15 results
Unraveling the genetic architecture of major depressive disorder: merits and pitfalls of the approaches used in genome-wide association studies
- I. Schwabe, Y. Milaneschi, Z. Gerring, P. F. Sullivan, E. Schulte, N. P. Suppli, J. G. Thorp, E. M. Derks, C. M. Middeldorp
-
- Journal:
- Psychological Medicine / Volume 49 / Issue 16 / December 2019
- Published online by Cambridge University Press:
- 27 September 2019, pp. 2646-2656
-
- Article
-
- You have access Access
- Open access
- HTML
- Export citation
-
To identify genetic risk loci for major depressive disorder (MDD), two broad study design approaches have been applied: (1) to maximize sample size by combining data from different phenotype assessment modalities (e.g. clinical interview, self-report questionnaires) and (2) to reduce phenotypic heterogeneity through selecting more homogenous MDD subtypes. The value of these strategies has been debated. In this review, we summarize the most recent findings of large genomic studies that applied these approaches, and we highlight the merits and pitfalls of both approaches with particular attention to methodological and psychometric issues. We also discuss the results of analyses that investigated the heterogeneity of MDD. We conclude that both study designs are essential for further research. So far, increasing sample size has led to the identification of a relatively high number of genomic loci linked to depression. However, part of the identified variants may be related to a phenotype common to internalizing disorders and related traits. As such, samples containing detailed clinical information are needed to dissect depression heterogeneity and enable the potential identification of variants specific to a more restricted MDD phenotype. A balanced portfolio reconciling both study design approaches is the optimal approach to progress further in unraveling the genetic architecture of depression.
Evidence of causal effect of major depression on alcohol dependence: findings from the psychiatric genomics consortium
- Renato Polimanti, Roseann E. Peterson, Jue-Sheng Ong, Stuart MacGregor, Alexis C. Edwards, Toni-Kim Clarke, Josef Frank, Zachary Gerring, Nathan A. Gillespie, Penelope A. Lind, Hermine H. Maes, Nicholas G. Martin, Hamdi Mbarek, Sarah E. Medland, Fabian Streit, Major Depressive Disorder Working Group of the Psychiatric Genomics Consortium, Substance Use Disorder Working Group of the Psychiatric Genomics Consortium, 23andMe Research Team, Arpana Agrawal, Howard J. Edenberg, Kenneth S. Kendler, Cathryn M. Lewis, Patrick F. Sullivan, Naomi R. Wray, Joel Gelernter, Eske M. Derks
-
- Journal:
- Psychological Medicine / Volume 49 / Issue 7 / May 2019
- Published online by Cambridge University Press:
- 01 April 2019, pp. 1218-1226
-
- Article
- Export citation
-
Background
Despite established clinical associations among major depression (MD), alcohol dependence (AD), and alcohol consumption (AC), the nature of the causal relationship between them is not completely understood. We leveraged genome-wide data from the Psychiatric Genomics Consortium (PGC) and UK Biobank to test for the presence of shared genetic mechanisms and causal relationships among MD, AD, and AC.
MethodsLinkage disequilibrium score regression and Mendelian randomization (MR) were performed using genome-wide data from the PGC (MD: 135 458 cases and 344 901 controls; AD: 10 206 cases and 28 480 controls) and UK Biobank (AC-frequency: 438 308 individuals; AC-quantity: 307 098 individuals).
ResultsPositive genetic correlation was observed between MD and AD (rgMD−AD = + 0.47, P = 6.6 × 10−10). AC-quantity showed positive genetic correlation with both AD (rgAD−AC quantity = + 0.75, P = 1.8 × 10−14) and MD (rgMD−AC quantity = + 0.14, P = 2.9 × 10−7), while there was negative correlation of AC-frequency with MD (rgMD−AC frequency = −0.17, P = 1.5 × 10−10) and a non-significant result with AD. MR analyses confirmed the presence of pleiotropy among these four traits. However, the MD-AD results reflect a mediated-pleiotropy mechanism (i.e. causal relationship) with an effect of MD on AD (beta = 0.28, P = 1.29 × 10−6). There was no evidence for reverse causation.
ConclusionThis study supports a causal role for genetic liability of MD on AD based on genetic datasets including thousands of individuals. Understanding mechanisms underlying MD-AD comorbidity addresses important public health concerns and has the potential to facilitate prevention and intervention efforts.
