1. Schizophr Res. 2011 Feb;125(2-3):304-6. Epub 2010 Nov 26. A neuropsychological investigation o... more 1. Schizophr Res. 2011 Feb;125(2-3):304-6. Epub 2010 Nov 26. A neuropsychological investigation of the genome wide associated schizophrenia risk variant NRGN rs12807809. Donohoe G, Walters J, Morris DW, Da Costa A, Rose E, Hargreaves A, Maher K, Hayes E, Giegling I, Hartmann AM, Möller HJ, Muglia P, Moskvina V, Owen MJ, O'Donovan MC, Gill M, Corvin A, Rujescu D. PMID: 21112188 [PubMed - indexed for MEDLINE]. Publication Types: Letter; Research Support, Non-US Gov't. MeSH Terms. ...
Cognitive deficits are core to the disability associated with many psychiatric disorders. Both va... more Cognitive deficits are core to the disability associated with many psychiatric disorders. Both variation in cognition and psychiatric risk show substantial heritability, with overlapping genetic variants contributing to both. Unsurprisingly, therefore, these fields have been mutually beneficial: just as cognitive studies of psychiatric risk variants may identify genes involved in cognition, so too can genome-wide studies based on cognitive phenotypes lead to genes relevant to psychiatric aetiology. The purpose of this review is to consider the main issues involved in the phenotypic characterization of cognition, and to describe the challenges associated with the transition to genome-wide approaches. We conclude by describing the approaches currently being taken by the international consortia involving many investigators in the field internationally (e.g. Cognitive Genomics Consortium; COGENT) to overcome these challenges.(Received May 18 2012)(Revised September 20 2012)(Accepted October 11 2012)(Online publication November 30 2012)
Classification in psychiatry is heavily dependent on clinical symptoms and illness course. This i... more Classification in psychiatry is heavily dependent on clinical symptoms and illness course. This ignores the critical role that cognitive problems play in neuropsychiatric disorders affecting different domains across the lifespan, from ADHD and autism to schizophrenia and Alzheimers disease. At this point, it is unclear whether cognitive mechanisms are specific to disorders, whether multiple processes can contribute to the same disorder, or whether aberrant neural processing can result in many different phenotypic outcomes. Understanding this would allow us to better grasp normal as well as pathological brain function. This could inform diagnostics based on understanding of neurophysiological processes and the consequent development of new therapeutics. Genetics, and the development of genomic research, offers real opportunities to understand the molecular mechanisms relevant to cognition. This chapter defines and describes the main cognitive phenotypes, which are investigated in psychiatric disorders. We review evidence for their heritability and early progress in the field using cytogenetic, linkage and candidate gene-based research methodologies. With high-throughput genomics it is now possible to explore novel common and rare risk variants for psychiatric disorders and their role in cognitive function at a genome-wide level. We review the results of early genomic studies and discuss the novel insights that they are starting to provide. Finally, we review the analysis of whole-genome DNA sequence data and the challenges that this will bring for cognitive genomics research.
The world journal of biological psychiatry : the official journal of the World Federation of Societies of Biological Psychiatry, 2012
Objectives. SNP rs2473277 upstream of the cell division cycle 42 (CDC42) gene was associated with... more Objectives. SNP rs2473277 upstream of the cell division cycle 42 (CDC42) gene was associated with schizophrenia in a recent genome-wide association study (GWAS). Reduced expression of CDC42 in schizophrenia has previously been reported. Our objective was to test whether the associated SNP affected CDC42 expression. Methods. Two available SNP × gene expression datasets were accessed to test the effect of rs2473277 on CDC42 expression: (i) the mRNA by SNP Browser, which presents results of a genome-wide linkage study of gene expression, and (ii) the Genevar HapMap expression dataset. rs2473277 is in strong linkage disequilibrium (LD) with the SNP rs2473307 (r(2) = 0.96), which is predicted to affect transcription factor binding. rs2473307 was directly tested for allelic effects on gene expression using a gene reporter assay in a human neuronal cell line. Results. In both datasets, the schizophrenia risk allele at rs2473277 was associated with a reduction in CDC42 mRNA levels. In the reporter gene assay the risk allele at rs2473307 similarly reduced gene expression. Conclusions. We found evidence that rs2473307, in strong LD with the schizophrenia associated SNP rs2473277, is a functional variant at CDC42 that may increase risk for schizophrenia by reducing expression of CDC42.
