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1. Cortical similarities in psychiatric and mood disorders identified in federated VBM analysis via COINSTAC.

Author: Kelly Rootes-Murdy, Sandeep R. Panta, Ross Kelly, Javier Tomas Romero, Yann Quidé, Murray J. Cairns, C. M. Loughland, Vaughan J. Carr, Stanley V. Catts, Assen Jablensky, Melissa J. Green, Frans Henskens, Dylan Kiltschewskij, Patricia T. Michie, Bryan J. Mowry, Christos Pantelis, Paul E. Rasser, William R. Reay, Ulrich Schall, Rodney J. Scott, Oliver J. Watkeys, Gloria M. P. Roberts, Philip B. Mitchell, Janice M. Fullerton, Bronwyn J. Overs, Masataka Kikuchi, Ryota Hashimoto, Junya Matsumoto, Masaki Fukunaga, Perminder S. Sachdev, Henry Brodaty, Wei Wen, Jiyang Jiang, Negar Fani, Timothy D. Ely, Adriana Lorio, Jennifer S. Stevens, Kerry J. Ressler, Tanja Jovanovic, Sanne J. H. van Rooij, Lydia M. Federmann, Christiane Jockwitz, Alexander Teumer, Andreas J. Forstner, Svenja Caspers, Sven Cichon, Sergey M. Plis, Anand D. Sarwate, and Vince D. Calhoun
Published: 2024
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2. Epigenetic signatures relating to disease-associated genotypic burden in familial risk of bipolar disorder

Author: Sonia Hesam-Shariati, Bronwyn J. Overs, Gloria Roberts, Claudio Toma, Oliver J. Watkeys, Melissa J. Green, Kerrie D. Pierce, Howard J. Edenberg, Holly C. Wilcox, Emma K. Stapp, Melvin G. McInnis, Leslie A. Hulvershorn, John I. Nurnberger, Peter R. Schofield, Philip B. Mitchell, and Janice M. Fullerton
Subjects: Neurosciences. Biological psychiatry. Neuropsychiatry, RC321-571
Abstract: Abstract Environmental factors contribute to risk of bipolar disorder (BD), but how environmental factors impact the development of psychopathology within the context of elevated genetic risk is unknown. We herein sought to identify epigenetic signatures operating in the context of polygenic risk for BD in young people at high familial risk (HR) of BD. Peripheral blood-derived DNA was assayed using Illumina PsychArray, and Methylation-450K or -EPIC BeadChips. Polygenic risk scores (PRS) were calculated using summary statistics from recent genome-wide association studies for BD, major depressive disorder (MDD) and cross-disorder (meta-analysis of eight psychiatric disorders). Unrelated HR participants of European ancestry (n = 103) were stratified based on their BD-PRS score within the HR-population distribution, and the top two quintiles (High-BD-PRS; n = 41) compared against the bottom two quintiles (Low-BD-PRS; n = 41). The High-BD-PRS stratum also had higher mean cross-disorder-PRS and MDD-PRS (ANCOVA p = 0.035 and p = 0.024, respectively). We evaluated DNA methylation differences between High-BD-PRS and Low-BD-PRS strata using linear models. One differentially methylated probe (DMP) (cg00933603; p = 3.54 × 10−7) in VARS2, a mitochondrial aminoacyl-tRNA synthetase, remained significantly hypomethylated after multiple-testing correction. Overall, BD-PRS appeared to broadly impact epigenetic processes, with 1,183 genes mapped to nominal DMPs (p
Published: 2022
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3. The Medical Genome Reference Bank contains whole genome and phenotype data of 2570 healthy elderly

Author: Mark Pinese, Paul Lacaze, Emma M. Rath, Andrew Stone, Marie-Jo Brion, Adam Ameur, Sini Nagpal, Clare Puttick, Shane Husson, Dmitry Degrave, Tina Navin Cristina, Vivian F. S. Kahl, Aaron L. Statham, Robyn L. Woods, John J. McNeil, Moeen Riaz, Margo Barr, Mark R. Nelson, Christopher M. Reid, Anne M. Murray, Raj C. Shah, Rory Wolfe, Joshua R. Atkins, Chantel Fitzsimmons, Heath M. Cairns, Melissa J. Green, Vaughan J. Carr, Mark J. Cowley, Hilda A. Pickett, Paul A. James, Joseph E. Powell, Warren Kaplan, Greg Gibson, Ulf Gyllensten, Murray J. Cairns, Martin McNamara, Marcel E. Dinger, and David M. Thomas
Subjects: Science
Abstract: Healthspan and healthy aging are areas of research with potential socioeconomic impact. Here, the authors present the Medical Genome Reference Bank (MGRB) which consist of over 4,000 individuals aged 70 years and older without a history of the major age-related diseases and report on results from whole-genome sequencing and association analyses.
Published: 2020
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4. Item response theory analysis of self-reported social–emotional learning competencies in an Australian population cohort aged 11 years

Author: Emma J. Carpendale, Melissa J. Green, Kate E. Williams, Stacy Tzoumakis, Vaughan J. Carr, and Kristin R. Laurens
Subjects: Developmental and Educational Psychology, Education
Published: 2023
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5. Investigating the neural correlates of affective mentalizing and their association with general intelligence in patients with schizophrenia

Author: Wladimir Tantchik, Melissa J. Green, Yann Quidé, Susanne Erk, Sebastian Mohnke, Carolin Wackerhagen, Nina Romanczuk-Seiferth, Heike Tost, Kristina Schwarz, Carolin Moessnang, Danilo Bzdok, Andreas Meyer-Lindenberg, Andreas Heinz, and Henrik Walter
Subjects: Psychiatry and Mental health, Biological Psychiatry
Published: 2023
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6. Relationships between parental mental illness and/or offending and offspring contact with the police in childhood: Findings from a longitudinal record‐linkage study

Author: Ulrika Athanassiou, Melissa J. Green, Stacy Tzoumakis, Tyson Whitten, Kristin R. Laurens, Felicity Harris, Vaughan J. Carr, and Kimberlie Dean
Subjects: Psychiatry and Mental health, Psychology (miscellaneous), General Medicine, Pathology and Forensic Medicine
Published: 2023
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7. Increased power by harmonizing structural MRI site differences with the ComBat batch adjustment method in ENIGMA

Author: Joaquim Radua, Eduard Vieta, Russell Shinohara, Peter Kochunov, Yann Quidé, Melissa J. Green, Cynthia S. Weickert, Thomas Weickert, Jason Bruggemann, Tilo Kircher, Igor Nenadić, Murray J. Cairns, Marc Seal, Ulrich Schall, Frans Henskens, Janice M. Fullerton, Bryan Mowry, Christos Pantelis, Rhoshel Lenroot, Vanessa Cropley, Carmel Loughland, Rodney Scott, Daniel Wolf, Theodore D. Satterthwaite, Yunlong Tan, Kang Sim, Fabrizio Piras, Gianfranco Spalletta, Nerisa Banaj, Edith Pomarol-Clotet, Aleix Solanes, Anton Albajes-Eizagirre, Erick J. Canales-Rodríguez, Salvador Sarro, Annabella Di Giorgio, Alessandro Bertolino, Michael Stäblein, Viola Oertel, Christian Knöchel, Stefan Borgwardt, Stefan du Plessis, Je-Yeon Yun, Jun Soo Kwon, Udo Dannlowski, Tim Hahn, Dominik Grotegerd, Clara Alloza, Celso Arango, Joost Janssen, Covadonga Díaz-Caneja, Wenhao Jiang, Vince Calhoun, Stefan Ehrlich, Kun Yang, Nicola G. Cascella, Yoichiro Takayanagi, Akira Sawa, Alexander Tomyshev, Irina Lebedeva, Vasily Kaleda, Matthias Kirschner, Cyril Hoschl, David Tomecek, Antonin Skoch, Therese van Amelsvoort, Geor Bakker, Anthony James, Adrian Preda, Andrea Weideman, Dan J. Stein, Fleur Howells, Anne Uhlmann, Henk Temmingh, Carlos López-Jaramillo, Ana Díaz-Zuluaga, Lydia Fortea, Eloy Martinez-Heras, Elisabeth Solana, Sara Llufriu, Neda Jahanshad, Paul Thompson, Jessica Turner, Theo van Erp, David Glahn, Godfrey Pearlson, Elliot Hong, Axel Krug, Vaughan Carr, Paul Tooney, Gavin Cooper, Paul Rasser, Patricia Michie, Stanley Catts, Raquel Gur, Ruben Gur, Fude Yang, Fengmei Fan, Jingxu Chen, Hua Guo, Shuping Tan, Zhiren Wang, Hong Xiang, Federica Piras, Francesca Assogna, Raymond Salvador, Peter McKenna, Aurora Bonvino, Margaret King, Stefan Kaiser, Dana Nguyen, and Julian Pineda-Zapata
Subjects: Brain, Cortical thickness, Gray matter, Mega-analysis, Neuroimaging, Schizophrenia, Neurosciences. Biological psychiatry. Neuropsychiatry, RC321-571
Abstract: A common limitation of neuroimaging studies is their small sample sizes. To overcome this hurdle, the Enhancing Neuro Imaging Genetics through Meta-Analysis (ENIGMA) Consortium combines neuroimaging data from many institutions worldwide. However, this introduces heterogeneity due to different scanning devices and sequences. ENIGMA projects commonly address this heterogeneity with random-effects meta-analysis or mixed-effects mega-analysis. Here we tested whether the batch adjustment method, ComBat, can further reduce site-related heterogeneity and thus increase statistical power. We conducted random-effects meta-analyses, mixed-effects mega-analyses and ComBat mega-analyses to compare cortical thickness, surface area and subcortical volumes between 2897 individuals with a diagnosis of schizophrenia and 3141 healthy controls from 33 sites. Specifically, we compared the imaging data between individuals with schizophrenia and healthy controls, covarying for age and sex. The use of ComBat substantially increased the statistical significance of the findings as compared to random-effects meta-analyses. The findings were more similar when comparing ComBat with mixed-effects mega-analysis, although ComBat still slightly increased the statistical significance. ComBat also showed increased statistical power when we repeated the analyses with fewer sites. Results were nearly identical when we applied the ComBat harmonization separately for cortical thickness, cortical surface area and subcortical volumes. Therefore, we recommend applying the ComBat function to attenuate potential effects of site in ENIGMA projects and other multi-site structural imaging work. We provide easy-to-use functions in R that work even if imaging data are partially missing in some brain regions, and they can be trained with one data set and then applied to another (a requirement for some analyses such as machine learning).
Published: 2020
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8. Pathways from developmental vulnerabilities in early childhood to schizotypy in middle childhood

Author: Kirstie O'Hare, Oliver Watkeys, Johanna C. Badcock, Kristin R. Laurens, Stacy Tzoumakis, Kimberlie Dean, Felicity Harris, Vaughan J. Carr, and Melissa J. Green
Subjects: Clinical Psychology, General Medicine
Abstract: Childhood disturbances in social, emotional, language, motor and cognitive functioning, and schizotypy have each been implicated as precursors of schizophrenia-spectrum disorders. We investigated whether relationships between early childhood developmental vulnerabilities and childhood schizotypy are mediated by educational underachievement in middle childhood.Participants were members of a large Australian (n = 19,216) population cohort followed longitudinally. Path analyses were used to model relationships between developmental vulnerabilities at age ~5 years, educational underachievement from ages ~8 to 10 years and three distinct profiles of schizotypy at age ~11 years (true, introverted and affective schizotypy).Early childhood developmental vulnerabilities on five broad domains (related to physical, emotional, social, cognitive and communication development) were associated with schizotypy profiles in middle childhood. Educational underachievement in middle childhood was associated with all schizotypy profiles, but most strongly with the true schizotypy profile (OR = 3.92, 95% CI = 3.12, 4.91). The relationships between schizotypy profiles and early childhood developmental vulnerabilities in 'language and cognitive skills (school-based)' and 'communication skills and general knowledge' domains were fully mediated by educational underachievement in middle childhood, and the relationships with early childhood 'physical health and well-being' and 'emotional maturity' domains were partially mediated.Developmental continuity from early childhood developmental vulnerabilities to schizotypy in middle childhood is mediated by educational underachievement in middle childhood. While some domains of early developmental functioning showed differential relationships with distinct schizotypy profiles, these findings support a developmental pathway to schizotypy in which cognitive vulnerability operates from early childhood through to middle childhood.
Published: 2022
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9. Genetics-informed precision treatment formulation in schizophrenia and bipolar disorder

Author: William R. Reay, Michael P. Geaghan, Joshua R. Atkins, Vaughan J. Carr, Melissa J. Green, and Murray J. Cairns
Subjects: Multifactorial Inheritance, Bipolar Disorder, Risk Factors, Schizophrenia, Genetics, Humans, Genetic Predisposition to Disease, Genetics (clinical), Genome-Wide Association Study
Abstract: Genetically informed drug development and repurposing is an attractive prospect for improving patient outcomes in psychiatry; however, the effectiveness of these endeavors is confounded by heterogeneity. We propose an approach that links interventions implicated by disorder-associated genetic risk, at the population level, to a framework that can target these compounds to individuals. Specifically, results from genome-wide association studies are integrated with expression data to prioritize individual "directional anchor" genes for which the predicted risk-increasing direction of expression could be counteracted by an existing drug. While these compounds represent plausible therapeutic candidates, they are not likely to be equally efficacious for all individuals. To account for this heterogeneity, we constructed polygenic scores restricted to variants annotated to the network of genes that interact with each directional anchor gene. These metrics, which we call a pharmagenic enrichment score (PES), identify individuals with a higher burden of genetic risk, localized in biological processes related to the candidate drug target, to inform precision drug repurposing. We used this approach to investigate schizophrenia and bipolar disorder and reveal several compounds targeting specific directional anchor genes that could be plausibly repurposed. These genetic risk scores, mapped to the networks associated with target genes, revealed biological insights that cannot be observed in undifferentiated genome-wide polygenic risk score (PRS). For example, an enrichment of these partitioned scores in schizophrenia cases with otherwise low PRS. In summary, genetic risk could be used more specifically to direct drug repurposing candidates that target particular genes implicated in psychiatric and other complex disorders.
Published: 2022
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10. Cumulative environmental risk in early life is associated with mental disorders in childhood

Author: Kirstie O'Hare, Oliver Watkeys, Tyson Whitten, Kimberlie Dean, Kristin R. Laurens, Felicity Harris, Vaughan J. Carr, and Melissa J. Green
Subjects: Psychiatry and Mental health, Applied Psychology
Abstract: Background No single environmental factor is a necessary or sufficient cause of mental disorder; multifactorial and transdiagnostic approaches are needed to understand the impact of the environment on the development of mental disorders across the life course. Method Using linked multi-agency administrative data for 71 932 children from the New South Wales Child Developmental Study, using logistic regression, we examined associations between 16 environmental risk factors in early life (prenatal period to Results The ERS was associated with all types of mental disorder diagnoses in a dose–response fashion, such that 2.8% of children with no exposure to any of the environmental factors (ERS = 0), compared to 18.3% of children with an ERS of 8 or more indicating exposure to 8 or more environmental factors (ERS ⩾ 8), had been diagnosed with any type of mental disorder up to age 13–14 years. Thirteen of the 16 environmental factors measured (including prenatal factors, neighbourhood characteristics and more proximal experiences of trauma or neglect) were positively associated with at least one category of mental disorder. Conclusion Exposure to cumulative environmental risk factors in early life is associated with an increased likelihood of presenting to health services in childhood for any kind of mental disorder. In many instances, these factors are preventable or capable of mitigation by appropriate public policy settings.
Published: 2022
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11. Genetic Overlap Between Alzheimer’s Disease and Bipolar Disorder Implicates the MARK2 and VAC14 Genes

Author: Ole Kristian Drange, Olav Bjerkehagen Smeland, Alexey A. Shadrin, Per Ivar Finseth, Aree Witoelar, Oleksandr Frei, Psychiatric Genomics Consortium Bipolar Disorder Working Group, Yunpeng Wang, Sahar Hassani, Srdjan Djurovic, Anders M. Dale, Ole A. Andreassen, Eli A Stahl, Gerome Breen, Andreas J Forstner, Andrew McQuillin, Stephan Ripke, Vassily Trubetskoy, Manuel Mattheisen, Jonathan R I Coleman, Heìleìna A Gaspar, Christiaan A de Leeuw, Stacy Steinberg, Jennifer M Whitehead Pavlides, Maciej Trzaskowski, Tune H Pers, Peter A Holmans, Liam Abbott, Esben Agerbo, Huda Akil, Diego Albani, Ney Alliey-Rodriguez, Thomas D Als, Adebayo Anjorin, Verneri Antilla, Swapnil Awasthi, Judith A Badner, Marie Bækvad-Hansen, Jack D Barchas, Nicholas Bass, Michael Bauer, Richard Belliveau, Sarah E Bergen, Carsten Bøcker Pedersen, Erlend Bøen, Marco Boks, James Boocock, Monika Budde, William Bunney, Margit Burmeister, Jonas Bybjerg-Grauholm, William Byerley, Miquel Casas, Felecia Cerrato, Pablo Cervantes, Kimberly Chambert, Alexander W Charney, Danfeng Chen, Claire Churchhouse, Toni-Kim Clarke, William Coryell, David W Craig, Cristiana Cruceanu, David Curtis, Piotr M Czerski, Anders M Dale, Simone de Jong, Franziska Degenhardt, Jurgen Del-Favero, J Raymond DePaulo, Amanda L Dobbyn, Ashley Dumont, Torbjørn Elvsåshagen, Valentina Escott-Price, Chun Chieh Fan, Sascha B Fischer, Matthew Flickinger, Tatiana M Foroud, Liz Forty, Josef Frank, Christine Fraser, Nelson B Freimer, Louise Friseìn, Katrin Gade, Diane Gage, Julie Garnham, Claudia Giambartolomei, Marianne Giørtz Pedersen, Jaqueline Goldstein, Scott D Gordon, Katherine Gordon-Smith, Elaine K Green, Melissa J Green, Tiffany A Greenwood, Jakob Grove, Weihua Guan, Joseì Guzman Parra, Marian L Hamshere, Martin Hautzinger, Urs Heilbronner, Stefan Herms, Maria Hipolito, Per Hoffmann, Dominic Holland, Laura Huckins, Steìphane Jamain, Jessica S Johnson, Anders Jureìus, Radhika Kandaswamy, Robert Karlsson, James L Kennedy, Sarah Kittel-Schneider, Sarah V Knott, James A Knowles, Manolis Kogevinas, Anna C Koller, Ralph Kupka, Catharina Lavebratt, Jacob Lawrence, William B Lawson, Markus Leber, Phil H Lee, Shawn E Levy, Jun Z Li, Chunyu Liu, Susanne Lucae, Anna Maaser, Donald J MacIntyre, Pamela B Mahon, Wolfgang Maier, Lina Martinsson, Steve McCarroll, Peter McGuffin, Melvin G McInnis, James D McKay, Helena Medeiros, Sarah E Medland, Fan Meng, Lili Milani, Grant W Montgomery, Derek W Morris, Thomas W Mühleisen, Niamh Mullins, Hoang Nguyen, Caroline M Nievergelt, Annelie Nordin Adolfsson, Evaristus A Nwulia, Claire O’Donovan, Loes M Olde Loohuis, Anil P S Ori, Lilijana Oruc, Urban Ösby, Roy H Perlis, Amy Perry, Andrea Pfennig, James B Potash, Shaun M Purcell, Eline J Regeer, Andreas Reif, Ceìline S Reinbold, John P Rice, Fabio Rivas, Margarita Rivera, Panos Roussos, Douglas M Ruderfer, Euijung Ryu, Cristina Saìnchez-Mora, Alan F Schatzberg, William A Scheftner, Nicholas J Schork, Cynthia Shannon Weickert, Tatyana Shehktman, Paul D Shilling, Engilbert Sigurdsson, Claire Slaney, Olav B Smeland, Janet L Sobell, Christine Søholm Hansen, Anne T Spijker, David St Clair, Michael Steffens, John S Strauss, Fabian Streit, Jana Strohmaier, Szabolcs Szelinger, Robert C Thompson, Thorgeir E Thorgeirsson, Jens Treutlein, Helmut Vedder, Weiqing Wang, Stanley J Watson, Thomas W Weickert, Stephanie H Witt, Simon Xi, Wei Xu, Allan H Young, Peter Zandi, Peng Zhang, Sebastian Zollner, Rolf Adolfsson, Ingrid Agartz, Martin Alda, Lena Backlund, Bernhard T Baune, Frank Bellivier, Wade H Berrettini, Joanna M Biernacka, Douglas H R Blackwood, Michael Boehnke, Anders D Børglum, Aiden Corvin, Nicholas Craddock, Mark J Daly, Udo Dannlowski, ToÞnu Esko, Bruno Etain, Mark Frye, Janice M Fullerton, Elliot S Gershon, Michael Gill, Fernando Goes, Maria Grigoroiu-Serbanescu, Joanna Hauser, David M Hougaard, Christina M Hultman, Ian Jones, Lisa A Jones, Reneì S Kahn, George Kirov, Mikael Landeìn, Marion Leboyer, Cathryn M Lewis, Qingqin S Li, Jolanta Lissowska, Nicholas G Martin, Fermin Mayoral, Susan L McElroy, Andrew M McIntosh, Francis J McMahon, Ingrid Melle, Andres Metspalu, Philip B Mitchell, Gunnar Morken, Ole Mors, Preben Bo Mortensen, Bertram Müller-Myhsok, Richard M Myers, Benjamin M Neale, Vishwajit Nimgaonkar, Merete Nordentoft, Markus M Nöthen, Michael C O’Donovan, Ketil J Oedegaard, Michael J Owen, Sara A Paciga, Carlos Pato, Michele T Pato, Danielle Posthuma, Josep Antoni Ramos-Quiroga, Marta Ribaseìs, Marcella Rietschel, Guy A Rouleau, Martin Schalling, Peter R Schofield, Thomas G Schulze, Alessandro Serretti, Jordan W Smoller, Hreinn Stefansson, Kari Stefansson, Eystein Stordal, Patrick F Sullivan, Gustavo Turecki, Arne E Vaaler, Eduard Vieta, John B Vincent, Thomas Werge, John I Nurnberger, Naomi R Wray, Arianna Di Florio, Howard J Edenberg, Sven Cichon, Roel A Ophoff, Laura J Scott, Ole A Andreassen, John Kelsoe, and Pamela Sklar
Subjects: Alzheimer’s disease, bipolar disorder, GWAS, pleiotropy, cognitive symptoms, affective symptoms, Neurosciences. Biological psychiatry. Neuropsychiatry, RC321-571
Abstract: Background: Alzheimer’s disease (AD) and bipolar disorder (BIP) are complex traits influenced by numerous common genetic variants, most of which remain to be detected. Clinical and epidemiological evidence suggest that AD and BIP are related. However, it is not established if this relation is of genetic origin. Here, we applied statistical methods based on the conditional false discovery rate (FDR) framework to detect genetic overlap between AD and BIP and utilized this overlap to increase the power to identify common genetic variants associated with either or both traits.Methods: We obtained genome wide association studies data from the International Genomics of Alzheimer’s Project part 1 (17,008 AD cases and 37,154 controls) and the Psychiatric Genetic Consortium Bipolar Disorder Working Group (20,352 BIP cases and 31,358 controls). We used conditional QQ-plots to assess overlap in common genetic variants between AD and BIP. We exploited the genetic overlap to re-rank test-statistics for AD and BIP and improve detection of genetic variants using the conditional FDR framework.Results: Conditional QQ-plots demonstrated a polygenic overlap between AD and BIP. Using conditional FDR, we identified one novel genomic locus associated with AD, and nine novel loci associated with BIP. Further, we identified two novel loci jointly associated with AD and BIP implicating the MARK2 gene (lead SNP rs10792421, conjunctional FDR = 0.030, same direction of effect) and the VAC14 gene (lead SNP rs11649476, conjunctional FDR = 0.022, opposite direction of effect).Conclusion: We found polygenic overlap between AD and BIP and identified novel loci for each trait and two jointly associated loci. Further studies should examine if the shared loci implicating the MARK2 and VAC14 genes could explain parts of the shared and distinct features of AD and BIP.
Published: 2019
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12. Large-scale analysis of structural brain asymmetries in schizophrenia via the ENIGMA consortium

