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Article: Systematic Review and Meta-Analysis of Damage Associated Molecular Patterns HMGB1 and S100B in Schizophrenia.

Mackey, Michael / Holleran, Laurena / Donohoe, Gary / McKernan, Declan P

2024 Volume 21, Issue 1, Page(s) 109

Language	English
Publishing date	2024-01-22
Publishing country	Korea (South)
Document type	Published Erratum
ZDB-ID	2414364-9
ISSN	1976-3026 ; 1738-3684
ISSN (online)	1976-3026
ISSN	1738-3684
DOI	10.30773/pi.2022.0173e
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Article: Systematic Review and Meta-Analysis of Damage Associated Molecular Patterns HMGB1 and S100B in Schizophrenia.

Mackey, Michael / Holleran, Laurena / Donohoe, Gary / McKernan, Declan P

Psychiatry investigation

2022 Volume 19, Issue 12, Page(s) 981–990

Abstract: Objective: Immune system dysregulation is hypothesised to be central to the aetiopathogenesis of schizophrenia; however, the role of sterile inflammation remains unclear. Damage associated molecular patterns are key initiators of sterile inflammation ... ...

Abstract	Objective: Immune system dysregulation is hypothesised to be central to the aetiopathogenesis of schizophrenia; however, the role of sterile inflammation remains unclear. Damage associated molecular patterns are key initiators of sterile inflammation and are detectable in peripheral blood. Methods: A defined systematic search of the Web of Science, PubMed, and Scopus was performed to identify adult case-control studies published between January 1990 and June 2022. Three studies consisting of 242 cases and 83 controls met inclusion for the systematic review and meta-analysis of HMGB1 while twenty-eight studies consisting of 1,544 cases and 1,248 healthy controls were included for S100B. Results: A significant standardised mean difference in peripheral S100B and HMGB1 concentrations was detected between cases and controls. S100B subgroup analysis determined the largest significant effect size for unmedicated individuals diagnosed with schizophrenia. Conclusion: This study provides evidence that peripheral S100B and HMGB1 concentrations are elevated in individuals diagnosed with schizophrenia when compared with healthy controls. These results should be interpreted with caution as significant heterogeneity was present during meta-analysis of S100B in the entire sample and in sub-group analysis. The persistence of significant heterogeneity throughout subgroup analysis indicates that the current diagnostic groupings may be a barrier to understanding human behaviours and emotions.
Language	English
Publishing date	2022-12-22
Publishing country	Korea (South)
Document type	Journal Article
ZDB-ID	2414364-9
ISSN	1976-3026 ; 1738-3684
ISSN (online)	1976-3026
ISSN	1738-3684
DOI	10.30773/pi.2022.0173
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Article ; Online: Thirteen Independent Genetic Loci Associated with Preserved Processing Speed in a Study of Cognitive Resilience in 330,097 Individuals in the UK Biobank.

Fitzgerald, Joan / Fahey, Laura / Holleran, Laurena / Ó Broin, Pilib / Donohoe, Gary / Morris, Derek W

Genes

2022 Volume 13, Issue 1

Abstract: Cognitive resilience is the ability to withstand the negative effects of stress on cognitive functioning and is important for maintaining quality of life while aging. The UK Biobank does not have measurements of the same cognitive phenotype at distal ... ...

Abstract	Cognitive resilience is the ability to withstand the negative effects of stress on cognitive functioning and is important for maintaining quality of life while aging. The UK Biobank does not have measurements of the same cognitive phenotype at distal time points. Therefore, we used education years (EY) as a proxy phenotype for past cognitive performance and current cognitive performance was based on processing speed. This represented an average time span of 40 years between past and current cognitive performance in 330,097 individuals. A confounding factor was that EY is highly polygenic and masked the genetics of resilience. To overcome this, we employed Genomics Structural Equation Modelling (GenomicSEM) to perform a genome-wide association study (GWAS)-by-subtraction using two GWAS, one GWAS of EY and resilience and a second GWAS of EY but not resilience, to generate a GWAS of
MeSH term(s)	Adaptation, Psychological ; Biological Specimen Banks ; Cognition/physiology ; Genetic Loci ; Genetic Predisposition to Disease ; Humans ; Memory/physiology ; Middle Aged ; Multifactorial Inheritance ; Polymorphism, Single Nucleotide ; Psychomotor Performance ; Resilience, Psychological ; United Kingdom
Language	English
Publishing date	2022-01-10
Publishing country	Switzerland
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2527218-4
ISSN	2073-4425 ; 2073-4425
ISSN (online)	2073-4425
ISSN	2073-4425
DOI	10.3390/genes13010122
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Article ; Online: Social isolation-induced transcriptomic changes in mouse hippocampus impact the synapse and show convergence with human genetic risk for neurodevelopmental phenotypes.

