Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:2.7.10.1 (ERK)
95,504 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

This study evaluated the structural reliability, construct-related validity, and cultural validity generalization of the Hare Psychopathy Checklist: Screening Version (PCL:SV) in a sample of more than 560 male and female Swedish forensic psychiatric treatment patients, forensic evaluation patients, and criminal offenders. Structural reliability was excellent for most indices. PCL:SV scores were higher for males than females for total and Part 1 scores (interpersonal/affective features) but not for Part 2 (behavioral features). With some exceptions, PCL:SV scores were meaningfully related to aggression to others, a measure of risk for violence, substance use problems, personality disorder (positive), and psychosis (negative). Correlations between PCL:SV and aggression were larger for females than males, although the difference was smaller when personality disorder was held constant. The structural reliability and pattern of validity coefficients were comparable in these Swedish samples to other non-North American samples. Implications for the cross-cultural manifestation and correlates of psychopathy are discussed.
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PMID:Reliability and Validity Evaluation of the Psychopathy Checklist: Screening Version (PCL:SV) in Swedish correctional and forensic psychiatric samples. 1591 17

Controversy surrounds the use of the Hare Psychopathy Checklist--Revised (Hare, 1991, 2003) in capital murder cases, where it has been introduced to support prosecution claims that a defendant represents a "continuing threat to society". Although widely presumed to have a prejudicial impact (e.g., American Psychological Association, 2004), little is known about how the lay public reacts to data derived from ostensibly stigmatizing assessment instruments such as the PCL-R. The present study examined the effect of psychopathy data on layperson attitudes by having 203 undergraduates review a capital murder case where the results of the defendant's psychological evaluation were experimentally manipulated. When expert testimony described the defendant as psychopathic, a much larger percentage of participants supported a death sentence (60%) than when testimony indicated that he was psychotic (30%) or not mentally disordered (38%). Interestingly, participant ratings of how psychopathic they perceived the defendant to be--regardless of the testimony condition to which they had been assigned--also predicted support for a death sentence. Given the limited probative value of the PCL-R in capital cases and the prejudicial nature of the effects noted in this study, we recommend that forensic examiners avoid using it in these trials.
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PMID:The impact of mental health evidence on support for capital punishment: are defendants labeled psychopathic considered more deserving of death? 1617 Jul 87

Repeated administrations of NMDA receptor antagonists induce behavioural changes which resemble the symptoms of schizophrenia in animals. ERK and GSK-3beta associated signalling pathways have been implicated in the pathogenesis of psychosis and in the action mechanisms of various psychotropic agents. Here, we observed the phosphorylations of ERK and GSK-3beta and related molecules in the rat frontal cortex after repeated intraperitoneal injections of MK-801, over periods of 1, 5, and 10 d. Repeated treatment with 0.5, 1, and 2 mg/kg MK-801 increased the phosphorylation levels of the MEK-ERK-p90RSK and Akt-GSK-3beta pathways and concomitantly and significantly increased CREB phosphorylation in the rat frontal cortex. However, single MK-801 treatment did not induce these significant changes. In addition, the immunoreactivities of HSP72, Bax, and PARP were not altered, which suggests that neuronal damage may not occur in the rat frontal cortex in response to chronic MK-801 treatment. These findings suggest that chronic exposure to MK-801 may induce pro-survival and anti-apoptotic activity without significant neuronal damage in the rat frontal cortex. Moreover, this adaptive change might be associated with the psychotomimetic action of MK-801.
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PMID:The effects of repeated administrations of MK-801 on ERK and GSK-3beta signalling pathways in the rat frontal cortex. 1678 Jun 7

Phosphodiesterase 10A (PDE10A) is a recently identified cyclic nucleotide phosphodiesterase expressed primarily in dopaminoreceptive medium spiny neurons of the striatum. We report that papaverine is a potent, specific inhibitor of PDE10A and use this compound to explore the role of PDE10A in regulating striatal function. Papaverine administration produces an increase in striatal tissue levels of cGMP and an increase in extracellular cAMP measured by microdialysis. These cyclic nucleotide changes are accompanied by increases in the phosphorylation of CREB and ERK, downstream markers of neuronal activation. In rats, papaverine potentiates haloperidol-induced catalepsy, consistent with the hypothesis that inhibition of PDE10A can increase striatal output and prompting a further evaluation of papaverine in models predictive of antipsychotic activity. Papaverine is found to inhibit conditioned avoidance responding in rats and mice and to inhibit PCP- and amphetamine-stimulated locomotor activity in rats. The effects of papaverine on striatal cGMP and CREB and ERK phosphorylation, as well as on conditioned avoidance responding, were absent in PDE10A knockout mice, indicating that the effects of the compound are the result of PDE10A inhibition. These results indicate that PDE10A regulates the activation of striatal medium spiny neurons through effects on cAMP- and cGMP-dependent signaling cascades. Furthermore, the present results demonstrate that papaverine has efficacy in behavioral models predictive of antipsychotic activity. Thus, inhibition of PDE10A may represent a novel approach to the treatment of psychosis.
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PMID:Inhibition of the striatum-enriched phosphodiesterase PDE10A: a novel approach to the treatment of psychosis. 1678 Aug 99