Author: Dick Schijven, Merel C. Postema, Masaki Fukunaga, Junya Matsumoto, Kenichiro Miura, Sonja M. C. de Zwarte, Neeltje E. M. van Haren, Wiepke Cahn, Hilleke E. Hulshoff Pol, René S. Kahn, Rosa Ayesa-Arriola, Víctor Ortiz-García de la Foz, Diana Tordesillas-Gutierrez, Javier Vázquez-Bourgon, Benedicto Crespo-Facorro, Dag Alnæs, Andreas Dahl, Lars T. Westlye, Ingrid Agartz, Ole A. Andreassen, Erik G. Jönsson, Peter Kochunov, Jason M. Bruggemann, Stanley V. Catts, Patricia T. Michie, Bryan J. Mowry, Yann Quidé, Paul E. Rasser, Ulrich Schall, Rodney J. Scott, Vaughan J. Carr, Melissa J. Green, Frans A. Henskens, Carmel M. Loughland, Christos Pantelis, Cynthia Shannon Weickert, Thomas W. Weickert, Lieuwe de Haan, Katharina Brosch, Julia-Katharina Pfarr, Kai G. Ringwald, Frederike Stein, Andreas Jansen, Tilo T. J. Kircher, Igor Nenadić, Bernd Krämer, Oliver Gruber, Theodore D. Satterthwaite, Juan Bustillo, Daniel H. Mathalon, Adrian Preda, Vince D. Calhoun, Judith M. Ford, Steven G. Potkin, Jingxu Chen, Yunlong Tan, Zhiren Wang, Hong Xiang, Fengmei Fan, Fabio Bernardoni, Stefan Ehrlich, Paola Fuentes-Claramonte, Maria Angeles Garcia-Leon, Amalia Guerrero-Pedraza, Raymond Salvador, Salvador Sarró, Edith Pomarol-Clotet, Valentina Ciullo, Fabrizio Piras, Daniela Vecchio, Nerisa Banaj, Gianfranco Spalletta, Stijn Michielse, Therese van Amelsvoort, Erin W. Dickie, Aristotle N. Voineskos, Kang Sim, Simone Ciufolini, Paola Dazzan, Robin M. Murray, Woo-Sung Kim, Young-Chul Chung, Christina Andreou, André Schmidt, Stefan Borgwardt, Andrew M. McIntosh, Heather C. Whalley, Stephen M. Lawrie, Stefan du Plessis, Hilmar K. Luckhoff, Freda Scheffler, Robin Emsley, Dominik Grotegerd, Rebekka Lencer, Udo Dannlowski, Jesse T. Edmond, Kelly Rootes-Murdy, Julia M. Stephen, Andrew R. Mayer, Linda A. Antonucci, Leonardo Fazio, Giulio Pergola, Alessandro Bertolino, Covadonga M. Díaz-Caneja, Joost Janssen, Noemi G. Lois, Celso Arango, Alexander S. Tomyshev, Irina Lebedeva, Simon Cervenka, Carl M. Sellgren, Foivos Georgiadis, Matthias Kirschner, Stefan Kaiser, Tomas Hajek, Antonin Skoch, Filip Spaniel, Minah Kim, Yoo Bin Kwak, Sanghoon Oh, Jun Soo Kwon, Anthony James, Geor Bakker, Christian Knöchel, Michael Stäblein, Viola Oertel, Anne Uhlmann, Fleur M. Howells, Dan J. Stein, Henk S. Temmingh, Ana M. Diaz-Zuluaga, Julian A. Pineda-Zapata, Carlos López-Jaramillo, Stephanie Homan, Ellen Ji, Werner Surbeck, Philipp Homan, Simon E. Fisher, Barbara Franke, David C. Glahn, Ruben C. Gur, Ryota Hashimoto, Neda Jahanshad, Eileen Luders, Sarah E. Medland, Paul M. Thompson, Jessica A. Turner, Theo G. M. van Erp, Clyde Francks, Neurology, and Child and Adolescent Psychiatry / Psychology
Subjects: subcortical, Neuroinformatics, Multidisciplinary, All institutes and research themes of the Radboud University Medical Center, Neurodevelopmental disorders Donders Center for Medical Neuroscience [Radboudumc 7], Schizophrenia, brain imaging, cortical, asymmetry
Abstract: Contains fulltext : 291574.pdf (Publisher’s version ) (Open Access) Left-right asymmetry is an important organizing feature of the healthy brain that may be altered in schizophrenia, but most studies have used relatively small samples and heterogeneous approaches, resulting in equivocal findings. We carried out the largest case-control study of structural brain asymmetries in schizophrenia, with MRI data from 5,080 affected individuals and 6,015 controls across 46 datasets, using a single image analysis protocol. Asymmetry indexes were calculated for global and regional cortical thickness, surface area, and subcortical volume measures. Differences of asymmetry were calculated between affected individuals and controls per dataset, and effect sizes were meta-analyzed across datasets. Small average case-control differences were observed for thickness asymmetries of the rostral anterior cingulate and the middle temporal gyrus, both driven by thinner left-hemispheric cortices in schizophrenia. Analyses of these asymmetries with respect to the use of antipsychotic medication and other clinical variables did not show any significant associations. Assessment of age- and sex-specific effects revealed a stronger average leftward asymmetry of pallidum volume between older cases and controls. Case-control differences in a multivariate context were assessed in a subset of the data (N = 2,029), which revealed that 7% of the variance across all structural asymmetries was explained by case-control status. Subtle case-control differences of brain macrostructural asymmetry may reflect differences at the molecular, cytoarchitectonic, or circuit levels that have functional relevance for the disorder. Reduced left middle temporal cortical thickness is consistent with altered left-hemisphere language network organization in schizophrenia.
Published: 2023
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13. Developmental profiles of schizotypy in the general population: A record linkage study of Australian children aged 11–12 years

Author: Melissa J. Green, Kirstie O’Hare, Kristin R. Laurens, Stacy Tzoumakis, Kimberlie Dean, Johanna C. Badcock, Felicity Harris, Richard J. Linscott, and Vaughan J. Carr
Subjects: Schizotypal Personality Disorder, Clinical Psychology, Mental Health, Adolescent, Psychotic Disorders, Pregnancy, Child, Preschool, Australia, Schizophrenia, Humans, Female, General Medicine, Child
Abstract: The detection of young people at high risk for psychotic disorders has been somewhat narrowly focused on overt symptom-based markers that reflect mild reality distortion (e.g., psychotic-like experiences), or prodromal syndromes that are proximal to psychosis onset. The concept of schizotypy represents a broader framework for investigating risk for schizophrenia (and other disorders) in childhood, before the onset of prodromal or overt symptoms. We sought to detect profiles of risk for psychosis (schizotypy) in a general population sample of 22,137 Australian children aged 11-12 years, and to determine early life risk factors associated with these profiles from data available in linked records (registers).Fifty-nine self-reported items were used as indicators of schizotypy across six broad domains; z-scores for each domain were subjected to latent profile analyses (LPA). A series of multinomial logistic regressions was used to examine the association between resulting profile (class) membership and several childhood and parental risk factors, and the proportion of children with mental disorders among each schizotypy profile was examined.The LPA revealed three person-centred profiles referred to as True Schizotypy (n = 1,323; 6.0%), Introverted Schizotypy (n = 4,473; 20.2%), and Affective Schizotypy (n = 4,261; 19.2%), as well as a group of children showing no risk (n = 12,080; 54.6%). Prior exposure to perinatal and familial adversities including childhood maltreatment, as well as poor early childhood development and academic functioning, was variously associated with all risk groups. There was a higher proportion of childhood mental disorder diagnoses among children in the True Schizotypy group, relative to other profiles.Subtle differences in the pattern of exposures and antecedents among schizophrenia liability profiles in childhood may reflect distinct pathogenic pathways to psychotic or other mental illness.Children aged 11-12 years report characteristics of schizotypy which can be classified into three distinct profiles that may represent different pathological processes towards later mental ill-health. Early life exposure to perinatal and familial adversities including childhood maltreatment, early childhood developmental vulnerability, and poor academic functioning predict membership in all three childhood schizotypy profiles. Latent liability for schizophrenia (and potentially other mental disorders) may be represented by different profiles of functioning observable in childhood.
Published: 2022
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14. What we learn about bipolar disorder from large-scale neuroimaging

Author: Christian K. Tamnes, Bartholomeus C M Haarman, Jair C. Soares, Ole A. Andreassen, Viola Oertel, Theodore D. Satterthwaite, G. Tronchin, Michael Stäblein, Bradley J. MacIntosh, Melissa Pauling, Christopher R.K. Ching, Daniel H. Wolf, Dick J. Veltman, Ingrid Agartz, Bernhard T. Baune, Salvador Sarró, Mon-Ju Wu, Scott C Fears, Eduard Vieta, Melissa J. Green, Neeltje E.M. van Haren, Yann Quidé, Erlend Bøen, Yash Patel, Igor Nenadic, Martin Alda, Lisa T. Eyler, Arnaud Pouchon, Danai Dima, Tomáš Paus, Irene Bollettini, Torbjørn Elvsåshagen, Rachel M. Brouwer, Lakshmi N. Yatham, Michael Bauer, Caterina del Mar Bonnín, C. McDonald, Udo Dannlowski, Bronwyn Overs, Edith Pomarol-Clotet, Cristian Vargas Upegui, Oliver Gruber, Henricus G. Ruhé, Márcio Gerhardt Soeiro-de-Souza, Edouard Duchesnay, Hilary P. Blumberg, Tilo Kircher, Miho Ota, Michael Berk, Christoph Abé, Andreas Jansen, Kang Sim, Heather C. Whalley, Derrek P. Hibar, Roel A. Ophoff, Georgios V Thomaidis, Henrik Walter, Sophia Frangou, Michèle Wessa, Dara M. Cannon, Cara M. Altimus, Allison C. Nugent, Rodrigo Machado-Vieira, Orwa Dandash, Marcella Bellani, Unn K. Haukvik, Philip B. Mitchell, Ling-Li Zeng, Christian Knöchel, Jose Manuel Goikolea, Sonja M C de Zwarte, Francesco Benedetti, Sara Poletti, Janice M. Fullerton, Carlos A. Zarate, Aart H. Schene, Dan J. Stein, Chantal Henry, Tristram A. Lett, Mikael Landén, Daniel L Pham, Paolo Brambilla, Silvia Alonso-Lana, Sophia I. Thomopoulos, Carlos López-Jaramillo, Tomas Hajek, Bernd Kramer, G. Delvecchio, Maria M. Rive, Lars T. Westlye, Erick J. Canales-Rodríguez, Victoria L. Ives-Deliperi, Dominik Grotegerd, Beny Lafer, Abraham Nunes, Carrie E. Bearden, Raymond Salvador, Joaquim Radua, Amy C Bilderbeck, Xavier Caseras, Paul M. Thompson, Jorge R. C. Almeida, Pauline Favre, Gloria Roberts, David C. Glahn, Dag Alnæs, Julian A Pineda-Zapata, Tiril P. Gurholt, Mircea Polosan, Josselin Houenou, Fabiano G. Nery, Leila Nabulsi, Mary L. Phillips, Fleur M. Howells, Ana M. Díaz-Zuluaga, Elisa M T Melloni, Ching, C. R. K., Hibar, D. P., Gurholt, T. P., Nunes, A., Thomopoulos, S. I., Abe, C., Agartz, I., Brouwer, R. M., Cannon, D. M., de Zwarte, S. M. C., Eyler, L. T., Favre, P., Hajek, T., Haukvik, U. K., Houenou, J., Landen, M., Lett, T. A., Mcdonald, C., Nabulsi, L., Patel, Y., Pauling, M. E., Paus, T., Radua, J., Soeiro-de-Souza, M. G., Tronchin, G., van Haren, N. E. M., Vieta, E., Walter, H., Zeng, L. -L., Alda, M., Almeida, J., Alnaes, D., Alonso-Lana, S., Altimus, C., Bauer, M., Baune, B. T., Bearden, C. E., Bellani, M., Benedetti, F., Berk, M., Bilderbeck, A. C., Blumberg, H. P., Boen, E., Bollettini, I., del Mar Bonnin, C., Brambilla, P., Canales-Rodriguez, E. J., Caseras, X., Dandash, O., Dannlowski, U., Delvecchio, G., Diaz-Zuluaga, A. M., Dima, D., Duchesnay, E., Elvsashagen, T., Fears, S. C., Frangou, S., Fullerton, J. M., Glahn, D. C., Goikolea, J. M., Green, M. J., Grotegerd, D., Gruber, O., Haarman, B. C. M., Henry, C., Howells, F. M., Ives-Deliperi, V., Jansen, A., Kircher, T. T. J., Knochel, C., Kramer, B., Lafer, B., Lopez-Jaramillo, C., Machado-Vieira, R., Macintosh, B. J., Melloni, E. M. T., Mitchell, P. B., Nenadic, I., Nery, F., Nugent, A. C., Oertel, V., Ophoff, R. A., Ota, M., Overs, B. J., Pham, D. L., Phillips, M. L., Pineda-Zapata, J. A., Poletti, S., Polosan, M., Pomarol-Clotet, E., Pouchon, A., Quide, Y., Rive, M. M., Roberts, G., Ruhe, H. G., Salvador, R., Sarro, S., Satterthwaite, T. D., Schene, A. H., Sim, K., Soares, J. C., Stablein, M., Stein, D. J., Tamnes, C. K., Thomaidis, G. V., Upegui, C. V., Veltman, D. J., Wessa, M., Westlye, L. T., Whalley, H. C., Wolf, D. H., Wu, M. -J., Yatham, L. N., Zarate, C. A., Thompson, P. M., and Andreassen, O. A.
Subjects: mega-analysis, Stress-related disorders Donders Center for Medical Neuroscience [Radboudumc 13], cortical surface area, Review Article, 0302 clinical medicine, Manic-depressive illness, Multicenter Studies as Topic, Spectrum disorder, Review Articles, bipolar disorder, Cerebral Cortex, Trastorn bipolar, neuroimaging, Radiological and Ultrasound Technology, 05 social sciences, ENIGMA, HUMAN BRAIN, Magnetic Resonance Imaging, psychiatry, 3. Good health, Neurology, Meta-analysis, Scale (social sciences), Anatomy, Psychology, Clinical risk factor, Clinical psychology, MRI, MAJOR PSYCHIATRIC-DISORDERS, Schizoaffective disorder, 050105 experimental psychology, 03 medical and health sciences, Magnetic resonance imaging, Neuroimaging, Meta-Analysis as Topic, SDG 3 - Good Health and Well-being, Imatges per ressonància magnètica, medicine, Humans, 0501 psychology and cognitive sciences, Radiology, Nuclear Medicine and imaging, Bipolar disorder, HIPPOCAMPAL VOLUMES, mega‐analysis, GRAY-MATTER VOLUME, SPECTRUM DISORDER, volume, DIABETES-MELLITUS, cortical thickness, COGNITIVE IMPAIRMENT, medicine.disease, Mental illness, meta-analysis, meta‐analysis, RC0321, Neurology (clinical), SCHIZOAFFECTIVE DISORDER, PSYCHOTIC FEATURES, 030217 neurology & neurosurgery
Abstract: MRI‐derived brain measures offer a link between genes, the environment and behavior and have been widely studied in bipolar disorder (BD). However, many neuroimaging studies of BD have been underpowered, leading to varied results and uncertainty regarding effects. The Enhancing Neuro Imaging Genetics through Meta‐Analysis (ENIGMA) Bipolar Disorder Working Group was formed in 2012 to empower discoveries, generate consensus findings and inform future hypothesis‐driven studies of BD. Through this effort, over 150 researchers from 20 countries and 55 institutions pool data and resources to produce the largest neuroimaging studies of BD ever conducted. The ENIGMA Bipolar Disorder Working Group applies standardized processing and analysis techniques to empower large‐scale meta‐ and mega‐analyses of multimodal brain MRI and improve the replicability of studies relating brain variation to clinical and genetic data. Initial BD Working Group studies reveal widespread patterns of lower cortical thickness, subcortical volume and disrupted white matter integrity associated with BD. Findings also include mapping brain alterations of common medications like lithium, symptom patterns and clinical risk profiles and have provided further insights into the pathophysiological mechanisms of BD. Here we discuss key findings from the BD working group, its ongoing projects and future directions for large‐scale, collaborative studies of mental illness., This review discusses the major challenges facing neuroimaging research of bipolar disorder and highlights the major accomplishments, ongoing challenges and future goals of the ENIGMA Bipolar Disorder Working Group.
Published: 2022
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15. Self‐harm and suicidal ideation in children and adolescents in contact with child protection services

Author: Kirstie O'Hare, Oliver Watkeys, Felicity Harris, Kimberlie Dean, Vaughan J Carr, and Melissa J Green
Subjects: General Medicine
Published: 2023
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16. Parental mental disorders and offspring schizotypy in middle childhood: an intergenerational record linkage study

Author: Kirstie O’Hare, Kristin R. Laurens, Oliver Watkeys, Stacy Tzoumakis, Kimberlie Dean, Felicity Harris, Richard J. Linscott, Vaughan J. Carr, and Melissa J. Green
Subjects: Psychiatry and Mental health, Health (social science), Social Psychology, Epidemiology
Abstract: Purpose To investigate relationships between distinct schizotypy risk profiles in childhood and the full spectrum of parental mental disorders. Methods Participants were 22,137 children drawn from the New South Wales Child Development Study, for whom profiles of risk for schizophrenia-spectrum disorders in middle childhood (age ~ 11 years) were derived in a previous study. A series of multinomial logistic regression analyses examined the likelihood of child membership in one of three schizotypy profiles (true schizotypy, introverted schizotypy, and affective schizotypy) relative to the children showing no risk, according to maternal and paternal diagnoses of seven types of mental disorders. Results All types of parental mental disorders were associated with membership in all childhood schizotypy profiles. Children in the true schizotypy group were more than twice as likely as children in the no risk group to have a parent with any type of mental disorder (unadjusted odds ratio [OR] = 2.27, 95% confidence intervals [CI] = 2.01–2.56); those in the affective (OR = 1.54, 95% CI = 1.42–1.67) and introverted schizotypy profiles (OR = 1.39, 95% CI = 1.29–1.51) were also more likely to have been exposed to any parental mental disorder, relative to children showing no risk. Conclusion Childhood schizotypy risk profiles appear not to be related specifically to familial liability for schizophrenia-spectrum disorders; this is consistent with a model where liability for psychopathology is largely general rather than specific to particular diagnostic categories.
Published: 2023
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17. Connectome architecture shapes large-scale cortical reorganization in schizophrenia: a worldwide ENIGMA study

Author: Foivos Georgiadis, Sara Larivière, David Glahn, L. Elliot Hong, Peter Kochunov, Bryan Mowry, Carmel Loughland, Christos Pantelis, Frans A. Henskens, Melissa J. Green, Murray J. Cairns, Patricia T Michie, Paul E. Rasser, Paul Tooney, Rodney J. Scott, Stanley Catts, Ulrich Schall, Vaughan Carr, Yann Quidé, Axel Krug, Frederike Stein, Igor Nenadić, Katharina Brosch, Tilo Kircher, Raquel Gur, Ruben Gur, Theodore D. Satterthwaite, Andriana Karuk, Edith Pomarol-Clotet, Joaquim Radua, Paola Fuentes-Claramonte, Raymond Salvador, Gianfranco Spalletta, Aristotle Voineskos, Kang Sim, Benedicto Crespo-Facorro, Diana Tordesillas Gutiérrez, Stefan Ehrlich, Nicolas Crossley, Dominik Grotegerd, Jonathan Repple, Rebekka Lencer, Udo Dannlowski, Vince Calhoun, Caroline Demro, Ian S. Ramsay, Scott. Sponheim, Andre Schmidt, Stefan Borgwardt, Alexander S. Tomyshev, Irina Lebedeva, Cyril Hoschl, Filip Spaniel, Adrian Preda, Dana Nguyen, Anne Uhlmann, Dan J Stein, Fleur M Howells, Henk S. Temmingh, Ana M. Diaz Zuluaga, Carlos López Jaramillo, Felice Iasevoli, Ellen Ji, Stephanie Homan, Wolfgang Omlor, Philipp Homan, Stefan Kaiser, Erich Seifritz, Bratislav Misic, Paul Thompson, Theo G.M. van Erp, Jessica Turner, Boris Bernhardt, and Matthias Kirschner
Abstract: ObjectiveSchizophrenia is associated with widespread brain-morphological alterations, believed to be shaped by the underlying connectome architecture. This study tests whether large-scale structural reorganization in schizophrenia relates to normative network architecture, in particular regional centrality/hubness and connectivity patterns. We examine network effects in schizophrenia across different disease stages, and transdiagnostically explore consistency of such relationships in patients with bipolar and major depressive disorder.MethodsWe studied anatomical MRI scans from 2,439 adults with schizophrenia and 2,867 healthy controls from 26 ENIGMA sites. Case-control patterns of structural alterations were evaluated against two network susceptibility models: 1) hub vulnerability, which examines associations between regional network centrality and magnitude of disease-related alterations; 2) epicenter models, which identify regions whose typical connectivity profile most closely resembles the disease-related morphological alteration patterns. Both susceptibility models were tested across schizophrenia disease stages and compared to meta-analytic bipolar and major depressive disorder case-control maps.ResultsIn schizophrenia, regional gray matter reductions co-localized with interconnected hubs, in both the functional (r=0.58, pspinspin=0.01). Epicenters were identified in temporo-paralimbic regions, extending to frontal areas. We found unique epicenters for first-episode and early stages, and a shift from occipital to temporal-frontal epicenters in chronic stages. Transdiagnostic comparisons revealed shared epicenters in schizophrenia and bipolar, but not major depressive disorders.ConclusionsCortical reorganization over the course of schizophrenia closely reflects brain network architecture, emphasizing marked hub susceptibility and temporo-frontal epicenters. The observed overlapping epicenters for schizophrenia and bipolar disorder furthermore suggest shared pathophysiological processes within the schizophrenia-bipolar-spectrum.
Published: 2023
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18. School-Based Mental Health Promotion and Early Intervention Programs in New South Wales, Australia: Mapping Practice to Policy and Evidence

Author: Linda J. Graham, Kristin R. Laurens, Stacy Tzoumakis, Felicity Harris, Vaughan J. Carr, Jill Schofield, Traci Prendergast, Katherine Dix, Mary Taiwo, Kate E. Williams, Melissa J. Green, and Neale Waddy
Subjects: Medical education, 4. Education, media_common.quotation_subject, education, 05 social sciences, 050301 education, Mental health, 3. Good health, Education, 03 medical and health sciences, 0302 clinical medicine, Promotion (rank), Intervention (counseling), Developmental and Educational Psychology, School based, 030212 general & internal medicine, School community, Empirical evidence, Psychology, 0503 education, media_common
Abstract: Limited empirical evidence is available regarding the uptake and effectiveness of school-based mental health and wellbeing programs implemented in Australian schools. This study aimed to characterise the delivery of programs in primary (elementary) schools across New South Wales, Australia, and to assess this information against published ratings of program effectiveness. Delivery of programs in four health-promoting domains—creating a positive school community; teaching social and emotional skills; engaging the parent community; and supporting students experiencing mental health difficulties—were reported by 597 school principals/leaders via online survey. Although three quarters of principals reported implementing at least one program, many of these programs were supported by little or no evidence of effectiveness. There was also variability in the use of evidence-based programs across the four domains. Findings indicate a need to provide educators with improved support to identify, implement, and evaluate effective evidenced-based programs that promote student mental health.
Published: 2021
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19. Schizotypy, childhood trauma and brain morphometry

