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4. Treatment Approaches for First Episode and Early-Phase Schizophrenia in Adolescents and Young Adults: A Delphi Consensus Report from Europe

Author

Correll CU, Fusar-Poli P, Leucht S, Karow A, Maric N, Moreno C, Nordentoft M, and Raballo A

Subjects
schizophrenia, delphi, psychosis, early onset, management, Neurosciences. Biological psychiatry. Neuropsychiatry, RC321-571, Neurology. Diseases of the nervous system, RC346-429
Abstract

Christoph U Correll,1– 3 Paolo Fusar-Poli,4– 6 Stefan Leucht,7 Anne Karow,8 Nadja Maric,9 Carmen Moreno,10 Merete Nordentoft,11 Andrea Raballo12,13 1Department of Child and Adolescent Psychiatry, Charité Universitätsmedizin, Berlin, Germany; 2Department of Psychiatry and Molecular Medicine, Zucker School of Medicine at Hofstra/Northwell, Hempstead, NY, USA; 3Department of Psychiatry, The Zucker Hillside Hospital, Glen Oaks, NY, USA; 4Early Psychosis: Interventions and Clinical-detection (EPIC) Lab, Department of Psychosis Studies, Institute of Psychiatry, Psychology & Neuroscience, King’s College London, London, UK; 5OASIS service, South London and Maudsley NHS Foundation Trust, London, UK; 6Department of Brain and Behavioural Sciences, University of Pavia, Pavia, Italy; 7Section Evidence-Based Medicine in Psychiatry and Psychotherapy, Department of Psychiatry and Psychotherapy, Technical University of Munich, School of Medicine, Munich, Germany; 8Department of Psychiatry and Psychotherapy, University Medical Centre Hamburg-Eppendorf, Hamburg, Germany; 9Faculty of Medicine, University of Belgrade and Institute of Mental Health, Belgrade, Serbia; 10Department of Child and Adolescent Psychiatry, Institute of Psychiatry and Mental Health, Hospital General Universitario Gregorio Marañón, School of Medicine, Universidad Complutense, IiSGM, CIBERSAM, Madrid, Spain; 11CORE-Copenhagen Research Centre for Mental Health, Mental Health Services in the Capital Region, Department of Clinical Medicine, Faculty of Health Sciences, University of Copenhagen, Copenhagen, Denmark; 12Section of Psychiatry, Clinical Psychology and Rehabilitation, Department of Medicine, University of Perugia, Perugia, Italy; 13Centre for Translational, Phenomenological and Developmental Psychopathology (CTPDP), Perugia University Hospital, Perugia, ItalyCorrespondence: Christoph U CorrellDepartment of Child and Adolescent Psychiatry, Charité Universitätsmedizin, Augustenburger Platz 1, Berlin, 13353, Germany, Tel +49-30-450-566202, Fax +49-30-450-566921, Email christoph.correll@charite.dePurpose: Although first-episode psychosis (FEP) in youth, particularly early-onset schizophrenia (EOS), is managed similarly to adult-onset schizophrenia, few antipsychotics are approved for people aged 13– 18 years. We aimed to explore areas of uncertainty in EOS management and provide evidence-based recommendations to mental health specialists. We used the Delphi methodology to gain knowledge in areas lacking evidence-based strategies. This standardized methodology consists of the development of a questionnaire by content experts, which is then submitted to a broader panel of professionals (panelists) to survey their level of agreement on the topics proposed.Materials and Methods: The developed questionnaire covered patient management from diagnosis to maintenance treatment and was administered to a broader panel of specialists across Europe. Based on an analysis of responses received in this first round, the items that needed further insight were submitted to the panel for a second round and then reanalysed.Results: An initial set of 90 items was developed; in round I, consensus was reached for 83/90 items (92%), while it was reached for 7/11 (64%) of the items sent out for rerating in round II. Feedback for rounds I and II was obtained from 54/92 and 48/54 approached experts, respectively. There was broad agreement on diagnostic standards, multimodal approaches and focus on adverse events, but uncertainty in terms of pharmacological strategies (including clozapine) in case of failure and antipsychotic dosing in younger patients.Conclusion: Despite knowledge about diagnostic clues and integrated management of EOS, this study highlights the lack of standardization in treating EOS, with safety arguments having a major role in the decision-making process. Targeted clinical trials and systematic dissemination across Europe of current scientific evidence on the value of early intervention services is hoped to contribute to standardized and improved quality care for patients with early-phase psychosis and schizophrenia.Keywords: schizophrenia, Delphi, psychosis, early onset, management

Published
2022

5. Basic symptoms in young people at ultra-high risk of psychosis: Association with clinical characteristics and outcomes

Author

Youn, S., Phillips, L.J., Amminger, G.P., Berger, G., Chen, E.Y.H., de Haan, L., Hartmann, J.A., Hickie, I.B., Lavoie, S., Markulev, C., McGorry, P.D., Mossaheb, N., Nieman, D.H., Nordentoft, M., Riecher-Rössler, A., Schäfer, M.R., Schlögelhofer, M., Smesny, S., Thompson, A., Verma, S., Yuen, H.P., Yung, A.R., and Nelson, B.

Published
2020
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7. Dynamic prediction of transition to psychosis using joint modelling

Author

Yuen, H.P., Mackinnon, A., Hartmann, J., Amminger, G.P., Markulev, C., Lavoie, S., Schäfer, M.R., Polari, A., Mossaheb, N., Schlögelhofer, M., Smesny, S., Hickie, I.B., Berger, G., Chen, E.Y.H., de Haan, L., Nieman, D.H., Nordentoft, M., Riecher-Rössler, A., Verma, S., Thompson, A., Yung, A.R., McGorry, P.D., and Nelson, B.

Published
2018
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9. Genome-wide study of association and interaction with maternal cytomegalovirus infection suggests new schizophrenia loci

Author

Børglum, AD, Demontis, D, Grove, J, Pallesen, J, Hollegaard, MV, Pedersen, CB, Hedemand, A, Mattheisen, M, Uitterlinden, A, Nyegaard, M, Ørntoft, T, Wiuf, C, Didriksen, M, Nordentoft, M, Nöthen, MM, Rietschel, M, Ophoff, RA, Cichon, S, Yolken, RH, Hougaard, DM, Mortensen, PB, and Mors, O

Subjects
Genetics, Schizophrenia, Brain Disorders, Mental Health, Human Genome, Infectious Diseases, Serious Mental Illness, 2.1 Biological and endogenous factors, Aetiology, Mental health, ARNTL Transcription Factors, Cadherins, Case-Control Studies, Cytomegalovirus Infections, Denmark, Female, Gene-Environment Interaction, Genetic Predisposition to Disease, Genome-Wide Association Study, Germany, Homeodomain Proteins, Humans, Maternal Exposure, Polymorphism, Single Nucleotide, Sorting Nexins, Transcription Factors, White People, Zinc Finger E-box-Binding Homeobox 1, alpha Catenin, CTNNA3, gene-environment interaction, GWAS, GWIS, region-wise analysis, ZEB1, GROUP investigators10, Biological Sciences, Medical and Health Sciences, Psychology and Cognitive Sciences, Psychiatry
Abstract

Genetic and environmental components as well as their interaction contribute to the risk of schizophrenia, making it highly relevant to include environmental factors in genetic studies of schizophrenia. This study comprises genome-wide association (GWA) and follow-up analyses of all individuals born in Denmark since 1981 and diagnosed with schizophrenia as well as controls from the same birth cohort. Furthermore, we present the first genome-wide interaction survey of single nucleotide polymorphisms (SNPs) and maternal cytomegalovirus (CMV) infection. The GWA analysis included 888 cases and 882 controls, and the follow-up investigation of the top GWA results was performed in independent Danish (1396 cases and 1803 controls) and German-Dutch (1169 cases, 3714 controls) samples. The SNPs most strongly associated in the single-marker analysis of the combined Danish samples were rs4757144 in ARNTL (P=3.78 × 10(-6)) and rs8057927 in CDH13 (P=1.39 × 10(-5)). Both genes have previously been linked to schizophrenia or other psychiatric disorders. The strongest associated SNP in the combined analysis, including Danish and German-Dutch samples, was rs12922317 in RUNDC2A (P=9.04 × 10(-7)). A region-based analysis summarizing independent signals in segments of 100 kb identified a new region-based genome-wide significant locus overlapping the gene ZEB1 (P=7.0 × 10(-7)). This signal was replicated in the follow-up analysis (P=2.3 × 10(-2)). Significant interaction with maternal CMV infection was found for rs7902091 (P(SNP × CMV)=7.3 × 10(-7)) in CTNNA3, a gene not previously implicated in schizophrenia, stressing the importance of including environmental factors in genetic studies.

Published
2014

11. Associations between treatment with melatonin and suicidal behavior: a nationwide cohort study

Author

Hoier, N, Madsen, T, Spira, A, Hawton, K, Jennum, P, Nordentoft, M, and Erlangsen, A

Subjects
Cohort Studies, Pulmonary and Respiratory Medicine, Neurology, Risk Factors, Mental Disorders, Humans, Suicide, Attempted, Neurology (clinical), Melatonin, Suicidal Ideation
Abstract

Melatonin is often prescribed to patients with sleep disorders who are known to have elevated suicide risks, yet melatonin's association with suicidal behavior remains to be examined. We investigated whether individuals prescribed melatonin had higher rates of suicide and suicide attempts when compared to individuals who were not prescribed this drug, including both those with and without known mental disorders.A cohort design was applied to longitudinal, register data on all persons aged ≥ 10 years in Denmark during 2007-2016. Based on data from the National Prescription Registry, periods of being in treatment with melatonin were defined using information on the number of tablets and the daily defined dose. We calculated incidence rate ratios for suicide and suicide attempts, as identified in register records, comparing those in treatment with melatonin to those not in treatment.Among 5,798,923 individuals, 10,577 (0.2%) were treated with melatonin (mean treatment length, 50 days) during the study period. Of those, 22 died by suicide and 134 had at least 1 suicide attempt. People in treatment with melatonin had a 4-fold higher rate of suicide (incidence rate ratio, 4.8; 95% CI, 3.0-7.5) and a 5-fold higher rate of suicide attempt (incidence rate ratio, 5.9; 95% CI, 4.4-8.0) than those not in treatment and when adjusting for sex and age group.Treatment with melatonin was associated with suicide and suicide attempt. Although there are several possible explanations, attention to suicide risk is particularly warranted for people with mental comorbidity who are in treatment with melatonin.Høier NK, Madsen T, Spira AP, et al. Associations between treatment with melatonin and suicidal behavior: a nationwide cohort study.

