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RGS4 polymorphisms associated with variability of cognitive performance in a family-based schizophrenia sample.

ABSTRACT: Polymorphisms of the gene encoding the regulator of G protein signaling, subtype 4 (RGS4), may be associated with schizophrenia. Among first-episode schizophrenia patients, they are also associated with dorsolateral prefrontal cortex (DLPFC) volume. The DLPFC is a key region that regulates heritable cognitive functions implicated in schizophrenia pathogenesis. To further understand the relationship of RGS4 variants to schizophrenia, we examined their associations with cognitive functions among schizophrenia patients and their relatives. We analyzed 31 multiplex, multigenerational Caucasian families with schizophrenia recruited on the basis of 2 affected first-degree relatives. All participants underwent a computerized neurocognitive battery that evaluates accuracy and speed (response time) of performance on abstraction/mental flexibility; attention; verbal, spatial, and face memory; and spatial ability. "Tag" single-nucleotide polymorphisms (SNPs) representing common polymorphisms were genotyped. Measured genotype analyses accounting for family relationships were performed using Sequential Oligogenic Linkage Analysis Routines. SNPs rs10917670 ("SNP1") and rs951439 ("SNP7") were associated with face memory speed (P = .0003) at a significance level that survived Bonferroni correction (P = .039). The same SNPs have earlier been reported to be associated with schizophrenia. There also were uncorrected associations with rs10917670 ("SNP1") and rs951439 ("SNP7") on face memory efficiency (P = .03) and verbal memory efficiency (P = 0.02), rs28757217 on abstraction/mental flexibility speed (P = .02) and verbal memory efficiency (P = .03), SNP18 (rs2661319) on spatial memory accuracy (P = 0.02) and face memory speed (P = .03). RGS4 polymorphisms are associated with variations in cognitive functions and contribute a small but statistically significant proportion of variance in a family-based sample.

SUBMITTER: Prasad KM

PROVIDER: S-EPMC2930339 | biostudies-literature | 2010 Sep

REPOSITORIES: biostudies-literature

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RGS4 polymorphisms associated with variability of cognitive performance in a family-based schizophrenia sample.

Prasad Konasale M KM Almasy Laura L Gur Ruben C RC Gur Raquel E RE Pogue-Geile Michael M Chowdari Kodavali V KV Talkowski Michael E ME Nimgaonkar Vishwajit L VL

Schizophrenia bulletin 20090312 5

Polymorphisms of the gene encoding the regulator of G protein signaling, subtype 4 (RGS4), may be associated with schizophrenia. Among first-episode schizophrenia patients, they are also associated with dorsolateral prefrontal cortex (DLPFC) volume. The DLPFC is a key region that regulates heritable cognitive functions implicated in schizophrenia pathogenesis. To further understand the relationship of RGS4 variants to schizophrenia, we examined their associations with cognitive functions among s ...[more]

PMID: 19282471

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Project description:BackgroundCognitive training is effective for improving cognitive performance among people with schizophrenia. An individual's perception of their own cognition is dissociable from performance on objective cognitive tests. Since subjective cognitive benefit may impact engagement, motivation, and satisfaction with time-intensive cognitive interventions, this study aimed to determine whether subjective cognitive difficulties improve in conjunction with cognitive gains following 30 h of cognitive training.MethodsPatients with schizophrenia or schizoaffective disorder (N = 46) were randomized to treatment as usual (TAU) or TAU augmented with auditory-targeted cognitive training (TCT). All participants completed assessment batteries at baseline and follow-up. As previously reported, the TCT group showed significant improvements in verbal learning and memory and reductions in auditory hallucinations relative to the TAU group.ResultsSubjective cognitive difficulties did not significantly improve following TCT, even among TCT participants who showed improvements in cognitive performance (all ps > 0.05). Subjective cognitive difficulties were significantly associated with severity of depressive symptoms and hallucinations (r = 0.48 and r = 0.28, p < 0.001), but not global or specific domains of cognition (all rs < 0.1) at baseline. There were no significant relationships between change in subjective cognitive difficulties and change in cognitive or clinical variables (all ps > 0.05).DiscussionPatients with schizophrenia do not detect change in their cognition following cognitive training, even among those who showed robust gains in cognitive performance. Failure to detect improvement may undermine treatment engagement, motivation, and satisfaction. Translating score improvements on the cognitive exercises into tangible metrics, and providing ongoing, clinician-delivered feedback on performance may facilitate patient ability to detect improvements and improve motivation to engage with cognitive training interventions.

Project description:Background–objective:Prevalence data of cognitive impairment in Schizophrenia based on large population samples are scarce. Our goal is to relate cognition and functional outcomes, and estimate prevalence of cognitive impairment in a large sample of schizophrenia outpatients treated with second-generation antipsychotics. Method:A cross-sectional outpatient evaluation conducted during follow-up visits. Selection criteria included six-months stable treatment. The brief battery, EPICOG-SCH, covered four cognitive domains related to functional outcomes: working memory (WAIS-III-Letter-Number-Sequencing), executive function (Category Fluency Test; CFT), verbal memory (WMS-III-Logical-Memory), and information processing speed (Digit-Symbol-Coding and CFT). Clinical severity and functional impairment were assessed with CGI-SCH and WHO DAS-S. Impairment prevalence was calculated at ? 1.5 SD. Results:Among patients recruited (n = 848) in 234 participating centers, 672 were under 6-month treatment. 61.5% (n = 413) reported cognitive impairment according to CGI-SCH Cognitive Subscale. Estimated prevalences were 85.9% (95% CI 85.6-86.2%) CFT-Fruits; 68.3% (95% CI 67.8-68.8%) CFT-Animals; 38.1% (95% CI 37.5-38.3%) Digit-Symbol-Coding; 24.8% (95% CI 24.1-25.5%) Verbal Memory-Units; 20.9% (95% CI 20.2-21.6%) Letter-Number Sequencing; 11.7% (95% CI 11.0-12.4%) Verbal Memory-Items. Negative and Depressive symptoms, Deficit Syndrome, and functional disability were related to poor performance. Functional disability was predicted by CGI-SCH-Overall severity (OR = 1.34635, p < 0.0001), CGI-SCH-Negative Symptoms (OR = 0.75540, p < 0.0001), working memory (Letter-Number-Sequencing) (OR = - 0.16442, p = 0.0004) and the time-course (OR = 0.05083, p = 0.0094), explaining 47% of the observed variability. Conclusion:Most prevalent impairments were on executive function and processing speed domains; however, working memory showed the strongest relationship to functional disability. Monitoring cognitive function during follow up is critical to understand patient's everyday functional capacity.

Dataset Information

RGS4 polymorphisms associated with variability of cognitive performance in a family-based schizophrenia sample.

Publications

RGS4 polymorphisms associated with variability of cognitive performance in a family-based schizophrenia sample.

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