UMLS:C0036341 - FACTA Search

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Query: UMLS:C0036341 (schizophrenia)
60,220 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Treatment of schizophrenia is often complicated by substance abuse. We report here findings of a retrospective study evaluating readmission rates of patients meeting DSM IV criteria comorbid for schizophrenia and alcohol or drug dependence treated with depot haloperidol or fluphenazine over a 2-year period. During the study period, 14 of the 26 (54%) male veteran patients were admitted to the VAMC, Charleston; 46% of patients met criteria for alcohol, marijuana or cocaine dependence. Patients with alcohol dependence appeared to be at highest risk for hospital admission (p < 0.05). Moreover, patients with alcohol dependence had longer hospital stays (p < 0.05) than patients without alcohol dependence. Marijuana or cocaine dependence was slightly, but not statistically more common among admitted patients. Marijuana or cocaine dependence did not predict length of stay or number of admissions. Alcohol dependence may be an important factor in schizophrenic exacerbation, and may be an important target for treatment.
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PMID:Alcohol dependence and hospitalization in schizophrenia. 1042 12

Rigorous experimental design can minimize the high risk of false positives and false negatives in the behavioral phenotyping of a new transgenic or knockout mouse. Use of well established, quantitative, reproducible behavioral tasks, appropriate Ns, correct statistical methods, consideration of background genes contributed by the parental strains, and attention to litter and gender issues, will maximize meaningful comparisons of -/-, +/-, and +/+ genotypes. Strategies developed and used by our laboratory are described in this review. Preliminary observations evaluate general health and neurological reflexes. Sensory abilities and motor functions are extensively quantitated. Specific tests include observations of home cage behaviors, body weight, body temperature, appearance of the fur and whiskers, righting reflex, acoustic startle, eye blink, pupil constriction, vibrissae reflex, pinna reflex, Digiscan open field locomotion, rotarod motor coordination, hanging wire, footprint pathway, visual cliff, auditory threshold, pain threshold, and olfactory acuity. Hypothesis testing then focuses on at least three well-validated tasks within each relevant behavioral domain. Specific tests for mice are described herein for the domains of learning and memory, feeding, nociception, and behaviors relevant to discrete symptoms of human anxiety, depression, schizophrenia, and drug addiction. An example of our approach is illustrated in the behavioral phenotyping of C/EBPdelta knockout mice, which appear to be normal on general health, neurological reflexes, sensory and motor tasks, and the Morris water task, but show remarkably enhanced performance on contextual fear conditioning.
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PMID:Behavioral phenotyping of transgenic and knockout mice: experimental design and evaluation of general health, sensory functions, motor abilities, and specific behavioral tests. 1044 92

There are two families of dopamine (DA) receptors, called D1 and D2, respectively. The D1 family consists of D1- and D5-receptor subtypes and the D2 family consists of D2-, D3-, and D4-receptor subtypes. The amino acid sequences of these receptors show that they all belong to a large superfamily of receptors with seven transmembrane domains, which are coupled to their intracellular signal transduction systems by G-proteins. The implications of DA receptors in neuropsychiatry and cardiovascular and renal diseases are discussed. Neuropsychiatry indications include Parkinson's disease, schizophrenia, migraine, drug dependence, mania and depression, and Gilles de la Tourette syndrome. The underlying dysfunction of dopaminergic systems and the potential benefits of dopaminergic therapy in these different indications are critically examined. With respect to the pharmacological treatment of Parkinson's disease, a range of DA agonists are in various stages of preclinical and clinical development. D2-receptor agonist activity is predominant in most effective antiparkinsonian DA agonists. However, in practice, it is difficult to treat patients for several years with DA agonists alone; therapeutic benefit is not sustained. Rather, the use of a combination of DA agonists and levodopa is considered preferable. Reports of the efficacy of DA partial agonists await confirmation, and recent clinical investigations also suggest the potential of D1 receptor agonists as antiparkinson drugs. Regarding migraine pathogenesis, clinical and pharmacological evidence suggests that DA is involved in this disorder. Most prodromal and accompanying symptoms may be related to dopaminergic activation. Several drugs acting on DA receptors are effective in migraine treatment. Furthermore, migraine patients show a higher incidence of dopaminergic symptoms following acute DA agonist administration, when compared with normal controls. In cardiology, the therapeutic benefits of DA agonists are noted in the treatment of heart failure. Low doses of DA are widely used for its specific dopaminergic effects on renal function, which are suggested to be beneficial, and for its alpha- and beta-adrenergic-mediated responses that occur with higher doses. However, studies have been unable to demonstrate that DA can prevent acute renal failure or reduce mortality. It appears that the significant progress that is being made in the molecular understanding of DA receptors will continue to have a tremendous impact in the pharmacological treatment of neuropsychiatric, cardiovascular, and renal diseases.
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PMID:Dopamine receptors--physiological understanding to therapeutic intervention potential. 1059 3

