Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0036341 (schizophrenia)
 60,220 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We measured the reaction times (RTs) of schizophrenic (n = 25), matched normal (n = 69), and bipolar (n = 14) subjects to a tone preceded by a preparatory interval (PI; the time between the warning signal and imperative stimulus) of varying length. RTs increase when the PI for the immediately preceding trial (the PPI) is longer than the PI for the current trial. Several studies have shown that this PPI effect (difference score) is heightened in schizophrenia. We replicated this finding. However, we found that the size of the PPI effect within groups increased with overall slowness and that the least squares regression line relating the PPI effect difference score to overall slowness did not differ between groups, nor did schizophrenic subjects' regression line differ from that of normal subjects. Group differences on the PPI effect were also analyzed by taking residuals for members of all groups from the normal subjects' regression line of the PPI effect difference score on overall slowness. Groups did not differ on these residuals, nor did schizophrenic subjects differ from normal subjects. We conclude that the heightening of the PPI effect in schizophrenia is like that observed in equally slow normal subjects. This finding suggests that the PPI effect does not appear to be a promising marker of a distinctive schizophrenic pathology.
 ...
PMID:Slowness and the preceding preparatory interval effect in schizophrenia. 843 90

Animals depleted of dopamine (DA) in the neonatal period and tested in adulthood exhibit some similarities to patients with schizophrenia, including increased sensitivity to DA agonists, altered sensitivity to DA receptor antagonists, and abnormalities of the acoustic startle response (ASR). In this study, we examined the contributions of D1-like and D2-like DA receptors to ASR measures in animals depleted of DA as neonates. Male rat pups received intracerebroventricular injections of 6-hydroxydopamine (DA depleted) or its vehicle (controls) at 3 days of age. Animals underwent startle testing as adults (60-75 days of age) after administration of DA antagonists (haloperidol: 0.1 or 0.3 mg/kg, SCH 23390:0.01 or 0.05 mg/kg) with and without DA agonist administration (apomorphine 0.5 mg/kg). ASR amplitude and prepulse inhibition (PPI: percentage decrease in startle amplitude due to a low intensity prepulse) were measured. DA depleted animals showed increased ASR amplitude and reduced PPI compared to controls. Administration of D1-like or D2-like DA antagonists significantly reduced overall ASR and increased PPI in both control and DA depleted animals, with DA depleted animals showing a relatively greater sensitivity to the D1-like antagonist SCH 23390. Findings are discussed in terms of the role of residual DA in mediating ASR phenomena in depleted animals, differences between D1/D2 DA receptor mediation of ASR compared to other behaviors in DA depleted animals, and potential implications for neuropsychiatric syndromes such as schizophrenia.
 ...
PMID:Effects of haloperidol and SCH 23390 on acoustic startle in animals depleted of dopamine as neonates: implications for neuropsychiatric syndromes. 883 19

Somatostatin is a neuropeptide that has been shown to interact with dopamine. Low concentrations of cysteamine selectively depletes somatostatin and has been used to investigate the role of endogenous somatostatin in lieu of an available selective receptor antagonist. We examined the effects of various doses of subcutaneous cysteamine on baseline and amphetamine-disrupted sensorimotor gating as measured by prepulse inhibition of the acoustic startle reflex. Cysteamine in doses ranging from 50-300 mg/kg reversed decreases in PPI induced by systemic injections of amphetamine (2 mg/kg). Cysteamine had no effect on the amplitude of the acoustic startle reflex itself. The results lend further support to a somatostatin-dopamine interaction within the brain in which endogenous somatostatin facilitates dopaminergic activity. These findings also suggest that endogenous somatostatin might play a significant role in regulation of sensorimotor gating deficits. This has clinical implications as deficient prepulse inhibition is recorded in humans suffering from neuropsychiatric conditions such as schizophrenia.
 ...
PMID:Cysteamine blocks amphetamine-induced deficits in sensorimotor gating. 932 60

Stress has long been recognized as a factor that contributes to the induction of schizophrenia and results in abnormal sensorimotor functioning and information processing. Patients with schizophrenia show disrupted habituation and prepulse inhibition of the acoustic startle response. This study examined the effects of maternal isolation in rats on the habituation of startle and PPI to assess the potential impact of developmental stress on schizophrenic symptomatology. Evaluation of performance in young adulthood (3-4 months) revealed a disruption of habituation in the isolated group; response amplitude increased over time. PPI was not altered. These results suggest that the disruption of habituation may involve acute effects of elevated stress hormones on neuronal functions. In contrast, disturbance of PPI may require an accrual of neuronal insult and damage to ultimately undermine neurologic function, possibly through impact on N-methyl-D-aspartate-mediated transmission. An analysis of effects at middle age is planned to address this possibility.
 ...
PMID:Developmental stress disrupts habituation but spares prepulse inhibition in young rats. 1091 92

