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

The authors reviewed the charts of all women and a randomly selected sample of men over a 6-month period on two addiction treatment units at Bellevue Hospital Center in New York. The men were more likely to be admitted with schizophrenia and to have used substances of abuse other than alcohol, and the women were more likely to be admitted with affective disorders. Also, the women on the dual-diagnosis ward were more likely to be domiciled (i.e., not homeless), and the women on both units were significantly more likely to report having been crime victims. These findings suggest that dually diagnosed women need a substantially different treatment paradigm from men.
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PMID:Differences between men and women in dual-diagnosis treatment. 939 29

Drug dependence is common in schizophrenia. Two main models explain this association: drugs precipitate psychosis in a vulnerable subject, and drugs use to self-medicate positive and negative symptoms and neuroleptics side effects. We investigated the prevalence of psychoactive substance use and dependence in schizophrenia and its association with the subtype of schizophrenia. The sample consisted of 56 outpatients with schizophrenia according to ICD-10, between 18 and 40 years, and a control group with 56 subjects with other different disorder. They were evaluated with Addiction Severity Index (ASI) and Positive And Negative Syndrome Scale (PANSS), sociodemographical, clinical and toxicological characteristics were evaluated too. Patients were classified in subtype negative, positive or mixed according to scoring in PANSS. Schizophrenics were reevaluates at six months of development. There were higher cocaine, alcohol, cannabis and nicotine use in schizophrenics. The patients with negative subtype of schizophrenia had more clinical severity, less scoring in alcohol and drugs subscales of ASI, lower prevalence of nicotine dependence and cocaine, amphetamines, cannabis and opioids use. Drugs use were associated with a poor compliance of treatment. Therefore, cannabis and cocaine dependence, regular alcohol use and tobacco use are more prevalent in schizophrenic than control group with other mental disorders. Negative subtype had lower drug use.
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PMID:[Drug use and dependence in schizophrenia]. 947 6

Interactions between dopamine and glutamate play prominent roles in memory, addiction, and schizophrenia. Several lines of evidence have suggested that the ventral midbrain dopamine neurons that give rise to the major CNS dopaminergic projections may also be glutamatergic. To examine this possibility, we double immunostained ventral midbrain sections from rat and monkey for the dopamine-synthetic enzyme tyrosine hydroxylase and for glutamate; we found that most dopamine neurons immunostained for glutamate, both in rat and monkey. We then used postnatal cell culture to examine individual dopamine neurons. Again, most dopamine neurons immunostained for glutamate; they were also immunoreactive for phosphate-activated glutaminase, the major source of neurotransmitter glutamate. Inhibition of glutaminase reduced glutamate staining. In single-cell microculture, dopamine neurons gave rise to varicosities immunoreactive for both tyrosine hydroxylase and glutamate and others immunoreactive mainly for glutamate, which were found near the cell body. At the ultrastructural level, dopamine neurons formed occasional dopaminergic varicosities with symmetric synaptic specializations, but they more commonly formed nondopaminergic varicosities with asymmetric synaptic specializations. Stimulation of individual dopamine neurons evoked a fast glutamatergic autaptic EPSC that showed presynaptic inhibition caused by concomitant dopamine release. Thus, dopamine neurons may exert rapid synaptic actions via their glutamatergic synapses and slower modulatory actions via their dopaminergic synapses. Together with evidence for glutamate cotransmission in serotonergic raphe neurons and noradrenergic locus coeruleus neurons, the present results suggest that glutamatergic cotransmission may be the rule for central monoaminergic neurons.
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PMID:Dopamine neurons make glutamatergic synapses in vitro. 961 34

Glutamatergic abnormalities have been associated with several psychiatric disorders, including schizophrenia and addiction. Group II metabotropic glutamate receptors were targeted to normalize glutamatergic disruptions associated with an animal model of schizophrenia, the phencyclidine model. An agonist of this group of receptors, at a dose that was without effects on spontaneous activity and corticolimbic dopamine neurotransmission, attenuated the disruptive effects of phencyclidine on working memory, stereotypy, locomotion, and cortical glutamate efflux. This behavioral reversal occurred in spite of sustained dopamine hyperactivity. Thus, targeting this group of receptors may present a nondopaminergic therapeutic strategy for treatment of psychiatric disorders.
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PMID:Reversal of phencyclidine effects by a group II metabotropic glutamate receptor agonist in rats. 973 37

