Substantial genetic overlap between neurocognition and schizophrenia: genetic modeling in twin samples

Published on Apr 1, 2008in Archives of General Psychiatry
· DOI :10.1186/1744-859X-7-S1-S8
Timothea Toulopoulou37
Estimated H-index: 37
(Harvard University),
Marco Picchioni34
Estimated H-index: 34
('KCL': King's College London)
+ 4 AuthorsRobin M. Murrayand143
Estimated H-index: 143
('KCL': King's College London)
Context The use of endophenotypes, biological traits that increase the liability to a disorder, represents one strategy to facilitate the detection of susceptibility genes for complex behavioral disorders such as schizophrenia. Establishing that a candidate trait is both heritable and linked genetically to schizophrenia is integral to its validity as an endophenotypic marker. Neurocognitive deficits are among the most promising indicators of increased risk for schizophrenia; however, it is not clear to what extent these deficits are genetically linked to the disorder. Objectives To quantify the genetic and environmental contributions to the variability of selected neurocognitive measures and to estimate the genetic relationship between these and schizophrenia. Design Genetic model fitting to monozygotic and dizygotic twin data. Setting United Kingdom psychiatric research institute. Participants Two hundred sixty-seven monozygotic and dizygotic twins concordant and discordant for schizophrenia, and healthy monozygotic and dizygotic control twin pairs. Main Outcome Measures The heritabilities of intelligence, working memory, processing speed, perceptual organization, and verbal comprehension were estimated, and the genetic relationship between each of these and schizophrenia was quantified. Results Genetic influences contributed substantially to all of the cognitive domains, but intelligence and working memory were the most heritable. A significant correlation was found between intelligence and schizophrenia ( r  = −0.61; 95% confidence interval, −0.71 to −0.48), with shared genetic variance accounting for 92% of the covariance between the two. Genetic influences also explained most of the covariance between working memory and schizophrenia. Significant but lesser portions of covariance between the other cognitive domains and schizophrenia were also found to be genetically shared. Environmental effects, although separately linked to neurocognition and schizophrenia, did not generally contribute to their covariance. Conclusion Genomewide searches using factorial designs stratifying for levels of intelligence and working memory will assist in the search for finding quantitative trait loci for schizophrenia.
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  • Citations (142)
Published on Nov 10, 2014
C Andreasen Nancy125
Estimated H-index: 125
Disclosed herein is a self-propelled lawn mower including a prime mover, a drive mechanism selectively connecting the prime mover in driving engagement with the mower wheels and including a control mechanism movable between a drive position and a neutral or non-driving position and a starter interlock connected to the control mechanism for preventing initiation or starting of the prime mover when the control mechanism is in the drive position. In one embodiment, the prime mover is an internal co...
Published on May 1, 2007in American Journal of Psychiatry13.65
Mei Hua-Hall28
Estimated H-index: 28
('KCL': King's College London),
Fruhling Rijsdijk48
Estimated H-index: 48
+ 6 AuthorsPak Sham106
Estimated H-index: 106
Objective: Several components of event-related potentials—P50 suppression, P300 amplitude and latency, and mismatch negativity—have been proposed as potential endophenotypes for schizophrenia on the basis of family studies. The present study used a twin design to estimate the extent of genetic overlap between these indices and the liability to schizophrenia. Method: The authors measured mismatch negativity, P300, and P50 suppression in 16 monozygotic twin pairs concordant for schizophrenia, nine...
Published on Apr 1, 2007in Archives of General Psychiatry
Ulrich Ettinger40
Estimated H-index: 40
Marco Picchioni34
Estimated H-index: 34
+ 10 AuthorsN Davies8
Estimated H-index: 8
('KCL': King's College London)
Context Abnormalities of the thalamus are thought to be central to the pathophysiology of schizophrenia. These abnormalities include altered structure and shape of the thalamus itself and possibly changes to the adhesio interthalamica (or massa intermedia), the gray matter bridge connecting the 2 thalamic lobes. However, it is not clear to what extent these abnormalities are determined by the genetic liability for schizophrenia. Objective To investigate thalamic volume and the presence of the ad...
Published on Dec 7, 2006in Schizophrenia Bulletin7.29
Raquel E. Gur108
Estimated H-index: 108
(UPenn: University of Pennsylvania),
Monica E. Calkins42
Estimated H-index: 42
(UPenn: University of Pennsylvania)
+ 4 AuthorsWilliam S. Stone41
Estimated H-index: 41
(Harvard University)
The Consortium on the Genetics of Schizophrenia (COGS) is a 7-site collaboration that examines the genetic architecture of quantitative endophenotypes in families with schizophrenia. Here we review the background and rationale for selecting neurocognitive tasks as endophenotypic measures in genetic studies. Criteria are outlined for the potential of measures as endophenotypic vulnerability markers. These include association with illness, state independence (ie, adequate test-retest stability, ad...
