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)

Compelling evidence that tobacco-smoking is a form of drug addiction exists. The aim of this study is to determine the following: (1) prevalence of tobacco-smoking and of nicotine dependence in French psychiatric patients; (2) rates and patterns of tobacco smoking and of nicotine dependence according to diagnosis; (3) relationship between current smoking status and antipsychotic medications; and (4) relationship between cigarette smoking and neurological side effects induced by neuroleptics. A population of 711 psychiatric in- and outpatients was assessed using: (1) a detailed smoking self-questionnaire for smoking history and nicotine dependence; and (2) a questionnaire for staff covering treatments and DSMIII-R diagnoses. Data were analyzed using chi2 analysis of variance (ANOVA) tests (one factor) for quantitative comparisons between groups of patients, and analysis of covariance (ANCOVA) test with age covariate was performed for age-dependent variables. Prevalence of smoking in the population of psychiatric patients was significantly higher than in the French general population. Diagnoses among current smokers were mainly substance-related disorder and schizophrenia. The authors established correlations between prevalence of smoking and age, sex, marital and socioeconomic status, alcohol use, coffee consumption and other psychoactive substance use or abuse. The authors did not find relationship between smoking prevalence and institutionalization. Neuroleptic neurological side effects were significantly fewer among smokers compared to nonsmokers. However, the rate of smokers was significantly higher in psychiatric patients receiving neuroleptic drugs. Nicotine abuse in psychiatric patients, and especially in schizophrenic patients, could support the hypothesis that smoking is consistent with self-medication.
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PMID:Prevalence of smoking in psychiatric patients. 1199 4

High rate of tobacco smoking reported in schizophrenia has been related to the effect of nicotine on the neurobiology of schizophrenia. Nicotine is said to alleviate psychotic symptoms in some patients. The relationship between smoking and psychiatric status may not be simply a biological one as several sociocultural and economic factors could influence smoking behaviour. In this study in India on 286 urban male outpatients with schizophrenia, only 38% were found to be current smokers. This was significantly more than in other psychiatric patients studied (major affective disorders and non-psychotic disorders) but not medically ill controls and not higher than the rates for the general male population in India. Smokeless use of tobacco was infrequent in the study population. More than half of the patients did not experience any positive effects due to smoking. Lack of economic independence and restrictions imposed by the family appeared to be crucial factors that controlled the prevalence of smoking among schizophrenia patients. As smoking is a leading cause of preventable morbidity and mortality, there is a serious need to review the neurobiological issue of smoking in schizophrenia considering the influence culture and social practices could have upon the behaviour.
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PMID:Smoking in schizophrenia -- all is not biological. 1208 21

Schizophrenic patients have among the highest rates of smoking of any group of patients. Previous studies have identified psychophysiological and potential nicotinic receptor abnormalities which may be associated with this phenomenon. The effects of acute smoking or acute administration of nicotine nasal spray, after smoking abstinence, on negative symptoms and neurocognitive function have been less extensively studied in experimental designs. This study investigated the effects of smoking of high nicotine or denicotinized cigarettes, and receiving active or placebo nicotine nasal sprays, on positive and negative symptoms and cognitive functions in schizophrenic patients. The study utilized a placebo controlled crossover experimental design with pre- and post-drug evaluations on each experimental day. Smoking high nicotine cigarettes decreased negative symptoms more than denicotinized cigarettes, but smoking neither cigarette changed scores of positive symptoms, anxiety, or depression. Active nicotine nasal spray did not differentially decrease negative symptoms compared with placebo, but did improve performance on a spatial organization task, and tended to improve some measures of verbal memory and two-choice reaction time in schizophrenic patients. Both high and denicotinized cigarettes improved performance on the spatial processing task, but there was no statistically significant differential drug (Cigarette type) effect. These results suggest that acute smoking of cigarettes may transiently decrease negative symptoms in patients with schizophrenia, but it is unclear whether this effect is attributable to nicotine, other components of cigarettes, or the act of smoking. Nicotine nasal spray may modestly improve some selected aspects of cognitive function in schizophrenia.
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PMID:Effects of cigarette smoking and nicotine nasal spray on psychiatric symptoms and cognition in schizophrenia. 1222 5

Nicotine has been shown in a variety of studies to improve memory performance. The cognitive effects of nicotine are particularly important with regard to schizophrenia. In the current studies nicotine interactions with three different antipsychotic drugs, haloperidol, clozapine and risperidone, were assessed with regard to memory function. Female Sprague-Dawley rats were trained on the radial-arm maze to asymptotic levels of choice accuracy. They were then administered nicotine alone or in combination with haloperidol, clozapine or risperidone. Acute haloperidol (0.04 mg/kg) did not by itself affect memory performance. Co-administration of haloperidol with nicotine, however, decreased memory performance compared with nicotine administration in isolation. Acute clozapine (1.25 and 2.5 mg/kg) caused a significant memory impairment, an effect reversed by acute nicotine co-treatment. Risperidone (0.05 mg/kg), like haloperidol, did not by itself affect memory performance. Risperidone co-administration with nicotine, however, did significantly attenuate the improvement caused by nicotine administration in isolation. The similar interaction of haloperidol and risperidone with nicotine may be due to their common action of blocking D(2) receptors, a mechanism of action not shared by clozapine. In contrast to the interaction of nicotine with haloperidol or risperidone, nicotine effectively reversed clozapine-induced memory impairment. These studies demonstrate interactions between nicotine and antipsychotic drugs in terms of memory, which may have important impacts on the treatment of schizophrenia.
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PMID:Nicotine interactions with haloperidol, clozapine and risperidone and working memory function in rats. 1237 90

