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)

Most of psychoactive substances abuse or dependence disorders are associated to another psychiatric disorders. Depression, anxiety and psychotic disorders are the more frequent comorbid disorders. Psychiatric comorbidity is induced by acute consumption of psychoactive agents, chronic consumption or withdrawal. Psychiatric disorders are more frequent when patient are assessed immediately after the withdrawal. Main biological factors implicated in the pathophysiology of psychiatric disorders associated to dependence disorders are: increase in norepinephrine activity, during withdrawal, activation of locus coeruleus, kinding induced by repeated withdrawals. Psychotic disorders in opiate dependent patients can be induced by withdrawals. These psychotic disorders are more often described after methadone discontinuation. Consumption of cocaine can provocate paranoid delusions. Phenylcyclidine provocates sensorial distortion or delusive disorders resembling schizophrenia. Flash backs, following withdrawal realized brief and transient psychotic disorders. They can occur up to one year after the end of the intoxication. The occurrence of depression in dependent patients is frequent. Depressed patients are at risk for suicide. Retrospective studies showed that near of 40% of the subjects died from suicide have presented alcohol or drug abuse or dependence. Withdrawal from opiates provocates depression. Clinical picture included apathy, blunting of the affects, sadness and loss of interest. Cocaine consumption provocates manic-like disinhibition at the beginning of the intoxication. Long term consumption and withdrawal increase the risk of depression.
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PMID:[Psychiatric disorders induced by drug dependence other than alcohol]. 1085 11

The effect of ritanserin on dopamine (DA) re-uptake and efflux was studied in rat frontal cortex synaptosomes. When compared to other 5HT2 receptor antagonists such as ketanserin and risperidone or DA D2 receptor antagonists such as haloperidol and raclopride, the effect of ritanserin proved to be more potent. Ritanserin blocked the DA transporter with a Ki of 0.18 +/- 0.06 microM, similar to cocaine (0.11 +/- 0.005 microM), while ketanserin had a Ki of 0.93 +/- 0.045; haloperidol of 2.07 +/- 0.12; risperidone of 18.01 +/- 0.62 and raclopride of 24.01 +/- 1.55. In addition, 15 min from its local application to the synaptosomes, ritanserin potently released [3]H-DA leaving only 29.6 +/- 1.6% of DA content, while ketanserin effect was equal to 46.5 +/- 0.9%; haloperidol to 70.4 +/- 2.2% and risperidone to 73.9 +/- 1.5%, all tested at the dose of 10 microM. Cocaine had no effect on DA efflux. These results suggest that ritanserin has a intrinsic dopaminergic effect which may help to explain its reported improvement on mood, cognition and negative symptoms of schizophrenia.
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PMID:The 5-HT2 antagonist ritanserin blocks dopamine re-uptake in the rat frontal cortex. 1112 98

This study was designed to assess whether cocaine abuse was associated with a different set of antecedents and course for hospitalized schizophrenic patients. Forty-three cocaine-using and 27 non-cocaine-using patients with schizophrenia admitted to a dual diagnosis unit were compared with regard to antecedents to hospitalization such as prior treatment episodes, reliance on drugs for pleasure and tension reduction, and criminal history as well as course of hospital treatment. Cocaine-using patients were more likely to have had a history of prior inpatient drug treatment and to rely on drugs to a greater extent for tension reduction and pleasure. There was a trend for cocaine users to have a history of arrests for violent crimes. Although cocaine-using patients exhibited lower levels of global distress during the first week of hospitalization, they were no different from their counterparts who abused nonpsychostimulant drugs with regard to outcome of hospital treatment. These findings suggest that the lifetime course of illness among schizophrenic patients presenting for hospitalization who abuse cocaine may be characterized by episodes of repeated inpatient drug treatment and impaired impulse control. More rigorous discharge planning and aftercare program monitoring in the community as well as stress management interventions directed to tension reduction are therefore warranted.
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PMID:Schizophrenic Patients and Cocaine Use: Antecedents to Hospitalization and Course of Treatment. 1251 14