Published
2022

12. Suicide numbers during the first 9-15 months of the COVID-19 pandemic compared with pre-existing trends: An interrupted time series analysis in 33 countries

Author

Pirkis, J, Gunnell, D, Shin, S, Del Pozo-Banos, M, Arya, V, Aguilar, P, Appleby, L, Arafat, S, Arensman, E, Ayuso-Mateos, J, Balhara, Y, Bantjes, J, Baran, A, Behera, C, Bertolote, J, Borges, G, Bray, M, Brečić, P, Caine, E, Calati, R, Carli, V, Castelpietra, G, Chan, L, Chang, S, Colchester, D, Coss-Guzmán, M, Crompton, D, Ćurković, M, Dandona, R, De Jaegere, E, De Leo, D, Deisenhammer, E, Dwyer, J, Erlangsen, A, Faust, J, Fornaro, M, Fortune, S, Garrett, A, Gentile, G, Gerstner, R, Gilissen, R, Gould, M, Gupta, S, Hawton, K, Holz, F, Kamenshchikov, I, Kapur, N, Kasal, A, Khan, M, Kirtley, O, Knipe, D, Kõlves, K, Kölzer, S, Krivda, H, Leske, S, Madeddu, F, Marshall, A, Memon, A, Mittendorfer-Rutz, E, Nestadt, P, Neznanov, N, Niederkrotenthaler, T, Nielsen, E, Nordentoft, M, Oberlerchner, H, O'Connor, R, Papsdorf, R, Partonen, T, Phillips, M, Platt, S, Portzky, G, Psota, G, Qin, P, Radeloff, D, Reif, A, Reif-Leonhard, C, Rezaeian, M, Román-Vázquez, N, Roskar, S, Rozanov, V, Sara, G, Scavacini, K, Schneider, B, Semenova, N, Sinyor, M, Tambuzzi, S, Townsend, E, Ueda, M, Wasserman, D, Webb, R, Winkler, P, Yip, P, Zalsman, G, Zoja, R, John, A, Spittal, M, Pirkis J, Gunnell D, Shin S, Del Pozo-Banos M, Arya V, Aguilar PA, Appleby L, Arafat SMY, Arensman E, Ayuso-Mateos JL, Balhara YPS, Bantjes J, Baran A, Behera C, Bertolote J, Borges G, Bray M, Brečić P, Caine E, Calati R, Carli V, Castelpietra G, Chan LF, Chang SS, Colchester D, Coss-Guzmán M, Crompton D, Ćurković M, Dandona R, De Jaegere E, De Leo D, Deisenhammer EA, Dwyer J, Erlangsen A, Faust JS, Fornaro M, Fortune S, Garrett A, Gentile G, Gerstner R, Gilissen R, Gould M, Gupta SK, Hawton K, Holz F, Kamenshchikov I, Kapur N, Kasal A, Khan M, Kirtley OJ, Knipe D, Kõlves K, Kölzer SC, Krivda H, Leske S, Madeddu F, Marshall A, Memon A, Mittendorfer-Rutz E, Nestadt P, Neznanov N, Niederkrotenthaler T, Nielsen E, Nordentoft M, Oberlerchner H, O'Connor RC, Papsdorf R, Partonen T, Phillips MR, Platt S, Portzky G, Psota G, Qin P, Radeloff D, Reif A, Reif-Leonhard C, Rezaeian M, Román-Vázquez N, Roskar S, Rozanov V, Sara G, Scavacini K, Schneider B, Semenova N, Sinyor M, Tambuzzi S, Townsend E, Ueda M, Wasserman D, Webb RT, Winkler P, Yip PSF, Zalsman G, Zoja R, John A, Spittal MJ, Pirkis, J, Gunnell, D, Shin, S, Del Pozo-Banos, M, Arya, V, Aguilar, P, Appleby, L, Arafat, S, Arensman, E, Ayuso-Mateos, J, Balhara, Y, Bantjes, J, Baran, A, Behera, C, Bertolote, J, Borges, G, Bray, M, Brečić, P, Caine, E, Calati, R, Carli, V, Castelpietra, G, Chan, L, Chang, S, Colchester, D, Coss-Guzmán, M, Crompton, D, Ćurković, M, Dandona, R, De Jaegere, E, De Leo, D, Deisenhammer, E, Dwyer, J, Erlangsen, A, Faust, J, Fornaro, M, Fortune, S, Garrett, A, Gentile, G, Gerstner, R, Gilissen, R, Gould, M, Gupta, S, Hawton, K, Holz, F, Kamenshchikov, I, Kapur, N, Kasal, A, Khan, M, Kirtley, O, Knipe, D, Kõlves, K, Kölzer, S, Krivda, H, Leske, S, Madeddu, F, Marshall, A, Memon, A, Mittendorfer-Rutz, E, Nestadt, P, Neznanov, N, Niederkrotenthaler, T, Nielsen, E, Nordentoft, M, Oberlerchner, H, O'Connor, R, Papsdorf, R, Partonen, T, Phillips, M, Platt, S, Portzky, G, Psota, G, Qin, P, Radeloff, D, Reif, A, Reif-Leonhard, C, Rezaeian, M, Román-Vázquez, N, Roskar, S, Rozanov, V, Sara, G, Scavacini, K, Schneider, B, Semenova, N, Sinyor, M, Tambuzzi, S, Townsend, E, Ueda, M, Wasserman, D, Webb, R, Winkler, P, Yip, P, Zalsman, G, Zoja, R, John, A, Spittal, M, Pirkis J, Gunnell D, Shin S, Del Pozo-Banos M, Arya V, Aguilar PA, Appleby L, Arafat SMY, Arensman E, Ayuso-Mateos JL, Balhara YPS, Bantjes J, Baran A, Behera C, Bertolote J, Borges G, Bray M, Brečić P, Caine E, Calati R, Carli V, Castelpietra G, Chan LF, Chang SS, Colchester D, Coss-Guzmán M, Crompton D, Ćurković M, Dandona R, De Jaegere E, De Leo D, Deisenhammer EA, Dwyer J, Erlangsen A, Faust JS, Fornaro M, Fortune S, Garrett A, Gentile G, Gerstner R, Gilissen R, Gould M, Gupta SK, Hawton K, Holz F, Kamenshchikov I, Kapur N, Kasal A, Khan M, Kirtley OJ, Knipe D, Kõlves K, Kölzer SC, Krivda H, Leske S, Madeddu F, Marshall A, Memon A, Mittendorfer-Rutz E, Nestadt P, Neznanov N, Niederkrotenthaler T, Nielsen E, Nordentoft M, Oberlerchner H, O'Connor RC, Papsdorf R, Partonen T, Phillips MR, Platt S, Portzky G, Psota G, Qin P, Radeloff D, Reif A, Reif-Leonhard C, Rezaeian M, Román-Vázquez N, Roskar S, Rozanov V, Sara G, Scavacini K, Schneider B, Semenova N, Sinyor M, Tambuzzi S, Townsend E, Ueda M, Wasserman D, Webb RT, Winkler P, Yip PSF, Zalsman G, Zoja R, John A, and Spittal MJ

Abstract

Background: Predicted increases in suicide were not generally observed in the early months of the COVID-19 pandemic. However, the picture may be changing and patterns might vary across demographic groups. We aimed to provide a timely, granular picture of the pandemic's impact on suicides globally. Methods: We identified suicide data from official public-sector sources for countries/areas-within-countries, searching websites and academic literature and contacting data custodians and authors as necessary. We sent our first data request on 22nd June 2021 and stopped collecting data on 31st October 2021. We used interrupted time series (ITS) analyses to model the association between the pandemic's emergence and total suicides and suicides by sex-, age- and sex-by-age in each country/area-within-country. We compared the observed and expected numbers of suicides in the pandemic's first nine and first 10-15 months and used meta-regression to explore sources of variation. Findings: We sourced data from 33 countries (24 high-income, six upper-middle-income, three lower-middle-income; 25 with whole-country data, 12 with data for area(s)-within-the-country, four with both). There was no evidence of greater-than-expected numbers of suicides in the majority of countries/areas-within-countries in any analysis; more commonly, there was evidence of lower-than-expected numbers. Certain sex, age and sex-by-age groups stood out as potentially concerning, but these were not consistent across countries/areas-within-countries. In the meta-regression, different patterns were not explained by countries’ COVID-19 mortality rate, stringency of public health response, economic support level, or presence of a national suicide prevention strategy. Nor were they explained by countries’ income level, although the meta-regression only included data from high-income and upper-middle-income countries, and there were suggestions from the ITS analyses that lower-middle-income countries fared less well

Published
2022

14. Transgenerational concordance in parent-to-child transmission of suicidal behaviour: a retrospective, nationwide, register-based cohort study of 4 419 642 individuals in Denmark

Author

Ranning, A, Madsen, T, Hawton, K, Nordentoft, M, and Erlangsen, A

Subjects
Adult, Cohort Studies, Parents, Psychiatry and Mental health, Risk Factors, Denmark, Humans, Biological Psychiatry, Retrospective Studies, Suicidal Ideation
Abstract

Suicidal behaviour runs in families, but the nature of transgenerational concordance needs elucidation. The aim of this study was to examine parent-to-child transmission by investigating whether presence and nature of parental suicidal behaviour was associated with suicidal behaviour in children.We did a retrospective, nationwide, register-based cohort study in Demark using register data. We included all individuals born after 1953 who were 10 years or older and who were recorded as living in Denmark at some point between Jan 1, 1980, and Dec 31, 2016. Adults listed as living with their child at first registration in the Civil Registration System were considered as parents; later records of different legal parents allowed identification of potential step-parents. Self-reported ethnicity data were not available. Exposure to parental suicide attempt and suicide was identified using information from hospital contacts and causes of death from national registers. The examined outcomes were suicide attempt and death by suicide. We calculated incidence rate ratios (IRRs) and cumulative hazards for children's suicide attempt and suicide, taking into account type of parental suicidal behaviour, child's age of exposure, and sex.In total, 4 419 642 individuals aged 10-63 years were observed during 1980-2016. Of these individuals, 150 222 (3·4%) were exposed to one or more parents with a suicide attempt, 31 564 (0·7%) to at least one parent who died by suicide, and 12 834 (0·3%) to both events. Individuals exposed to parental suicide attempt had higher rates of suicide attempt (IRR 2·72 [95% CI 2·33-3·17]) than individuals exposed to parental suicide (1·77 [1·50-2·09]) when compared with unexposed individuals. Higher rates of suicide were found for individuals exposed to parental suicide (IRR 3·18 [95% CI 2·84-3·58]) than for those exposed to parental suicide attempt (2·37 [2·19-2·57]). The cumulative hazard of suicide attempt was 0·07 for individuals exposed to parental suicide attempt, and the cumulative hazard of suicide was 0·009 for individuals exposed to parental suicide. Individuals exposed to parental suicide had higher odds of violent suicidal methods than those exposed to suicide attempt alone (odds ratio 2·0 [95% CI 1·7-2·3]).A concordant pattern of higher rates of the same type of suicidal behaviour as the one of the parents was observed, including type of suicide method. Preventive, family-oriented interventions are warranted to mitigate familial transmission of risk, as are clinical considerations of familial exposure in risk assessment of patients.Mental Health Services, Capital Region of Denmark.