A continuum of symptoms between "normality" and overt psychosis has been documented in relatives of schizophrenia patients, SPD, and individuals who may be in the early stages of a psychotic illness with "subsyndromal" symptoms. The empirically derived criteria for SPD have been refined to define a clinical phenotype that is linked to schizophrenia. The clinical SPD symptoms define a heterogeneous group of individuals who are often comorbid for Axis I and II disorders, may or may not have a family history of schizophrenia, and are at risk for developing schizophrenia themselves. SPD subjects have similar abnormalities to those observed in schizophrenia patients on various psychophysiologic paradigms designed to study central inhibition, including P50 event-related potential suppression, PPI of the startle response, and the antisaccade task. Because SPD subjects do not have many of the confounding variables observed in schizophrenia patients (i.e., medication effects), these paradigms might represent vulnerability markers that are possible endophenotypes for schizophrenia spectrum illness. Questions still remain as to whether SPD is genotypically linked to schizophrenia but has genes of lesser penetrance, fewer affected genes, lack of a second hit, or perhaps protective factors. It is also possible that SPD, like schizophrenia, is a common final pathway that can come about because of several etiologic factors that affect crucial neurodevelopmental periods. Future directions in SPD work might include the use of vulnerability markers to essentially subtype schizophrenia spectrum patients and create simpler endophenotypes to understand the phenomenologic and neurobiologic substrate. The use of vulnerability markers along with clinical symptoms may help to improve the predictive power for identifying individuals at risk for schizophrenia for early intervention. Finally, genetic studies have yet to be performed in SPD.
 ...
PMID:Vulnerability markers in the schizophrenia spectrum: implications for phenomenology, genetics, and the identification of the schizophrenia prodrome. 1246 63

Studies of the acoustic startle response and of its inhibition by the presentation of a non-startling preliminary stimulus (prepulse inhibition, PPI) have revealed deficits in PPI in schizophrenic subjects compared to healthy controls. Animal studies indicate that atypical antipsychotics improve PPI deficits induced by NMDA antagonists more consistently than typical antipsychotics. The effect of medication status on PPI in schizophrenia is unresolved in the literature. In the current study the effects on PPI of the atypical antipsychotic olanzapine and the typical antipsychotic haloperidol were compared to the unmedicated state in subjects with schizophrenia. In a between-group design, 11 schizophrenic subjects on olanzapine, 16 subjects on haloperidol, and 14 subjects who were on no medication received acoustic startle testing with PPI determination. ANOVAs revealed no significant differences in startle to pulse alone stimuli, habituation of startle, or PPI between the olanzapine, haloperidol and unmedicated groups. These 41 subjects with schizophrenia were compared to a group of 21 historical healthy controls and found to have reduced PPI. These data do not indicate a preferential effect of olanzapine compared to haloperidol on sensorimotor gating in schizophrenia. The results are consistent with the hypothesis that PPI impairments are relatively stable across treatment conditions.
 ...
PMID:Prepulse inhibition of acoustic startle in subjects with schizophrenia treated with olanzapine or haloperidol. 1450 Jan 9

Prepulse inhibition of startle is a model of sensorimotor gating, which is disrupted in alcoholism, as well as mental illnesses such as schizophrenia. The fawn-hooded (FH) rat strain has been used as an animal model of alcoholism. FH rats showed significantly lower startle amplitude than Wistar-Kyoto (WKY) rats and Sprague-Dawley (SD) rats. Increasing doses of the 5-HT(1A) receptor agonist 8-OH-DPAT caused disruption of PPI, with the effect being significantly greater in FH rats compared to WKY rats. In all strains, treatment with 0.5 mg/kg of 8-OH-DPAT significantly reduced PPI. In contrast, 0.1 mg/kg of 8-OH-DPAT caused disruption only in the FH strain. Treatment with amphetamine, apomorphine and MK-801 also significantly reduced PPI, however, there was no difference between the strains. This study shows increased sensitivity of FH rats to the disruption of PPI caused by 5-HT(1A) receptor stimulation, suggesting a link between 5-HT(1A) receptors, sensorimotor gating and aspects of the FH rat phenotype.
 ...
PMID:Prepulse inhibition in fawn-hooded rats: increased sensitivity to 5-HT1A receptor stimulation. 1533 98

