Gary Donohoe | National University of Ireland, Galway (original) (raw)

Papers by Gary Donohoe

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. ...

Psychological medicine, 2012

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)

Current topics in behavioral neurosciences, 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.

Molecular psychiatry, 2012

NeuroImage, 2012

A common polymorphism within the nitric oxide sythanse-1 (NOS1) gene (rs6490121), initially ident... more A common polymorphism within the nitric oxide sythanse-1 (NOS1) gene (rs6490121), initially identified as risk variant for schizophrenia, has been associated with variation in working memory and IQ. Here we investigated how this variation might be mediated at the level of brain structure and function. In healthy individuals (N = 157), voxel based morphometry was used to compare grey matter (GM) volume between homozygous and heterozygous carriers of the 'G' allele (i.e. the allele associated with impaired cognition and schizophrenia risk) and homozygous carriers of the non-risk 'A' allele. Functional brain imaging data were also acquired from 48 participants during performance of a spatial working memory (SWM) task, and analysed to determine any effect of NOS1 risk status. An a priori region-of-interest analysis identified a significant reduction in ventromedial prefrontal GM volume in 'G' allele carriers. Risk carriers also exhibited altered patterns of activation in the prefrontal cortex, caudate, and superior parietal lobe, which were characteristic of abnormal increases in activation in frontoparietal working memory networks and a failure to disengage regions of the default mode network. These functional changes suggest a NOS1-mediated processing inefficiency, which may contribute to cognitive dysfunction in schizophrenia. While the mechanisms by which NOS1 may influence brain structure and/or function have not yet been well delineated, these data provide further evidence for a role of NOS1 in risk for schizophrenia via an impact upon cognitive function.

Human brain mapping, 2012

Background: The nitric oxide synthasase-1 gene (NOS1) has been implicated in mental disorders inc... more Background: The nitric oxide synthasase-1 gene (NOS1) has been implicated in mental disorders including schizophrenia and variation in cognition. The NOS1 variant rs6490121 identified in a genome wide association study of schizophrenia has recently been associated with variation in general intelligence and working memory in both patients and healthy participants. Whether this variant is also associated with variation in early sensory processing remains unclear. Methods: We investigated differences in the P1 visual evoked potential in a high density EEG study of 54 healthy participants. Given both NOS1's association with cognition and recent evidence that cognitive performance and P1 response are correlated, we investigated whether NOS1's effect on P1 response was independent of its effects on cognition using CANTAB's spatial working memory (SWM) task. Results: We found that carriers of the previously identified risk “G” allele showed significantly lower P1 responses than non-carriers. We also found that while P1 response and SWM performance were correlated, NOS1 continued to explain a significant proportion of variation in P1 response even when its effects on cognition were accounted for. Conclusion: The schizophrenia implicated NOS1 variants rs6490121 influences visual sensory processing as measured by the P1 response, either as part of the gene's pleiotropic effects on multiple aspects of brain function, or because of a primary influence on sensory processing that mediates the effects already seen in higher cognitive processes. Hum Brain Mapp, 2011. © 2011 Wiley-Liss, Inc.

European psychiatry : the journal of the Association of European Psychiatrists, 2010

This study examined associations between the tendency to ruminate and two polymorphisms: the Val6... more This study examined associations between the tendency to ruminate and two polymorphisms: the Val66Met polymorphism in the brain-derived neurotrophic factor (BDNF) gene and 5-HTTLPR polymorphism in the serotonin transporter gene (SLC6A4). Participants were a homogenous group of healthy, unmedicated, never depressed individuals with few current symptoms of depression (N = 71). Results indicated that met heterozygotes of the BDNF allele were significantly more likely to ruminate than individuals homozygous for the val BDNF allele. There was no association between rumination and the 5-HTTLPR polymorphism. Further, the interaction between the 5-HTTLPR and BDNF polymorphisms did not predict rumination. Results suggest that variation in the BDNF gene may contribute to the tendency to ruminate. Since this association exists in healthy adults, it may represent a susceptibility factor for affective disorders.

