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)

Initial studies have indicated that stimulant abuse is prevalent among schizophrenic persons. To assess the phenomenon of cocaine abuse by patients with schizophrenia, 17 male cocaine-abusing schizophrenic patients were compared with 22 male schizophrenic patients who did not use cocaine. The cocaine-abusing subjects had been hospitalized more frequently, were more likely to be of the paranoid subtype, and were more likely to be depressed at the time of interview. It appears that cocaine abuse may influence both the psychopathologic presentation of schizophrenic patients and the intensity of care that they require.
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PMID:Cocaine abuse among schizophrenic patients. 238 50

Central dopaminergic activation is hypothesized to underly schizophrenia and, paradoxically, stimulant euphoria. Four cocaine abusers with histories of stimulant-induced paranoid psychoses reported selective reduction in psychotic symptoms but not euphoria when treated with dopamine blockers. This provides preliminary evidence against efficacy of neuroleptics in cocaine abuse prevention, and suggests euphoria and paranoia may have discriminable neurophysiological substrates.
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PMID:Neuroleptic reduction of cocaine-induced paranoia but not euphoria? 287 52

The nonpathological age-related changes in the dopamine- and serotonin-containing neurotransmitter systems in human and rodent brain are reviewed. The dopamine system exhibits age-related declines both presynaptically and postsynaptically. Presynaptically, both the levels of dopamine and the number of midbrain dopamine-containing neurons decline by up to 50% at advanced ages in the absence of neurological disease. Postsynaptically, the density of D-2 dopamine receptors decreases by 40%, while D-1 dopamine receptors either increase (man) or remain stable (rodents). Additional reductions of dopamine levels and D-2 receptors have been reported in Alzheimer's disease (AD), but these changes are relatively small, and not consistently observed. The levels of serotonin appear stable during normal aging, and presynaptic markers such as (3H)imipramine binding may actually increase. In human brain, the two major classes of serotonin receptor (S-1 and S-2) decrease by 30 to 50% over the lifespan. In AD, both presynaptic and postsynaptic markers of the serotonin system are reduced, including a loss of the serotonin-containing raphe neurons. The additional loss of serotonin receptors in AD approaches 80% when compared with young normals. A hypothesis is presented to explain the typically young age at onset of schizophrenia (usually before 30 years of age) and the older age at onset of parkinsonism (rarely before 50 years of age) within the context of normal age-related declines in the dopamine system occurring in the absence of neurological disorders. The possibility that chronic cocaine abuse might accelerate the development of parkinsonism is discussed.
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PMID:Dopamine and serotonin systems in human and rodent brain: effects of age and neurodegenerative disease. 354 45

There is growing evidence that substance abuse is a major problem in patients with schizophrenia. With respect to alcohol, alledegly the most frequently abused drug among schizophrenics, clinical and epidemiological studies would suggest that the risk of alcoholism is approximately four times greater (Cuffel, 1992; Mueser et al., 1990; Soyka et al., 1993; Soyka, 1994). A variety of hypotheses have been proposed to explain this phenomenon, including the so-called "self-medication hypothesis". Some authors feel that substance abuse in schizophrenics might be due to extrapyramidal and other side-effects caused by neuroleptic treatment or inadequate remission of psychotic symptoms. There remains, at present, an obvious lack of both psychosocial and psychopharmacological studies of treatment in "dual diagnosis" schizophrenics (Mueser et al., 1992). Changes in dopaminergic neurotransmission and dopamine-receptor dysfunction have been linked both to the development of psychotic symptoms and to alcoholism/substance abuse, and thus give rise to the question as to whether some dual diagnosis patients might benefit from neuroleptic treatment in both domains. A number of dopamine receptor subtypes in different regions of the brain seems to be involved in the development of schizophrenia and substance abuse. Modifications of D2-receptor subtype function have been implicated in psychotic symptoms, and changes in the D1- and D2-receptor function in substance abuse such as cocaine abuse and alcoholism (Spealman et al., 1990; 1991; 1992), especially in the mesolimbic dopaminergic reward system. Accordingly, the "ideal" neuroleptic drug for dual diagnosis schizophrenics should be effective in both receptor subtypes.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Successful treatment with flupenthixol decanoate of a patient with both schizophrenia and alcoholism. 762 88