Letter to the Editor: Schizophrenia does not represent the extreme of a normally distributed trait
- D. Curtis, E. M. Derks
-
- Journal:
- Psychological Medicine / Volume 48 / Issue 3 / February 2018
- Published online by Cambridge University Press:
- 29 August 2017, pp. 521-522
-
- Article
-
- You have access Access
- HTML
- Export citation
Contributors
-
- By Mitchell Aboulafia, Frederick Adams, Marilyn McCord Adams, Robert M. Adams, Laird Addis, James W. Allard, David Allison, William P. Alston, Karl Ameriks, C. Anthony Anderson, David Leech Anderson, Lanier Anderson, Roger Ariew, David Armstrong, Denis G. Arnold, E. J. Ashworth, Margaret Atherton, Robin Attfield, Bruce Aune, Edward Wilson Averill, Jody Azzouni, Kent Bach, Andrew Bailey, Lynne Rudder Baker, Thomas R. Baldwin, Jon Barwise, George Bealer, William Bechtel, Lawrence C. Becker, Mark A. Bedau, Ernst Behler, José A. Benardete, Ermanno Bencivenga, Jan Berg, Michael Bergmann, Robert L. Bernasconi, Sven Bernecker, Bernard Berofsky, Rod Bertolet, Charles J. Beyer, Christian Beyer, Joseph Bien, Joseph Bien, Peg Birmingham, Ivan Boh, James Bohman, Daniel Bonevac, Laurence BonJour, William J. Bouwsma, Raymond D. Bradley, Myles Brand, Richard B. Brandt, Michael E. Bratman, Stephen E. Braude, Daniel Breazeale, Angela Breitenbach, Jason Bridges, David O. Brink, Gordon G. Brittan, Justin Broackes, Dan W. Brock, Aaron Bronfman, Jeffrey E. Brower, Bartosz Brozek, Anthony Brueckner, Jeffrey Bub, Lara Buchak, Otavio Bueno, Ann E. Bumpus, Robert W. Burch, John Burgess, Arthur W. Burks, Panayot Butchvarov, Robert E. Butts, Marina Bykova, Patrick Byrne, David Carr, Noël Carroll, Edward S. Casey, Victor Caston, Victor Caston, Albert Casullo, Robert L. Causey, Alan K. L. Chan, Ruth Chang, Deen K. Chatterjee, Andrew Chignell, Roderick M. Chisholm, Kelly J. Clark, E. J. Coffman, Robin Collins, Brian P. Copenhaver, John Corcoran, John Cottingham, Roger Crisp, Frederick J. Crosson, Antonio S. Cua, Phillip D. Cummins, Martin Curd, Adam Cureton, Andrew Cutrofello, Stephen Darwall, Paul Sheldon Davies, Wayne A. Davis, Timothy Joseph Day, Claudio de Almeida, Mario De Caro, Mario De Caro, John Deigh, C. F. Delaney, Daniel C. Dennett, Michael R. DePaul, Michael Detlefsen, Daniel Trent Devereux, Philip E. Devine, John M. Dillon, Martin C. Dillon, Robert DiSalle, Mary Domski, Alan Donagan, Paul Draper, Fred Dretske, Mircea Dumitru, Wilhelm Dupré, Gerald Dworkin, John Earman, Ellery Eells, Catherine Z. Elgin, Berent Enç, Ronald P. Endicott, Edward Erwin, John Etchemendy, C. Stephen Evans, Susan L. Feagin, Solomon Feferman, Richard Feldman, Arthur Fine, Maurice A. Finocchiaro, William FitzPatrick, Richard E. Flathman, Gvozden Flego, Richard Foley, Graeme Forbes, Rainer Forst, Malcolm R. Forster, Daniel Fouke, Patrick Francken, Samuel Freeman, Elizabeth Fricker, Miranda Fricker, Michael Friedman, Michael Fuerstein, Richard A. Fumerton, Alan Gabbey, Pieranna Garavaso, Daniel Garber, Jorge L. A. Garcia, Robert K. Garcia, Don Garrett, Philip Gasper, Gerald Gaus, Berys Gaut, Bernard Gert, Roger F. Gibson, Cody Gilmore, Carl Ginet, Alan H. Goldman, Alvin I. Goldman, Alfonso Gömez-Lobo, Lenn E. Goodman, Robert M. Gordon, Stefan Gosepath, Jorge J. E. Gracia, Daniel W. Graham, George A. Graham, Peter J. Graham, Richard E. Grandy, I. Grattan-Guinness, John Greco, Philip T. Grier, Nicholas Griffin, Nicholas Griffin, David A. Griffiths, Paul J. Griffiths, Stephen R. Grimm, Charles L. Griswold, Charles B. Guignon, Pete A. Y. Gunter, Dimitri Gutas, Gary Gutting, Paul Guyer, Kwame Gyekye, Oscar A. Haac, Raul Hakli, Raul Hakli, Michael Hallett, Edward C. Halper, Jean Hampton, R. James Hankinson, K. R. Hanley, Russell Hardin, Robert M. Harnish, William Harper, David Harrah, Kevin Hart, Ali Hasan, William Hasker, John Haugeland, Roger Hausheer, William Heald, Peter Heath, Richard Heck, John F. Heil, Vincent F. Hendricks, Stephen