Disrupted-in-schizophrenia 1 (DISC1), identified in a pedigree with a familial psychosis with the chromosome translocation (1:11), is a putative susceptibility gene for psychoses such as schizophrenia and bipolar disorder. Although there are a number of patients with major depressive disorder (MDD) in the family members with the chromosome translocation, the possible association with MDD has not yet been studied. We therefore performed an association study of the DISC1 gene with MDD and schizophrenia. We found that Cys704 allele of the Ser704Cys single-nucleotide polymorphism (SNP) was associated with an increased risk of developing MDD (P=0.005, odds ratio=1.46) and stronger evidence for association in a multi-marker haplotype analysis containing this SNP (P=0.002). We also explored possible impact of Ser704Cys on brain morphology in healthy volunteers using MR imaging. We found a reduction in gray matter volume in cingulate cortex and a decreased fractional anisotropy in prefrontal white matter of individuals carrying the Cys704 allele compared with Ser/Ser704 subjects. In primary neuronal culture, knockdown of endogenous DISC1 protein by small interfering RNA resulted in the suppression of phosphorylation of ERK and Akt, whose signaling pathways are implicated in MDD. When effects of sDISC1 (Ser704) and cDISC1 (Cys704) proteins were examined separately, phosphorylation of ERK was greater in sDISC1 compared with cDISC1. A possible biological mechanism of MDD might be implicated by these convergent data that Cys704 DISC1 is associated with the lower biological activity on ERK signaling, reduced brain gray matter volume and an increased risk for MDD.
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PMID:Impact of the DISC1 Ser704Cys polymorphism on risk for major depression, brain morphology and ERK signaling. 1695 94

Alcohol and drugs have been linked to severe violent offending among women as well as men. The purpose of this study was to make a contribution to the limited knowledge of characteristics related to the state of intoxication in violent female offenders. The putative differences in the characteristics of female offenders and their violent offenses in relation to the state of intoxication at the time of the violent offending were examined. Of a nation-wide sample of 109 female offenders found guilty of homicide and other violent crimes and incarcerated in 1999-2000 in Finland, 60 offenders participated in the study. Of these offenders 49 (81.7%) had been intoxicated at the time the of index offenses. These were compared with 11 (18.3%) non-intoxicated offenders using a structured interview, the Structured Clinical Interview II for DSM-IV (SCID-II) and the Hare Psychopathy Checklist-Revised (PCL-R). The prevalence of substance abuse or dependence (73.3% and 0%), personality disorder (89.6% and 36.4%), particularly antisocial personality disorder (66.7% and 0%), as well as a history of criminality (69.4% and 0%) were significantly higher among the intoxicated women than among the non-intoxicated. The PCL-R scores were also significantly higher among the intoxicated offenders than among non-intoxicated offenders. The victims of the intoxicated women (23.9%) were less often emotionally close to the perpetrator than were the victims of the non-intoxicated women (66.6%). No differences emerged between the groups in experiences of childhood and adulthood abuse or stressful life events prior to the index crime. The findings indicate that intoxicated violent female offenders exhibit more of the characteristics previously found in violent men, than do the non-intoxicated female offenders. Moreover, the non-intoxicated group comprises both psychotic non-responsible and non-psychotic, fairly well-adjusted women, who are educated, working or studying at the time of the offense and has no history of criminality. Substance misuse constitutes an obvious risk factor for violent behavior in women, and therefore the prevention should include substance abuse treatment.
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PMID:Intoxication and violent women. 1903 13

Actuarial violence risk assessments, many of which include the construct of psychopathy, have been shown to be superior to clinical judgment in the prediction of long-term risk of community violence and recidivism. While these instruments initially appeared to provide similarly accurate judgments of risk of institutional aggression, recent research has indicated that such assessments may be less robust in this setting. One explanation may lie in the types of aggression most frequently observed in each setting. Impulsive (or reactive/affective) is the type of physical aggression most commonly exhibited in psychiatric facilities. This research examines the relationship between risk assessments and aggression in an inpatient forensic setting, with such aggression categorized as impulsive, predatory or psychotic aggression. Consistent with previous research, impulsive aggression was the most frequent type observed (58%). Anger (as measured by the Novaco Anger Scale) and clinical issues (as measured by the HCR-20) were most associated with impulsive aggression, with AUC values of .73 and .71 respectively. In contrast, anger and psychopathy (as measured by the PCL-R) were more associated with predatory aggression, with AUC values of .95 and .84 respectively. Psychotic symptoms were highly associated with psychotically motivated aggression (AUC=.90). These results suggest that traditional violence risk assessments may have limited utility in predicting aggression in an institutional setting and that psychiatric symptoms and heightened affect are more relevant.
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PMID:The accuracy of risk assessment instruments in the prediction of impulsive versus predatory aggression. 1903 2