The carrier molecule that transports dopamine (DA) across the synaptic membrane is known as the dopamine transporter (DAT). Depending on the ionic conditions, DAT may function as a mediator of both the inward directed DA transport known as the "reuptake" and the outward directed DA transport known as the "release." The functional significance of DAT is in the regulation of DA neurotransmission by terminating the action of DA in the synapse via reuptake. With use of DAT binding as a presynaptic marker to measure altered DA innervation, abnormalities of the DAT binding have been demonstrated in idiopathic Parkinson's disease, 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) neurotoxicity, and progressive supranuclear palsy. Moreover, the identification of DAT as the neuronal element that mediates the addictive properties of cocaine highlights its significance in cocaine addiction. Cocaine binding in the brain is heterogeneous, and there is an uneven distribution of the high- and low-affinity binding sites across the anatomical regions. Regional differences in ligand binding are observed by using both [3H]cocaine and the diphenyl-substituted piperazine derivatives known as the "GBR series" of ligands. The identification of compounds that inhibit the binding of medications for cocaine abuse. Furthermore, clarification of the various binding domains that may be relevant to transporter function in human neuropsychiatric disorders may lead to the development of new medications for schizophrenia, Tourette's disease, and drug addiction.
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PMID:Molecular, functional and biochemical characteristics of the dopamine transporter: regional differences and clinical relevance. 814 55

The prevalence of cocaine abuse by patients with schizophrenia has led researchers to investigate features of the disorder correlated with abuse. Although abuse has been found to be more common among patients with a diagnosis of paranoid subtype and a history of earlier and more frequent hospitalizations, it is unclear if it is related to any particular pattern of negative or positive symptoms. This study examines the severity of positive and negative symptoms for patients with and without histories of cocaine abuse. Subjects with a history of at least 2 months of cocaine abuse (N = 25), no lifetime substance abuse (N = 20), and 2 months of alcohol abuse with no other substance abuse (N = 23) are compared on five-factor analytically and three rationally derived scores from the Positive and Negative Syndrome Scale (PANSS). Following a multivariate analyses of variance (p < .01), univariate analyses indicated significant differences on the negative syndrome scales, with cocaine-abusing subjects exhibiting less severe negative symptoms than subjects with no substance-abuse history. Cocaine-abusing subjects were also found to have been younger at time of first psychiatric hospitalization and more likely to qualify for a diagnosis of the paranoid subtype.
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PMID:Relationship of positive and negative symptoms to cocaine abuse in schizophrenia. 830 28

The dopamine transporter (DAT) is the carrier protein that transports dopamine across the presynaptic membrane. The DAT terminates the action of dopamine (DA) in the synapse via reuptake and thus regulates DA neurotransmission. The transporter has been studied by direct binding techniques using a variety of ligands which are inhibitors of DA transport. DAT binding, both in vivo (positron emission tomography) and in vitro (post mortem) may serve as a presynaptic marker to measure altered DA innervation in several neuropsychiatric diseases such as idiopathic Parkinson's disease, Tourette's disease, schizophrenia or cocaine addiction. In Parkinson's disease, a reduction in the density of binding sites could be due either to a degeneration of the terminal dopaminergic projections or to a compensatory readjustment in the level of dopamine synaptic transmission. This dopaminergic cell specific marker could also aid in attempts to elucidate the rate at which dopaminergic cells are lost in this disease. MPTP (a neurotoxin which induces a parkinsonian-like syndrome after conversion in MPP+) uses DAT to enter the neuron and exert its toxic effect which may be prevented by pretreatment with DA uptake blockers. In cocaine abuse, DAT mediates the addictive properties of cocaine. Cocaine binding sites on the carrier may be distinct from DA binding sites allowing the development of medication sparing the DA function but impairing the cocaine effects. In schizophrenia, functional DA uptake was reported to be increased in the striatum in post mortem brains, whereas the kinetic parameters of the uptake sites were unchanged using different transporter labeling ligands. Thus, this marker does not provide any evidence for the dopaminergic hypothesis, but an impairment of the DAT itself could possibly be involved in the etiology of schizophrenia. However, the possible interaction of drugs such as L-Dopa or neuroleptic treatment with transporter binding may be taken into account in the results analysis. Finally, the DAT gene is also an important candidate gene for psychiatric diseases such as schizophrenia or cocaine abuse.
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PMID:[The dopamine transporter: characterization and physiopathologic implications]. 867 69