Hetherington, Francis Heylighen, Kathleen Marie Higgins, Risto Hilpinen, Harold T. Hodes, Joshua Hoffman, Alan Holland, Robert L. Holmes, Richard Holton, Brad W. Hooker, Terence E. Horgan, Tamara Horowitz, Paul Horwich, Vittorio Hösle, Paul Hoβfeld, Daniel Howard-Snyder, Frances Howard-Snyder, Anne Hudson, Deal W. Hudson, Carl A. Huffman, David L. Hull, Patricia Huntington, Thomas Hurka, Paul Hurley, Rosalind Hursthouse, Guillermo Hurtado, Ronald E. Hustwit, Sarah Hutton, Jonathan Jenkins Ichikawa, Harry A. Ide, David Ingram, Philip J. Ivanhoe, Alfred L. Ivry, Frank Jackson, Dale Jacquette, Joseph Jedwab, Richard Jeffrey, David Alan Johnson, Edward Johnson, Mark D. Jordan, Richard Joyce, Hwa Yol Jung, Robert Hillary Kane, Tomis Kapitan, Jacquelyn Ann K. Kegley, James A. Keller, Ralph Kennedy, Sergei Khoruzhii, Jaegwon Kim, Yersu Kim, Nathan L. King, Patricia Kitcher, Peter D. Klein, E. D. Klemke, Virginia Klenk, George L. Kline, Christian Klotz, Simo Knuuttila, Joseph J. Kockelmans, Konstantin Kolenda, Sebastian Tomasz Kołodziejczyk, Isaac Kramnick, Richard Kraut, Fred Kroon, Manfred Kuehn, Steven T. Kuhn, Henry E. Kyburg, John Lachs, Jennifer Lackey, Stephen E. Lahey, Andrea Lavazza, Thomas H. Leahey, Joo Heung Lee, Keith Lehrer, Dorothy Leland, Noah M. Lemos, Ernest LePore, Sarah-Jane Leslie, Isaac Levi, Andrew Levine, Alan E. Lewis, Daniel E. Little, Shu-hsien Liu, Shu-hsien Liu, Alan K. L. Chan, Brian Loar, Lawrence B. Lombard, John Longeway, Dominic McIver Lopes, Michael J. Loux, E. J. Lowe, Steven Luper, Eugene C. Luschei, William G. Lycan, David Lyons, David Macarthur, Danielle Macbeth, Scott MacDonald, Jacob L. Mackey, Louis H. Mackey, Penelope Mackie, Edward H. Madden, Penelope Maddy, G. B. Madison, Bernd Magnus, Pekka Mäkelä, Rudolf A. Makkreel, David Manley, William E. Mann (W.E.M.), Vladimir Marchenkov, Peter Markie, Jean-Pierre Marquis, Ausonio Marras, Mike W. Martin, A. P. Martinich, William L. McBride, David McCabe, Storrs McCall, Hugh J. McCann, Robert N. McCauley, John J. McDermott, Sarah McGrath, Ralph McInerny, Daniel J. McKaughan, Thomas McKay, Michael McKinsey, Brian P. McLaughlin, Ernan McMullin, Anthonie Meijers, Jack W. Meiland, William Jason Melanson, Alfred R. Mele, Joseph R. Mendola, Christopher Menzel, Michael J. Meyer, Christian B. Miller, David W. Miller, Peter Millican, Robert N. Minor, Phillip Mitsis, James A. Montmarquet, Michael S. Moore, Tim Moore, Benjamin Morison, Donald R. Morrison, Stephen J. Morse, Paul K. Moser, Alexander P. D. Mourelatos, Ian Mueller, James Bernard Murphy, Mark C. Murphy, Steven Nadler, Jan Narveson, Alan Nelson, Jerome Neu, Samuel Newlands, Kai Nielsen, Ilkka Niiniluoto, Carlos G. Noreña, Calvin G. Normore, David Fate Norton, Nikolaj Nottelmann, Donald Nute, David S. Oderberg, Steve Odin, Michael O’Rourke, Willard G. Oxtoby, Heinz Paetzold, George S. Pappas, Anthony J. Parel, Lydia Patton, R. P. Peerenboom, Francis Jeffry Pelletier, Adriaan T. Peperzak, Derk Pereboom, Jaroslav Peregrin, Glen Pettigrove, Philip Pettit, Edmund L. Pincoffs, Andrew Pinsent, Robert B. Pippin, Alvin Plantinga, Louis P. Pojman, Richard H. Popkin, John F. Post, Carl J. Posy, William J. Prior, Richard Purtill, Michael Quante, Philip L. Quinn, Philip L. Quinn, Elizabeth S. Radcliffe, Diana Raffman, Gerard Raulet, Stephen L. Read, Andrews Reath, Andrew Reisner, Nicholas Rescher, Henry S. Richardson, Robert C. Richardson, Thomas Ricketts, Wayne D. Riggs, Mark Roberts, Robert C. Roberts, Luke Robinson, Alexander Rosenberg, Gary Rosenkranz, Bernice Glatzer Rosenthal, Adina L. Roskies, William L. Rowe, T. M. Rudavsky, Michael Ruse, Bruce Russell, Lilly-Marlene Russow, Dan Ryder, R. M. Sainsbury, Joseph Salerno, Nathan Salmon, Wesley C. Salmon, Constantine Sandis, David H. Sanford, Marco Santambrogio, David Sapire, Ruth A. Saunders, Geoffrey Sayre-McCord, Charles Sayward, James P. Scanlan, Richard Schacht, Tamar Schapiro, Frederick