Nicotinic acetylcholine receptors are ligand-gated ion channels present in muscle and brain. These allosteric oligomers may exist in several conformational states which include a resting state, an open-channel state, and a desensitized refractory state. Recent work has shown that point mutations in the nicotinic receptor may, altogether, abolish desensitization, increase apparent affinity for agonists and convert the effect of a competitive antagonist into an agonist response. These pleiotropic effects are interpreted in terms of the allosteric model. This paper reviews recent evidence that such mutations occur spontaneously in humans and may cause diseases such as congenital myasthenia or familial frontal lobe epilepsy. In addition, nicotinic receptors are involved in tobacco smoking. Accumulating evidence, including experiments with knock-out animals, indicates that addiction to nicotine is linked to the activation of beta 2-subunit containing nicotinic receptors in the dopaminergic mesolimbic neurons which are part of the reward systems in the brain. Current research also indicates that nicotinic agonists might serve as therapeutic agents for Alzheimer's disease and Tourette's syndrome, as well as for schizophrenia. This paper extends and updates a recently published review.
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PMID:Allosteric nicotinic receptors, human pathologies. 978 46

Neuronal nicotinic receptors (nAChRs) have been implicated in pathology associated with neurological diseases and aberrant cognitive states such as addiction and schizophrenia. The design of subtype-specific cholinergic drugs is dependent on identification of key amino acids that play a significant role in determining subunit-specific agonist efficacy. 1,1-Dimethyl-4-phenylpiperazinium (DMPP) and a series of piperazium (PIP)-derived cholinergic agonists (1,1 dimethyl-4-acetylpiperizinium iodide, EthylPIP, PropylPIP, and ButylPIP) were used to identify a site (position 84) in homomeric neuronal nAChRs, which is a partial determinant of pharmacological specificity. In contrast to absolutely conserved amino acids within the nicotinic superfamily, the amino acid in position 84 can be polar or nonpolar. The addition of one methylene to PropylPIP to form ButylPIP eliminated channel activation of but not binding to the chick alpha7 homomeric nAChR (leucine in position 84). In rat alpha7 (glutamine in position 84), ButylPIP was an agonist. 1, 1-Dimethyl-4-phenylpiperazinium, a structural analog of ButylPIP, activates the rat alpha7 but is a weak partial agonist of the chick alpha7. Mutation of the chick alpha7 (L84Q) restored activation by ButylPIP, and the corresponding mutation in rat alpha7 (Q84L) abolished activation by ButylPIP. These mutations had moderate effects on the apparent affinity for acetylcholine, increasing its affinity for chick alpha7 and decreasing it for rat alpha7. Thus, the amino acid in position 84 (a residue on the periphery of the highly conserved loop A of the cys-loop superfamily of receptors) can potentially be exploited to produce subtype-specific drugs and can provide insights into the structure of the binding domain.
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PMID:Identification of a new amino acid residue capable of modulating agonist efficacy at the homomeric nicotinic acetylcholine receptor, alpha7. 988 91

Sydnocarb (3-(beta-phenylisopropyl)-N-phenylcarbamoylsydnonimine) is a psychostimulant in clinical practice in Russia as a primary and adjunct therapy for a host of psychiatric disorders, including schizophrenia and depression. It has been described as a stimulant with an addiction liability and toxicity less than that of amphetamines. The present study undertook to evaluate the psychomotor stimulant effects of sydnocarb in comparison to those of methamphetamine. Sydnocarb increased locomotor activity of mice with reduced potency (approximately 10-fold) and efficacy compared with methamphetamine. Sydnocarb blocked the locomotor depressant effects of haloperidol at doses that were inactive when given alone. The locomotor stimulant effects of both methamphetamine and sydnocarb were dose-dependently blocked by the dopamine D1 and D2 antagonists SCH 39166 and spiperone, respectively; blockade generally occurred at doses of the antagonists that did not depress locomotor activity when given alone. In mice trained to discriminate methamphetamine from saline, sydnocarb fully substituted for methamphetamine with a 9-fold lower potency. When substituted for methamphetamine under self-administration experiments in rats, 10-fold higher concentrations of sydnocarb maintained responding by its i.v. presentation. Sydnocarb engendered stereotypy in high doses with approximately a 2-fold lower potency than methamphetamine. However, sydnocarb was much less efficacious than methamphetamine in inducing stereotyped behavior. Both sydnocarb and methamphetamine increased dialysate levels of dopamine in mouse striatum; however, the potency and efficacy of sydnocarb was less than methamphetamine. The convulsive effects of cocaine were significantly enhanced by the coadministration of nontoxic doses of methamphetamine but not of sydnocarb. Taken together, the present findings indicate that sydnocarb has psychomotor stimulant effects that are shared by methamphetamine while demonstrating a reduced behavioral toxicity.
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PMID:Behavioral, toxic, and neurochemical effects of sydnocarb, a novel psychomotor stimulant: comparisons with methamphetamine. 1002 71

