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8. Healthy Adolescent Performance With Standardized Scoring Tables for the MATRICS Consensus Cognitive Battery: A Multisite Study

Author

Smelror, Runar Elle, Jørgensen, Kjetil Nordbø, Lonning, Vera, Kelleher, Ian, Cannon, Mary, DeRosse, Pamela, Malhotra, Anil K, Karlsgodt, Katherine H, Andreassen, Ole A, Lundberg, Mathias, Edbom, Tobias, Cleland, Neil, Ueland, Torill, Myhre, Anne Margrethe, Rund, Bjørn Rishovd, and Agartz, Ingrid

Subjects
Behavioral and Social Science, Pediatric, Mental Health, Clinical Research, Mental health, Adolescent, Adult, Child, Female, Humans, Male, Neuropsychological Tests, Reference Standards, Sex Factors, Task Performance and Analysis, Young Adult, early-onset, psychosis, schizophrenia, neurocognition, neuropsychology, Medical and Health Sciences, Psychology and Cognitive Sciences, Psychiatry
Abstract

ObjectiveThe aim of this study was to develop standardized scores and scoring tables for test performance in healthy adolescents for the Measurement and Treatment Research to Improve Cognition in Schizophrenia (MATRICS) Consensus Cognitive Battery (MCCB) for each year from 11 to 19 years of age, by sex, with T scores and percentile ranks.MethodsA total of 502 healthy participants (aged 11-19 years) from 7 cohorts from Ireland, Norway, Sweden, and United States, were included in this multisite study. Regression-predicted means for the MCCB tests, except the social cognition subtest, were calculated using the MCCB test scores as outcome variables and age, age2, sex, age × sex as predictors. The regression-predicted means for each combination of age and sex were added with the residuals from the entire cohort to yield the expected distribution of that group. Age effects were examined using regression models with age and age2 as predictors. Sex differences were examined using Student's t-tests.ResultsSignificant positive age effects were found for all tests, except for the Brief Visuospatial Memory Test, revised (BVMT-R; measure of visual learning). Females performed significantly better than males on BACS Symbol coding (measure of speed of processing) and BVMT-R, while males performed significantly better than females on NAB Mazes (measure of reasoning and problem solving). Based on the regression-predicted distributions of scores, 19 standardized scoring tables for each test and domain were created.ConclusionsWith the results from this study, we have developed an accessible standardized data set of healthy adolescent test performance for the MCCB.

Published
2019

12. Enrichment of genetic markers of recent human evolution in educational and cognitive traits.

Author

Srinivasan, Saurabh, Bettella, Francesco, Frei, Oleksandr, Hill, W David, Wang, Yunpeng, Witoelar, Aree, Schork, Andrew J, Thompson, Wesley K, Davies, Gail, Desikan, Rahul S, Deary, Ian J, Melle, Ingrid, Ueland, Torill, Dale, Anders M, Djurovic, Srdjan, Smeland, Olav B, and Andreassen, Ole A

Subjects
Brain, Humans, Genetic Markers, Intelligence, Cognition, Multifactorial Inheritance, Phenotype, Polymorphism, Single Nucleotide, Genome, Educational Status, Female, Male, Genome-Wide Association Study, Biological Evolution, Polymorphism, Single Nucleotide, Human Genome, Genetics, Biotechnology, Clinical Research, Mental Health, Biochemistry and Cell Biology, Other Physical Sciences
Abstract

Higher cognitive functions are regarded as one of the main distinctive traits of humans. Evidence for the cognitive evolution of human beings is mainly based on fossil records of an expanding cranium and an increasing complexity of material culture artefacts. However, the molecular genetic factors involved in the evolution are still relatively unexplored. Here, we investigated whether genomic regions that underwent positive selection in humans after divergence from Neanderthals are enriched for genetic association with phenotypes related to cognitive functions. We used genome wide association data from a study of college completion (N = 111,114), one of educational attainment (N = 293,623) and two different studies of general cognitive ability (N = 269,867 and 53,949). We found nominally significant polygenic enrichment of associations with college completion (p = 0.025), educational attainment (p = 0.043) and general cognitive ability (p = 0.015 and 0.025, respectively), suggesting that variants influencing these phenotypes are more prevalent in evolutionarily salient regions. The enrichment remained significant after controlling for other known genetic enrichment factors, and for affiliation to genes highly expressed in the brain. These findings support the notion that phenotypes related to higher order cognitive skills typical of humans have a recent genetic component that originated after the separation of the human and Neanderthal lineages.

Published
2018

14. Identification of Genetic Loci Jointly Influencing Schizophrenia Risk and the Cognitive Traits of Verbal-Numerical Reasoning, Reaction Time, and General Cognitive Function.

Author

Smeland, Olav B, Frei, Oleksandr, Kauppi, Karolina, Hill, W David, Li, Wen, Wang, Yunpeng, Krull, Florian, Bettella, Francesco, Eriksen, Jon A, Witoelar, Aree, Davies, Gail, Fan, Chun C, Thompson, Wesley K, Lam, Max, Lencz, Todd, Chen, Chi-Hua, Ueland, Torill, Jönsson, Erik G, Djurovic, Srdjan, Deary, Ian J, Dale, Anders M, Andreassen, Ole A, and NeuroCHARGE (Cohorts for Heart and Aging Research in Genomic Epidemiology) Cognitive Working Group

