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)

Ziprasidone (Geodon, Zeldox), a recently approved atypical antipsychotic agent for the treatment of schizophrenia, undergoes extensive metabolism in humans with very little (<5%) of the dose excreted as unchanged drug. Two enzyme systems have been implicated in ziprasidone metabolism: the cytosolic enzyme, aldehyde oxidase, catalyzes the predominant reductive pathway, and cytochrome P4503A4 (CYP3A4) is responsible for two alternative oxidation pathways. The involvement of two competing pathways in ziprasidone metabolism greatly reduces the potential for pharmacokinetic interactions between ziprasidone and other drugs. Because CYP3A4 only mediates one third of ziprasidone metabolism, the likelihood of interactions between ziprasidone and CYP3A4 inhibitors/ substrates is low. Furthermore, aldehyde oxidase activity does not appear to be altered when drugs or xenobiotics are coadministered. Aldehyde oxidase, a molybdenum-containing enzyme, catalyzes the oxidation of N-heterocyclic drugs such as famciclovir and zaleplon, in addition to reducing some agents such as zonisamide. Both reactions can occur simultaneously. Although in vitro inhibitors of aldehyde oxidase have been identified, there are no reported clinical interactions with aldehyde oxidase inhibitors or inducers. There is no evidence of genetic polymorphism in aldehyde oxidase, and thus it not surprising that ziprasidone exposure demonstrates unimodality in humans. Aldehyde oxidase is unrelated to the similarly named enzyme aldehyde dehydrogenase, which is predominantly responsible for the oxidation of acetaldehyde during ethanol metabolism. Consequently, it is unlikely that there would be any pharmacokinetic interaction between ethanol and ziprasidone.
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PMID:Ziprasidone metabolism, aldehyde oxidase, and clinical implications. 1523 43

Thirty subjects with comorbid schizophrenia and alcohol use disorders were randomly assigned to receive either a Motivational Interviewing (MI) or Educational Treatment (ET) intervention with treatment goals of abstinence and/or decreased alcohol use. Subjects were followed up at 4, 8 and 24-weeks upon completion of the interventions. Outcome measures included number of drinking days, abstinence rates, average blood alcohol concentration and standard ethanol content per drinking day. Subjects randomized to the MI intervention had a significant reduction in drinking days and an increase in abstinence rates when compared to subjects receiving ET. Motivational Interviewing may be a useful treatment intervention for individuals with schizophrenia and alcoholism.
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PMID:A pilot study comparing motivational interviewing and an educational intervention in patients with schizophrenia and alcohol use disorders. 1283 1

This article represents the proceedings of a symposium at the 2003 annual meeting RSA in Fort Lauderdale, FL. It was organized and cochaired by Charlene E. Le Fauve and Carrie L. Randall. The presentations were (1) Introduction, by Charlene E. Le Fauve and Raye Z. Litten; (2) Treatment of co-occurring alcohol use and anxiety disorders, by Carrie L. Randall and Sarah W. Book; (3) Pharmacological treatment of alcohol dependent patients with comorbid depression, by Darlene H. Moak; (4) Efficacy of valproate in bipolar alcoholics: a double blind, placebo-controlled study, by Ihsan M. Salloum, Jack R. Cornelius, Dennis C. Daley, Levent Kirisci, Johnathan Himmelhoch, and Michael E. Thase; (5) Alcoholism and schizophrenia: effects of antipsychotics, by Alan I. Green, Robert E. Drake, Suzannah V. Zimmet, Rael D. Strous, Melinda Salomon, and Mark Brenner; and (6) Conclusions, by Charlene E. Le Fauve; discussant, Raye Z. Litten. Alcohol-dependent individuals have exceptionally high rates of co-occurring psychiatric disorders. Although this population is more likely to seek alcoholism treatment than noncomorbid alcoholics, the prognosis for treatment is often poor, particularly among patients with more severe psychiatric illnesses. Development of effective interventions to treat this population is in the early stages of research. Although the interaction between the psychiatric condition and alcoholism is complex, progress has been made. The NIAAA has supported a number of state-of-the-art pharmacological and behavioral trials in a variety of comorbid psychiatric disorders. Some of these trials have been completed and are presented here. The symposium presented some new research findings from clinical studies with the aim of facilitating the development of treatments that improve alcohol and psychiatric outcomes among individuals with alcohol-use disorders and co-occurring psychiatric disorders. The panel focused on social anxiety disorder, depression, bipolar disorder, and schizophrenia.
Alcohol Clin Exp Res 2004 Feb
PMID:Pharmacological treatment of alcohol abuse/dependence with psychiatric comorbidity. 1511 38

