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)

Fifty-one schizophrenic inpatients were divided into two groups, those with and without history of cocaine use, and compared on historical, demographic, cognitive, and psychopathological measures. Patients with a cocaine history were found to be significantly more depressed, less socialized, and more impaired in conceptual encoding and verbal memory, while less disordered in attention. The two groups did not differ in severity of illness or positive and negative syndromes. There were also no differences in control variables such as age, gender, education, intelligence, premorbid adjustment, neuroleptic dose, onset and chronicity of illness, continuity of hospitalization, paranoid subtype, and psychiatric illness in the family. Cocaine history was associated with multiple illicit drug use, but for other substances there was no increased liability for depression or cognitive deficits. The results suggest that the clinical presentation in schizophrenia is significantly associated with prior cocaine experience.
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PMID:Significance of cocaine history in schizophrenia. 223 Jul 49

We assessed psychiatric states in 223 men at first entry to New York, NY, municipal men's shelters, overall and differentiated by prior experience of homelessness. Instruments included a diagnostic interview (Structured Clinical Interview for DSM-III-R: Psychotic Disorders), the Short Michigan Alcoholism Screening Test, and the Center for Epidemiologic Studies of Depression Scale. The use of a "first timer" sample, and of a clinical diagnostic interview, had not, to our knowledge, been previously attempted in studies of psychiatric problems in the homeless. The majority of men had a history of mental disorder or of heavy substance use. On diagnostic interview, 17% of the men had a definite or probable history of psychosis, and another 8% had a possible history of psychosis. A confident diagnosis of schizophrenia was made in 8%. A history of alcohol or other drug abuse was evident in 58%. Cocaine was already (in 1985) the drug of choice; 27% of the study sample had used it more than 50 times. One third of the men were in extreme distress, much of it apparently acute and associated with the transition to the shelter, and 7% reported suicidal thoughts at the time of the interview. The newly homeless, compared with those who had been homeless for much of the 5 years prior to shelter entry, were younger and had fewer psychiatric problems.
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PMID:Psychiatric problems in homeless men. Lifetime psychosis, substance use, and current distress in new arrivals at New York City shelters. 277 50

The authors selected at random every fourth inpatient chart (N = 79) of patients enrolled in a schizophrenia clinic for analysis of substance use patterns and psychiatric hospitalizations. Patients were divided into three groups based on operationally defined lifetime drug use histories: a) cocaine and other substance use; b) substance use without cocaine; and c) no substance use. All available hospital records were examined for presenting symptoms and psychosocial functioning at admission, neuroleptic dosing, and hospital management. Cocaine-using schizophrenics had significantly higher hospitalization rates than other substance-using or non-using patients. No differences were found in hospital presenting symptoms among any cohort. However, the cocaine-using schizophrenic patients demonstrated significantly higher rates of suicidal ideation after cocaine use compared with their own non-cocaine-associated hospitalizations or the other groups. The cocaine group also received higher neuroleptic doses by the fifth and sixth weeks of hospitalization compared with their own non-cocaine-associated hospitalizations and with the other groups. This suggests that cocaine use in schizophrenia is associated with poorer illness course and increased hospitalization, including higher rates of suicidal ideation and greater neuroleptic dose.
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PMID:Effects of cocaine on hospital course in schizophrenia. 809 75

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

Aromatic L-amino acid decarboxylase (AADC) has previously been shown to be up-regulated at the level of its protein activity and its mRNA abundance by antipsychotic drugs. Its activity has also been shown to be down-regulated by dopamine agonists including amphetamine. In this study we have injected rats for up to 32 days with amphetamine and the anti-epileptic drug vigabatrin, both of which can cause psychosis with similarities to schizophrenia. We have shown that AADC mRNA levels are reduced in most brain regions by both drugs. Cocaine and other non-psychotogenic anti-epileptic drugs had no effect in this paradigm. Two products of this enzyme are implicated in psychotogenesis.
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PMID:Amphetamine and vigabatrin down regulate aromatic L-amino acid decarboxylase mRNA levels. 871 41

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

Cocaine, 10 mg/kg, I.P., twice daily, was given to rats for 1 week. At 1 and 4 weeks following discontinuation of cocaine, the initial rate of 3,4-dihydroxyphenylacetic acid (DOPAC) formation was assessed. The initial rate of DOPAC formation was found to be decreased in the frontal and cingulate cortices at 1 week, but was only decreased in the frontal cortex at 4 weeks. When administered in conjunction with cocaine, haloperidol, clozapine, and vitamin E, but not MK-801, were found to prevent cocaine's effects. In addition to the potential value these findings have for further understanding cocaine abuse, it is proposed that the alteration in dopamine metabolism produced by cocaine, and the ability of haloperidol, clozapine and vitamin E to decrease cocaine's effects, model some biochemical aspects of schizophrenia.
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PMID:Effects of antipsychotics, vitamin E, and MK-801 on dopamine dynamics in the rat brain following discontinuation of cocaine. 979 37

Deficient sensorimotor gating, as measured by a relative loss of prepulse inhibition (PPI) of the startle reflex, has been reported in schizophrenia patients and in rats treated acutely with dopamine (DA) agonists or other psychotomimetic agents. For this reason, PPI has been used as a cross-species measure for studying the neurochemistry of specific information processing deficits in schizophrenia. Cocaine is a DA reuptake inhibitor which can precipitate psychosis after sustained use in humans. In rats, sustained exposure to cocaine results in neuropathological and neurochemical changes in several brain regions, and is also associated with specific prolonged behavioral abnormalities. In the present study, we examined the effects of both acute and sustained cocaine administration on PPI and other measures of the startle reflex in rats. Cocaine produced a significant, dose-dependent reduction in PPI, both after acute administration, and after 3 days of sustained administration via implanted subcutaneous pellets. PPI returned to control levels when rats were tested 10 days after sustained (5 day) cocaine administration. The effects of acute cocaine administration on PPI are consistent with those of other DA agonists and psychotomimetics, but PPI does not appear to be sensitive to lasting effects of a method of prolonged cocaine administration associated with neuropathological and neurochemical changes in several brain regions.
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PMID:Effects of sustained cocaine exposure on sensorimotor gating of startle in rats. 1020 17


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