Frontiers in psychiatry, 2012

† Omar Mothersill and Sinead Kelly have contributed equally to this work.

Schizophrenia research, 2011

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. ...

Schizophrenia bulletin, 2010

As the first gene to have achieved genome-wide significance for psychosis, ZNF804A has predictabl... more As the first gene to have achieved genome-wide significance for psychosis, ZNF804A has predictably been a subject of intense research activity. We review the evidence to date for the association between schizophrenia and the original risk variant rs1344706 identified as well as additional common and rare variants at this locus. We describe the still scant literature on the biological function of ZNF804A and discuss the efforts being made to characterize and refine the associated phenotype using imaging and neuropsychological approaches. We conclude that ZNF804A is robustly, if modestly, associated with schizophrenia risk, with much work still remaining to elucidate its role in schizophrenia biology.

NeuroImage, 2011

ZNF804A risk allele is associated with relatively intact gray matter volume in patients with schi... more ZNF804A risk allele is associated with relatively intact gray matter volume in patients with schizophrenia, NeuroImage (2010),

European psychiatry : the journal of the Association of European Psychiatrists, 2010

Post hoc analysis of occupational attainment and performance on a standard neurocognitive battery... more Post hoc analysis of occupational attainment and performance on a standard neurocognitive battery suggests that performance on letter-number sequencing is strongly associated with work attainment. Letter-number sequencing may warrant further investigation as a clinically useful tool to inform decisions around vocational rehabilitation. #

Schizophrenia research, 2009

An association between deficits in executive control, particularly inhibitory control, and more s... more An association between deficits in executive control, particularly inhibitory control, and more severe negative and disorganised symptoms of schizophrenia has been widely reported. The importance of more basic aspects of attention, often referred to as 'vigilant' or 'sustained' attention, to this relationship remains unclear. This study examined the contribution of sustained attention to symptom severity using the Sustained Attention to Response Task (SART) in 69 patients with schizophrenia. We found that negative and disorganised symptom severity scores were correlated with sustained attention, working memory, and psychomotor speed. The ability to sustain attention significantly predicted variance in negative symptom severity but not disorganised symptoms, which were instead predicted by working memory performance. These data suggest that this component of attention at least partly explains variance in negative symptoms.

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)

Schizophrenia research, 2010

... 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. ...

Neuroscience Letters, 2010

Schizophrenia bulletin, 2013

Genetic variants associated with increased risk for schizophrenia (SZ) are hypothesized to be mor... more Genetic variants associated with increased risk for schizophrenia (SZ) are hypothesized to be more penetrant at the level of brain structure and function than at the level of behavior. However, to date the relative sensitivity of imaging vs cognitive measures of these variants has not been quantified. We considered effect sizes associated with cognitive and imaging studies of 9 robust SZ risk genes (DAOA, DISC1, DTNBP1, NRG1, RGS4, NRGN, CAC-NA1C, TCF4, and ZNF804A) published between January 2005-November 2011. Summary data was used to calculate estimates of effect size for each significant finding. The mean effect size for each study was categorized as small, medium, or large and the relative frequency of each category was compared between modalities and across genes. Random effects meta-analysis was used to consider the impact of experimental methodology on effect size. Imaging studies reported mostly medium or large effects, whereas cognitive investigations commonly reported small effects. Meta-analysis confirmed that imaging studies were associated with larger effects. Effect size estimates were negatively correlated with sample size but did not differ as a function of gene nor imaging modality. These observations support the notion that SZ risk variants show larger effects, and hence greater penetrance, when characterized using indices of brain structure and function than when indexed by cognitive measures. However, it remains to be established whether this holds true for individual risk variants, imaging modalities, or cognitive functions, and how such effects may be mediated by a relationship with sample size and other aspects of experimental variability.

