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Ventromedial prefrontal cortex mediates guessing

R Elliott, G Rees, R.J Dolan
1999 Neuropsychologia  
Guessing is an important component of everyday cognition[ The present study examined the neural substrates of guessing using a simple card!playing task in conjunction with functional magnetic resonance imaging "fMRI#[ Subjects were scanned under four conditions[ In two\ they were shown images of the back of a playing card and had to guess either the colour or the suit of the card[ In the other two they were shown the face of a card and had to report either the colour or the suit[ Guessing
more » ... ed to reporting was associated with signi_cant activations in lateral prefrontal cortex "right more than left#\ right orbitofrontal cortex\ anterior cingulate\ bilateral inferior parietal cortex and right thalamus[ Increasing the guessing demands by manipulating the number of alternative outcomes was associated with activation of the left lateral and medial orbitofrontal cortex[ These data suggest that while simple two choice guessing depends on an extensive neural system including regions of the right lateral prefrontal cortex\ activation of orbitofrontal cortex increases as the probabilistic contingencies become more complex[ Guessing thus involves not only systems implicated in working memory processes but also depends upon orbitofrontal cortex[ This region is not typically activated in working memory tasks and its activation may re~ect additional requirements of dealing with uncertainty[ Þ 0888 Elsevier Science Ltd[ All rights reserved[ Keywords] Decision!making^Working memory^Orbitofrontal cortex^Dorsolateral prefrontal cortex Corresponding author[ Tel[] ¦33 "9#060 722 6361^fax] ¦33 "9#060 702 0319^e!mail] r[elliottÝ_l [ion[ucl[ac[uk
doi:10.1016/s0028-3932(98)00107-9 pmid:10215087 fatcat:p75mxoti5jhx3gxwqogbjycotq

Authors' reply

Elliott Rees, James T. R. Walters, Michael J. Owen, George Kirov
2014 British Journal of Psychiatry  
Rees, MRes, James T.  ...  Email: doi: 10.1192/bjp.205.1.78 Kirov G, Rees E, Walters JT, Escott-Price V, Georgieva L, Richards AL, et al.  ... 
doi:10.1192/bjp.205.1.78 pmid:24986392 fatcat:edwkivnnrfeilkstjqcolgd7di

Genetics of schizophrenia

Elliott Rees, Michael C O'Donovan, Michael J Owen
2015 Current Opinion in Behavioral Sciences  
Szatkiewicz et al. [20] and Rees et al. [19] , respectively.  ...  It is established Genetics of Schizophrenia Rees, O'Donovan and Owen 9 de novo CNVs, SNVs and indels in ARC and NMDAR complexes.  ... 
doi:10.1016/j.cobeha.2014.07.001 fatcat:lxf4svy67bfxzdmxbxxx52p6e4

Enrichment of heavy REE and Th in carbonatite-derived fenite breccia

Sam Broom-Fendley, Holly AL Elliott, Charles D Beard, Frances Wall, Paul EB Armitage, Aoife E Brady, Eimear Deady, William Dawes
2021 Geological Magazine  
Enrichment of the heavy rare earth elements (HREE) in carbonatites is rare as carbonatite petrogenesis favours the light (L)REE.  ...  REE can be transferred from carbonatite into the surrounding fenite aureole (Dowman et al. 2017a; Elliott et al. 2018) or as small-scale (in situ) dissolution and reprecipitation of REE-bearing phases  ...  While the REE grades in fenite are typically low (Fig. 8b ; Elliott et al. 2018) , REE mineralization can still occur in this rock up to several kilometres from the parent carbonatite intrusion (Dowman  ... 
doi:10.1017/s0016756821000601 fatcat:5zpqkxewxfhwrb5hhe7yosraby

Translating insights from neuropsychiatric genetics and genomics for precision psychiatry

Elliott Rees, Michael J. Owen
2020 Genome Medicine  
The primary aim of precision medicine is to tailor healthcare more closely to the needs of individual patients. This requires progress in two areas: the development of more precise treatments and the ability to identify patients or groups of patients in the clinic for whom such treatments are likely to be the most effective. There is widespread optimism that advances in genomics will facilitate both of these endeavors. It can be argued that of all medical specialties psychiatry has most to gain
more » ... in these respects, given its current reliance on syndromic diagnoses, the minimal foundation of existing mechanistic knowledge, and the substantial heritability of psychiatric phenotypes. Here, we review recent advances in psychiatric genomics and assess the likely impact of these findings on attempts to develop precision psychiatry. Emerging findings indicate a high degree of polygenicity and that genetic risk maps poorly onto the diagnostic categories used in the clinic. The highly polygenic and pleiotropic nature of psychiatric genetics will impact attempts to use genomic data for prediction and risk stratification, and also poses substantial challenges for conventional approaches to gaining biological insights from genetic findings. While there are many challenges to overcome, genomics is building an empirical platform upon which psychiatry can now progress towards better understanding of disease mechanisms, better treatments, and better ways of targeting treatments to the patients most likely to benefit, thus paving the way for precision psychiatry.
doi:10.1186/s13073-020-00734-5 pmid:32349784 pmcid:PMC7189552 fatcat:66v5ee7nvrftthdgqfvid3w5n4