Laighneach, Aodán / Kelly, John P / Desbonnet, Lieve / Holleran, Laurena / Kerr, Daniel M / McKernan, Declan / Donohoe, Gary / Morris, Derek W

PloS one

2023 Volume 18, Issue 12, Page(s) e0295855

Abstract: Early life stress (ELS) can impact brain development and is a risk factor for neurodevelopmental disorders such as schizophrenia. Post-weaning social isolation (SI) is used to model ELS in animals, using isolation stress to disrupt a normal developmental ...

Abstract	Early life stress (ELS) can impact brain development and is a risk factor for neurodevelopmental disorders such as schizophrenia. Post-weaning social isolation (SI) is used to model ELS in animals, using isolation stress to disrupt a normal developmental trajectory. We aimed to investigate how SI affects the expression of genes in mouse hippocampus and to investigate how these changes related to the genetic basis of neurodevelopmental phenotypes. BL/6J mice were exposed to post-weaning SI (PD21-25) or treated as group-housed controls (n = 7-8 per group). RNA sequencing was performed on tissue samples from the hippocampus of adult male and female mice. Four hundred and 1,215 differentially-expressed genes (DEGs) at a false discovery rate of < 0.05 were detected between SI and control samples for males and females respectively. DEGS for both males and females were significantly overrepresented in gene ontologies related to synaptic structure and function, especially the post-synapse. DEGs were enriched for common variant (SNP) heritability in humans that contributes to risk of neuropsychiatric disorders (schizophrenia, bipolar disorder) and to cognitive function. DEGs were also enriched for genes harbouring rare de novo variants that contribute to autism spectrum disorder and other developmental disorders. Finally, cell type analysis revealed populations of hippocampal astrocytes that were enriched for DEGs, indicating effects in these cell types as well as neurons. Overall, these data suggest a convergence between genes dysregulated by the SI stressor in the mouse and genes associated with neurodevelopmental disorders and cognitive phenotypes in humans.
MeSH term(s)	Adult ; Humans ; Male ; Animals ; Mice ; Female ; Autism Spectrum Disorder ; Gene Expression Profiling ; Hippocampus/metabolism ; Social Isolation ; Synapses ; Phenotype ; Risk Factors ; Human Genetics
Language	English
Publishing date	2023-12-21
Publishing country	United States
Document type	Journal Article
ZDB-ID	2267670-3
ISSN	1932-6203 ; 1932-6203
ISSN (online)	1932-6203
ISSN	1932-6203
DOI	10.1371/journal.pone.0295855
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Article ; Online: The impact of early adversity and education on genetic and brain morphological predictors of cognitive ability.

Corley, Emma / Fahey, Laura / Fitzgerald, Joan / Holleran, Laurena / Walton, Esther / Morris, Derek W / Donohoe, Gary

Genes, brain, and behavior

2023 Volume 22, Issue 4, Page(s) e12850

Abstract: Cognitive ability is a strong predictor of occupational achievement, quality of life and physical health. While variation in cognition is strongly heritable and has been robustly associated with early environment and brain morphology, little is known ... ...

Abstract	Cognitive ability is a strong predictor of occupational achievement, quality of life and physical health. While variation in cognition is strongly heritable and has been robustly associated with early environment and brain morphology, little is known about how these factors combine and interact to explain this variation in cognition. To address this, we modelled the relationship between common genetic variation, grey matter volume, early life adversity and education and cognitive ability in a UK Biobank sample of N = 5237 individuals using structural equation modelling. We tested the hypotheses that total grey matter volume would mediate the association between genetic variation and cognitive ability, and that early life adversity and educational attainment would moderate this relationship. Common genetic variation, grey matter volume and early life adversity were each significant predictors in the model, explaining ~15% of variation in cognitive ability. Contrary to our hypothesis, grey matter volume did not mediate the relation between genetic variation and cognition performance. Neither did early life adversity or educational attainment moderate this relation, although educational attainment was observed to moderate the relationship between grey matter volume and cognitive performance. We interpret these findings in terms of the modest explanatory value of currently estimated polygenic scores accounting for variation in cognitive performance (~5%), making potential mediating and moderating variables difficult to confirm.
MeSH term(s)	Humans ; Quality of Life ; Cognition ; Educational Status ; Academic Success ; Gray Matter/diagnostic imaging ; Brain
Language	English
Publishing date	2023-07-04
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2075819-4
ISSN	1601-183X ; 1601-1848
ISSN (online)	1601-183X
ISSN	1601-1848
DOI	10.1111/gbb.12850
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Article: Thirteen Independent Genetic Loci Associated with Preserved Processing Speed in a Study of Cognitive Resilience in 330,097 Individuals in the UK Biobank