The prevalence of tobacco smoking is known to be higher in patients with schizophrenia than other psychiatric disorders and general population. These patients also show reduced prepulse inhibition (PPI) of the startle response. PPI refers to a reduction in response to a strong startling stimulus if preceded shortly by a stimulus of sub-threshold intensity. PPI is thought of as an objective index of sensorimotor gating. Nicotine administered subcutaneously or via cigarette smoking enhances PPI in healthy human beings. It also enhances PPI at low, but not high, doses in the rat. We examined the influence of smoking on PPI of the acoustic startle response in 46 male patients with chronic schizophrenia. In a naturalistic design, patients (n = 9) who smoked a cigarette less than 10 min prior to being tested on PPI were compared with other smoking (n = 23) and non-smoking patients (n = 14). We found that the group of patients who smoked a cigarette prior to being tested had significantly greater PPI than other two groups. These observations suggest a PPI-enhancing effect of cigarette smoking on PPI in patents with schizophrenia. Higher prevalence of cigarette smoking in schizophrenic patients may reflect an attempt to improve sensorimotor gating deficits. Copyright 2001 John Wiley & Sons, Ltd.
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PMID:Influence of cigarette smoking on prepulse inhibition of the acoustic startle response in schizophrenia. 1240 67

Nicotinic receptor systems are involved in a wide variety of behavioral functions including cognitive function. Nicotinic medications may provide beneficial treatment for cognitive dysfunction such as Alzheimer's disease, schizophrenia, and attention deficit hyperactivity disorder (ADHD). Nicotine has been shown to improve attentional performance in all of these disorders. Better efficacy with fewer side effects might be achieved with novel nicotinic ligands selective for particular nicotinic subtypes. To develop these novel selective nicotinic ligands it is important to use animal models to determine the critical neurobehavioral bases for nicotinic involvement in cognitive function. Nicotine-induced cognitive improvement in rats is most consistently seen in working memory tasks. We have found that both acute and chronic nicotine administration significantly improves working memory performance of rats in the radial-arm maze. The pharmacologic and anatomic mechanisms for this effect have been examined in our laboratory in a series of local drug infusion studies. Both alpha 4 beta 2 and alpha 7 nicotinic receptors in the ventral hippocampus and basolateral amygdala are involved in working memory function. Working memory impairments were caused by local infusion of either alpha 4 beta 2 or alpha 7 antagonists. Ventral hippocampal alpha 4 beta 2 blockade-induced working memory deficits are reversed by chronic systemic nicotine treatment, while ventral hippocampal alpha 7 blockade-induced working memory deficits were not found to be reversed by the same nicotine regimen. Interestingly, alpha 4 beta 2 and alpha 7 induced deficits were not found to be additive in either the ventral hippocampus or the basolateral amygdala. In fact, in the amygdala, alpha 7 antagonist cotreatment actually reversed the working memory impairment caused by alpha 4 beta 2 antagonist administration. These studies of the neural nicotinic mechanisms underlying cognitive function are key for opening avenues for development of safe and effective nicotinic treatments for cognitive dysfunction.
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PMID:Nicotinic receptor subtypes and cognitive function. 1243 26

We investigated the effect of nicotine on three behavioral markers of risk for schizophrenia: sustained attention (using the Continuous Performance Task (CPT)), antisaccade performance, and smooth pursuit. Smooth pursuit was investigated in two conditions, one in which attention was enhanced (monitoring target changes) and one in which attention was not enhanced (no monitoring). Patients with schizophrenia (n = 15) and controls (n = 14) were given a 14-mg nicotine patch in a double-blind, placebo-controlled, crossover design and plasma nicotine concentrations were monitored. Nicotine concentrations were similar in both groups. A Group x Drug interaction (p <.02) on CPT hits indicated that nicotine improved sustained attention in patients but not in controls. Nicotine significantly decreased antisaccade errors (p <.01) in both groups. A Drug x Monitoring condition interaction (p <.01) on pursuit gain indicated that nicotine significantly increased pursuit gain in the no-monitoring condition in patients and controls equally, but did not improve pursuit in the monitoring condition. Thus, improvement in pursuit may have been mediated via an effect on attention rather than by an effect on oculomotor function per se. In patients, the magnitude of improvement in attention on nicotine was correlated with the improvement on eye movement tasks. Thus, nicotine improves performance on both attention and oculomotor markers of risk for schizophrenia, possibly via common mechanisms.
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PMID:Nicotine and behavioral markers of risk for schizophrenia: a double-blind, placebo-controlled, cross-over study. 1246 63