Subjects
NeuroCHARGE (Cohorts for Heart and Aging Research in Genomic Epidemiology) Cognitive Working Group, Humans, GTPase-Activating Proteins, Cognition, Reaction Time, Schizophrenia, Quantitative Trait, Heritable, Linkage Disequilibrium, Polymorphism, Single Nucleotide, Adult, Female, Male, alpha Catenin, Genetic Variation, Genome-Wide Association Study, Genetic Loci, Cognitive Dysfunction, Brain Disorders, Biotechnology, Mental Health, Human Genome, Serious Mental Illness, Genetics, Clinical Research, Aetiology, 2.1 Biological and endogenous factors, Mental health, Other Medical and Health Sciences, Psychology, Cognitive Sciences
Abstract

ImportanceSchizophrenia is associated with widespread cognitive impairments. Although cognitive deficits are one of the factors most strongly associated with functional outcome in schizophrenia, current treatment strategies largely fail to ameliorate these impairments. To develop more efficient treatment strategies in patients with schizophrenia, a better understanding of the pathogenesis of these cognitive deficits is needed. Accumulating evidence indicates that genetic risk of schizophrenia may contribute to cognitive dysfunction.ObjectiveTo identify genomic regions jointly influencing schizophrenia and the cognitive domains of reaction time and verbal-numerical reasoning, as well as general cognitive function, a phenotype that captures the shared variation in performance across cognitive domains.Design, setting, and participantsCombining data from genome-wide association studies from multiple phenotypes using conditional false discovery rate analysis provides increased power to discover genetic variants and could elucidate shared molecular genetic mechanisms. Data from the following genome-wide association studies, published from July 24, 2014, to January 17, 2017, were combined: schizophrenia in the Psychiatric Genomics Consortium cohort (n = 79 757 [cases, 34 486; controls, 45 271]); verbal-numerical reasoning (n = 36 035) and reaction time (n = 111 483) in the UK Biobank cohort; and general cognitive function in CHARGE (Cohorts for Heart and Aging Research in Genomic Epidemiology) (n = 53 949) and COGENT (Cognitive Genomics Consortium) (n = 27 888).Main outcomes and measuresGenetic loci identified by conditional false discovery rate analysis. Brain messenger RNA expression and brain expression quantitative trait locus functionality were determined.ResultsAmong the participants in the genome-wide association studies, 21 loci jointly influencing schizophrenia and cognitive traits were identified: 2 loci shared between schizophrenia and verbal-numerical reasoning, 6 loci shared between schizophrenia and reaction time, and 14 loci shared between schizophrenia and general cognitive function. One locus was shared between schizophrenia and 2 cognitive traits and represented the strongest shared signal detected (nearest gene TCF20; chromosome 22q13.2), and was shared between schizophrenia (z score, 5.01; P = 5.53 × 10-7), general cognitive function (z score, -4.43; P = 9.42 × 10-6), and verbal-numerical reasoning (z score, -5.43; P = 5.64 × 10-8). For 18 loci, schizophrenia risk alleles were associated with poorer cognitive performance. The implicated genes are expressed in the developmental and adult human brain. Replicable expression quantitative trait locus functionality was identified for 4 loci in the adult human brain.Conclusions and relevanceThe discovered loci improve the understanding of the common genetic basis underlying schizophrenia and cognitive function, suggesting novel molecular genetic mechanisms.

Published
2017

20. Multivariate genetic analysis of personality and cognitive traits reveals abundant pleiotropy

Author

Hindley, Guy, Shadrin, Alexey A., van der Meer, Dennis, Parker, Nadine, Cheng, Weiqiu, O’Connell, Kevin S., Bahrami, Shahram, Lin, Aihua, Karadag, Naz, Holen, Børge, Bjella, Thomas, Deary, Ian J., Davies, Gail, Hill, W. David, Bressler, Jan, Seshadri, Sudha, Fan, Chun Chieh, Ueland, Torill, Djurovic, Srdjan, Smeland, Olav B., Frei, Oleksandr, Dale, Anders M., and Andreassen, Ole A.

Subjects
human behaviour, genetic variation
Abstract

Personality and cognitive function are heritable mental traits whose genetic foundations may be distributed across interconnected brain functions. Previous studies have typically treated these complex mental traits as distinct constructs. We applied the ‘pleiotropy-informed’ multivariate omnibus statistical test to genome-wide association studies of 35 measures of neuroticism and cognitive function from the UK Biobank (n = 336,993). We identified 431 significantly associated genetic loci with evidence of abundant shared genetic associations, across personality and cognitive function domains. Functional characterization implicated genes with significant tissue-specific expression in all tested brain tissues and brain-specific gene sets. We conditioned independent genome-wide association studies of the Big 5 personality traits and cognitive function on our multivariate findings, boosting genetic discovery in other personality traits and improving polygenic prediction. These findings advance our understanding of the polygenic architecture of these complex mental traits, indicating a prominence of pleiotropic genetic effects across higher order domains of mental function such as personality and cognitive function.

Published
2023

21. Early identification of treatment non-response in first-episode psychosis

Author

Wold, Kristin Fjelnseth, primary, Ottesen, Akiah, additional, Flaathen, Camilla, additional, Johnsen, Erik, additional, Lagerberg, Trine Vik, additional, Romm, Kristin Lie, additional, Simonsen, Carmen, additional, Ueland, Torill, additional, Widing, Line, additional, Åsbø, Gina, additional, and Melle, Ingrid, additional

Published
2023
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24. Long-term Outcomes of People With DSM Psychotic Disorder NOS

Author

Widing, Line, primary, Simonsen, Carmen, additional, Bjella, Thomas, additional, Engen, Magnus Johan, additional, Flaaten, Camilla Bärthel, additional, Gardsjord, Erlend, additional, Haatveit, Beathe, additional, Haug, Elisabeth, additional, Lyngstad, Siv Hege, additional, Svendsen, Ingrid Hartveit, additional, Vik, Ruth Kristine, additional, Wold, Kristin Fjelnseth, additional, Åsbø, Gina, additional, Ueland, Torill, additional, and Melle, Ingrid, additional