Published
2022

17. Genome-wide analyses of ADHD identify 27 risk loci, refine the genetic architecture and implicate several cognitive domains.

Author

Demontis, D., Walters, G.B., Athanasiadis, G., Walters, R., Therrien, K., Nielsen, T.T., Farajzadeh, L., Voloudakis, G., Bendl, J., Zeng, B., Zhang, W, Grove, J, Als, T.D., Duan, J., Satterstrom, F.K., Bybjerg-Grauholm, J., Bækved-Hansen, M., Gudmundsson, O.O., Magnusson, S.H., Baldursson, G., Davidsdottir, K., Haraldsdottir, G.S., Agerbo, E., Hoffman, G.E., Dalsgaard, S., Martin, J., Ribasés, M., Boomsma, D.I., Soler Artigas, M., Roth Mota, N., Howrigan, D., Medland, S.E., Zayats, T., Rajagopal, V.M., Nordentoft, M., Mors, O., Hougaard, D.M., Mortensen, P.B., Daly, M.J., Faraone, S.V, Stefansson, H., Roussos, P., Franke, B., Werge, T., Neale, B.M., Stefansson, K., Børglum, A.D., Demontis, D., Walters, G.B., Athanasiadis, G., Walters, R., Therrien, K., Nielsen, T.T., Farajzadeh, L., Voloudakis, G., Bendl, J., Zeng, B., Zhang, W, Grove, J, Als, T.D., Duan, J., Satterstrom, F.K., Bybjerg-Grauholm, J., Bækved-Hansen, M., Gudmundsson, O.O., Magnusson, S.H., Baldursson, G., Davidsdottir, K., Haraldsdottir, G.S., Agerbo, E., Hoffman, G.E., Dalsgaard, S., Martin, J., Ribasés, M., Boomsma, D.I., Soler Artigas, M., Roth Mota, N., Howrigan, D., Medland, S.E., Zayats, T., Rajagopal, V.M., Nordentoft, M., Mors, O., Hougaard, D.M., Mortensen, P.B., Daly, M.J., Faraone, S.V, Stefansson, H., Roussos, P., Franke, B., Werge, T., Neale, B.M., Stefansson, K., and Børglum, A.D.

Abstract

01 februari 2023, Item does not contain fulltext, Attention-deficit hyperactivity disorder (ADHD) is a prevalent neurodevelopmental disorder with a major genetic component. Here, we present a genome-wide association study meta-analysis of ADHD comprising 38,691 individuals with ADHD and 186,843 controls. We identified 27 genome-wide significant loci, highlighting 76 potential risk genes enriched among genes expressed particularly in early brain development. Overall, ADHD genetic risk was associated with several brain-specific neuronal subtypes and midbrain dopaminergic neurons. In exome-sequencing data from 17,896 individuals, we identified an increased load of rare protein-truncating variants in ADHD for a set of risk genes enriched with probable causal common variants, potentially implicating SORCS3 in ADHD by both common and rare variants. Bivariate Gaussian mixture modeling estimated that 84-98% of ADHD-influencing variants are shared with other psychiatric disorders. In addition, common-variant ADHD risk was associated with impaired complex cognition such as verbal reasoning and a range of executive functions, including attention.

Published
2023

18. Impact of adverse childhood experiences on educational achievements in young people at clinical high risk of developing psychosis

Author

Tognin, S, Catalan, A, Kempton, MJ, Nelson, B, McGorry, P, Riecher-Rossler, A, Bressan, R, Barrantes-Vidal, N, Krebs, M-O, Nordentoft, M, Ruhrmann, S, Sachs, G, Rutten, BPF, van Os, J, de Haan, L, van der Gaag, M, McGuire, PR, Valmaggia, L, Tognin, S, Catalan, A, Kempton, MJ, Nelson, B, McGorry, P, Riecher-Rossler, A, Bressan, R, Barrantes-Vidal, N, Krebs, M-O, Nordentoft, M, Ruhrmann, S, Sachs, G, Rutten, BPF, van Os, J, de Haan, L, van der Gaag, M, McGuire, PR, and Valmaggia, L

Abstract

BACKGROUND: Adverse childhood experiences (ACE) can affect educational attainments, but little is known about their impact on educational achievements in people at clinical high risk of psychosis (CHR). METHODS: In total, 344 CHR individuals and 67 healthy controls (HC) were recruited as part of the European Community's Seventh Framework Programme-funded multicenter study the European Network of National Schizophrenia Networks Studying Gene-Environment Interactions (EU-GEI). The brief version of the Child Trauma Questionnaire was used to measure ACE, while educational attainments were assessed using a semi-structured interview. RESULTS: At baseline, compared with HC, the CHR group spent less time in education and had higher rates of ACE, lower rates of employment, and lower estimated intelligence quotient (IQ). Across both groups, the total number of ACE was associated with fewer days in education and lower level of education. Emotional abuse was associated with fewer days in education in HC. Emotional neglect was associated with a lower level of education in CHR, while sexual abuse was associated with a lower level of education in HC. In the CHR group, the total number of ACE, physical abuse, and neglect was significantly associated with unemployment, while emotional neglect was associated with employment. CONCLUSIONS: ACE are strongly associated with developmental outcomes such as educational achievement. Early intervention for psychosis programs should aim at integrating specific interventions to support young CHR people in their educational and vocational recovery. More generally, public health and social interventions focused on the prevention of ACE (or reduce their impact if ACE occur) are recommended.

Published
2023

19. How effective are organizational-level interventions in improving the psychosocial work environment, health, and retention of workers? A systematic overview of systematic reviews

Author

Aust, B., Moller, J.L., Nordentoft, M., Frydendall, K.B., Bengtsen, E., Jensen, A.B., Garde, A.H., Kompier, M.A.J., Semmer, N., Rugulies, R., Jaspers, S.O., Aust, B., Moller, J.L., Nordentoft, M., Frydendall, K.B., Bengtsen, E., Jensen, A.B., Garde, A.H., Kompier, M.A.J., Semmer, N., Rugulies, R., and Jaspers, S.O.

Abstract

Contains fulltext : 296348.pdf (Publisher’s version ) (Open Access), Objective: This study aimed to systematically review the effectiveness of organizational-level interventions in improving the psychosocial work environment and workers’ health and retention. Methods: We conducted an overview of systematic reviews on organizational-level interventions published between 2000 and 2020. We systematically searched academic databases, screened reference lists, and contacted experts, yielding 27 736 records. Of the 76 eligible reviews, 24 of weak quality were excluded, yielding 52 reviews of moderate (N=32) or strong (N=20) quality, covering 957 primary studies. We assessed quality of evidence based on quality of review, consistency of results, and proportion of controlled studies. Results: Of the 52 reviews, 30 studied a specific intervention approach and 22 specific outcomes. Regarding intervention approaches, we found strong quality of evidence for interventions focusing on "changes in working time arrangements" and moderate quality of evidence for "influence on work tasks or work organization", "health care approach changes", and "improvements of the psychosocial work environment". Regarding outcomes, we found strong quality of evidence for interventions about "burnout" and moderate quality evidence for "various health and wellbeing outcomes". For all other types of interventions, quality of evidence was either low or inconclusive, including interventions on retention. Conclusions: This overview of reviews identified strong or moderate quality of evidence for the effectiveness of organizational-level interventions for four specific intervention approaches and two health outcomes. This suggests that the work environment and the health of employees can be improved by certain organizational-level interventions. We need more research, especially about implementation and context, to improve the evidence.

Published
2023

20. Update to the study protocol Face Your Fears:Virtual reality-based cognitive behavioral therapy (VR-CBT) versus standard CBT for paranoid ideations in patients with schizophrenia spectrum disorders: a randomized clinical trial

Author

Jeppesen, Ulrik, Due, A. S., Mariegaard, L., Pinkham, A., Vos, M., Veling, W., Nordentoft, M., Glenthøj, L. B., Jeppesen, Ulrik, Due, A. S., Mariegaard, L., Pinkham, A., Vos, M., Veling, W., Nordentoft, M., and Glenthøj, L. B.

Abstract

We unfortunately need to make an update to our published study protocol that describes a significant change in the design of the study. The Committee on Health Research Ethics of the Capital Region Denmark recently rejected the approval of changing the primary outcome in the trial, on the invariable grounds that the trial has already commenced. It is therefore necessary to retain the Green Paranoid Thought Scale (GPTS) part B, ideas of persecution, as our primary outcome, and GPTS part A, ideas of social reference, as a secondary outcome, which is described opposite in our published study protocol. The exchange of outcomes has not affected participation in our trial or the informed consent. Intervention in both groups and assessments are unchanged. The two outcomes together constitute GPTS and the unifying concept we attempt to treat, namely paranoid ideations. As this is a blinded, methodologically rigorous trial, we did not have—and still do not have—access to preliminary data, and therefore, we have no knowledge of the distribution of our two intervention groups nor the potential effect of the intervention. The power calculation remains unchanged irrespective of the selection of the primary outcome. We have been fully transparent with the changes in primary and secondary outcomes on ClinicalTrials.gov throughout the trial. Due to the considerations mentioned above, we assumed that there would not be any ethical implications of the change of primary outcome. We sincerely apologize for the irregularity caused because of this assumption.

