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)

Cigarette smoking and other forms of drug abuse are more prevalent among schizophrenics than the general population. Despite the clinical importance of this problem, there has been relatively little experimental study of schizophrenic drug use. We examined under controlled laboratory conditions the effects of response requirement and the availability of an alternative (monetary) reinforcer on cigarette smoking by schizophrenics. Subjects were six heavy smokers with diagnoses of schizophrenia or schizoaffective disorder. Before each session, subjects provided carbon monoxide samples indicating recent smoking abstinence. During 3-h sessions, subjects obtained opportunities to smoke (2 puffs/opportunity) under a fixed ratio (FR) schedule of reinforcement, which varied across sessions from FR50 to FR6400. In half of the sessions, subjects also were able to earn a small amount of money ($0.25/ratio completed) under an FR400 schedule. Increasing the response requirement for smoking decreased smoking and increased smoking-maintained responding. The availability of the monetary reinforcer decreased smoking and smoking-maintained responding by approximately half. These results are consistent with those seen previously in community volunteers without major mental illness studied under the same experimental conditions, suggesting that smoking by these two populations is controlled, at least in part, by a common set of determinants.
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PMID:Effects of response requirement and the availability of an alternative reinforcer on cigarette smoking by schizophrenics. 1044 72

The authors of this study examined the effects of brief smoking abstinence on smoking among 6 individuals with schizophrenia or schizoaffective disorder. Before 6 of 12 experimental sessions, participants were required to provide breath carbon monoxide (CO) samples indicative of smoking abstinence; before the remaining sessions, participants provided CO samples indicating no abstinence. During sessions, participants obtained smoking opportunities (2 puffs/opportunity) under either fixed ratio-1 or progressive ratio (PR) schedules of reinforcement. Abstinence increased smoking under both schedules and increased breakpoint for smoking under the PR schedule. These data offer further evidence that smoking by individuals with schizophrenia is orderly, operant behavior that is modulated, at least in part, by variables that also affect smoking in people without major mental illness.
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PMID:Effects of abstinence on cigarette smoking among outpatients with schizophrenia. 1060 69

The authors examined whether smoking while wearing a transdermal nicotine patch over 32 h was well-tolerated and led to smoking suppression in heavy smokers with schizophrenia. In a crossover design, 10 male veteran smokers with schizophrenia were admitted for two brief inpatient stays to smoke while wearing a transdermal nicotine or placebo patch. Carbon monoxide in expired air, self-reported cigarettes per day, nicotine plasma levels, and psychiatric ratings were measured. Nicotine levels increased during active patch treatment, without evidence of nicotine toxicity. Psychiatric symptoms, carbon monoxide and cigarettes per day did not change, although eight subjects had a decrease in expired carbon monoxide on the active patch. Dyskinesias showed a small, but significant, increase during smoking plus active patch. The heaviest smokers (identified by placebo phase nicotine plasma level or CO level above group median; n = 5) had a statistically significant decrease in expired carbon monoxide of at least 20%. Smoking while wearing the nicotine patch over 32 h was well tolerated. Significant decreases in carbon monoxide smoking indices were seen for the heaviest smokers. These findings suggest further investigation of a smoking reduction intervention in this population.
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PMID:Acute feasibility and safety of a smoking reduction strategy for smokers with schizophrenia. 1107 88

The high prevalence of smoking among individuals diagnosed with schizophrenia is well recognized and documented. Many explanations have been put forth to explain this phenomenon including the effects of antipsychotic medication. We sought to determine if there is a difference in smoking behaviour between patients treated with clozapine and depot neuroleptics. This cross-sectional study recruited patients with schizophrenia from the Forensic Psychiatric Institute of British Columbia. Eligibility for the study required that patients be on either clozapine or depot neuroleptic for at least 2 months. The patient's smoking behaviour was evaluated using expired carbon monoxide (CO) measurements, the Fagerstrom Test for Nicotine Dependence (FTND), and a semi-structured interview. Our results showed that patients treated with clozapine had significantly lower expired CO values than patients treated with depot neuroleptics (11.8 +/- 9.2 versus 21.2 +/- 7.1 p.p.m., respectively, P < 0.01). This finding was further supported by the noted trend in which patients receiving clozapine self-reported smoking less than patients treated with depot neuroleptics (13.7 +/- 11.3 versus 26.8 +/- 18.3 cigarettes per day, respectively, P = 0.08). Thus, according to measurements of expired CO levels, patients treated with clozapine smoke less than patients treated with depot neuroleptics.
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PMID:A comparison of smoking behaviours between patients treated with clozapine and depot neuroleptics. 1155 73