Published
2023
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25. Composite immune marker scores associated with severe mental disorders and illness course

Author

Elkjaer Greenwood Ormerod, Monica Bettina, primary, Ueland, Thor, additional, Frogner Werner, Maren Caroline, additional, Hjell, Gabriela, additional, Rødevand, Linn, additional, Sæther, Linn Sofie, additional, Lunding, Synve Hoffart, additional, Johansen, Ingrid Torp, additional, Ueland, Torill, additional, Lagerberg, Trine Vik, additional, Melle, Ingrid, additional, Djurovic, Srdjan, additional, Andreassen, Ole Andreas, additional, and Steen, Nils Eiel, additional

Published
2022
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28. Developing “MinDag” – an app to capture symptom variation and illness mechanisms in bipolar disorder

Author

Bjella, Thomas D., primary, Collier Høegh, Margrethe, additional, Holmstul Olsen, Stine, additional, Aminoff, Sofie R., additional, Barrett, Elizabeth, additional, Ueland, Torill, additional, Icick, Romain, additional, Andreassen, Ole A., additional, Nerhus, Mari, additional, Myhre Ihler, Henrik, additional, Hagen, Marthe, additional, Busch-Christensen, Cecilie, additional, Melle, Ingrid, additional, and Lagerberg, Trine Vik, additional

Published
2022
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29. The Time is Ripe for a Consensus Definition of Clinical Recovery in First-episode Psychosis: Suggestions Based on a 10-Year Follow-up Study

Author

Åsbø, Gina, primary, Ueland, Torill, additional, Haatveit, Beathe, additional, Bjella, Thomas, additional, Flaaten, Camilla Bärthel, additional, Wold, Kristin Fjelnseth, additional, Widing, Line, additional, Engen, Magnus Johan, additional, Lyngstad, Siv Hege, additional, Gardsjord, Erlend, additional, Romm, Kristin Lie, additional, Melle, Ingrid, additional, and Simonsen, Carmen, additional

Published
2022
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30. Cognitive and Global Functioning in Patients With First-Episode Psychosis Stratified by Level of Negative Symptoms. A 10-Year Follow-Up Study

Author

Engen, Magnus Johan, primary, Vaskinn, Anja, additional, Melle, Ingrid, additional, Færden, Ann, additional, Lyngstad, Siv Hege, additional, Flaaten, Camilla Bärthel, additional, Widing, Line Hustad, additional, Wold, Kristin Fjelnseth, additional, Åsbø, Gina, additional, Haatveit, Beathe, additional, Simonsen, Carmen, additional, and Ueland, Torill, additional

Published
2022
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31. Negative Symptom Domains Are Associated With Verbal Learning in Adolescents With Early Onset Psychosis

Author

Mørch-Johnsen, Lynn, primary, Smelror, Runar Elle, additional, Andreou, Dimitrios, additional, Barth, Claudia, additional, Johannessen, Cecilie, additional, Wedervang-Resell, Kirsten, additional, Wortinger, Laura A., additional, Díaz, Ricardo, additional, Victoria, Gamaliel, additional, Ueland, Torill, additional, Andreassen, Ole A., additional, Myhre, Anne M., additional, Rund, Bjørn Rishovd, additional, Ulloa, Rosa Elena, additional, and Agartz, Ingrid, additional

Published
2022
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32. Premorbid characteristics of patients with DSM-IV psychotic disorders

Author

Widing, Line Hustad, Simonsen, Carmen Elisabeth, Flaaten, Camilla Bärthel, Haatveit, Beathe, Vik, Ruth Kristine, Wold, Kristin Fjelnseth, Åsbø, Gina, Ueland, Torill, and Melle, Ingrid

Subjects
Diagnostic and Statistical Manual of Mental Disorders, Psychiatry and Mental health, Clinical Psychology, Bipolar Disorder, Psychotic Disorders, Schizophrenia, Humans, Social Adjustment, Cannabis
Abstract

Introduction Psychotic disorder not otherwise specified (PNOS) is considered part of the psychosis spectrum, together with schizophrenia spectrum disorders (SSD) and psychotic bipolar spectrum disorders (PBD). The atypical clinical presentations of PNOS conditions may lead to uncertainty regarding treatment choices and expected outcomes. PNOS is understudied, and little is known about patients' premorbid characteristics including premorbid adjustment, prevalence of early cannabis use and childhood trauma. Knowledge about early illness phases can increase our understanding of this diagnostic group. Methods We included 1099 participants from the Norwegian TOP-study; 688 with narrow SSD diagnoses (schizophrenia, schizoaffective disorder, schizophreniform disorder), 274 with PBD (psychotic bipolar 1 and bipolar NOS) and 137 with PNOS diagnosed with the SCID-I for DSM-IV. Participants were assessed with the Premorbid Adjustment Scale (PAS) divided into the areas of premorbid academic and social functioning. We obtained information on age at first exposure to cannabis and use of cannabis before the age of 16. The participants also provided information regarding early traumatic experiences using the Childhood Trauma Questionnaire (CTQ). Results Participants with PNOS and SSD had poorer premorbid academic functioning than those with PBD (F2, 1029 = 7.81, p

Published
2021

38. Physical activity and childhood trauma experiences in patients with schizophrenia or bipolar disorders

Author

Aas, Monica, Ueland, Torill, Mørch, Ragni H., Laskemoen, Jannicke F., Synve Hoffart Lunding, Reponen, Elina J., Cattaneo, Annamaria, Agartz, Ingrid, Melle, Ingrid, Steen, Nils E., and Andreassen, Ole A.