F. Schmitt, Jerome B. Schneewind, Calvin O. Schrag, Alan D. Schrift, George F. Schumm, Jean-Loup Seban, David N. Sedley, Kenneth Seeskin, Krister Segerberg, Charlene Haddock Seigfried, Dennis M. Senchuk, James F. Sennett, William Lad Sessions, Stewart Shapiro, Tommie Shelby, Donald W. Sherburne, Christopher Shields, Roger A. Shiner, Sydney Shoemaker, Robert K. Shope, Kwong-loi Shun, Wilfried Sieg, A. John Simmons, Robert L. Simon, Marcus G. Singer, Georgette Sinkler, Walter Sinnott-Armstrong, Matti T. Sintonen, Lawrence Sklar, Brian Skyrms, Robert C. Sleigh, Michael Anthony Slote, Hans Sluga, Barry Smith, Michael Smith, Robin Smith, Robert Sokolowski, Robert C. Solomon, Marta Soniewicka, Philip Soper, Ernest Sosa, Nicholas Southwood, Paul Vincent Spade, T. L. S. Sprigge, Eric O. Springsted, George J. Stack, Rebecca Stangl, Jason Stanley, Florian Steinberger, Sören Stenlund, Christopher Stephens, James P. Sterba, Josef Stern, Matthias Steup, M. A. Stewart, Leopold Stubenberg, Edith Dudley Sulla, Frederick Suppe, Jere Paul Surber, David George Sussman, Sigrún Svavarsdóttir, Zeno G. Swijtink, Richard Swinburne, Charles C. Taliaferro, Robert B. Talisse, John Tasioulas, Paul Teller, Larry S. Temkin, Mark Textor, H. S. Thayer, Peter Thielke, Alan Thomas, Amie L. Thomasson, Katherine Thomson-Jones, Joshua C. Thurow, Vzalerie Tiberius, Terrence N. Tice, Paul Tidman, Mark C. Timmons, William Tolhurst, James E. Tomberlin, Rosemarie Tong, Lawrence Torcello, Kelly Trogdon, J. D. Trout, Robert E. Tully, Raimo Tuomela, John Turri, Martin M. Tweedale, Thomas Uebel, Jennifer Uleman, James Van Cleve, Harry van der Linden, Peter van Inwagen, Bryan W. Van Norden, René van Woudenberg, Donald Phillip Verene, Samantha Vice, Thomas Vinci, Donald Wayne Viney, Barbara Von Eckardt, Peter B. M. Vranas, Steven J. Wagner, William J. Wainwright, Paul E. Walker, Robert E. Wall, Craig Walton, Douglas Walton, Eric Watkins, Richard A. Watson, Michael V. Wedin, Rudolph H. Weingartner, Paul Weirich, Paul J. Weithman, Carl Wellman, Howard Wettstein, Samuel C. Wheeler, Stephen A. White, Jennifer Whiting, Edward R. Wierenga, Michael Williams, Fred Wilson, W. Kent Wilson, Kenneth P. Winkler, John F. Wippel, Jan Woleński, Allan B. Wolter, Nicholas P. Wolterstorff, Rega Wood, W. Jay Wood, Paul Woodruff, Alison Wylie, Gideon Yaffe, Takashi Yagisawa, Yutaka Yamamoto, Keith E. Yandell, Xiaomei Yang, Dean Zimmerman, Günter Zoller, Catherine Zuckert, Michael Zuckert, Jack A. Zupko (J.A.Z.)
- Edited by Robert Audi, University of Notre Dame, Indiana
-
- Book:
- The Cambridge Dictionary of Philosophy
- Published online:
- 05 August 2015
- Print publication:
- 27 April 2015, pp ix-xxx
-
- Chapter
- Export citation
Genetic and environmental influences on the relationship between adult ADHD symptoms and self-reported problem drinking in 6024 Dutch twins
- E. M. Derks, J. M. Vink, G. Willemsen, W. van den Brink, D. I. Boomsma
-
- Journal:
- Psychological Medicine / Volume 44 / Issue 12 / September 2014
- Published online by Cambridge University Press:
- 03 March 2014, pp. 2673-2683
-
- Article
- Export citation
-
Background
Cross-sectional and longitudinal studies have shown a positive association between attention deficit hyperactivity disorder (ADHD) and problematic alcohol use in adults. To what extent this association is explained by genetic and environmental factors is largely unknown.
MethodData on ADHD and alcohol consumption were collected by self-report in 6024 adult Dutch twins. ADHD symptoms were assessed by three subscales of the Conners' Adult ADHD Rating Scales – Self-Report: Screening Version (CAARS–S:SV): inattentiveness, hyperactivity and the ADHD index (ADHD-I). Problem drinking was defined as at least two self-reported alcohol-related problems on the CAGE questionnaire. Structural equation modelling was applied to the bivariate twin data to estimate genetic and environmental influences.