1. Schizophr Res. 2011 Feb;125(2-3):304-6. Epub 2010 Nov 26. A neuropsychological investigation o... more 1. Schizophr Res. 2011 Feb;125(2-3):304-6. Epub 2010 Nov 26. A neuropsychological investigation of the genome wide associated schizophrenia risk variant NRGN rs12807809. Donohoe G, Walters J, Morris DW, Da Costa A, Rose E, Hargreaves A, Maher K, Hayes E, Giegling I, Hartmann AM, Möller HJ, Muglia P, Moskvina V, Owen MJ, O'Donovan MC, Gill M, Corvin A, Rujescu D. PMID: 21112188 [PubMed - indexed for MEDLINE]. Publication Types: Letter; Research Support, Non-US Gov't. MeSH Terms. ...
Journal of the International Neuropsychological Society : JINS, 2009
Poor insight is associated with impaired cognitive function in psychosis. Whether poor clinical i... more Poor insight is associated with impaired cognitive function in psychosis. Whether poor clinical insight overlaps with other aspects of self-awareness in schizophrenia, such as cognitive self-awareness, is unclear. We investigated whether awareness of clinical state (“clinical insight”) and awareness of cognitive deficits (“cognitive insight”) overlap in schizophrenia in a sample of 51 stabilized patients with chronic schizophrenia. Cognitive insight was assessed in terms of the agreement between subjective self-report and neuropsychological assessment. Patients who show good cognitive insight did not necessarily show good clinical insight. By contrast, self-report and objective neuropsychological assessment only correlated for patients in the intact clinical insight group and not for those in the impairment clinical insight group. We conclude that while good cognitive insight may not be necessary for good clinical insight, good cognitive awareness is at least partly reliant on the processes involved in clinical insight. (JINS, 2009, 15, 471–475.)(Received August 20 2008)(Reviewed January 19 2009)(Accepted January 19 2009)
... Dr. Aiden Corvin, Professor Michael Gill and Dr Derek Morris conceived the study. ... Essling... more ... Dr. Aiden Corvin, Professor Michael Gill and Dr Derek Morris conceived the study. ... Esslinger, C., Walter, H., Kirsch, P., Erk, S., Schnell, K., Arnold, C., Haddad, L., Mier, D., Opitz von Boberfeld, C., Raab, K., Witt, SH, Rietschel, M., Cichon, S., Meyer-Lindenberg, A., 2009. ...
1. Schizophr Res. 2011 Feb;125(2-3):304-6. Epub 2010 Nov 26. A neuropsychological investigation o... more 1. Schizophr Res. 2011 Feb;125(2-3):304-6. Epub 2010 Nov 26. A neuropsychological investigation of the genome wide associated schizophrenia risk variant NRGN rs12807809. Donohoe G, Walters J, Morris DW, Da Costa A, Rose E, Hargreaves A, Maher K, Hayes E, Giegling I, Hartmann AM, Möller HJ, Muglia P, Moskvina V, Owen MJ, O'Donovan MC, Gill M, Corvin A, Rujescu D. PMID: 21112188 [PubMed - indexed for MEDLINE]. Publication Types: Letter; Research Support, Non-US Gov't. MeSH Terms. ...
Cognitive deficits are core to the disability associated with many psychiatric disorders. Both va... more Cognitive deficits are core to the disability associated with many psychiatric disorders. Both variation in cognition and psychiatric risk show substantial heritability, with overlapping genetic variants contributing to both. Unsurprisingly, therefore, these fields have been mutually beneficial: just as cognitive studies of psychiatric risk variants may identify genes involved in cognition, so too can genome-wide studies based on cognitive phenotypes lead to genes relevant to psychiatric aetiology. The purpose of this review is to consider the main issues involved in the phenotypic characterization of cognition, and to describe the challenges associated with the transition to genome-wide approaches. We conclude by describing the approaches currently being taken by the international consortia involving many investigators in the field internationally (e.g. Cognitive Genomics Consortium; COGENT) to overcome these challenges.(Received May 18 2012)(Revised September 20 2012)(Accepted October 11 2012)(Online publication November 30 2012)
Classification in psychiatry is heavily dependent on clinical symptoms and illness course. This i... more Classification in psychiatry is heavily dependent on clinical symptoms and illness course. This ignores the critical role that cognitive problems play in neuropsychiatric disorders affecting different domains across the lifespan, from ADHD and autism to schizophrenia and Alzheimers disease. At this point, it is unclear whether cognitive mechanisms are specific to disorders, whether multiple processes can contribute to the same disorder, or whether aberrant neural processing can result in many different phenotypic outcomes. Understanding this would allow us to better grasp normal as well as pathological brain function. This could inform diagnostics based on understanding of neurophysiological processes and the consequent development of new therapeutics. Genetics, and the development of genomic research, offers real opportunities to understand the molecular mechanisms relevant to cognition. This chapter defines and describes the main cognitive phenotypes, which are investigated in psychiatric disorders. We review evidence for their heritability and early progress in the field using cytogenetic, linkage and candidate gene-based research methodologies. With high-throughput genomics it is now possible to explore novel common and rare risk variants for psychiatric disorders and their role in cognitive function at a genome-wide level. We review the results of early genomic studies and discuss the novel insights that they are starting to provide. Finally, we review the analysis of whole-genome DNA sequence data and the challenges that this will bring for cognitive genomics research.