Published
2023

21. Genetic analyses identify widespread sex-differential participation bias

Author

Pirastu N., Cordioli M., Nandakumar P., Mignogna G., Abdellaoui A., Hollis B., Kanai M., Rajagopal V. M., Parolo P. D. B., Baya N., Carey C. E., Karjalainen J., Als T. D., Van der Zee M. D., Day F. R., Ong K. K., Agee M., Aslibekyan S., Bell R. K., Bryc K., Clark S. K., Elson S. L., Fletez-Brant K., Fontanillas P., Furlotte N. A., Gandhi P. M., Heilbron K., Hicks B., Huber K. E., Jewett E. M., Jiang Y., Kleinman A., Lin K. -H., Litterman N. K., Luff M. K., McIntyre M. H., McManus K. F., Mountain J. L., Mozaffari S. V., Noblin E. S., Northover C. A. M., O'Connell J., Petrakovitz A. A., Pitts S. J., Poznik G. D., Sathirapongsasuti J. F., Shelton J. F., Shringarpure S., Tian C., Tung J. Y., Tunney R. J., Vacic V., Wang X., Zare A., Mortensen P. B., Mors O., Werge T., Nordentoft M., Hougaard D. M., Bybjerg-Grauholm J., Baekvad-Hansen M., Morisaki T., de Geus E., Bellocco R., Okada Y., Borglum A. D., Joshi P., Auton A., Hinds D., Neale B. M., Walters R. K., Nivard M. G., Perry J. R. B., Ganna A., Pirastu, N, Cordioli, M, Nandakumar, P, Mignogna, G, Abdellaoui, A, Hollis, B, Kanai, M, Rajagopal, V, Parolo, P, Baya, N, Carey, C, Karjalainen, J, Als, T, Van der Zee, M, Day, F, Ong, K, Agee, M, Aslibekyan, S, Bell, R, Bryc, K, Clark, S, Elson, S, Fletez-Brant, K, Fontanillas, P, Furlotte, N, Gandhi, P, Heilbron, K, Hicks, B, Huber, K, Jewett, E, Jiang, Y, Kleinman, A, Lin, K, Litterman, N, Luff, M, Mcintyre, M, Mcmanus, K, Mountain, J, Mozaffari, S, Noblin, E, Northover, C, O'Connell, J, Petrakovitz, A, Pitts, S, Poznik, G, Sathirapongsasuti, J, Shelton, J, Shringarpure, S, Tian, C, Tung, J, Tunney, R, Vacic, V, Wang, X, Zare, A, Mortensen, P, Mors, O, Werge, T, Nordentoft, M, Hougaard, D, Bybjerg-Grauholm, J, Baekvad-Hansen, M, Morisaki, T, de Geus, E, Bellocco, R, Okada, Y, Borglum, A, Joshi, P, Auton, A, Hinds, D, Neale, B, Walters, R, Nivard, M, Perry, J, Ganna, A, Biological Psychology, APH - Personalized Medicine, APH - Mental Health, and Adult Psychiatry

Subjects
Adult, Inheritance Pattern, Male, Sex Characteristics, Inheritance Patterns, Sex Characteristic, Polymorphism, Single Nucleotide, Article, United Kingdom, Bias, Genetic Loci, Sample Size, Bia, Artifact, Biological Specimen Bank, Humans, Chromosomes, Human, Female, Artifacts, Biological Specimen Banks, Genome-Wide Association Study, Human
Abstract

Genetic association results are often interpreted with the assumption that study participation does not affect downstream analyses. Understanding the genetic basis of participation bias is challenging since it requires the genotypes of unseen individuals. Here we demonstrate that it is possible to estimate comparative biases by performing a genome-wide association study contrasting one subgroup versus another. For example, we showed that sex exhibits artifactual autosomal heritability in the presence of sex-differential participation bias. By performing a genome-wide association study of sex in approximately 3.3 million males and females, we identified over 158 autosomal loci spuriously associated with sex and highlighted complex traits underpinning differences in study participation between the sexes. For example, the body mass index-increasing allele at FTO was observed at higher frequency in males compared to females (odds ratio = 1.02, P = 4.4 × 10-36). Finally, we demonstrated how these biases can potentially lead to incorrect inferences in downstream analyses and propose a conceptual framework for addressing such biases. Our findings highlight a new challenge that genetic studies may face as sample sizes continue to grow.

Published
2021

22. The Danish Schizophrenia Registry

Author

Baandrup L, Cerqueira C, Haller L, Korshoej L, Voldsgaard I, and Nordentoft M

Subjects
schizophrenia, national registry, quality of care, Infectious and parasitic diseases, RC109-216
Abstract

Lone Baandrup,1 Charlotte Cerqueira,2 Lea Haller,3 Lene Korshøj,3 Inge Voldsgaard,4 Merete Nordentoft5 1Centre for Neuropsychiatric Schizophrenia Research (CNSR) and Centre for Clinical Intervention and Neuropsychiatric Schizophrenia Research (CINS), Mental Health Centre Glostrup, Copenhagen University Hospital, Glostrup, 2Registry Support Centre (East) – Epidemiology and Biostatistics, Research Centre for Prevention and Health, Capital Region of Denmark, Copenhagen, 3The Danish Clinical Registries, Registry Support Centre for Health Quality and Informatics (KCKS-West), Aarhus, 4Psychosis Ward, Section P, Aarhus University Hospital, Risskov, 5Mental Health Centre Copenhagen, Mental Health Services in the Capital Region of Denmark, University of Copenhagen, Copenhagen, DenmarkAim of database: To systematically monitor and improve the quality of treatment and care of patients with schizophrenia in Denmark. In addition, the database is accessible as a resource for research.Study population: Patients diagnosed with schizophrenia and receiving mental health care in psychiatric hospitals or outpatient clinics. During the first year after the diagnosis, patients are classified as incident patients, and after this period as prevalent patients.Main variables: The registry currently contains 21 clinical quality measures in relation to the following domains: diagnostic evaluation, antipsychotic treatment including adverse reactions, cardiovascular risk factors including laboratory values, family intervention, psychoeducation, postdischarge mental health care, assessment of suicide risk in relation to discharge, and assessment of global functioning.Descriptive data: The recorded data are available electronically for the reporting clinicians and responsible administrative personnel, and they are updated monthly. The registry publishes the national and regional results of all included quality measures in the annual audit reports. External researchers may obtain access to the data for use in specific research projects by applying to the steering committee.Conclusion: The Danish Schizophrenia Registry represents a valuable source of informative data to monitor and improve the quality of care of patients with schizophrenia in Denmark. However, continuous resources and time devoted is necessary to maintain the integrity of the registry and the validity of the data. Keywords: schizophrenia, national registry, quality of care, antipsychotic, adverse reactions, family intervention

Published
2016

25. The future of human behaviour research

Author

Box-Steffensmeier, JM, Burgess, J, Corbetta, M, Crawford, K, Duflo, E, Fogarty, L, Gopnik, A, Hanafi, S, Herrero, M, Hong, Y-Y, Kameyama, Y, Lee, TMC, Leung, GM, Nagin, DS, Nobre, AC, Nordentoft, M, Okbay, A, Perfors, A, Rival, LM, Sugimoto, CR, Tungodden, B, Wagner, C, Economics, Tinbergen Institute, and Amsterdam Neuroscience - Complex Trait Genetics

Subjects
Sozialwissenschaften, Soziologie, Social Psychology, Social Sciences, Experimental and Cognitive Psychology, Behavioral Neuroscience, ddc:150, Allgemeines zu den Sozialwissenschaften, Entwicklung und Geschichte der Sozialwissenschaften, Artificial Intelligence, Anthropology, ddc:300, Humans, Social sciences, sociology, anthropology, General Problems, History of the Social Sciences, Behavioral Research
Abstract

Nature human behaviour 6(1), 15-24 (2022). doi:10.1038/s41562-021-01275-6, Published by Nature Research, London

Published
2022

26. Impact of adverse childhood experiences on educational achievements in young people at clinical high risk of developing psychosis

Author

Tognin, S., Catalan, A., Kempton, M.J., Nelson, B., McGorry, P., Riecher-Rossler, A., Bressan, R., Barrantes-Vidal, N., Krebs, M.O., Nordentoft, M., Ruhrmann, S., Sachs, G., Rutten, B.P.F., van Os, J., de Haan, L., van der Gaag, M., McGuire, P., Valmaggia, L.R., RS: MHeNs - R3 - Neuroscience, Psychiatrie & Neuropsychologie, and MUMC+: MA Psychiatrie (3)

Subjects
education, EMOTION RECOGNITION, ADULTS, clinical high risk for psychosis, Psychiatry and Mental health, INDIVIDUALS, ULTRA-HIGH RISK, SCHOOL, ACADEMIC-ACHIEVEMENT, EMPLOYMENT, Adverse childhood experiences, PROTECTIVE FACTORS, MENTAL-HEALTH, TRAUMA
Abstract

Background Adverse childhood experiences (ACE) can affect educational attainments, but little is known about their impact on educational achievements in people at clinical high risk of psychosis (CHR). Methods In total, 344 CHR individuals and 67 healthy controls (HC) were recruited as part of the European Community’s Seventh Framework Programme-funded multicenter study the European Network of National Schizophrenia Networks Studying Gene–Environment Interactions (EU-GEI). The brief version of the Child Trauma Questionnaire was used to measure ACE, while educational attainments were assessed using a semi-structured interview. Results At baseline, compared with HC, the CHR group spent less time in education and had higher rates of ACE, lower rates of employment, and lower estimated intelligence quotient (IQ). Across both groups, the total number of ACE was associated with fewer days in education and lower level of education. Emotional abuse was associated with fewer days in education in HC. Emotional neglect was associated with a lower level of education in CHR, while sexual abuse was associated with a lower level of education in HC. In the CHR group, the total number of ACE, physical abuse, and neglect was significantly associated with unemployment, while emotional neglect was associated with employment. Conclusions ACE are strongly associated with developmental outcomes such as educational achievement. Early intervention for psychosis programs should aim at integrating specific interventions to support young CHR people in their educational and vocational recovery. More generally, public health and social interventions focused on the prevention of ACE (or reduce their impact if ACE occur) are recommended.

Published
2023

28. EPA guidance on assessment of cognitive impairment in schizophrenia

Author

Vita A., Gaebel W., Mucci A., Sachs G., Erfurth A., Barlati S., Zanca F., Giordano G. M., Glenthoj L. B., Nordentoft M., Galderisi S., Vita, A., Gaebel, W., Mucci, A., Sachs, G., Erfurth, A., Barlati, S., Zanca, F., Giordano, G. M., Glenthoj, L. B., Nordentoft, M., and Galderisi, S.

Subjects
Assessment instrument, Psychotic Disorder, cognitive functioning, high-risk for psychosi, schizophrenia, Cognition Disorder, early psychosi, systematic review, evidence-based, psychosocial functioning, Neuropsychological Test, Schizophrenic Psychology, Cognitive Dysfunction, Human
Abstract

Background. Impairment in a wide range of cognitive abilities has been consistently reported in individuals with schizophrenia. Both neurocognitive and social cognitive deficits are thought to underlie severe functional disabilities associated with schizophrenia. Despite the key role in schizophrenia outcome, cognition is still poorly assessed in both research and clinical settings. Methods. In this guidance paper, we provide a systematic review of the scientific literature and elaborate several recommendations for the assessment of cognitive functions in schizophrenia both in research settings and in real-world clinical practice. Results. Expert consensus and systematic reviews provided guidance for the optimal assessment of cognitive functions in schizophrenia. Based on the reviewed evidence, we recommend a comprehensive and systematic assessment of neurocognitive and social cognitive domains in schizophrenia, in all phases of the disorder, as well as in subjects at risk to develop psychosis. This European Psychiatric Association guidance recommends not only the use of observer reports, but also self-reports and interview-based cognitive assessment tools. The guidance also provides a systematic review of the state of the art of assessment in first episode of psychosis patients and in individuals at risk for psychosis. Conclusion. The comprehensive review of the evidence and the recommendations might contribute to advance the field, allowing a better cognitive assessment, avoiding overlaps with other psychopathological dimensions. The dissemination of this guidance paper may promote the development of shared guidelines concerning the assessment of cognitive functions in schizophrenia, with the purpose to improve the quality of care and to obtain recovery.