ResultsHeritability of ADHD symptoms ranged between 32% and 40% and heritability of problem drinking was 50%. The positive correlation between ADHD symptoms and problem drinking was confirmed in this general population sample, with phenotypic correlations between 0.20 and 0.28 and genetic correlations between 0.39 and 0.50. Phenotypic correlations are primarily (61–100%) explained by genetic influences with non-shared environmental influences explaining the remaining covariance. No significant quantitative or qualitative gender differences in covariance structure were found.
ConclusionsThis study convincingly shows that ADHD symptoms and problem drinking are moderately but significantly correlated in adults and that genetic correlations are primarily underlying this association. This suggests that early interventions are required to prevent adolescents with ADHD from developing problematic levels of alcohol use. Furthermore, clinicians who treat alcohol-dependent patients should be aware that the patient may have a co-morbid condition of ADHD; integrated interventions are required.
Contributors
-
- By Ted Abel, Antoine Adamantidis, Karla V. Allebrandt, Simon N. Archer, Amelie Baud, Michel Billiard, Carlos Blanco-Centurion, Diane B. Boivin, Ethan Buhr, Matthew E. Carter, Nicolas Cermakian, Jennifer H.K. Choi, S.Y. Christin Chong, Chiara Cirelli, Marc Cuesta, Thomas Curie, Yves Dauvilliers, Luis de Lecea, Derk-Jan Dijk, Stephane Dissel, Annette C. Fedson, Jonathan Flint, Marcos G. Frank, Paul Franken, Ying-Hui Fu, Thorarinn Gislason, David Gozal, Devon A. Grant, Hakon Hakonarson, Makoto Honda, Hyun Hor, Christer Hublin, Peng Jiang, Takashi Kanbayashi, Jaakko Kaprio, Andrew Kasarskis, Leila Kheirandish-Gozal, RodaRani Konadhode, Michael Lazarus, Meng Liu, Michael March, Mark F. Mehler, Keivan Kaveh Moghadam, Valérie Mongrain, Charles M. Morin, Benjamin M. Neale, Seiji Nishino, Allan I. Pack, Dheeraj Pelluru, Rosa Peraita-Adrados, Giuseppe Plazzi, David A. Prober, Louis J. Ptáček, Irfan A. Qureshi, David M. Raizen, John J. Renger, Till Roenneberg, Elizabeth J. Rossin, Takeshi Sakurai, Paul Salin, Karen D. Schilli, Eva C. Schulte, Laurent Seugnet, Paul J. Shaw, Priyattam J. Shiromani, Patrick Sleiman, Mehdi Tafti, Joseph S. Takahashi, Matthew S. Thimgan, Katsushi Tokunaga, Giulio Tononi, Fred W. Turek, Yoshihiro Urade, Hans P.A. Van Dongen, Juliane Winkelmann, Christopher J. Winrow
- Edited by Paul Shaw, Mehdi Tafti, Michael J. Thorpy
-
- Book:
- The Genetic Basis of Sleep and Sleep Disorders
- Published online:
- 05 November 2013
- Print publication:
- 24 October 2013, pp xi-xiv
-
- Chapter
- Export citation
Cognitive biases and auditory verbal hallucinations in healthy and clinical individuals
- K. Daalman, I. E. C. Sommer, E. M. Derks, E. R. Peters
-
- Journal:
- Psychological Medicine / Volume 43 / Issue 11 / November 2013
- Published online by Cambridge University Press:
- 01 March 2013, pp. 2339-2347
-
- Article
- Export citation
-
Background
Several cognitive biases are related to psychotic symptoms, including auditory verbal hallucinations (AVH). It remains unclear whether these biases differ in voice-hearers with and without a ‘need-for-care’.
MethodA total of 72 healthy controls, 72 healthy voice-hearers and 72 clinical voice-hearers were compared on the Cognitive Biases Questionnaire for psychosis (CBQp), which assesses ‘intentionalizing’, ‘jumping to conclusions’, ‘catastrophizing’, ‘dichotomous thinking’ and ‘emotional reasoning’ in vignettes characterized by two themes, ‘threatening events’ and ‘anomalous perceptions’.
ResultsHealthy voice-hearers scored intermediately on total CBQp between the control and clinical groups, differing significantly from both. However, on four out of five biases the scores of the healthy voice-hearers were comparable with those of the healthy controls. The only exception was ‘emotional reasoning’, on which their scores were comparable with the clinical group. Healthy voice-hearers demonstrated fewer biases than the psychotic patients on the ‘threatening events’, but not the ‘anomalous perceptions’, vignettes. CBQp scores were related to both cognitive and emotional, but not physical, characteristics of voices.
ConclusionsMost cognitive biases prevalent in clinical voice-hearers, particularly with threatening events themes, are absent in healthy voice-hearers, apart from emotional reasoning which may be specifically related to the vulnerability to develop AVH. The association between biases and both beliefs about voices and distress/emotional valence is consistent with the close links between emotions and psychotic phenomena identified by cognitive models of psychosis. The absence of reasoning biases might prevent the formation of threatening appraisals about anomalous experiences, thereby reducing the likelihood of distress and ‘need for care’.
