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)

Neurological dysfunction, seizures and brain atrophy occur in a broad spectrum of acute and chronic neurological diseases. In certain instances, over-stimulation of N-methyl-D-aspartate receptors has been implicated. Quinolinic acid (QUIN) is an endogenous N-methyl-D-aspartate receptor agonist synthesized from L-tryptophan via the kynurenine pathway and thereby has the potential of mediating N-methyl-D-aspartate neuronal damage and dysfunction. Conversely, the related metabolite, kynurenic acid, is an antagonist of N-methyl-D-aspartate receptors and could modulate the neurotoxic effects of QUIN as well as disrupt excitatory amino acid neurotransmission. In the present study, markedly increased concentrations of QUIN were found in both lumbar cerebrospinal fluid (CSF) and post-mortem brain tissue of patients with inflammatory diseases (bacterial, viral, fungal and parasitic infections, meningitis, autoimmune diseases and septicaemia) independent of breakdown of the blood-brain barrier. The concentrations of kynurenic acid were also increased, but generally to a lesser degree than the increases in QUIN. In contrast, no increases in CSF QUIN were found in chronic neurodegenerative disorders, depression or myoclonic seizure disorders, while CSF kynurenic acid concentrations were significantly lower in Huntington's disease and Alzheimer's disease. In inflammatory disease patients, proportional increases in CSF L-kynurenine and reduced L-tryptophan accompanied the increases in CSF QUIN and kynurenic acid. These responses are consistent with induction of indoleamine-2,3-dioxygenase, the first enzyme of the kynurenine pathway which converts L-tryptophan to kynurenic acid and QUIN. Indeed, increases in both indoleamine-2,3-dioxygenase activity and QUIN concentrations were observed in the cerebral cortex of macaques infected with retrovirus, particularly those with local inflammatory lesions. Correlations between CSF QUIN, kynurenic acid and L-kynurenine with markers of immune stimulation (neopterin, white blood cell counts and IgG levels) indicate a relationship between accelerated kynurenine pathway metabolism and the degree of intracerebral immune stimulation. We conclude that inflammatory diseases are associated with accumulation of QUIN, kynurenic acid and L-kynurenine within the central nervous system, but that the available data do not support a role for QUIN in the aetiology of Huntington's disease or Alzheimer's disease. In conjunction with our previous reports that CSF QUIN concentrations are correlated to objective measures of neuropsychological deficits in HIV-1-infected patients, we hypothesize that QUIN and kynurenic acid are mediators of neuronal dysfunction and nerve cell death in inflammatory diseases. Therefore, strategies to attenuate the neurological effects of kynurenine pathway metabolites or attenuate the rate of their synthesis offer new approaches to therapy.
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PMID:Quinolinic acid and kynurenine pathway metabolism in inflammatory and non-inflammatory neurological disease. 142 88

Neopterin is a validated marker of the activation of cell-mediated immunity in a variety of disease states. We measured neopterin and creatinine concentrations in the plasma and urine of 22 schizophrenic and 26 depressed patients admitted acutely to hospital, and compared results with those in a large group of normal controls. Neopterin/creatinine ratios were normal in the schizophrenic patients, but significantly elevated in the plasma of depressed patients. In each diagnostic group, the use of psychotropic drugs before admission had no effect on the neopterin ratios observed. Our findings indicate altered cell-mediated immunity in depression.
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PMID:Neopterin measurement provides evidence of altered cell-mediated immunity in patients with depression, but not with schizophrenia. 148 78

Urinary excretion of neopterins and biopterins was measured in 23 patients with severe depression before and after receiving electroconvulsive therapy (ECT) and 26 healthy control subjects. Patients with psychotic depression and those responding to ECT had neopterin:biopterin (N:B) ratio significantly higher than controls before commencing ECT and positive therapeutic response was associated with reduction of N:B ratio towards control values. As a raised N:B ratio implies failure to convert neopterin to biopterin it is possible that reduced availability of tetrahydrobiopterin, the essential cofactor for the formation of noradrenaline, serotonin and dopamine, may exert rate limiting control over the synthesis of monoamines implicated in the pathogenesis of depressive disorders. The N:B ratio may be a marker for certain depressive subtypes and response to ECT.
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PMID:Pterin metabolism in depression: an extension of the amine hypothesis and possible marker of response to ECT. 148 84

Tetrahydrobiopterin is essential for brain cells to make monoamine neurotransmitters. It has been reported that the concentrations of tetrahydrobiopterin in plasma and urine are low in certain mental disorders and that oral supplements are beneficial. A group of Japanese investigators have been conducting clinical trials of the effect of administration of tetrahydrobiopterin to autistic children and reported that it is beneficial with no significant side effects. We, therefore, initiated a study to assess plasma and urinary levels of tetrahydrobiopterin in infantile autism to see if they are reduced. Besides tetrahydrobiopterin, we also determined plasma and urinary levels of neopterin and monapterin in these individuals in order to evaluate the status of dihydroneopterin triphosphate, a key biosynthetic precursor of tetrahydrobiopterin. Sixteen autistic children and 12 healthy controls were included in this study. Results indicated that the plasma and urinary levels of tetrahydrobiopterin are not statistically different between the two groups and, therefore, no simple explanation for the beneficial effects of administration of tetrahydrobiopterin on autistic children can be offered at the present time. In contrast, plasma and urinary levels of neopterin were depressed (.01 less than p less than .05) and plasma monapterin was also significantly depressed (p less than .01) in autistic subjects compared with controls. Levels of other pterins, including folate, were not statistically different between the two groups. The basis for this depression in neopterin and monapterin is unknown. It does not seem likely that this depression could be attributed to a difference in age or T-lymphocyte/macrophage activity. However, further studies are needed to investigate these possibilities.
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PMID:Plasma and urinary levels of biopterin, neopterin, and related pterins and plasma levels of folate in infantile autism. 162 10