1-(2-ethoxy-phenyl)-4-[3-(3-thiophen-2-yl-isoxazolin-5-yl)-propyl]-piperazine (KCH-1110), has a high affinity for human dopamine D3 (hD3) receptor (Ki=1.28 nM) with about 90-fold selectivity over the human dopamine D2L (hD2L) receptor. Antipsychotic or antidopaminergic activity of KCH-1110 was investigated in the models for the positive symptoms of schizophrenia, apomorphine-induced climbing and cocaine-induced hyperlocomotion, in mice. Intraperitoneal (i.p.) or oral (p.o.) administration of KCH-1110 potently inhibited the apomorphine-induced cage climbing without any rotarod ataxia in mice. Cocaine-induced hyperactivity was also antagonised by KCH-1110. In addition, KCH-1110 attenuated the hypothermia induced by a selective dopamine D3 agonist, 7-OH-DPAT in mice. KCH-1110 did not induce catalepsy in mice, but at much higher doses only a slight catalepsy response was shown. Although high doses of KCH-1110 significantly enhanced serum prolactin secretion in rats, low dose of KCH-1110 did not increase prolactin levels in rats. The present studies, therefore, suggest that KCH-1110 is a potent and relatively selective dopamine D3 receptor antagonist with antipsychotic actions.
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PMID:Pharmacological actions of a novel and selective dopamine D3 receptor antagonist, KCH-1110. 1452 27

This small-scale study was conducted to examine the feasibility of using voucher-based reinforcement therapy (VBRT) as a treatment modality for cocaine abuse among individuals with schizophrenia. Cocaine use was reduced in three individuals with a diagnosis of schizophrenia during a VBRT intervention. Interestingly, all of the abstinence occurred during the first half of the intervention. This early period of sobriety may represent a clinically relevant window of opportunity during which intensive psychosocial or social work interventions might have a greater chance for success.
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PMID:Investigating the use of contingency management in the treatment of cocaine abuse among individuals with schizophrenia: a feasibility study. 1496 53

Patients with schizophrenia and related psychoses frequently use, abuse and become dependent on psychoactive substances. Local surveys indicate differences in both types and patterns of substances used. A cross-sectional survey was conducted to document abuse in 207 successive outpatients presenting to a psychiatric continuing care facility in a large Canadian city. Nicotine, alcohol and cannabis were the most frequently abused substances in the cohort. Excluding nicotine, 44.9% met criteria for lifetime and 14.0% for current abuse/dependence. Cocaine, heroin, hallucinogen, amphetamine, and inhalant use were rarely reported. Patients with current substance abuse/dependence and a psychotic disorder (dual diagnosis, DD) had significantly higher Positive and Negative Symptom Scale (PANSS) positive scores than lifetime-DD or those with a single diagnosis (SD). Significantly more current-DD (69.0%) patients were depressed (HAM-D score > or =12) compared to SD (45.6%). Furthermore, current-DD (27.6%) patients were more likely than SD (4.5%) to be medication non-compliant. Patients with current-DD were more likely to smoke cigarettes (88.9%) compared to those with SD (49.6%) and they had significantly longer histories of cigarette smoking (19.1 for DD vs. 11.5 years for SD). The smoking behavior of the DD population is discussed in terms of enhanced risk for alcohol abuse, as well as effects on antipsychotic blood levels and metabolism.
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PMID:Drug and alcohol use among patients with schizophrenia and related psychoses: levels and consequences. 1498 74

Cocaine- and amphetamine-regulated transcript (CART) peptide is a novel neuropeptide involved in feeding, drug reward, and stress. We hypothesized that the polymorphism of CART gene might be related with susceptibility to neuropsychiatric diseases such as alcoholism, bipolar disorder, and schizophrenia. The polymorphism (rs2239670) in intron 1 was selected for study among other single nucleotide polymorphisms (SNPs) located at the area of CART gene, because it had not been tested until to date. The study included patients of alcoholism (100), bipolar disorder (76) and schizophrenia (169) from the Korean population. Healthy controls for bipolar disorder and schizophrenia consisted of 333 individuals. For alcoholism, both patient group and control subjects included only male. The restriction fragment length polymorphism (RFLP) using the AvaII restriction enzyme was designed to analyze the selected SNP. The distribution of GG, GA, and AA genotypes in the 333 controls was 50.2, 41.1, and 8.7%, respectively. The frequency of G and A alleles in the 333 controls was 70.7 and 29.3%, respectively. The distribution of genotype and allele frequencies of the AvaII polymorphism showed a significant difference between alcoholism and controls (P = 0.037 and P = 0.044). However, the AvaII polymorphism of the CART gene did not show association with bipolar disorder and schizophrenia. In conclusion, we report for the first time that the AvaII polymorphism (rs2239670) in intron 1 of the CART gene is associated with alcoholism in the Korean male population.
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PMID:Association between polymorphism in intron 1 of cocaine- and amphetamine-regulated transcript gene with alcoholism, but not with bipolar disorder and schizophrenia in Korean population. 1523 72