The world journal of biological psychiatry : the official journal of the World Federation of Societies of Biological Psychiatry, 2012
Objectives. SNP rs2473277 upstream of the cell division cycle 42 (CDC42) gene was associated with... more Objectives. SNP rs2473277 upstream of the cell division cycle 42 (CDC42) gene was associated with schizophrenia in a recent genome-wide association study (GWAS). Reduced expression of CDC42 in schizophrenia has previously been reported. Our objective was to test whether the associated SNP affected CDC42 expression. Methods. Two available SNP × gene expression datasets were accessed to test the effect of rs2473277 on CDC42 expression: (i) the mRNA by SNP Browser, which presents results of a genome-wide linkage study of gene expression, and (ii) the Genevar HapMap expression dataset. rs2473277 is in strong linkage disequilibrium (LD) with the SNP rs2473307 (r(2) = 0.96), which is predicted to affect transcription factor binding. rs2473307 was directly tested for allelic effects on gene expression using a gene reporter assay in a human neuronal cell line. Results. In both datasets, the schizophrenia risk allele at rs2473277 was associated with a reduction in CDC42 mRNA levels. In the reporter gene assay the risk allele at rs2473307 similarly reduced gene expression. Conclusions. We found evidence that rs2473307, in strong LD with the schizophrenia associated SNP rs2473277, is a functional variant at CDC42 that may increase risk for schizophrenia by reducing expression of CDC42.
1. Schizophr Res. 2011 Feb;125(2-3):304-6. Epub 2010 Nov 26. A neuropsychological investigation o... more 1. Schizophr Res. 2011 Feb;125(2-3):304-6. Epub 2010 Nov 26. A neuropsychological investigation of the genome wide associated schizophrenia risk variant NRGN rs12807809. Donohoe G, Walters J, Morris DW, Da Costa A, Rose E, Hargreaves A, Maher K, Hayes E, Giegling I, Hartmann AM, Möller HJ, Muglia P, Moskvina V, Owen MJ, O'Donovan MC, Gill M, Corvin A, Rujescu D. PMID: 21112188 [PubMed - indexed for MEDLINE]. Publication Types: Letter; Research Support, Non-US Gov't. MeSH Terms. ...
Journal of the International Neuropsychological Society : JINS, 2009
Poor insight is associated with impaired cognitive function in psychosis. Whether poor clinical i... more Poor insight is associated with impaired cognitive function in psychosis. Whether poor clinical insight overlaps with other aspects of self-awareness in schizophrenia, such as cognitive self-awareness, is unclear. We investigated whether awareness of clinical state (“clinical insight”) and awareness of cognitive deficits (“cognitive insight”) overlap in schizophrenia in a sample of 51 stabilized patients with chronic schizophrenia. Cognitive insight was assessed in terms of the agreement between subjective self-report and neuropsychological assessment. Patients who show good cognitive insight did not necessarily show good clinical insight. By contrast, self-report and objective neuropsychological assessment only correlated for patients in the intact clinical insight group and not for those in the impairment clinical insight group. We conclude that while good cognitive insight may not be necessary for good clinical insight, good cognitive awareness is at least partly reliant on the processes involved in clinical insight. (JINS, 2009, 15, 471–475.)(Received August 20 2008)(Reviewed January 19 2009)(Accepted January 19 2009)
... Dr. Aiden Corvin, Professor Michael Gill and Dr Derek Morris conceived the study. ... Essling... more ... Dr. Aiden Corvin, Professor Michael Gill and Dr Derek Morris conceived the study. ... Esslinger, C., Walter, H., Kirsch, P., Erk, S., Schnell, K., Arnold, C., Haddad, L., Mier, D., Opitz von Boberfeld, C., Raab, K., Witt, SH, Rietschel, M., Cichon, S., Meyer-Lindenberg, A., 2009. ...
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Papers by Gary Donohoe