34 results on '"Smart, Sophie E"'
Search Results
2. Treatment resistance NMDA receptor pathway polygenic score is associated with brain glutamate in schizophrenia
- Author
-
Griffiths, Kira, Smart, Sophie E., Barker, Gareth J., Deakin, Bill, Lawrie, Stephen M., Lewis, Shon, Lythgoe, David J., Pardiñas, Antonio F., Singh, Krishna, Semple, Scott, Walters, James T.R., Williams, Stephen R., Egerton, Alice, and MacCabe, James H. more...
- Published
- 2023
- Full Text
- View/download PDF
Catalog
3. Cognitive performance at first episode of psychosis and the relationship with future treatment resistance: Evidence from an international prospective cohort study
- Author
-
Millgate, Edward, Smart, Sophie E., Pardiñas, Antonio F., Kravariti, Eugenia, Ajnakina, Olesya, Kępińska, Adrianna P., Andreassen, Ole A., Barnes, Thomas R.E., Berardi, Domenico, Crespo-Facorro, Benedicto, D'Andrea, Giuseppe, Demjaha, Arsime, Di Forti, Marta, Doody, Gillian A., Kassoumeri, Laura, Ferchiou, Aziz, Guidi, Lorenzo, Joyce, Eileen M., Lastrina, Ornella, Melle, Ingrid, Pignon, Baptiste, Richard, Jean-Romain, Simonsen, Carmen, Szöke, Andrei, Tarricone, Ilaria, Tortelli, Andrea, Vázquez-Bourgon, Javier, Murray, Robin M., Walters, James T.R., and MacCabe, James H. more...
- Published
- 2023
- Full Text
- View/download PDF
4. Gene set enrichment analysis of pathophysiological pathways highlights oxidative stress in psychosis
- Author
-
Pistis, Giorgio, Vázquez-Bourgon, Javier, Fournier, Margot, Jenni, Raoul, Cleusix, Martine, Papiol, Sergi, Smart, Sophie E., Pardiñas, Antonio F., Walters, James T. R., MacCabe, James H., Kutalik, Zoltán, Conus, Philippe, Crespo-Facorro, Benedicto, and Q Do, Kim more...
- Published
- 2022
- Full Text
- View/download PDF
5. Clinical predictors of antipsychotic treatment resistance: Development and internal validation of a prognostic prediction model by the STRATA-G consortium
- Author
-
Smart, Sophie E., Agbedjro, Deborah, Pardiñas, Antonio F., Ajnakina, Olesya, Alameda, Luis, Andreassen, Ole A., Barnes, Thomas R.E., Berardi, Domenico, Camporesi, Sara, Cleusix, Martine, Conus, Philippe, Crespo-Facorro, Benedicto, D'Andrea, Giuseppe, Demjaha, Arsime, Di Forti, Marta, Do, Kim, Doody, Gillian, Eap, Chin B., Ferchiou, Aziz, Guidi, Lorenzo, Homman, Lina, Jenni, Raoul, Joyce, Eileen, Kassoumeri, Laura, Lastrina, Ornella, Melle, Ingrid, Morgan, Craig, O'Neill, Francis A., Pignon, Baptiste, Restellini, Romeo, Richard, Jean-Romain, Simonsen, Carmen, Španiel, Filip, Szöke, Andrei, Tarricone, Ilaria, Tortelli, Andrea, Üçok, Alp, Vázquez-Bourgon, Javier, Murray, Robin M., Walters, James T.R., Stahl, Daniel, and MacCabe, James H. more...
- Published
- 2022
- Full Text
- View/download PDF
6. Artificial Intelligence for Analyzing Psychiatric Disorders in Social Media: A Quarter-Century Narrative Review of Progress and Challenges (Preprint)
- Author
-
Owen, David, primary, Lynham, Amy J, additional, Smart, Sophie E, additional, Pardiñas, Antonio F, additional, and Camacho Collados, Jose, additional
- Published
- 2024
- Full Text
- View/download PDF
7. Assessing the validity of a self-reported clinical diagnosis of schizophrenia
- Author
-
Woolway, Grace E, primary, Legge, Sophie E, additional, Lynham, Amy, additional, Smart, Sophie E, additional, Hubbard, Leon, additional, Daniel, Ellie R, additional, Pardinas, Antonio F, additional, Escott-Price, Valentina F, additional, O'Donovan, Michael C, additional, Owen, Michael J, additional, Jones, Ian R, additional, and Walters, James TR, additional more...
- Published
- 2023
- Full Text
- View/download PDF
8. Gene set enrichment analysis of pathophysiological pathways highlights oxidative stress in psychosis
- Author
-
National Centres of Competence in Research (Switzerland), Swiss National Science Foundation, Fondation Alamaya, European Commission, Instituto de Salud Carlos III, Ministerio de Sanidad (España), Fundació Seny, Fundación Marques de Valdecilla, Ministerio de Economía y Competitividad (España), Comisión Asesora de Investigación Científica y Técnica, CAICYT (España), Instituto de Investigación Marqués de Valdecilla, Université de Lausanne, Pistis, Giorgio [0000-0002-4525-4608], Vázquez-Bourgon, Javier [0000-0002-5478-3376], Papiol, Sergi [0000-0001-9366-8728], Smart, Sophie E. [0000-0002-6709-5425], Pardiñas, Antonio F. [0000-0001-6845-7590], MacCabe, James H. [0000-0002-6754-1018], Kutalik, Zoltán [0000-0001-8285-7523], Do, Kim Q. [0000-0003-1968-1646], Pistis, Giorgio, Vázquez-Bourgon, Javier, Fournier, Margot, Jenni, Raoul, Cleusix, Martine, Papiol, Sergi, Smart, Sophie E., Pardiñas, Antonio F., Walters, James T. R., MacCabe, James H., Kutalik, Zoltán, Conus, Philippe, Crespo-Facorro, Benedicto, Do, Kim Q., National Centres of Competence in Research (Switzerland), Swiss National Science Foundation, Fondation Alamaya, European Commission, Instituto de Salud Carlos III, Ministerio de Sanidad (España), Fundació Seny, Fundación Marques de Valdecilla, Ministerio de Economía y Competitividad (España), Comisión Asesora de Investigación Científica y Técnica, CAICYT (España), Instituto de Investigación Marqués de Valdecilla, Université de Lausanne, Pistis, Giorgio [0000-0002-4525-4608], Vázquez-Bourgon, Javier [0000-0002-5478-3376], Papiol, Sergi [0000-0001-9366-8728], Smart, Sophie E. [0000-0002-6709-5425], Pardiñas, Antonio F. [0000-0001-6845-7590], MacCabe, James H. [0000-0002-6754-1018], Kutalik, Zoltán [0000-0001-8285-7523], Do, Kim Q. [0000-0003-1968-1646], Pistis, Giorgio, Vázquez-Bourgon, Javier, Fournier, Margot, Jenni, Raoul, Cleusix, Martine, Papiol, Sergi, Smart, Sophie E., Pardiñas, Antonio F., Walters, James T. R., MacCabe, James H., Kutalik, Zoltán, Conus, Philippe, Crespo-Facorro, Benedicto, and Do, Kim Q. more...