Basic neurocognition and social cognition appear to influence the social impairments of persons with schizophrenia. This study examined relationships between two very basic automatic processes (i.e., sensorimotor gating and orienting) and social perception in schizophrenic patients. Thirty outpatients with schizophrenia completed psychophysiological measures of sensorimotor gating (prepulse inhibition, PPI), orienting (prepulse facilitation, PPF), and social perception (the Half Profile of Nonverbal Sensitivity, Half PONS). A median split was used to divide patients into poor and good gaters and poor and good orienters. Analyses revealed that patients with good PPI scored significantly higher on the Half PONS than patients with poor PPI. PPI showed a significant correlation (r=-0.54) with Half PONS performance, indicating that schizophrenia patients who were better able to gate out competing stimuli (i.e., less startle) were also better at detecting relevant social cues. Orienting (PPF) and social perception were not related. This study is the first to our knowledge to demonstrate an association between sensorimotor gating and social perception. The findings are consistent with other studies that have demonstrated relationships between basic neurocognition and social cognition. By showing a link between sensorimotor gating and social perception, this study supports social cognition's potential role as a mediator of the relationship between neurocognition and social functioning in schizophrenia.
 ...
PMID:Sensorimotor gating, orienting and social perception in schizophrenia. 1565 77

Prepulse inhibition of startle ('PPI'), a cross-species measure of sensorimotor gating, is impaired in schizophrenia patients. Suppression of P50 event-related potentials (ERPs) in response to the second of two clicks ('P50 gating') is also impaired in schizophrenia. Suppression of N40 ERPs to the second of two clicks ('N40 gating') is thought by some to be a rat homolog of human P50 gating. Emerging evidence suggests differences in the neurobiology of deficits detected by PPI vs P50 (or N40) gating. We recorded PPI and N40 gating contemporaneously in rats, to assess convergence and divergence in the neurochemical regulation of these measures. Dose-response studies examined the effects of apomorphine (APO), phencyclidine (PCP) or the 5HT2A agonist DOI on PPI, and on motor responses to stimuli (S1 and S2) that elicit N40 gating. Effects of optimal drug doses on PPI and N40 gating were then assessed in other rats with implanted cortical surface electrodes. APO, PCP and DOI caused dose-dependent disruptions of both PPI and gating of motor responses to N40 stimuli. Reduced PPI reflected diminished prepulse effectiveness, demonstrated by increased startle levels on prepulse+pulse trials. In contrast, reduced gating of motor responses to N40 stimuli reflected a reduced motor response to S1. In separate rats, robust PPI, N40 potentials and N40 gating could be detected within one test. PPI and N40 gating were disrupted by APO, PCP, and DOI. Again, drug effects on PPI reflected increased startle on prepulse+pulse trials, while those on N40 gating reflected reduced ERP responses to S1. In conclusion, when PPI and N40 gating were studied concurrently in rats, drug effects on PPI reflected reduced inhibition of startle by the prepulse, while diminished N40 gating reflected S1 response suppression. Despite similarities in drug sensitivity, these results suggest that distinct neurobiological mechanisms underlie drug-induced deficits in PPI and N40 gating.
 ...
PMID:Convergence and divergence in the neurochemical regulation of prepulse inhibition of startle and N40 suppression in rats. 1612 72

Rearing rats in isolation produces behavioural and neurochemical alterations similar to those observed in schizophrenia. Cannabinoids have also been implicated in inducing psychotic symptoms. In this study, we investigate the effect of the major psychoactive constituent of cannabis and partial cannabinoid CB(1) receptor agonist Delta(9)-tetrahydrocannabinol (THC) on prepulse inhibition (%PPI) of the acoustic startle reflex and on habituation in socially isolated and grouped rats. Deficits in %PPI are reminiscent of sensorimotor gating deficits observed in psychoses. Male Sprague-Dawley rat pups (21 days old) were housed in either single cages (isolated) or in group cages of six per cage (grouped). Eight weeks later the effect of vehicle, THC and the CB(1) receptor antagonist SR 141716 on %PPI was tested. Vehicle treated isolated rats exhibited significantly reduced PPI compared with grouped rats. Isolated rats treated with THC had significantly lower %PPI than vehicle treated groups. This further decrease of %PPI by THC was reversed by pre-treatment with SR 141716, indicating that this effect was mediated by CB(1) receptors. THC had no significant effect on %PPI in grouped rats. SR 141716 had no significant effect on %PPI in either grouped or isolated rats. Habituation did not significantly alter in any treatment group in any treatment group. These results suggest that THC produces significant decreases in sensorimotor gating in rats with already dysfunctional sensorimotor gating processes, but not in normal rats. The lack of effect of SR 141716 in either grouped or isolated rats suggests that normal endocannabinoid function is not critical in sensorimotor gating processes.
 ...
PMID:The effect of Delta9-tetrahydrocannabinol on sensorimotor gating in socially isolated rats. 1614 10


1 2 3 4 5 6 7 Next >>