Normal Genetic Variation, Cognition, and Aging

Greenwood, Pamela M.; Parasuraman, Raja

doi:10.1177/1534582303260641

Cited by 92 publications

(75 citation statements)

References 290 publications

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“…Although the genetic architecture of these endophenotypes may also be somewhat complex (Flint and Munafo 2007), the expectation is that they more directly reflect the activities of neuronal mechanisms than the illness itself. Several promising polymorphisms in candidate genes associated with WM performance have already been identified in both healthy subjects and in schizophrenia patients (e.g., (Cannon 2005;Goldberg and Weinberger 2004;Greenwood and Parasuraman 2003;Parasuraman et al 2005;Wedenoja et al in press). The endophenotype strategy adopted by COGS is complementary to 20 years of genetic linkage and association studies using the clinical diagnosis of schizophrenia that have had modest success in identifying disease-related genes.…”

Section: Discussionmentioning

confidence: 99%

Verbal working memory impairments in individuals with schizophrenia and their first-degree relatives: Findings from the Consortium on the Genetics of Schizophrenia

Horan

Braff

Nuechterlein

et al. 2008

Schizophrenia Research

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Working memory (WM) impairment is a promising candidate endophenotype for schizophrenia that could facilitate the identification of susceptibility genes for this disorder. The validity of this putative endophenotype was assessed by determining whether 149 probands with schizophrenia and 337 of their first-degree relatives demonstrated WM impairment as compared to 190 unaffected community comparison subjects. Subjects were participants in the Consortium on the Genetics of Schizophrenia (COGS) project, a seven-site research network that was established to investigate the genetic Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. Schizophrenia probands performed worse than the other groups on both tasks, with larger deficits found for the more challenging reordering WM task. The probands' relatives performed more poorly than community comparison subjects on both tasks, but the difference was significant only for the more challenging maintenance plus complex manipulation WM task. This WM impairment was not attributable to diagnoses of schizophrenia spectrum disorder, mood disorders, or substance use disorders in the relatives. In conjunction with evidence that WM abilities are substantially heritable, the current results support the validity and usefulness of verbal WM impairments in manipulation of information as endophenotypes for schizophrenia in large-scale genetic linkage and association studies. NIH Public Access

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Section: Discussionmentioning

confidence: 99%

Verbal working memory impairments in individuals with schizophrenia and their first-degree relatives: Findings from the Consortium on the Genetics of Schizophrenia

Horan

Braff

Nuechterlein

et al. 2008

Schizophrenia Research

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“…That is, DA stimulation in low span participants made both their brain activation and performance more like that of high span participants. Individual differences in WM span and underlying PFC function are, at least in part, related to genetic differences, particularly, the possession of certain polymorphisms of genes which impact on DA activity in PFC (such as COMT, MAOA, DRD4, and DAT-1, e.g., Blasi et al, 2005;Diamond et al, 2004;Fan et al, 2003;Greenwood and Parasuraman, 2003;Parasuraman et al, 2005). For example, in the Rueda et al (2005) study, children with the pure long homozygous DAT-1 allele showed better performance on tests of attention and intelligence than those with the heterozygous alleles.…”

Section: Item-specific Versus Process-specific Effects In Working Memorymentioning

confidence: 99%

Flexible cognitive control: Effects of individual differences and brief practice on a complex cognitive task

et al. 2006

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Brain activations underlying cognitive processes are subject to modulation as a result of increasing cognitive demands, individual differences, and practice. The present study investigated these modulatory effects in a cognitive control task which required inhibition of prepotent responses based on the contents of working memory (WM) and which enabled a novel dissociation of item-specific and taskskill effects resulting from brief practice. Distinct responses in areas underlying WM and inhibitory control in the absence of behavioral changes reflected different effects of item repetition and general task practice on tonic working memory and phasic inhibitory processes. Item repetition was associated with decreases in both unique and common areas subserving WM and inhibitory control. In contrast, general task practice was reflected in decreases in the level of tonic WM activity required to maintain a consistently high level of task performance but increased activity in a number of core inhibitory regions including dorsolateral and inferior PFC and inferior parietal cortex. Furthermore, both practice and individual differences in task performance were associated with the ability to modulate and maintain activity in frontostriatal areas mediating attentional control, suggesting that the areas that differ between individuals can be modulated by practice within an individual. These results raise the possibility that a fundamental human ability, reflexive cognitive control, is amenable to practice. D