Published
2022

29. EPA Guidance on treatment of cognitive impairment in schizophrenia

Author

Vita A., Gaebel W., Mucci A., Sachs G., Barlati S., Giordano G. M., Nibbio G., Nordentoft M., Wykes T., Galderisi S., Vita, A., Gaebel, W., Mucci, A., Sachs, G., Barlati, S., Giordano, G. M., Nibbio, G., Nordentoft, M., Wykes, T., and Galderisi, S.

Subjects
schizophrenia, Antipsychotic Agent, Benzodiazepine, systematic review, treatment, evidence-based, cognitive remediation, Cholinergic Antagonist, Schizophrenic Psychology, Cognitive Dysfunction, cognitive enhancement, Cognitive functioning, Human
Abstract

Background. Although cognitive impairment is a core symptom of schizophrenia related to poorer outcomes in different functional domains, it still remains a major therapeutic challenge. To date, no comprehensive treatment guidelines for cognitive impairment in schizophrenia are implemented. Methods. The aim of the present guidance paper is to provide a comprehensive meta-review of the current available evidence-based treatments for cognitive impairment in schizophrenia. The guidance is structured into three sections: pharmacological treatment, psychosocial interventions, and somatic treatments. Results. Based on the reviewed evidence, this European Psychiatric Association guidance recommends an appropriate pharmacological management as a fundamental starting point in the treatment of cognitive impairment in schizophrenia. In particular, second-generation antipsychotics are recommended for their favorable cognitive profile compared to first generation antipsychotics, although no clear superiority of a single second-generation antipsychotic has currently been found. Anticholinergic and benzodiazepine burden should be kept to a minimum, considering the negative impact on cognitive functioning. Among psychosocial interventions, cognitive remediation and physical exercise are recommended for the treatment of cognitive impairment in schizophrenia. Non-invasive brain stimulation techniques could be taken into account as add on therapy. Conclusion. Overall, there is definitive progress in the field, but further research is needed to develop specific treatments for cognitive impairment in schizophrenia. The dissemination of this guidance paper may promote the development of shared guidelines concerning the treatment of cognitive functions in schizophrenia, with the purpose to improve the quality of care and to achieve recovery in this population.

Published
2022

30. Genetic analyses identify widespread sex-differential participation bias

Author

Pirastu, N, Cordioli, M, Nandakumar, P, Mignogna, G, Abdellaoui, A, Hollis, B, Kanai, M, Rajagopal, V, Parolo, P, Baya, N, Carey, C, Karjalainen, J, Als, T, Van der Zee, M, Day, F, Ong, K, Agee, M, Aslibekyan, S, Bell, R, Bryc, K, Clark, S, Elson, S, Fletez-Brant, K, Fontanillas, P, Furlotte, N, Gandhi, P, Heilbron, K, Hicks, B, Huber, K, Jewett, E, Jiang, Y, Kleinman, A, Lin, K, Litterman, N, Luff, M, Mcintyre, M, Mcmanus, K, Mountain, J, Mozaffari, S, Noblin, E, Northover, C, O'Connell, J, Petrakovitz, A, Pitts, S, Poznik, G, Sathirapongsasuti, J, Shelton, J, Shringarpure, S, Tian, C, Tung, J, Tunney, R, Vacic, V, Wang, X, Zare, A, Mortensen, P, Mors, O, Werge, T, Nordentoft, M, Hougaard, D, Bybjerg-Grauholm, J, Baekvad-Hansen, M, Morisaki, T, de Geus, E, Bellocco, R, Okada, Y, Borglum, A, Joshi, P, Auton, A, Hinds, D, Neale, B, Walters, R, Nivard, M, Perry, J, Ganna, A, Pirastu N., Cordioli M., Nandakumar P., Mignogna G., Abdellaoui A., Hollis B., Kanai M., Rajagopal V. M., Parolo P. D. B., Baya N., Carey C. E., Karjalainen J., Als T. D., Van der Zee M. D., Day F. R., Ong K. K., Agee M., Aslibekyan S., Bell R. K., Bryc K., Clark S. K., Elson S. L., Fletez-Brant K., Fontanillas P., Furlotte N. A., Gandhi P. M., Heilbron K., Hicks B., Huber K. E., Jewett E. M., Jiang Y., Kleinman A., Lin K. -H., Litterman N. K., Luff M. K., McIntyre M. H., McManus K. F., Mountain J. L., Mozaffari S. V., Noblin E. S., Northover C. A. M., O'Connell J., Petrakovitz A. A., Pitts S. J., Poznik G. D., Sathirapongsasuti J. F., Shelton J. F., Shringarpure S., Tian C., Tung J. Y., Tunney R. J., Vacic V., Wang X., Zare A., Mortensen P. B., Mors O., Werge T., Nordentoft M., Hougaard D. M., Bybjerg-Grauholm J., Baekvad-Hansen M., Morisaki T., de Geus E., Bellocco R., Okada Y., Borglum A. D., Joshi P., Auton A., Hinds D., Neale B. M., Walters R. K., Nivard M. G., Perry J. R. B., Ganna A., Pirastu, N, Cordioli, M, Nandakumar, P, Mignogna, G, Abdellaoui, A, Hollis, B, Kanai, M, Rajagopal, V, Parolo, P, Baya, N, Carey, C, Karjalainen, J, Als, T, Van der Zee, M, Day, F, Ong, K, Agee, M, Aslibekyan, S, Bell, R, Bryc, K, Clark, S, Elson, S, Fletez-Brant, K, Fontanillas, P, Furlotte, N, Gandhi, P, Heilbron, K, Hicks, B, Huber, K, Jewett, E, Jiang, Y, Kleinman, A, Lin, K, Litterman, N, Luff, M, Mcintyre, M, Mcmanus, K, Mountain, J, Mozaffari, S, Noblin, E, Northover, C, O'Connell, J, Petrakovitz, A, Pitts, S, Poznik, G, Sathirapongsasuti, J, Shelton, J, Shringarpure, S, Tian, C, Tung, J, Tunney, R, Vacic, V, Wang, X, Zare, A, Mortensen, P, Mors, O, Werge, T, Nordentoft, M, Hougaard, D, Bybjerg-Grauholm, J, Baekvad-Hansen, M, Morisaki, T, de Geus, E, Bellocco, R, Okada, Y, Borglum, A, Joshi, P, Auton, A, Hinds, D, Neale, B, Walters, R, Nivard, M, Perry, J, Ganna, A, Pirastu N., Cordioli M., Nandakumar P., Mignogna G., Abdellaoui A., Hollis B., Kanai M., Rajagopal V. M., Parolo P. D. B., Baya N., Carey C. E., Karjalainen J., Als T. D., Van der Zee M. D., Day F. R., Ong K. K., Agee M., Aslibekyan S., Bell R. K., Bryc K., Clark S. K., Elson S. L., Fletez-Brant K., Fontanillas P., Furlotte N. A., Gandhi P. M., Heilbron K., Hicks B., Huber K. E., Jewett E. M., Jiang Y., Kleinman A., Lin K. -H., Litterman N. K., Luff M. K., McIntyre M. H., McManus K. F., Mountain J. L., Mozaffari S. V., Noblin E. S., Northover C. A. M., O'Connell J., Petrakovitz A. A., Pitts S. J., Poznik G. D., Sathirapongsasuti J. F., Shelton J. F., Shringarpure S., Tian C., Tung J. Y., Tunney R. J., Vacic V., Wang X., Zare A., Mortensen P. B., Mors O., Werge T., Nordentoft M., Hougaard D. M., Bybjerg-Grauholm J., Baekvad-Hansen M., Morisaki T., de Geus E., Bellocco R., Okada Y., Borglum A. D., Joshi P., Auton A., Hinds D., Neale B. M., Walters R. K., Nivard M. G., Perry J. R. B., and Ganna A.

Abstract

Genetic association results are often interpreted with the assumption that study participation does not affect downstream analyses. Understanding the genetic basis of participation bias is challenging since it requires the genotypes of unseen individuals. Here we demonstrate that it is possible to estimate comparative biases by performing a genome-wide association study contrasting one subgroup versus another. For example, we showed that sex exhibits artifactual autosomal heritability in the presence of sex-differential participation bias. By performing a genome-wide association study of sex in approximately 3.3 million males and females, we identified over 158 autosomal loci spuriously associated with sex and highlighted complex traits underpinning differences in study participation between the sexes. For example, the body mass index–increasing allele at FTO was observed at higher frequency in males compared to females (odds ratio = 1.02, P = 4.4 × 10−36). Finally, we demonstrated how these biases can potentially lead to incorrect inferences in downstream analyses and propose a conceptual framework for addressing such biases. Our findings highlight a new challenge that genetic studies may face as sample sizes continue to grow.