According to the literature, Cyclosporine A (CsA) is said to suppress specifically the activity of T and B cells. A significant influence on phagocyte function has been neglected. However, aggravated courses of bacterial and fungal infections have been frequently reported under the treatment with CsA, suggesting that a latent depression of phagocytic activity may possibly occur under clinical circumstances. Therefore, this study set out to assess whether CsA can also change granulocyte function under therapy conditions or not. Thirty-seven patients, 3 months-10 years after kidney transplantation being under immunosuppressive treatment with CsA + Prednisolone (n = 25), Azathioprine + Prednisolone (n = 6) and under Prednisolone alone (n = 6) underwent the study. 18 healthy persons served as a normal control group. Granulocyte function was tested ex vivo by chemiluminescence (CL) after stimulation with phorbolmyristate acetate (PMA) and with zymosan (zym) activated autologous or pool-serum. The obtained data were correlated to corresponding serum or plasma levels of CsA, human leukocyte elastase (HLE) and neopterin. Comparing the three therapy groups with the healthy control and with each other no differences could be seen in median CL values; but there was a significant (p = 0.05) negative correlation between CsA blood levels and maximum CL values of PMN. Such inhibition of CL could be calculated for zym but not for PMA stimulated PMN; suggesting that the CsA mediated inhibition of granulocyte function may be only partial and restricted to phagocytosis. In addition, a positive correlation between serum levels of human leukocyte elastase (HLE) and neopterin could be found. This indicates a simultaneous influence of CsA on both PMN and macrophages.
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PMID:Latent inhibition of granulocyte function by cyclosporine A. 227 42

The elevated neopterin levels observed in numerous haemotological diseases and parenchymatous malignomas suggested neopterin might be useful as a tumor marker. In a group of 60 patients suffering from advanced lung (18) or breast (42) cancer, serial determinations of serum neopterin were made before, during and after radiation and/or chemotherapy, during an observation period of 18 months, to check the potential value of neopterin in the therapeutic management of these tumor types. The neopterin profiles were compared with the clinical course and analysed with regard to response to therapy. Numbers of pathologically elevated serum neopterin levels were low. In only few cases was any agreement detected between changes in neopterin levels and therapeutic effects. Even chemotherapeutically induced depression in white blood counts generally did not increase serum neopterin levels. Thus the clinical suitability of neopterin as an adjuvant parameter in assessing therapeutic effects in lung or breast cancer could not be documented.
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PMID:Serum neopterin levels in lung and breast cancer patients undergoing radiotherapy and/or chemotherapy. 285 49

Levels of urinary neopterin and biopterin were determined in patients having a diagnosis of schizophrenia, unipolar depression, or bipolar depression. Both neopterin and biopterin levels were significantly higher in the urine of patients with unipolar depression than in the urine of the control group. Subclassification of patients into primary and secondary depression demonstrated a significant elevation of urinary biopterin in both groups, whereas urinary neopterin was elevated only in those patients with primary depression. In patients with bipolar depression, neopterin excretion was elevated, but biopterin excretion did not differ from controls. No significant differences were found in schizophrenic patients.
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PMID:Urinary excretion of biopterin and neopterin in psychiatric disorders. 658 38

This study investigates serum levels of zinc in 48 unipolar depressed subjects (16 minor, 14 simple major and 18 melancholic subjects) and 32 normal volunteers, and the relationships between zincemia and plasma neopterin levels, postdexamethasone adrenocorticotropic hormone and cortisol values, and anorexia-weight loss. Serum zinc levels were significantly lower in major depressed subjects than in normal controls, whereas minor depressed subjects showed intermediate values. There were significant negative correlations between serum zinc, and severity of depression and plasma neopterin concentrations. No significant relationships between zincemia and either postdexamethasone hormone values or anorexia/weight loss were found. The findings suggest that hypozincemia in major depression may be related to activation of cell-mediated immunity in that illness.
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PMID:Hypozincemia in depression. 807 76

Urinary excretion of neopterins (N) and biopterins (B) was measured in 48 patients with depression before and after treatment with placebo, antidepressants, or electroconvulsive therapy (ECT), and in 26 healthy control subjects. Patients prior to and after treatment had a significantly greater neopterin/biopterin (N:B) ratio than control subjects. There was a significant correlation between N:B ratios and the severity of depression and plasma cortisol. As a raised N:B ratio implies failure to convert neopterin to biopterin, it is possible that reduced availability of tetrahydrobiopterin, the essential cofactor for the formation of noradrenaline, serotonin and dopamine, may exert rate-limiting control over the synthesis of monoamines implicated in the pathogenesis of depressive illness.
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PMID:The role of pterins in depression and the effects of antidepressive therapy. 867 6

Plasma 5-hydroxytryptamine (serotonin), tryptophan, neopterin and cortisol levels were measured in patients with depressive cancer cachexia and in healthy controls during the same time period. Patients with advanced cancers had significantly raised neopterin, a marker of endogenous gamma-interferon (IFN-gamma) production, and cortisol values, but decreased serotonin and tryptophan levels. Much work has been done to elucidate the possible role of serotonin in depressive states. IFN-gamma induces a high level of indoleamine dioxygenase (IDO), a tryptophan degrading enzyme, and high cortisol levels induce high tryptophan oxygenase activity, which in turn increases metabolism along the tryptophan-nicotinic acid pathway. These results suggest that persistent immune activation and intense adrenal activity occur in patients with cancer cachexia, resulting in disorders involving tryptophan metabolism followed by depression in cancer cachexia.
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PMID:Cancer cachexia and depressive states: a neuro-endocrine-immunological disease? 928 72


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