- Abstract
Polygenic risk prediction remains an important aim of genetic association studies. Currently, the predictive power of schizophrenia polygenic risk scores (PRSs) is not large enough to allow highly accurate discrimination between cases and controls and thus is not adequate for clinical integration. Since PRSs are rarely used to reveal biological functions or to validate candidate pathways, to fill this gap, we investigated whether their predictive ability could be improved by building genome-wide (GW-PRSs) and pathway-specific PRSs, using distance- or expression quantitative trait loci (eQTLs)- based mapping between genetic variants and genes. We focused on five pathways (glutamate, oxidative stress, GABA/interneurons, neuroimmune/neuroinflammation and myelin) which belong to a critical hub of schizophrenia pathophysiology, centred on redox dysregulation/oxidative stress. Analyses were first performed in the Lausanne Treatment and Early Intervention in Psychosis Program (TIPP) study (n = 340, cases/controls: 208/132), a sample of first-episode of psychosis patients and matched controls, and then validated in an independent study, the epidemiological and longitudinal intervention program of First-Episode Psychosis in Cantabria (PAFIP) (n = 352, 224/128). Our results highlighted two main findings. First, GW-PRSs for schizophrenia were significantly associated with early psychosis status. Second, oxidative stress was the only significantly associated pathway that showed an enrichment in both the TIPP (p = 0.03) and PAFIP samples (p = 0.002), and exclusively when gene-variant linking was done using eQTLs. The results suggest that the predictive accuracy of polygenic risk scores could be improved with the inclusion of information from functional annotations, and through a focus on specific pathways, emphasizing the need to build and study functionally informed risk scores. more...
- Published
- 2022
9. AI for Analyzing Mental Health Disorders Among Social Media Users: Quarter-Century Narrative Review of Progress and Challenges.
- Author
-
Owen, David, Lynham, Amy J, Smart, Sophie E, Pardiñas, Antonio F, and Camacho Collados, Jose
- Subjects
MENTAL health services ,SOCIAL media ,NATURAL language processing ,MENTAL illness ,SOCIAL status - Abstract
Background: Mental health disorders are currently the main contributor to poor quality of life and years lived with disability. Symptoms common to many mental health disorders lead to impairments or changes in the use of language, which are observable in the routine use of social media. Detection of these linguistic cues has been explored throughout the last quarter century, but interest and methodological development have burgeoned following the COVID-19 pandemic. The next decade may see the development of reliable methods for predicting mental health status using social media data. This might have implications for clinical practice and public health policy, particularly in the context of early intervention in mental health care. Objective: This study aims to examine the state of the art in methods for predicting mental health statuses of social media users. Our focus is the development of artificial intelligence–driven methods, particularly natural language processing, for analyzing large volumes of written text. This study details constraints affecting research in this area. These include the dearth of high-quality public datasets for methodological benchmarking and the need to adopt ethical and privacy frameworks acknowledging the stigma experienced by those with a mental illness. Methods: A Google Scholar search yielded peer-reviewed articles dated between 1999 and 2024. We manually grouped the articles by 4 primary areas of interest: datasets on social media and mental health, methods for predicting mental health status, longitudinal analyses of mental health, and ethical aspects of the data and analysis of mental health. Selected articles from these groups formed our narrative review. Results: Larger datasets with precise dates of participants' diagnoses are needed to support the development of methods for predicting mental health status, particularly in severe disorders such as schizophrenia. Inviting users to donate their social media data for research purposes could help overcome widespread ethical and privacy concerns. In any event, multimodal methods for predicting mental health status appear likely to provide advancements that may not be achievable using natural language processing alone. Conclusions: Multimodal methods for predicting mental health status from voice, image, and video-based social media data need to be further developed before they may be considered for adoption in health care, medical support, or as consumer-facing products. Such methods are likely to garner greater public confidence in their efficacy than those that rely on text alone. To achieve this, more high-quality social media datasets need to be made available and privacy concerns regarding the use of these data must be formally addressed. A social media platform feature that invites users to share their data upon publication is a possible solution. Finally, a review of literature studying the effects of social media use on a user's depression and anxiety is merited. [ABSTRACT FROM AUTHOR] more...
- Published
- 2024
- Full Text
- View/download PDF
10. Clinical correlates of early onset antipsychotic treatment resistance
- Author
-
Fonseca de Freitas, Daniela, primary, Agbedjro, Deborah, additional, Kadra-Scalzo, Giouliana, additional, Francis, Emma, additional, Ridler, Isobel, additional, Pritchard, Megan, additional, Shetty, Hitesh, additional, Segev, Aviv, additional, Casetta, Cecilia, additional, Smart, Sophie E., additional, Morris, Anna, additional, Downs, Johnny, additional, Christensen, Søren Rahn, additional, Bak, Nikolaj, additional, Kinon, Bruce J., additional, Stahl, Daniel, additional, Hayes, Richard D., additional, and MacCabe, James H., additional more...
- Published
- 2022
- Full Text
- View/download PDF
11. A predictor model of treatment resistance in schizophrenia using data from electronic health records
- Author
-
Kadra-Scalzo, Giouliana, primary, Fonseca de Freitas, Daniela, additional, Agbedjro, Deborah, additional, Francis, Emma, additional, Ridler, Isobel, additional, Pritchard, Megan, additional, Shetty, Hitesh, additional, Segev, Aviv, additional, Casetta, Cecilia, additional, Smart, Sophie E., additional, Morris, Anna, additional, Downs, Johnny, additional, Christensen, Søren Rahn, additional, Bak, Nikolaj, additional, Kinon, Bruce J., additional, Stahl, Daniel, additional, Hayes, Richard D., additional, and MacCabe, James H., additional more...
- Published
- 2022
- Full Text
- View/download PDF
12. A Volunteer-Run, Face-to-Face, Early Intervention Service for Reducing Suicidality
- Author
-
Smart, Sophie E., primary, Dimes, Hollie, additional, Lumley, Cordelia, additional, Spooner, Steve, additional, Anderson, Sarah, additional, Platt, Stephen, additional, and Davidson, Sarah, additional more...
- Published
- 2022
- Full Text
- View/download PDF
13. Corrigendum to “Cognitive performance at first episode of psychosis and the relationship with future treatment resistance: Evidence from an international prospective cohort study” [Schizophr. Res. volume 225 (May 2023) 173–181]
- Author
-
Millgate, Edward, Smart, Sophie E., Pardiñas, Antonio F., Kravariti, Eugenia, Ajnakina, Olesya, Kępińska, Adrianna P., Andreassen, Ole A., Barnes, Thomas R.E., Berardi, Domenico, Crespo-Facorro, Benedicto, D'Andrea, Giuseppe, Demjaha, Arsime, Di Forti, Marta, Doody, Gillian A., Üçok, Alp, Kassoumeri, Laura, Ferchiou, Aziz, Guidi, Lorenzo, Joyce, Eileen M., Lastrina, Ornella, Melle, Ingrid, Pignon, Baptiste, Richard, Jean-Romain, Simonsen, Carmen, Szöke, Andrei, Tarricone, Ilaria, Tortelli, Andrea, Vázquez-Bourgon, Javier, Murray, Robin M., Walters, James T.R., and MacCabe, James H. more...