Schizophrenia genetic variants are not associated with intelligence
- A. F. Terwisscha van Scheltinga, S. C. Bakker, N. E. M. van Haren, E. M. Derks, J. E. Buizer-Voskamp, W. Cahn, S. Ripke, R. A. Ophoff, R. S. Kahn
-
- Journal:
- Psychological Medicine / Volume 43 / Issue 12 / December 2013
- Published online by Cambridge University Press:
- 15 February 2013, pp. 2563-2570
-
- Article
- Export citation
-
Background
Schizophrenia is associated with lower pre-morbid intelligence (IQ) in addition to (pre-morbid) cognitive decline. Both schizophrenia and IQ are highly heritable traits. Therefore, we hypothesized that genetic variants associated with schizophrenia, including copy number variants (CNVs) and a polygenic schizophrenia (risk) score (PSS), may influence intelligence.
MethodIQ was estimated with the Wechsler Adult Intelligence Scale (WAIS). CNVs were determined from single nucleotide polymorphism (SNP) data using the QuantiSNP and PennCNV algorithms. For the PSS, odds ratios for genome-wide SNP data were calculated in a sample collected by the Psychiatric Genome-Wide Association Study (GWAS) Consortium (8690 schizophrenia patients and 11 831 controls). These were used to calculate individual PSSs in our independent sample of 350 schizophrenia patients and 322 healthy controls.
ResultsAlthough significantly more genes were disrupted by deletions in schizophrenia patients compared to controls (p = 0.009), there was no effect of CNV measures on IQ. The PSS was associated with disease status (R2 = 0.055, p = 2.1 × 10−7) and with IQ in the entire sample (R2 = 0.018, p = 0.0008) but the effect on IQ disappeared after correction for disease status.
ConclusionsOur data suggest that rare and common schizophrenia-associated variants do not explain the variation in IQ in healthy subjects or in schizophrenia patients. Thus, reductions in IQ in schizophrenia patients may be secondary to other processes related to schizophrenia risk.
Contributors
-
- By Luis G. Acevedo, Schahram Akbarian, Ioanna Andreou, Krishnarao Appasani, Raghu K. Appasani, Julia Arand, David M. Ashley, Alexander R. Ball, Yehudit Bergman, Marina Bibikova, Angela Bithell, Francesca Bonafè, Eric E. Bouhassira, Victoria L. Boyd, Noel J. Buckley, Lars Olov Bygren, Claudio M. Caldarera, Gemma Carvill, James W. F. Catto, Sarah Derks, Ewa Dudziec, Jeffrey D. Falk, Jian-Bing Fan, Joseph M. Fernandez, David E. Fisher, Emanuela Fiumana, Tamara B. Franklin, Fei Gao, Arkadiusz Gertych, Emanuele Giordano, David Goldman, Markus Grammel, Carlo Guarnieri, Kevin L. Gunderson, Victoria (Fatemeh) G. Haghighi, Xu Han, Yong-Mahn Han, Howard C. Hang, Aditi Hazra, Laura B.K. Herzing, Norbert Hochstein, Robin Holliday, Dorothee Honsel, Mary A. Jelinek, Guanyu Ji, Yan Jiang, Atsushi Kaneda, Richard A. Katz, Hyemin Kim, Richard Kroon, Tapas K. Kundu, Benoit Labonté, Daeyoup Lee, Konstantin Lepikhov, Andrea Linnemann-Florl, Dirk Loeffert, Dylan Maixner, Isabelle M. Mansuy, Andreas Missel, D. V. Mohankrishna, Joana Carvalho Moreira de Mello, Paolo G. Morselli, Rituparna Mukhopadhyay, Claudio Muscari, Takashi Nagano, Frank Narz, Shuji Ogino, Carlo M. Oranges, Shari Orlanski, Alice Pasini, Ralf Peist, Lygia V. Pereira, Andrey Poleshko, Claire Rougeulle, Thea Rütjes, Ana Sanz, Benjamin G. Schroeder, Gerald Schock, Kornel Schuebel, B. Ruthrotha Selvi, Hogyu Seo, Natalia Shalginskikh, Andrew Sharp, Jun S. Song, Lennart Suckau, Azim Surani, Jian Tajbakhsh, Gustavo Turecki, Céline Vallot, Manon van Engeland, Jörn Walter, Nicholas C. Wong, Mark Wossidlo, Honglong Wu, Yurong Xin, Zhixiang Yan, Yu-Ying Yang, Mingzhi Ye, Kyoko Yokomori, Sephorah Zaman, Weihua Zeng, Gerald Zon
- Edited by Krishnarao Appasani
- Foreword by Azim Surani, University of Cambridge
-
- Book:
- Epigenomics
- Published online:
- 05 August 2012
- Print publication:
- 02 August 2012, pp x-xxiv
-
- Chapter
- Export citation
Childhood trauma and auditory verbal hallucinations
- K. Daalman, K. M. J. Diederen, E. M. Derks, R. van Lutterveld, R. S. Kahn, Iris E. C. Sommer
-
- Journal:
- Psychological Medicine / Volume 42 / Issue 12 / December 2012
- Published online by Cambridge University Press:
- 16 April 2012, pp. 2475-2484
-
- Article
- Export citation
-
Background
Hallucinations have consistently been associated with traumatic experiences during childhood. This association appears strongest between physical and sexual abuse and auditory verbal hallucinations (AVH). It remains unclear whether traumatic experiences mainly colour the content of AVH or whether childhood trauma triggers the vulnerability to experience hallucinations in general. In order to investigate the association between hallucinations, childhood trauma and the emotional content of hallucinations, experienced trauma and phenomenology of AVH were investigated in non-psychotic individuals and in patients with a psychotic disorder who hear voices.