Fitzgerald, Joan / Fahey, Laura / Holleran, Laurena / Ó Broin, Pilib / Donohoe, Gary / Morris, Derek W.

Genes. 2022 Jan. 10, v. 13, no. 1

2022

Abstract	Cognitive resilience is the ability to withstand the negative effects of stress on cognitive functioning and is important for maintaining quality of life while aging. The UK Biobank does not have measurements of the same cognitive phenotype at distal time points. Therefore, we used education years (EY) as a proxy phenotype for past cognitive performance and current cognitive performance was based on processing speed. This represented an average time span of 40 years between past and current cognitive performance in 330,097 individuals. A confounding factor was that EY is highly polygenic and masked the genetics of resilience. To overcome this, we employed Genomics Structural Equation Modelling (GenomicSEM) to perform a genome-wide association study (GWAS)-by-subtraction using two GWAS, one GWAS of EY and resilience and a second GWAS of EY but not resilience, to generate a GWAS of Resilience. Using independent discovery and replication samples, we found 13 independent genetic loci for Resilience. Functional analyses showed enrichment in several brain regions and specific cell types. Gene-set analyses implicated the biological process “neuron differentiation”, the cellular component “synaptic part” and the “WNT signalosome”. Mendelian randomisation analysis showed a causative effect of white matter volume on cognitive resilience. These results may contribute to the neurobiological understanding of resilience.
Keywords	brain ; cognition ; education ; equations ; genome-wide association study ; genomics ; phenotype ; quality of life
Language	English
Dates of publication	2022-0110
Publishing place	Multidisciplinary Digital Publishing Institute
Document type	Article
ZDB-ID	2527218-4
ISSN	2073-4425
ISSN	2073-4425
DOI	10.3390/genes13010122
Database	NAL-Catalogue (AGRICOLA)

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Article ; Online: Correction to: Progressive subcortical volume loss in treatment-resistant schizophrenia patients after commencing clozapine treatment.

Tronchin, Giulia / Akudjedu, Theophilus N / Ahmed, Mohamed / Holleran, Laurena / Hallahan, Brian / Cannon, Dara M / McDonald, Colm

Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology

2021 Volume 46, Issue 10, Page(s) 1857–1858

Language	English
Publishing date	2021-06-24
Publishing country	England
Document type	Published Erratum
ZDB-ID	639471-1
ISSN	1740-634X ; 0893-133X
ISSN (online)	1740-634X
ISSN	0893-133X
DOI	10.1038/s41386-021-01062-x
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Article ; Online: Corrigendum to 'Childhood trauma is associated with altered white matter microstructural organization in schizophrenia' Psychiatry Research: Neuroimaging, 330 (2023) 111616.

Costello, Laura / Dauvermann, Maria R / Tronchin, Giulia / Holleran, Laurena / Mothersill, David / Rokita, Karolina I / Kane, Ruán / Hallahan, Brian / Corvin, Aiden / Morris, Derek / McKernan, Declan P / Kelly, John / McDonald, Colm / Donohoe, Gary / Cannon, Dara M

Psychiatry research. Neuroimaging

2023 Volume 332, Page(s) 111639

Language	English
Publishing date	2023-04-05
Publishing country	Netherlands
Document type	Published Erratum
ZDB-ID	445361-x
ISSN	1872-7506 ; 1872-7123 ; 0925-4927 ; 0165-1781
ISSN (online)	1872-7506 ; 1872-7123
ISSN	0925-4927 ; 0165-1781
DOI	10.1016/j.pscychresns.2023.111639
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Article ; Online: Microglial-expressed genetic risk variants, cognitive function and brain volume in patients with schizophrenia and healthy controls.

Corley, Emma / Holleran, Laurena / Fahey, Laura / Corvin, Aiden / Morris, Derek W / Donohoe, Gary

Translational psychiatry

2021 Volume 11, Issue 1, Page(s) 490

Abstract: Changes in immune function are associated with variance in cognitive functioning in schizophrenia. Given that microglia are the primary innate immune cells in the brain, we examined whether schizophrenia risk-associated microglial genes (measured via ... ...

