patients.
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PMID:[Fatigue syndrome in chronic neurological disorders]. 1787 43

Poor appetite in older adults is a common problem in clinical practice, but prevalence of this symptom and its risk factors in community-dwelling older adults are not well understood. As part of the Health, Aging and Body Composition Study, we ascertained self-reported impaired appetite and related factors in 2,169 older adults aged 70-79 years. About 12% of participants reported impaired appetite. Those reporting impaired appetite were more likely to be older, female, and black and to report having illness or physical conditions interfering with appetite than those not reporting impaired appetite. Hierarchical logistic regression suggested that multiple factors contributed to impaired appetite. In particular, symptomatic depression (OR (95% CI) = 2.5 (1.6- 4.1)), poor self-reported health (2.4 (1.7-3.2)), current smoking, chewing problems, reported visual impairment, weight loss since age 50, and log (TNF-alpha) were significantly related to impaired appetite.
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PMID:Factors associated with impaired appetite in well-functioning community-dwelling older adults. 1789 Feb 2

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

Studies suggest that cytokines have a role in the biology of depression. In this study, we evaluated depression and cytokine levels in patients with and without chronic hepatitis C (HCV) to better assess how chronic infection alters cytokines levels and may contribute to depressive symptomotology. Twenty-three adults with (n=16) and without (n=7) HCV were recruited through the Portland VA Medical Center. Research participants were excluded for current substance abuse, psychotic disorder, liver cirrhosis, or interferon (IFN) therapy. Participants completed the Beck Depression Inventory-II (BDI-II) and a blood draw to evaluate plasma cytokine levels [i.e., interleukin (IL)-1beta, IL-10 and tumor necrosis factor (TNF)-alpha]. t-Tests were performed to compare cytokine levels in patients with or without HCV. HCV patients showed higher TNF-alpha values compared to patients without HCV (group means=7.94 vs. 3.41pg/mL, respectively, p=0.047). There were no significant differences between the groups for the other cytokines assessed. In patients with HCV, TNF-alpha and IL-1beta levels (but not IL-10) were correlated with BDI-II scores [r=0.594, p=0.020 and r=0.489, p=0.055 (trend), respectively]. Taken together, these results show an association between severity of depressive symptoms and expression of pro-inflammatory cytokines in patients with HCV. Future studies should investigate how inflammatory mediators play a role in the expression of specific depressive symptoms in patients with chronic infection. Patients with HCV represent an interesting model to examine this relationship.
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PMID:Depressive symptoms in patients with chronic hepatitis C are correlated with elevated plasma levels of interleukin-1beta and tumor necrosis factor-alpha. 1806 7

Acceleration of blood leukocyte apoptosis in major depression has been described. The present studies have been undertaken to estimate the level of apoptosis of blood leukocytes in patients with depression and to examine the mechanisms leading to apoptosis. Blood was taken from 29 patients with depression (age 48.2+/-11.2, 14 males, 15 females) and 30 healthy controls (age 41.3+/-4.1, 15 males, 15 females), and apoptosis was estimated by the cytometric method by measurements of annexin V binding, mitochondrial membrane potential (DeltaPsi), bcl-2, bax, and Fas (CD95) expression in CD4+, CD8+ and CD14+ cells. The amounts of cytochrome c released from mitochondria to cytosol of peripheral blood mononuclear cells (PBMCs) and polymorphonuclear cells (PMNs) were also measured. The levels of reactive oxygen species (ROS) released from PMNs were examined as was the serum activity of superoxide dismutase (SOD), catalase (CAT), and total peroxidase (PER). Additionally, serum levels of the tumor necrosis factor (TNF-alpha) and interleukin-6 (IL-6) were estimated. Our experiments indicated accelerated apoptosis of CD4+ T lymphocytes and CD14+ cells (mainly neutrophils) of depressed patients as well as a significant increase in the percent of Fas-expressing cells. Bcl-2 and bax expression was higher in cells of depressed patients than in control, however, bcl-2/bax ratio was significantly decreased in CD14+ cells of depressed patients. PMNs isolated from the blood of the patients produced more ROS spontaneously and after induction with phorbol ester (PMA) than PMNs of the healthy control. A significant increase in serum activity of SOD, CAT and PER was also detected. Overproduction of superoxide anion correlated positively with the level of PMNs apoptosis (measured by cytochrome c release), suggesting that superoxide anion might be an important factor inducing apoptotic death of blood cells. The result of our experiment indicated that apoptosis of immune cells may affect patient's susceptibility to different infections and application of antioxidants in medication of patients with depression will be beneficial for them. The increased level of IL-6 in sera of the depressed patients did not correlate with overproduction of ROS, suggesting that this cytokine is not involved in oxidative stress and apoptosis of leukocytes.
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PMID:Accelerated apoptosis of blood leukocytes and oxidative stress in blood of patients with major depression. 1808 80


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