The standardized evaluation of alcoholism and other psychopathologies in minority populations, particularly American Indians, has long been questioned. This study investigated the validity of one of the most commonly applied assessments for alcoholism--the Short Michigan Alcohol Screening Test (SMAST)--in two distinct American Indian tribal groups. We analyzed data collected from 1989 to 1995 from largely community representative samples of 456 Southwestern and 214 Plains Indians ages 21 or older. For comparison, alcohol dependence was diagnosed using Diagnostic and Statistical Manual of Mental Disorders, Third Edition-Revised (DSM-III-R) criteria from a detailed, modified version of the Schedule for Affective Disorders and Schizophrenia--Lifetime (SADS-L). Accuracy of the SMAST was quantified as sensitivity, specificity, likelihood ratios, and the area under the curve for receiver operating characteristics, using the DSM-III-R diagnosis as the reference. The standard SMAST cutoff score of > or = 3 had a demonstrated sensitivity 86% to 95%, but did not perform well in terms of specificity (23%-47%). Significantly higher cutoff scores (> or = 5 for both genders in the Southwestern tribe and 8 and > or = 6 for men and women in the Plains tribe) were required to demonstrate acceptable levels of specificity in both tribes. The findings suggest that the SMAST is not a valid tool to screen for alcohol misuse in these two tribal populations. The highly elevated and different thresholds required from one population to the next and from one gender to the next constitute a significant obstacle to the use of the instrument.
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PMID:Validity of the SMAST in two American Indian tribal populations. 1511 15

Alcohol abuse contributes substantially to the overall morbidity of schizophrenia. While typical antipsychotic medications do not limit alcohol use in patients with schizophrenia, emerging data suggest that the atypical antipsychotic clozapine does. To further elucidate the effects of these antipsychotics on alcohol use, we initiated a study in alcohol-preferring rodents. Syrian golden hamsters were given free-choice, unlimited access to alcohol. Nine days of treatment (s.c. injection) with clozapine (2-4 mg/kg/day), but not haloperidol (0.2-0.4 mg/kg/day), reduced alcohol drinking. Clozapine reduced alcohol drinking by 88% (from 11.3+/-1.7 to 1.4+/-0.2 g/kg/day) while increasing both water and food intake. Alcohol drinking gradually (during 24 days) returned toward baseline in the clozapine-treated animals when vehicle was substituted for clozapine. Further increasing the doses of haloperidol (0.6-1.0 mg/kg/day) had no effect on alcohol drinking; moreover, very low doses of haloperidol (0.025-0.1 mg/kg/day) tested in separate groups of hamsters also had no effect on alcohol drinking. This study demonstrates that clozapine, but not haloperidol, can effectively and reversibly decrease alcohol consumption in alcohol-preferring hamsters. The results are compatible with the observations that clozapine, but not haloperidol, limits alcohol use in patients with schizophrenia. These data further suggest that clozapine may serve as a prototype for developing novel treatments for alcohol abuse.
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PMID:Clozapine reduces alcohol drinking in Syrian golden hamsters. 1545 Sep 10