Published on Oct 1, 2006in Archives of General Psychiatry
Kenneth S. Kendler153
Estimated H-index: 153
Margaret Gatz67
Estimated H-index: 67
+ 1 AuthorsNancy L. Pedersen102
Estimated H-index: 102
Context Prior studies suggest that the personality traits of neuroticism and extroversion may be related to the liability to major depression (MD). Objective To clarify the magnitude and nature of the association between neuroticism and extroversion and the risk for MD. Design Longitudinal population-based twin cohort. Setting General community. Participants A total of 20 692 members of same-sex twin pairs from the population-based Swedish Twin Registry who completed a self-report questionnaire ...
Published on Feb 1, 2006in Journal of Clinical and Experimental Neuropsychology1.99
Timothea Toulopoulou37
Estimated H-index: 37
Seema Quraishi9
Estimated H-index: 9
+ 1 AuthorsRobin M. Murrayand143
Estimated H-index: 143
The distinction of psychosis into schizophrenia and bipolar disorder has been increasingly challenged with some evidence suggesting that the two conditions may have common etiologic and pathogenic mechanisms. We compared the premorbid and current intellectual function of bipolar patients from multiply affected families, and those of their first-degree relatives, with those of a similar series of schizophrenic subjects, as well as their relatives, and normal controls. Only schizophrenic subjects ...
Published on Feb 1, 2006in Genes, Brain and Behavior3.16
Ian Craig59
Estimated H-index: 59
Robert Plomin124
Estimated H-index: 124
Similar to other complex traits, it is likely that many DNA polymorphisms of small effect size [quantitative trait loci (QTLs)] are responsible for the high heritability of intelligence, in addition to many rare monogenic disorders known to contribute to lowered intelligence. We review the current status of approaches to identify QTLs associations for intelligence employing genome-wide strategies using pooled DNA from many individuals and evaluate the innovative approach of microarray analysis t...
Published on Jan 1, 2006in Behavior Genetics2.31
Michelle Luciano41
Estimated H-index: 41
(QIMR: QIMR Berghofer Medical Research Institute),
Margaret J. Wright65
Estimated H-index: 65
(QIMR: QIMR Berghofer Medical Research Institute)
+ 6 AuthorsNicholas G. Martin150
Estimated H-index: 150
(QIMR: QIMR Berghofer Medical Research Institute)
A genome-wide linkage scan of 795 microsatellite markers (761 autosomal, 34 X chromosome) was performed on Multidimensional Aptitude Battery subtests and verbal, performance and full scale scores, the WAIS-R Digit Symbol subtest, and two word-recognition tests (Schonell Graded Word Reading Test, Cambridge Contextual Reading Test) highly predictive of IQ. The sample included 361 families comprising 2-5 siblings who ranged in age from 15.7 to 22.2 years; genotype, but not phenotype, data were avai...
Published on Dec 1, 2005in Biological Psychiatry11.50
Tiia Pirkola6
Estimated H-index: 6
Annamari Tuulio-Henriksson42
Estimated H-index: 42
+ 5 AuthorsTyrone D. Cannon87
Estimated H-index: 87
(UCLA: University of California, Los Angeles)
Background Family studies are in conflict as to whether schizophrenia and bipolar disorder have independent genetic etiologies. Given the relatively low prevalence (approximately 1%) of these disorders, the use of quantitative endophenotypic markers of genetic liability might provide a more sensitive strategy for evaluating their genetic overlap. We have previously demonstrated that spatial working memory deficits increase in a dose-dependent fashion with increasing genetic proximity to a proban...
Published on Jun 16, 2005in Psychological Medicine5.64
Fruhling Rijsdijk48
Estimated H-index: 48
Nem van Haren50
Estimated H-index: 50
+ 6 AuthorsPak Sham106
Estimated H-index: 106
(HKU: University of Hong Kong)
Background. Structural brain volume abnormalities are among the most extensively studied endo- phenotypes in schizophrenia. Bivariate genetic model fitting (adjusted to account for selection) was used to quantify the genetic relationship between schizophrenia and brain volumes and to estimate the heritability of these volumes. Method. We demonstrated by simulation that the adjusted genetic model produced unbiased esti- mates for endophenotype heritability and the genetic and environmental correl...
Cited By142
Published on Feb 1, 2019in Neuropsychopharmacology7.16
Christian Legind (UCPH: University of Copenhagen), Brian V. Broberg10
Estimated H-index: 10
(UCPH: University of Copenhagen)
+ 9 AuthorsBirgitte Fagerlund16
Estimated H-index: 16
(UCPH: University of Copenhagen)
Research findings implicate cerebral glutamate in the pathophysiology of schizophrenia, including genetic studies reporting associations with glutamatergic neurotransmission. The extent to which aberrant glutamate levels can be explained by genetic factors is unknown, and if glutamate can serve as a marker of genetic susceptibility for schizophrenia remains to be established. We investigated the heritability of cerebral glutamate levels and whether a potential association with schizophrenia spec...