The purpose of this study was to investigate the effect of adding sustained-release (SR) bupropion to cognitive behavioral therapy (CBT) on smoking behavior and stability of psychiatric symptoms in patients with schizophrenia. We conducted a 3-month, double-blind, placebo-controlled trial of bupropion SR, 150 mg/day, added to a concurrent CBT program with 3-month follow-up in 19 stable outpatients with schizophrenia who wanted to quit smoking. Eighteen subjects completed the trial. Bupropion treatment was associated with significantly greater reduction in smoking, as measured by self-report verified by expired-air carbon monoxide (6/9 subjects, 66%), than placebo (1/9 subjects, 11%) during the 3-month active treatment period and the 3-month follow-up period. One subject in the bupropion group (11%) and no subjects in the placebo group achieved sustained tobacco abstinence for the 6-month trial. Bupropion treatment was associated with improvement in negative symptoms and greater stability of psychotic and depressive symptoms, compared with placebo, during the quit attempt. Subjects in the bupropion group experienced significant weight loss, compared with those on placebo during the smoking cessation attempt. These data suggest that bupropion SR, 150 mg/day, combined with CBT, may facilitate smoking reduction in patients with schizophrenia while stabilizing psychiatric symptoms during a quit attempt.
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PMID:A pilot trial of bupropion added to cognitive behavioral therapy for smoking cessation in schizophrenia. 1169 8

This study was conducted to examine the effects of contingent monetary reinforcement (CM) for smoking reduction, with and without transdermal nicotine, on cigarette smoking in individuals with schizophrenia. Fourteen outpatients participated in each of 3 conditions: (a) CM combined with 21 mg transdermal nicotine, (b) CM combined with placebo patch, and (c) noncontingent reinforcement combined with placebo patch. Each condition lasted 5 days. Carbon monoxide levels were measured 3 times daily, and nicotine withdrawal symptoms were measured once daily in each condition. Results indicated that CM reduced smoking but that 21 mg transdermal nicotine did not enhance that effect. These results offer further evidence supporting the efficacy of CM for reducing smoking among people with schizophrenia, but higher doses of nicotine replacement therapy, or another pharmacotherapy, may be needed to enhance that effect.
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PMID:Contingent monetary reinforcement of smoking reductions, with and without transdermal nicotine, in outpatients with schizophrenia. 1223 84

The metabolism of biogenic amines and blood chemistry of psychiatric patients were investigated. Eighty newly admitted psychiatric patients suffering from schizophrenia, hypomania, mania and paranoid disorder, and matched with fifteen normal subjects were used for the study. Blood was collected and centrifuged, after which serum was extracted. Serum concentrations of biogenic amines, namely epinephrine, norepinephrine, dopamine and serotonin were determined using spectrofluorimetric method. Serum concentration of 5-HIAA, activities of alanine transaminase and aspartate transaminase were determined. The concentrations of serum protein, albumin, Na+, K+, Cl- and CO2 in the psychiatric patients and control subjects were determined using Synchron CX5 automated spectrophotometer. Results of the study showed that the concentrations of serum epinephrine and norepinephrine in the psychiatric patients were significantly increased, while the concentrations of dopamine and serotonin were significantly decreased, as compared with the controls. Serum 5-HIAA levels were significantly elevated in all psychiatric patients compared with the controls. There was a marked elevation of the activities of alanine transaminase and aspartate transaminase in all psychiatric syndromes, with the exception of paranoid disorder, which was reduced. Data of the study indicate that metabolism of biogenic amines and concentrations of serum proteins, enzymes and some electrolytes were significantly affected in psychiatric patients suffering form schizophrenia, hypomania, mania and paranoid disorder.
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PMID:Biogenic amines metabolism and blood chemistry of psychiatric patients. 1451 Jan 2