Author: Emiliana Tonini, Yann Quidé, Vaughan J. Carr, Oliver J. Watkeys, and Melissa J. Green
Subjects: Adult, Male, Psychosis, Schizotypy, Population, Grey matter, Schizotypal Personality Disorder, Adverse Childhood Experiences, medicine, Humans, Middle frontal gyrus, education, Biological Psychiatry, education.field_of_study, business.industry, Brain morphometry, Brain, medicine.disease, Magnetic Resonance Imaging, Psychiatry and Mental health, medicine.anatomical_structure, Schizophrenia, Female, business, Insula, Parahippocampal gyrus, Clinical psychology
Abstract: Background Childhood trauma confers risk for psychosis and is associated with increased ‘schizotypy’ (a multi-dimensional construct reflecting risk for psychosis in the general population). Structural brain alterations are associated with both childhood trauma and schizotypy, but the potential role of trauma exposure in moderating associations between schizotypy and brain morphology has yet to be determined. Methods Participants were 160 healthy individuals (mean age: 40.08 years, SD = 13.64, range 18–64; 52.5% female). Childhood trauma exposure was assessed using the Childhood Adversity Questionnaire, and schizotypy was assessed using the Schizotypal Personality Questionnaire. Univariate voxel-based morphometry and multivariate analyses of grey matter volume covariation (GMC; derived from independent component analysis) were performed to determine the main effects of schizotypy, trauma exposure and their interaction on these indices of grey matter volume. Moderation analyses were performed following significant interaction. Results Levels of schizotypy, in particular the Cognitive-Perceptual and Interpersonal dimensions, were negatively associated with GMC in the striatum, the hippocampus/parahippocampal gyrus, thalamus and insulae. Trauma exposure was negatively associated with GMC of the middle frontal gyrus and parietal lobule, while negatively associated with GMC in the cerebellum. Levels of schizotypy (total scores, and the cognitive-perceptual dimension) were negatively associated with striatal GMC in individuals not exposed to trauma, but not in those exposed to trauma. Conclusions Schizotypy and childhood trauma were independently associated with changes of grey matter in brain regions critical for cognition and social cognition. In individuals not exposed to trauma, increased schizotypy was associated with decreased striatal and limbic grey matter.
Published: 2021
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20. Familial clustering of birth risk for adverse childhood outcomes

Author: Kristin R. Laurens, Melissa J. Green, Vaughan J. Carr, Felicity Harris, Oliver J. Watkeys, and Kimberlie Dean
Subjects: Longitudinal study, business.industry, Psychological intervention, Obstetrics and Gynecology, Familial clustering, 16. Peace & justice, Multiple risk factors, Mental illness, medicine.disease, Logistic regression, Mental health, Latent class model, 030227 psychiatry, 03 medical and health sciences, 0302 clinical medicine, Pediatrics, Perinatology and Child Health, medicine, 030212 general & internal medicine, business, Demography
Abstract: OBJECTIVE To identify classes of children exposed to distinct clusters of perinatal and familial risk factors at the time of birth, and examine relationships between class membership and a variety of adverse outcomes in childhood. DESIGN A prospective longitudinal study of children (and their parents) born between 2002 and 2004 and who have been followed-up until 12-13 years of age. A combination of latent class analysis and logistic regression analyses were used. RESULTS Adverse developmental, social, and mental health outcomes in early and middle childhood were greatest for children with 'pervasive familial risk' (i.e., parental mental illness, parental criminality, and perinatal risk factors) at the time of birth; some associations were stronger among girls. CONCLUSION Pervasive exposure to multiple risk factors in the pre- and perinatal period increases the risk of adverse outcomes in childhood. Future interventions should tailor strategies to address unique combinations of adverse risk exposures in vulnerable families.
Published: 2021
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21. Childhood trauma moderates schizotypy-related brain morphology: Analyses of 1,182 healthy individuals from the ENIGMA Schizotypy working group

Author: Yann Quidé, Oliver J. Watkeys, Emiliana Tonini, Dominik Grotegerd, Udo Dannlowski, Igor Nenadić, Tilo Kircher, Axel Krug, Tim Hahn, Susanne Meinert, Janik Goltermann, Marius Gruber, Frederike Stein, Katharina Brosch, Adrian Wroblewski, Florian Thomas-Odenthal, Paula Usemann, Benjamin Straube, Nina Alexander, Elisabeth J. Leehr, Jochen Bauer, Nils R. Winter, Lukas Fisch, Katharina Dohm, Wulf Rössler, Lukasz Smigielski, Pamela DeRosse, Ashley Moyett, Josselin Houenou, Marion Leboyer, James Gilleen, Sophia I. Thomopoulos, Paul M. Thompson, André Aleman, Gemma Modinos, and Melissa J. Green
Abstract: Schizotypy represents an index of psychosis-proneness in the general population often associated with childhood trauma exposure. Both schizotypy and childhood trauma are linked to structural brain alterations, and it is possible that trauma exposure moderates the extent of brain morphological differences associated with schizotypy. We addressed this question using data from a total of 1,182 healthy adults (age range: 18-65 years old, 647 females/535 males), pooled from nine sites worldwide, contributing to the Enhancing NeuroImaging Genetics through Meta-Analysis (ENIGMA) Schizotypy working group. All participants completed both the Schizotypal Personality Questionnaire Brief version (SPQ-B), and the Childhood Trauma Questionnaire (CTQ), and underwent a 3D T1-weighted brain MRI scan from which regional indices of subcortical grey matter volume and cortical thickness were determined. A series of multiple linear regressions revealed that differences in cortical thickness in four regions-of-interest were significantly associated with interactions between schizotypy and trauma; subsequent moderation analyses indicated that increasing levels of schizotypy were associated with thicker left caudal anterior cingulate gyrus, right middle temporal gyrus and insula, and thinner left caudal middle frontal gyrus, in people exposed to higher (but not low or average) levels of childhood trauma. This was found in the context of thicker bilateral medial orbitofrontal gyri, right rostral anterior cingulate gyrus, left temporal pole, left insula, and thinner left paracentral lobule directly associated with increasing levels of schizotypy. In addition, thinner left postcentral, superior parietal and lingual gyri, as well as thicker left caudal middle frontal gyrus and smaller left thalamus and right caudate were associated with increasing levels of childhood trauma exposure. These results suggest that alterations in brain regions critical for higher cognitive and integrative processes that are associated with schizotypy may be enhanced in individuals exposed to high levels of trauma.
Published: 2022
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22. Cumulative Environmental Risk in Early Life: Associations With Schizotypy in Childhood

Author: Kirstie O’Hare, Oliver Watkeys, Tyson Whitten, Kimberlie Dean, Kristin R Laurens, Stacy Tzoumakis, Felicity Harris, Vaughan J Carr, and Melissa J Green
Subjects: Psychiatry and Mental health
Abstract: Background and Hypothesis Psychotic disorders are associated with a growing number of recognized environmental exposures. Cumulative exposure to multiple environmental risk factors in childhood may contribute to the development of different patterns of schizotypy evident in early life. Hypotheses were that distinct profiles of schizotypy would have differential associations with a cumulative score of environmental risk factors. Study Design We prospectively examined the relationship between 19 environmental exposures (which had demonstrated replicated associations with psychosis) measured from the prenatal period through to age 11 years, and 3 profiles of schizotypy in children (mean age = 11.9 years, n = 20 599) that have been established in population data from the New South Wales-Child Development Study. Multinomial logistic regression was used to examine associations between membership in each of 3 schizotypy profiles (true schizotypy, introverted schizotypy, and affective schizotypy) and exposure to a range of 19 environmental risk factors for psychosis (both individually and summed as a cumulative environmental risk score [ERS]), relative to children showing no risk. Results Almost all environmental factors were associated with at least 1 schizotypy profile. The cumulative ERS was most strongly associated with the true schizotypy profile (OR = 1.61, 95% CI = 1.52–1.70), followed by the affective (OR = 1.33, 95% CI = 1.28–1.38), and introverted (OR = 1.32, 95% CI = 1.28–1.37) schizotypy profiles. Conclusions Consistent with the cumulative risk hypothesis, results indicate that an increased number of risk exposures is associated with an increased likelihood of membership in the 3 schizotypy profiles identified in middle childhood, relative to children with no schizotypy profile.
Published: 2022

23. An approach for automatically measuring facial activity in depressed subjects.

Author: Gordon McIntyre, Roland Göcke, Matthew Hyett, Melissa J. Green, and Michael Breakspear
Published: 2009
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24. Self-reported mental health of children known to child protection services: an Australian population-based record linkage study

Author: Kirstie O’Hare, Aniqa Hussain, Stacy Tzoumakis, Felicity Harris, Vaughan J. Carr, Gabrielle Hindmarsh, Melissa J. Green, and Kristin R. Laurens
Subjects: medicine.medical_specialty, General Medicine, Child development, Mental health, Psychiatry and Mental health, Foster care, Child protection, Intervention (counseling), Pediatrics, Perinatology and Child Health, Developmental and Educational Psychology, Child and adolescent psychiatry, medicine, Record Linkage Study, Psychiatry, Psychopathology
Abstract: Maltreated children are vulnerable to adverse mental health outcomes. Information about how children's mental health needs vary according to different levels of child protection contact (potentially culminating in out-of-home care [OOHC]) is valuable for the effective provision of services. This study aimed to examine associations between different levels of contact with child protection services before the age of 10 years and self-reported mental health difficulties at age 11 years. Participants (n = 26,960) were drawn from the New South Wales Child Development Study, a multiagency, multigenerational, longitudinal record linkage study that combines administrative records with cross-sectional survey data. We examined associations between four levels of child protection response (non-threshold reports, unsubstantiated reports, substantiated reports, OOHC; each relative to no report) and six domains of self-reported mental health difficulties (including internalising and externalising symptoms, and psychotic-like experiences). All levels of contact with child protection services were associated with increased odds of mental health difficulties in all domains. Children who had been placed in OOHC and children with substantiated reports had the highest odds of reporting clinical levels of mental health difficulties; 48.1% of children with an OOHC placement and 45.6% of those with substantiated child protection reports showed clinical levels of mental health difficulties in at least one domain. Children with child protection reports that were unsubstantiated, or determined not to meet the threshold for risk-of-significant harm, were also at increased risk of mental health difficulties in middle childhood. These findings underscore the importance of early detection and intervention for all children at risk of maltreatment.
Published: 2021
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25. Multivariate neuroanatomical classification of cognitive subtypes in schizophrenia: A support vector machine learning approach

Author: Ian C. Gould, Alana M. Shepherd, Kristin R. Laurens, Murray J. Cairns, Vaughan J. Carr, and Melissa J. Green
Subjects: Cognition, Cognitive deficit, Subtypes, Voxel based morphometry, Magnetic resonance imaging, Sex differences, Computer applications to medicine. Medical informatics, R858-859.7, Neurology. Diseases of the nervous system, RC346-429
Abstract: Heterogeneity in the structural brain abnormalities associated with schizophrenia has made identification of reliable neuroanatomical markers of the disease difficult. The use of more homogenous clinical phenotypes may improve the accuracy of predicting psychotic disorder/s on the basis of observable brain disturbances. Here we investigate the utility of cognitive subtypes of schizophrenia – ‘cognitive deficit’ and ‘cognitively spared’ – in determining whether multivariate patterns of volumetric brain differences can accurately discriminate these clinical subtypes from healthy controls, and from each other. We applied support vector machine classification to grey- and white-matter volume data from 126 schizophrenia patients previously allocated to the cognitive spared subtype, 74 cognitive deficit schizophrenia patients, and 134 healthy controls. Using this method, cognitive subtypes were distinguished from healthy controls with up to 72% accuracy. Cross-validation analyses between subtypes achieved an accuracy of 71%, suggesting that some common neuroanatomical patterns distinguish both subtypes from healthy controls. Notably, cognitive subtypes were best distinguished from one another when the sample was stratified by sex prior to classification analysis: cognitive subtype classification accuracy was relatively low (
Published: 2014
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26. Examining the overlap of young people’s early contact with the police as a person of interest and victim or witness

Author: Felicity Harris, Ulrika Athanassiou, Melissa J. Green, Kimberlie Dean, Vaughan J. Carr, Gabrielle Hindmarsh, Kristin R. Laurens, Stacy Tzoumakis, and Tyson Whitten
Subjects: 050901 criminology, 05 social sciences, 0501 psychology and cognitive sciences, Social disadvantage, 0509 other social sciences, Criminology, Psychology, Law, Witness, Young adolescents, 050104 developmental & child psychology
Abstract: There is known to be considerable overlap among the victims and perpetrators of crime. However, the extent of this overlap early in life among children and young adolescents is not clear. We examined the sociodemographic profiles of young people who had early contact with police regarding a criminal incident as a person of interest, victim and/or witness, as well as the patterns of multiple police contact types from birth to 13 years of age. Data were drawn from a longitudinal, population-based sample of 91,631 young people from New South Wales, Australia. Among the 10.6% (n = 9677) of young people who had contact with police, 14.4% (n = 1393) had contact as a person of interest and as a victim and/or witness on two or more separate occasions. The most common first contact type was as a victim/witness, but those children with a first contact as a person of interest were most likely to have at least one further contact. Young people with both types of police contact were younger at first police contact, were more likely to reside in a socioeconomically disadvantaged area, and to be recorded as having an Aboriginal and/or Torres Strait Islander background. Our findings demonstrate that, by 13 years of age, 1 in 10 young people had been in early contact with police and that a minority have contact with the police as both a person of interest and a victim/witness. These young people may represent a particularly disadvantaged group in the community who are likely to be at risk of future adversity, including repeated contact with the criminal justice system.
Published: 2021
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27. Out-of-home care characteristics associated with childhood educational underachievement, mental disorder, and police contacts in an Australian population sample

Author: Kirstie O'Hare, Stacy Tzoumakis, Oliver Watkeys, Ilan Katz, Kristin R. Laurens, Merran Butler, Felicity Harris, Vaughan J. Carr, and Melissa J. Green
Subjects: Psychiatry and Mental health, Pediatrics, Perinatology and Child Health, Developmental and Educational Psychology
Published: 2023
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28. Dysregulation of circRNA expression in the peripheral blood of individuals with schizophrenia and bipolar disorder

Author: Murray J. Cairns, Ebrahim Mahmoudi, and Melissa J. Green
Subjects: Male, Bipolar Disorder, Biology, Bioinformatics, Transcriptome, 03 medical and health sciences, 0302 clinical medicine, Drug Discovery, microRNA, medicine, Humans, Bipolar disorder, Gene, Genetics (clinical), Alternative splicing, RNA, RNA, Circular, medicine.disease, Human genetics, MicroRNAs, Schizophrenia, Leukocytes, Mononuclear, Molecular Medicine, Female, 030215 immunology
Abstract: Circular RNAs (circRNAs) are head-to-tail back-spliced RNA transcripts that have been linked to several biological processes and their perturbation is evident in human disease, including neurological disorders. There is also emerging research suggesting circRNA expression may also be altered in psychiatric and behavioural syndromes. Here, we provide a comprehensive analysis of circRNA expression in peripheral blood mononuclear cells (PBMCs) from 39 patients with schizophrenia and bipolar disorder as well as 20 healthy individuals using deep RNA-seq. We observed systematic alternative splicing leading to a complex and diverse profile of RNA transcripts including 8762 high confidence circRNAs. More specific scrutiny of the circular transcriptome in schizophrenia and bipolar disorder, compared to a non-psychiatric control group, revealed significant dysregulation of 55 circRNAs with a bias towards downregulation. These molecules were predicted to interact with a large number of miRNAs that target genes enriched in psychiatric disorders. Further replication and cross-validation to determine the specificity of these circRNAs across broader diagnostic groups and subgroups in psychiatry will enable their potential utility as biomarkers to be established. KEY MESSAGES: • We identified 8762 high confidence circRNAs with systematic alternative splicing in human PBMCs. • CircRNAs were dysregulated in schizophrenia and bipolar disorder, compared to a non-psychiatric control group. • The DE circRNAs were predicted to interact with miRNAs with target genes enriched in psychiatric disorders. • Some circRNAs have the potential to serve as biomarkers in psychiatry.
Published: 2021
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29. Brain morphology does not clearly map to cognition in individuals on the bipolar-schizophrenia-spectrum: a cross-diagnostic study of cognitive subgroups

Author: Melissa J. Green, Sean P. Carruthers, Matthew Hughes, James A Karantonis, Susan L. Rossell, Vanessa Cropley, Katherine E. Burdick, Tamsyn E Van Rheenen, Christos Pantelis, and Philip Sumner
Subjects: Normal subgroup, medicine.medical_specialty, Bipolar Disorder, Audiology, 03 medical and health sciences, Cognition, 0302 clinical medicine, Neuroimaging, medicine, Humans, Bipolar disorder, business.industry, Working memory, Brain morphometry, Brain, medicine.disease, Magnetic Resonance Imaging, 030227 psychiatry, Psychiatry and Mental health, Clinical Psychology, Schizophrenia, Brain size, business, 030217 neurology & neurosurgery
Abstract: Background Characterisation of brain morphological features common to cognitively similar individuals with bipolar disorder (BD) and schizophrenia spectrum disorders (SSD) may be key to understanding their shared neurobiological deficits. In the current study we examined whether three previously characterised cross-diagnostic cognitive subgroups differed among themselves and in comparison to healthy controls across measures of brain morphology. Method T1-weighted structural magnetic resonance imaging scans were obtained for 143 individuals; 65 healthy controls and 78 patients (SSD, n = 40; BD I, n = 38) classified into three cross-diagnostic cognitive subgroups: Globally Impaired (n = 24), Selectively Impaired (n = 32), and Superior/Near-Normal (n = 22). Cognitive subgroups were compared to each other and healthy controls on three separate analyses investigating (1) global, (2) regional, and (3) vertex-wise comparisons of brain volume, thickness, and surface area. Results No significant subgroup differences were evident in global measures of brain morphology. In region of interest analyses, the Selectively Impaired subgroup had greater right accumbens volume than those Superior/Near-Normal subgroup and healthy controls, and the Superior/Near-Normal subgroup had reduced volume of the left entorhinal region compared to all other groups. In vertex-wise comparisons, the Globally Impaired subgroup had greater right precentral volume than the Selectively Impaired subgroup, and thicker cortex in the postcentral region relative to the Superior/Near-Normal subgroup. Limitations Exploration of medication effects was limited in our data. Conclusions Although some differences were evident in this sample, generally cross-diagnostic cognitive subgroups of individuals with SSD and BD did not appear to be clearly distinguished by patterns in brain morphology.
Published: 2021
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30. Genetic estimates of correlation and causality between blood-based biomarkers and psychiatric disorders

Author: William R. Reay, Dylan J. Kiltschewskij, Michael P. Geaghan, Joshua R. Atkins, Vaughan J. Carr, Melissa J. Green, and Murray J. Cairns
Subjects: C-Reactive Protein, Multidisciplinary, Mental Disorders, Humans, Mendelian Randomization Analysis, Biomarkers, Genome-Wide Association Study
Abstract: There is a long-standing interest in exploring the relationship between blood-based biomarkers and psychiatric disorders, despite their causal role being difficult to resolve in observational studies. In this study, we leverage genome-wide association study data for a large panel of heritable serum biochemical traits to refine our understanding of causal effect in biochemical-psychiatric trait pairings. We observed widespread positive and negative genetic correlation between psychiatric disorders and biochemical traits. Causal inference was then implemented to distinguish causation from correlation, with strong evidence that C-reactive protein (CRP) exerts a causal effect on psychiatric disorders. Notably, CRP demonstrated both protective and risk-increasing effects on different disorders. Multivariable models that conditioned CRP effects on interleukin-6 signaling and body mass index supported that the CRP-schizophrenia relationship was not driven by these factors. Collectively, these data suggest that there are shared pathways that influence both biochemical traits and psychiatric illness.
Published: 2022
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31. Child protection services for children with special healthcare needs: A population record linkage study

Author: Gabrielle Hindmarsh, Ilan Katz, Melissa J. Green, Kristin R. Laurens, Felicity Harris, Merran Butler, and Vaughan J. Carr
Subjects: education.field_of_study, medicine.medical_specialty, Sociology and Political Science, 05 social sciences, Population, 0211 other engineering and technologies, 021107 urban & regional planning, Special needs, 02 engineering and technology, Child development, 050906 social work, Physical abuse, Child protection, Family medicine, medicine, 0509 other social sciences, education, Psychology, Human services, Social policy, Convention on the Rights of the Child
Abstract: Children with disabilities are known to have high rates of contact with child protection services. However, little is known about child protection contacts for a broader group of children with special healthcare needs (SHCN; i.e., special needs or other impairments of concern that affect learning). This study examined the characteristics of contact with child protection services (prior to the age of 6 years) for children with SHCN identified at school entry using the 2009 Australian Early Development Census, using administrative data from more than 65,000 children in the New South Wales Child Development Study. Child protection contacts prior to age 6 years were more prevalent among children with SHCN compared with those without; in particular, children with SHCN had higher odds of a history of exposure to neglect and physical abuse, and higher odds of being placed in out-of-home care, compared with their typically developing peers. Understanding the characteristics of child protection contacts among children with SHCN, with consideration of factors that may influence their patterns of contact with these and other human services agencies, will inform the development of appropriate social policy initiatives to fulfil Australia’s obligations under the United Nations Convention on the Rights of the Child.
Published: 2020
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32. The relationship between cortisol reactivity and emotional brain function is differently moderated by childhood trauma, in bipolar disorder, schizophrenia and healthy individuals

Author: Vaughan J. Carr, Yann Quidé, Leah Girshkin, Melissa J. Green, and Oliver J. Watkeys
Subjects: Bipolar I disorder, medicine.diagnostic_test, business.industry, General Medicine, medicine.disease, Amygdala, 030227 psychiatry, Dorsolateral prefrontal cortex, 03 medical and health sciences, Psychiatry and Mental health, 0302 clinical medicine, medicine.anatomical_structure, Mood disorders, Schizophrenia, Medicine, Cingulum (brain), Pharmacology (medical), Bipolar disorder, business, Functional magnetic resonance imaging, 030217 neurology & neurosurgery, Biological Psychiatry, Clinical psychology
Abstract: Childhood trauma is a risk factor for psychotic and mood disorders that is associated with abnormal hypothalamic-pituitary-adrenal (HPA) axis function in response to stress and abnormal social brain function. Here, we aimed to determine whether childhood trauma exposure would differently moderate associations between cortisol reactivity and social brain function, among cases with schizophrenia (SZ), bipolar disorder (BD) and in healthy individuals (HC). Forty cases with SZ, 35 with BD and 34 HCs underwent functional magnetic resonance imaging while performing an emotional face-matching task. Participants completed the Childhood Trauma Questionnaire and cortisol reactivity (i.e. the slope indexing the within-subject difference between pre- and post-imaging salivary cortisol levels) was determined. The severity of childhood trauma moderated the relationship between cortisol reactivity and brain activation in the bilateral temporo-parieto-insular junctions, right middle cingulum, right pre/postcentral gyri, left cerebellum and right lingual gyrus, differently depending on the clinical group. When exposed to high levels of trauma, the cortisol slope was negatively associated with activation in these regions in HC, while the cortisol slope was positively associated with activation in these regions in SZ cases. Similarly, there were differences between the groups in how trauma severity moderated the relationship between cortisol reactivity and functional connectivity between the amygdala and dorsolateral prefrontal cortex. In addition to reflecting typical associations between cortisol reactivity and emotional brain function when not exposed to childhood trauma, these findings provide new evidence that trauma exposure disrupts these relationships in both healthy individuals and in cases with SZ or BD.
Published: 2020
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33. Transitions between socio-emotional and cognitive vulnerability profiles from early to middle childhood: a population study using multi-agency administrative records