MethodA total of 127 non-psychotic individuals with frequent AVH, 124 healthy controls and 100 psychotic patients with AVH were assessed for childhood trauma. Prevalence of childhood trauma was compared between groups and the relation between characteristics of voices, especially emotional valence of content, and childhood trauma was investigated.
ResultsBoth non-psychotic individuals with AVH and patients with a psychotic disorder and AVH experienced more sexual and emotional abuse compared with the healthy controls. No difference in the prevalence of traumatic experiences could be observed between the two groups experiencing AVH. In addition, no type of childhood trauma could distinguish between positive or negative emotional valence of the voices and associated distress. No correlations were found between sexual abuse and emotional abuse and other AVH characteristics.
ConclusionsThese results suggest that sexual and emotional trauma during childhood render a person more vulnerable to experience AVH in general, which can be either positive voices without associated distress or negative voices as part of a psychotic disorder.
The Latent Class Structure of ADHD Is Stable Across Informants
- Robert R. Althoff, William E. Copeland, Catherine Stanger, Eske M. Derks, Richard D. Todd, Rosalind J. Neuman, Toos C. E. M. Van Beijsterveldt, Dorret I. Boomsma, James J. Hudziak
-
- Journal:
- Twin Research and Human Genetics / Volume 9 / Issue 4 / 01 August 2006
- Published online by Cambridge University Press:
- 21 February 2012, pp. 507-522
-
- Article
-
- You have access Access
- Export citation
-
Previous studies have looked at the structure of attention-deficit/hyperactivity disorder (ADHD) using latent class analysis (LCA) of Child Behavior Checklist (CBCL) or Diagnostic and Statistical Manual of Mental Disorders (DSM) symptom structure. These studies have identified distinct classes of children with inattentive, hyperactive, or combined subtypes and have used these classes to refine genetic analyses. The objective of the current report is to determine if the latent class structure of ADHD subtypes is consistent across informant using the Conners' Rating Scales (CRS). LCA was applied to CRS forms from mother, father, and teacher reports of 1837, 1329 and 1048 latency aged Dutch twins, respectively. The optimal solution for boys was a 5-class solution for mothers, a 3-class solution for fathers, and a 4-class solution for teachers. For girls, a 4-class solution for mothers and a 3-class for fathers and teachers was optimal. Children placed into a class by one informant had markedly increased odds ratio of being placed into the same or similar class by the other informants. Results from LCA using Dutch twins with the CRS show stability across informants suggesting that more stable phenotypes may be accessible for genotyping using a multi-informant approach.
Young Netherlands Twin Register (Y-NTR): A Longitudinal Multiple Informant Study of Problem Behavior
- Meike Bartels, C. E. M. (Toos) van Beijsterveldt, Eske M. Derks, Therese M. Stroet, Tinca J. C. Polderman, James J. Hudziak, Dorret I. Boomsma
-
- Journal:
- Twin Research and Human Genetics / Volume 10 / Issue 1 / 01 February 2007
- Published online by Cambridge University Press:
- 21 February 2012, pp. 3-11
-
- Article
-
- You have access Access
- Export citation
-
The Netherlands Twin Register (NTR) was established around 1987 at the Vrije Universiteit in Amsterdam, the Netherlands. The current article summarizes the longitudinal genetic analyses of maternal and paternal ratings of twins' behavior as a function of the sex of the children for the traits of aggression (AGG), attention problems (AP), anxious/depression (ANX), internalizing behavior (INT) and externalizing behavior (EXT). We found that genetic influences are the most important factor in explaining individual differences in these traits. For most phenotypes, influences of genetic factors fluctuate throughout development, with the exception of AP, for which genetic influences remain of similar magnitude. Changes in genetic influences parallel those in shared environmental influences, while nonshared environmental influences remain relatively constant. Around 10% to 20% of the variance is accounted for by parent-specific shared environment, which includes rater bias. For all phenotypes, stability throughout childhood is accounted for by genetic and shared environmental factors, while nonshared environmental influences are mainly age/measurement specific. About 15% of the phenotypic stability is accounted for by rater-specific shared environmental influences, which include rater bias. In conclusion, between ages 3 and 12 genetic factors are the most important cause of individual differences in emotional and behavioral problems.