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“…Greenwood & Parasuraman, 2003). Greenwood and Parasuraman point to the variable heritability of a number of cognitive functions.…”

Section: Genetic Factors In Cognitive Function and Neural Structurementioning

confidence: 99%

A multilevel analysis of cognitive dysfunction and psychopathology associated with chromosome 22q11.2 deletion syndrome in children

Simon

Bish

Bearden

et al. 2005

Develop. Psychopathol.

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We present a multilevel approach to developing potential explanations of cognitive impairments and psychopathologies common to individuals with chromosome 22q11.2 deletion syndrome. Results presented support our hypothesis of posterior parietal dysfunction as a central determinant of characteristic visuospatial and numerical cognitive impairments. Converging data suggest that brain development anomalies, primarily tissue reductions in the posterior brain and changes to the corpus callosum, may affect parietal connectivity. Further findings indicate that dysfunction in "frontal" attention systems may explain some executive cognition impairments observed in affected children, and that there may be links between these domains of cognitive function and some of the serious psychiatric conditions, such as attention-deficit/hyperactivity disorder, autism, and schizophrenia, that have elevated incidence rates in the syndrome. Linking the neural structure and the cognitive processing levels in this way enabled us to develop an elaborate structure/function mapping hypothesis for the impairments that are observed. We show also, that in the case of the catechol-Omethyltransferase gene, a fairly direct relationship between gene expression, cognitive function, and psychopathology exists in the affected population. Beyond that, we introduce the idea that variation in other genes may further explain the phenotypic variation in cognitive function and possibly the anomalies in brain development.In recent years, a great deal has been learned about a disorder that is one of the most common genetic causes of developmental disability, mental retardation, and psychopathology. Resulting from a 1.5-to 3-Mb microdeletion on the long (q) arm of chromosome 22 , this disorder is most accurately characterized as the "chromosome 22q11.2 deletion syndrome" (DS22q11.2). Thus defined, the disorder encompasses previously described phenotypes including DiGeorge (1965), velocardiofacial (Shprintzen, Goldberg, Lewin, Sidoti, Berkman, Argamaso, & Young, 1978, and conotruncal anomaly face (Burn, Takao, Wilson, Cross, Momma, Wadey, Scambler, & Goodship, 1993) syndromes, and some cases of Cayler cardiofacial syndrome (Giannotti, Digilio, Marino, Mingarelli, & Dallapiccola, 1994) and Opitz G/BBB syndrome (McDonald-McGinn, Driscoll, Bason, Christensen, Lynch, Sullivan, Canning, Zavod, Quinn, & Rome, 1995). A molecular fluorescence in situ hybridization probe for the deletion set the prevalence at 1 in 4,000 live (Burn & Goodship, 1996), an estimate currently thought to be quite conservative (e.g., Shashi, Muddasani, Santos, Berry, Kwapil, Lewandowski, & Keshavan, 2004). Furthermore, several factors point to a significant growth in the identified population of individuals with DS22q11.2 in the near future. One is that the major cause for mortality in the syndrome, congenital heart defects, is now routinely resolved surgically. Another is that, because this is a contiguous gene deletion syndrome with no effect on reproductive fitness, adults with...

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Normal Genetic Variation, Cognition, and Aging

Cited by 92 publications

References 290 publications

Verbal working memory impairments in individuals with schizophrenia and their first-degree relatives: Findings from the Consortium on the Genetics of Schizophrenia

Verbal working memory impairments in individuals with schizophrenia and their first-degree relatives: Findings from the Consortium on the Genetics of Schizophrenia

Flexible cognitive control: Effects of individual differences and brief practice on a complex cognitive task

A multilevel analysis of cognitive dysfunction and psychopathology associated with chromosome 22q11.2 deletion syndrome in children

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