Author: Stacy Tzoumakis, Vaughan J. Carr, Tyson Whitten, Patrycja J. Piotrowska, Melissa J. Green, Kristin R. Laurens, Ilan Katz, and Felicity Harris
Subjects: Male, medicine.medical_specialty, Emotions, Population, Medical Records, Developmental psychology, 03 medical and health sciences, Cognition, 0302 clinical medicine, Developmental and Educational Psychology, Child and adolescent psychiatry, medicine, Humans, 0501 psychology and cognitive sciences, Early childhood, Cognitive skill, Child, education, Cognitive vulnerability, education.field_of_study, 05 social sciences, General Medicine, 16. Peace & justice, Child development, 030227 psychiatry, Psychiatry and Mental health, Cross-Sectional Studies, Child protection, Research Design, Child, Preschool, Pediatrics, Perinatology and Child Health, Female, Psychology, Psychosocial, 050104 developmental & child psychology
Abstract: Adult psychosocial difficulties, including psychiatric disorders, are often preceded by childhood psychosocial vulnerabilities, presenting critical windows of opportunity for preventative intervention. The present study aimed to identify longitudinal patterns (representing transitions between profiles) of childhood socio-emotional and cognitive vulnerability in the general population from early to middle childhood, in relation to key risk factors (e.g. parental mental illness and offending). Data were drawn from the New South Wales Child Development Study, which combines intergenerational multi-agency administrative records with cross-sectional assessments using data linkage methods. We analysed data from childhood assessments of socio-emotional and cognitive functioning at two time points (ages 5-6 and 10-11 years) that were linked with administrative data from government departments of health, child protection, and education for 19,087 children and their parents. Latent profile analyses were used to identify socio-emotional and cognitive profiles at each time point, and latent transition analyses were used to determine the probability and potential moderators of transition between profiles at each age. Three developmental profiles were identified in early childhood, reflecting typically developing, emotionally vulnerable, and cognitively vulnerable children, respectively; two profiles were identified in middle childhood, reflecting typically developing and vulnerable children. Child's sex, child protection services contact, parental mental illness, and parental offending influenced children's transitions between different vulnerability profiles, with the strongest effects for parental mental illness and child protection contact. Early detection of vulnerable children and factors promoting resilience are important steps in directing future health and social policy, and service planning for vulnerable children.
Published: 2020
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34. Children’s contact with police as a victim, person of interest and witness in New South Wales, Australia

Author: Kimberlie Dean, Tyson Whitten, Kristin R. Laurens, Vaughan J. Carr, Stacy Tzoumakis, Melissa J. Green, and Felicity Harris
Subjects: education.field_of_study, Social Psychology, Adverse outcomes, 05 social sciences, Population, Psychological intervention, Demographic profile, Criminology, 16. Peace & justice, Health outcomes, Witness, Pathology and Forensic Medicine, 050501 criminology, 0501 psychology and cognitive sciences, education, Psychology, Law, Record linkage, 050104 developmental & child psychology, 0505 law, Criminal justice
Abstract: Contact with the police, as the first contact with the criminal justice system for young people and children, may signify individuals who are vulnerable to later adverse social and health outcomes. However, little is known about how often children have contact with police or for what reason. In this paper, we provide a demographic profile of the prevalence and reasons for police contact among a representative, longitudinal, population-based sample of 91,631 young people in New South Wales, Australia. By 13 years of age, almost one in six (15.6%) children had contact with police as a victim, person of interest and/or witness on at least one occasion. The most common reason for contact with police was in relation to an assault. There was considerable overlap among children who had been in contact with police on more than one occasion for different reasons, with those having police contact as a person of interest or witness being seven times more likely to have also been in contact with police as a victim in a separate incident, than children not known to police. We show that contact with the police is surprisingly common among children and suggest that early interventions for children in contact with police might prevent a range of adverse outcomes not limited to criminal offending.
Published: 2020
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35. The Medical Genome Reference Bank contains whole genome and phenotype data of 2570 healthy elderly

Author: Adam Ameur, Aaron L. Statham, Vaughan J. Carr, Marcel E. Dinger, Sini Nagpal, David Thomas, Greg Gibson, Mark J. Cowley, Robyn L. Woods, Christopher M. Reid, Moeen Riaz, Emma M Rath, Hilda A. Pickett, Murray J. Cairns, Ulf Gyllensten, Raj C. Shah, Joseph E. Powell, Paul A. James, Marie-Jo Brion, Anne M. Murray, Dmitry Degrave, Clare Puttick, Heath M. Cairns, Chantel Fitzsimmons, Paul Lacaze, Shane Husson, Rory Wolfe, John J McNeil, Vivian Francília Silva Kahl, Martin McNamara, Joshua R. Atkins, Mark Pinese, Melissa J. Green, Margo Barr, Andrew Stone, Mark Nelson, Tina Navin Cristina, and Warren Kaplan
Subjects: 0301 basic medicine, Male, General Physics and Astronomy, Genome, Cohort Studies, 0302 clinical medicine, Gene Frequency, Neoplasms, Databases, Genetic, Genetics research, lcsh:Science, Genetics, Aged, 80 and over, Multidisciplinary, Middle Aged, Physical Functional Performance, Biobank, Healthy Volunteers, 3. Good health, Mitochondria, Medical genetics, Female, Medical genomics, Medical Genetics, medicine.medical_specialty, Science, Biology, Polymorphism, Single Nucleotide, General Biochemistry, Genetics and Molecular Biology, Article, Structural variation, 03 medical and health sciences, medicine, Humans, Genetic Predisposition to Disease, Indel, Genetic association, Aged, Medicinsk genetik, Whole genome sequencing, Whole Genome Sequencing, Genome, Human, Genetic Variation, Rare variants, General Chemistry, Ageing, 030104 developmental biology, Human genome, lcsh:Q, 030217 neurology & neurosurgery
Abstract: Population health research is increasingly focused on the genetic determinants of healthy ageing, but there is no public resource of whole genome sequences and phenotype data from healthy elderly individuals. Here we describe the first release of the Medical Genome Reference Bank (MGRB), comprising whole genome sequence and phenotype of 2570 elderly Australians depleted for cancer, cardiovascular disease, and dementia. We analyse the MGRB for single-nucleotide, indel and structural variation in the nuclear and mitochondrial genomes. MGRB individuals have fewer disease-associated common and rare germline variants, relative to both cancer cases and the gnomAD and UK Biobank cohorts, consistent with risk depletion. Age-related somatic changes are correlated with grip strength in men, suggesting blood-derived whole genomes may also provide a biologic measure of age-related functional deterioration. The MGRB provides a broadly applicable reference cohort for clinical genetics and genomic association studies, and for understanding the genetics of healthy ageing., Healthspan and healthy aging are areas of research with potential socioeconomic impact. Here, the authors present the Medical Genome Reference Bank (MGRB) which consist of over 4,000 individuals aged 70 years and older without a history of the major age-related diseases and report on results from whole-genome sequencing and association analyses.
Published: 2020
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36. Directional anchor genes refine polygenic informed treatment selection in schizophrenia and bipolar disorder

Author: William R Reay, Michael P Geaghan, Joshua Ronald Atkins, Vaughan J Carr, Melissa J Green, and Murray J Cairns
Abstract: Genetically informed drug development and repurposing is an attractive prospect for improving outcomes in patients with psychiatric illness; however, the effectiveness of these endeavours can be confounded by heterogeneity. In this study, we propose a novel approach that links interventions implicated by disorder-associated genetic risk, at the population level, to a framework that can target these compounds to individuals. Specifically, results from genome-wide association studies are integrated with expression data to prioritise individual 'directional anchor' genes for which the predicted risk-increasing direction of expression could be counteracted by an existing drug. While these compounds represent plausible therapeutic candidates, they are not likely to be equally efficacious for all individuals. To account for this heterogeneity, we constructed polygenic scores restricted to variants annotated to the network of genes that interact with each directional anchor gene. These metrics, we call pharmagenic enrichment scores (PES), identify individuals with a higher burden of genetic risk, localised in biological processes related to the candidate drug target, to inform precision drug repurposing. We used this approach to investigate schizophrenia and bipolar disorder and reveal several compounds targeting specific directional anchor genes that could be plausibly repurposed, including antioxidants, vitamins, antiarrhythmics, and lipid modifying agents. These genetic risk scores, mapped to the networks associated with target genes, revealed biological insights that cannot be observed in undifferentiated genome-wide polygenic risk score (PRS). For example, an enrichment of these partitioned scores in schizophrenia cases with otherwise low PRS and distinct correlations with measured biochemical traits. In summary, genetic risk could be used more specifically to direct drug repurposing candidates that target particular genes implicated in psychiatric and other complex disorders.
Published: 2022
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37. Early developmental vulnerabilities following exposure to domestic violence and abuse: Findings from an Australian population cohort record linkage study

Author: Tyson Whitten, Melissa J. Green, Stacy Tzoumakis, Kristin R. Laurens, Felicity Harris, Vaughan J. Carr, and Kimberlie Dean
Subjects: Male, Psychiatry and Mental health, Domestic Violence, Child Development, Child, Preschool, Australia, Humans, Mothers, Female, Child Abuse, Child, Biological Psychiatry
Abstract: Early life exposure to Domestic Violence and Abuse (DVA) is associated with poor psychosocial and cognitive development in childhood. However, most prior research uses mother-reported involvement in DVA as a proxy indicator of child exposure; studies using direct measures of child exposure to DVA are scarce, especially among representative population-based samples. We address this gap by using longitudinal, population-based data from an Australian record linkage study of children to examine the associations between early life exposure to DVA and early childhood developmental vulnerability. Exposure to DVA was measured using police contact records for children involved in a DVA incident either as a victim or witness. Developmental vulnerability at school entry was measured using the Australian Early Development Census, providing indices of five broad domains of function and person-centred classes of developmental risk (referred to as 'mild generalized risk', 'misconduct risk', and 'pervasive risk', each compared to a group showing 'no risk'). Children exposed to DVA showed significantly greater odds of developmental vulnerability on all five domains and were more likely to be members of the three developmental risk classes. Girls who were victims of DVA (OR = 1.65) had significantly poorer developmental outcomes than boys who were victims (OR = 1.26) within the domain of communication skills and general knowledge (d = 0.29 [SE = 0.16], p = .04). No other sex differences were found. These preliminary findings hold important implications for policy regarding the early intervention and implementation of support services for young children exposed to DVA.
Published: 2022

38. Sex-Dependent Shared and Nonshared Genetic Architecture Across Mood and Psychotic Disorders

Author: Gabriëlla A.M. Blokland, Jakob Grove, Chia-Yen Chen, Chris Cotsapas, Stuart Tobet, Robert Handa, David St Clair, Todd Lencz, Bryan J. Mowry, Sathish Periyasamy, Murray J. Cairns, Paul A. Tooney, Jing Qin Wu, Brian Kelly, George Kirov, Patrick F. Sullivan, Aiden Corvin, Brien P. Riley, Tõnu Esko, Lili Milani, Erik G. Jönsson, Aarno Palotie, Hannelore Ehrenreich, Martin Begemann, Agnes Steixner-Kumar, Pak C. Sham, Nakao Iwata, Daniel R. Weinberger, Pablo V. Gejman, Alan R. Sanders, Joseph D. Buxbaum, Dan Rujescu, Ina Giegling, Bettina Konte, Annette M. Hartmann, Elvira Bramon, Robin M. Murray, Michele T. Pato, Jimmy Lee, Ingrid Melle, Espen Molden, Roel A. Ophoff, Andrew McQuillin, Nicholas J. Bass, Rolf Adolfsson, Anil K. Malhotra, Nicholas G. Martin, Janice M. Fullerton, Philip B. Mitchell, Peter R. Schofield, Andreas J. Forstner, Franziska Degenhardt, Sabrina Schaupp, Ashley L. Comes, Manolis Kogevinas, José Guzman-Parra, Andreas Reif, Fabian Streit, Lea Sirignano, Sven Cichon, Maria Grigoroiu-Serbanescu, Joanna Hauser, Jolanta Lissowska, Fermin Mayoral, Bertram Müller-Myhsok, Beata Świątkowska, Thomas G. Schulze, Markus M. Nöthen, Marcella Rietschel, John Kelsoe, Marion Leboyer, Stéphane Jamain, Bruno Etain, Frank Bellivier, John B. Vincent, Martin Alda, Claire O’Donovan, Pablo Cervantes, Joanna M. Biernacka, Mark Frye, Susan L. McElroy, Laura J. Scott, Eli A. Stahl, Mikael Landén, Marian L. Hamshere, Olav B. Smeland, Srdjan Djurovic, Arne E. Vaaler, Ole A. Andreassen, Bernhard T. Baune, Tracy Air, Martin Preisig, Rudolf Uher, Douglas F. Levinson, Myrna M. Weissman, James B. Potash, Jianxin Shi, James A. Knowles, Roy H. Perlis, Susanne Lucae, Dorret I. Boomsma, Brenda W.J.H. Penninx, Jouke-Jan Hottenga, Eco J.C. de Geus, Gonneke Willemsen, Yuri Milaneschi, Henning Tiemeier, Hans J. Grabe, Alexander Teumer, Sandra Van der Auwera, Uwe Völker, Steven P. Hamilton, Patrik K.E. Magnusson, Alexander Viktorin, Divya Mehta, Niamh Mullins, Mark J. Adams, Gerome Breen, Andrew M. McIntosh, Cathryn M. Lewis, David M. Hougaard, Merete Nordentoft, Ole Mors, Preben B. Mortensen, Thomas Werge, Thomas D. Als, Anders D. Børglum, Tracey L. Petryshen, Jordan W. Smoller, Jill M. Goldstein, Stephan Ripke, Benjamin M. Neale, James T.R. Walters, Kai-How Farh, Peter A. Holmans, Phil Lee, Brendan Bulik-Sullivan, David A. Collier, Hailiang Huang, Tune H. Pers, Ingrid Agartz, Esben Agerbo, Margot Albus, Madeline Alexander, Farooq Amin, Silviu A. Bacanu, Richard A. Belliveau, Judit Bene, Sarah E. Bergen, Elizabeth Bevilacqua, Tim B. Bigdeli, Donald W. Black, Richard Bruggeman, Nancy G. Buccola, Randy L. Buckner, William Byerley, Wiepke Cahn, Guiqing Cai, Dominique Campion, Rita M. Cantor, Vaughan J. Carr, Noa Carrera, Stanley V. Catts, Kimberly D. Chambert, Raymond C.K. Chan, Ronald Y.L. Chen, Eric Y.H. Chen, Wei Cheng, Eric F.C. Cheung, Siow Ann Chong, C. Robert Cloninger, David Cohen, Nadine Cohen, Paul Cormican, Nick Craddock, James J. Crowley, David Curtis, Michael Davidson, Kenneth L. Davis, Jurgen Del Favero, Ditte Demontis, Dimitris Dikeos, Timothy Dinan, Gary Donohoe, Elodie Drapeau, Jubao Duan, Frank Dudbridge, Naser Durmishi, Peter Eichhammer, Johan Eriksson, Valentina Escott-Price, Laurent Essioux, Ayman H. Fanous, Martilias S. Farrell, Josef Frank, Lude Franke, Robert Freedman, Nelson B. Freimer, Marion Friedl, Joseph I. Friedman, Menachem Fromer, Giulio Genovese, Lyudmila Georgieva, Paola Giusti-Rodríguez, Stephanie Godard, Jacqueline I. Goldstein, Vera Golimbet, Srihari Gopal, Jacob Gratten, Lieuwe de Haan, Christian Hammer, Mark Hansen, Thomas Hansen, Vahram Haroutunian, Frans A. Henskens, Stefan Herms, Joel N. Hirschhorn, Per Hoffmann, Andrea Hofman, Mads V. Hollegaard, Masashi Ikeda, Inge Joa, Antonio Julià, René S. Kahn, Luba Kalaydjieva, Sena Karachanak-Yankova, Juha Karjalainen, David Kavanagh, Matthew C. Keller, James L. Kennedy, Andrey Khrunin, Yunjung Kim, Janis Klovins, Vaidutis Kucinskas, Zita Ausrele Kucinskiene, Hana Kuzelova-Ptackova, Anna K. Kähler, Claudine Laurent, Jimmy Lee Chee Keong, S. Hong Lee, Sophie E. Legge, Bernard Lerer, Miaoxin Li, Tao Li, Kung-Yee Liang, Jeffrey Lieberman, Svetlana Limborska, Carmel M. Loughland, Jan Lubinski, Jouko Lönnqvist, Milan Macek, Brion S. Maher, Wolfgang Maier, Jacques Mallet, Sara Marsal, Manuel Mattheisen, Morten Mattingsdal, Robert W. McCarley, Colm McDonald, Sandra Meier, Carin J. Meijer, Bela Melegh, Raquelle I. Mesholam-Gately, Andres Metspalu, Patricia T. Michie, Vihra Milanova, Younes Mokrab, Derek W. Morris, Kieran C. Murphy, Inez Myin-Germeys, Mari Nelis, Igor Nenadic, Deborah A. Nertney, Gerald Nestadt, Kristin K. Nicodemus, Liene Nikitina-Zake, Laura Nisenbaum, Annelie Nordin, Eadbhard O’Callaghan, Colm O’Dushlaine, F. Anthony O’Neill, Sang-Yun Oh, Ann Olincy, Line Olsen, Jim Van Os, Christos Pantelis, George N. Papadimitriou, Sergi Papiol, Elena Parkhomenko, Tiina Paunio, Milica Pejovic-Milovancevic, Diana O. Perkins, Olli Pietiläinen, Jonathan Pimm, Andrew J. Pocklington, John Powell, Alkes Price, Ann E. Pulver, Shaun M. Purcell, Digby Quested, Henrik B. Rasmussen, Abraham Reichenberg, Mark A. Reimers, Alexander L. Richards, Joshua L. Roffman, Panos Roussos, Douglas M. Ruderfer, Veikko Salomaa, Ulrich Schall, Christian R. Schubert, Sibylle G. Schwab, Edward M. Scolnick, Rodney J. Scott, Larry J. Seidman, Engilbert Sigurdsson, Teimuraz Silagadze, Jeremy M. Silverman, Kang Sim, Petr Slominsky, Hon-Cheong So, Chris C.A. Spencer, Hreinn Stefansson, Stacy Steinberg, Elisabeth Stogmann, Richard E. Straub, Eric Strengman, Jana Strohmaier, T. Scott Stroup, Mythily Subramaniam, Jaana Suvisaari, Dragan M. Svrakic, Jin P. Szatkiewicz, Erik Söderman, Srinivas Thirumalai, Draga Toncheva, Sarah Tosato, Juha Veijola, John Waddington, Dermot Walsh, Dai Wang, Qiang Wang, Bradley T. Webb, Mark Weiser, Dieter B. Wildenauer, Nigel M. Williams, Stephanie Williams, Stephanie H. Witt, Aaron R. Wolen, Emily H.M. Wong, Brandon K. Wormley, Hualin Simon Xi, Clement C. Zai, Xuebin Zheng, Fritz Zimprich, Naomi R. Wray, Kari Stefansson, Peter M. Visscher, Douglas H.R. Blackwood, Ariel Darvasi, Enrico Domenici, Michael Gill, Hugh Gurling, Christina M. Hultman, Assen V. Jablensky, Kenneth S. Kendler, Jo Knight, Qingqin S. Li, Jianjun Liu, Steven A. McCarroll, Jennifer L. Moran, Michael J. Owen, Carlos N. Pato, Danielle Posthuma, Pamela Sklar, Jens R. Wendland, Mark J. Daly, Michael C. O’Donovan, Peter Donnelly, Ines Barroso, Jenefer M. Blackwell, Matthew A. Brown, Juan P. Casas, Panos Deloukas, Audrey Duncanson, Janusz Jankowski, Hugh S. Markus, Christopher G. Mathew, Colin N.A. Palmer, Robert Plomin, Anna Rautanen, Stephen J. Sawcer, Richard C. Trembath, Ananth C. Viswanathan, Nicholas W. Wood, Gavin Band, Céline Bellenguez, Colin Freeman, Eleni Giannoulatou, Garrett Hellenthal, Richard Pearson, Matti Pirinen, Amy Strange, Zhan Su, Damjan Vukcevic, Cordelia Langford, Hannah Blackburn, Suzannah J. Bumpstead, Serge Dronov, Sarah Edkins, Matthew Gillman, Emma Gray, Rhian Gwilliam, Naomi Hammond, Sarah E. Hunt, Alagurevathi Jayakumar, Jennifer Liddle, Owen T. McCann, Simon C. Potter, Radhi Ravindrarajah, Michelle Ricketts, Avazeh Tashakkori-Ghanbaria, Matthew Waller, Paul Weston, Pamela Whittaker, Sara Widaa, Mark I. McCarthy, Maria J. Arranz, Steven Bakker, Stephan Bender, Benedicto Crespo-Facorro, Jeremy Hall, Conrad Iyegbe, Stephen Lawrie, Kuang Lin, Don H. Linszen, Ignacio Mata, Muriel Walshe, Matthias Weisbrod, Durk Wiersma, Vassily Trubetskoy, Yunpeng Wang, Jonathan R.I. Coleman, Héléna A. Gaspar, Christiaan A. de Leeuw, Jennifer M. Whitehead Pavlides, Maciej Trzaskowski, Enda M. Byrne, Liam Abbott, Huda Akil, Diego Albani, Ney Alliey-Rodriguez, Adebayo Anjorin, Verneri Antilla, Swapnil Awasthi, Judith A. Badner, Marie Bækvad-Hansen, Jack D. Barchas, Nicholas Bass, Michael Bauer, Richard Belliveau, Carsten Bøcker Pedersen, Erlend Bøen, Marco P. Boks, James Boocock, Monika Budde, William Bunney, Margit Burmeister, Jonas Bybjerg-Grauholm, Miquel Casas, Felecia Cerrato, Kimberly Chambert, Alexander W. Charney, Danfeng Chen, Claire Churchhouse, Toni-Kim Clarke, William Coryell, David W. Craig, Cristiana Cruceanu, Piotr M. Czerski, Anders M. Dale, Simone de Jong, Jurgen Del-Favero, J. Raymond DePaulo, Amanda L. Dobbyn, Ashley Dumont, Torbjørn Elvsåshagen, Chun Chieh Fan, Sascha B. Fischer, Matthew Flickinger, Tatiana M. Foroud, Liz Forty, Christine Fraser, Katrin Gade, Diane Gage, Julie Garnham, Claudia Giambartolomei, Marianne Giørtz Pedersen, Jaqueline Goldstein, Scott D. Gordon, Katherine Gordon-Smith, Elaine K. Green, Melissa J. Green, Tiffany A. Greenwood, Weihua Guan, Martin Hautzinger, Urs Heilbronner, Maria Hipolito, Dominic Holland, Laura Huckins, Jessica S. Johnson, Radhika Kandaswamy, Robert Karlsson, Sarah Kittel-Schneider, Anna C. Koller, Ralph Kupka, Catharina Lavebratt, Jacob Lawrence, William B. Lawson, Markus Leber, Phil H. Lee, Shawn E. Levy, Jun Z. Li, Chunyu Liu, Anna Maaser, Donald J. MacIntyre, Pamela B. Mahon, Lina Martinsson, Steve McCarroll, Peter McGuffin, Melvin G. McInnis, James D. McKay, Helena Medeiros, Sarah E. Medland, Fan Meng, Grant W. Montgomery, Thomas W. Mühleisen, Hoang Nguyen, Caroline M. Nievergelt, Annelie Nordin Adolfsson, Evaristus A. Nwulia, Claire O'Donovan, Loes M. Olde Loohuis, Anil P.S. Ori, Lilijana Oruc, Urban Ösby, Amy Perry, Andrea Pfennig, Eline J. Regeer, Céline S. Reinbold, John P. Rice, Fabio Rivas, Margarita Rivera, Euijung Ryu, Cristina Sánchez-Mora, Alan F. Schatzberg, William A. Scheftner, Nicholas J. Schork, Cynthia Shannon Weickert, Tatyana Shehktman, Paul D. Shilling, Claire Slaney, Janet L. Sobell, Christine Søholm Hansen, Anne T. Spijker, Michael Steffens, John S. Strauss, Szabolcs Szelinger, Robert C. Thompson, Thorgeir E. Thorgeirsson, Jens Treutlein, Helmut Vedder, Weiqing Wang, Stanley J. Watson, Thomas W. Weickert, Simon Xi, Wei Xu, Allan H. Young, Peter Zandi, Peng Zhang, Sebastian Zöllner, Abdel Abdellaoui, Tracy M. Air, Till F.M. Andlauer, Silviu-Alin Bacanu, Aartjan T.F. Beekman, Elisabeth B. Binder, Julien Bryois, Henriette N. Buttenschøn, Na Cai, Enrique Castelao, Jane Hvarregaard Christensen, Lucía Colodro-Conde, Baptiste Couvy-Duchesne, Gregory E. Crawford, Gail Davies, Ian J. Deary, Eske M. Derks, Nese Direk, Conor V. Dolan, Erin C. Dunn, Thalia C. Eley, Farnush Farhadi Hassan Kiadeh, Hilary K. Finucane, Jerome C. Foo, Fernando S. Goes, Lynsey S. Hall, Thomas F. Hansen, Ian B. Hickie, Georg Homuth, Carsten Horn, David M. Howard, Marcus Ising, Rick Jansen, Ian Jones, Lisa A. Jones, Eric Jorgenson, Isaac S. Kohane, Julia Kraft, Warren W. Kretzschmar, Zoltán Kutalik, Yihan Li, Penelope A. Lind, Dean F. MacKinnon, Robert M. Maier, Jonathan Marchini, Hamdi Mbarek, Patrick McGrath, Christel M. Middeldorp, Evelin Mihailov, Francis M. Mondimore, Sara Mostafavi, Matthias Nauck, Bernard Ng, Michel G. Nivard, Dale R. Nyholt, Paul F. O'Reilly, Hogni Oskarsson, Jodie N. Painter, Roseann E. Peterson, Wouter J. Peyrot, Giorgio Pistis, Jorge A. Quiroz, Per Qvist, Saira Saeed Mirza, Robert Schoevers, Eva C. Schulte, Ling Shen, Stanley I. Shyn, Grant C.B. Sinnamon, Johannes H. Smit, Daniel J. Smith, Katherine E. Tansey, Henning Teismann, Wesley Thompson, Pippa A. Thomson, Matthew Traylor, André G. Uitterlinden, Daniel Umbricht, Albert M. van Hemert, Shantel Marie Weinsheimer, Jürgen Wellmann, Yang Wu, Hualin S. Xi, Jian Yang, Futao Zhang, Volker Arolt, Klaus Berger, Udo Dannlowski, Katharina Domschke, Caroline Hayward, Andrew C. Heath, Stefan Kloiber, Glyn Lewis, Pamela AF. Madden, Patrik K. Magnusson, Preben Bo Mortensen, Michael C. O'Donovan, Sara A. Paciga, Nancy L. Pedersen, David J. Porteous, Catherine Schaefer, Henry Völzke, Marco Bortolato, Janita Bralten, Cynthia M. Bulik, Christie L. Burton, Caitlin E. Carey, Lea K. Davis, Laramie E. Duncan, Howard J. Edenberg, Lauren Erdman, Stephen V. Faraone, Slavina B. Goleva, Wei Guo, Christopher Hübel, Laura M. Huckins, Ekaterina A. Khramtsova, Joanna Martin, Carol A. Mathews, Elise Robinson, Eli Stahl, Barbara E. Stranger, Michela Traglia, Raymond K. Walters, Lauren A. Weiss, Stacey J. Winham, Yin Yao, Kristjar Skajaa, Markus Nöthen, Michael Owen, Robert H. Yolken, Niels Plath, Jonathan Mill, Daniel Geschwind, Psychiatry 1, RS: MHeNs - R2 - Mental Health, Psychiatrie & Neuropsychologie, Centre of Excellence in Complex Disease Genetics, Research Programme of Molecular Medicine, Research Programs Unit, Aarno Palotie / Principal Investigator, Institute for Molecular Medicine Finland, Genomics of Neurological and Neuropsychiatric Disorders, Functional Genomics, Biological Psychology, APH - Mental Health, APH - Methodology, Sociology and Social Gerontology, APH - Personalized Medicine, APH - Health Behaviors & Chronic Diseases, Blokland, Gabriella AM, Grove, Jakob, Chen, Chia Yen, Cotsapas, Chris, Tobet, Stuart, Handa, Robert, Lee, Sang Hong, Schizophrenia Working Group of the Psychiatric Genomics Consortium, Bipolar Disorder Working Group of the Psychiatric Genomics Consortium, Major Depressive Disorder Working Group of the Psychiatric Genomics Consortium, Sex Differences Cross-Disorder Analysis Group of the Psychiatric Genomics Consortium, iPSYCH, Psychiatry, Amsterdam Neuroscience - Complex Trait Genetics, Amsterdam Neuroscience - Mood, Anxiety, Psychosis, Stress & Sleep, Human genetics, Amsterdam Neuroscience - Compulsivity, Impulsivity & Attention, Amsterdam Reproduction & Development (AR&D), Child and Adolescent Psychiatry / Psychology, Adult Psychiatry, ANS - Complex Trait Genetics, and ANS - Mood, Anxiety, Psychosis, Stress & Sleep
Subjects: 0301 basic medicine, Male, Bipolar Disorder, Schizophrenia/genetics, LD SCORE REGRESSION, Genome-wide association study, 0302 clinical medicine, Receptors, SCHIZOPHRENIA, Psychotic Disorders/genetics, KYNURENINE PATHWAY METABOLISM, Genetics, RISK, Sex Characteristics, Vascular Endothelial Growth Factor, Bipolar Disorder/genetics, Major/genetics, Single Nucleotide, AFFECTIVE STIMULI IMPACT, Schizophrenia, Sulfurtransferases, Major depressive disorder, Female, Depressive Disorder, Major/genetics, Bipolar disorder, Locus (genetics), Genomics, Biology, Polymorphism, Single Nucleotide, Article, DYSPHORIC MOOD, 03 medical and health sciences, Sex differences, medicine, Humans, Genetic Predisposition to Disease, ddc:610, Polymorphism, GENOME-WIDE ASSOCIATION, Genotype-by-sex interaction, Biological Psychiatry, Depressive Disorder, Major, Depressive Disorder, GENDER-DIFFERENCES, Neurodevelopmental disorders Donders Center for Medical Neuroscience [Radboudumc 7], PARAVENTRICULAR NUCLEUS, 3112 Neurosciences, Endothelial Cells, MAJOR DEPRESSION, medicine.disease, Genetic architecture, 030104 developmental biology, Mood, Receptors, Vascular Endothelial Growth Factor, Psychotic Disorders, 3111 Biomedicine, 030217 neurology & neurosurgery, Genome-Wide Association Study
Abstract: Contains fulltext : 248656.pdf (Publisher’s version ) (Closed access) BACKGROUND: Sex differences in incidence and/or presentation of schizophrenia (SCZ), major depressive disorder (MDD), and bipolar disorder (BIP) are pervasive. Previous evidence for shared genetic risk and sex differences in brain abnormalities across disorders suggest possible shared sex-dependent genetic risk. METHODS: We conducted the largest to date genome-wide genotype-by-sex (G×S) interaction of risk for these disorders using 85,735 cases (33,403 SCZ, 19,924 BIP, and 32,408 MDD) and 109,946 controls from the PGC (Psychiatric Genomics Consortium) and iPSYCH. RESULTS: Across disorders, genome-wide significant single nucleotide polymorphism-by-sex interaction was detected for a locus encompassing NKAIN2 (rs117780815, p = 3.2 × 10(-8)), which interacts with sodium/potassium-transporting ATPase (adenosine triphosphatase) enzymes, implicating neuronal excitability. Three additional loci showed evidence (p < 1 × 10(-6)) for cross-disorder G×S interaction (rs7302529, p = 1.6 × 10(-7); rs73033497, p = 8.8 × 10(-7); rs7914279, p = 6.4 × 10(-7)), implicating various functions. Gene-based analyses identified G×S interaction across disorders (p = 8.97 × 10(-7)) with transcriptional inhibitor SLTM. Most significant in SCZ was a MOCOS gene locus (rs11665282, p = 1.5 × 10(-7)), implicating vascular endothelial cells. Secondary analysis of the PGC-SCZ dataset detected an interaction (rs13265509, p = 1.1 × 10(-7)) in a locus containing IDO2, a kynurenine pathway enzyme with immunoregulatory functions implicated in SCZ, BIP, and MDD. Pathway enrichment analysis detected significant G×S interaction of genes regulating vascular endothelial growth factor receptor signaling in MDD (false discovery rate-corrected p < .05). CONCLUSIONS: In the largest genome-wide G×S analysis of mood and psychotic disorders to date, there was substantial genetic overlap between the sexes. However, significant sex-dependent effects were enriched for genes related to neuronal development and immune and vascular functions across and within SCZ, BIP, and MDD at the variant, gene, and pathway levels.
Published: 2022
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39. Dissecting the Shared Genetic Architecture of Suicide Attempt, Psychiatric Disorders, and Known Risk Factors

