The influence of genes on “positive valence systems” constructs: A systematic review Item Type Article Authors Hess, Jonathan L.; Kawaguchi, Daniel M.; Wagner, Kayla E.; Faraone, Stephen V.; Glatt, Stephen J. Citation Hess, JL, Kawaguchi, DM, Wagner, KE, Faraone, SV, Glatt, SJ. 2015. The Influence of Genes on “Positive Valence Systems” Constructs: A Systematic Review. Am J Med Genet Part B 171B: 92– 110. DOI 10.1002/ajmg.b.32382 Publisher Wiley Rights Attribution-NonCommercial-NoDerivatives 4.0 International Download date 26/09/2021 01:12:21 Item License http://doi.wiley.com/10.1002/tdm_license_1.1 Link to Item http://hdl.handle.net/20.500.12648/1795 See discussions, stats, and author profiles for this publication at: https://www.researchgate.net/publication/281608624 Genetics of Aggressive Behavior: An Overview Article in American Journal of Medical Genetics Part B Neuropsychiatric Genetics · September 2015 DOI: 10.1002/ajmg.b.32364 CITATIONS READS 81 1,596 6 authors, including: Yanli Zhang-James Noèlia Fernàndez-Castillo State University of New York Upstate Medical University University of Barcelona 65 PUBLICATIONS 1,992 CITATIONS 102 PUBLICATIONS 848 CITATIONS SEE PROFILE SEE PROFILE Mireille J. Bakker Bru Cormand Radboud University Medical Centre (Radboudumc) University of Barcelona 8 PUBLICATIONS 272 CITATIONS 311 PUBLICATIONS 10,197 CITATIONS SEE PROFILE SEE PROFILE Some of the authors of this publication are also working on these related projects: Aggression Genetics View project Trastorno por deficit de atencion con hiperactividad en la clinica pediatrica View project All content following this page was uploaded by Noèlia Fernàndez-Castillo on 25 November 2017. The user has requested enhancement of the downloaded file. RESEARCH ARTICLE Neuropsychiatric Genetics Genetics of Aggressive Behavior: An Overview Kim Veroude,1 Yanli Zhang-James,2,3 Noelia Fernandez-Castillo,4,5,6 Mireille J. Bakker,1 Bru Cormand,4,5,6 and Stephen V. Faraone2,3,7* 1Department of Cognitive Neuroscience, Donders Institute for Brain, Cognition and Behaviour, Radboudumc, Nijmegen, The Netherlands 2Departments of Psychiatry and of Neuroscience and Physiology, SUNY Upstate Medical University, Syracuse, New York 3Departments of Neuroscience and Physiology, SUNY Upstate Medical University, Syracuse, New York 4Departament de Genetica, Facultat de Biologia, Universitat de Barcelona, Catalonia, Spain 5Institut de Biomedicina de la Universitat de Barcelona (IBUB), Catalonia, Spain 6Centro de Investigacion Biomedica en Red de Enfermedades Raras (CIBERER), Spain 7K.G. Jebsen Centre for Research on Neuropsychiatric Disorders, University of Bergen, Bergen, Norway Manuscript Received: 22 April 2015; Manuscript Accepted: 5 August 2015 The Research Domain Criteria (RDoC) address three types of aggression: frustrative non-reward, defensive aggression and How to Cite this Article: offensive/proactive aggression. This review sought to present Veroude K, Zhang-James Y, Fernandez- the evidence for genetic underpinnings of aggression and to Castillo N, Bakker MJ, Cormand B, determine to what degree prior studies have examined pheno- Faraone SV. 2016. Genetics of Aggressive types that fit into the RDoC framework. Although the constructs Behavior: An Overview. of defensive and offensive aggression have been widely used in the animal genetics literature, the human literature is mostly Am J Med Genet Part B 171B:3–43. agnostic with regard to all the RDoC constructs. We know from twin studies that about half the variance in behavior may be explained by genetic risk factors. This is true for both dimen- seems logical that during this period of time people who had the sional, trait-like, measures of aggression and categorical defi- variants of genes that promoted aggression were more likely to nitions of psychopathology. The non-shared environment seems survive than other people. These variants have persisted in the to have a moderate influence with the effects of shared environ- human genome and partly explain why some people exhibit ment being unclear. Human molecular genetic studies of ag- aggressive behaviors. gression are in an early stage. The most promising candidates are Although the word “irascibilem” comes from the Latin “iras- in the dopaminergic and serotonergic systems along with hor- cibilem”, meaning “to attack,” in current language aggression monal regulators. Genome-wide association studies have not yet means much more. In the genetics literature aggression has been achieved genome-wide significance, but current samples are too small to detect variants having the small effects one would expect for a complex disorder. The strongest molecular evidence for a Kim Veroude, Yanli Zhang-James, Noelia Fernandez-Castillo, and genetic basis for