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Query: UMLS:C0011570 (depression)
 172,036 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

To understand the factors associated with interest in assisted suicide among terminally ill patients, we surveyed 50 caregivers of decedent amyotrophic lateral sclerosis (ALS) patients from Oregon and Washington regarding perceptions of patients' interest in assisted suicide and their physical and emotional state in the last month of life. For 38 caregivers, we had baseline information from the patients themselves, gathered a median of 11 months before death, regarding depression, hopelessness, sense of burden, social support, quality of life, pain, and suffering. According to our respondents, one-third of ALS patients discussed wanting assisted suicide in the last month of life. Hopelessness and interest in assisted suicide at baseline predicted desire for assisted suicide later on. ALS patients who were interested in assisted suicide, compared to those who were not, had greater distress at being a burden to others and more insomnia, pain, and discomfort other than pain.
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PMID:Predictors and correlates of interest in assisted suicide in the final month of life among ALS patients in Oregon and Washington. 1245 12

Twenty-five ALS subjects filled out five questionnaires: the ALS Functional Rating Scale, Multidimensional Fatigue Inventory, multidimensional McGill Quality of Life, Center of Epidemiologic Study--Depression Scale, and the Epworth Sleepiness Scale. Fatigue, depression, and excessive somnolence are more pronounced in ALS subjects than in normal controls. Both fatigue and depression are associated with poorer quality of life in subjects with ALS, and should be treated aggressively.
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PMID:Fatigue and depression are associated with poor quality of life in ALS. 1515 19

Nerve growth factor was the first identified protein with anti-apoptotic activity on neurons. This prototypic neurotrophic factor, together with the three structurally and functionally related growth factors brain-derived neurotrophic factor (BDNF), neurotrophin-3 (NT3) and neurotrophin-4/5 (NT4/5), forms the neurotrophin protein family. Target T cells for neurotrophins include many neurons affected by neurodegenerative diseases such as Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis and peripheral polyneuropathies. In addition, the neurotrophins act on neurons affected by other neurological and psychiatric pathologies including ischemia, epilepsy, depression and eating disorders. Work with cell cultures and animal models provided solid support for the hypothesis that neurotrophins prevent neuronal death. While no evidence exists that a lack of neurotrophins underlies the etiology of any neurodegenerative disease, these studies have spurred on hopes that neurotrophins might be useful symptomatic-therapeutic agents. However first clinical trials led to variable results and severe side effects were observed. For future therapeutic use of the neurotrophins it is therefore crucial to expand our knowledge about their physiological functions as well as their pharmacokinetic properties. A major challenge is to develop methods for their application in effective doses and in a precisely timed and localized fashion.
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PMID:Neurotrophins. 1257 26

Apart from the extensive loss of motor neurons, degeneration of midbrain dopaminergic cells has been described in both familial and sporadic forms of amyotrophic lateral sclerosis (ALS). Mice overexpressing the mutant human Cu/Zn superoxide dismutase (SOD1) show an ALS-like phenotype in that they show a progressive death of motor neurons accompanied by degeneration of dopaminergic cells. To describe the functional alterations specifically associated with this dopaminergic dysfunction, we have investigated the corticostriatal synaptic plasticity in mice overexpressing the human SOD1 (SOD1+) and the mutated (Gly(93)-->Ala) form (G93A+) of the same enzyme. We show that repetitive stimulation of the corticostriatal pathway generates long-term depression (LTD) in SOD1+ mice and in control (G93A-/SOD1-) animals, whereas in G93A+ mice the same stimulation generates an N-methyl-D-aspartic acid receptor-dependent long-term potentiation. No significant alterations were found in the intrinsic membrane properties of striatal medium spiny neurons and basal corticostriatal synaptic transmission of G93A+ mice. Bath perfusion of dopamine or the D(2) dopamine receptor agonist quinpirole restored LTD in G93A+ mice. Consistent with these in vitro results, habituation of locomotor activity and striatal-dependent active avoidance learning were impaired in G93A+ mice. Thus, degeneration of dopaminergic neurons in the substantia nigra of G93A+ mice causes substantial modifications in striatal synaptic plasticity and related behaviors, and may be a cellular substrate of the extrapyramidal motor and cognitive disorders observed in familial and sporadic ALS.
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PMID:Altered long-term corticostriatal synaptic plasticity in transgenic mice overexpressing human CU/ZN superoxide dismutase (GLY(93)-->ALA) mutation. 1269 76