Netherlands Twin Register: A Focus on Longitudinal Research
- Dorret I. Boomsma, Jacqueline M. Vink, Toos C. E .M. van Beijsterveldt, Eco J. C. de Geus, A. Leo Beem, Elles J. C. M. Mulder, Eske M. Derks, Harriette Riese, Gonneke A. H. M. Willemsen, Meike Bartels, Mireille van den Berg, Nina H. M. Kupper, Tinca J. C. Polderman, Danielle Posthuma, Marjolein J. H. Rietveld, Janine H. Stubbe, Louise I. Knol, Therese Stroet, G. Caroline M. van Baal
-
- Journal:
- Twin Research / Volume 5 / Issue 5 / 01 October 2002
- Published online by Cambridge University Press:
- 21 February 2012, pp. 401-406
-
- Article
-
- You have access Access
- Export citation
-
In 1986 we began The Netherlands Twin Register (NTR) by recruiting young twins and multiples a few weeks or months after birth. Currently we register around 50% of all newborn multiples in The Netherlands. Their parents receive a questionnaire at registration and afterwards when the children are 2, 3, 5, 7, 10 and 12 years of age. Teachers are asked to rate the behavior of the children at ages 7, 10 and 12 years. Adolescent and young-adult twins were recruited through City Councils in the early 1990s. These twins, their parents and siblings participate in longitudinal survey studies that include items about health, fertility, lifestyle, addiction, personality and psychopathology, religion, socioeconomic status, and educational attainment. The total number of twins and multiples registered with the NTR is currently over 60,000. Subgroups of twins and siblings take part in studies of cognitive development, brain function and neuropsychological indices of attention processes, and molecular genetic studies of classical and behavioral cardiovascular risk factors. DNA samples are currently collected in selected twin families for two large linkage studies, which aim to find QTLs for anxious depression and for nicotine addiction. Sisters who are mothers of DZ twins contribute DNA samples for a linkage study of DZ twinning. Large cohorts of phenotyped family members from the general population are very valuable for genetic epidemiological studies and permit selection of informative families for gene finding studies.
The Influence of Informant Characteristics on the Reliability of Family History Interviews
- Kim H. W. Verweij, Eske M. Derks, Eva J. E. Hendriks, Wiepke Cahn
-
- Journal:
- Twin Research and Human Genetics / Volume 14 / Issue 3 / 01 June 2011
- Published online by Cambridge University Press:
- 21 February 2012, pp. 217-220
-
- Article
-
- You have access Access
- Export citation
-
Family history interviews are widely used in psychiatric research, as well as in genetic and twin studies, and provide a way to collect family history information quickly and economically. To obtain a valid assessment of family history, it is important to investigate which family member will be able to provide accurate information. Previous research shows that the validity of family history reporting can be influenced by characteristics of the informant, such as age, gender and personal history of psychiatric disorder. The aim of this study was to investigate the role of a subject's position in a pedigree on the validity of data collection. Family history data on diabetes and psychiatric disorders were collected in three generations of 33 families by interviewing both an index subject (3rd generation) and his or her mother (2nd generation). Mothers were shown to report higher rates of diabetes and psychiatric disorder in the family compared to the index subjects. There was no significant difference in the disease rate reported by male and female index subject. Mothers who experienced a depressive episode indicated significantly more family members as having a psychiatric disorder than mothers who never experienced such an episode. This could be explained by the presence of informant bias, but may also result from the fact that depression is a heritable disorder and is therefore actually more prevalent in these families. Our findings suggest that family interview data should be collected by interviewing subjects who have a central position in the pedigree and can therefore provide information on his/her own generation, the previous and the next. In addition, psychiatric status of the informant should be carefully addressed.
Unmet needs in patients with first-episode schizophrenia: a longitudinal perspective
- K. Landolt, W. Rössler, T. Burns, V. Ajdacic-Gross, S. Galderisi, J. Libiger, D. Naber, E. M. Derks, R. S. Kahn, W. W. Fleischhacker
-
- Journal:
- Psychological Medicine / Volume 42 / Issue 7 / July 2012
- Published online by Cambridge University Press:
- 21 November 2011, pp. 1461-1473
-
- Article
- Export citation
-
Background
This study aimed to identify the course of unmet needs by patients with a first episode of schizophrenia and to determine associated variables.
MethodWe investigated baseline assessments in the European First Episode Schizophrenia Trial (EUFEST) and also follow-up interviews at 6 and 12 months. Latent class growth analysis was used to identify patient groups based on individual differences in the development of unmet needs. Multinomial logistic regression determined the predictors of group membership.
ResultsFour classes were identified. Three differed in their baseline levels of unmet needs whereas the fourth had a marked decrease in such needs. Main predictors of class membership were prognosis and depression at baseline, and the quality of life and psychosocial intervention at follow-up. Depression at follow-up did not vary among classes.
ConclusionsWe identified subtypes of patients with different courses of unmet needs. Prognosis of clinical improvement was a better predictor for the decline in unmet needs than was psychopathology. Needs concerning social relationships were particularly persistent in patients who remained high in their unmet needs and who lacked additional psychosocial treatment.