Published
2021

33. List of Contributors

Author

Aas, M., primary, Abalo, R., additional, Abdel-Salam, O.M.E., additional, Abilio, V.C., additional, Adelli, G.R., additional, Ahmed, M.H., additional, Alhouayek, M., additional, Allen, J., additional, Allsop, D.J., additional, Almada, R.C., additional, Almeida, V., additional, Aloway, A., additional, Amanullah, S., additional, Ames, S.L., additional, Annaheim, B., additional, Appendino, G., additional, Aramaki, H., additional, Arias-Horcajadas, F., additional, Ariza, C., additional, Arnold, J.C., additional, Asmaro, D., additional, Auwärter, V., additional, Bachmann, S., additional, Baker, A., additional, Balter, R.E., additional, Baraldi, P.G., additional, Barber, P.A., additional, Barbería, E., additional, Bar-Sela, G., additional, Bastiani, L., additional, Basu, D., additional, Basurte, I., additional, Beck, O., additional, Behrendt, S., additional, Bergen-Cico, D., additional, Berrendero, F., additional, Bhagav, P., additional, Bhattacharyya, S., additional, Bioque, M., additional, Bolkent, S., additional, Boman, J.H., additional, Bondallaz, P., additional, Bonnet, U., additional, Borges, R.S., additional, Borowiak, K., additional, Boschi, I., additional, Brents, L.K., additional, Bridts, C.H., additional, Bruno, A., additional, Burrows, B.T., additional, Busatto, G.F., additional, Callaghan, R.C., additional, Campos, A.C., additional, Camsari, U.M., additional, Canfield, A., additional, Carra, E., additional, Carrillo-Salinas, F.-J., additional, Cascini, F., additional, Castelli, M.P., additional, Cawich, S.O., additional, Cawston, E.E., additional, Cedro, C., additional, Chagas, M.H.N., additional, Chen, C., additional, Chisari, C., additional, Chtioui, H., additional, Cico, R.D., additional, Ciechomska, I.A., additional, Coimbra, N.C., additional, Cole, J., additional, Cookey, J., additional, Copeland, J., additional, Coskun, Z.M., additional, Crano, W.D., additional, Crippa, J.A.S., additional, Crocker, C.E., additional, Cuesta, M.J., additional, Cunha, P.J., additional, Cutando, L., additional, da Silva, A.B.F., additional, da Silva, J.A., additional, da Silva, V.K., additional, Dan, D., additional, De Boni, R.B., additional, Rodríguez de Fonseca, F., additional, Gómez de Heras, R., additional, de Oliveira, A.C.P., additional, de Souza Crippa, A.C., additional, de Souza Crippa, J.A., additional, Degenhardt, F., additional, Degenhardt, L., additional, Deiana, S., additional, Deonarine, U., additional, Di Forti, M., additional, dos Anjos-Garcia, T., additional, Guimarães dos Santos, R., additional, Drozd, M., additional, Duran, F.L.S., additional, Earleywine, M., additional, Ebo, D.G., additional, Egashira, N., additional, Egnatios, J., additional, Ellert-Miklaszewska, A., additional, ElShebiney, S.A., additional, ElSohly, M.A., additional, Evren, C., additional, Fañanás, L., additional, Faber, M.M., additional, Farag, S., additional, Farré, A., additional, Farré, M., additional, Fatjó-Vilas, M., additional, Favrat, B., additional, Feingold, D., additional, Feliú, A., additional, Fernández, A.A., additional, Fernández-Artamendi, S., additional, Ferrari, A.J., additional, Ferraro, L., additional, Fichna, J., additional, Finlay, D.B., additional, Fiz, J., additional, Flores, Á., additional, Fogel, J.S., additional, Fornari, E., additional, Fortunato, L., additional, Fyfe, T., additional, Gaafar, A.E.D.M., additional, Gade, S., additional, Gaffal, E., additional, Galal, A.F., additional, Gandhi, R., additional, Gates, P., additional, Gatley, J.M., additional, Giroud, C., additional, Glass, M., additional, Goldberg, S.R., additional, González-Ortega, I., additional, González-Pinto, A., additional, Guaza, C., additional, Guillon, V., additional, Guimarães, F.S., additional, Gul, W., additional, Guven, F.M., additional, Hall, W.D., additional, Hallak, J.E.C., additional, Hamerle, M., additional, Haney, M., additional, Harding, H.E., additional, Hassan, S., additional, Haugland, K., additional, Healey, A., additional, Heck, C., additional, Helander, A., additional, Hernandez-Folgado, L., additional, Herzig, D.A., additional, Hesse, M., additional, Hill, M.G., additional, Hirst, R., additional, Hjorthøj, C.R., additional, Hoch, E., additional, Holder, M.D., additional, Holtkamp, M., additional, Hunter, M.R., additional, Ikeda, E., additional, Izumi, Y., additional, Janus, T., additional, Kaminska, B., additional, Kanaan, A.S., additional, Karinen, R., additional, Karl, T., additional, Katsu, T., additional, Kay-Lambkin, F., additional, Kayser, O., additional, Kells, M., additional, Kelly, B.C., additional, Kelly, T.H., additional, Kokona, A., additional, Kumar, A., additional, Kumar, P., additional, La Barbera, D., additional, Lagerberg, T.V., additional, Lahat, A., additional, Larsen, H.J., additional, Laun, A.S., additional, Lecomte, T., additional, Legleye, S., additional, Lev-Ran, S., additional, Lile, J.A., additional, Limberger, R.P., additional, Linares, I.M.P., additional, Lisdahl, K.M., additional, Little, M., additional, Liu, W., additional, Loflin, M.J., additional, Lorente-Omeñaca, R., additional, Lorenzetti, V., additional, Lu, D., additional, Mørland, J., additional, Müller-Vahl, K.R., additional, Machoy-Mokrzyńska, A., additional, Maeder, P., additional, Majumdar, S., additional, Maldonado, R., additional, Maple, K.E., additional, Marrón, T., additional, Martínez-Cengotitabengoa, M., additional, Martín-Fontelles, M. Isabel, additional, Martín-Santos, R., additional, Masuda, K., additional, McRae-Clark, A.L., additional, Mecha, M., additional, Medallo, J., additional, Melle, I., additional, Menahem, S., additional, Mendes-Gomes, J., additional, Mesías, B., additional, Miller, S., additional, Mizrahi, R., additional, Molinaro, S., additional, Moore, C., additional, Moraes, M.F., additional, Moreira, F.A., additional, Moreno-Izco, L., additional, Morris, H.A., additional, Muñoz, E., additional, Muccioli, G.G., additional, Muscatello, M.R.A., additional, Nada, S.A., additional, Naraynsingh, V., additional, Narimatsu, S., additional, Nogueira-Filho, G., additional, Nordentoft, M., additional, Oguz, G., additional, Øiestad, Å.M.L., additional, Øiestad, E.L., additional, Okazaki, H., additional, Olive, M.F., additional, Orio, L., additional, Ozaita, A., additional, Pérez, A., additional, Panagis, G., additional, Pandolfo, G., additional, Panlilio, L.V., additional, Paquin, K., additional, Parakh, P., additional, Parker, L.A., additional, Patel, V.B., additional, Pawson, M., additional, Peres, F.F., additional, Petras, H., additional, Pollastro, F., additional, Porcu, A., additional, Potente, R., additional, Potter, D.E., additional, Potvin, S., additional, Prats, C., additional, Preedy, V.R., additional, Rajendram, R., additional, Rathke, L., additional, Reed, K.L., additional, Repka, M.A., additional, Rigter, H., additional, Rock, E.M., additional, Rohrbacher, H., additional, Rosa, P.G.P., additional, Sánchez-Martínez, F., additional, Sánchez-Torres, A.M., additional, Sałaga, M., additional, Sabato, V., additional, Sanders, A.N., additional, Santos, L.C., additional, Scalese, M., additional, Schaufelberger, M.S., additional, Schröder, N., additional, Scimeca, G., additional, Secades-Villa, R., additional, Selvarajah, D., additional, Senormanci, O., additional, Shivakumar, K., additional, Shrier, L.A., additional, Siciliano, V., additional, Sideli, L., additional, Siegel, J.T., additional, Sleem, A.A., additional, Sobczyński, J., additional, Sodos, L., additional, Solowij, N., additional, Song, Z.-H., additional, Stacy, A.W., additional, Stehle, F., additional, Stogner, J.M., additional, Sussman, S., additional, Swift, W., additional, Szerman, N., additional, Tüting, T., additional, Aghazadeh Tabrizi, M., additional, Taglialatela-Scafati, O., additional, Takahashi, R.N., additional, Takeda, S., additional, Tarricone, I., additional, Tashkin, D.P., additional, Tellioğlu, T., additional, Tellioğlu, Z., additional, Tesfaye, S., additional, Thornton, L., additional, Thylstrup, B., additional, Tibbo, P.G., additional, Todd, G., additional, Torrens, M., additional, Tsai, J., additional, Tseng, H.-H., additional, Turner, A., additional, Tuv, S.S., additional, Ullah, F., additional, Van der Linden, T., additional, Van Gasse, A.L., additional, Vega, P., additional, Vera, G., additional, Verdichevski, M., additional, Vieira Sousa, T.R., additional, Vilela, L.R., additional, Vindenes, V., additional, Walsh, Z., additional, Watanabe, K., additional, Watterson, L.R., additional, White, J.M., additional, Wright, N.E., additional, Yücel, M., additional, Yamamoto, I., additional, Yamaori, S., additional, Zalesky, A., additional, Zalman, D., additional, Zhang, J., additional, Zhang, Y., additional, Zoccali, R., additional, Zorumski, C.F., additional, and Zuardi, A.W., additional

Published
2017
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36. NEURAPRO: a multi-centre RCT of omega-3 polyunsaturated fatty acids versus placebo in young people at ultra-high risk of psychotic disorders—medium-term follow-up and clinical course

Author

Nelson, B., Amminger, G. P., Yuen, H. P., Markulev, C., Lavoie, S., Schäfer, M. R., Hartmann, J. A., Mossaheb, N., Schlögelhofer, M., Smesny, S., Hickie, I. B., Berger, G., Chen, E. Y. H., de Haan, L., Nieman, D. H., Nordentoft, M., Riecher-Rössler, A., Verma, S., Thompson, A., Yung, A. R., and McGorry, P. D.

Published
2018
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37. CHALLENGE and Face Your Fears: Virtual Reality Treatment for Auditory Hallucinations and Paranoid Ideations

Author

Glenthøj, L., Smith, L., Mariegaard, L., Due, A. S., Christensen, A., Christensen, M., Vernal, D, Jeppesen, U., and Nordentoft, M.

Subjects
Psychiatry and Mental health
Abstract

Background: Many patients suffering from schizophrenia spectrum disorders continue having distressing auditory hallucinations and paranoid ideations despite receiving current treatment. Virtual reality assisted treatment offers the potential of advancing current psychotherapies for psychotic symptoms by creating virtual environments that can elicit responses (e.g. thoughts, feelings, behaviours) mirroring real-world settings. In two large-scale randomised clinical trials, we are investigating whether targeted virtual reality assisted psychotherapy can reduce psychotic symptoms and increase daily life functioning and quality of life. The CHALLENGE trial examines whether nine sessions of virtual reality-assisted psychotherapy is superior to nine sessions of standard treatments in reducing the severity, frequency, and distress of auditory hallucinations in patients with psychosis. In the Face your Fears trial we are investigating whether virtual reality assisted cognitive behavioral therapy (CBT) is superior to standard CBT in reducing levels of paranoid ideation in patients with psychosis spectrum disorders. Methods: The CHALLENGE and Face your Fears trials are randomised, assessor-blinded parallel-groups superiority clinical trials, allocating a total of 266 and 256 patients, respectively to either the experimental intervention or a control condition. The trials are currently enrolling patients; thus, no quantitative data is available yet. The main objective of this presentation is to give a qualitative account of this new psychotherapeutic methods as it is applied in both trials. Results: Qualitative data comprising case descriptions and video material will be presented at the conference. Discussion: The preliminary findings indicate great potential for these innovative treatments albeit important concerns regarding implementation will be raised. Disclosure No significant relationships.