Abstract

Physical activity promotes resilience and reduces stress. Here we aimed to clarify the impact of physical activity and childhood trauma experiences on current mood and cognitive function in patients with schizophrenia (SZ) or bipolar disorders (BD). Three-hundred-and-six patients with a DSM-IV schizophrenia (SZ) or bipolar disorder (BD) were included in the study. Diagnoses were assessed using the Structured Clinical Interview for DSM-IV Axis I disorders (SCID-I). Physical activity was measured as hours spent on any regular physical activity per week. All patients underwent a neuropsychological test battery. A history of Childhood trauma was assessed using the Childhood Trauma Questionnaire and mood symptoms were assessed with the Inventory of Depressive Symptoms. Patients with childhood trauma who were physically inactive (˂ 90 min. per week) had the most severe clinical profile, characterized by the highest depressive symptoms (P˂0.001) and lowest performance on working memory tasks (P˂0.001). Among patients with childhood trauma, those who were physically active (≥90 min. per week) had better working memory performance than physically inactive patients (p=0.02). A history of childhood trauma was associated with poorer working memory and more depressive symptoms only in patients who were physically inactive, suggesting a possible protective factor of physical activity in severe mental disorder.

Published
2021
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40. Evidence for Reduced Long-Term Potentiation-Like Visual Cortical Plasticity in Schizophrenia and Bipolar Disorder

Author

Valstad, Mathias, primary, Roelfs, Daniël, additional, Slapø, Nora B, additional, Timpe, Clara M F, additional, Rai, Ahsan, additional, Matziorinis, Anna Maria, additional, Beck, Dani, additional, Richard, Geneviève, additional, Sæther, Linn Sofie, additional, Haatveit, Beathe, additional, Nordvik, Jan Egil, additional, Hatlestad-Hall, Christoffer, additional, Einevoll, Gaute T, additional, Mäki-Marttunen, Tuomo, additional, Haram, Marit, additional, Ueland, Torill, additional, Lagerberg, Trine V, additional, Steen, Nils Eiel, additional, Melle, Ingrid, additional, Westlye, Lars T, additional, Jönsson, Erik G, additional, Andreassen, Ole A, additional, Moberget, Torgeir, additional, and Elvsåshagen, Torbjørn, additional

Published
2021
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41. Time is Ripe for a Consensus Definition of Clinical Recovery in First-episode Psychosis: Suggestions Based on a 10-Year Follow-up Study.

Author

Åsbø, Gina, Ueland, Torill, Haatveit, Beathe, Bjella, Thomas, Flaaten, Camilla Bärthel, Wold, Kristin Fjelnseth, Widing, Line, Engen, Magnus Johan, Lyngstad, Siv Hege, Gardsjord, Erlend, Romm, Kristin Lie, Melle, Ingrid, and Simonsen, Carmen

Subjects
SCHIZOPHRENIA treatment, CONSENSUS (Social sciences), PATIENT aftercare, PSYCHOTHERAPY patients, SCHIZOPHRENIA, CONVALESCENCE, RESEARCH methodology, INTERVIEWING, FUNCTIONAL assessment, COMPARATIVE studies, PSYCHOSOCIAL factors, DESCRIPTIVE statistics, BIPOLAR disorder, DISEASE remission, PSYCHIATRIC treatment, LONGITUDINAL method, SYMPTOMS
Abstract

Objectives A consensus definition of clinical recovery in first-episode psychosis (FEP) is required to improve knowledge about recovery rates in this population. To propose criteria for a future consensus definition, this study aims to investigate rates of clinical recovery when using a standard definition (full psychotic symptom remission and adequate functioning for minimum one year) across both affective and nonaffective FEP groups (bipolar spectrum and schizophrenia spectrum disorders). Second, we aim to explore changes in rates when altering the standard definition criteria. Third, to examine the extent to which healthy controls meet the functioning criteria. Study design In total, 142 FEP participants and 117 healthy controls preselected with strict criteria, were re-assessed with structured clinical interviews at 10-year follow-up. Study results A total of 31.7% were in clinical recovery according to the standard definition, with significantly higher recovery rates in bipolar (50.0%) than in schizophrenia spectrum disorders (22.9%). Both groups' recovery rates decreased equally when extending duration and adding affective symptom remission criteria and increased with looser functioning criteria. In healthy controls, 18.8% did not meet the standard criteria for adequate functioning, decreasing to 4.3% with looser criteria. Conclusions Findings suggest that clinical recovery is common in FEP, although more in bipolar than in schizophrenia spectrum disorders, also when altering the recovery criteria. We call for a future consensus definition of clinical recovery for FEP, and suggest it should include affective symptom remission and more reasonable criteria for functioning that are more in line with the general population. [ABSTRACT FROM AUTHOR]

Published
2022
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42. Correction: Genome-wide analysis reveals extensive genetic overlap between schizophrenia, bipolar disorder, and intelligence (Molecular Psychiatry, (2019), 10.1038/s41380-018-0332-x):Genome-wide analysis reveals extensive genetic overlap between schizophrenia, bipolar disorder, and intelligence (Molecular Psychiatry, (2020), 25, 4, (844-853), 10.1038/s41380-018-0332-x)

Author

Smeland, Olav B., Bahrami, Shahram, Frei, Oleksandr, Shadrin, Alexey, O’Connell, Kevin, Savage, Jeanne, Watanabe, Kyoko, Krull, Florian, Bettella, Francesco, Steen, Nils Eiel, Ueland, Torill, Posthuma, Danielle, Djurovic, Srdjan, Dale, Anders M., and Andreassen, Ole A.