Smoking is highly prevalent among people with schizophrenia, and little is known about factors that affect smoking in these patients. One basic question is whether smoking behavior differs for smokers with schizophrenia compared to equally nicotine-dependent smokers who do not have a major mental illness. In this study, 20 smokers with schizophrenia or schizoaffective disorder (SCZ) and 20 non-psychiatric smokers (CON) underwent smoking topography assessments. The groups were matched on age, gender, daily smoking rate, years of regular smoking and nicotine dependence rating. Results indicate that, compared to the CON participants, the SCZ participants smoked significantly more total puffs (SCZ: 58.5 +/- 48.3; CON: 21.3 +/- 9.4) and puffs per cigarette (SCZ: 12.3 +/- 6.0; CON: 8.9 +/- 2.3) and had shorter inter-puff intervals (SCZ: 21.9 +/- 9.7 s; CON: 42.0 +/- 21.5 s), larger total cigarette puff volumes (SCZ: 583 +/- 169 ml; CON: 429 +/- 159 ml) and higher carbon monoxide boosts (SCZ: 3.8+/-5.4 ppm; CON: 1.0 +/- 2.5 ppm). Test-retest reliabilities were good to excellent for most smoking measures in both groups. These findings suggest that smokers with schizophrenia smoke more intensely than matched non-psychiatric smokers and that their smoking behavior is reliable when assessed under laboratory conditions.
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PMID:Cigarette smoking topography in smokers with schizophrenia and matched non-psychiatric controls. 1586 44

HO-2 is a constitutive isoform of heme oxygenase (HO), a microsomal enzyme that catalyzes the cleavage of the heme ring to form ferrous iron, carbon monoxide, and biliverdin. In contrast to HO-1, which is inducible, HO-2 is not responsive to stimuli tested to date except for prolonged exposure to the adrenal glucocorticoids (GCs). Previous studies have shown that high GC concentrations or stress damage or kill hippocampal neurons. In the present study, it was found that chronic restraint stress decreased HO-2 protein levels in hippocampal neurons, as demonstrated by immunohistochemistry and Western blot analysis. Moreover, our results showed that the combination of 2.5mg/kg of venlafaxine and 5mg/kg of quetiapine effectively prevented the HO-2 protein decrease in hippocampal neurons of stressed rats, whereas either of the drugs alone did not show any effect. At higher dose levels, both quetiapine (10mg/kg) and venlafaxine (5mg/kg) produced significant effects comparable to that of their combination. Quetiapine is an atypical antipsychotic and venlafaxine an antidepressant. In previous studies, these two drugs have been shown to prevent or protect against the stress-induced decrease in hippocampal neurogenesis and BDNF expression. These data suggest that both quetiapine and venlafaxine share the hippocampus as their common target by enhancing hippocampal resilience, which may be impaired in patients with schizophrenia or depression.
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PMID:Quetiapine and venlafaxine synergically regulate heme oxygenase-2 protein expression in the hippocampus of stressed rats. 1611 34

Dopamine D2 partial agonists have been successfully used as schizophrenia therapeutics. Radiolabeled D2 partial agonists may have application in elucidating dopaminergic transmission. It was the goal of this work to radiolabel (S)-(-)propyl-3-(3-hydroxyphenyl)piperidine (preclamol; (-)3-PPP), a partial dopamine D2 agonist with carbon-11 (half-life=20.4 min) and to evaluate this novel radiopharmaceutical for dopaminergic imaging in rodent models. [11C]Preclamol was synthesized by acylation of (S)-3-(3-hydroxyphenyl)piperidine hydrochloride with [11C]propionyl chloride, followed by LiAlH4 reduction, and HPLC purification. Male Sprague-Dawley rats were injected in the tail vein with a saline solution of [11C]preclamol (1.1 mug/kg) and sacrificed at 5, 15, 30 and 60 min postinjection. Brain regions were excised, weighed, and measured for radioactivity. In vivo binding kinetics of [11C]preclamol were determined with beta-sensitive microprobes implanted into the striatum and cerebellum of an anesthetized rat. A full production of [11C]preclamol resulted in 34 mCi ready for injection (corresponding to 4% uncorrected radiochemical yield, based on starting [11C]CO2) with specific activity of 535 mCi/micromol. The total synthesis time was 45 min and resulted in chemically and radiochemically pure [11C]preclamol (>99%; n=3). High levels of radioactivity were observed in rat brain indicating good blood-brain barrier penetration of [11C]preclamol, with 0.5 to 0.7% injected dose per gram of wet tissue present in all brain regions at 5 minutes postinjection. Unfortunately, [11C]preclamol displayed minimal preferential uptake in dopaminergic brain regions. A low striatal specific binding (SB) ratio of 0.32 was determined ex vivo at 60 min postinjection and was in close agreement with the microprobe study over 60 min (peaked at 27 min postinjection; SB ratio=0.6). The binding potential value was only 0.34 over a 1 hour time course, suggesting that [11C]preclamol is not suitable for cerebral PET studies.
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PMID:Radiosynthesis, ex vivo and in vivo evaluation of [11C]preclamol as a partial dopamine D2 agonist radioligand for positron emission tomography. 1678 38


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