Many common neurological and psychiatric disorders are accompanied by extensive neuronal loss, either acutely or chronically. These include stroke, head trauma, spinal cord injury, epilepsy, perinatal and perioperative hypoxia-ischaemia, Alzheimer's and Parkinson's diseases, amyotrophic lateral sclerosis (ALS) and even some aspects of schizophrenia and depression. Despite considerable research effort, no agent has been found that can protect the brain from any of these neurodegenerative conditions. 'Clinical Trials in Neuroprotection,' sponsored by the University of Pennsylvania, was held to address this situation in a unique way. Rather than focus on one neurodegenerative condition, the conference brought together researchers from a variety of neuroprotection areas. They reviewed basic mechanisms of neuronal injury, the animal models used in a variety of paradigms and the design and results of clinical trials in many neuroprotection areas. The presentations and extensive discussions focused on common issues encountered and lessons learned, and on developing innovative strategies for clinical evaluation of potential neuroprotective agents. Conference participants came to a general consensus that some mechanisms were the same for all conditions, models need to be improved, new clinical trial paradigms should consider drug combinations and/or sequential administration of neuroprotective agents, new biomarkers should be developed and a 'proof-of-principle' trial would be widely valuable and should be developed.
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PMID:Clinical trials in neuroprotection. 23-25 January 2003, Key Biscayne, Florida, USA. 1461 Sep 26

Cannabis (marijuana) has been proposed as treatment for a widening spectrum of medical conditions and has many properties that may be applicable to the management of amyotrophic lateral sclerosis (ALS). This study is the first, anonymous survey of persons with ALS regarding the use of cannabis. There were 131 respondents, 13 of whom reported using cannabis in the last 12 months. Although the small number of people with ALS that reported using cannabis limits the interpretation of the survey findings, the results indicate that cannabis may be moderately effective at reducing symptoms of appetite loss, depression, pain, spasticity, and drooling. Cannabis was reported ineffective in reducing difficulties with speech and swallowing, and sexual dysfunction. The longest relief was reported for depression (approximately two to three hours).
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PMID:Survey of cannabis use in patients with amyotrophic lateral sclerosis. 1505 8

The cognitive impairment revealed in some non- demented amyotrophic lateral sclerosis (ALS) patients is characterized by executive dysfunction with widely repeated deficits on tests of verbal (letter) fluency. However, conflicting evidence exists of an impairment on other word retrieval tasks, such as confrontation naming, which do not place heavy demands on executive processes. Previous research has demonstrated intact confrontation naming in the presence of verbal fluency deficits, although naming deficits have been described in other studies. In this investigation, functional MRI (fMRI) techniques were employed to explore whether word retrieval deficits and underlying cerebral abnormalities were specific to letter fluency, which are more likely to indicate executive dysfunction, or were also present in confrontation naming, indicating language dysfunction. Twenty-eight non-demented ALS patients were compared with 18 healthy controls. The two groups were matched for age, intelligence quotient, years of education, and anxiety and depression scores. Two compressed-sequence overt fMRI activation paradigms were employed, letter fluency and confrontation naming, which were developed for use with an older and potentially impaired population. In ALS patients relative to controls, the letter fluency fMRI task revealed significantly impaired activation in the middle and inferior frontal gyri and anterior cingulate gyrus, in addition to regions of the parietal and temporal lobes. The confrontation naming fMRI task also revealed impaired activation in less extensive prefrontal regions, including the inferior frontal gyrus and regions of the temporal, parietal and occipital lobes. These changes were present despite matched performance between patients and controls during each activation paradigm. The pattern of dysfunction corresponded to the presence of cognitive deficits on both letter fluency and confrontation naming in the ALS group. This study provides evidence of cerebral abnormalities in ALS in the network of regions involved in language and executive functions. Moreover, the findings further illustrate the heterogeneity of cognitive and cerebral change in ALS.
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PMID:Word retrieval in amyotrophic lateral sclerosis: a functional magnetic resonance imaging study. 1516 10

The authors provide an extensive review of new data related to the role of glutamate in CNS disorders, describing new aspects in glutamate and glutamatergic receptors-NMDA receptors, NR2B-selective antagonists, non-NMDA ionotropic glutamate receptors, N-acetylaspartylglutamate, and glutamate and glycine transporters. New findings in animal models and in human diseases-stroke, traumatic brain injury, Alzheimer's, Parkinson's and Huntington's diseases, tardive dyskinesia, ALS, olivopontcerebellar degeneration, AIDS, allergic encephalomyelitis, epilepsy, anxiety, depression, schizophrenia, liver disease, aminoglycoside antibiotic-induced hearing loss, hemiplegia, chronic pain and drug tolerance and abuse-are presented. Finally, the authors cite the progress achieved in the development of agents that interact with the glutamatergic system: NMDA channel blockers, competitive NMDA receptor antagonists, NR2B-selective antagonists, glutamate release inhibitors, glycineB antagonists, AMPA and kainate receptor antagonists, AMPA receptor-positive modulators and agents that act by modifying endogenous kynurenic acid metabolism.
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PMID:Glutamate in CNS disorders as a target for drug development: an update. 1561 69