Author: Niamh Mullins, JooEun Kang, Adrian I. Campos, Jonathan R.I. Coleman, Alexis C. Edwards, Hanga Galfalvy, Daniel F. Levey, Adriana Lori, Andrey Shabalin, Anna Starnawska, Mei-Hsin Su, Hunna J. Watson, Mark Adams, Swapnil Awasthi, Michael Gandal, Jonathan D. Hafferty, Akitoyo Hishimoto, Minsoo Kim, Satoshi Okazaki, Ikuo Otsuka, Stephan Ripke, Erin B. Ware, Andrew W. Bergen, Wade H. Berrettini, Martin Bohus, Harry Brandt, Xiao Chang, Wei J. Chen, Hsi-Chung Chen, Steven Crawford, Scott Crow, Emily DiBlasi, Philibert Duriez, Fernando Fernández-Aranda, Manfred M. Fichter, Steven Gallinger, Stephen J. Glatt, Philip Gorwood, Yiran Guo, Hakon Hakonarson, Katherine A. Halmi, Hai-Gwo Hwu, Sonia Jain, Stéphane Jamain, Susana Jiménez-Murcia, Craig Johnson, Allan S. Kaplan, Walter H. Kaye, Pamela K. Keel, James L. Kennedy, Kelly L. Klump, Dong Li, Shih-Cheng Liao, Klaus Lieb, Lisa Lilenfeld, Chih-Min Liu, Pierre J. Magistretti, Christian R. Marshall, James E. Mitchell, Eric T. Monson, Richard M. Myers, Dalila Pinto, Abigail Powers, Nicolas Ramoz, Stefan Roepke, Vsevolod Rozanov, Stephen W. Scherer, Christian Schmahl, Marcus Sokolowski, Michael Strober, Laura M. Thornton, Janet Treasure, Ming T. Tsuang, Stephanie H. Witt, D. Blake Woodside, Zeynep Yilmaz, Lea Zillich, Rolf Adolfsson, Ingrid Agartz, Tracy M. Air, Martin Alda, Lars Alfredsson, Ole A. Andreassen, Adebayo Anjorin, Vivek Appadurai, María Soler Artigas, Sandra Van der Auwera, M. Helena Azevedo, Nicholas Bass, Claiton H.D. Bau, Bernhard T. Baune, Frank Bellivier, Klaus Berger, Joanna M. Biernacka, Tim B. Bigdeli, Elisabeth B. Binder, Michael Boehnke, Marco P. Boks, Rosa Bosch, David L. Braff, Richard Bryant, Monika Budde, Enda M. Byrne, Wiepke Cahn, Miguel Casas, Enrique Castelao, Jorge A. Cervilla, Boris Chaumette, Sven Cichon, Aiden Corvin, Nicholas Craddock, David Craig, Franziska Degenhardt, Srdjan Djurovic, Howard J. Edenberg, Ayman H. Fanous, Jerome C. Foo, Andreas J. Forstner, Mark Frye, Janice M. Fullerton, Justine M. Gatt, Pablo V. Gejman, Ina Giegling, Hans J. Grabe, Melissa J. Green, Eugenio H. Grevet, Maria Grigoroiu-Serbanescu, Blanca Gutierrez, Jose Guzman-Parra, Steven P. Hamilton, Marian L. Hamshere, Annette Hartmann, Joanna Hauser, Stefanie Heilmann-Heimbach, Per Hoffmann, Marcus Ising, Ian Jones, Lisa A. Jones, Lina Jonsson, René S. Kahn, John R. Kelsoe, Kenneth S. Kendler, Stefan Kloiber, Karestan C. Koenen, Manolis Kogevinas, Bettina Konte, Marie-Odile Krebs, Mikael Landén, Jacob Lawrence, Marion Leboyer, Phil H. Lee, Douglas F. Levinson, Calwing Liao, Jolanta Lissowska, Susanne Lucae, Fermin Mayoral, Susan L. McElroy, Patrick McGrath, Peter McGuffin, Andrew McQuillin, Sarah E. Medland, Divya Mehta, Ingrid Melle, Yuri Milaneschi, Philip B. Mitchell, Esther Molina, Gunnar Morken, Preben Bo Mortensen, Bertram Müller-Myhsok, Caroline Nievergelt, Vishwajit Nimgaonkar, Markus M. Nöthen, Michael C. O’Donovan, Roel A. Ophoff, Michael J. Owen, Carlos Pato, Michele T. Pato, Brenda W.J.H. Penninx, Jonathan Pimm, Giorgio Pistis, James B. Potash, Robert A. Power, Martin Preisig, Digby Quested, Josep Antoni Ramos-Quiroga, Andreas Reif, Marta Ribasés, Vanesa Richarte, Marcella Rietschel, Margarita Rivera, Andrea Roberts, Gloria Roberts, Guy A. Rouleau, Diego L. Rovaris, Dan Rujescu, Cristina Sánchez-Mora, Alan R. Sanders, Peter R. Schofield, Thomas G. Schulze, Laura J. Scott, Alessandro Serretti, Jianxin Shi, Stanley I. Shyn, Lea Sirignano, Pamela Sklar, Olav B. Smeland, Jordan W. Smoller, Edmund J.S. Sonuga-Barke, Gianfranco Spalletta, John S. Strauss, Beata Świątkowska, Maciej Trzaskowski, Gustavo Turecki, Laura Vilar-Ribó, John B. Vincent, Henry Völzke, James T.R. Walters, Cynthia Shannon Weickert, Thomas W. Weickert, Myrna M. Weissman, Leanne M. Williams, Naomi R. Wray, Clement C. Zai, Allison E. Ashley-Koch, Jean C. Beckham, Elizabeth R. Hauser, Michael A. Hauser, Nathan A. Kimbrel, Jennifer H. Lindquist, Benjamin McMahon, David W. Oslin, Xuejun Qin, Esben Agerbo, Anders D. Børglum, Gerome Breen, Annette Erlangsen, Tõnu Esko, Joel Gelernter, David M. Hougaard, Ronald C. Kessler, Henry R. Kranzler, Qingqin S. Li, Nicholas G. Martin, Andrew M. McIntosh, Ole Mors, Merete Nordentoft, Catherine M. Olsen, David Porteous, Robert J. Ursano, Danuta Wasserman, Thomas Werge, David C. Whiteman, Cynthia M. Bulik, Hilary Coon, Ditte Demontis, Anna R. Docherty, Po-Hsiu Kuo, Cathryn M. Lewis, J. John Mann, Miguel E. Rentería, Daniel J. Smith, Eli A. Stahl, Murray B. Stein, Fabian Streit, Virginia Willour, Douglas M. Ruderfer, Manuel Mattheisen, Abdel Abdellaoui, Mark J. Adams, Till F.M. Andlauer, Silviu-Alin Bacanu, Marie Bækvad-Hansen, Aartjan T.F. Beekman, Julien Bryois, Henriette N. Buttenschøn, Jonas Bybjerg-Grauholm, Na Cai, Jane Hvarregaard Christensen, Toni-Kim Clarke, Lucía Colodro-Conde, Baptiste Couvy-Duchesne, Nick Craddock, Gregory E. Crawford, Gail Davies, Eske M. Derks, Nese Direk, Conor V. Dolan, Erin C. Dunn, Thalia C. Eley, Valentina Escott-Price, Farnush Farhadi Hassan Kiadeh, Hilary K. Finucane, Josef Frank, Héléna A. Gaspar, Michael Gill, Fernando S. Goes, Scott D. Gordon, Shantel Marie Weinsheimer, Jürgen Wellmann, Gonneke Willemsen, Yang Wu, Hualin S. Xi, Jian Yang, Futao Zhang, Volker Arolt, Dorret I. Boomsma, Udo Dannlowski, E.J.C. de Geus, J. Raymond Depaulo, Enrico Domenici, Katharina Domschke, Jakob Grove, Lynsey S. Hall, Christine Søholm Hansen, Thomas F. Hansen, Stefan Herms, Ian B. Hickie, Georg Homuth, Carsten Horn, Jouke-Jan Hottenga, David M. Howard, Rick Jansen, Eric Jorgenson, James A. Knowles, Isaac S. Kohane, Julia Kraft, Warren W. Kretzschmar, Zoltán Kutalik, Yihan Li, Penelope A. Lind, Donald J. MacIntyre, Dean F. MacKinnon, Robert M. Maier, Wolfgang Maier, Jonathan Marchini, Hamdi Mbarek, Christel M. Middeldorp, Evelin Mihailov, Lili Milani, Francis M. Mondimore, Grant W. Montgomery, Sara Mostafavi, Matthias Nauck, Bernard Ng, Michel G. Nivard, Dale R. Nyholt, Paul F. O’Reilly, Hogni Oskarsson, Caroline Hayward, Andrew C. Heath, Glyn Lewis, Pamela A.F. Madden, Patrik K. Magnusson, Andres Metspalu, Sara A. Paciga, Nancy L. Pedersen, Jodie N. Painter, Carsten Bøcker Pedersen, Marianne Giørtz Pedersen, Roseann E. Peterson, Wouter J. Peyrot, Danielle Posthuma, Jorge A. Quiroz, Per Qvist, John P. Rice, Brien P. Riley, Saira Saeed Mirza, Robert Schoevers, Eva C. Schulte, Ling Shen, Engilbert Sigurdsson, Grant C.B. Sinnamon, Johannes H. Smit, Hreinn Stefansson, Stacy Steinberg, Jana Strohmaier, Katherine E. Tansey, Henning Teismann, Alexander Teumer, Wesley Thompson, Pippa A. Thomson, Thorgeir E. Thorgeirsson, Matthew Traylor, Jens Treutlein, Vassily Trubetskoy, André G. Uitterlinden, Daniel Umbricht, Albert M. van Hemert, Alexander Viktorin, Peter M. Visscher, Yunpeng Wang, Bradley T. Webb, Roy H. Perlis, David J. Porteous, Catherine Schaefer, Kari Stefansson, Henning Tiemeier, Rudolf Uher, Patrick F. Sullivan, Kevin S. O’Connell, Brandon Coombes, Zhen Qiao, Thomas D. Als, Sigrid Børte, Alexander W. Charney, Ole Kristian Drange, Michael J. Gandal, Saskia P. Hagenaars, Masashi Ikeda, Nolan Kamitaki, Kristi Krebs, Georgia Panagiotaropoulou, Brian M. Schilder, Laura G. Sloofman, Bendik S. Winsvold, Hong-Hee Won, Liliya Abramova, Kristina Adorjan, Mariam Al Eissa, Diego Albani, Ney Alliey-Rodriguez, Verneri Antilla, Anastasia Antoniou, Ji Hyun Baek, Michael Bauer, Eva C. Beins, Sarah E. Bergen, Armin Birner, Erlend Bøen, Murielle Brum, Ben M. Brumpton, Nathalie Brunkhorst-Kanaan, William Byerley, Murray Cairns, Miquel Casas, Pablo Cervantes, Cristiana Cruceanu, Alfredo Cuellar-Barboza, Julie Cunningham, David Curtis, Piotr M. Czerski, Anders M. Dale, Nina Dalkner, Friederike S. David, Amanda L. Dobbyn, Athanassios Douzenis, Torbjørn Elvsåshagen, I. Nicol Ferrier, Alessia Fiorentino, Tatiana M. Foroud, Liz Forty, Oleksandr Frei, Nelson B. Freimer, Louise Frisén, Katrin Gade, Julie Garnham, Ian R. Gizer, Katherine Gordon-Smith, Tiffany A. Greenwood, José Guzman-Parra, Kyooseob Ha, Magnus Haraldsson, Martin Hautzinger, Urs Heilbronner, Dennis Hellgren, Peter A. Holmans, Laura Huckins, Jessica S. Johnson, Janos L. Kalman, Yoichiro Kamatani, Sarah Kittel-Schneider, Maria Koromina, Thorsten M. Kranz, Michiaki Kubo, Ralph Kupka, Steven A. Kushner, Catharina Lavebratt, Markus Leber, Heon-Jeong Lee, Shawn E. Levy, Catrin Lewis, Martin Lundberg, Sigurdur H. Magnusson, Adam Maihofer, Dolores Malaspina, Eirini Maratou, Lina Martinsson, Nathaniel W. McGregor, James D. McKay, Helena Medeiros, Vincent Millischer, Jennifer L. Moran, Derek W. Morris, Thomas W. Mühleisen, Niamh O’Brien, Claire O’Donovan, Loes M. Olde Loohuis, Lilijana Oruc, Sergi Papiol, Antonio F. Pardiñas, Amy Perry, Andrea Pfennig, Evgenia Porichi, Towfique Raj, Mark H. Rapaport, J. Raymond DePaulo, Eline J. Regeer, Fabio Rivas, Julian Roth, Panos Roussos, Fanny Senner, Sally Sharp, Paul D. Shilling, Claire Slaney, Janet L. Sobell, Maria Soler Artigas, Anne T. Spijker, Dan J. Stein, Chikashi Terao, Claudio Toma, Paul Tooney, Evangelia-Eirini Tsermpini, Marquis P. Vawter, Helmut Vedder, Simon Xi, Wei Xu, Jessica Mei Kay Yang, Allan H. Young, Hannah Young, Peter P. Zandi, Hang Zhou, null HUNT All-In Psychiatry, Gulja Babadjanova, Lena Backlund, Susanne Bengesser, Douglas H.R. Blackwood, Vaughan J. Carr, Stanley Catts, Dimitris Dikeos, Bruno Etain, Panagiotis Ferentinos, Micha Gawlik, Elliot S. Gershon, Frans Henskens, Jan Hillert, Kyung Sue Hong, Christina M. Hultman, Kristian Hveem, Nakao Iwata, Assen V. Jablensky, George Kirov, Christine Lochner, Carmel Loughland, Carol A. Mathews, Francis J. McMahon, Patricia Michie, Bryan Mowry, Benjamin M. Neale, Caroline M. Nievergelt, Ketil J. Oedegaard, Tomas Olsson, Chris Pantelis, George P. Patrinos, Eva Z. Reininghaus, Takeo Saito, Ulrich Schall, Martin Schalling, Rodney J. Scott, Eystein Stordal, Arne E. Vaaler, Eduard Vieta, Irwin D. Waldman, John-Anker Zwart, John I. Nurnberger, Arianna Di Florio, Roger A.H. Adan, Tetsuya Ando, Harald Aschauer, Jessica H. Baker, Vladimir Bencko, Andreas Birgegård, Joseph M. Boden, Ilka Boehm, Claudette Boni, Vesna Boraska Perica, Katharina Buehren, Roland Burghardt, Laura Carlberg, Matteo Cassina, Maurizio Clementi, Roger D. Cone, Philippe Courtet, James J. Crowley, Unna N. Danner, Oliver S.P. Davis, Martina de Zwaan, George Dedoussis, Daniela Degortes, Janiece E. DeSocio, Danielle M. Dick, Christian Dina, Monika Dmitrzak-Weglarz, Elisa Docampo Martinez, Laramie E. Duncan, Karin Egberts, Morten Mattingsdal, Sara McDevitt, Ingrid Meulenbelt, Nadia Micali, James Mitchell, Karen Mitchell, Palmiero Monteleone, Alessio Maria Monteleone, Melissa A. Munn-Chernoff, Benedetta Nacmias, Marie Navratilova, Ioanna Ntalla, Julie K. O’Toole, Leonid Padyukov, Aarno Palotie, Jacques Pantel, Hana Papezova, Richard Parker, John F. Pearson, Stefan Ehrlich, Geòrgia Escaramís, Thomas Espeseth, Xavier Estivill, Anne Farmer, Angela Favaro, Krista Fischer, James A.B. Floyd, Manuel Föcker, Lenka Foretova, Monica Forzan, Christopher S. Franklin, Giovanni Gambaro, Johanna Giuranna, Paola Giusti-Rodríquez, Fragiskos Gonidakis, Scott Gordon, Monica Gratacos Mayora, Sébastien Guillaume, Ken B. Hanscombe, Konstantinos Hatzikotoulas, Johannes Hebebrand, Sietske G. Helder, Anjali K. Henders, Beate Herpertz-Dahlmann, Wolfgang Herzog, Anke Hinney, L. John Horwood, Christopher Hübel, Liselotte V. Petersen, Kirstin L. Purves, Anu Raevuori, Ted Reichborn-Kjennerud, Valdo Ricca, Samuli Ripatti, Franziska Ritschel, Marion Roberts, Filip Rybakowski, Paolo Santonastaso, André Scherag, Ulrike Schmidt, Nicholas J. Schork, Alexandra Schosser, Jochen Seitz, Lenka Slachtova, P. Eline Slagboom, Margarita C.T. Slof-Op ‘t Landt, Agnieszka Slopien, Nicole Soranzo, Sandro Sorbi, Lorraine Southam, Vidar W. Steen, Laura M. Huckins, James I. Hudson, Hartmut Imgart, Hidetoshi Inoko, Vladimir Janout, Jennifer Jordan, Antonio Julià, Gursharan Kalsi, Deborah Kaminská, Jaakko Kaprio, Leila Karhunen, Andreas Karwautz, Martien J.H. Kas, Martin A. Kennedy, Anna Keski-Rahkonen, Kirsty Kiezebrink, Youl-Ri Kim, Katherine M. Kirk, Lars Klareskog, Gun Peggy S. Knudsen, Janne T. Larsen, Stephanie Le Hellard, Virpi M. Leppä, Paul Lichtenstein, Bochao Danae Lin, Astri Lundervold, Jurjen Luykx, Mario Maj, Katrin Mannik, Sara Marsal, Garret D. Stuber, Jin P. Szatkiewicz, Ioanna Tachmazidou, Elena Tenconi, Alfonso Tortorella, Federica Tozzi, Artemis Tsitsika, Marta Tyszkiewicz-Nwafor, Konstantinos Tziouvas, Annemarie A. van Elburg, Eric F. van Furth, Tracey D. Wade, Gudrun Wagner, Esther Walton, H. Erich Wichmann, Elisabeth Widen, Shuyang Yao, Eleftheria Zeggini, Stephanie Zerwas, Stephan Zipfel, Martin Jungkunz, Lydie Dietl, Cornelia E. Schwarze, Norbert Dahmen, Björn H. Schott, Arian Mobascher, Silvia Crivelli, Michelle F. Dennis, Phillip D. Harvey, Bruce W. Carter, Jennifer E. Huffman, Daniel Jacobson, Ravi Madduri, Maren K. Olsen, John Pestian, J. Michael Gaziano, Sumitra Muralidhar, Rachel Ramoni, Jean Beckham, Kyong-Mi Chang, Christopher J. O’Donnell, Philip S. Tsao, James Breeling, Grant Huang, J.P. Casas Romero, Jennifer Moser, Stacey B. Whitbourne, Jessica V. Brewer, Mihaela Aslan, Todd Connor, Dean P. Argyres, Brady Stephens, Mary T. Brophy, Donald E. Humphries, Luis E. Selva, Nhan Do, Shahpoor Shayan, Kelly Cho, Saiju Pyarajan, Elizabeth Hauser, Yan Sun, Hongyu Zhao, Peter Wilson, Rachel McArdle, Louis Dellitalia, Kristin Mattocks, John Harley, Clement J. Zablocki, Jeffrey Whittle, Frank Jacono, Salvador Gutierrez, Gretchen Gibson, Kimberly Hammer, Laurence Kaminsky, Gerardo Villareal, Scott Kinlay, Junzhe Xu, Mark Hamner, Roy Mathew, Sujata Bhushan, Pran Iruvanti, Michael Godschalk, Zuhair Ballas, Douglas Ivins, Stephen Mastorides, Jonathan Moorman, Saib Gappy, Jon Klein, Nora Ratcliffe, Hermes Florez, Olaoluwa Okusaga, Maureen Murdoch, Peruvemba Sriram, Shing Shing Yeh, Neeraj Tandon, Darshana Jhala, Samuel Aguayo, David Cohen, Satish Sharma, Suthat Liangpunsakul, Kris Ann Oursler, Mary Whooley, Sunil Ahuja, Joseph Constans, Paul Meyer, Jennifer Greco, Michael Rauchman, Richard Servatius, Melinda Gaddy, Agnes Wallbom, Timothy Morgan, Todd Stapley, Scott Sherman, George Ross, Philip Tsao, Patrick Strollo, Edward Boyko, Laurence Meyer, Samir Gupta, Mostaqul Huq, Joseph Fayad, Adriana Hung, Jack Lichy, Robin Hurley, Brooks Robey, Robert Striker, Dietl, Lydie, Schwarze, Cornelia E., Dahmen, Norbert, Schott, Björn H., Nöthen, Markus M., Ripke, Stephan, Mobascher, Arian, Rujescu, Dan, Lieb, Klaus, Roepke, Stefan, Schmahl, Christian, Bohus, Martin, Rietschel, Marcella, Crivelli, Silvia, Dennis, Michelle F., Harvey, Phillip D., Carter, Bruce W., Huffman, Jennifer E., Jacobson, Daniel, Madduri, Ravi, Olsen, Maren K., Pestian, John, Gaziano, J. Michael, Muralidhar, Sumitra, Ramoni, Rachel, Beckham, Jean, Chang, Kyong-Mi, O'Donnell, Christopher J., Tsao, Philip S., Breeling, James, Huang, Grant, Romero, J. P. Casas, Moser, Jennifer, Whitbourne, Stacey B., Brewer, Jessica V., Aslan, Mihaela, Connor, Todd, Argyres, Dean P., Stephens, Brady, Brophy, Mary T., Humphries, Donald E., Selva, Luis E., Do, Nhan, Shayan, Shahpoor, Cho, Kelly, Pyarajan, Saiju, Hauser, Elizabeth, Sun, Yan, Zhao, Hongyu, Wilson, Peter, McArdle, Rachel, Dellitalia, Louis, Mattocks, Kristin, Harley, John, Zablocki, Clement J., Whittle, Jeffrey, Jacono, Frank, Gutierrez, Salvador, Gibson, Gretchen, Hammer, Kimberly, Kaminsky, Laurence, Villareal, Gerardo, Kinlay, Scott, Xu, Junzhe, Hamner, Mark, Mathew, Roy, Bhushan, Sujata, Iruvanti, Pran, Godschalk, Michael, Ballas, Zuhair, Ivins, Douglas, Mastorides, Stephen, Moorman, Jonathan, Gappy, Saib, Klein, Jon, Ratcliffe, Nora, Florez, Hermes, Okusaga, Olaoluwa, Murdoch, Maureen, Sriram, Peruvemba, Yeh, Shing Shing, Tandon, Neeraj, Jhala, Darshana, Aguayo, Samuel, Cohen, David, Sharma, Satish, Liangpunsakul, Suthat, Oursler, Kris Ann, Whooley, Mary, Ahuja, Sunil, Constans, Joseph, Meyer, Paul, Greco, Jennifer, Rauchman, Michael, Servatius, Richard, Gaddy, Melinda, Wallbom, Agnes, Morgan, Timothy, Stapley, Todd, Sherman, Scott, Ross, George, Tsao, Philip, Strollo, Patrick, Boyko, Edward, Meyer, Laurence, Gupta, Samir, Huq, Mostaqul, Fayad, Joseph, Hung, Adriana, Lichy, Jack, Hurley, Robin, Robey, Brooks, Striker, Robert, Wray, Naomi R., Mattheisen, Manuel, Trzaskowski, Maciej, Byrne, Enda M., Abdellaoui, Abdel, Adams, Mark J., Agerbo, Esben, Air, Tracy M., Andlauer, Till F. M., Bacanu, Silviu-Alin, Bækvad-Hansen, Marie, Beekman, Aartjan T. F., Bigdeli, Tim B., Binder, Elisabeth B., Bryois, Julien, Buttenschøn, Henriette N., Bybjerg-Grauholm, Jonas, Cai, Na, Castelao, Enrique, Christensen, Jane Hvarregaard, Clarke, Toni-Kim, Coleman, Jonathan R. I., Colodro-Conde, Lucía, Couvy-Duchesne, Baptiste, Craddock, Nick, Crawford, Gregory E., Davies, Gail, Degenhardt, Franziska, Derks, Eske M., Direk, Nese, Dolan, Conor V., Dunn, Erin C., Eley, Thalia C., Escott-Price, Valentina, Hassan Kiadeh, Farnush Farhadi, Finucane, Hilary K., Foo, Jerome C., Forstner, Andreas J., Frank, Josef, Gaspar, Héléna A., Gill, Michael, Goes, Fernando S., Gordon, Scott D., Weinsheimer, Shantel Marie, Wellmann, Jürgen, Willemsen, Gonneke, Witt, Stephanie H., Wu, Yang, Xi, Hualin S., Yang, Jian, Zhang, Futao, Arolt, Volker, Baune, Bernhard T., Berger, Klaus, Boomsma, Dorret I., Cichon, Sven, Dannlowski, Udo, de Geus, E. J. C., DePaulo, J. Raymond, Domenici, Enrico, Domschke, Katharina, Esko, Tõnu, Grabe, Hans J., Hamilton, Steven P., Grove, Jakob, Hall, Lynsey S., Hansen, Christine Søholm, Hansen, Thomas F., Herms, Stefan, Hickie, Ian B., Hoffmann, Per, Homuth, Georg, Horn, Carsten, Hottenga, Jouke-Jan, Hougaard, David M., Howard, David M., Ising, Marcus, Jansen, Rick, Jones, Ian, Jones, Lisa A., Jorgenson, Eric, Knowles, James A., Kohane, Isaac S., Kraft, Julia, Kretzschmar, Warren W., Kutalik, Zoltán, Li, Yihan, Lind, Penelope A., MacIntyre, Donald J., MacKinnon, Dean F., Maier, Robert M., Maier, Wolfgang, Marchini, Jonathan, Mbarek, Hamdi, McGrath, Patrick, McGuffin, Peter, Medland, Sarah E., Mehta, Divya, Middeldorp, Christel M., Mihailov, Evelin, Milaneschi, Yuri, Milani, Lili, Mondimore, Francis M., Montgomery, Grant W., Mostafavi, Sara, Mullins, Niamh, Nauck, Matthias, Ng, Bernard, Nivard, Michel G., Nyholt, Dale R., O'Reilly, Paul F., Oskarsson, Hogni, Hayward, Caroline, Heath, Andrew C., Kendler, Kenneth S., Kloiber, Stefan, Lewis, Glyn, Li, Qingqin S., Lucae, Susanne, Madden, Pamela A. F., Magnusson, Patrik K., Martin, Nicholas G., McIntosh, Andrew M., Metspalu, Andres, Mors, Ole, Mortensen, Preben Bo, Müller-Myhsok, Bertram, Nordentoft, Merete, O'Donovan, Michael C., Paciga, Sara A., Pedersen, Nancy L., Owen, Michael J., Painter, Jodie N., Pedersen, Carsten Bøcker, Pedersen, Marianne Giørtz, Peterson, Roseann E., Peyrot, Wouter J., Pistis, Giorgio, Posthuma, Danielle, Quiroz, Jorge A., Qvist, Per, Rice, John P., Riley, Brien P., Rivera, Margarita, Mirza, Saira Saeed, Schoevers, Robert, Schulte, Eva C., Shen, Ling, Shi, Jianxin, Shyn, Stanley I., Sigurdsson, Engilbert, Sinnamon, Grant C. B., Smit, Johannes H., Smith, Daniel J., Stefansson, Hreinn, Steinberg, Stacy, Streit, Fabian, Strohmaier, Jana, Tansey, Katherine E., Teismann, Henning, Teumer, Alexander, Thompson, Wesley, Thomson, Pippa A., Thorgeirsson, Thorgeir E., Traylor, Matthew, Treutlein, Jens, Trubetskoy, Vassily, Uitterlinden, André G., Umbricht, Daniel, Van der Auwera, Sandra, van Hemert, Albert M., Viktorin, Alexander, Visscher, Peter M., Wang, Yunpeng, Webb, Bradley T., Penninx, Brenda W. J. H., Perlis, Roy H., Porteous, David J., Potash, James B., Preisig, Martin, Schaefer, Catherine, Schulze, Thomas G., Smoller, Jordan W., Stefansson, Kari, Tiemeier, Henning, Uher, Rudolf, Völzke, Henry, Weissman, Myrna M., Werge, Thomas, Lewis, Cathryn M., Levinson, Douglas F., Breen, Gerome, Børglum, Anders D., Sullivan, Patrick F., O'Connell, Kevin S., Coombes, Brandon, Qiao, Zhen, Als, Thomas D., Børte, Sigrid, Charney, Alexander W., Drange, Ole Kristian, Gandal, Michael J., Hagenaars, Saskia P., Ikeda, Masashi, Kamitaki, Nolan, Kim, Minsoo, Krebs, Kristi, Panagiotaropoulou, Georgia, Schilder, Brian M., Sloofman, Laura G., Winsvold, Bendik S., Won, Hong-Hee, Abramova, Liliya, Adorjan, Kristina, Al Eissa, Mariam, Albani, Diego, Alliey-Rodriguez, Ney, Anjorin, Adebayo, Antilla, Verneri, Antoniou, Anastasia, Awasthi, Swapnil, Baek, Ji Hyun, Bass, Nicholas, Bauer, Michael, Beins, Eva C., Bergen, Sarah E., Birner, Armin, Bøen, Erlend, Boks, Marco P., Bosch, Rosa, Brum, Murielle, Brumpton, Ben M., Brunkhorst-Kanaan, Nathalie, Budde, Monika, Byerley, William, Cairns, Murray, Casas, Miquel, Cervantes, Pablo, Cruceanu, Cristiana, Cuellar-Barboza, Alfredo, Cunningham, Julie, Curtis, David, Czerski, Piotr M., Dale, Anders M., Dalkner, Nina, David, Friederike S., Djurovic, Srdjan, Dobbyn, Amanda L., Douzenis, Athanassios, Elvsåshagen, Torbjørn, Ferrier, I. Nicol, Fiorentino, Alessia, Foroud, Tatiana M., Forty, Liz, Frei, Oleksandr, Freimer, Nelson B., Frisén, Louise, Gade, Katrin, Garnham, Julie, Gelernter, Joel, Gizer, Ian R., Gordon-Smith, Katherine, Greenwood, Tiffany A., Guzman-Parra, José, Ha, Kyooseob, Haraldsson, Magnus, Hautzinger, Martin, Heilbronner, Urs, Hellgren, Dennis, Holmans, Peter A., Huckins, Laura, Jamain, Stéphane, Johnson, Jessica S., Kalman, Janos L., Kamatani, Yoichiro, Kennedy, James L., Kittel-Schneider, Sarah, Kogevinas, Manolis, Koromina, Maria, Kranz, Thorsten M., Kranzler, Henry R., Kubo, Michiaki, Kupka, Ralph, Kushner, Steven A., Lavebratt, Catharina, Lawrence, Jacob, Leber, Markus, Lee, Heon-Jeong, Lee, Phil H., Levy, Shawn E., Lewis, Catrin, Liao, Calwing, Lundberg, Martin, Magnusson, Sigurdur H., Maihofer, Adam, Malaspina, Dolores, Maratou, Eirini, Martinsson, Lina, McGregor, Nathaniel W., McKay, James D., Medeiros, Helena, Millischer, Vincent, Moran, Jennifer L., Morris, Derek W., Mühleisen, Thomas W., O'Brien, Niamh, O'Donovan, Claire, Olde Loohuis, Loes M., Oruc, Lilijana, Papiol, Sergi, Pardiñas, Antonio F., Perry, Amy, Pfennig, Andrea, Porichi, Evgenia, Quested, Digby, Raj, Towfique, Rapaport, Mark H., Regeer, Eline J., Rivas, Fabio, Roth, Julian, Roussos, Panos, Ruderfer, Douglas M., Sánchez-Mora, Cristina, Senner, Fanny, Sharp, Sally, Shilling, Paul D., Sirignano, Lea, Slaney, Claire, Smeland, Olav B., Sobell, Janet L., Artigas, Maria Soler, Spijker, Anne T., Stein, Dan J., Strauss, John S., Świątkowska, Beata, Terao, Chikashi, Toma, Claudio, Tooney, Paul, Tsermpini, Evangelia-Eirini, Vawter, Marquis P., Vedder, Helmut, Walters, James T. R., Xi, Simon, Xu, Wei, Kay Yang, Jessica Mei, Young, Allan H., Young, Hannah, Zandi, Peter P., Zhou, Hang, Zillich, Lea, Adolfsson, Rolf, Agartz, Ingrid, Alda, Martin, Alfredsson, Lars, Babadjanova, Gulja, Backlund, Lena, Bellivier, Frank, Bengesser, Susanne, Berrettini, Wade H., Blackwood, Douglas H. R., Boehnke, Michael, Carr, Vaughan J., Catts, Stanley, Corvin, Aiden, Craddock, Nicholas, Dikeos, Dimitris, Etain, Bruno, Ferentinos, Panagiotis, Frye, Mark, Fullerton, Janice M., Gawlik, Micha, Gershon, Elliot S., Green, Melissa J., Grigoroiu-Serbanescu, Maria, Hauser, Joanna, Henskens, Frans, Hillert, Jan, Hong, Kyung Sue, Hultman, Christina M., Hveem, Kristian, Iwata, Nakao, Jablensky, Assen V., Kahn, René S., Kelsoe, John R., Kirov, George, Landén, Mikael, Leboyer, Marion, Lissowska, Jolanta, Lochner, Christine, Loughland, Carmel, Mathews, Carol A., Mayoral, Fermin, McElroy, Susan L., McMahon, Francis J., Melle, Ingrid, Michie, Patricia, Mitchell, Philip B., Morken, Gunnar, Mowry, Bryan, Myers, Richard M., Neale, Benjamin M., Nievergelt, Caroline M., Oedegaard, Ketil J., Olsson, Tomas, Pantelis, Chris, Pato, Carlos, Pato, Michele T., Patrinos, George P., Ramos-Quiroga, Josep Antoni, Reif, Andreas, Reininghaus, Eva Z., Ribasés, Marta, Rouleau, Guy A., Saito, Takeo, Schall, Ulrich, Schalling, Martin, Schofield, Peter R., Scott, Laura J., Scott, Rodney J., Serretti, Alessandro, Weickert, Cynthia Shannon, Stordal, Eystein, Turecki, Gustavo, Vaaler, Arne E., Vieta, Eduard, Vincent, John B., Waldman, Irwin D., Weickert, Thomas W., Zwart, John-Anker, Biernacka, Joanna M., Nurnberger, John I., Edenberg, Howard J., Stahl, Eli A., McQuillin, Andrew, Di Florio, Arianna, Ophoff, Roel A., Andreassen, Ole A., Adan, Roger A. H., Ando, Tetsuya, Aschauer, Harald, Baker, Jessica H., Bencko, Vladimir, Bergen, Andrew W., Birgegård, Andreas, Boden, Joseph M., Boehm, Ilka, Boni, Claudette, Perica, Vesna Boraska, Brandt, Harry, Buehren, Katharina, Bulik, Cynthia M., Burghardt, Roland, Carlberg, Laura, Cassina, Matteo, Clementi, Maurizio, Cone, Roger D., Courtet, Philippe, Crawford, Steven, Crow, Scott, Crowley, James J., Danner, Unna N., Davis, Oliver S. P., de Zwaan, Martina, Dedoussis, George, Degortes, Daniela, DeSocio, Janiece E., Dick, Danielle M., Dina, Christian, Dmitrzak-Weglarz, Monika, Martinez, Elisa Docampo, Duncan, Laramie E., Egberts, Karin, Marshall, Christian R., Mattingsdal, Morten, McDevitt, Sara, Meulenbelt, Ingrid, Micali, Nadia, Mitchell, James, Mitchell, Karen, Monteleone, Palmiero, Monteleone, Alessio Maria, Munn-Chernoff, Melissa A., Nacmias, Benedetta, Navratilova, Marie, Ntalla, Ioanna, Olsen, Catherine M., O'Toole, Julie K., Padyukov, Leonid, Palotie, Aarno, Pantel, Jacques, Papezova, Hana, Parker, Richard, Pearson, John F., Ehrlich, Stefan, Escaramís, Geòrgia, Espeseth, Thomas, Estivill, Xavier, Farmer, Anne, Favaro, Angela, Fernández-Aranda, Fernando, Fichter, Manfred M., Fischer, Krista, Floyd, James A. B., Föcker, Manuel, Foretova, Lenka, Forzan, Monica, Franklin, Christopher S., Gallinger, Steven, Gambaro, Giovanni, Giegling, Ina, Giuranna, Johanna, Giusti-Rodríquez, Paola, Gonidakis, Fragiskos, Gordon, Scott, Gorwood, Philip, Mayora, Monica Gratacos, Guillaume, Sébastien, Guo, Yiran, Hakonarson, Hakon, Halmi, Katherine A., Hanscombe, Ken B., Hatzikotoulas, Konstantinos, Hebebrand, Johannes, Helder, Sietske G., Henders, Anjali K., Herpertz-Dahlmann, Beate, Herzog, Wolfgang, Hinney, Anke, Horwood, L. John, Hübel, Christopher, Petersen, Liselotte V., Pinto, Dalila, Purves, Kirstin L., Raevuori, Anu, Ramoz, Nicolas, Reichborn-Kjennerud, Ted, Ricca, Valdo, Ripatti, Samuli, Ritschel, Franziska, Roberts, Marion, Rybakowski, Filip, Santonastaso, Paolo, Scherag, André, Scherer, Stephen W., Schmidt, Ulrike, Schork, Nicholas J., Schosser, Alexandra, Seitz, Jochen, Slachtova, Lenka, Slagboom, P. Eline, Slof-Op 't Landt, Margarita C. T., Slopien, Agnieszka, Soranzo, Nicole, Sorbi, Sandro, Southam, Lorraine, Steen, Vidar W., Strober, Michael, Huckins, Laura M., Hudson, James I., Imgart, Hartmut, Inoko, Hidetoshi, Janout, Vladimir, Jiménez-Murcia, Susana, Johnson, Craig, Jordan, Jennifer, Julià, Antonio, Kalsi, Gursharan, Kaminská, Deborah, Kaplan, Allan S., Kaprio, Jaakko, Karhunen, Leila, Karwautz, Andreas, Kas, Martien J. H., Kaye, Walter H., Kennedy, Martin A., Keski-Rahkonen, Anna, Kiezebrink, Kirsty, Kim, Youl-Ri, Kirk, Katherine M., Klareskog, Lars, Klump, Kelly L., Knudsen, Gun Peggy S., Larsen, Janne T., Le Hellard, Stephanie, Leppä, Virpi M., Li, Dong, Lichtenstein, Paul, Lilenfeld, Lisa, Lin, Bochao Danae, Lundervold, Astri, Luykx, Jurjen, Magistretti, Pierre J., Maj, Mario, Mannik, Katrin, Marsal, Sara, Stuber, Garret D., Szatkiewicz, Jin P., Tachmazidou, Ioanna, Tenconi, Elena, Thornton, Laura M., Tortorella, Alfonso, Tozzi, Federica, Treasure, Janet, Tsitsika, Artemis, Tyszkiewicz-Nwafor, Marta, Tziouvas, Konstantinos, van Elburg, Annemarie A., van Furth, Eric F., Wade, Tracey D., Wagner, Gudrun, Walton, Esther, Watson, Hunna J., Whiteman, David C., Wichmann, H. Erich, Widen, Elisabeth, Woodside, D. Blake, Yao, Shuyang, Yilmaz, Zeynep, Zeggini, Eleftheria, Zerwas, Stephanie, Zipfel, Stephan, Jungkunz, Martin, Mullins, N., Kang, J., Campos, A. I., Coleman, J. R. I., Edwards, A. C., Galfalvy, H., Levey, D. F., Lori, A., Shabalin, A., Starnawska, A., Su, M. -H., Watson, H. J., Adams, M., Awasthi, S., Gandal, M., Hafferty, J. D., Hishimoto, A., Kim, M., Okazaki, S., Otsuka, I., Ripke, S., Ware, E. B., Bergen, A. W., Berrettini, W. H., Bohus, M., Brandt, H., Chang, X., Chen, W. J., Chen, H. -C., Crawford, S., Crow, S., Diblasi, E., Duriez, P., Fernandez-Aranda, F., Fichter, M. M., Gallinger, S., Glatt, S. J., Gorwood, P., Guo, Y., Hakonarson, H., Halmi, K. A., Hwu, H. -G., Jain, S., Jamain, S., Jimenez-Murcia, S., Johnson, C., Kaplan, A. S., Kaye, W. H., Keel, P. K., Kennedy, J. L., Klump, K. L., Li, D., Liao, S. -C., Lieb, K., Lilenfeld, L., Liu, C. -M., Magistretti, P. J., Marshall, C. R., Mitchell, J. E., Monson, E. T., Myers, R. M., Pinto, D., Powers, A., Ramoz, N., Roepke, S., Rozanov, V., Scherer, S. W., Schmahl, C., Sokolowski, M., Strober, M., Thornton, L. M., Treasure, J., Tsuang, M. T., Witt, S. H., Woodside, D. B., Yilmaz, Z., Zillich, L., Adolfsson, R., Agartz, I., Air, T. M., Alda, M., Alfredsson, L., Andreassen, O. A., Anjorin, A., Appadurai, V., Soler Artigas, M., Van der Auwera, S., Azevedo, M. H., Bass, N., Bau, C. H. D., Baune, B. T., Bellivier, F., Berger, K., Biernacka, J. M., Bigdeli, T. B., Binder, E. B., Boehnke, M., Boks, M. P., Bosch, R., Braff, D. L., Bryant, R., Budde, M., Byrne, E. M., Cahn, W., Casas, M., Castelao, E., Cervilla, J. A., Chaumette, B., Cichon, S., Corvin, A., Craddock, N., Craig, D., Degenhardt, F., Djurovic, S., Edenberg, H. J., Fanous, A. H., Foo, J. C., Forstner, A. J., Frye, M., Fullerton, J. M., Gatt, J. M., Gejman, P. V., Giegling, I., Grabe, H. J., Green, M. J., Grevet, E. H., Grigoroiu-Serbanescu, M., Gutierrez, B., Guzman-Parra, J., Hamilton, S. P., Hamshere, M. L., Hartmann, A., Hauser, J., Heilmann-Heimbach, S., Hoffmann, P., Ising, M., Jones, I., Jones, L. A., Jonsson, L., Kahn, R. S., Kelsoe, J. R., Kendler, K. S., Kloiber, S., Koenen, K. C., Kogevinas, M., Konte, B., Krebs, M. -O., Landen, M., Lawrence, J., Leboyer, M., Lee, P. H., Levinson, D. F., Liao, C., Lissowska, J., Lucae, S., Mayoral, F., Mcelroy, S. L., Mcgrath, P., Mcguffin, P., Mcquillin, A., Medland, S. E., Mehta, D., Melle, I., Milaneschi, Y., Mitchell, P. B., Molina, E., Morken, G., Mortensen, P. B., Muller-Myhsok, B., Nievergelt, C., Nimgaonkar, V., Nothen, M. M., O'Donovan, M. C., Ophoff, R. A., Owen, M. J., Pato, C., Pato, M. T., Penninx, B. W. J. H., Pimm, J., Pistis, G., Potash, J. B., Power, R. A., Preisig, M., Quested, D., Ramos-Quiroga, J. A., Reif, A., Ribases, M., Richarte, V., Rietschel, M., Rivera, M., Roberts, A., Roberts, G., Rouleau, G. A., Rovaris, D. L., Rujescu, D., Sanchez-Mora, C., Sanders, A. R., Schofield, P. R., Schulze, T. G., Scott, L. J., Serretti, A., Shi, J., Shyn, S. I., Sirignano, L., Sklar, P., Smeland, O. B., Smoller, J. W., Sonuga-Barke, E. J. S., Spalletta, G., Strauss, J. S., Swiatkowska, B., Trzaskowski, M., Turecki, G., Vilar-Ribo, L., Vincent, J. B., Volzke, H., Walters, J. T. R., Shannon Weickert, C., Weickert, T. W., Weissman, M. M., Williams, L. M., Wray, N. R., Zai, C. C., Ashley-Koch, A. E., Beckham, J. C., Hauser, E. R., Hauser, M. A., Kimbrel, N. A., Lindquist, J. H., Mcmahon, B., Oslin, D. W., Qin, X., Mattheisen, M., Abdellaoui, A., Adams, M. J., Agerbo, E., Andlauer, T. F. M., Bacanu, S. -A., Baekvad-Hansen, M., Beekman, A. T. F., Bryois, J., Buttenschon, H. N., Bybjerg-Grauholm, J., Cai, N., Christensen, J. H., Clarke, T. -K., Colodro-Conde, L., Couvy-Duchesne, B., Crawford, G. E., Davies, G., Derks, E. M., Direk, N., Dolan, C. V., Dunn, E. C., Eley, T. C., Escott-Price, V., Hassan Kiadeh, F. F., Finucane, H. K., Frank, J., Gaspar, H. A., Gill, M., Goes, F. S., Gordon, S. D., Weinsheimer, S. M., Wellmann, J., Willemsen, G., Wu, Y., Xi, H. S., Yang, J., Zhang, F., Arolt, V., Boomsma, D. I., Dannlowski, U., Depaulo, J. R., Domenici, E., Domschke, K., Esko, T., Grove, J., Hall, L. S., Hansen, C. S., Hansen, T. F., Herms, S., Hickie, I. B., Homuth, G., Horn, C., Hottenga, J. -J., Hougaard, D. M., Howard, D. M., Jansen, R., Jorgenson, E., Knowles, J. A., Kohane, I. S., Kraft, J., Kretzschmar, W. W., Kutalik, Z., Li, Y., Lind, P. A., Macintyre, D. J., Mackinnon, D. F., Maier, R. M., Maier, W., Marchini, J., Mbarek, H., Middeldorp, C. M., Mihailov, E., Milani, L., Mondimore, F. M., Montgomery, G. W., Mostafavi, S., Nauck, M., Ng, B., Nivard, M. G., Nyholt, D. R., O'Reilly, P. F., Oskarsson, H., Hayward, C., Heath, A. C., Lewis, G., Li, Q. S., Madden, P. A. F., Magnusson, P. K., Martin, N. G., Mcintosh, A. M., Metspalu, A., Mors, O., Nordentoft, M., Paciga, S. A., Pedersen, N. L., Painter, J. N., Pedersen, C. B., Pedersen, M. G., Peterson, R. E., Peyrot, W. J., Posthuma, D., Quiroz, J. A., Qvist, P., Rice, J. P., Riley, B. P., Mirza, S. S., Schoevers, R., Schulte, E. C., Shen, L., Sigurdsson, E., Sinnamon, G. C. B., Smit, J. H., Smith, D. J., Stefansson, H., Steinberg, S., Streit, F., Strohmaier, J., Tansey, K. E., Teismann, H., Teumer, A., Thompson, W., Thomson, P. A., Thorgeirsson, T. E., Traylor, M., Treutlein, J., Trubetskoy, V., Uitterlinden, A. G., Umbricht, D., der Auwera, S. V., van Hemert, A. M., Viktorin, A., Visscher, P. M., Wang, Y., Webb, B. T., Perlis, R. H., Porteous, D. J., Schaefer, C., Stefansson, K., Tiemeier, H., Uher, R., Werge, T., Lewis, C. M., Breen, G., Borglum, A. D., Sullivan, P. F., O'Connell, K. S., Coombes, B., Qiao, Z., Als, T. D., Borte, S., Charney, A. W., Drange, O. K., Gandal, M. J., Hagenaars, S. P., Ikeda, M., Kamitaki, N., Krebs, K., Panagiotaropoulou, G., Schilder, B. M., Sloofman, L. G., Winsvold, B. S., Won, H. -H., Abramova, L., Adorjan, K., Al Eissa, M., Albani, D., Alliey-Rodriguez, N., Antilla, V., Antoniou, A., Baek, J. H., Bauer, M., Beins, E. C., Bergen, S. 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A., Keski-Rahkonen, A., Kiezebrink, K., Kim, Y. -R., Kirk, K. M., Klareskog, L., Knudsen, G. P. S., Larsen, J. T., Le Hellard, S., Leppa, V. M., Lichtenstein, P., Lin, B. D., Lundervold, A., Luykx, J., Maj, M., Mannik, K., Marsal, S., Stuber, G. D., Szatkiewicz, J. P., Tachmazidou, I., Tenconi, E., Tortorella, A., Tozzi, F., Tsitsika, A., Tyszkiewicz-Nwafor, M., Tziouvas, K., van Elburg, A. A., van Furth, E. F., Wade, T. D., Wagner, G., Walton, E., Whiteman, D. C., Wichmann, H. E., Widen, E., Yao, S., Zeggini, E., Zerwas, S., Zipfel, S., Jungkunz, M., Dietl, L., Schwarze, C. E., Dahmen, N., Schott, B. H., Mobascher, A., Crivelli, S., Dennis, M. F., Harvey, P. D., Carter, B. W., Huffman, J. E., Jacobson, D., Madduri, R., Olsen, M. K., Pestian, J., Gaziano, J. M., Muralidhar, S., Ramoni, R., Beckham, J., Chang, K. -M., O'Donnell, C. J., Tsao, P. S., Breeling, J., Huang, G., Romero, J. P. C., Moser, J., Whitbourne, S. B., Brewer, J. V., Aslan, M., Connor, T., Argyres, D. P., Stephens, B., Brophy, M. T., Humphries, D. E., Selva, L. E., Do, N., Shayan, S., Cho, K., Pyarajan, S., Hauser, E., Sun, Y., Zhao, H., Wilson, P., Mcardle, R., Dellitalia, L., Mattocks, K., Harley, J., Zablocki, C. J., Whittle, J., Jacono, F., Gutierrez, S., Gibson, G., Hammer, K., Kaminsky, L., Villareal, G., Kinlay, S., Xu, J., Hamner, M., Mathew, R., Bhushan, S., Iruvanti, P., Godschalk, M., Ballas, Z., Ivins, D., Mastorides, S., Moorman, J., Gappy, S., Klein, J., Ratcliffe, N., Florez, H., Okusaga, O., Murdoch, M., Sriram, P., Yeh, S. S., Tandon, N., Jhala, D., Aguayo, S., Cohen, D., Sharma, S., Liangpunsakul, S., Oursler, K. A., Whooley, M., Ahuja, S., Constans, J., Meyer, P., Greco, J., Rauchman, M., Servatius, R., Gaddy, M., Wallbom, A., Morgan, T., Stapley, T., Sherman, S., Ross, G., Tsao, P., Strollo, P., Boyko, E., Meyer, L., Gupta, S., Huq, M., Fayad, J., Hung, A., Lichy, J., Hurley, R., Robey, B., Striker, R., Erlangsen, A., Kessler, R. C., Porteous, D., Ursano, R. J., Wasserman, D., Coon, H., Demontis, D., Docherty, A. R., Kuo, P. -H., Mann, J. J., Renteria, M. E., Stein, M. B., Willour, V., Psychiatry, Biological Psychology, APH - Methodology, APH - Mental Health, APH - Health Behaviors & Chronic Diseases, AMS - Sports, AMS - Ageing & Vitality, APH - Personalized Medicine, Amsterdam Neuroscience - Complex Trait Genetics, Complex Trait Genetics, Institute for Molecular Medicine Finland, Centre of Excellence in Complex Disease Genetics, Aarno Palotie / Principal Investigator, Genomics of Neurological and Neuropsychiatric Disorders, HUS Psychiatry, Department of Public Health, Clinicum, Nuorisopsykiatria, Faculty Common Matters (Faculty of Social Sciences), Samuli Olli Ripatti / Principal Investigator, Complex Disease Genetics, Biostatistics Helsinki, Anna Keski-Rahkonen / Principal Investigator, Elisabeth Ingrid Maria Widen / Principal Investigator, Genomic Discoveries and Clinical Translation, Internal medicine, Amsterdam Neuroscience - Mood, Anxiety, Psychosis, Stress & Sleep, APH - Digital Health, Mullins N., Kang J., Campos A.I., Coleman J.R.I., Edwards A.C., Galfalvy H., Levey D.F., Lori A., Shabalin A., Starnawska A., Su M.-H., Watson H.J., Adams M., Awasthi S., Gandal M., Hafferty J.D., Hishimoto A., Kim M., Okazaki S., Otsuka I., Ripke S., Ware E.B., Bergen A.W., Berrettini W.H., Bohus M., Brandt H., Chang X., Chen W.J., Chen H.-C., Crawford S., Crow S., DiBlasi E., Duriez P., Fernandez-Aranda F., Fichter M.M., Gallinger S., Glatt S.J., Gorwood P., Guo Y., Hakonarson H., Halmi K.A., Hwu H.-G., Jain S., Jamain S., Jimenez-Murcia S., Johnson C., Kaplan A.S., Kaye W.H., Keel P.K., Kennedy J.L., Klump K.L., Li D., Liao S.-C., Lieb K., Lilenfeld L., Liu C.-M., Magistretti P.J., Marshall C.R., Mitchell J.E., Monson E.T., Myers R.M., Pinto D., Powers A., Ramoz N., Roepke S., Rozanov V., Scherer S.W., Schmahl C., Sokolowski M., Strober M., Thornton L.M., Treasure J., Tsuang M.T., Witt S.H., Woodside D.B., Yilmaz Z., Zillich L., Adolfsson R., Agartz I., Air T.M., Alda M., Alfredsson L., Andreassen O.A., Anjorin A., Appadurai V., Soler 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F., Tsitsika A., Tyszkiewicz-Nwafor M., Tziouvas K., van Elburg A.A., van Furth E.F., Wade T.D., Wagner G., Walton E., Whiteman D.C., Wichmann H.E., Widen E., Yao S., Zeggini E., Zerwas S., Zipfel S., Jungkunz M., Dietl L., Schwarze C.E., Dahmen N., Schott B.H., Mobascher A., Crivelli S., Dennis M.F., Harvey P.D., Carter B.W., Huffman J.E., Jacobson D., Madduri R., Olsen M.K., Pestian J., Gaziano J.M., Muralidhar S., Ramoni R., Beckham J., Chang K.-M., O'Donnell C.J., Tsao P.S., Breeling J., Huang G., Romero J.P.C., Moser J., Whitbourne S.B., Brewer J.V., Aslan M., Connor T., Argyres D.P., Stephens B., Brophy M.T., Humphries D.E., Selva L.E., Do N., Shayan S., Cho K., Pyarajan S., Hauser E., Sun Y., Zhao H., Wilson P., McArdle R., Dellitalia L., Mattocks K., Harley J., Zablocki C.J., Whittle J., Jacono F., Gutierrez S., Gibson G., Hammer K., Kaminsky L., Villareal G., Kinlay S., Xu J., Hamner M., Mathew R., Bhushan S., Iruvanti P., Godschalk M., Ballas Z., Ivins D., Mastorides S., Moorman J., Gappy S., Klein J., Ratcliffe N., Florez H., Okusaga O., Murdoch M., Sriram P., Yeh S.S., Tandon N., Jhala D., Aguayo S., Cohen D., Sharma S., Liangpunsakul S., Oursler K.A., Whooley M., Ahuja S., Constans J., Meyer P., Greco J., Rauchman M., Servatius R., Gaddy M., Wallbom A., Morgan T., Stapley T., Sherman S., Ross G., Tsao P., Strollo P., Boyko E., Meyer L., Gupta S., Huq M., Fayad J., Hung A., Lichy J., Hurley R., Robey B., Striker R., Erlangsen A., Kessler R.C., Porteous D., Ursano R.J., Wasserman D., Coon H., Demontis D., Docherty A.R., Kuo P.-H., Mann J.J., Renteria M.E., Stein M.B., and Willour V.
Subjects: LD SCORE REGRESSION, Genome-wide association study, Suicide, Attempted, 3124 Neurology and psychiatry, 0302 clinical medicine, Risk Factors, Insomnia, Suicide attempt, GWAS, Suïcidi, Depression (differential diagnoses), Cause of death, Psychiatry, 0303 health sciences, Factors de risc en les malalties, Mental Disorders, Genetic Correlation, Genome-wide Association Study, Pleiotropy, Polygenicity, Suicide, Suicide Attempt, DEPRESSION, 3. Good health, Genetic correlation, Genome-Wide Association Study, Humans, Polymorphism, Single Nucleotide, Depressive Disorder, Major, Mental illness, Cohort, SEX, medicine.symptom, Human, medicine.medical_specialty, Risk factors in diseases, BF, Locus (genetics), BEHAVIORS, Psykiatri, EVENTS, 03 medical and health sciences, SDG 3 - Good Health and Well-being, medicine, ddc:610, GENOME-WIDE ASSOCIATION, IDEATION, Socioeconomic status, METAANALYSIS, Biological Psychiatry, 030304 developmental biology, business.industry, Risk Factor, Genetic architecture, THOUGHTS, RC0321, business, Malalties mentals, 030217 neurology & neurosurgery
Abstract: Statistical analyses were carried out on the NL Genetic Cluster Computer (http://www.geneticcluster.org) hosted by SURFsara and the Mount Sinai high performance computing cluster (http://hpc.mssm.edu), which is supported by the Office of Research Infrastructure of the National Institutes of Health (Grant Nos. S10OD018522 and S10OD026880). This work was conducted in part using the resources of the Advanced Computing Center for Research and Education at Vanderbilt University, Nashville, TN. This work was funded by the National Institutes of Health (Grant Nos. R01MH116269 and R01MH121455 [to DMR]), NIGMS of the National Institutes of Health (Grant No. T32GM007347 [to JK]), and the Brain & Behavior Research Foundation (NARSAD Young Investigator Award No. 29551 [to NM])., BACKGROUND: Suicide is a leading cause of death worldwide, and nonfatal suicide attempts, which occur far more frequently, are a major source of disability and social and economic burden. Both have substantial genetic etiology, which is partially shared and partially distinct from that of related psychiatric disorders. METHODS: We conducted a genome-wide association study (GWAS) of 29,782 suicide attempt (SA) cases and 519,961 controls in the International Suicide Genetics Consortium (ISGC). The GWAS of SA was conditioned on psychiatric disorders using GWAS summary statistics via multitrait-based conditional and joint analysis, to remove genetic effects on SA mediated by psychiatric disorders. We investigated the shared and divergent genetic architectures of SA, psychiatric disorders, and other known risk factors. RESULTS: Two loci reached genome-wide significance for SA: the major histocompatibility complex and an intergenic locus on chromosome 7, the latter of which remained associated with SA after conditioning on psychiatric disorders and replicated in an independent cohort from the Million Veteran Program. This locus has been implicated in risk-taking behavior, smoking, and insomnia. SA showed strong genetic correlation with psychiatric disorders, particularly major depression, and also with smoking, pain, risk-taking behavior, sleep disturbances, lower educational attainment, reproductive traits, lower socioeconomic status, and poorer general health. After conditioning on psychiatric disorders, the genetic correlations between SA and psychiatric disorders decreased, whereas those with nonpsychiatric traits remained largely unchanged. CONCLUSIONS: Our results identify a risk locus that contributes more strongly to SA than other phenotypes and suggest a shared underlying biology between SA and known risk factors that is not mediated by psychiatric disorders., Office of Research Infrastructure of the National Institutes of Health S10OD018522 S10OD026880, United States Department of Health & Human Services, National Institutes of Health (NIH) - USA R01MH116269 R01MH121455, NIH National Institute of General Medical Sciences (NIGMS) T32GM007347 NARSAD 29551
Published: 2022
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40. Cortical and subcortical neuroanatomical signatures of schizotypy in 3004 individuals assessed in a worldwide ENIGMA study