- Published
- 2024
- Full Text
- View/download PDF
14. Interaction Testing and Polygenic Risk Scoring to Estimate the Association of Common Genetic Variants With Treatment Resistance in Schizophrenia
- Author
-
Pardiñas, Antonio F., Smart, Sophie E., Willcocks, Isabella R., Holmans, Peter A., Dennison, Charlotte A., Lynham, Amy J., Legge, Sophie E., Baune, Bernhard T., Bigdeli, Tim B., Cairns, Murray J., Corvin, Aiden, Fanous, Ayman H., Frank, Josef, Kelly, Brian, McQuillin, Andrew, Melle, Ingrid, Mortensen, Preben B., Mowry, Bryan J., Pato, Carlos N., Periyasamy, Sathish, Rietschel, Marcella, Rujescu, Dan, Simonsen, Carmen, St Clair, David, Tooney, Paul, Wu, Jing Qin, Andreassen, Ole A., Kowalec, Kaarina, Sullivan, Patrick F., Murray, Robin M., Owen, Michael J., MacCabe, James H., O’Donovan, Michael C., Walters, James T. R., Ripke, Stephan, Neale, Benjamin M., Farh, Kai-How, Lee, Phil, Bulik-Sullivan, Brendan, Collier, David A., Huang, Hailiang, Pers, Tune H., Agartz, Ingrid, Agerbo, Esben, Albus, Margot, Alexander, Madeline, Amin, Farooq, Bacanu, Silviu A., Begemann, Martin, Homman, Lina, Belliveau, Richard A ., Pardiñas, Antonio F., Smart, Sophie E., Willcocks, Isabella R., Holmans, Peter A., Dennison, Charlotte A., Lynham, Amy J., Legge, Sophie E., Baune, Bernhard T., Bigdeli, Tim B., Cairns, Murray J., Corvin, Aiden, Fanous, Ayman H., Frank, Josef, Kelly, Brian, McQuillin, Andrew, Melle, Ingrid, Mortensen, Preben B., Mowry, Bryan J., Pato, Carlos N., Periyasamy, Sathish, Rietschel, Marcella, Rujescu, Dan, Simonsen, Carmen, St Clair, David, Tooney, Paul, Wu, Jing Qin, Andreassen, Ole A., Kowalec, Kaarina, Sullivan, Patrick F., Murray, Robin M., Owen, Michael J., MacCabe, James H., O’Donovan, Michael C., Walters, James T. R., Ripke, Stephan, Neale, Benjamin M., Farh, Kai-How, Lee, Phil, Bulik-Sullivan, Brendan, Collier, David A., Huang, Hailiang, Pers, Tune H., Agartz, Ingrid, Agerbo, Esben, Albus, Margot, Alexander, Madeline, Amin, Farooq, Bacanu, Silviu A., Begemann, Martin, Homman, Lina, and Belliveau, Richard A . more...
- Abstract
Importance: About 20% to 30% of people with schizophrenia have psychotic symptoms that do not respond adequately to first-line antipsychotic treatment. This clinical presentation, chronic and highly disabling, is known as treatment-resistant schizophrenia (TRS). The causes of treatment resistance and their relationships with causes underlying schizophrenia are largely unknown. Adequately powered genetic studies of TRS are scarce because of the difficulty in collecting data from well-characterized TRS cohorts. Objective: To examine the genetic architecture of TRS through the reassessment of genetic data from schizophrenia studies and its validation in carefully ascertained clinical samples. Design, setting, and participants: Two case-control genome-wide association studies (GWASs) of schizophrenia were performed in which the case samples were defined as individuals with TRS (n = 10 501) and individuals with non-TRS (n = 20 325). The differences in effect sizes for allelic associations were then determined between both studies, the reasoning being such differences reflect treatment resistance instead of schizophrenia. Genotype data were retrieved from the CLOZUK and Psychiatric Genomics Consortium (PGC) schizophrenia studies. The output was validated using polygenic risk score (PRS) profiling of 2 independent schizophrenia cohorts with TRS and non-TRS: a prevalence sample with 817 individuals (Cardiff Cognition in Schizophrenia [CardiffCOGS]) and an incidence sample with 563 individuals (Genetics Workstream of the Schizophrenia Treatment Resistance and Therapeutic Advances [STRATA-G]). Main outcomes and measures: GWAS of treatment resistance in schizophrenia. The results of the GWAS were compared with complex polygenic traits through a genetic correlation approach and were used for PRS analysis on the independent validation cohorts using the same TRS definition. Results: The study included a total of 85 490 participants (48 635 [56.9%] male) in its GWAS stage and 1380, Funding/Support: This work was supported by Medical Research Council Centre grant MR/L010305/1, Medical Research Council Program grant MR/P005748/1, and Medical Research Council Project grants MR/L011794/1 and MC_PC_17212 to Cardiff University and by the National Centre for Mental Health, funded by the Welsh Government through Health and Care Research Wales. This work acknowledges the support of the Supercomputing Wales project, which is partially funded by the European Regional Development Fund via the Welsh Government. Dr Pardiñas was supported by an Academy of Medical Sciences Springboard Award (SBF005\1083). Dr Andreassen was supported by the Research Council of Norway (grants 283798, 262656, 248980, 273291, 248828, 248778, and 223273); KG Jebsen Stiftelsen, South-East Norway Health Authority, and the European Union’s Horizon 2020 Research and Innovation Programme (grant 847776). Dr Ajnakina was supported by an National Institute for Health Research postdoctoral fellowship (PDF-2018-11-ST2-020). Dr Joyce was supported by the University College London Hospitals/UCL University College London Biomedical Research Centre. Dr Kowalec received funding from the European Union’s Horizon 2020 Research and Innovation Programme under the Marie Skłodowska-Curie grant agreement (793530) from the government of Canada Banting postdoctoral fellowship programme and the University of Manitoba. Dr Sullivan was supported by the Swedish Research Council (Vetenskapsrådet, D0886501), the European Union’s Horizon 2020 programme (COSYN, 610307) and the US National Institute of Mental Health (U01 MH109528 and R01 MH077139). The Psychiatric Genomics Consortium was partly supported by the National Institute Of Mental Health (grants R01MH124873). The Sweden Schizophrenia Study was supported by the National Institute Of Mental Health (grant R01MH077139). The STRATA consortium was supported by a Stratified Medicine Programme grant to Dr MacCabe from the Medical Research Council (grant MR/L0, STRATA more...
- Published
- 2022
- Full Text
- View/download PDF
15. Interaction testing and polygenic risk scoring to estimate the association of common genetic variants with treatment resistance in schizophrenia
- Author
-
Universidad de Sevilla. Departamento de Psiquiatría, Pardiñas, Antonio F., Smart, Sophie E., Willcocks, Isabella R., Holmans, Peter A., Dennison, Charlotte A, Lynham, Amy J, Crespo Facorro, Benedicto, Universidad de Sevilla. Departamento de Psiquiatría, Pardiñas, Antonio F., Smart, Sophie E., Willcocks, Isabella R., Holmans, Peter A., Dennison, Charlotte A, Lynham, Amy J, and Crespo Facorro, Benedicto more...