Cannabis dependence is a prevalent comorbid substance use disorder among patients early in the course of a schizophrenia-spectrum disorder. Determining risk factors for substance abuse may be helpful in designing interventions to reduce the psychosocial morbidity associated with substance abuse among this population. This study aimed to determine whether or not African American, socially disadvantaged, first-episode schizophrenia-spectrum patients with cannabis dependence experienced greater levels of childhood abuse and neglect compared to similar patients without comorbid cannabis dependence. Among 29 eligible patients, 18 participated in this pilot study. First-episode patients with comorbid cannabis dependence (n = 8) reported significantly greater childhood physical and sexual abuse compared to those without comorbid cannabis dependence (n = 10). This represents preliminary evidence of an association between childhood maltreatment and cannabis dependence among this especially vulnerable population. Childhood physical and sexual abuse may be a risk factor for the initiation of cannabis dependence and other substance use disorders in the early course of schizophrenia.
Drug Alcohol Depend 2004 Dec 07
PMID:Preliminary evidence of an association between childhood abuse and cannabis dependence among African American first-episode schizophrenia-spectrum disorder patients. 1556 82

Dopamine supersensitivity occurs in schizophrenia and other psychoses, and after hippocampal lesions, antipsychotics, ethanol, amphetamine, phencyclidine, gene knockouts of Dbh (dopamine beta-hydroxylase), Drd4 receptors, Gprk6 (G protein-coupled receptor kinase 6), Comt (catechol-O-methyltransferase), or Th-/-, DbhTh/+ (tyrosine hydroxylase), and in rats born by Cesarean-section. The functional state of D2, or the high-affinity state for dopamine (D2High), was measured in these supersensitive animal brain striata. Increased levels and higher proportions (40-900%) for D2High were found in all these tissues. If many types of brain impairment cause dopamine behavioral supersensitivity and a common increase in D2High states, it suggests that there are many pathways to psychosis, any one of which can be disrupted.
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PMID:Dopamine supersensitivity correlates with D2High states, implying many paths to psychosis. 1571 60

This paper evaluates three hypotheses about the relationship between cannabis use and psychosis in the light of recent evidence from prospective epidemiological studies. These are that: (1) cannabis use causes a psychotic disorder that would not have occurred in the absence of cannabis use; (2) that cannabis use may precipitate schizophrenia or exacerbate its symptoms; and (3) that cannabis use may exacerbate the symptoms of psychosis. There is limited support for the first hypothesis. As a consequence of recent prospective studies, there is now stronger support for the second hypothesis. Four recent prospective studies in three countries have found relationships between the frequency with which cannabis had been used and the risk of receiving a diagnosis of schizophrenia or of reporting psychotic symptoms. These relationships are stronger in people with a history of psychotic symptoms and they have persisted after adjustment for potentially confounding variables. The absence of any change in the incidence of schizophrenia during the three decades in which cannabis use in Australia has increased makes it unlikely that cannabis use can produce psychoses that would not have occurred in its absence. It seems more likely that cannabis use can precipitate schizophrenia in vulnerable individuals. There is also reasonable evidence for the third hypothesis that cannabis use exacerbates psychosis.
Drug Alcohol Rev 2004 Dec
PMID:Cannabis use and psychotic disorders: an update. 1576 48

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.
Drug Alcohol Depend 2005 Nov 01
PMID:Cigarette smoking topography in smokers with schizophrenia and matched non-psychiatric controls. 1586 44

Olfactory identification deficits in schizophrenia patients are well documented. Less is known about the functioning of other olfactory domains and the possibility of lateralized dysfunctions. Thirty male schizophrenia patients and 30 male healthy controls underwent unirhinal assessment of various olfactory domains: detection threshold (dimethyl disulfide, phenyl ethanol), quality discrimination, and odor ratings (familiarity, pleasantness, edibility, intensity) of pure chemicals (Munich Olfaction Test), as well as familiarity and edibility judgments and identification of everyday odors. Aside from impaired identification, patients showed impaired familiarity and edibility judgments of everyday odors. With regard to odor ratings of pure chemicals, group differences were observed only in pleasantness ratings, with higher ratings in patients. Furthermore, patients had reduced sensitivity with dimethyl disulfide and reduced quality discrimination compared with controls. Further analyses showed that identification deficits were not attributable to reduced sensitivity but may be associated with impairments in quality discrimination. Olfactory dysfunctions were found across both nostrils. Results suggest specific dysfunctions in olfactory processing in schizophrenia patients, including early stages of the odor identification process.
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PMID:Various bilateral olfactory deficits in male patients with schizophrenia. 1588 33


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