Quetiapine is an effective atypical antipsychotic medication that was reported to reduce substance use and craving in patients with schizophrenia. This clinical effect of quetiapine is hypothesized to be due to its low affinity for dopamine receptors and its weak attenuation of central reward functions. The present study was designed to determine the magnitude of the reward attenuation induced by different doses of quetiapine and its effectiveness at reducing the effect of cocaine. Experiments were performed on male Sprague-Dawley rats that were trained to produce operant responses to receive rewarding stimulations to the medial forebrain bundle. In a first study, we tested the effects of three doses of quetiapine (5, 10, 20 mg/kg) on brain stimulation reward using a within-subject design and the curve-shift method. In a second study, we tested the effectiveness of a low and high dose of quetiapine (5 and 20 mg/kg) at blocking the reward enhancing effect of cocaine (4 mg/kg) in different groups of animals. Quetiapine produced a weak (20%) but significant attenuation of reward. Cocaine enhanced reward by 20% and the combination of cocaine with the high dose of quetiapine lead to cancellation of each drug effect. The low dose of quetiapine did not alter baseline reward but completely blocked the effect of cocaine. The magnitude of the reward attenuation induced by quetiapine is consistent with its low affinity for dopamine receptors. Its actions on dopamine and non-dopamine neurotransmission are likely to account for its effectiveness at blocking the enhancement of reward by cocaine.
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PMID:Quetiapine blocks cocaine-induced enhancement of brain stimulation reward. 1994 9

Changes in the brain's cholinergic receptor systems underlie several neuropsychiatric disorders, including Alzheimer's disease, schizophrenia, and depression. An emerging preclinical literature also reveals that acetylcoholine may have an important function in addictive processes, including reward, learning, and memory. This study was designed to assess alterations in cholinergic receptor systems in limbic regions of abstinent cocaine-addicted subjects compared with healthy controls. On three separate days, 23 1- to 6-week abstinent, cocaine- (and mostly nicotine-) addicted subjects and 22 sex-, age-, and race-matched control subjects were administered the muscarinic and nicotinic cholinergic agonist physostigmine, the muscarinic antagonist scopolamine, and saline. Regional cerebral blood flow (rCBF) after each infusion was determined using single photon emission-computed tomography. Both cholinergic probes induced rCBF changes (p<0.005) in relatively distinct, cholinergic-rich, limbic brain regions. After physostigmine, cocaine-addicted subjects showed altered rCBF, relative to controls, in limbic regions, including the left hippocampus, left amygdala, and right insula. Group differences in the right dorsolateral prefrontal cortex, posterior cingulate, and middle temporal gyrus were also evident. Scopolamine also revealed group differences in the left hippocampus and right insula as well as the posterior cingulate and middle temporal gyrus. Cocaine addicted and controls differ in their subcortical, limbic, and cortical response to cholinergic probes in areas relevant to craving, learning, and memory. Cholinergic systems may offer a pharmacologic target for cocaine addiction treatment.
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PMID:Altered neural cholinergic receptor systems in cocaine-addicted subjects. 2039 57

We perform prediction of diverse disorders (Cocaine Use, Schizophrenia and Alzheimers disease) in unseen subjects from brain fMRI. First, we show that for multi-subject prediction of simple cognitive states (e.g. motor vs. calculation and reading), voxels-as-features methods produce clusters that are similar for different leave-one-subject-out folds; while for group classification (e.g. cocaine addicted vs. control subjects), voxels are scattered and less stable. Therefore, we chose to use a single region per experimental condition and a majority vote classifier. Interestingly, our method outperforms state-of-the-art techniques. Our method can integrate multiple experimental conditions and successfully predict disorders in unseen subjects (leave-one-subjectout generalization accuracy: 89.3% and 90.9% for Cocaine Use, 96.4% for Schizophrenia and 81.5% for Alzheimers disease). Our experimental results not only span diverse disorders, but also different experimental designs (block design and event related tasks), facilities, magnetic fields (1.5Tesla, 3Tesla, 4Tesla) and speed of acquisition (interscan interval from 1600ms to 3500ms). We further argue that our method produces a meaningful low dimensional representation that retains discriminability.
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PMID:Can a single brain region predict a disorder? 2275 19


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