- Abstract
Importance About 20% to 30% of people with schizophrenia have psychotic symptoms that do not respond adequately to first-line antipsychotic treatment. This clinical presentation, chronic and highly disabling, is known as treatment-resistant schizophrenia (TRS). The causes of treatment resistance and their relationships with causes underlying schizophrenia are largely unknown. Adequately powered genetic studies of TRS are scarce because of the difficulty in collecting data from well-characterized TRS cohorts. Objective To examine the genetic architecture of TRS through the reassessment of genetic data from schizophrenia studies and its validation in carefully ascertained clinical samples. Conclusions and Relevance In this GWAS, common genetic variants were differentially associated with TRS, and these associations may have been obscured through the amalgamation of large GWAS samples in previous studies of broadly defined schizophrenia. Findings of this study suggest the validity of meta-analytic approaches for studies on patient outcomes, including treatment resistance. Design, Setting, and Participants Two case-control genome-wide association studies (GWASs) of schizophrenia were performed in which the case samples were defined as individuals with TRS (n = 10 501) and individuals with non-TRS (n = 20 325). The differences in effect sizes for allelic associations were then determined between both studies, the reasoning being such differences reflect treatment resistance instead of schizophrenia. Genotype data were retrieved from the CLOZUK and Psychiatric Genomics Consortium (PGC) schizophrenia studies. The output was validated using polygenic risk score (PRS) profiling of 2 independent schizophrenia cohorts with TRS and non-TRS: a prevalence sample with 817 individuals (Cardiff Cognition in Schizophrenia [CardiffCOGS]) and an incidence sample with 563 individuals (Genetics Workstream of the Schizophrenia Treatment Resistance and Therapeutic Advances [STRATA-G]). Mai more...
- Published
- 2022
16. Clinical predictors of antipsychotic treatment resistance: Development and internal validation of a prognostic prediction model by the STRATA-G consortium
- Author
-
Universidad de Sevilla. Departamento de Psiquiatría, Collaboration for Leadership in Applied Health Research and Care (CLAHRC) South London at King's College Hospital National Health Service Foundation Trust, European Community (EC), European Community's Seventh Framework Program, European Commission (EC). Fondo Europeo de Desarrollo Regional (FEDER), Fundación Marqués de Valdecilla, Institute of Psychiatry, Psychology, and Neuroscience at King's College London; Psychiatry Research Trust, Fondation Alamaya, Instituto de Salud Carlos III, King's College London, Maudsley Charity Research Fund., Medical Research Council, Ministerio de Economia, Industria y Competitividad (MINECO). España, Ministry of Health of the Czech Republic, National Center of Competence in Research (NCCR) "SYNAPSY - The Synaptic Bases of Mental Diseases" from the Swiss National Science Foundation, National Institute for Health Research Biomedical Research Centre at South London and Maudsley National Health Service Foundation Trust, Plan Nacional de Drogas. Beca de investigación, Research and Development Office of Northern Ireland, Research Council of Norway, SENY Fundatio Research Grant, South-Eastern Norway Regional Health Authority, Swiss National Science Foundation (SNFS), UK Medical Research Council, UK National Institute of Health Research (NIHR) Specialist Biomedical Research Centre for Mental Health, South London and Maudsley NHS Mental Health Foundation Trust (SLaM), Wellcome Trust, Smart, Sophie E., Agbedjro, Deborah, Pardiñas, Antonio F., Ajnakina, Olesya, Alameda, Luis, Andreassen, Ole A., Crespo Facorro, Benedicto, MacCabe, James H., Universidad de Sevilla. Departamento de Psiquiatría, Collaboration for Leadership in Applied Health Research and Care (CLAHRC) South London at King's College Hospital National Health Service Foundation Trust, European Community (EC), European Community's Seventh Framework Program, European Commission (EC). Fondo Europeo de Desarrollo Regional (FEDER), Fundación Marqués de Valdecilla, Institute of Psychiatry, Psychology, and Neuroscience at King's College London; Psychiatry Research Trust, Fondation Alamaya, Instituto de Salud Carlos III, King's College London, Maudsley Charity Research Fund., Medical Research Council, Ministerio de Economia, Industria y Competitividad (MINECO). España, Ministry of Health of the Czech Republic, National Center of Competence in Research (NCCR) "SYNAPSY - The Synaptic Bases of Mental Diseases" from the Swiss National Science Foundation, National Institute for Health Research Biomedical Research Centre at South London and Maudsley National Health Service Foundation Trust, Plan Nacional de Drogas. Beca de investigación, Research and Development Office of Northern Ireland, Research Council of Norway, SENY Fundatio Research Grant, South-Eastern Norway Regional Health Authority, Swiss National Science Foundation (SNFS), UK Medical Research Council, UK National Institute of Health Research (NIHR) Specialist Biomedical Research Centre for Mental Health, South London and Maudsley NHS Mental Health Foundation Trust (SLaM), Wellcome Trust, Smart, Sophie E., Agbedjro, Deborah, Pardiñas, Antonio F., Ajnakina, Olesya, Alameda, Luis, Andreassen, Ole A., Crespo Facorro, Benedicto, and MacCabe, James H. more...
- Abstract
Introduction Our aim was to, firstly, identify characteristics at first-episode of psychosis that are associated with later antipsychotic treatment resistance (TR) and, secondly, to develop a parsimonious prediction model for TR. Methods We combined data from ten prospective, first-episode psychosis cohorts from across Europe and categorised patients as TR or non-treatment resistant (NTR) after a mean follow up of 4.18 years (s.d. = 3.20) for secondary data analysis. We identified a list of potential predictors from clinical and demographic data recorded at first-episode. These potential predictors were entered in two models: a multivariable logistic regression to identify which were independently associated with TR and a penalised logistic regression, which performed variable selection, to produce a parsimonious prediction model. This model was internally validated using a 5-fold, 50-repeat cross-validation optimism-correction. Results Our sample consisted of N = 2216 participants of which 385 (17 %) developed TR. Younger age of psychosis onset and fewer years in education were independently associated with increased odds of developing TR. The prediction model selected 7 out of 17 variables that, when combined, could quantify the risk of being TR better than chance. These included age of onset, years in education, gender, BMI, relationship status, alcohol use, and positive symptoms. The optimism-corrected area under the curve was 0.59 (accuracy = 64 %, sensitivity = 48 %, and specificity = 76 %). Implications Our findings show that treatment resistance can be predicted, at first-episode of psychosis. Pending a model update and external validation, we demonstrate the potential value of prediction models for TR. more...