The present study investigates the modulation of the ventral tegmental area (VTA)-ventral pallidum (VP) dopaminergic system by glutamate agonists in rats. The glutamate receptor agonists N-methyl-D-aspartate (NMDA) and alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) were infused via reversed microdialysis into the VTA, and dopamine (DA), glutamate, and aspartate levels in the VTA and ipsilateral VP were monitored together with motor behavior screened in an open field. NMDA (750 microM) infusion, as well as AMPA (50 microM) infusion, induced an increase of DA and glutamate levels in the VTA, followed by an increase of DA levels in the ipsilateral VP and by enhanced locomotor activity. The increase of DA in the VP was similar after administration of these two glutamate agonists, although motor activity was more pronounced and showed an earlier onset after NMDA infusion. Glutamate levels in the VP were not increased by the stimulation of DA release. It is concluded that DA is released from mesencephalic DA neurons projecting to the VP and that these neurons are controlled by glutamatergic systems, via NMDA and AMPA receptors. Thus, DA in the VP has to be considered as a substantial modulator. Dysregulation of the mesopallidal DA neurons, as well as their glutamatergic control, may play an additional or distinct role in disorders like schizophrenia and drug addiction.
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PMID:Effect of intracerebral administration of NMDA and AMPA on dopamine and glutamate release in the ventral pallidum and on motor behavior. 1080 Sep 48

Cocaine abuse is a significant problem not only in the general population but also among pregnant women. Since cocaine readily crosses the placenta and is metabolized slowly in fetuses, they can be exposed to significant levels of cocaine for long periods. In humans the most common consequences of cocaine abuse during pregnancy include premature birth, lower birth weight, respiratory distress, bowel infarctions, cerebral infarctions, reduced head circumference, and increased risk of seizures. Behaviorally these newborns show an increased degree of "tremulousness," crying and irritability, and are over-reactive to environmental stimuli. Within a month these behaviors have recovered dramatically, but not to normal levels. Thus while there are a number of abnormalities associated with cocaine-exposed neonates, they are not imminently debilitating or life-threatening. However, the long-term consequences of this prenatal cocaine exposure remain to be elucidated. We have examined a rat model for neurochemical, neuroanatomical and behavioral changes resulting from prenatal cocaine exposure. Since cocaine is known to act by blocking the inactivation of the neurotransmitters dopamine, serotonin and norepinephrine, our studies have focused on brain dopamine (DA) and serotonin (5-HT) pathways. In this model system we have found neurochemical changes that are present at birth and that return to normal as the rat ages--similar to the recovery observed in infants. However, there are other neurochemical, anatomical and behavioral changes that persist after birth which may provide insights into the long-term consequences. It is hoped that by understanding the changes occurring in this rat model we will be better prepared to devise pharmacological interventions to circumvent the secondary consequences of prenatal cocaine exposure. These consequences might include increased susceptibility to drug addiction, seizures, depression, schizophrenia, Parkinson's disease, etc.
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PMID:Prenatal cocaine exposure. 1091 32

