Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0036341 (schizophrenia)
 60,220 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

This study examined whether smoking menthol cigarettes was associated with increased biochemical measures of smoke intake. Expired carbon monoxide (CO) and serum nicotine and cotinine were measured in 89 smokers with schizophrenia and 53 control smokers immediately after smoking an afternoon cigarette. Serum nicotine levels (27 vs. 22 ng/ml, p = .010), serum cotinine levels (294 vs. 240 ng/ml, p = .041), and expired CO (25 vs. 21 ppm, p = .029) were higher in smokers of menthol compared with nonmenthol cigarettes, with no differences in 3-hydroxycotinine/cotinine ratios between groups when controlling for race. Backward stepwise linear regression models showed that, in addition to having a diagnosis of schizophrenia, smoking menthol cigarettes was a significant predictor of nicotine and cotinine levels. Individuals with schizophrenia or schizoaffective disorder smoked more generic or discount value brands (Basic, Doral, Monarch, USA, Wave, others) compared with control smokers (28% vs. 6%, p = .002) but did not smoke more brands with high nicotine delivery as estimated by the U.S. Federal Trade Commission method. Although rates of mentholated cigarette smoking were not higher in smokers with schizophrenia overall, they were significantly higher in non-Hispanic White people with schizophrenia compared with controls of the same ethnic/racial subgroup (51% vs. 28%, p<.0001). The higher exhaled CO in menthol smokers suggests that the higher nicotine levels are at least partly related to increased intake of smoke from menthol cigarettes, although menthol-mediated inhibition of nicotine metabolism also may be a factor. Menthol is an important cigarette additive that may help explain why some groups have lower quit rates and more smoking-caused disease.
Nicotine Tob Res 2007 Aug
PMID:Higher nicotine and carbon monoxide levels in menthol cigarette smokers with and without schizophrenia. 1765

People with schizophrenia often have substantial cognitive impairments, which may be related to nicotinic receptor deficits, (alpha7 and alpha4beta2), documented in the brains of people with schizophrenia. The large majority of people with schizophrenia smoke cigarettes. Thus, nicotinic interactions with antipsychotic drugs are widespread. Complementary co-therapies of novel nicotinic ligands are being developed to add to antipsychotic therapy to treat the cognitive impairment of schizophrenia. Thus, it is critical to understand the interaction between nicotinic treatments and antipsychotic drugs. Nicotinic interactions with antipsychotic drugs, are complex since both nicotine and antipsychotics have complex actions. Nicotine stimulates and desensitizes nicotinic receptors of various subtypes and potentiates the release of different neurotransmitters. Antipsychotics also act on a verity of receptor systems. For example, clozapine acts as an antagonist at a variety of neurotransmitter receptors such as those for dopamine, serotonin, norepinepherine and histamine. In a series of studies, we have found that in normally functioning rats, moderate doses of clozapine impair working memory and that clozapine blocks nicotine-induced memory and attentional improvement. Clozapine and nicotine can attenuate each other's beneficial effects in reversing the memory impairment caused by the psychototmimetic drug dizocilpine. A key to the clozapine-induced attenuation of nicotine-induced cognitive improvement appears to be its 5HT(2) antagonist properties. The selective 5HT(2) antagonist ketanserin has a similar action of blocking nicotine-induced memory and attentional improvements. It is important to consider the interactions between nicotinic and antipsychotic drugs to develop the most efficacious treatment for cognitive improvement in people with schizophrenia.
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PMID:Nicotinic interactions with antipsychotic drugs, models of schizophrenia and impacts on cognitive function. 1771 91

Acoustic prepulse inhibition (PPI) is considered an important biomarker in animal studies of psychosis and a number of psychiatric conditions. Nicotine has been shown to improve acoustic PPI in some animal strains and in humans. However, there is little data on effects of nicotine on acoustic PPI in schizophrenia patients using a double-blind, placebo-controlled study design. The primary aim of the current study was to test the effect of nicotine nasal spray on acoustic PPI in schizophrenia patients. The secondary aim was to test nicotine effect on prepulse facilitation (PPF). The study included 18 schizophrenia patient smokers and 12 healthy control smokers, tested in a double-blind, placebo-controlled, crossover, randomized design immediately after nicotine or saline placebo nasal sprays. PPI was tested using 120 ms prepulse-pulse interval. PPF was tested using 4500 ms prepulse-pulse interval. The results showed a significant main effect of drug on PPI in that nicotine improved PPI compared to placebo (p=0.008) with no drug by diagnosis interaction (p=0.90). Improvement in PPI in response to nicotine was significantly correlated with the baseline severity of clinical symptoms (r=0.59, p=0.02) in patients. There was no significant drug or drug by diagnosis interaction for the 4500 ms prepulse-pulse interval condition. However, nicotine improved inhibition in a subgroup of subjects exhibiting PPF (p=0.002). In conclusion, the findings confirmed that nicotine transiently improves acoustic PPI in schizophrenia patients. Additionally, schizophrenia patients with more clinical symptoms may have benefited more from nicotinic effect on PPI.
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PMID:Nicotine effect on prepulse inhibition and prepulse facilitation in schizophrenia patients. 1795 13