- Published
- 2022
17. Interaction Testing and Polygenic Risk Scoring to Estimate the Association of Common Genetic Variants With Treatment Resistance in Schizophrenia
- Author
-
Medical Research Council (UK), Cardiff University, Welsh Government, Health and Care Research Wales, European Commission, Academy of Medical Sciences (UK), Research Council of Norway, K. G. Jebsen Centres for Medical Research, National Institute for Health Research (UK), University College London, Government of Canada, University of Manitoba, Swedish Research Council, National Institute of Mental Health (US), Kings College London, Public Health Agency (Northern Ireland), The Psychiatry Research Trust, Maudsley Charity, Swiss National Science Foundation, Fondation Alamaya, Ministry of Health of the Czech Republic, Instituto de Salud Carlos III, Plan Nacional sobre Drogas (España), Fundació Seny, Fundación Marques de Valdecilla, Ministerio de Economía y Competitividad (España), Wellcome Trust, Pardiñas, Antonio F., Smart, Sophie E., Willcocks, Isabella R., Holmans, Peter A., Dennison, Charlotte A., Lynham, Amy, Legge, Sophie E., Baune, Bernhard T., Bigdeli, Tim B., Cairns, Murray J., Corvin, Aiden, Fanous, Ayman H., Frank, Josef, Kelly, Brian, McQuillin, Andrew, Melle, Ingrid, Mortensen, Preben B., Mowry, Bryan J., Pato, Carlos N., Periyasamy, Sathish, Rietschel, Marcella, Rujescu, Dan, Simonsen, Carmen, St Clair, David, Tooney, Paul, Wu, Jing Qin, Andreassen, Ole A., Kowalec, Kaarina, Sullivan, Patrick F., Murray, Robin M., Owen, Michael J., MacCabe, James H., O'Donovan, Michael C., Walters, James T. R., Genetics Workstream of the Schizophrenia Treatment Resistance and Therapeutic Advances (STRATA), Consortium and the Schizophrenia Working Group of the Psychiatric Genomics Consortium (PGC), Medical Research Council (UK), Cardiff University, Welsh Government, Health and Care Research Wales, European Commission, Academy of Medical Sciences (UK), Research Council of Norway, K. G. Jebsen Centres for Medical Research, National Institute for Health Research (UK), University College London, Government of Canada, University of Manitoba, Swedish Research Council, National Institute of Mental Health (US), Kings College London, Public Health Agency (Northern Ireland), The Psychiatry Research Trust, Maudsley Charity, Swiss National Science Foundation, Fondation Alamaya, Ministry of Health of the Czech Republic, Instituto de Salud Carlos III, Plan Nacional sobre Drogas (España), Fundació Seny, Fundación Marques de Valdecilla, Ministerio de Economía y Competitividad (España), Wellcome Trust, Pardiñas, Antonio F., Smart, Sophie E., Willcocks, Isabella R., Holmans, Peter A., Dennison, Charlotte A., Lynham, Amy, Legge, Sophie E., Baune, Bernhard T., Bigdeli, Tim B., Cairns, Murray J., Corvin, Aiden, Fanous, Ayman H., Frank, Josef, Kelly, Brian, McQuillin, Andrew, Melle, Ingrid, Mortensen, Preben B., Mowry, Bryan J., Pato, Carlos N., Periyasamy, Sathish, Rietschel, Marcella, Rujescu, Dan, Simonsen, Carmen, St Clair, David, Tooney, Paul, Wu, Jing Qin, Andreassen, Ole A., Kowalec, Kaarina, Sullivan, Patrick F., Murray, Robin M., Owen, Michael J., MacCabe, James H., O'Donovan, Michael C., Walters, James T. R., Genetics Workstream of the Schizophrenia Treatment Resistance and Therapeutic Advances (STRATA), and Consortium and the Schizophrenia Working Group of the Psychiatric Genomics Consortium (PGC) more...
- Abstract
[Importance] About 20% to 30% of people with schizophrenia have psychotic symptoms that do not respond adequately to first-line antipsychotic treatment. This clinical presentation, chronic and highly disabling, is known as treatment-resistant schizophrenia (TRS). The causes of treatment resistance and their relationships with causes underlying schizophrenia are largely unknown. Adequately powered genetic studies of TRS are scarce because of the difficulty in collecting data from well-characterized TRS cohorts., [Objective] To examine the genetic architecture of TRS through the reassessment of genetic data from schizophrenia studies and its validation in carefully ascertained clinical samples., [Design, Setting, and Participants] Two case-control genome-wide association studies (GWASs) of schizophrenia were performed in which the case samples were defined as individuals with TRS (n = 10 501) and individuals with non-TRS (n = 20 325). The differences in effect sizes for allelic associations were then determined between both studies, the reasoning being such differences reflect treatment resistance instead of schizophrenia. Genotype data were retrieved from the CLOZUK and Psychiatric Genomics Consortium (PGC) schizophrenia studies. The output was validated using polygenic risk score (PRS) profiling of 2 independent schizophrenia cohorts with TRS and non-TRS: a prevalence sample with 817 individuals (Cardiff Cognition in Schizophrenia [CardiffCOGS]) and an incidence sample with 563 individuals (Genetics Workstream of the Schizophrenia Treatment Resistance and Therapeutic Advances [STRATA-G])., [Main Outcomes and Measures] GWAS of treatment resistance in schizophrenia. The results of the GWAS were compared with complex polygenic traits through a genetic correlation approach and were used for PRS analysis on the independent validation cohorts using the same TRS definition., [Results] The study included a total of 85 490 participants (48 635 [56.9%] male) in its GWAS stage and 1380 participants (859 [62.2%] male) in its PRS validation stage. Treatment resistance in schizophrenia emerged as a polygenic trait with detectable heritability (1% to 4%), and several traits related to intelligence and cognition were found to be genetically correlated with it (genetic correlation, 0.41-0.69). PRS analysis in the CardiffCOGS prevalence sample showed a positive association between TRS and a history of taking clozapine (r2 = 2.03%; P = .001), which was replicated in the STRATA-G incidence sample (r2 = 1.09%; P = .04)., [Conclusions and Relevance] In this GWAS, common genetic variants were differentially associated with TRS, and these associations may have been obscured through the amalgamation of large GWAS samples in previous studies of broadly defined schizophrenia. Findings of this study suggest the validity of meta-analytic approaches for studies on patient outcomes, including treatment resistance. more...
- Published
- 2022
18. Schizophrenia Polygenic Risk and Experiences of Childhood Adversity: A Systematic Review and Meta-analysis
- Author
-
Woolway, Grace E, primary, Smart, Sophie E, additional, Lynham, Amy J, additional, Lloyd, Jennifer L, additional, Owen, Michael J, additional, Jones, Ian R, additional, Walters, James T R, additional, and Legge, Sophie E, additional more...
- Published
- 2022
- Full Text
- View/download PDF
19. sj-docx-1-jop-10.1177_02698811221078746 ��� Supplemental material for Using a statistical learning approach to identify sociodemographic and clinical predictors of response to clozapine
- Author
-
Fonseca de Freitas, Daniela, Kadra-Scalzo, Giouliana, Agbedjro, Deborah, Francis, Emma, Ridler, Isobel, Pritchard, Megan, Shetty, Hitesh, Segev, Aviv, Casetta, Cecilia, Smart, Sophie E, Downs, Johnny, Christensen, S��ren Rahn, Bak, Nikolaj, Kinon, Bruce J, Stahl, Daniel, MacCabe, James H, and Hayes, Richard D more...
- Subjects
FOS: Psychology ,FOS: Clinical medicine ,170199 Psychology not elsewhere classified ,110319 Psychiatry (incl. Psychotherapy) ,111599 Pharmacology and Pharmaceutical Sciences not elsewhere classified ,110904 Neurology and Neuromuscular Diseases - Abstract
Supplemental material, sj-docx-1-jop-10.1177_02698811221078746 for Using a statistical learning approach to identify sociodemographic and clinical predictors of response to clozapine by Daniela Fonseca de Freitas, Giouliana Kadra-Scalzo, Deborah Agbedjro, Emma Francis, Isobel Ridler, Megan Pritchard, Hitesh Shetty, Aviv Segev, Cecilia Casetta, Sophie E Smart, Johnny Downs, S��ren Rahn Christensen, Nikolaj Bak, Bruce J Kinon, Daniel Stahl, James H MacCabe and Richard D Hayes in Journal of Psychopharmacology more...