Abstract	Changes in immune function are associated with variance in cognitive functioning in schizophrenia. Given that microglia are the primary innate immune cells in the brain, we examined whether schizophrenia risk-associated microglial genes (measured via polygenic score analysis) explained variation in cognition in patients with schizophrenia and controls (n = 1,238) and tested whether grey matter mediated this association. We further sought to replicate these associations in an independent sample of UK Biobank participants (n = 134,827). We then compared the strength of these microglial associations to that of neuronal and astroglial (i.e., other brain-expressed genes) polygenic scores, and used MAGMA to test for enrichment of these gene-sets with schizophrenia risk. Increased microglial schizophrenia polygenic risk was associated with significantly lower performance across several measures of cognitive functioning in both samples; associations which were then found to be mediated via total grey matter volume in the UK Biobank. Unlike neuronal genes which did show evidence of enrichment, the microglial gene-set was not significantly enriched for schizophrenia, suggesting that the relevance of microglia may be for neurodevelopmental processes related more generally to cognition. Further, the microglial polygenic score was associated with performance on a range of cognitive measures in a manner comparable to the neuronal schizophrenia polygenic score, with fewer cognitive associations observed for the astroglial score. In conclusion, our study supports the growing evidence of the importance of immune processes to understanding cognition and brain structure in both patients and in the healthy population.
MeSH term(s)	Brain/diagnostic imaging ; Cognition ; Genetic Predisposition to Disease ; Genome-Wide Association Study ; Humans ; Microglia ; Multifactorial Inheritance ; Schizophrenia/genetics
Language	English
Publishing date	2021-09-23
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2609311-X
ISSN	2158-3188 ; 2158-3188
ISSN (online)	2158-3188
ISSN	2158-3188
DOI	10.1038/s41398-021-01616-z
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Article ; Online: Cognitive Predictors of Social and Occupational Functioning in Early Psychosis: A Systematic Review and Meta-analysis of Cross-Sectional and Longitudinal Data.

Cowman, Megan / Holleran, Laurena / Lonergan, Edgar / O'Connor, Karen / Birchwood, Max / Donohoe, Gary

Schizophrenia bulletin

2021 Volume 47, Issue 5, Page(s) 1243–1253

Abstract: Many individuals with early psychosis experience impairments in social and occupational function. Identification of modifiable predictors of function such as cognitive performance has the potential to inform effective treatments. Our aim was to estimate ... ...

Abstract	Many individuals with early psychosis experience impairments in social and occupational function. Identification of modifiable predictors of function such as cognitive performance has the potential to inform effective treatments. Our aim was to estimate the strength of the relationship between psychosocial function in early psychosis and different domains of cognitive and social cognitive performance. We conducted a systematic review and meta-analysis of peer-reviewed, cross-sectional, and longitudinal studies examining cognitive predictors of psychosocial function. Literature searches were conducted in PsycINFO, PubMed, and reference lists of relevant articles to identify studies for inclusion. Of the 2565 identified, 46 studies comprising 3767 participants met inclusion criteria. Separate meta-analyses were conducted for 9 cognitive domains. Pearson correlation values between cognitive variables and function were extracted. All cognitive domains were related to psychosocial function both cross-sectionally and longitudinally. Importantly, these associations remained significant even after the effects of symptom severity, duration of untreated psychosis, and length of illness were accounted for. Overall, general cognitive ability and social cognition were most strongly associated with both concurrent and long-term function. Associations demonstrated medium effect sizes. These findings suggest that treatments targeting cognitive deficits, in particular those focusing on social cognition, are likely to be important for improving functional outcomes in early psychosis.
MeSH term(s)	Cognitive Dysfunction/etiology ; Cognitive Dysfunction/physiopathology ; Cross-Sectional Studies ; Employment ; Humans ; Longitudinal Studies ; Psychosocial Functioning ; Psychotic Disorders/complications ; Psychotic Disorders/physiopathology ; Social Cognition
Language	English
Publishing date	2021-07-05
Publishing country	United States
Document type	Journal Article ; Meta-Analysis ; Research Support, Non-U.S. Gov't ; Systematic Review
ZDB-ID	439173-1
ISSN	1745-1701 ; 0586-7614
ISSN (online)	1745-1701
ISSN	0586-7614
DOI	10.1093/schbul/sbab033
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