Although patients with have low motivations to quit smoking, smoking cessation treatment can be effective for these patients. Patients schizophrenia who achieve significant smoking reduction during a treatment intervention can at least maintain that level of reduction at 2 years. Cigarette smoking by patients with frequently goes unaddressed, contributing to excess mortality in this population. Behavioural interventions improve smoking cessation in schizophrenia patients. Nicotine replacement can substantially reduce withdrawal symptoms. Bupropion enhances smoking abstinence rates. Bupropion is well-tolerated and safe for use in schizophrenia patients: bupropion does not worsen clinical symptoms of schizophrenia. Atypical antipsychotics may reduce smoking consumption in schizophrenia patients, in particular clozapine. Atypical antipsychotic medication, in combination with the nicotine transdermal patch, significantly enhance the rate of smoking cessation. Interactions between smoking and antipsychotic medication - Smoking increases the metabolism of the antipsychotic medications by inducing the cytochrome P450 1A2 isoform. Smoking lowers the blood levels of typical or atypical antipsychotic medication, in particular haloperidol, chlorpromazine, olanzapine and clozapine. -Abstinence can increase many psychotropics' blood levels. Accordingly, smoking appears to reduce neuroleptic-induced parkinsonism. In contrast, smoking is a risk factor for tardive dyskinesia, independent of neuroleptic exposure.
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PMID:[Tobacco and schizophrenia: therapeutic aspects]. 1803 54

Blockade of NMDA glutamate receptors with dizocilpine (MK-801) has been shown to cause substantial cognitive deficits and has been used to model symptoms of schizophrenia. Nicotine or nicotinic agonists, in contrast, may enhance cognitive or attentional functions and be of therapeutic potential in schizophrenia. Nicotinic-glutamatergic interactions, therefore, may have important implications in cognitive functions and antipsychotic treatments. Clozapine, a widely used antipsychotic drug, has been shown in some studies to be effective in ameliorating the cognitive deficits associated with schizophrenia. However, there is some evidence to suggest that clozapine similar to haloperidol may impair sustained attention in rats. In this study, we sought to determine whether chronic nicotine or dizocilpine may modify the effects of acute clozapine on attentional parameters and whether the behavioral effects would correlate with nicotinic or NMDA receptor densities in discrete brain regions. Adult female rats trained on an operant visual signal detection task were given 4 weeks of nicotine (5 mg/kg/day), dizocilpine (0.15 mg/kg/day), the same doses of both nicotine and dizocilpine as a mixture, or saline by osmotic minipump. While on chronic treatment, rats received acute injections of various doses of clozapine (0, 0.625, 1.25, 2.5 mg/kg, sc) 10 min prior to tests on attentional tasks. The pumps were removed on day 28 and 24 h later the animals were sacrificed for measurements of receptor densities in specific brain regions. The percent correct hit as a measure of sustained attention was significantly impaired by clozapine in a dose-related manner. Neither chronic nicotine nor dizocilpine affected this measure on their own or modified the effects of clozapine. Both nicotine and dizocilpine affected the receptor bindings in a region specific manner and their combination further modified the effects of each other in selective regions. Attentional performance was inversely correlated with alpha-bungarotoxin binding in the frontal cortex only. In conclusion, the data suggest attentional impairments with clozapine alone and no modification of this effect with nicotine or dizocilpine. Moreover, cortical low affinity nicotinic receptors may have a role in attentional functions.
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PMID:Chronic nicotine and dizocilpine effects on nicotinic and NMDA glutamatergic receptor regulation: interactions with clozapine actions and attentional performance in rats. 1834 6

Many risk genes interact synergistically to produce schizophrenia and many neurotransmitter interactions have been implicated. We have developed a circuit-based framework for understanding gene and neurotransmitter interactions. NMDAR hypofunction has been implicated in schizophrenia because NMDAR antagonists reproduce symptoms of the disease. One action of antagonists is to reduce the excitation of fast-spiking interneurons, resulting in disinhibition of pyramidal cells. Overactive pyramidal cells, notably those in the hippocampus, can drive a hyperdopaminergic state that produces psychosis. Additional aspects of interneuron function can be understood in this framework, as follows. (i) In animal models, NMDAR antagonists reduce parvalbumin and GAD67, as found in schizophrenia. These changes produce further disinhibition and can be viewed as the aberrant response of a homeostatic system having a faulty activity sensor (the NMDAR). (ii) Disinhibition decreases the power of gamma oscillation and might thereby produce negative and cognitive symptoms. (iii) Nicotine enhances the output of interneurons, and might thereby contribute to its therapeutic effect in schizophrenia.
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PMID:Circuit-based framework for understanding neurotransmitter and risk gene interactions in schizophrenia. 1839 5