- Published
- 2022
- Full Text
- View/download PDF
20. sj-docx-1-jop-10.1177_02698811221132537 – Supplemental material for Clinical correlates of early onset antipsychotic treatment resistance
- Author
-
Fonseca de Freitas, Daniela, Agbedjro, Deborah, Kadra-Scalzo, Giouliana, Francis, Emma, Ridler, Isobel, Pritchard, Megan, Shetty, Hitesh, Segev, Aviv, Casetta, Cecilia, Smart, Sophie E., Morris, Anna, Downs, Johnny, Christensen, Søren Rahn, Bak, Nikolaj, Kinon, Bruce J., Stahl, Daniel, Hayes, Richard D., and MacCabe, James H. more...
- Subjects
FOS: Psychology ,FOS: Clinical medicine ,170199 Psychology not elsewhere classified ,110319 Psychiatry (incl. Psychotherapy) ,111599 Pharmacology and Pharmaceutical Sciences not elsewhere classified ,110904 Neurology and Neuromuscular Diseases - Abstract
Supplemental material, sj-docx-1-jop-10.1177_02698811221132537 for Clinical correlates of early onset antipsychotic treatment resistance by Daniela Fonseca de Freitas, Deborah Agbedjro, Giouliana Kadra-Scalzo, Emma Francis, Isobel Ridler, Megan Pritchard, Hitesh Shetty, Aviv Segev, Cecilia Casetta, Sophie E. Smart, Anna Morris, Johnny Downs, Søren Rahn Christensen, Nikolaj Bak, Bruce J. Kinon, Daniel Stahl, Richard D. Hayes and James H. MacCabe in Journal of Psychopharmacology more...
- Published
- 2022
- Full Text
- View/download PDF
21. Using a statistical learning approach to identify sociodemographic and clinical predictors of response to clozapine
- Author
-
Fonseca de Freitas, Daniela, primary, Kadra-Scalzo, Giouliana, additional, Agbedjro, Deborah, additional, Francis, Emma, additional, Ridler, Isobel, additional, Pritchard, Megan, additional, Shetty, Hitesh, additional, Segev, Aviv, additional, Casetta, Cecilia, additional, Smart, Sophie E, additional, Downs, Johnny, additional, Christensen, Søren Rahn, additional, Bak, Nikolaj, additional, Kinon, Bruce J, additional, Stahl, Daniel, additional, MacCabe, James H, additional, and Hayes, Richard D, additional more...
- Published
- 2022
- Full Text
- View/download PDF
22. A Volunteer-Run, Face-to-Face, Early Intervention Service for Reducing Suicidality: A Service Evaluation of The Listening Place.
- Author
-
Smart, Sophie E., Dimes, Hollie, Lumley, Cordelia, Spooner, Steve, Anderson, Sarah, Platt, Stephen, and Davidson, Sarah
- Published
- 2023
- Full Text
- View/download PDF
23. Neural circuitry of novelty salience processing in psychosis risk: association with clinical outcome
- Author
-
McGuire, Philip, Grace, Anthony A., Stone, James M., Howes, Oliver D., Perez, Jesus, Broome, Matthew R., Bossong, Matthijs G., Antoniades, Mathilde, Smart, Sophie E., Gifford, George W. G., Quinn, Beverly, Bonoldi, Ilaria, Samson, Carly, Azis, Matilda, Dima, Danai, Zugman, Andre, Allen, Paul, and Modinos, Gemma more...
- Subjects
nervous system - Abstract
Psychosis has been proposed to develop from dysfunction in a hippocampal-striatal-midbrain circuit, leading to aberrant salience processing. Here, we used functional magnetic resonance imaging (fMRI) during novelty salience processing to investigate this model in people at clinical high-risk (CHR) for psychosis according to their subsequent clinical outcomes. Seventy-six CHR participants as defined using the Comprehensive Assessment of At-Risk Mental States (CAARMS) and 31 healthy controls (HC) were studied while performing a novelty salience fMRI task that engaged an a priori hippocampal-striatal-midbrain circuit of interest. The CHR sample was then followed clinically for a mean of 59.7 months (~5 years), when clinical outcomes were assessed in terms of transition (CHR-T) or non-transition (CHR-NT) to psychosis (CAARMS criteria): during this period, 13 individuals (17%) developed a psychotic disorder (CHR-T) and 63 did not. Functional activation and effective connectivity within a hippocampal-striatal-midbrain circuit were compared between groups. In CHR individuals compared to HC, hippocampal response to novel stimuli was significantly attenuated (P=0.041 family-wise error corrected). Dynamic Causal Modelling revealed that stimulus novelty modulated effective connectivity from the hippocampus to the striatum, and from the midbrain to the hippocampus, significantly more in CHR participants than in HC. Conversely, stimulus novelty modulated connectivity from the midbrain to the striatum significantly less in CHR participants than in HC, and less in CHR participants who subsequently developed psychosis than in CHR individuals who did not become psychotic. Our findings are consistent with preclinical evidence implicating hippocampal-striatal-midbrain circuit dysfunction in altered salience processing and the onset of psychosis. more...
- Published
- 2020
- Full Text
- View/download PDF
24. Integrated metastate functional connectivity networks predict change in symptom severity in clinical high risk for psychosis
- Author
-
Brain, Onderzoek, Gifford, George, Crossley, Nicolas, Morgan, Sarah, Kempton, Matthew J, Dazzan, Paola, Modinos, Gemma, Azis, Matilda, Samson, Carly, Bonoldi, Ilaria, Quinn, Beverly, Smart, Sophie E, Antoniades, Mathilde, Bossong, Matthijs G, Broome, Matthew R, Perez, Jesus, Howes, Oliver D, Stone, James M, Allen, Paul, Grace, Anthony A, McGuire, Philip, Brain, Onderzoek, Gifford, George, Crossley, Nicolas, Morgan, Sarah, Kempton, Matthew J, Dazzan, Paola, Modinos, Gemma, Azis, Matilda, Samson, Carly, Bonoldi, Ilaria, Quinn, Beverly, Smart, Sophie E, Antoniades, Mathilde, Bossong, Matthijs G, Broome, Matthew R, Perez, Jesus, Howes, Oliver D, Stone, James M, Allen, Paul, Grace, Anthony A, and McGuire, Philip more...
- Published
- 2021
25. Rates of treatment-resistant schizophrenia from first-episode cohorts: systematic review and meta-analysis
- Author
-
Siskind, Dan, primary, Orr, Stacy, additional, Sinha, Surabhi, additional, Yu, Ou, additional, Brijball, Bhavna, additional, Warren, Nicola, additional, MacCabe, James H, additional, Smart, Sophie E, additional, and Kisely, Steve, additional more...
- Published
- 2021
- Full Text
- View/download PDF
26. Integrated metastate functional connectivity networks predict change in symptom severity in clinical high risk for psychosis
- Author
-
Gifford, George, primary, Crossley, Nicolas, additional, Morgan, Sarah, additional, Kempton, Matthew J, additional, Dazzan, Paola, additional, Modinos, Gemma, additional, Azis, Matilda, additional, Samson, Carly, additional, Bonoldi, Ilaria, additional, Quinn, Beverly, additional, Smart, Sophie E, additional, Antoniades, Mathilde, additional, Bossong, Matthijs G, additional, Broome, Matthew R, additional, Perez, Jesus, additional, Howes, Oliver D, additional, Stone, James M, additional, Allen, Paul, additional, Grace, Anthony A, additional, and McGuire, Philip, additional more...