Author: Igor Nenadic, André Aleman, Martin Debbané, Verena Enneking, Ashley Moyett, Tilo Kircher, Elisabeth J. Leehr, Axel Krug, Carina Hülsmann, Paul M. Thompson, Bernhard T. Baune, Benazir Hodzic-Santor, Imke Lemmers-Jansen, Dominik Grotegerd, Iris E. C. Sommer, Yi Wang, Alex Fornito, Casey Paquola, Irina Lebedeva, Petya Kozhuharova, Yann Quidé, Gemma Modinos, Kristina Wiebels, Raymond C.K. Chan, Preethi Premkumar, Kelly M. J. Diederen, Mark A. Bellgrove, Lukasz Smigielski, Boris C. Bernhardt, Matthias Kirschner, Phillip Grant, Jessica A. Turner, Jeggan Tiego, Tina Meller, Jan-Bernard C Marsman, Paul Allen, Veena Kumari, Thomas J. Spencer, Haeme R.P. Park, Alain Dagher, Melissa J. Green, Theo G.M. van Erp, Paul C. Fletcher, Mathilde Antoniades, Ulrich Ettinger, David M. A. Mehler, Christian Gaser, Melodie Derome, Aurina Arnatkeviciute, Christos Pantelis, James Gilleen, Melissa Klug, Pamela DeRosse, Sanne Schuite-Koops, Wulf Rössler, Alexander Tomyshev, Stefan Kaiser, Anne-Kathrin Fett, Sara Larivière, Katharina Koch, Joscha Böhnlein, Anna Mukhorina, Bianca Besteher, Marius Gruber, Udo Dannlowski, Harald Kugel, Clinical Developmental Psychology, APH - Mental Health, Kirschner, Matthias [0000-0002-9486-1439], Fornito, Alex [0000-0003-0866-3477], Bellgrove, Mark A [0000-0003-0186-8349], Tiego, Jeggan [0000-0001-7835-6398], Dannlowski, Udo [0000-0002-0623-3759], Kugel, Harald [0000-0002-4349-1984], Böhnlein, Joscha [0000-0002-9870-5599], DeRosse, Pamela [0000-0003-0823-8163], Pantelis, Christos [0000-0002-9565-0238], Chan, Raymond [0000-0001-7571-6933], Kumari, Veena [0000-0002-9635-5505], Wiebels, Kristina [0000-0002-5360-5965], Mukhorina, Anna [0000-0003-2369-5493], Larivière, Sara [0000-0001-5701-1307], Dagher, Alain [0000-0002-0945-5779], van Erp, Theo GM [0000-0002-2465-2797], Turner, Jessica A [0000-0003-0076-8434], Modinos, Gemma [0000-0002-7870-066X], Apollo - University of Cambridge Repository, Perceptual and Cognitive Neuroscience (PCN), Clinical Cognitive Neuropsychiatry Research Program (CCNP), Movement Disorder (MD), and Clinical Neuropsychology
Subjects: Male, Psychosis, Bipolar Disorder, Schizotypy, medicine.medical_treatment, Population, Ventromedial prefrontal cortex, BF, psychology, Schizotypal Personality Disorder, 03 medical and health sciences, Cellular and Molecular Neuroscience, 0302 clinical medicine, medicine, Humans, Bipolar disorder, Antipsychotic, education, Molecular Biology, education.field_of_study, business.industry, Brain morphometry, medicine.disease, Magnetic Resonance Imaging, 030227 psychiatry, schizophrenia, Psychiatry and Mental health, medicine.anatomical_structure, Psychotic Disorders, Schizophrenia, RC0321, Female, business, Neuroscience, 030217 neurology & neurosurgery
Abstract: Neuroanatomical abnormalities have been reported along a continuum from at-risk stages, including high schizotypy, to early and chronic psychosis. However, a comprehensive neuroanatomical mapping of schizotypy remains to be established. The authors conducted the first large-scale meta-analyses of cortical and subcortical morphometric patterns of schizotypy in healthy individuals, and compared these patterns with neuroanatomical abnormalities observed in major psychiatric disorders. The sample comprised 3004 unmedicated healthy individuals (12–68 years, 46.5% male) from 29 cohorts of the worldwide ENIGMA Schizotypy working group. Cortical and subcortical effect size maps with schizotypy scores were generated using standardized methods. Pattern similarities were assessed between the schizotypy-related cortical and subcortical maps and effect size maps from comparisons of schizophrenia (SZ), bipolar disorder (BD) and major depression (MDD) patients with controls. Thicker right medial orbitofrontal/ventromedial prefrontal cortex (mOFC/vmPFC) was associated with higher schizotypy scores (r = 0.067, pFDR = 0.02). The cortical thickness profile in schizotypy was positively correlated with cortical abnormalities in SZ (r = 0.285, pspin = 0.024), but not BD (r = 0.166, pspin = 0.205) or MDD (r = −0.274, pspin = 0.073). The schizotypy-related subcortical volume pattern was negatively correlated with subcortical abnormalities in SZ (rho = −0.690, pspin = 0.006), BD (rho = −0.672, pspin = 0.009), and MDD (rho = −0.692, pspin = 0.004). Comprehensive mapping of schizotypy-related brain morphometry in the general population revealed a significant relationship between higher schizotypy and thicker mOFC/vmPFC, in the absence of confounding effects due to antipsychotic medication or disease chronicity. The cortical pattern similarity between schizotypy and schizophrenia yields new insights into a dimensional neurobiological continuity across the extended psychosis phenotype.
Published: 2021
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41. Polygenic risk for schizophrenia as a moderator of associations between childhood trauma and schizotypy