Dopamine D3 receptors may be involved in drug addiction and in disorders such as schizophrenia and Parkinson's disease. To determine the pharmacological properties of dopamine D3 receptors in the rat caudate-putamen, we have investigated R(+)-[3H]7-hydroxy-N,N-di-n-propyl-2-aminotetralin ([3H]R(+)-7-OH-DPAT) binding to membrane preparations from the rat caudate-putamen. Kinetic analyses showed that [3H]R(+)-7-OH-DPAT binding reached equilibrium in approximately 1 h and that both association and dissociation curves were composed of at least two components. Likewise, saturation curves showed at least two binding components with a combined Bmax value of about 600 fmol/mg protein, which is three times higher than what is present in the subcortical limbic area. Competition curves were performed with agonists such as R(-)-propylnorapomorphine, dopamine, PD 128907, quinpirole, and bromocriptine, and antagonists such as haloperidol, raclopride, clozapine, GR 218231x, remoxipride, and U99194A. These experiments revealed that [3H]R(+)-7-OH-DPAT binding could be resolved into three specific binding sites (R1-R3) and one nonspecific binding site, with R1-R2 probably representing D3 receptor binding and the minor R3 representing D2 receptor binding. The low affinities of (+/-)-8-OH-DPAT and 1,3-di(2-tolyl)guanidine to inhibit [3H]R(+)-7-OH-DPAT binding indicate negligible involvement of 5-HT1A or sigma binding sites, respectively. The pharmacological profile of [3H]R(+)-7-OH-DPAT (2 nM) binding in the caudate-putamen was similar to that of dopamine on [125I]iodosulpride binding in the cerebellar lobule X, which contain D3 but not D2 receptors. Mg2+ increased and GTP and Na+ decreased the binding of [3H]R(+)-7-OH-DPAT, suggesting a coupling of endogenous D3 receptors to G proteins. Taken together, these results suggest that dopamine D3 receptors display multiple agonist binding states, and that D3 receptors are present in high concentrations in the rat caudate-putamen. These results may have implications for the physiological and pathological roles of dopamine D3 receptors in the brain.
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PMID:Pharmacology of [3H]R(+)-7-OH-DPAT binding in the rat caudate-putamen. 1091 86

Persons in drug treatment with drug dependence were interviewed with the NIMH Diagnostic Interview Schedule to ascertain DSM-III-R disorders. Lifetime prevalence rates were 64% for alcohol dependence, 44% for antisocial personality disorder (ASPD), 39% for phobic disorders, 24% for major depression, 12% for dysthymia, 10% for generalized anxiety disorder, 3% for panic disorder, 3% for mania, 3% for obsessive compulsive disorder, 2% for bulimia, 1% for schizophrenia, and 1% for anorexia. When stratified by race and age, significant main effects were seen, but there were no significant interactions except in "any non-substance disorder" and in the mean number of non-substance use disorders. Caucasians had a higher mean number of drug dependence disorders and higher overall rates of "any other" disorder than African-Americans, and Caucasians and males had higher mean numbers of non-substance use disorders than African-Americans and females, respectively. This was related to rates of alcohol, cannabis, and hallucinogen dependence, and ASPD rates that were higher among men than women and higher among Caucasian respondents than African-American for alcohol, cannabis, hallucinogen, opiate and sedative dependence, major depression, dysthymia, and generalized anxiety disorder. In contrast, women had higher rates than men of amphetamine dependence, phobic disorder, major depression, dysthymia, panic disorder, obsessive compulsive disorder, and mania. African-Americans had higher rates than Caucasians of amphetamine, cocaine, and phencyclidine dependence, but for no comorbid disorders were the rates higher among African-Americans than Caucasians. The differences according to gender in rates of disorders among substance dependent persons are consistent with the results of general population surveys, but the differences in rates according to race are in contrast to these same community surveys. Limitations in the utility of the concept of race as a valid category diminish the generalizability of the findings; however, one possible explanation is differential treatment seeking in African-American and Caucasian populations that would result in the differences seen.
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PMID:Substance dependence and other psychiatric disorders among drug dependent subjects: race and gender correlates. 1093 73