- Published
- 2020
- Full Text
- View/download PDF
27. Neural Circuitry of Novelty Salience Processing in Psychosis Risk: Association With Clinical Outcome
- Author
-
Brain, Onderzoek, Modinos, Gemma, Allen, Paul, Zugman, Andre, Dima, Danai, Azis, Matilda, Samson, Carly, Bonoldi, Ilaria, Quinn, Beverly, Gifford, George W. G., Smart, Sophie E., Antoniades, Mathilde, Bossong, Matthijs G., Broome, Matthew R., Perez, Jesus, Howes, Oliver D., Stone, James M., Grace, Anthony A., McGuire, Philip, Brain, Onderzoek, Modinos, Gemma, Allen, Paul, Zugman, Andre, Dima, Danai, Azis, Matilda, Samson, Carly, Bonoldi, Ilaria, Quinn, Beverly, Gifford, George W. G., Smart, Sophie E., Antoniades, Mathilde, Bossong, Matthijs G., Broome, Matthew R., Perez, Jesus, Howes, Oliver D., Stone, James M., Grace, Anthony A., and McGuire, Philip more...
- Published
- 2020
28. Rates of treatment-resistant schizophrenia from first-episode cohorts: systematic review and meta-analysis.
- Author
-
Siskind, Dan, Orr, Stacy, Sinha, Surabhi, Yu, Ou, Brijball, Bhavna, Warren, Nicola, MacCabe, James H, Smart, Sophie E, and Kisely, Steve
- Subjects
SCHIZOPHRENIA ,CINAHL database ,PEOPLE with schizophrenia ,SOCIAL support ,LOCATION analysis - Abstract
Background: Treatment-resistant schizophrenia (TRS) is associated with high levels of functional impairment, healthcare usage and societal costs. Cross-sectional studies may overestimate TRS rates because of selection bias.Aims: We aimed to quantify TRS rates by using first-episode cohorts to improve resource allocation and clozapine access.Method: We undertook a systematic review of TRS rates among people with first-episode psychosis and schizophrenia, with a minimum follow-up of 8 weeks. We searched PubMed, PsycINFO, EMBASE, CINAHL and the Cochrane Database of Systematic Reviews, and meta-analysed TRS rates from included studies.Results: Twelve studies were included, totalling 11 958 participants; six studies were of high quality. The rate of TRS was 22.8% (95% CI 19.1-27.0%, P < 0.001) among all first-episode cohorts and 24.4% (95% CI 19.5-30.0%, P < 0.001) among first-episode schizophrenia cohorts. Subgroup sensitivity analyses by location of recruitment, TRS definition, study quality, time of data collection and retrospective versus prospective data collection did not lead to statistically significant differences in heterogeneity. In a meta-regression, duration of follow-up and percentage drop-out did not significantly affect the overall TRS rate. Men were 1.57 times more likely to develop TRS than women (95% CI 1.11-2.21, P = 0.010).Conclusions: Almost a quarter of people with first-episode psychosis or schizophrenia will develop TRS in the early stages of treatment. When including people with schizophrenia who relapse despite initial response and continuous treatment, rates of TRS may be as high as a third. These high rates of TRS highlight the need for improved access to clozapine and psychosocial supports. [ABSTRACT FROM AUTHOR] more...- Published
- 2022
- Full Text
- View/download PDF
29. Neural Circuitry of Novelty Salience Processing in Psychosis Risk: Association With Clinical Outcome
- Author
-
Modinos, Gemma, primary, Allen, Paul, primary, Zugman, Andre, primary, Dima, Danai, primary, Azis, Matilda, primary, Samson, Carly, primary, Bonoldi, Ilaria, primary, Quinn, Beverly, primary, Gifford, George W G, primary, Smart, Sophie E, primary, Antoniades, Mathilde, primary, Bossong, Matthijs G, primary, Broome, Matthew R, primary, Perez, Jesus, primary, Howes, Oliver D, primary, Stone, James M, primary, Grace, Anthony A, primary, and McGuire, Philip, primary more...
- Published
- 2019
- Full Text
- View/download PDF
30. Integrated metastate functional connectivity networks predict change in symptom severity in clinical high risk for psychosis.
- Author
-
Gifford, George, Crossley, Nicolas, Morgan, Sarah, Kempton, Matthew J, Dazzan, Paola, Modinos, Gemma, Azis, Matilda, Samson, Carly, Bonoldi, Ilaria, Quinn, Beverly, Smart, Sophie E, Antoniades, Mathilde, Bossong, Matthijs G, Broome, Matthew R, Perez, Jesus, Howes, Oliver D, Stone, James M, Allen, Paul, Grace, Anthony A, and McGuire, Philip more...
- Subjects
FUNCTIONAL connectivity ,PSYCHOSES ,K-means clustering ,SYMPTOMS ,SENSORIMOTOR integration ,22Q11 deletion syndrome - Abstract
The ability to identify biomarkers of psychosis risk is essential in defining effective preventive measures to potentially circumvent the transition to psychosis. Using samples of people at clinical high risk for psychosis (CHR) and Healthy controls (HC) who were administered a task fMRI paradigm, we used a framework for labelling time windows of fMRI scans as 'integrated' FC networks to provide a granular representation of functional connectivity (FC). Periods of integration were defined using the 'cartographic profile' of time windows and k‐means clustering, and sub‐network discovery was carried out using Network Based Statistics (NBS). There were no network differences between CHR and HC groups. Within the CHR group, using integrated FC networks, we identified a sub‐network negatively associated with longitudinal changes in the severity of psychotic symptoms. This sub‐network comprised brain areas implicated in bottom‐up sensory processing and in integration with motor control, suggesting it may be related to the demands of the fMRI task. These data suggest that extracting integrated FC networks may be useful in the investigation of biomarkers of psychosis risk. [ABSTRACT FROM AUTHOR] more...
- Published
- 2021
- Full Text
- View/download PDF
31. Neural Circuitry of Novelty Salience Processing in Psychosis Risk: Association With Clinical Outcome.
- Author
-
Modinos, Gemma, Allen, Paul, Zugman, Andre, Dima, Danai, Azis, Matilda, Samson, Carly, Bonoldi, Ilaria, Quinn, Beverly, Gifford, George W G, Smart, Sophie E, Antoniades, Mathilde, Bossong, Matthijs G, Broome, Matthew R, Perez, Jesus, Howes, Oliver D, Stone, James M, Grace, Anthony A, and McGuire, Philip more...