Molecular psychiatry, 2013

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. ...

Psychological medicine, 2012

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)

Current topics in behavioral neurosciences, 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.

Molecular psychiatry, 2012

NeuroImage, 2012

A common polymorphism within the nitric oxide sythanse-1 (NOS1) gene (rs6490121), initially ident... more A common polymorphism within the nitric oxide sythanse-1 (NOS1) gene (rs6490121), initially identified as risk variant for schizophrenia, has been associated with variation in working memory and IQ. Here we investigated how this variation might be mediated at the level of brain structure and function. In healthy individuals (N = 157), voxel based morphometry was used to compare grey matter (GM) volume between homozygous and heterozygous carriers of the 'G' allele (i.e. the allele associated with impaired cognition and schizophrenia risk) and homozygous carriers of the non-risk 'A' allele. Functional brain imaging data were also acquired from 48 participants during performance of a spatial working memory (SWM) task, and analysed to determine any effect of NOS1 risk status. An a priori region-of-interest analysis identified a significant reduction in ventromedial prefrontal GM volume in 'G' allele carriers. Risk carriers also exhibited altered patterns of activation in the prefrontal cortex, caudate, and superior parietal lobe, which were characteristic of abnormal increases in activation in frontoparietal working memory networks and a failure to disengage regions of the default mode network. These functional changes suggest a NOS1-mediated processing inefficiency, which may contribute to cognitive dysfunction in schizophrenia. While the mechanisms by which NOS1 may influence brain structure and/or function have not yet been well delineated, these data provide further evidence for a role of NOS1 in risk for schizophrenia via an impact upon cognitive function.

Human brain mapping, 2012

Background: The nitric oxide synthasase-1 gene (NOS1) has been implicated in mental disorders inc... more Background: The nitric oxide synthasase-1 gene (NOS1) has been implicated in mental disorders including schizophrenia and variation in cognition. The NOS1 variant rs6490121 identified in a genome wide association study of schizophrenia has recently been associated with variation in general intelligence and working memory in both patients and healthy participants. Whether this variant is also associated with variation in early sensory processing remains unclear. Methods: We investigated differences in the P1 visual evoked potential in a high density EEG study of 54 healthy participants. Given both NOS1's association with cognition and recent evidence that cognitive performance and P1 response are correlated, we investigated whether NOS1's effect on P1 response was independent of its effects on cognition using CANTAB's spatial working memory (SWM) task. Results: We found that carriers of the previously identified risk “G” allele showed significantly lower P1 responses than non-carriers. We also found that while P1 response and SWM performance were correlated, NOS1 continued to explain a significant proportion of variation in P1 response even when its effects on cognition were accounted for. Conclusion: The schizophrenia implicated NOS1 variants rs6490121 influences visual sensory processing as measured by the P1 response, either as part of the gene's pleiotropic effects on multiple aspects of brain function, or because of a primary influence on sensory processing that mediates the effects already seen in higher cognitive processes. Hum Brain Mapp, 2011. © 2011 Wiley-Liss, Inc.

European psychiatry : the journal of the Association of European Psychiatrists, 2010

This study examined associations between the tendency to ruminate and two polymorphisms: the Val6... more This study examined associations between the tendency to ruminate and two polymorphisms: the Val66Met polymorphism in the brain-derived neurotrophic factor (BDNF) gene and 5-HTTLPR polymorphism in the serotonin transporter gene (SLC6A4). Participants were a homogenous group of healthy, unmedicated, never depressed individuals with few current symptoms of depression (N = 71). Results indicated that met heterozygotes of the BDNF allele were significantly more likely to ruminate than individuals homozygous for the val BDNF allele. There was no association between rumination and the 5-HTTLPR polymorphism. Further, the interaction between the 5-HTTLPR and BDNF polymorphisms did not predict rumination. Results suggest that variation in the BDNF gene may contribute to the tendency to ruminate. Since this association exists in healthy adults, it may represent a susceptibility factor for affective disorders.