Immunological similarities between cytosolic and particulate tissue transglutaminase

C.R.L. Knight, R.C. Rees, B.M. Elliott, M. Griffin
1990 FEBS Letters  
doi:10.1016/0014-5793(90)80891-l pmid:1973123 fatcat:unghcoph3ngcjk74r6aveeplhq

What a psychiatrist needs to know about copy number variants

George Kirov, Elliott Rees, James Walters
2015 BJ Psych Advances  
Very similar mutation rates have also been estimated for the CNV loci associated with schizophrenia (Rees 2011) .  ...  The mutation rates for most Table 1 are indeed very high, ranging from 1:4000 to 1:26 000 newborns (Rees 2011) .  ... 
doi:10.1192/apt.bp.113.012039 fatcat:nlkegykjpbhidddqo4uwa62p5q

Schizophrenia-associated genomic copy number variants and subcortical brain volumes in the UK Biobank [article]

Anthony Warland, Kimberly Kendall, Elliott Rees, George Kirov, Xavier Caseras
2018 bioRxiv   pre-print
Schizophrenia (SZ) relative risk estimates for each CNV were taken from Rees et al 2016.  ... 
doi:10.1101/374678 fatcat:63qytno77jcjffc6n73nhrwmom

Uncommon low-grade brain tumors

Thankamma Ajithkumar, Naduni Imbulgoda, Elliott Rees, Fiona Harris, Gail Horan, Amos Burke, Sarah Jefferies, Stephen Price, Justin Cross, Kieren Allinson
2018 Neuro-Oncology  
The 2016 World Health Organization (WHO) classification of primary central nervous system (CNS) tumors includes numerous uncommon (representing ≤1% of tumors) low-grade (grades I-II) brain neoplasms with varying clinical behaviors and outcomes. Generally, gross tumor or maximal safe resection is the primary treatment. Adjuvant treatments, though their exact role is unknown, may be considered individually based on pathological subtypes and a proper assessment of risks and benefits. Targetable
more » ... ations such as BRAF (proto-oncogene B-Raf), TRAIL (tumor necrosis factor apoptosis inducing ligand), and PDGFR (platelet derived growth factor receptor) have promising roles in future management.
doi:10.1093/neuonc/noy151 pmid:30239861 pmcid:PMC6374757 fatcat:45ebz6zcjfh5ziyfsy7zl2vaam

The role of rare copy number variants in depression [article]

Kimberley M Kendall, Elliott Rees, Matthew Bracher-Smith, Lucy Riglin, Stanley Zammit, Michael C O'Donovan, Michael J Owen, Ian Jones, George Kirov, James TR Walters
2018 bioRxiv   pre-print
The role of large, rare copy number variants (CNVs) in neurodevelopmental disorders is well established, but their contribution to common psychiatric disorders, such as depression, remains unclear. We have previously shown that a substantial proportion of CNV enrichment in schizophrenia is explained by CNVs associated with neurodevelopmental disorders. Depression shares genetic risk with schizophrenia and is frequently comorbid with neurodevelopmental disorders, suggesting to us the hypothesis
more » ... hat if CNVs play a role in depression, neurodevelopmental CNVs are those most likely to be associated. We confirmed this in UK Biobank by showing that neurodevelopmental CNVs were associated with depression (24,575 cases, 5.87%; OR=1.36, 95% CI 1.22-1.51, p=1.61x10-8), whilst finding no evidence implicating other CNVs. Four individual neurodevelopmental CNVs increased risk of depression (1q21.1 duplication, PWS duplication, 16p13.11 deletion, 16p11.2 duplication). The association between neurodevelopmental CNVs and depression was partially explained by social deprivation but not by education attainment or physical illness.
doi:10.1101/378307 fatcat:cvywbojvozhrxmlnlmjvxtkf6u

Effects of pathogenic CNVs on biochemical markers: a study on the UK Biobank [article]

Matthew Bracher-Smith, Kimberley M Kendall, Elliott Rees, Mark Einon, Michael O'Donovan, Michael J Owen, George Kirov
2019 bioRxiv   pre-print
It . doi: bioRxiv preprint determined by selection pressure and mutation rates, rather than genetic drift (Rees et al, 2011) .  ... 
doi:10.1101/723270 fatcat:67ug67x37nhufjxete7xaokbpq