It is increasingly appreciated that amongst psychiatric cigarette smokers, those with schizophrenia have elevated rates of smoking compared to the general population. Nicotine seems to improve cognitive functions critically affected in schizophrenia. There is substantial evidence that nicotine could be used by patients with schizophrenia as a "self-medication" to improve deficits in attention, cognition, and information processing. Perhaps nicotine has influence on intensity of side effects of antipsychotic medication. Nicotine treatment modulates both dopaminergic and glutamatergic neurotransmission, and these effects are specific both to brain region and functional system. Understanding how and why schizophrenic individuals use nicotine may lead to the development of new treatments for both schizophrenia and nicotine dependence.
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PMID:[A review of the effects of nicotine on schizophrenia]. 1842 28

In order to develop a model of persistent sensorimotor gating that did not require acute NMDA (N-methyl-D-aspartate) receptor blockade, adult female Sprague-Dawley rats were pre-treated with N-methyl-scopolamine (1 mg/kg s.c.), then administered MK-801 (dizocilpine, 5 mg/kg i.p.) along with two separate doses (5 mg/kg) of pilocarpine. The drug regimen was repeated four and eight days later. Controls received saline in lieu of any drug. Ten days after the last neurotoxic treatment, rats had a significant impairment (reduction) in pre-pulse inhibition (PPI). Each treatment group (neurotoxic treated and control) was then divided into two groups for treatment with saline or 0.5 mg/kg nicotine, administered s.c. twice daily from days 10 to 23. The rats were tested for sensorimotor gating on days 17 and 22 shortly after the morning nicotine administration. Nicotine did not affect the PPI in control animals. On day 17, PPI impairment was sustained in neurotoxically treated rats, regardless of saline or nicotine treatment. On day 22, however, the effect of neurotoxic treatment on PPI was totally absent in saline treated rats, whereas in nicotine treated rats, PPI impairment was still evident. Combination of nicotine and neurotoxic treatment also caused an up-regulation of high affinity nicotinic receptors in the cortex and the thalamus and apparent normalization of low affinity nicotinic receptors in the hippocampus. The findings indicate that muscarinic activation, in conjunction with neurotoxic NMDA receptor antagonism, produces relatively long-term impairment in auditory gating, a result relevant to modeling clinical observations of schizophrenia-associated symptoms. Contrary to expectation, nicotine administration in this model resulted in further impairment rather than amelioration of PPI. The results suggest a sustainable model of PPI impairment and possible role of nicotinic receptors in selective brain regions in this behavior.
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PMID:Effects of nicotine on sensorimotor gating impairment induced by long-term treatment with neurotoxic NMDA antagonism. 1852 95

Nicotine evokes dopamine release through activation of nicotinic acetylcholine receptors, and tobacco cigarette smoking is more prevalent among individuals diagnosed with schizophrenia. Blockade of ionotropic glutamate (NMDA) receptors can induce changes in central dopamine and glutamate circuits, which models the symptoms of schizophrenia. The effect of the NMDA receptor antagonist, ketamine, on the effect of nicotine in rat prefrontal cortex was examined using a slice superfusion assay in which cortical slices were preloaded with [(3)H] dopamine. A wide range of ketamine concentrations (0.1-300 microM) did not evoke [(3)H] overflow from slices, indicating that NMDA receptor blockade did not induce dopamine release. Ketamine, at concentrations that model the symptoms of schizophrenia (1-10 microM), augmented the effect of nicotine (1-100 microM) to evoke [(3)H] overflow from slices and decreased the threshold nicotine concentration to evoke [(3)H] overflow. This indicates that NMDA receptor blockade increased the potency and efficacy of nicotine to evoke dopamine release from prefrontal cortex slices, suggesting that ketamine induced hypersensitivity to nicotine. The present results support a role for nicotinic acetylcholine receptors in the pathophysiology and treatment of schizophrenia.
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PMID:NMDA receptor blockade augmented nicotine-evoked dopamine release from rat prefrontal cortex slices. 1857 1

The mechanisms underlying the low smoking cessation rates among smokers with schizophrenia (SS) are unknown. In this laboratory study, we compared the responses of 21 SS and 21 non-psychiatric controls (CS) to manipulations of 5-hour smoking abstinence, transdermal nicotine replacement (0 mg, 21 mg and 42 mg), and in vivo smoking cues. Results indicate that SS were more sensitive than CS to the effects of acute abstinence on carbon monoxide (CO) boost, but not more sensitive to the effects of abstinence on urge levels or withdrawal symptoms. SS and CS did not differ in urge response to in vivo smoking cues, but SS were less consistent in their reactions. These findings suggest that heightened sensitivity to the effects of abstinence on smoke intake may partially account for the low cessation rates experienced by SS, but other potential mechanisms should be explored using behavioral laboratory models.
Nicotine Tob Res 2008 Jun
PMID:Effects of smoking abstinence, smoking cues and nicotine replacement in smokers with schizophrenia and controls. 1858 68


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