Frontiers in psychiatry, 2012

† Omar Mothersill and Sinead Kelly have contributed equally to this work.

Schizophrenia research, 2011

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. ...

Schizophrenia bulletin, 2010

As the first gene to have achieved genome-wide significance for psychosis, ZNF804A has predictabl... more As the first gene to have achieved genome-wide significance for psychosis, ZNF804A has predictably been a subject of intense research activity. We review the evidence to date for the association between schizophrenia and the original risk variant rs1344706 identified as well as additional common and rare variants at this locus. We describe the still scant literature on the biological function of ZNF804A and discuss the efforts being made to characterize and refine the associated phenotype using imaging and neuropsychological approaches. We conclude that ZNF804A is robustly, if modestly, associated with schizophrenia risk, with much work still remaining to elucidate its role in schizophrenia biology.

NeuroImage, 2011

ZNF804A risk allele is associated with relatively intact gray matter volume in patients with schi... more ZNF804A risk allele is associated with relatively intact gray matter volume in patients with schizophrenia, NeuroImage (2010),

European psychiatry : the journal of the Association of European Psychiatrists, 2010

Post hoc analysis of occupational attainment and performance on a standard neurocognitive battery... more Post hoc analysis of occupational attainment and performance on a standard neurocognitive battery suggests that performance on letter-number sequencing is strongly associated with work attainment. Letter-number sequencing may warrant further investigation as a clinically useful tool to inform decisions around vocational rehabilitation. #

Schizophrenia research, 2009

An association between deficits in executive control, particularly inhibitory control, and more s... more An association between deficits in executive control, particularly inhibitory control, and more severe negative and disorganised symptoms of schizophrenia has been widely reported. The importance of more basic aspects of attention, often referred to as 'vigilant' or 'sustained' attention, to this relationship remains unclear. This study examined the contribution of sustained attention to symptom severity using the Sustained Attention to Response Task (SART) in 69 patients with schizophrenia. We found that negative and disorganised symptom severity scores were correlated with sustained attention, working memory, and psychomotor speed. The ability to sustain attention significantly predicted variance in negative symptom severity but not disorganised symptoms, which were instead predicted by working memory performance. These data suggest that this component of attention at least partly explains variance in negative symptoms.

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)

Schizophrenia research, 2010

... 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. ...

Neuroscience Letters, 2010

Schizophrenia bulletin, 2013

Genetic variants associated with increased risk for schizophrenia (SZ) are hypothesized to be mor... more Genetic variants associated with increased risk for schizophrenia (SZ) are hypothesized to be more penetrant at the level of brain structure and function than at the level of behavior. However, to date the relative sensitivity of imaging vs cognitive measures of these variants has not been quantified. We considered effect sizes associated with cognitive and imaging studies of 9 robust SZ risk genes (DAOA, DISC1, DTNBP1, NRG1, RGS4, NRGN, CAC-NA1C, TCF4, and ZNF804A) published between January 2005-November 2011. Summary data was used to calculate estimates of effect size for each significant finding. The mean effect size for each study was categorized as small, medium, or large and the relative frequency of each category was compared between modalities and across genes. Random effects meta-analysis was used to consider the impact of experimental methodology on effect size. Imaging studies reported mostly medium or large effects, whereas cognitive investigations commonly reported small effects. Meta-analysis confirmed that imaging studies were associated with larger effects. Effect size estimates were negatively correlated with sample size but did not differ as a function of gene nor imaging modality. These observations support the notion that SZ risk variants show larger effects, and hence greater penetrance, when characterized using indices of brain structure and function than when indexed by cognitive measures. However, it remains to be established whether this holds true for individual risk variants, imaging modalities, or cognitive functions, and how such effects may be mediated by a relationship with sample size and other aspects of experimental variability.

Molecular psychiatry, 2013