Galantamine, a drug used to treat Alzheimer's disease, inhibits acetylcholinesterase (AChE) and allosterically modulates nicotinic acetylcholine receptors (nAChRs) resulting in stimulation of catecholamine neurotransmission. In this study, we investigated whether galantamine exerts cognitive-improving effects through the allosteric modulation of nAChRs in an animal model of methamphetamine (Meth) psychosis. The mice treated with Meth (1 mg/kg.d) for 7 d showed memory impairment in a novel object recognition test. Galantamine (3 mg/kg) ameliorated the memory impairment, and it increased the extracellular dopamine release in the prefrontal cortex (PFC) of Meth-treated mice. Donepezil, an AChE inhibitor (1 mg/kg) increased the extracellular ACh release in the PFC, whereas it had no effect on the memory impairment in Meth-treated mice. The nAChR antagonist, mecamylamine, and dopamine D1 receptor antagonist, SCH 23390, blocked the ameliorating effect of galantamine on Meth-induced memory impairment, whereas the muscarinic AChR antagonist, scopolamine, had no effect. The effects of galantamine on extracellular dopamine release were also antagonized by mecamylamine. Galantamine attenuated the defect of the novelty-induced activation of extracellular signal-regulated kinase 1/2 (ERK1/2). The ameliorating effect of galantamine on recognition memory in Meth-treated mice was negated by microinjection of an ERK inhibitor, PD98059, into the PFC. These results suggest that the ameliorating effect of galantamine on Meth-induced memory impairment is associated with indirect activation of dopamine D1 receptor-ERK1/2 following augmentation with dopaminergic neurotransmission in the PFC through the allosteric activation of nAChRs. Galantamine could be a useful therapeutic agent for treating cognitive deficits in schizophrenia/Meth psychosis, as well as Alzheimer's disease.
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PMID:Galantamine ameliorates the impairment of recognition memory in mice repeatedly treated with methamphetamine: involvement of allosteric potentiation of nicotinic acetylcholine receptors and dopaminergic-ERK1/2 systems. 2021 55

2-Chloro-10-[3(-dimethylamino)propyl]phenothiazinemonohydrochloride (chlorpromazine) is a phenothiazine derivative used clinically to control psychotic disorders. It also exhibits an anticancer activity. Treatment with chlorpromazine (CPZ) results in cell-cycle arrest at the G2/M phase in rat C6 glioma cells. CPZ reduces the expression of cell cycle-related proteins, such as cyclin D1, cyclin A, and cyclin B1, but causes an increase in the p21(Waf1/Cip1) level. The molecular mechanism by which CPZ regulates p21(Waf1/Cip1) expression is unknown. Here, we provide evidence that CPZ activates the p21(Waf1/Cip1) gene promoter via induction of the transcription factor early growth response-1 (Egr-1) independently of p53 in C6 cells. A point mutation in the Egr-1-binding motif within the p21(Waf1/Cip1) promoter abrogated promoter inducibility due to CPZ. Forced expression of Egr-1 enhanced p21(Waf1/Cip1) promoter activity. In contrast, knockdown of endogenous Egr-1 by small interference RNA attenuated CPZ-induced p21(Waf1/Cip1) promoter activity. A chromatin immunoprecipitation assay demonstrated that Egr-1 binds to the p21(Waf1/Cip1) gene promoter. Further analysis showed that the ERK and JNK MAP kinases are required for induction of Egr-1 by CPZ. Finally, stable silencing of Egr-1 expression lead to attenuated CPZ-inducible p21(Waf1/Cip1) expression and inhibited G2/M phase cell-cycle arrest. These results demonstrate that a functional link between ERK and JNK MAP kinase pathways and p21(Waf1/Cip1) induction via Egr-1 contributes to CPZ-induced anticancer activity in C6 glioma cells.
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PMID:Chlorpromazine activates p21Waf1/Cip1 gene transcription via early growth response-1 (Egr-1) in C6 glioma cells. 2036 87

The aim of this study was to gain more insight in the backgrounds and characteristics of arsonists. For this, the psychiatric, psychological, personal, and criminal backgrounds of all arsonists (n=25), sentenced to forced treatment in the maximum security forensic hospital "De Kijvelanden", were compared to the characteristics of a control group of patients (n=50), incarcerated at the same institution for other severe crimes. Apart from DSM-IV Axis I and Axis II disorders, family backgrounds, level of education, treatment history, intelligence (WAIS scores), and PCL-R scores were included in the comparisons. Furthermore, the apparent motives for the arson offences were explored. It was found that arsonists had more often received psychiatric treatment, prior to committing their index offence, and had a history of severe alcohol abuse more often in comparison to the controls. The arsonists turned out to be less likely to suffer from a major psychotic disorder. Both groups did not differ significantly on the other variables, among which the PCL-R total scores and factor scores. Exploratory analyses however, did suggest that arsonists may differentiate from non-arsonists on three items of the PCL-R, namely impulsivity (higher scores), superficial charm (lower scores), and juvenile delinquency (lower scores). Although the number of arsonists with a major psychotic disorder was relatively low (28%), delusional thinking of some form was judged to play a role in causing arson crimes in about half of the cases (52%).
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PMID:Backgrounds and characteristics of arsonists. 2043 74


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