Author: Emiliana Tonini, Oliver Watkeys, Yann Quidé, Thomas J. Whitford, Murray J. Cairns, and Melissa J. Green
Subjects: Schizotypal Personality Disorder, Pharmacology, Multifactorial Inheritance, Psychotic Disorders, Adverse Childhood Experiences, Schizophrenia, Humans, Biological Psychiatry
Abstract: Recent evidence shows that genetic and environmental risk factors for psychotic disorders are associated with higher levels of schizotypy (or psychosis proneness) in the general population. However, little is known about how these risk factors interact. We specifically examined whether genetic loading for schizophrenia moderates the association between childhood trauma severity and schizotypy. Schizotypy was measured using the Schizotypal Personality Questionnaire (SPQ), and childhood trauma severity was measured with the Childhood Trauma Questionnaire (CTQ) among a total of 168 participants (comprising 51 healthy individuals, 56 diagnosed with schizophrenia, and 61 with bipolar disorder). Polygenic risk scores (PRS) for schizophrenia were calculated for all participants and examined as a potential moderator of associations between total scores on the CTQ and schizotypy total scores and dimensions (i.e., cognitive-perceptual, interpersonal, disorganised). Multiple linear regression models revealed associations between childhood trauma and all dimensions of schizotypy, but no associations between PRS and schizotypy. A significant interaction between PRS and childhood trauma was evident for the interpersonal and disorganised dimensions of schizotypy, as well as the total score, reflecting positive associations between childhood trauma severity and these two schizotypal dimensions, only for individuals with low or average PRS for schizophrenia. This suggests that trauma may be able to increase risk for psychosis independently of any genetic vulnerability. The present findings are consistent with the idea of several risk pathways for the development of psychotic disorders.
Published: 2022
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42. Profiles of Resilience from Early to Middle Childhood among Children Known to Child Protection Services