Abstract

A correction to this paper has been published and can be accessed via a link at the top of the paper.

Published
2020

43. Dose response of the 16p11.2 distal copy number variant on intracranial volume and basal ganglia

Author

Sonderby, Ida E., Gustafsson, Omar, Doan, Nhat Trung, Hibar, Derrek P., Martin-Brevet, Sandra, Abdellaoui, Abdel, Ames, David, Amunts, Katrin, Andersson, Micael, Armstrong, Nicola J., Bernard, Manon, Blackburn, Nicholas, Blangero, John, Boomsma, Dorret, I, Bralten, Janita, Brattbak, Hans-Richard, Brodaty, Henry, Brouwer, Rachel M., Buelow, Robin, Calhoun, Vince, Caspers, Svenja, Cavalleri, Gianpiero, Chen, Chi-Hua, Cichon, Sven, Ciufolini, Simone, Corvin, Aiden, Crespo-Facorro, Benedicto, Curran, Joanne E., Dale, Anders M., Dalvie, Shareefa, Dazzan, Paola, de Geus, Eco J. C., de Zubicaray, Greig, I, de Zwarte, Sonja M. C., Delanty, Norman, den Braber, Anouk, Desrivieres, Sylvane, Donohoe, Gary, Draganski, Bogdan, Ehrlich, Stefan, Espeseth, Thomas, Fisher, Simon E., Franke, Barbara, Frouin, Vincent, Fukunaga, Masaki, Gareau, Thomas, Glahn, David C., Grabe, Hans, Groenewold, Nynke A., Haavik, Jan, Haberg, Asta, Hashimoto, Ryota, Hehir-Kwa, Jayne Y., Heinz, Andreas, Hillegers, Manon H. J., Hoffmann, Per, Holleran, Laurena, Hottenga, Jouke-Jan, Hulshoff, Hilleke E., Ikeda, Masashi, Jahanshad, Neda, Jernigan, Terry, Jockwitz, Christiane, Johansson, Stefan, Jonsdottir, Gudrun A., Joensson, Erik G., Kahn, Rene, Kaufmann, Tobias, Kelly, Sinead, Kikuchi, Masataka, Knowles, Emma E. M., Kolskar, Knut K., Kwok, John B., Le Hellard, Stephanie, Leu, Costin, Liu, Jingyu, Lundervold, Astri J., Lundervold, Arvid, Martin, Nicholas G., Mather, Karen, Mathias, Samuel R., McCormack, Mark, McMahon, Katie L., McRae, Allan, Milaneschi, Yuri, Moreau, Clara, Morris, Derek, Mothersill, David, Muehleisen, Thomas W., Murray, Robin, Nordvik, Jan E., Nyberg, Lars, Loohuis, Loes M. Olde, Ophoff, Roel, Paus, Tomas, Pausova, Zdenka, Penninx, Brenda, Peralta, Juan M., Pike, Bruce, Prieto, Carlos, Pudas, Sara, Quinlan, Erin, Quintana, Daniel S., Reinbold, Celine S., Marques, Tiago Reis, Reymond, Alexandre, Richard, Genevieve, Rodriguez-Herreros, Borja, Roiz-Santianez, Roberto, Rokicki, Jarek, Rucker, James, Sachdev, Perminder, Sanders, Anne-Marthe, Sando, Sigrid B., Schmaal, Lianne, Schofield, Peter R., Schork, Andrew J., Schumann, Gunter, Shin, Jean, Shumskaya, Elena, Sisodiya, Sanjay, Steen, Vidar M., Stein, Dan J., Steinberg, Stacy, Strike, Lachlan, Teumer, Alexander, Thalamuthu, Anbu, Tordesillas-Gutierrez, Diana, Turner, Jessica, Ueland, Torill, Uhlmann, Anne, Ulfarsson, Magnus O., van't Ent, Dennis, van der Meer, Dennis, van Haren, Neeltje E. M., Vaskinn, Anja, Vassos, Evangelos, Walters, G. Bragi, Wang, Yunpeng, Wen, Wei, Whelan, Christopher D., Wittfeld, Katharina, Wright, Margie, Yamamori, Hidenaga, Zayats, Tetyana, Agartz, Ingrid, Westlye, Lars T., Jacquemont, Sebastien, Djurovic, Srdjan, Stefansson, Hreinn, Stefansson, Kari, Thompson, Paul, Andreassen, Ole A., Sonderby, Ida E., Gustafsson, Omar, Doan, Nhat Trung, Hibar, Derrek P., Martin-Brevet, Sandra, Abdellaoui, Abdel, Ames, David, Amunts, Katrin, Andersson, Micael, Armstrong, Nicola J., Bernard, Manon, Blackburn, Nicholas, Blangero, John, Boomsma, Dorret, I, Bralten, Janita, Brattbak, Hans-Richard, Brodaty, Henry, Brouwer, Rachel M., Buelow, Robin, Calhoun, Vince, Caspers, Svenja, Cavalleri, Gianpiero, Chen, Chi-Hua, Cichon, Sven, Ciufolini, Simone, Corvin, Aiden, Crespo-Facorro, Benedicto, Curran, Joanne E., Dale, Anders M., Dalvie, Shareefa, Dazzan, Paola, de Geus, Eco J. C., de Zubicaray, Greig, I, de Zwarte, Sonja M. C., Delanty, Norman, den Braber, Anouk, Desrivieres, Sylvane, Donohoe, Gary, Draganski, Bogdan, Ehrlich, Stefan, Espeseth, Thomas, Fisher, Simon E., Franke, Barbara, Frouin, Vincent, Fukunaga, Masaki, Gareau, Thomas, Glahn, David C., Grabe, Hans, Groenewold, Nynke A., Haavik, Jan, Haberg, Asta, Hashimoto, Ryota, Hehir-Kwa, Jayne Y., Heinz, Andreas, Hillegers, Manon H. J., Hoffmann, Per, Holleran, Laurena, Hottenga, Jouke-Jan, Hulshoff, Hilleke E., Ikeda, Masashi, Jahanshad, Neda, Jernigan, Terry, Jockwitz, Christiane, Johansson, Stefan, Jonsdottir, Gudrun A., Joensson, Erik G., Kahn, Rene, Kaufmann, Tobias, Kelly, Sinead, Kikuchi, Masataka, Knowles, Emma E. M., Kolskar, Knut K., Kwok, John B., Le Hellard, Stephanie, Leu, Costin, Liu, Jingyu, Lundervold, Astri J., Lundervold, Arvid, Martin, Nicholas G., Mather, Karen, Mathias, Samuel R., McCormack, Mark, McMahon, Katie L., McRae, Allan, Milaneschi, Yuri, Moreau, Clara, Morris, Derek, Mothersill, David, Muehleisen, Thomas W., Murray, Robin, Nordvik, Jan E., Nyberg, Lars, Loohuis, Loes M. Olde, Ophoff, Roel, Paus, Tomas, Pausova, Zdenka, Penninx, Brenda, Peralta, Juan M., Pike, Bruce, Prieto, Carlos, Pudas, Sara, Quinlan, Erin, Quintana, Daniel S., Reinbold, Celine S., Marques, Tiago Reis, Reymond, Alexandre, Richard, Genevieve, Rodriguez-Herreros, Borja, Roiz-Santianez, Roberto, Rokicki, Jarek, Rucker, James, Sachdev, Perminder, Sanders, Anne-Marthe, Sando, Sigrid B., Schmaal, Lianne, Schofield, Peter R., Schork, Andrew J., Schumann, Gunter, Shin, Jean, Shumskaya, Elena, Sisodiya, Sanjay, Steen, Vidar M., Stein, Dan J., Steinberg, Stacy, Strike, Lachlan, Teumer, Alexander, Thalamuthu, Anbu, Tordesillas-Gutierrez, Diana, Turner, Jessica, Ueland, Torill, Uhlmann, Anne, Ulfarsson, Magnus O., van't Ent, Dennis, van der Meer, Dennis, van Haren, Neeltje E. M., Vaskinn, Anja, Vassos, Evangelos, Walters, G. Bragi, Wang, Yunpeng, Wen, Wei, Whelan, Christopher D., Wittfeld, Katharina, Wright, Margie, Yamamori, Hidenaga, Zayats, Tetyana, Agartz, Ingrid, Westlye, Lars T., Jacquemont, Sebastien, Djurovic, Srdjan, Stefansson, Hreinn, Stefansson, Kari, Thompson, Paul, and Andreassen, Ole A.