The P300 wave is one of the cognitive components of the event-related potential (ERP) that is used to investigate the cognitive processes, and which can be used to study patient populations with a variety of psychiatric disorders. Its clinical utility has been increased by the identification of factors that contribute to the variability in its amplitude and latency. However, its value as a diagnostic index has not been entirely established. It can provide a useful recording of patients' information processing, and indicate the severity of the clinical state and its possible evolution. It can also assist in determining what therapeutic approach to adopt. In the present review, the findings in the literature concerning interindividual variation in the P300 wave are first described; several variables significantly influence the amplitude and latency of this wave, such as age, gender, intelligence and personality. Following this, the relevance of the data in the literature on the clinical applications of P300 in psychopathology is examined, including the studies undertaken to obtain an objective diagnostic index for mental disorders and also those carried out to assess the problems concerning the interpretation of information connected with the mental pathologies examined. P300-associated findings on dementia, schizophrenia, depression, alcoholism, drug addiction, anxiety disorders (panic disorder, obsessive-compulsive disorder, and post-traumatic stress syndrome) and on personality disorders (schizoid, antisocial or borderline personality disorder) have been examined in detail.
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PMID:[The p300 cognitive event-related potential. II. Individual variability and clinical application in psychopathology]. 1101 95

The mesoaccumbens projection, formed by ventral tegmental area dopamine neurons synapsing on nucleus accumbens gamma-aminobutyric acid neurons, has been implicated in the pathogenesis of schizophrenia and drug addiction. Despite intensive study, the nature of the signal conveyed by dopamine neurons has not been fully resolved. In addition to several slower, dopamine-mediated, modulatory actions, several lines of evidence suggest that dopamine neurons have fast excitatory actions. To test this, we placed dopamine neurons together with accumbens neurons in microcultures. Surprisingly, most dopamine neurons made excitatory recurrent connections (autapses), which provided a basis for their identification; accumbens gamma-aminobutyric acid neurons were identified by their distinctive size. In 75% of mesoaccumbens cell pairs, stimulation of the dopamine neuron evoked a glutamate-mediated, excitatory synaptic response in the accumbens neuron. Immunostaining revealed dopamine neuron varicosities that were predominantly dopaminergic, ones that were predominantly glutamatergic, and ones that were both dopaminergic and glutamatergic. Despite close appositions of both glutamatergic and dopaminergic varicosities to the dendrites of accumbens neurons, only glutamatergic synaptic responses were seen. In the majority of cell pairs, pharmacologic activation of D2-type dopamine receptors inhibited glutamatergic responses, presumably via immunocytochemically-visualized presynaptic D2 receptors. In some cell pairs, the evoked autaptic and synaptic responses were discordant, suggesting that D2 receptors may be differentially trafficked to different presynaptic varicosities.Thus, dopamine neurons appear to mediate both slow dopaminergic and fast glutamatergic actions via separate sets of synapses. Together with evidence for glutamate cotransmission in serotonergic raphe neurons and noradrenergic locus coeruleus neurons, these results add a new dimension to monoamine neuron signaling that may have important implications for neuropsychiatric disorders.
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PMID:Mesoaccumbens dopamine neuron synapses reconstructed in vitro are glutamatergic. 1102 37

The 5-HT(3) receptor is a ligand-gated ion channel widely distributed in the central and peripheral nervous systems. Many selective 5-HT(3) receptor antagonists have been developed; animal studies with such compounds suggested their potential therapeutic value in combating emesis and a wide range of CNS diseases including anxiety, schizophrenia, drug dependence and Alzheimer's disease. Their successful introduction as anti-emetics, with irritable bowel syndrome emerging as a further indication have partially fulfilled this initial promise. However, the CNS area has been less productive and, to date, no selective 5-HT(3) receptor antagonist has been approved for use in a CNS disease.
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PMID:5-HT(3) receptor antagonists. 1113 47

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