Published
2022

38. High loading of polygenic risk in cases with chronic schizophrenia

Author

Meier, S M, Agerbo, E, Maier, R, Pedersen, C B, Lang, M, Grove, J, Hollegaard, M V, Demontis, D, Trabjerg, B B, Hjorthøj, C, Ripke, S, Degenhardt, F, Nöthen, M M, Rujescu, D, Maier, W, Werge, T, Mors, O, Hougaard, D M, Børglum, A D, Wray, N R, Rietschel, M, Nordentoft, M, Mortensen, P B, and Mattheisen, M

Published
2016
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46. Physical and mental health impact of COVID-19 on children, adolescents, and their families: The Collaborative Outcomes study on Health and Functioning during Infection Times - Children and Adolescents (COH-FIT-C&A)

Author

Solmi, M, Estradé, A, Thompson, T, Agorastos, A, Radua, J, Cortese, S, Dragioti, E, Leisch, F, Vancampfort, D, Thygesen, LC, Aschauer, H, Schloegelhofer, M, Akimova, E, Schneeberger, A, Huber, CG, Hasler, G, Conus, P, Cuénod, KQD, von Känel, R, Arrondo, G, Fusar-Poli, P, Gorwood, P, Llorca, PM, Krebs, MO, Scanferla, E, Kishimoto, T, Rabbani, G, Skonieczna-Żydecka, K, Brambilla, P, Favaro, A, Takamiya, A, Zoccante, L, Colizzi, M, Bourgin, J, Kamiński, K, Moghadasin, M, Seedat, S, Matthews, E, Wells, J, Vassilopoulou, E, Gadelha, A, Su, KP, Kwon, JS, Kim, M, Lee, TY, Papsuev, O, Manková, D, Boscutti, A, Gerunda, C, Saccon, D, Righi, E, Monaco, F, Croatto, G, Cereda, G, Demurtas, J, Brondino, N, Veronese, N, Enrico, P, Politi, P, Ciappolino, V, Pfennig, A, Bechdolf, A, Meyer-Lindenberg, A, Kahl, KG, Domschke, K, Bauer, M, Koutsouleris, N, Winter, S, Borgwardt, S, Bitter, I, Balazs, J, Czobor, P, Unoka, Z, Mavridis, D, Tsamakis, K, Bozikas, VP, Tunvirachaisakul, C, Maes, M, Rungnirundorn, T, Supasitthumrong, T, Haque, A, Brunoni, AR, Costardi, CG, Schuch, FB, Polanczyk, G, Luiz, JM, Fonseca, L, Aparicio, LV, Valvassori, SS, Nordentoft, M, Vendsborg, P, Hoffmann, SH, Sehli, J, Sartorius, N, Heuss, S, Guinart, D, Hamilton, J, Kane, J, Rubio, J, Sand, M, Marx, Wolf, Solmi, M, Estradé, A, Thompson, T, Agorastos, A, Radua, J, Cortese, S, Dragioti, E, Leisch, F, Vancampfort, D, Thygesen, LC, Aschauer, H, Schloegelhofer, M, Akimova, E, Schneeberger, A, Huber, CG, Hasler, G, Conus, P, Cuénod, KQD, von Känel, R, Arrondo, G, Fusar-Poli, P, Gorwood, P, Llorca, PM, Krebs, MO, Scanferla, E, Kishimoto, T, Rabbani, G, Skonieczna-Żydecka, K, Brambilla, P, Favaro, A, Takamiya, A, Zoccante, L, Colizzi, M, Bourgin, J, Kamiński, K, Moghadasin, M, Seedat, S, Matthews, E, Wells, J, Vassilopoulou, E, Gadelha, A, Su, KP, Kwon, JS, Kim, M, Lee, TY, Papsuev, O, Manková, D, Boscutti, A, Gerunda, C, Saccon, D, Righi, E, Monaco, F, Croatto, G, Cereda, G, Demurtas, J, Brondino, N, Veronese, N, Enrico, P, Politi, P, Ciappolino, V, Pfennig, A, Bechdolf, A, Meyer-Lindenberg, A, Kahl, KG, Domschke, K, Bauer, M, Koutsouleris, N, Winter, S, Borgwardt, S, Bitter, I, Balazs, J, Czobor, P, Unoka, Z, Mavridis, D, Tsamakis, K, Bozikas, VP, Tunvirachaisakul, C, Maes, M, Rungnirundorn, T, Supasitthumrong, T, Haque, A, Brunoni, AR, Costardi, CG, Schuch, FB, Polanczyk, G, Luiz, JM, Fonseca, L, Aparicio, LV, Valvassori, SS, Nordentoft, M, Vendsborg, P, Hoffmann, SH, Sehli, J, Sartorius, N, Heuss, S, Guinart, D, Hamilton, J, Kane, J, Rubio, J, Sand, M, and Marx, Wolf

Published
2022

47. The collaborative outcomes study on health and functioning during infection times in adults (COH-FIT-Adults): Design and methods of an international online survey targeting physical and mental health effects of the COVID-19 pandemic

Author

Solmi, M, Estradé, A, Thompson, T, Agorastos, A, Radua, J, Cortese, S, Dragioti, E, Leisch, F, Vancampfort, D, Thygesen, LC, Aschauer, H, Schloegelhofer, M, Akimova, E, Schneeberger, A, Huber, CG, Hasler, G, Conus, P, Cuénod, KQD, von Känel, R, Arrondo, G, Fusar-Poli, P, Gorwood, P, Llorca, PM, Krebs, MO, Scanferla, E, Kishimoto, T, Rabbani, G, Skonieczna-Żydecka, K, Brambilla, P, Favaro, A, Takamiya, A, Zoccante, L, Colizzi, M, Bourgin, J, Kamiński, K, Moghadasin, M, Seedat, S, Matthews, E, Wells, J, Vassilopoulou, E, Gadelha, A, Su, KP, Kwon, JS, Kim, M, Lee, TY, Papsuev, O, Manková, D, Boscutti, A, Gerunda, C, Saccon, D, Righi, E, Monaco, F, Croatto, G, Cereda, G, Demurtas, J, Brondino, N, Veronese, N, Enrico, P, Politi, P, Ciappolino, V, Pfennig, A, Bechdolf, A, Meyer-Lindenberg, A, Kahl, KG, Domschke, K, Bauer, M, Koutsouleris, N, Winter, S, Borgwardt, S, Bitter, I, Balazs, J, Czobor, P, Unoka, Z, Mavridis, D, Tsamakis, K, Bozikas, VP, Tunvirachaisakul, C, Maes, M, Rungnirundorn, T, Supasitthumrong, T, Haque, A, Brunoni, AR, Costardi, CG, Schuch, FB, Polanczyk, G, Luiz, JM, Fonseca, L, Aparicio, LV, Valvassori, SS, Nordentoft, M, Vendsborg, P, Hoffmann, SH, Sehli, J, Sartorius, N, Heuss, S, Guinart, D, Hamilton, J, Kane, J, Rubio, J, Sand, M, Berk, Michael, Solmi, M, Estradé, A, Thompson, T, Agorastos, A, Radua, J, Cortese, S, Dragioti, E, Leisch, F, Vancampfort, D, Thygesen, LC, Aschauer, H, Schloegelhofer, M, Akimova, E, Schneeberger, A, Huber, CG, Hasler, G, Conus, P, Cuénod, KQD, von Känel, R, Arrondo, G, Fusar-Poli, P, Gorwood, P, Llorca, PM, Krebs, MO, Scanferla, E, Kishimoto, T, Rabbani, G, Skonieczna-Żydecka, K, Brambilla, P, Favaro, A, Takamiya, A, Zoccante, L, Colizzi, M, Bourgin, J, Kamiński, K, Moghadasin, M, Seedat, S, Matthews, E, Wells, J, Vassilopoulou, E, Gadelha, A, Su, KP, Kwon, JS, Kim, M, Lee, TY, Papsuev, O, Manková, D, Boscutti, A, Gerunda, C, Saccon, D, Righi, E, Monaco, F, Croatto, G, Cereda, G, Demurtas, J, Brondino, N, Veronese, N, Enrico, P, Politi, P, Ciappolino, V, Pfennig, A, Bechdolf, A, Meyer-Lindenberg, A, Kahl, KG, Domschke, K, Bauer, M, Koutsouleris, N, Winter, S, Borgwardt, S, Bitter, I, Balazs, J, Czobor, P, Unoka, Z, Mavridis, D, Tsamakis, K, Bozikas, VP, Tunvirachaisakul, C, Maes, M, Rungnirundorn, T, Supasitthumrong, T, Haque, A, Brunoni, AR, Costardi, CG, Schuch, FB, Polanczyk, G, Luiz, JM, Fonseca, L, Aparicio, LV, Valvassori, SS, Nordentoft, M, Vendsborg, P, Hoffmann, SH, Sehli, J, Sartorius, N, Heuss, S, Guinart, D, Hamilton, J, Kane, J, Rubio, J, Sand, M, and Berk, Michael

Published
2022

48. The association of plasma inflammatory markers with omega-3 fatty acids and their mediating role in psychotic symptoms and functioning: An analysis of the NEURAPRO clinical trial

Author

Susai, SR, Mongan, D, Healy, C, Cannon, M, Nelson, B, Markulev, C, Schäfer, MR, Berger, M, Mossaheb, N, Schlögelhofer, M, Smesny, S, Hickie, IB, Berger, GE, Chen, EYH, de Haan, L, Nieman, DH, Nordentoft, M, Riecher-Rössler, A, Verma, S, Thompson, A, Yung, Alison, McGorry, PD, Föcking, M, Cotter, D, Amminger, GP, Susai, SR, Mongan, D, Healy, C, Cannon, M, Nelson, B, Markulev, C, Schäfer, MR, Berger, M, Mossaheb, N, Schlögelhofer, M, Smesny, S, Hickie, IB, Berger, GE, Chen, EYH, de Haan, L, Nieman, DH, Nordentoft, M, Riecher-Rössler, A, Verma, S, Thompson, A, Yung, Alison, McGorry, PD, Föcking, M, Cotter, D, and Amminger, GP

Published
2022

49. Verbal memory performance predicts remission and functional outcome in people at clinical high-risk for psychosis

Author

Hedges, EP, Dickson, H, Tognin, S, Modinos, G, Antoniades, M, van der Gaag, M, de Haan, L, McGorry, P, Pantelis, C, Riecher-Rossler, A, Bressan, R, Barrantes-Vidal, N, Krebs, M-O, Nordentoft, M, Ruhrmann, S, Sachs, G, Rutten, BP, van Os, J, Valmaggia, LR, McGuire, P, Kempton, MJ, Hedges, EP, Dickson, H, Tognin, S, Modinos, G, Antoniades, M, van der Gaag, M, de Haan, L, McGorry, P, Pantelis, C, Riecher-Rossler, A, Bressan, R, Barrantes-Vidal, N, Krebs, M-O, Nordentoft, M, Ruhrmann, S, Sachs, G, Rutten, BP, van Os, J, Valmaggia, LR, McGuire, P, and Kempton, MJ