Abstract

Carriers of large recurrent copy number variants (CNVs) have a higher risk of developing neurodevelopmental disorders. The 16p11.2 distal CNV predisposes carriers to e.g., autism spectrum disorder and schizophrenia. We compared subcortical brain volumes of 12 16p11.2 distal deletion and 12 duplication carriers to 6882 non-carriers from the large-scale brain Magnetic Resonance Imaging collaboration, ENIGMA-CNV. After stringent CNV calling procedures, and standardized FreeSurfer image analysis, we found negative dose-response associations with copy number on intracranial volume and on regional caudate, pallidum and putamen volumes (β = −0.71 to −1.37; P < 0.0005). In an independent sample, consistent results were obtained, with significant effects in the pallidum (β = −0.95, P = 0.0042). The two data sets combined showed significant negative dose-response for the accumbens, caudate, pallidum, putamen and ICV (P = 0.0032, 8.9 × 10−6, 1.7 × 10−9, 3.5 × 10−12 and 1.0 × 10−4, respectively). Full scale IQ was lower in both deletion and duplication carriers compared to non-carriers. This is the first brain MRI study of the impact of the 16p11.2 distal CNV, and we demonstrate a specific effect on subcortical brain structures, suggesting a neuropathological pattern underlying the neurodevelopmental syndromes., Correction: Sønderby, I.E., Gústafsson, Ó., Doan, N.T. et al. Correction: Dose response of the 16p11.2 distal copy number variant on intracranial volume and basal ganglia. Mol Psychiatry 25, 692–695 (2020). https://doi.org/10.1038/s41380-019-0358-8

Published
2020
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44. Correction : Dose response of the 16p11.2 distal copy number variant on intracranial volume and basal ganglia (Molecular Psychiatry, (2020), 25, 3, (584-602), 10.1038/s41380-018-0118-1)