We derived a statistical model that discriminates between substance-induced psychosis (i.e., DSM-III-R organic delusional disorder or organic hallucinosis; ODD-OH) and DSM-III-R schizophrenia in patients who have both DSM-III-R psychoactive substance use disorders (PSUD) and prominent delusions or hallucinations. A sample of 211 PSUD inpatients was divided by year of admission into data sets A and B, each of which was divided between those with concurrent schizophrenia and those with concurrent ODD-OH. A six-predictor discriminant function correctly classified 76.2 percent of all set A patients, including 83.1 percent with schizophrenia. Formal thought disorder and bizarre delusions significantly predict a diagnosis of schizophrenia, with odds ratios (OR) of 3.55:1 and 6.09:1, respectively. Suicidal ideation (OR = 0.32:1), intravenous cocaine abuse (0.18:1), and a history of drug detoxification (0.26:1) or methadone maintenance (0.18:1) demonstrate inverse relationships with a schizophrenia diagnosis. The model was validated in set B, correctly predicting the diagnostic status of 70.4 percent of patients (72.5% with schizophrenia). The pattern of presenting symptoms and clinical history differs in patients with psychosis due to PSUD and in those whose psychosis is due to schizophrenia. The model presented here contributes to the differential diagnosis of schizophrenia and ODD-OH among patients with PSUD.
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PMID:Differential diagnosis of substance-induced psychosis and schizophrenia in patients with substance use disorders. 916 29

The combined problems of substance abuse, mental illness, and homelessness among the urban poor represent a major public health issue. The study evaluated 340 patients attending a cocaine day treatment program that integrates peer leadership and professional supervision. Thirty-six percent of the sample had a major mental illness, and 39 percent were homeless. Sixty-nine percent achieved an acceptable final urine toxicology status, and the median number of program visits was 46. Homelessness, a longer history of cocaine use, and a diagnosis of schizophrenia were associated with positive treatment outcomes. The results support the feasibility of a cocaine abuse treatment model combining professional and peer leadership.
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PMID:Homelessness and mental illness in a professional- and peer-led cocaine treatment clinic. 955 Feb 49

Cocaine use is common among individuals with schizophrenia and schizoaffective illness, with a prevalence ranging from 15-60% of patient samples. It is hypothesized that some schizophrenic cocaine abusers may use cocaine as an attempt to improve anhedonic symptoms or combat neuroleptic side-effects. Flupenthixol (FLX) has the distinct advantage of being both a neuroleptic medication and a potential treatment for cocaine abuse. We evaluated the efficacy of FLX in this dually diagnosed population in an open pilot study consisting of a 4-week inpatient phase and a 6-week outpatient phase. Eight individuals were initially cross-tapered off their neuroleptic medication and were given FLX in a dose of 40 mg of the decanoate every 2 weeks. Psychiatric symptomatology was assessed weekly, using the Positive and Negative Symptom Scale (PANSS) and the Beck Depression Inventory (BDI). Medication side-effects were monitored weekly, using the Simpson Neurological Rating Scale and the Abnormal Involuntary Movement Scale (AIMS). Substantial improvement in psychiatric symptomatology was noted when preadmission scores were compared to scores obtained during the last week of study enrollment. On the PANSS, positive symptom scores and negative symptom scores decreased by 31% and 29%, respectively. Similarly, BDI scores decreased by 57%. Comparing preadmission urine results to those for the last 6 weeks of enrollment in the study showed that cocaine-positive urines decreased by 28%, although most of the patients had a reduction of >75%. Missed clinic visits decreased by 26%. Thus, FLX was well-tolerated by schizophrenic cocaine abusers, suggesting that FLX may be useful for the treatment of this dually diagnosed population.
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PMID:Flupenthixol treatment for cocaine abusers with schizophrenia: a pilot study. 974 39


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