It has been proposed that activation of nicotinic acetylcholine receptors (nAChRs) can activate the prefrontal cortex, enhancing attention and cognition. Nicotine can stimulate the release of several different neurotransmitters in many brain regions. In the present study, we found that stimulation of nAChRs by nicotine or the endogenous agonist, acetylcholine (ACh), induces a large spontaneous increase in glutamate release onto layer V pyramidal neurons of the prefrontal cortex. This release of glutamate, measured by spontaneous excitatory postsynaptic currents (sEPSCs) in the prefrontal cortical slice, depends on intact thalamocortical terminals. It can be suppressed by mu-opioids or eliminated by blocking action potentials. The increase in sEPSCs is sensitive to low concentrations of nicotine, suggesting the involvement of high-affinity (eg alpha(4)beta(2)) nAChRs. Recent work has shown alterations in prefrontal alpha(4)beta(2) nAChRs in autism and schizophrenia, two conditions that are distinguished by abnormal prefrontal cortical activation as well as difficulty in certain aspects of cognition and integrating social and emotional cues. We show that mice lacking the beta(2) nAChR subunit do not show increased sEPSCs with either nicotine or ACh, again implicating high-affinity nicotinic receptors. These findings give new insight into the mechanism by which nicotine affects excitatory neurotransmission to the output neurons of the cerebral cortex in a pathway that is critical for cognitive function and reward expectation.
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PMID:Nicotine induces glutamate release from thalamocortical terminals in prefrontal cortex. 1258 74

Nicotinic systems have been shown to be critically involved in cognitive function including attention. Nicotine has been shown to improve performance on attentional tasks in humans with Alzheimer's disease, schizophrenia and attention deficit hyperactivity disorder. Nicotine has mixed effects on attentional accuracy in unimpaired rats with findings of increased, reduced or unaltered accuracy under different conditions. Nicotine effects on attentional function in rats might be more clearly seen in reversing impaired performance. The current study determined nicotine effects on attentional accuracy reduced by the NMDA receptor antagonist dizocilpine (MK-801). Sprague-Dawley rats (N=35) were trained on a food-motivated two-lever operant task with one lever correct after a brief visual signal (0.027-1.22 lx) for hits and the other lever correct after the absence of a signal for correct rejections. First, a dose response study of dizocilpine was conducted to determine the threshold for impairment. The rats were administered acute doses of dizocilpine (0, 12.5, 25 and 50 microg/kg, sc). The 50 microg/kg dose caused significant (p<0.0005) reduction in percent hit at the four highest signal intensities. Percent correct rejection was also significantly lowered by this dose (p<0.005). No effect was seen with 12.5 microg/kg and only minimal effect seen with 25 microg/kg. Then, nicotine-dizocilpine interactions were investigated. The rats were administered acute doses of dizocilpine (0, 37.5 and 50 microg/kg, sc) and nicotine (0, 25 and 50 microg/kg, sc), alone or in combination. Percent hit was affected by nicotine and dizocilpine in a complex fashion with only the nicotinexdizocilpinexsignal intensity interaction being significant (p<0.05). Percent correct rejection showed a more straightforward effect. Percent correct rejection was significantly reduced by 50 microg/kg dizocilpine (p<0.025). The addition of 25 microg/kg of nicotine significantly (p<0.025) reversed the dizocilpine-induced reduction of correct rejection. This study shows that dizocilpine reduces signal detection accuracy in a dose-dependent fashion. Nicotine can partially counteract an aspect of this reduction by reversing the dizocilpine-induced reduction of correct rejection.
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PMID:Nicotinic-glutamatergic interactions and attentional performance on an operant visual signal detection task in female rats. 1265 Aug 36

As the prevalence of tobacco use has decreased, it has become clear that individuals with mental illness comprise a substantial portion of the remaining smokers. Seventy to eighty percent of patients with schizophrenia smoke and their smoking is established before their first psychotic episodes or the initiation of treatment. Many patients with schizophrenia, and approximately 50% of their first degree relatives have abnormalities in auditory sensory gating and/or smooth pursuit eye movements. These abnormalities are corrected by nicotine, and they appear to be transmitted as autosomal dominant traits. Evidence is accumulating that these abnormalities reflect genetic variations in nicotine receptor number and function, that may increase susceptibility for schizophrenia. Recent studies suggest that bupropion, added to treatment with an atypical antipsychotic, can enhance the likelihood of smoking cessation or reduction in patients with schizophrenia. The prevalence of smoking is also substantially increased among patients with bipolar disorder, perhaps especially so among those with psychotic features. Nicotine delivered by gum or transdermal patch can provide short term relief for exacerbations of Tourette's Syndrome, but its use is limited by frequent toxicity, primarily nausea.
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PMID:The importance of nicotinic acetylcholine receptors in schizophrenia, bipolar disorder and Tourette's syndrome. 1276 15


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