Author: Patrycja J. Piotroswka, Ilan Katz, Felicity Harris, Tyson Whitten, Merran Butler, Kristin R. Laurens, Stacy Tzoumakis, Vaughan J. Carr, and Melissa J. Green
Subjects: Clinical Psychology, Child protection, Social work, Developmental and Educational Psychology, Resilience (network), Psychology, Middle childhood, Developmental psychology
Abstract: The processes facilitating resilience are likely to be influenced by individual, familial and contextual factors that are dynamic across the life-course. These factors have been less studied in relation to resilience profiles evident in the developmental period between early to middle childhood, relative to later periods of adolescence or adulthood.This study examined factors associated withFactors associated with resilience profiles included being female, and personality characteristics of openness and extraversion; other factors associated withResilience processes appear to involve a complex interplay between individual, family, and community characteristics requiring interagency support.
Published: 2021

43. Epigenetic signatures relating to disease-associated genotypic burden in familial risk of bipolar disorder

Author: Sonia, Hesam-Shariati, Bronwyn J, Overs, Gloria, Roberts, Claudio, Toma, Oliver J, Watkeys, Melissa J, Green, Kerrie D, Pierce, Howard J, Edenberg, Holly C, Wilcox, Emma K, Stapp, Melvin G, McInnis, Leslie A, Hulvershorn, John I, Nurnberger, Peter R, Schofield, Philip B, Mitchell, and Janice M, Fullerton
Subjects: Depressive Disorder, Major, Multifactorial Inheritance, Bipolar Disorder, Adolescent, HLA Antigens, Valine-tRNA Ligase, Humans, Genetic Predisposition to Disease, Epigenesis, Genetic, Genome-Wide Association Study
Abstract: Environmental factors contribute to risk of bipolar disorder (BD), but how environmental factors impact the development of psychopathology within the context of elevated genetic risk is unknown. We herein sought to identify epigenetic signatures operating in the context of polygenic risk for BD in young people at high familial risk (HR) of BD. Peripheral blood-derived DNA was assayed using Illumina PsychArray, and Methylation-450K or -EPIC BeadChips. Polygenic risk scores (PRS) were calculated using summary statistics from recent genome-wide association studies for BD, major depressive disorder (MDD) and cross-disorder (meta-analysis of eight psychiatric disorders). Unrelated HR participants of European ancestry (n = 103) were stratified based on their BD-PRS score within the HR-population distribution, and the top two quintiles (High-BD-PRS; n = 41) compared against the bottom two quintiles (Low-BD-PRS; n = 41). The High-BD-PRS stratum also had higher mean cross-disorder-PRS and MDD-PRS (ANCOVA p = 0.035 and p = 0.024, respectively). We evaluated DNA methylation differences between High-BD-PRS and Low-BD-PRS strata using linear models. One differentially methylated probe (DMP) (cg00933603; p = 3.54 × 10
Published: 2021

44. Cumulative sociodemographic disadvantage partially mediates associations between childhood trauma and schizotypy

Author: Melissa J. Green, Thomas J. Whitford, Yann Quidé, and Emiliana Tonini
Subjects: Adult, Psychosis, Mediation (statistics), Bipolar Disorder, media_common.quotation_subject, Schizotypy, Population, Schizoaffective disorder, Schizotypal Personality Disorder, Adverse Childhood Experiences, medicine, Personality, Humans, Bipolar disorder, education, Child, media_common, education.field_of_study, General Medicine, medicine.disease, Clinical Psychology, Psychotic Disorders, Schizophrenia, Psychology, Clinical psychology
Abstract: Objectives Risk for psychosis in the general population is characterized by a set of multidimensional traits that are referred to as schizotypy. Higher levels of schizotypy are associated with socioeconomic disadvantage and childhood trauma, just as these risk factors are associated with schizophrenia and bipolar disorder. Here, we set out to investigate whether cumulative sociodemographic disadvantage mediates associations between childhood trauma and schizotypy in adulthood. Methods A sociodemographic cumulative risk (SDCR) score was derived from six risk indices spanning employment, education, income, socioeconomic status, marital, and living circumstances for 197 participants that included both healthy (n = 57) and clinical samples with schizophrenia or schizoaffective disorder (n = 65) or bipolar disorder (n = 75). A series of multiple linear regressions was used to examine the direct and indirect associations among childhood trauma (measured with the Childhood Trauma Questionnaire), the SDCR index, and levels of schizotypy (measured with the Schizotypal Personality Questionnaire). Results Schizotypy was independently associated with trauma and the SDCR index. In addition, the SDCR index partially mediated associations between trauma and schizotypy. Conclusions These findings in a mixed sample of healthy and clinical participants represent the full spectrum of schizotypy across health and illness and suggest that effects of childhood trauma on schizotypal personality organization may operate via cumulative socioeconomic disadvantage in adulthood. Practitioner points The strong associations between trauma and schizotypy suggest that systematic health screening of children exposed to early life trauma may assist to identify those at risk of developing psychosis. Clinicians should pay attention to various indicators of sociodemographic disadvantage in patients prone to psychosis, in addition to any exposure to trauma during childhood.
Published: 2021

45. Parental and community risk factors for childhood self-harm thoughts and behaviours

Author: Kirstie O'Hare, Oliver Watkeys, Tyson Whitten, Kimberlie Dean, Kristin R. Laurens, Felicity Harris, Vaughan J. Carr, and Melissa J. Green
Subjects: Parents, Psychiatry and Mental health, Clinical Psychology, Risk Factors, Mental Disorders, Prevalence, Humans, Child, Self-Injurious Behavior, Suicidal Ideation
Abstract: Childhood self-harm is rare but increasing in frequency. Little is known about risk factors specifically for self-harm in preteen children.We examined self-harm thoughts and behaviours in children aged 3-14 years in association with parental and community-level risk factors, using a large general population-based record linkage sample (n = 74,479).Parental factors were strongly associated with childhood self-harm, with over three-quarters of children with self-harm having a parent with a history of mental disorder and/or criminal offending. Community-level factors (socioeconomic deprivation, remote or regional location, and neighbourhood crime rate) were not associated with childhood self-harm after adjustment for confounding factors.Measures of self-harm thoughts and behaviours derived from administrative data likely underestimate the prevalence of self-harm in the population.Intergenerational transmission of risk factors is likely an important contributor to childhood self-harm.
Published: 2021

46. Cell type-specific manifestations of cortical thickness heterogeneity in schizophrenia

Author: Maria A. Di Biase, Michael P. Geaghan, William R. Reay, Jakob Seidlitz, Cynthia Shannon Weickert, Alice Pébay, Melissa J. Green, Yann Quidé, Joshua R. Atkins, Michael J. Coleman, Sylvain Bouix, Evdokiya E. Knyazhanskaya, Amanda E. Lyall, Ofer Pasternak, Marek Kubicki, Yogesh Rathi, Andrew Visco, Megan Gaunnac, Jinglei Lv, Raquelle I. Mesholam-Gately, Kathryn E. Lewandowski, Daphne J. Holt, Matcheri S. Keshavan, Christos Pantelis, Dost Öngür, Alan Breier, Murray J. Cairns, Martha E. Shenton, and Andrew Zalesky
Subjects: Cerebral Cortex, Cellular and Molecular Neuroscience, Psychiatry and Mental health, Multifactorial Inheritance, Schizophrenia, Brain, Endothelial Cells, Humans, Molecular Biology, Magnetic Resonance Imaging
Abstract: Brain morphology differs markedly between individuals with schizophrenia, but the cellular and genetic basis of this heterogeneity is poorly understood. Here, we sought to determine whether cortical thickness (CTh) heterogeneity in schizophrenia relates to interregional variation in distinct neural cell types, as inferred from established gene expression data and person-specific genomic variation. This study comprised 1849 participants in total, including a discovery (140 cases and 1267 controls) and a validation cohort (335 cases and 185 controls). To characterize CTh heterogeneity, normative ranges were established for 34 cortical regions and the extent of deviation from these ranges was measured for each individual with schizophrenia. CTh deviations were explained by interregional gene expression levels of five out of seven neural cell types examined: (1) astrocytes; (2) endothelial cells; (3) oligodendrocyte progenitor cells (OPCs); (4) excitatory neurons; and (5) inhibitory neurons. Regional alignment between CTh alterations with cell type transcriptional maps distinguished broad patient subtypes, which were validated against genomic data drawn from the same individuals. In a predominantly neuronal/endothelial subtype (22% of patients), CTh deviations covaried with polygenic risk for schizophrenia (sczPRS) calculated specifically from genes marking neuronal and endothelial cells (r = −0.40, p = 0.010). Whereas, in a predominantly glia/OPC subtype (43% of patients), CTh deviations covaried with sczPRS calculated from glia and OPC-linked genes (r = −0.30, p = 0.028). This multi-scale analysis of genomic, transcriptomic, and brain phenotypic data may indicate that CTh heterogeneity in schizophrenia relates to inter-individual variation in cell-type specific functions. Decomposing heterogeneity in relation to cortical cell types enables prioritization of schizophrenia subsets for future disease modeling efforts.
Published: 2021

47. Familial clustering of birth risk for adverse childhood outcomes

Author: Oliver J, Watkeys, Kimberlie, Dean, Kristin R, Laurens, Felicity, Harris, Vaughan J, Carr, and Melissa J, Green
Subjects: Male, Pregnancy, Risk Factors, Cluster Analysis, Humans, Female, Genetic Predisposition to Disease, Longitudinal Studies, Prospective Studies, Child
Abstract: To identify classes of children exposed to distinct clusters of perinatal and familial risk factors at the time of birth, and examine relationships between class membership and a variety of adverse outcomes in childhood.A prospective longitudinal study of children (and their parents) born between 2002 and 2004 and who have been followed-up until 12-13 years of age. A combination of latent class analysis and logistic regression analyses were used.Adverse developmental, social, and mental health outcomes in early and middle childhood were greatest for children with 'pervasive familial risk' (i.e., parental mental illness, parental criminality, and perinatal risk factors) at the time of birth; some associations were stronger among girls.Pervasive exposure to multiple risk factors in the pre- and perinatal period increases the risk of adverse outcomes in childhood. Future interventions should tailor strategies to address unique combinations of adverse risk exposures in vulnerable families.
Published: 2021

48. A Systematic Review of Studies Reporting Data-Driven Cognitive Subtypes across the Psychosis Spectrum

Author: Leah Girshkin, Oliver J. Watkeys, Yann Quidé, Kyle Kremerskothen, and Melissa J. Green
Subjects: Adult, Male, Psychosis, Bipolar Disorder, Schizoaffective disorder, Neuropsychological Tests, 050105 experimental psychology, 03 medical and health sciences, Cognition, 0302 clinical medicine, medicine, Humans, 0501 psychology and cognitive sciences, Bipolar disorder, Cognitive deficit, 05 social sciences, Neuropsychology, Middle Aged, medicine.disease, Neuropsychology and Physiological Psychology, Psychotic Disorders, Schizophrenia, Endophenotype, Female, Schizophrenic Psychology, medicine.symptom, Psychology, 030217 neurology & neurosurgery, Clinical psychology
Abstract: The delineation of cognitive subtypes of schizophrenia and bipolar disorder may offer a means of determining shared genetic markers and neuropathology among individuals with these conditions. We systematically reviewed the evidence from published studies reporting the use of data-driven (i.e., unsupervised) clustering methods to delineate cognitive subtypes among adults diagnosed with schizophrenia, schizoaffective disorder, or bipolar disorder. We reviewed 24 studies in total, contributing data to 13 analyses of schizophrenia spectrum patients, 8 analyses of bipolar disorder, and 5 analyses of mixed samples of schizophrenia and bipolar disorder participants. Studies of bipolar disorder most consistently revealed a 3-cluster solution, comprising a subgroup with 'near-normal' (cognitively spared) cognition and two other subgroups demonstrating graded deficits across cognitive domains. In contrast, there was no clear consensus regarding the number of cognitive subtypes among studies of cognitive subtypes in schizophrenia, while four of the five studies of mixed diagnostic groups reported a 4-cluster solution. Common to all cluster solutions was a severe cognitive deficit subtype with cognitive impairments of moderate to large effect size relative to healthy controls. Our review highlights several key factors (e.g., symptom profile, sample size, statistical procedures, and cognitive domains examined) that may influence the results of data-driven clustering methods, and which were largely inconsistent across the studies reviewed. This synthesis of findings suggests caution should be exercised when interpreting the utility of particular cognitive subtypes for biological investigation, and demonstrates much heterogeneity among studies using unsupervised clustering approaches to cognitive subtyping within and across the psychosis spectrum.
Published: 2019
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49. Structural brain morphometry associated with theory of mind in bipolar disorder and schizophrenia

Author: Melissa J. Green, Yann Quidé, and Camille Wilhelmi
Subjects: Adult, Male, Psychosis, medicine.medical_specialty, Bipolar Disorder, Bipolar I disorder, Theory of Mind, Precuneus, Neuropsychological Tests, Audiology, Temporal lobe, Social Skills, 03 medical and health sciences, Cognition, 0302 clinical medicine, Social cognition, medicine, Humans, Bipolar disorder, Gray Matter, General Psychology, Brain morphometry, Brain, medicine.disease, Magnetic Resonance Imaging, 030227 psychiatry, medicine.anatomical_structure, Posterior cingulate, Schizophrenia, Female, Psychology, 030217 neurology & neurosurgery
Abstract: Schizophrenia (SZ) and bipolar I disorder (BD) share common functional and structural brain abnormalities, as well as various degrees of social cognitive deficits, suggesting shared brain mechanisms. This study examined the relationship between social cognitive skills and structural brain integrity in 60 cases with SZ, 65 cases with psychotic BD, and 61 healthy controls (HCs). All participants underwent structural MRI and completed The Awareness of Social Inference Test (TASIT). Associations between social cognitive performance on each task of the TASIT (Emotion Recognition, Theory of Mind [ToM], and Complex ToM) and indices of gray matter volume and cortical thickness were investigated within three separate groups comprising (a) all cases with a history of psychosis (independently of their diagnostic status), (b) each diagnostic category separately, and (c) an HC group. Cases with psychosis showed worse social cognitive performance compared to the HC group, and SZ cases performed worse than BD on all ToM tasks, but not the Emotion Recognition subtest. Poor ToM performance was associated with thinner anterior temporal lobe in the combined group of cases with psychosis, and with decreased volume of the left fusiform gyrus/cerebellum in the HC group. In the BD group alone, poor ToM performance was associated with similar pattern of thinner anterior temporal lobe, as well as with increased volume in the mid- and posterior cingulate cortex/precuneus. However, there were no associations between brain morphometry and social cognition in the SZ group when considered alone. Taken together, ToM behavioral deficits were associated with thinner right anterior temporal lobe, a critical region from a larger affective ToM network among all cases with psychosis, but aberrant morphology of brain regions key for self-processing were specific to the BD group. These findings may have important implications for targeted interventions for the affective social brain network in BD.
Published: 2019
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50. Mental disorders in children known to child protection services during early childhood

Author: Kristin R. Laurens, Felicity Harris, Amanda L. Neil, Ilan Katz, Gabrielle Hindmarsh, Maina Kariuki, Marilyn Chilvers, Melissa J. Green, and Vaughan J. Carr
Subjects: Male, Parents, medicine.medical_specialty, Adolescent, Population health, 03 medical and health sciences, 0302 clinical medicine, Child and adolescent psychiatry, medicine, Humans, Child Abuse, 030212 general & internal medicine, Social determinants of health, Early childhood, Child, Psychiatry, Retrospective Studies, business.industry, Child Protective Services, Mental Disorders, General Medicine, Odds ratio, Mental illness, medicine.disease, Child development, 3. Good health, Logistic Models, Socioeconomic Factors, Child protection, Female, New South Wales, business
Abstract: Objectives : To examine associations between being the subject of child protection reports in early childhood and diagnoses of mental disorders during middle childhood, by level of service response. Design, setting, participants : Retrospective analysis of linked New South Wales administrative data, 2001–2016, for a population cohort of children (mean age in 2016, 13.2 years; SD, 0.37 years) enrolled in the longitudinal NSW Child Development Study (NSW-CDS), wave 2 linkage. Main outcome measures : Associations between being the subject of a child protection report (any, and by level of child protection response) during early childhood (birth to 6 years of age) and diagnoses of mental disorders during middle childhood (6–14 years). Results : 13 796 of 74 462 children in the NSW-CDS (18.5%) had been the subjects of reports to child protection services during early childhood: 1148 children had been placed in out-of-home care at least once, and 1680 had been the subjects of substantiated risk-of- significant- harm reports but were not placed in care, while 9161 had non-substantiated reports, and 1807 had reports of facts that did not reach the threshold for significant harm. After adjusting for sex, socio-economic disadvantage, perinatal complications, and parental mental illness, early childhood contact with protection services was associated with increased frequency of being diagnosed with a mental disorder during middle childhood (adjusted odds ratio [aOR], 2.72; 95% CI, 2.51–2.95). The frequency was highest for children who had been placed in out-of-home care (aOR, 5.25; 95% CI, 4.46–6.18). Conclusion : Childhood-onset mental disorders are more frequently diagnosed in children who come to the attention of child protection services during early childhood, particularly in children placed in out-of- home care.
Published: 2019
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