Author

Sønderby, Ida E., Gústafsson, Ómar, Doan, Nhat Trung, Hibar, Derrek P., Martin-Brevet, Sandra, Abdellaoui, Abdel, Ames, David, Amunts, Katrin, Andersson, Michael, Armstrong, Nicola J., Bernard, Manon, Blackburn, Nicholas, Blangero, John, Boomsma, Dorret I., Bralten, Janita, Brattbak, Hans Richard, Brodaty, Henry, Brouwer, Rachel M., Bülow, Robin, Calhoun, Vince, Caspers, Svenja, Cavalleri, Gianpiero, Chen, Chi Hua, Cichon, Sven, Ciufolini, Simone, Corvin, Aiden, Crespo-Facorro, Benedicto, Curran, Joanne E., Dale, Anders M., Dalvie, Shareefa, Dazzan, Paola, de Geus, Eco J.C., de Zubicaray, Greig I., de Zwarte, Sonja M.C., Delanty, Norman, den Braber, Anouk, Desrivières, Sylvane, Donohoe, Gary, Draganski, Bogdan, Ehrlich, Stefan, Espeseth, Thomas, Fisher, Simon E., Franke, Barbara, Frouin, Vincent, Fukunaga, Masaki, Gareau, Thomas, Glahn, David C., Grabe, Hans, Groenewold, Nynke A., Haavik, Jan, Håberg, Asta, Hashimoto, Ryota, Hehir-Kwa, Jayne Y., Heinz, Andreas, Hillegers, Manon H.J., Hoffmann, Per, Holleran, Laurena, Hottenga, Jouke Jan, Hulshoff, Hilleke E., Ikeda, Masashi, Jahanshad, Neda, Jernigan, Terry, Jockwitz, Christiane, Johansson, Stefan, Jonsdottir, Gudrun A., Jönsson, Erik G., Kahn, Rene, Kaufmann, Tobias, Kelly, Sinead, Kikuchi, Masataka, Knowles, Emma E.M., Kolskår, Knut K., Kwok, John B., Hellard, Stephanie Le, Leu, Costin, Liu, Jingyu, Lundervold, Astri J., Lundervold, Arvid, Martin, Nicholas G., Mather, Karen, Mathias, Samuel R., McCormack, Mark, McMahon, Katie L., McRae, Allan, Milaneschi, Yuri, Moreau, Clara, Morris, Derek, Mothersill, David, Mühleisen, Thomas W., Murray, Robin, Nordvik, Jan E., Nyberg, Lars, Olde Loohuis, Loes M., Ophoff, Roel, Paus, Tomas, Pausova, Zdenka, Penninx, Brenda, Peralta, Juan M., Pike, Bruce, Prieto, Carlos, Pudas, Sara, Quinlan, Erin, Quintana, Daniel S., Reinbold, Céline S., Marques, Tiago Reis, Reymond, Alexandre, Richard, Genevieve, Rodriguez-Herreros, Borja, Roiz-Santiañez, Roberto, Rokicki, Jarek, Rucker, James, Sachdev, Perminder, Sanders, Anne Marthe, Sando, Sigrid B., Schmaal, Lianne, Schofield, Peter R., Schork, Andrew J., Schumann, Gunter, Shin, Jean, Shumskaya, Elena, Sisodiya, Sanjay, Steen, Vidar M., Stein, Dan J., Steinberg, Stacy, Strike, Lachlan, Teumer, Alexander, Thalamuthu, Anbu, Tordesillas-Gutierrez, Diana, Turner, Jessica, Ueland, Torill, Uhlmann, Anne, Ulfarsson, Magnus O., van 't Ent, Dennis, van der Meer, Dennis, van Haren, Neeltje E.M., Vaskinn, Anja, Vassos, Evangelos, Walters, G. Bragi, Wang, Yunpeng, Wen, Wei, Whelan, Christopher D., Wittfeld, Katharina, Wright, Margie, Yamamori, Hidenaga, Zayats, Tetyana, Agartz, Ingrid, Westlye, Lars T., Jacquemont, Sébastien, Djurovic, Srdjan, Stefánsson, Hreinn, Stefánsson, Kári, Thompson, Paul, Andreassen, Ole A., other, and, Sønderby, Ida E., Gústafsson, Ómar, Doan, Nhat Trung, Hibar, Derrek P., Martin-Brevet, Sandra, Abdellaoui, Abdel, Ames, David, Amunts, Katrin, Andersson, Michael, Armstrong, Nicola J., Bernard, Manon, Blackburn, Nicholas, Blangero, John, Boomsma, Dorret I., Bralten, Janita, Brattbak, Hans Richard, Brodaty, Henry, Brouwer, Rachel M., Bülow, Robin, Calhoun, Vince, Caspers, Svenja, Cavalleri, Gianpiero, Chen, Chi Hua, Cichon, Sven, Ciufolini, Simone, Corvin, Aiden, Crespo-Facorro, Benedicto, Curran, Joanne E., Dale, Anders M., Dalvie, Shareefa, Dazzan, Paola, de Geus, Eco J.C., de Zubicaray, Greig I., de Zwarte, Sonja M.C., Delanty, Norman, den Braber, Anouk, Desrivières, Sylvane, Donohoe, Gary, Draganski, Bogdan, Ehrlich, Stefan, Espeseth, Thomas, Fisher, Simon E., Franke, Barbara, Frouin, Vincent, Fukunaga, Masaki, Gareau, Thomas, Glahn, David C., Grabe, Hans, Groenewold, Nynke A., Haavik, Jan, Håberg, Asta, Hashimoto, Ryota, Hehir-Kwa, Jayne Y., Heinz, Andreas, Hillegers, Manon H.J., Hoffmann, Per, Holleran, Laurena, Hottenga, Jouke Jan, Hulshoff, Hilleke E., Ikeda, Masashi, Jahanshad, Neda, Jernigan, Terry, Jockwitz, Christiane, Johansson, Stefan, Jonsdottir, Gudrun A., Jönsson, Erik G., Kahn, Rene, Kaufmann, Tobias, Kelly, Sinead, Kikuchi, Masataka, Knowles, Emma E.M., Kolskår, Knut K., Kwok, John B., Hellard, Stephanie Le, Leu, Costin, Liu, Jingyu, Lundervold, Astri J., Lundervold, Arvid, Martin, Nicholas G., Mather, Karen, Mathias, Samuel R., McCormack, Mark, McMahon, Katie L., McRae, Allan, Milaneschi, Yuri, Moreau, Clara, Morris, Derek, Mothersill, David, Mühleisen, Thomas W., Murray, Robin, Nordvik, Jan E., Nyberg, Lars, Olde Loohuis, Loes M., Ophoff, Roel, Paus, Tomas, Pausova, Zdenka, Penninx, Brenda, Peralta, Juan M., Pike, Bruce, Prieto, Carlos, Pudas, Sara, Quinlan, Erin, Quintana, Daniel S., Reinbold, Céline S., Marques, Tiago Reis, Reymond, Alexandre, Richard, Genevieve, Rodriguez-Herreros, Borja, Roiz-Santiañez, Roberto, Rokicki, Jarek, Rucker, James, Sachdev, Perminder, Sanders, Anne Marthe, Sando, Sigrid B., Schmaal, Lianne, Schofield, Peter R., Schork, Andrew J., Schumann, Gunter, Shin, Jean, Shumskaya, Elena, Sisodiya, Sanjay, Steen, Vidar M., Stein, Dan J., Steinberg, Stacy, Strike, Lachlan, Teumer, Alexander, Thalamuthu, Anbu, Tordesillas-Gutierrez, Diana, Turner, Jessica, Ueland, Torill, Uhlmann, Anne, Ulfarsson, Magnus O., van 't Ent, Dennis, van der Meer, Dennis, van Haren, Neeltje E.M., Vaskinn, Anja, Vassos, Evangelos, Walters, G. Bragi, Wang, Yunpeng, Wen, Wei, Whelan, Christopher D., Wittfeld, Katharina, Wright, Margie, Yamamori, Hidenaga, Zayats, Tetyana, Agartz, Ingrid, Westlye, Lars T., Jacquemont, Sébastien, Djurovic, Srdjan, Stefánsson, Hreinn, Stefánsson, Kári, Thompson, Paul, Andreassen, Ole A., and other, and