Sophie K. Kirchner (LMU: Ludwig Maximilian University of Munich), Selen Ozkan (UPF: Pompeu Fabra University)+ 5 AuthorsSergi Papiol24
Estimated H-index: 24
(LMU: Ludwig Maximilian University of Munich)
Cognitive deficits are increasingly recognized as a core dimension rather than a consequence of schizophrenia (SCZ). The previous evidence supports the hypothesis of shared genetic factors between SCZ and cognitive ability. The objective of this study was to test whether and to what extent the variation of disease-relevant neurocognitive function in a sample of SCZ patients from the previous clinical interventional studies can be explained by SCZ polygenic risk scores (PRSs) or by hypothesis-dri...
Published on Dec 1, 2018in Translational Psychiatry5.18
Rebecca Shafee9
Estimated H-index: 9
(Broad Institute),
Pranav Nanda6
Estimated H-index: 6
(Columbia University)
+ 16 AuthorsScot K. Hill4
Estimated H-index: 4
(RFUMS: Rosalind Franklin University of Medicine and Science)
Psychotic disorders including schizophrenia are commonly accompanied by cognitive deficits. Recent studies have reported negative genetic correlations between schizophrenia and indicators of cognitive ability such as general intelligence and processing speed. Here we compare the effect of polygenetic risk for schizophrenia (PRSSCZ) on measures that differ in their relationships with psychosis onset: a measure of current cognitive abilities (the Brief Assessment of Cognition in Schizophrenia, BAC...
Published on Dec 1, 2018in Schizophrenia Research4.57
Ilanit Hasson-Ohayon25
Estimated H-index: 25
(BIU: Bar-Ilan University),
Gil Goldzweig15
Estimated H-index: 15
+ 2 AuthorsPaul H. Lysaker67
Estimated H-index: 67
(IU: Indiana University)
Abstract Schizophrenia involves a range of interrelated impairments in functioning due to symptoms and deficits in varying domains of cognition including neurocognition, social cognition and metacognition. Yet little is known whether certain symptoms or cognitive impairments play a more central role than others. To explore, we conducted a network analysis of five types of symptoms, six domains of neurocognition and multiple aspects of both social cognition and metacognition. Participants were 81...
Published on Nov 1, 2018in Psychiatry Research-neuroimaging2.21
Sarojini M. Sengupta16
Estimated H-index: 16
(McGill University),
Nellie Fotopoulos (McGill University)+ 8 AuthorsNatalie Grizenko26
Estimated H-index: 26
(McGill University)
Abstract Several epidemiological and genetic studies have provided evidence of an overlap between neurodevelopmental disorders. However, the details of the etiological pathways remain to be elucidated. In this study, we garnered the findings of previous GWAS, conducted with schizophrenia and bipolar disorder. We conducted an exploratory study to examine the association between these SNPs and quantitative clinical/ behavioural/ cognitive/ structural brain parameters, as well as response to treatm...
Anna V. Kirenskaya2
Estimated H-index: 2
Z. I. Storozheva6
Estimated H-index: 6
+ 1 AuthorsRobert David Edmund Sewell21
Estimated H-index: 21
(Cardiff University)
Genetic influences modulating executive functions engaging prefrontal cortical brain systems were investigated in 141 male subjects. The effects of variations in two genes implicated in dopamine and GABA activities in the prefrontal cortex: rs4680 (Val158/Met polymorphism of the catechol-o-methyltransferase gene—COMT) and rs3749034 (C/T) substitution in the promoter region of the glutamic acid decarboxylase gene (GAD1) were studied on antisaccade (AS) performance in healthy subjects and schizoph...
Published on Feb 1, 2018in Psychological Medicine5.64
Josephine Mollon6
Estimated H-index: 6
Avi Reichenberg52
Estimated H-index: 52
Published on Jan 1, 2018in American Journal of Medical Genetics
Siri Ranlund5
Estimated H-index: 5
(UCL: University College London),
Stella Calafato7
Estimated H-index: 7
(UCL: University College London)
+ 30 AuthorsConrad Iyegbe14
Estimated H-index: 14
('KCL': King's College London)
This large multi-center study investigates the relationships between genetic risk for schizophrenia and bipolar disorder, and multi-modal endophenotypes for psychosis. The sample included 4,242 individuals; 1,087 patients with psychosis, 822 unaffected first-degree relatives of patients, and 2,333 controls. Endophenotypes included the P300 event-related potential (N = 515), lateral ventricular volume (N = 798), and the cognitive measures block design (N = 3,089), digit span (N = 1,437), and the ...
View next paperNeurocognitive deficit in schizophrenia: A quantitative review of the evidence.