aggression comes from animal models compar- Mireille J. Bakker are joint first authors. Dr. Zhang-James, M.J. Bakker and Dr. K. Veroude state no financial ing aggressive and non-aggressive strains or documenting the interests or potential conflicts of interest. effects of gene knockouts. Although we have learned much from Grant sponsor: NIMH; Grant number: R01MH094469; Grant sponsor: these prior studies, future studies should improve the measure- Spanish “Ministerio de Economı´a y Competitividad”; Grant number: ment of aggression by using a systematic method of measure- SAF2012-33484; Grant sponsor: AGAUR; Grant number: 2014SGR932; ment such as that proposed by the RDoC initiative. Grant sponsor: European Community’s Seventh Framework Programme Ó 2015 Wiley Periodicals, Inc. (FP7/2007-2013); Grant numbers: n˚602805, n˚603016; Grant sponsor: Centro de Investigacion Biomedica en Red de Enfermedades Raras (CIBERER). Key words: aggression; genetics; twin; GWAS; candidate à genes; mutations Correspondence to: Stephen V. Faraone, Ph.D., Departments of Psychiatry and of Neuroscience and Physiology, SUNY Upstate Medical University, 750 E. Adams St., Syracuse, New York 33136. INTRODUCTION E-mail: [email protected] Article first published online in Wiley Online Library During the early stages of human evolution, aggression was proba- (wileyonlinelibrary.com): 8 September 2015 bly an adaptive trait, as it is for many animals in the wild today. It DOI 10.1002/ajmg.b.32364 Ó 2015 Wiley Periodicals, Inc. 3 4 AMERICAN JOURNAL OF MEDICAL GENETICS PART B operationalized in many ways. As a categorical disorder it has been environment, is attributed to influence of the non-shared envi- studied as conduct disorder (CD), oppositional defiant disorder ronment, e2 ¼ 1–rMZ, which also includes measurement error (ODD) and antisocial personality disorder (APD). These catego- [Holzinger, 1929; Falconer, 1960]. It is important to note here ries are convenient for diagnosticians because other work suggests that the non-shared (unique) environment includes all experi- aggression to be a quantitative trait that is better operationalized on ences that contribute to differences between children in the same dimensions of externalizing behavior, rule breaking, psychopathy family, i.e. a common event (for example parents’ divorce) can and violence. affect siblings differently. A dimensional view of aggression is consistent with the ap- Twin studies have investigated aggression from different per- proach taken by the NIMH Research Domain Criteria (RDoC) spectives, e.g. as a personality trait [Miles and Carey, 1997], as Initiative [Sanislow et al., 2010]. RDoC seeks to focus researchers antisocial behavior [Rhee and Waldman, 2002] or as a symptom of on the fundamental mechanisms underlying psychopathology. In childhood and adolescent psychopathology. Previous reviews of doing so, it has been creating a dimensional taxonomy of behavior twin studies and adoption studies on aggression have estimated that, hopefully, corresponds better to underlying mechanisms than heritability up to 0.50, with an additional large role for non-shared does a system of discrete diagnoses. environmental influences and a small influence of the shared In the RDoC nomenclature, aggression is categorized into three environment [Viding et al., 2008; Tuvblad and Baker, 2011]. areas: frustrative non-reward, defensive aggression and offensive Genetic effects seem to predominantly account for phenotypic (or proactive) aggression. Frustrative non-reward refers to behav- correlations between different forms of aggression, such as reactive iors that correspond to the withdrawal or prevention of reward. (defensive) and proactive (offensive) aggression, although few This derives from human and animal studies showing that aggres- studies have examined this [Rhee and Waldman, 2011]. To update sion occurs after repeated, failed attempts to obtain rewards even these prior reviews, we conducted a systematic search for studies after sustained efforts. Defensive aggression refers to behaviors in the period January 2009 until February 2015. PubMed and caused by the perception of an immediate threat, which have PsycINFO were searched for peer-reviewed papers to identify the goal of eliminating the threat. Offensive (or proactive) aggres- studies of twins with characteristics of externalizing behavior sive behaviors are instrumental behaviors aimed at achieving a and psychopathy, regardless of age. We used the following search positive goal, often in the face of competition or in the context of strategy: aggressà OR antisocial behavà OR aggressive traità OR social hierarchies. behavior problemà OR behaviour problemà OR problem behavià The long-term goal of RDoC is to map RDoC phenotypes to OR CD