Degeneration of nigrostriatal dopamine neurons and cholinergic cortical neurones are the main pathological features of Parkinson's disease (PD) and for the cognitive deficit in dementia of the Alzheimer' type (AD) and in dementia with Lewy bodies (DLB), respectively. Many PD and DLB subjects have dementia and depression resulting from possible degeneration of cholinergic and noradrenergic and serotonergic neurons. On the other hand, AD patients may also develop extrapyramidal features as well as depression. In both PD and AD there is, respectively, accumulation of iron within the melanin containing dopamine neurons of pars compacta and with in the plaques and tangle. It has been suggested that iron accumulation may contribute to the oxidative stress induced apoptosis reported in both diseases. This may result from increased glia hydrogen peroxide producing monoamine oxidase (MAO) activity that can generate of reactive hydroxyl radical formed from interaction of iron and hydrogen peroxide. We have therefore prepared a series of novel bifunctional drugs from the neuroprotective-antiapoptotic antiparkinson monoamine oxidase B inhibitor, rasagiline, by introducing a carbamate cholinesterase (ChE) inhibitory moiety into it. Ladostigil (TV-3326, N-propargyl-3R-aminoindan-5yl)-ethyl methylcarbamate), has both ChE and MAO-AB inhibitory activity, as potential treatment of AD and DLB or PD subjects with dementia Being a brain selective MAO-AB inhibitor it has limited potentiation of the pressor response to oral tyramine and exhibits antidepressant activity similar to classical non-selective MAO inhibitor antidepressants by increasing brain serotonin and noradrenaline. Ladostigil inhibits brain acetyl and butyrylcholinesterase in rats and antagonizes scopolamine-induced inhibition of spatial learning. Ladostigil like MAO-B inhibitor it prevents MPTP Parkinsonism in mice model and retains the in vitro and in vivo neuroprotective activity of rasagiline. Ladostigil, rasagiline and other propargylamines have been demonstrated to have neuroprotective activity in several in vitro and in vivo models, which have been shown be associated with propargylamines moiety, since propargylamines itself possess these properties. The mechanism of neuroprotective activity has been attributed to the ability of propargylamines-inducing the antiapoptotic family proteins Bcl-2 and Bcl-xl, while decreasing Bad and Bax and preventing opening of mitochondrial permeability transition pore. Iron accumulates in brain regions associated with neurodegenerative diseases of PD, AD, amyotrophic lateral sclerosis and Huntington disease. It is thought to be involved in Fenton chemistry oxidative stress observed in these diseases. The neuroprotective activity of propargylamines led us to develop several novel bifunctional iron chelator from our prototype brain permeable iron chelators, VK-28, possessing propargylamine moiety (HLA-20, M30 and M30A) to iron out iron from the brain. These compounds have been shown to have iron chelating and monoamine oxidase A and B selective brain inhibitory and neuroprotective-antiapoptotic actions.
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PMID:Bifunctional drug derivatives of MAO-B inhibitor rasagiline and iron chelator VK-28 as a more effective approach to treatment of brain ageing and ageing neurodegenerative diseases. 1562 Dec 13

This study aimed at investigating attitudes toward assisted suicide among individuals with amyotrophic lateral sclerosis, and the differences in health status (illness severity and functional disability) and psychosocial adjustment (depression, perceived stress, social support, and coping) between those in favor of and those against assisted suicide. This study also aimed at describing the characteristics of terminally-ill individuals who acknowledge contemplating assisted suicide. Forty-four individuals diagnosed with amyotrophic lateral sclerosis were surveyed about their attitudes and the circumstances that would make them contemplate assisted suicide and filled out standardized measures of mood, stress, social support, coping, and illness status. Seventy percent of the sample found assisted suicide morally acceptable and 60% thought it should be legalized. In addition, 60% of patients agreed they could foresee circumstances that would make them contemplate assisted suicide, but only three (7%) indicated they would have requested it already if it had been legal. Willingness to contemplate assisted suicide was associated with reports of elevated levels of depressive symptoms and reports of hopelessness. Results highlight the need to assess psychological status carefully when terminally ill individuals begin contemplating assisted suicide or voice a request for it.
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PMID:Attitudes toward and desire for assisted suicide among persons with amyotrophic lateral sclerosis. 1568 43


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