This study examines the relationship between diagnosis and life functioning using the Addiction Severity Index (ASI) with 467 hospitalized individuals with mental illness and substance abuse problems. Persons diagnosed with schizophrenia were the best functioning group across most of the ASI domains except employment and psychiatric functioning. More robust relationships were found between problem history (i.e., prior symptomatology or treatment) and current functioning. Respondents with histories of drug treatment, prior experience of anxiety and depression, self-injurious behavior, or violence control problems experienced more severe medical, drug, alcohol, psychiatric, legal, and family/social problems at the time of hospitalization. Violence control problems were related to drug use and criminal involvement, whereas self-injurious behavior was more often related to alcohol use and psychiatric distress. These findings suggest that problem history may be a stronger predictor of treatment need at the time of hospital entry than are more commonly used indexes, such as diagnosis.
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PMID:Correlates of functioning in a population with dual diagnoses: an examination of diagnosis and problem history. 1017 84

Comorbid substance abuse disorders have emerged as one of the greatest obstacles to the effective treatment of persons with schizophrenia. Estimates of the prevalence of such comorbidity vary, but as many as half of persons with schizophrenia may suffer from a comorbid drug or alcohol disorder. Younger age, male gender, and lower educational attainment are associated with greater risk for addiction. Persons with schizophrenia and comorbid addiction tend to have an earlier onset of schizophrenia than do those without comorbid addiction. Research does not support a link between specific symptoms of schizophrenia and choice of abused drugs. Rather, drug choice is correlated with the pattern of ambient drug use in the community. Comorbid substance disorders are associated with a variety of poorer outcomes, including increased psychotic symptoms, poorer treatment compliance, violence, housing instability and homelessness, medical problems (including human immunodeficiency virus infection), poor money management, and greater use of crisis-oriented services that result in higher costs of care. Considerable progress has been made over the past decade in understanding the need to integrate substance abuse treatment and mental health treatment to provide more effective care for this population.
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PMID:Dual diagnosis of substance abuse in schizophrenia: prevalence and impact on outcomes. 1019 Feb 30

Researchers interested in investigating the possible therapeutic effects and the mechanisms of action of nicotine in neuropsychiatric disorders face a social-scientific-ethical dilemma. This dilemma comprises three components: (1) the known addictive potential of nicotine makes careful evaluation of the therapeutic potential of this compound socially unattractive; (2) the potential misuse of scientifically determined data by the tobacco 'lobby' creates ethical concerns; and (3) the possible confusion between the differential effects of nicotine in human smokers versus non-smokers creates difficulties in study designs in voluntary human subjects. Therefore, it is imperative that, at the onset of this review, the authors stress that they do not advocate cigarette-smoking as a route of nicotine intake under any circumstances on the basis that controlled dosing of nicotine may be of potential benefit in some neuropsychiatric disorders. In this article, we review the psychopharmacology of nicotine and its effects in a variety of neuropsychiatric disorders including schizophrenia, depression, anxiety and Tourette's syndrome. Possible mechanisms of action of nicotine directly or indirectly via its interaction with other neurotransmitter systems (i.e. serotonin, dopamine and noradrenaline) in relation to its potential role in these disorders are discussed. It is postulated that new drugs may need to be developed that selectively interact with nicotinic receptors without addiction potential.
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PMID:Smoking, nicotine and psychiatric disorders: evidence for therapeutic role, controversies and implications for future research. 1034 Feb 89


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