G K Thaker

..As endophenotypes are present during childhood and adolescence, novel drugs that are developed on the basis of this subgroup could have implications for preventive strategies in schizophrenia...

..Subtle clinical signs and symptoms, cognitive impairment particularly in attention and memory, and neurophysiologic deficits such as in sensory gating and smooth-pursuit eye movements all define aspects of the schizophrenia phenotype...

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..These alternative phenotypes are likely to aid search for liability genes in schizophrenia and bipolar disorders and likely to be informative regarding the extent to which the 2 disorders share etio-pathophysiology...

..And finally, the clinical and functional consequences of the neurophysiological deficits both in the probands and their relatives are not well described...

..Further research is needed to identify subtle deficits underlying functional deterioration and to develop targets for treatment strategies...

..The relatively high prevalence rate of the abnormality in at-risk subjects may have relevance for use of these measures in linkage analysis...

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..This study examined associations between functional polymorphism (Val(108/158) Met) in the catechol O-methyltransferase (COMT) gene and eye tracking measures in schizophrenia...

..Based on recent findings in schizophrenia, we hypothesize that subtle deficits in the ability to hold online and/or use extraretinal motion information underlie the pursuit abnormality in vulnerable individuals...

..To examine the relationship between smooth pursuit eye movements and tardive dyskinesia (TD) in schizophrenia...

..The findings of an asymmetrical deficit in the disengagement and shift of covert visual attention in schizophrenia spectrum subjects are similar to the one's observed in patients with unilateral left hemisphere lesions...

..In an effort to group mental disorders on the basis of etiology, five clusters have been proposed. Here we consider the validity of the cluster comprising selected psychotic and related disorders...

..CONCLUSIONS: These results suggest that nicotine enhances delayed recognition memory in schizophrenic patients who smoke, but that similar performance enhancement is not observed for working memory...

..They also tested the hypothesis that dyskinetic-like movements would increase after repeated dextroamphetamine challenge to the dopaminergic system...

..These results provide support for a role of this variant in the etiopathophysiology of schizophrenia...

..These findings suggest an abnormality in neuronal nicotinic system functioning in schizophrenic patients...

..The authors tested the hypothesis that eye tracking disorder in schizophrenia is associated with neurological signs...

..CONCLUSION: These findings suggest effectiveness of a strategy of combining a GABA(gamma aminobutyric acid)mimetic drug with an enkephalin antagonist to treat dyskinesia...

..Ethnicity might also be a risk factor for dyskinesia in children. Side-effect profile of the atypical antipsychotic drugs in children may be much different than that in adults...

..The authors hypothesized that the relationship of the two measures may vary as a function of interstimulus intervals of stimulus presentations...

..A widely used surrogate measure of psychosis in animal models, PPI is considered a schizophrenia endophenotype. We hypothesized that if NRG1 influences PPI in rodents, then it should have a similar effect on PPI in humans...

..Previous work has shown a reduced predictive pursuit response to a briefly masked (i.e., invisible) moving object in schizophrenia. However, the overt awareness of target removal can confound the measurement...

..Results suggest that SSPD in the absence of a family history of psychosis may be a phenocopy...

..Imaging studies showed that nicotine challenges almost always involve the cingulate cortex, suggesting that this locus may be a key region associated with nicotine addiction and its treatment...

..Identifying where and how brain circuits link genes to smoking provides practical neural circuitry targets for new treatment development...

..002). In conclusion, the findings confirmed that nicotine transiently improves acoustic PPI in schizophrenia patients. Additionally, schizophrenia patients with more clinical symptoms may have benefited more from nicotinic effect on PPI...

..The results suggested that beta oscillation indexed a neural process associated with the strength of sensory gating...

..These electrical oscillatory indexes of subanesthetic ketamine can be potentially used to cross-examine glutamatergic pharmacological effects in translational animal and human studies...

..05), but higher expression in schizophrenia donors. Findings suggest regulatory effects of another gene(s) or etiological factor in schizophrenia, which modulate DAT1 gene function...

..Frequency-specific sensory gating may be less complex than the P50 response, and therefore closer to the direct genetic effects, and thus a more valid endophenotype...

..These findings provide guidance for developing new treatment strategies for the sustained attention deficit in schizophrenia...

..However, eye movement closely interacts with motion perception. The known eye-tracking difficulties in schizophrenia patients may interact with their motion perception...

..Findings from this preliminary study suggest SSP may be more receptive to the beneficial effects of repeated amphetamine on cognition than healthy controls...

..Recent studies have suggested that deficit in predictive pursuit, a specific component of the SPEMs, marks schizophrenia susceptibility...

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..Rather, the data are consistent with a more complex model in which nonspecific genetic factors that increase susceptibility to developmental abnormalities interact with insults and specific genetic factors...

..The results of the present study showed that post-SI beta frequency response was inversely correlated to the S2 P50 response in patients with schizophrenia...

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..The current study examines the anatomic distribution and course of TD in a cohort of schizophrenia patients of European and African descent with TD who were referred to the Motor Disorders Clinic (MDC)...

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..2%, P =0.050) forms of schizophrenia compared to controls (allele frequency 25.0%). We conclude that the DRP-2 *2236 C allele may mark another polymorphism in DRP-2, or in a nearby gene, that may influence susceptibility to schizophrenia...

..Data suggest that at-risk individuals for schizophrenia depend less on extraretinal and more on retinal motion signals to maintain pursuit than healthy individuals...

..These findings suggest that predictive smooth pursuit abnormality is associated with positive symptoms in schizophrenia, and that initiation abnormalities may be associated with the deficit syndrome...

..The authors examined the effects of ketamine on leading saccadic eye movements, a specific component of the smooth-pursuit response shown to be abnormal in schizophrenia patients and their relatives...

..96). This result suggests that the portable device is comparable with a lab-based system, which makes possible the collection of eye movement data in community-based and multicenter familial studies of schizophrenia...

..Combining specific measures provided greater predictive accuracy compared with single measures. Implications for the use of specific eye movement measures to define schizophrenia-related phenotypes in genetic studies are discussed...

..Our results provide suggestive evidence that the use of clinical criteria in research may, in fact, underidentify at-risk individuals--potentially distorting genetic and neurophysiological findings...

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..These results suggest that the limbic system, especially the hippocampus, is functionally involved in schizophrenic psychosis and that different manifestations of schizophrenia may involve different neuronal circuits...

..Overlapping and unique genetic and intermediate phenotypic signatures of the two psychoses are comprehensively recapitulated. Alternative strategies which may be implicated into genetic research are discussed...

..No effective treatments for TD are available. This lack of effective therapy is problematic, especially in the few patients in whom the disorder causes functional impairment and other complications, and in whom it may be irreversible...

..This is particularly relevant for research efforts to identify pathophysiological components of the disease...

..Moreover, many of these neurophysiological processes are phylogenetically conserved and can be modelled in preclinical studies, offering unique opportunities for use as translational biomarkers in schizophrenia drug discovery...

..The proposed project is a collaborative effort--involving clinical scientists studying schizophrenia pathophysiology and basic scientists studying motion perception and eye movements. ..

..Clinical information, electrophysiological and cognitive measures will be collected and compared among the groups using standard family case control analytic procedures. ..

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..Other neurocognitive measures will be compared in these four groups. And we will explore the ability of eye tracking measures alone, cognitive measures alone and the measures in combination in accurately predicting relative status. ..

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