Abstract

Prior to and following the publication of this article the authors noted that the complete list of authors was not included in the main article and was only present in Supplementary Table 1. The author list in the original article has now been updated to include all authors, and Supplementary Table 1 has been removed. All other supplementary files have now been updated accordingly. Furthermore, in Table 1 of this Article, the replication cohort for the row Close relative in data set, n (%) was incorrect. All values have now been corrected to 0(0%). The publishers would like to apologise for this error and the inconvenience it may have caused.

Published
2020

45. Genome-wide analysis reveals extensive genetic overlap between schizophrenia, bipolar disorder, and intelligence

Author

Smeland, Olav B., Bahrami, Shahram, Frei, Oleksandr, Shadrin, Alexey, O’Connell, Kevin, Savage, Jeanne, Watanabe, Kyoko, Krull, Florian, Bettella, Francesco, Steen, Nils Eiel, Ueland, Torill, Posthuma, Danielle, Djurovic, Srdjan, Dale, Anders M., Andreassen, Ole A., Smeland, Olav B., Bahrami, Shahram, Frei, Oleksandr, Shadrin, Alexey, O’Connell, Kevin, Savage, Jeanne, Watanabe, Kyoko, Krull, Florian, Bettella, Francesco, Steen, Nils Eiel, Ueland, Torill, Posthuma, Danielle, Djurovic, Srdjan, Dale, Anders M., and Andreassen, Ole A.

Abstract

Schizophrenia (SCZ) and bipolar disorder (BD) are severe mental disorders associated with cognitive impairment, which is considered a major determinant of functional outcome. Despite this, the etiology of the cognitive impairment is poorly understood, and no satisfactory cognitive treatments exist. Increasing evidence indicates that genetic risk for SCZ may contribute to cognitive impairment, whereas the genetic relationship between BD and cognitive function remains unclear. Here, we combined large genome-wide association study data on SCZ (n = 82,315), BD (n = 51,710), and general intelligence (n = 269,867) to investigate overlap in common genetic variants using conditional false discovery rate (condFDR) analysis. We observed substantial genetic enrichment in both SCZ and BD conditional on associations with intelligence indicating polygenic overlap. Using condFDR analysis, we leveraged this enrichment to increase statistical power and identified 75 distinct genomic loci associated with both SCZ and intelligence, and 12 loci associated with both BD and intelligence at conjunctional FDR < 0.01. Among these loci, 20 are novel for SCZ, and four are novel for BD. Most SCZ risk alleles (61 of 75, 81%) were associated with poorer cognitive performance, whereas most BD risk alleles (9 of 12, 75%) were associated with better cognitive performance. A gene set analysis of the loci shared between SCZ and intelligence implicated biological processes related to neurodevelopment, synaptic integrity, and neurotransmission; the same analysis for BD was underpowered. Altogether, the study demonstrates that both SCZ and BD share genetic influences with intelligence, albeit in a different manner, providing new insights into their genetic architectures.

Published
2020
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46. Childhood trauma and cardiometabolic risk in severe mental disorders: The mediating role of cognitive control

Author

Lunding, Synve Hoffart, primary, Simonsen, Carmen, additional, Aas, Monica, additional, Rødevand, Linn, additional, Werner, Maren Caroline Frogner, additional, Laskemoen, Jannicke Fjæra, additional, Hjell, Gabriela, additional, Ringen, Petter Andreas, additional, Lagerberg, Trine Vik, additional, Melle, Ingrid, additional, Andreassen, Ole A., additional, Ueland, Torill, additional, and Steen, Nils Eiel, additional

Published
2021
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