Heart transplantation for dilated cardiomyopathy

S S Adwani, B F Whitehead, P G Rees, P Whitmore, J W Fabre, M J Elliott, M R de Leval
1995 Archives of Disease in Childhood  
Between 1988 and 1994, 23 patients underwent heart transplantation for dilated cardiomyopathy. The age of the 13 boys and 10 girls was from 8 months to 16 years (mean 7*1 years). Selection criteria included failure to thrive despite maximal antifailure treatment and/or intravenous inotrope dependence. The aetiology of cardiomyopathy was idiopathic (n= 13), congenital (n=3), anthracycline induced (n=4), Barth's syndrome (n=l), and maternal systemic lupus erythematosus (n=2). The waiting period
more » ... heart transplantation ranged from one day to 147 days (mean 22 days). Maintenance immunosuppression included cyclosporin, azathioprine, and prednisolone. Follow up after transplantation was from one month to 62 months (median 27 months) with a mean actuarial survival of 95% at one year and 87% at three years. Four patients developed coronary artery disease, one of whom died as a consequence 15 months after heart transplantation. Heart transplantation has emerged as an acceptable therapeutic option, at least in the short term, for patients with dilated cardiomyopathy. (Arch Dis Child 1995; 73: 447-452)
doi:10.1136/adc.73.5.447 pmid:8554365 pmcid:PMC1511386 fatcat:kkwappzlcfb3dmux7am7ab2h2q

Effects of pathogenic CNVs on physical traits in participants of the UK Biobank [article]

David Owen, Mathew Bracher-Smith, Kimberley Kendall, Elliott Rees, Mark Einon, Valentina Escott-Price, Michael J Owen, Michael O'Donovan, George Kirov
2018 bioRxiv   pre-print
Genome Res., 17, 1665-1674. 29 Kendall,K.M., Rees,E., Escott-Price,V., Einon,M., Thomas,R., Hewitt,J., O'Donovan,M.C., Owen,M.J., Walters,J.T.R. and Kirov,G. (2017) Cognitive performance Among carriers  ...  ., Elliott,P. and Tzoulaki,I. (2017) Genetic Predisposition to High Blood Pressure and Lifestyle Factors: Associations With Midlife Blood Pressure Levels and Cardiovascular Events, Circulation., 137, 653  ... 
doi:10.1101/355297 fatcat:aolcrhxyibay7au7dvfzu5lsye

Schizophrenia-associated genomic copy number variants and subcortical brain volumes in the UK Biobank

Anthony Warland, Kimberley M. Kendall, Elliott Rees, George Kirov, Xavier Caseras
2019 Molecular Psychiatry  
Schizophrenia is a highly heritable disorder for which anatomical brain alterations have been repeatedly reported in clinical samples. Unaffected at-risk groups have also been studied in an attempt to identify brain changes that do not reflect reverse causation or treatment effects. However, no robust associations have been observed between neuroanatomical phenotypes and known genetic risk factors for schizophrenia. We tested subcortical brain volume differences between 49 unaffected
more » ... s carrying at least one of the 12 copy number variants associated with schizophrenia in UK Biobank and 9063 individuals who did not carry any of the 93 copy number variants reported to be pathogenic. Our results show that CNV carriers have reduced volume in some of the subcortical structures previously shown to be reduced in schizophrenia. Moreover, these associations partially accounted for the association between pathogenic copy number variants and cognitive impairment, which is one of the features of schizophrenia.
doi:10.1038/s41380-019-0355-y pmid:30679740 pmcid:PMC7156345 fatcat:u4vzkxwhhngu3m634wrssomohy

Genetic association of FMRP targets with psychiatric disorders [article]

Nicholas E Clifton, Elliott E Rees, Peter Holmans, Antonio F Pardinas, Janet C Harwood, Arianna Di Florio, George Kirov, James TR Walters, Michael C O'Donovan, Michael J Owen, Jeremy Hall, Andrew Pocklington
2020 bioRxiv   pre-print
Genes encoding the mRNA targets of Fragile X mental retardation protein (FMRP) are enriched for genetic association with psychiatric disorders. However, many FMRP targets possess functions that are themselves genetically associated with psychiatric disorders, including synaptic transmission and plasticity, making it unclear whether the genetic risk is truly related to binding by FMRP or is alternatively mediated by the sampling of genes better characterised by another trait or functional
more » ... ion. Using published common variant, rare coding variant and copy number variant data, we examined the relationship between FMRP binding and genetic association with schizophrenia, major depressive disorder and bipolar disorder. We then explored the partitioning of genetic association between overrepresented functional categories. High-confidence targets of FMRP were enriched for common schizophrenia risk alleles, as well as rare loss-of-function and de novo nonsynonymous variants in cases. Similarly, through common variation, FMRP targets were associated with major depressive disorder, and we present novel evidence of association with bipolar disorder. These relationships could not be explained by membership of other functional annotations known to be associated with psychiatric disorders, including those related to synaptic structure and function. This study reinforces the evidence that targeting by FMRP captures a subpopulation of genes enriched for genetic association with a range of psychiatric disorders, across traditional diagnostic boundaries.
doi:10.1101/2020.02.21.952226 fatcat:jefwon4y6naz7hje6g4qh4iewa
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