- Subjects
SCHIZOPHRENIA risk factors ,BASAL ganglia ,BRAIN ,BRAIN mapping ,HIPPOCAMPUS (Brain) ,MAGNETIC resonance imaging ,PSYCHOLOGICAL tests ,SCHIZOPHRENIA ,CAUSAL models ,NEURAL pathways - Abstract
Psychosis has been proposed to develop from dysfunction in a hippocampal-striatal-midbrain circuit, leading to aberrant salience processing. Here, we used functional magnetic resonance imaging (fMRI) during novelty salience processing to investigate this model in people at clinical high risk (CHR) for psychosis according to their subsequent clinical outcomes. Seventy-six CHR participants as defined using the Comprehensive Assessment of At-Risk Mental States (CAARMS) and 31 healthy controls (HC) were studied while performing a novelty salience fMRI task that engaged an a priori hippocampal-striatal-midbrain circuit of interest. The CHR sample was then followed clinically for a mean of 59.7 months (~5 y), when clinical outcomes were assessed in terms of transition (CHR-T) or non-transition (CHR-NT) to psychosis (CAARMS criteria): during this period, 13 individuals (17%) developed a psychotic disorder (CHR-T) and 63 did not. Functional activation and effective connectivity within a hippocampal-striatal-midbrain circuit were compared between groups. In CHR individuals compared to HC, hippocampal response to novel stimuli was significantly attenuated (P =.041 family-wise error corrected). Dynamic Causal Modelling revealed that stimulus novelty modulated effective connectivity from the hippocampus to the striatum, and from the midbrain to the hippocampus, significantly more in CHR participants than in HC. Conversely, stimulus novelty modulated connectivity from the midbrain to the striatum significantly less in CHR participants than in HC, and less in CHR participants who subsequently developed psychosis than in CHR individuals who did not become psychotic. Our findings are consistent with preclinical evidence implicating hippocampal-striatal-midbrain circuit dysfunction in altered salience processing and the onset of psychosis. [ABSTRACT FROM AUTHOR] more...
- Published
- 2020
- Full Text
- View/download PDF
32. Applying the Higher Education Academy Framework for Partnership in Learning and Teaching in Higher Education to Online Partnership Learning Communities: A Case Study and an Extended Model.
- Author
-
Kravariti, Eugenia, Gillespie, Amy, Diederen, Kelly, Smart, Sophie E., Mayberry, Caroline, Meehan, Alan J., Bream, Danielle, Musiat, Peter, Vitoratou, Silia, Stahl, Daniel, Dyer, Kyle R., Shergill, Sukhwinder S., Coate, Kelly, and Yiend, Jenny more...
- Subjects
FACILITATED learning ,ONLINE education - Abstract
As internet access and use increase exponentially, pedagogical practice becomes increasingly embedded in online platforms. We report on an online initiative of engaged student learning, the peer-led, staff-assisted e-helpdesk for research methods and statistics, which we evaluated and redeveloped using the lens and guiding principles of the framework for partnership in learning and teaching of the Higher Education Academy (HEA). The aim of the redevelopment was to steer the initiative towards a more integrative and sustainable implementation, as manifest in the applied construct of an online partnership learning community. Our evolving experience of the e-helpdesk highlighted the central role of the facilitator in engineering and maintaining social presence in the online community. We proposean extended model for building an online partnership learning community, whereby partnership encapsulates all the essential elements of student and staff partnership as outlined in the HEA framework, but is also critically defined by similar parameters of partnership between users and facilitators. In this model, the facilitator's role becomes more involved in instructional teaching as disciplinary expertise increases, but descending levels of disciplinary expertise can foster ascending levels of independent learning and shared discovery for both users and facilitators. [ABSTRACT FROM AUTHOR] more...
- Published
- 2018
- Full Text
- View/download PDF
33. SLC39A8.p.(Ala391Thr) is associated with poorer cognitive ability: a cross-sectional study of schizophrenia and the general UK population.
- Author
-
Smart SE, Legge SE, Fenner E, Pardiñas AF, Woolway G, Lynham AJ, Escott-Price V, Hall J, Wilkinson L, Holmans P, O'Donovan MC, Owen MJ, and Walters JTR
- Abstract
The missense SNP NC_000004.12:g.102267552C>T (SLC39A8.p.(Ala391Thr), rs13107325) in SLC39A8 , which encodes a zinc transporter, has been linked to schizophrenia and is the likely causal variant for one of the genome-wide association loci associated with the disorder. We tested whether the schizophrenia-risk allele at p.(Ala391Thr) was associated with schizophrenia-related phenotypes, including positive, negative, and disorganised symptoms, cognitive ability, educational attainment, and age of psychosis onset, within three schizophrenia cohorts (combined N=1,232) and, with equivalent phenotypes, in a sample of population controls (UK Biobank, N=355,069). We used regression analyses controlling for age, sex, and population stratification. Within the schizophrenia cohorts, after correction for multiple testing, p.(Ala391Thr) was not significantly associated with any schizophrenia-related phenotypes. In the unaffected participants from the UK Biobank, the schizophrenia-risk allele at p.(Ala391Thr) was associated with significantly poorer cognitive ability and fluid intelligence, a lower probability of obtaining GCSEs or a degree-level qualification, and fewer years in education. There was no association between p.(Ala391Thr) and self-reported psychotic experiences in this cohort. The schizophrenia-risk allele was associated with poorer cognitive ability, but not psychotic experiences, in a volunteer sample drawn from of the general population. To determine whether p.(Ala391Thr) is associated with cognitive phenotypes in people with schizophrenia, and to understand the role of p.(Ala391Thr) in the aetiology of cognitive impairment in schizophrenia, larger independent samples are required. more...
- Published
- 2024
- Full Text
- View/download PDF
34. Assessing the validity of a self-reported clinical diagnosis of schizophrenia.
- Author
-
Woolway GE, Legge SE, Lynham A, Smart SE, Hubbard L, Daniel ER, Pardiñas AF, Escott-Price V, O'Donovan MC, Owen MJ, Jones IR, and Walters JT
- Abstract
Background: Diagnoses in psychiatric research can be derived from various sources. This study assesses the validity of a self-reported clinical diagnosis of schizophrenia., Methods: The study included 3,029 clinically ascertained participants with schizophrenia or psychotic disorders diagnosed by self-report and/or research interview and 1,453 UK Biobank participants with self-report and/or medical record diagnosis of schizophrenia or schizoaffective disorder depressed-type (SA-D). We assessed positive predictive values (PPV) of self-reported clinical diagnoses against research interview and medical record diagnoses. We compared polygenic risk scores (PRS) and phenotypes across diagnostic groups, and compared the variance explained by schizophrenia PRS to samples in the Psychiatric Genomics Consortium (PGC)., Results: In the clinically ascertained sample, the PPV of self-reported schizophrenia to a research diagnosis of schizophrenia was 0.70, which increased to 0.81 when benchmarked against schizophrenia or SA-D. In UK Biobank, the PPV of self-reported schizophrenia to a medical record diagnosis was 0.74. Compared to self-report participants, those with a research diagnosis were younger and more likely to have a high school qualification (clinically ascertained sample) and those with a medical record diagnosis were less likely to be employed or have a high school qualification (UK Biobank). Schizophrenia PRS did not differ between participants that had a diagnosis from self-report, research diagnosis or medical record diagnosis. Polygenic liability r
2 , for all diagnosis definitions, fell within the distribution of PGC schizophrenia cohorts., Conclusions: Self-report measures of schizophrenia are justified in research to maximise sample size and representativeness, although within sample validation of diagnoses is recommended., Competing Interests: Conflict of Interest JTRW, MCO’D and MJO received a research grant to Cardiff University from Takeda Pharmaceuticals that funded this work and GW’s research position. Takeda Pharmaceuticals have not had any input into the study design, analysis, or interpretation of results. JTRW, MCO’D, MJO, IRJ and AFP have received research funding from Akrivia Health for work unrelated to this study. more...- Published
- 2023
- Full Text
- View/download PDF
Discovery Service for Jio Institute Digital Library
For full access to our library's resources, please sign in.