Abstract

Robust deficits in cognitive functioning are present in people with psychosis and are evident in the early stages of the disorder. Impairments in verbal memory and verbal fluency are reliably seen in individuals at clinical high-risk for psychosis (CHR) compared to healthy populations. As previous studies have shown a relationship between cognition and longer-term outcomes in schizophrenia, the aim of this paper was to explore whether verbal memory and verbal fluency performance predicted outcomes in a large CHR sample recruited as part of the EU-GEI High Risk Study. Participants included 316 CHR individuals, 90.8% of whom were not currently on antipsychotic medication, and 60 healthy controls. Verbal memory and verbal fluency performance were measured at baseline. At two-year follow-up, CHR individuals were assessed by three different outcome measures, those who did and did not (1) transition to psychosis, (2) experience burdening impairment or disabilities, or (3) remit clinically from CHR status. Individuals with CHR displayed significant verbal memory and verbal fluency deficits at baseline compared to healthy controls (Hedges' g effect size = 0.24 to 0.66). There were no significant differences in cognitive performance of those who did and did not transition to psychosis. However, impaired immediate verbal recall predicted both functional disability and non-remission from the CHR state. Results remained significant when analyses were restricted to only include antipsychotic-free CHR participants. These findings may inform the development of early interventions designed to improve cognitive deficits in the early stages of psychosis.

Published
2022

50. Enhancing Discovery of Genetic Variants for Posttraumatic Stress Disorder Through Integration of Quantitative Phenotypes and Trauma Exposure Information

Author

Maihofer, AX, Choi, KW, Coleman, JR, Daskalakis, NP, Denckla, CA, Ketema, E, Morey, RA, Polimanti, R, Ratanatharathorn, A, Torres, K, Wingo, AP, Zai, CC, Aiello, AE, Almli, LM, Amstadter, AB, Andersen, SB, Andreassen, OA, Arbisi, PA, Ashley-Koch, AE, Austin, SB, Avdibegovic, E, Borglum, AD, Babic, D, Baekvad-Hansen, M, Baker, DG, Beckham, JC, Bierut, LJ, Bisson, J, Boks, MP, Bolger, EA, Bradley, B, Brashear, M, Breen, G, Bryant, RA, Bustamante, AC, Bybjerg-Grauholm, J, Calabrese, JR, Caldas-de-Almeida, JM, Chen, C-Y, Dale, AM, Dalvie, S, Deckert, J, Delahanty, DL, Dennis, MF, Disner, SG, Domschke, K, Duncan, LE, Kulenovic, AD, Erbes, CR, Evans, A, Farrer, LA, Feeny, NC, Flory, JD, Forbes, D, Franz, CE, Galea, S, Garrett, ME, Gautam, A, Gelaye, B, Gelernter, J, Geuze, E, Gillespie, CF, Goci, A, Gordon, SD, Guffanti, G, Hammamieh, R, Hauser, MA, Heath, AC, Hemmings, SMJ, Hougaard, DM, Jakovljevic, M, Jett, M, Johnson, EO, Jones, I, Jovanovic, T, Qin, X-J, Karstoft, K-I, Kaufman, ML, Kessler, RC, Khan, A, Kimbrel, NA, King, AP, Koen, N, Kranzler, HR, Kremen, WS, Lawford, BR, Lebois, LAM, Lewis, C, Liberzon, I, Linnstaedt, SD, Logue, MW, Lori, A, Lugonja, B, Luykx, JJ, Lyons, MJ, Maples-Keller, JL, Marmar, C, Martin, NG, Maurer, D, Mavissakalian, MR, McFarlane, A, McGlinchey, RE, McLaughlin, KA, McLean, SA, Mehta, D, Mellor, R, Michopoulos, V, Milberg, W, Miller, MW, Morris, CP, Mors, O, Mortensen, PB, Nelson, EC, Nordentoft, M, Norman, SB, O'Donnell, M, Orcutt, HK, Panizzon, MS, Peters, ES, Peterson, AL, Peverill, M, Pietrzak, RH, Polusny, MA, Rice, JP, Risbrough, VB, Roberts, AL, Rothbaum, AO, Rothbaum, BO, Roy-Byrne, P, Ruggiero, KJ, Rung, A, Rutten, BPF, Saccone, NL, Sanchez, SE, Schijven, D, Seedat, S, Seligowski, A, Seng, JS, Sheerin, CM, Silove, D, Smith, AK, Smoller, JW, Sponheim, SR, Stein, DJ, Stevens, JS, Teicher, MH, Thompson, WK, Trapido, E, Uddin, M, Ursano, RJ, van den Heuvel, LL, Van Hooff, M, Vermetten, E, Vinkers, CH, Voisey, J, Wang, Y, Wang, Z, Werge, T, Williams, MA, Williamson, DE, Winternitz, S, Wolf, C, Wolf, EJ, Yehuda, R, Young, KA, Young, RM, Zhao, H, Zoellner, LA, Haas, M, Lasseter, H, Provost, AC, Salem, RM, Sebat, J, Shaffer, RA, Wu, T, Ripke, S, Daly, MJ, Ressler, KJ, Koenen, KC, Stein, MB, Nievergelt, CM, Maihofer, AX, Choi, KW, Coleman, JR, Daskalakis, NP, Denckla, CA, Ketema, E, Morey, RA, Polimanti, R, Ratanatharathorn, A, Torres, K, Wingo, AP, Zai, CC, Aiello, AE, Almli, LM, Amstadter, AB, Andersen, SB, Andreassen, OA, Arbisi, PA, Ashley-Koch, AE, Austin, SB, Avdibegovic, E, Borglum, AD, Babic, D, Baekvad-Hansen, M, Baker, DG, Beckham, JC, Bierut, LJ, Bisson, J, Boks, MP, Bolger, EA, Bradley, B, Brashear, M, Breen, G, Bryant, RA, Bustamante, AC, Bybjerg-Grauholm, J, Calabrese, JR, Caldas-de-Almeida, JM, Chen, C-Y, Dale, AM, Dalvie, S, Deckert, J, Delahanty, DL, Dennis, MF, Disner, SG, Domschke, K, Duncan, LE, Kulenovic, AD, Erbes, CR, Evans, A, Farrer, LA, Feeny, NC, Flory, JD, Forbes, D, Franz, CE, Galea, S, Garrett, ME, Gautam, A, Gelaye, B, Gelernter, J, Geuze, E, Gillespie, CF, Goci, A, Gordon, SD, Guffanti, G, Hammamieh, R, Hauser, MA, Heath, AC, Hemmings, SMJ, Hougaard, DM, Jakovljevic, M, Jett, M, Johnson, EO, Jones, I, Jovanovic, T, Qin, X-J, Karstoft, K-I, Kaufman, ML, Kessler, RC, Khan, A, Kimbrel, NA, King, AP, Koen, N, Kranzler, HR, Kremen, WS, Lawford, BR, Lebois, LAM, Lewis, C, Liberzon, I, Linnstaedt, SD, Logue, MW, Lori, A, Lugonja, B, Luykx, JJ, Lyons, MJ, Maples-Keller, JL, Marmar, C, Martin, NG, Maurer, D, Mavissakalian, MR, McFarlane, A, McGlinchey, RE, McLaughlin, KA, McLean, SA, Mehta, D, Mellor, R, Michopoulos, V, Milberg, W, Miller, MW, Morris, CP, Mors, O, Mortensen, PB, Nelson, EC, Nordentoft, M, Norman, SB, O'Donnell, M, Orcutt, HK, Panizzon, MS, Peters, ES, Peterson, AL, Peverill, M, Pietrzak, RH, Polusny, MA, Rice, JP, Risbrough, VB, Roberts, AL, Rothbaum, AO, Rothbaum, BO, Roy-Byrne, P, Ruggiero, KJ, Rung, A, Rutten, BPF, Saccone, NL, Sanchez, SE, Schijven, D, Seedat, S, Seligowski, A, Seng, JS, Sheerin, CM, Silove, D, Smith, AK, Smoller, JW, Sponheim, SR, Stein, DJ, Stevens, JS, Teicher, MH, Thompson, WK, Trapido, E, Uddin, M, Ursano, RJ, van den Heuvel, LL, Van Hooff, M, Vermetten, E, Vinkers, CH, Voisey, J, Wang, Y, Wang, Z, Werge, T, Williams, MA, Williamson, DE, Winternitz, S, Wolf, C, Wolf, EJ, Yehuda, R, Young, KA, Young, RM, Zhao, H, Zoellner, LA, Haas, M, Lasseter, H, Provost, AC, Salem, RM, Sebat, J, Shaffer, RA, Wu, T, Ripke, S, Daly, MJ, Ressler, KJ, Koenen, KC, Stein, MB, and Nievergelt, CM

Abstract

BACKGROUND: Posttraumatic stress disorder (PTSD) is heritable and a potential consequence of exposure to traumatic stress. Evidence suggests that a quantitative approach to PTSD phenotype measurement and incorporation of lifetime trauma exposure (LTE) information could enhance the discovery power of PTSD genome-wide association studies (GWASs). METHODS: A GWAS on PTSD symptoms was performed in 51 cohorts followed by a fixed-effects meta-analysis (N = 182,199 European ancestry participants). A GWAS of LTE burden was performed in the UK Biobank cohort (N = 132,988). Genetic correlations were evaluated with linkage disequilibrium score regression. Multivariate analysis was performed using Multi-Trait Analysis of GWAS. Functional mapping and annotation of leading loci was performed with FUMA. Replication was evaluated using the Million Veteran Program GWAS of PTSD total symptoms. RESULTS: GWASs of PTSD symptoms and LTE burden identified 5 and 6 independent genome-wide significant loci, respectively. There was a 72% genetic correlation between PTSD and LTE. PTSD and LTE showed largely similar patterns of genetic correlation with other traits, albeit with some distinctions. Adjusting PTSD for LTE reduced PTSD heritability by 31%. Multivariate analysis of PTSD and LTE increased the effective sample size of the PTSD GWAS by 20% and identified 4 additional loci. Four of these 9 PTSD loci were independently replicated in the Million Veteran Program. CONCLUSIONS: Through using a quantitative trait measure of PTSD, we identified novel risk loci not previously identified using prior case-control analyses. PTSD and LTE have a high genetic overlap that can be leveraged to increase discovery power through multivariate methods.

Published
2022

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